Criteria for the Classification and Diagnosis of the Rheumatic Diseases

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APPENDIX I Criteria for the Classiﬁ cation and Diagnosis of the Rheumatic Diseases

The criteria presented in the following section have The proposed criteria are empiric and not intended been developed with several different purposes in mind. to include or exclude a particular diagnosis in any indi- For a given disorder, one may have criteria for (1) clas- vidual patient. They are valuable in offering a standard sifi cation of groups of patients (e.g., for population to permit comparison of groups of patients from differ- surveys, selection of patients for therapeutic trials, or ent centers that take part in various clinical investiga- analysis of results on interinstitutional patient compari- tions, including therapeutic trials. sons); (2) diagnosis of individual patients; and (3) esti- The ideal criterion is absolutely sensitive (i.e., all mations of disease frequency, severity, and outcome. patients with the disorder show this physical fi nding or The original intention was to propose criteria as the positive laboratory test) and absolutely specifi c guidelines for classifi cation of disease syndromes for the (i.e., the positive fi nding or test is never present in any purpose of assuring correctness of diagnosis in patients other disease). Unfortunately, few such criteria or sets taking part in clinical investigation rather than for indi- of criteria exist. Usually, the greater the sensitivity of a vidual patient diagnosis. However, the proposed criteria fi nding, the lower its specifi city, and vice versa. When have in fact been used as guidelines for patient diagno- criteria are established attempts are made to select rea- sis as well as for research classifi cation. One must be sonable combinations of sensitivity and specifi city. cautious in such application because the various criteria An updated listing of additional criteria sets for rheu- are derived from the use of analytic techniques that matic and musculoskeletal disorders is available on the allow the minimum number of variables to achieve the American College of Rheumatology website (http:// best group discrimination, rather than to attempt to www.rheumatology.org/publications/classification/ arrive at a diagnosis in an individual patient. index.asp?aud=mem).

CRITERIA FOR THE CLASSIFICATION Of FIBROMYALGIAa

1. History of widespread pain Deﬁ nition. Pain is considered widespread when all of the following are present: pain in the left side of the body, pain in the right side of the body, pain above the waist, and pain below the waist. In addition, axial skeletal pain (cervical spine or anterior chest or thoracic spine or low back) must be present. In this deﬁ nition, shoulder and buttock pain is considered as pain for each involved side. “Low back” pain is considered lower segment pain.

2. Pain in 11 of 18 tender point sites on digital palpation.b Deﬁ nition. Pain, on digital palpation, must be present in at least 11 of the following 18 tender point sites: Occiput: bilateral, at the suboccipital muscle insertions. Low cervical: bilateral, at the anterior aspects of the intertransverse spaces at C5–C7. Trapezius: bilateral, at the midpoint of the upper border. Supraspinatus: bilateral, at origins, above the scapula spine near the medial border. Second rib: bilateral, at the second costochondral junctions, just lateral to the junctions on upper surfaces. Lateral epicondyle: bilateral, 2 cm distal to the epicondyles. Gluteal: bilateral, in upper outer quadrants of buttocks in anterior fold of muscle. Greater trochanter: bilateral, posterior to the trochanteric prominence. Knee: bilateral, at the medial fat pad proximal to the joint line.

SOURCE: Adapted from Wolfe F, Smythe HA, Yunus MS, et al. The American College of Rheumatology 1990 criteria for the classifi cation of fi bromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990;33:100–172, with permission of the American College of Rheumatology. a For classifi cation purposes, patients will be said to have fi bromyalgia if both criteria are satisfi ed. Widespread pain must have been present at least 3 months. The presence of a second clinical disorder does not exclude the diagnosis of fi bromyalgia. b Digital palpation should be performed with an approximate force of 4 kg. For a tender point to be considered “positive” the subject must state that the palpation was painful. “Tender” is not to be considered “painful.” 669 670 APPENDIX I

CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID ARTHRITISa

CRITERION DEFINITION

1. Morning stiffness Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement

2. Arthritis of three or more joint areas At least three joint areas simultaneously have had soft tissue swelling or ﬂ uid (not bony overgrowth alone) observed by a physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints

3. Arthritis of hand joints At least one area swollen (as deﬁ ned above) in a wrist, MCP, or PIP joint

4. Symmetric arthritis Simultaneous involvement of the same joint areas (as deﬁ ned in 2) on both sides of the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry)

5. Rheumatoid nodules Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician

6. Serum rheumatoid factor Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in ≤ 5% of normal control subjects

7. Radiographic changes Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include erosions or unequivocal bony decalciﬁ cation localized in or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify)

SOURCE: Reprinted from Arnett FC, Edworthy SM, Bloch DA. et al. The American Rheumatism Association 1987 revised criteria for the classifi cation of rheumatoid arthritis. Arthritis Rheum 1988;31:315–324, with permission of the American College of Rheumatology. ABBREVIATIONS: MCP, metacarpophalangeal; MTP, metatarsophalangeal; PIP, proxomal interphalangeal. a For classifi cation purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfi ed at least four of these seven criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients with two clinical diagnoses are not excluded. Designation as classic, defi nite, or probable rheumatoid arthritis is not to be made.

CLASSIFICATION OF PROGRESSION OF RHEUMATOID ARTHRITIS

Stage I, Early *1. No destructive changes on roentgenographic examination 2. Radiographic evidence of osteoporosis may be present

Stage II, Moderate *1. Radiographic evidence of osteoporosis, with or without slight subchondral bone destruction; slight cartilage destruction may be present *2. No joint deformities, although limitation of joint mobility may be present 3. Adjacent muscle atrophy 4. Extra-articular soft tissue lesions, such as nodules and tenosynovitis may be present

Stage III, Severe *1. Radiographic evidence of cartilage and bone destruction, in addition to osteoporosis *2. Joint deformity, such as subluxation, ulnar deviation, or hyperextension, without ﬁ brous or bony ankylosis 3. Extensive muscle atrophy 4. Extra-articular soft tissue lesions, such as nodules and tenosynovitis may be present

Stage IV, Terminal *1. Fibrous or bony ankylosis 2. Criteria of stage III

SOURCE: Reprinted from Steinbrocker O, Traeger CH. Batterman RC. Therapeutic criteria in rheumatoid arthritis. JAMA 1949;140:659–662, with permission. * The criteria prefaced by an asterisk are those that must be present to permit classiﬁ cation of a patient in any particular stage or grade. CRITERIA FOR THE CLASSIFICATION AND DIAGNOSIS 671

CRITERIA FOR CLINICAL REMISSION IN RHEUMATOID ARTHRITISa

Five or more of the following requirements must be fulﬁ lled for at least 2 consecutive months: 1. Duration of morning stiffness not exceeding 15 minutes 2. No fatigue 3. No joint pain (by history) 4. No joint tenderness or pain on motion 5. No soft tissue swelling in joints or tendon sheaths 6. Erythrocyte sedimentation rate (Westergren method) less than 30 mm/hour for a female or 20 mm/hour for a male

SOURCE: Reprinted from Pinals RS, Masi AT, Larsen RA. et al. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 1981;24:1308– 1315, with permission of the American College of Rheumatology. a These criteria are intended to describe either spontaneous remission or a state of drug-induced disease suppression, which simulates spontaneous remission. No alternative explanation may be invoked to account for the failure to meet a particular requirement. For instance, in the presence of knee pain, which might be related to degenerative arthritis, a point for “no joint pain” may not be awarded. Exclusions: Clinical manifestations of active vasculitis, pericarditis, pleuritis or myositis, and unexplained recent weight loss or fever attributable to rheumatoid arthritis will prohibit a designation of complete clinical remission.

CRITERIA FOR CLASSIFICATION OF FUNCTIONAL STATUS IN RHEUMATOID ARTHRITISa

Class I Completely able to perform usual activities of daily living (self-care, vocational, and avocational)

Class II Able to perform usual self-care and vocational activities, but limited in avocational activities

Class III Able to perform usual self-care activities, but limited in vocational and avocational activities

Class IV Limited in ability to perform usual self-care, vocational, and avocational activities

SOURCE: Reprinted from Hochberg MC, Chang RW, Dwosh I. et al. The American College of Rheumatology 1991 revised criteria for the classiﬁ cation of global functional status in rheumatoid arthritis. Arthritis Rheum 1992;35;498–502, with permission of the American College of Rheumatology. a Usual self-care activities include dressing, feeding, bathing, grooming, and toileting. Avocational (recreational and/or leisure) and vocational (work, school, homemaking) activities are patient-desired and age- and sex-speciﬁ c.

AMERICAN COLLEGE OF RHEUMATOLOGY PRELIMINARY DEFINITION OF IMPROVEMENT IN RHEUMATOID ARTHRITIS (ACR20)

≥ 20% improvement in tender joint count Required { ≥ 20% improvement in swollen joint count + ≥ 20% improvement in three of the following ﬁ ve: Patient pain assessment Patient global assessment APPENDIX I Physician global assessment Patient self-assessed disability Acute-phase reactant (ESR or CRP)

DISEASE ACTIVITY MEASURE METHOD OF ASSESSMENT

1. Tender joint count ACR tender joint count, an assessment of 28 or more joints. The joint count should be done by scoring several different aspects of tenderness, as assessed by pressure and joint manipulation on physical examination. The information on various types of tenderness should then be collapsed into a single tender-versus-nontender dichotomy.

2. Swollen joint count ACR swollen joint count, an assessment of 28 or more joints. Joints are classiﬁ ed as either swollen or not swollen.

3. Patient’s assessment of pain A horizontal visual analog scale (usually 10 cm) or Likert scale assessment of the patient’s current level of pain.

4. Patient’s global assessment of disease The patient’s overall assessment of how the arthritis is doing. One acceptable method for activity determining this is the question from the AIMS instrument: “Considering all the ways your arthritis affects you, mark ‘X’ on the scale for how well you are doing.” An anchored, horizontal, visual analog scale (usually 10 cm) should be provided. A Likert scale response is also acceptable.

(continued) 672 APPENDIX I

AMERICAN COLLEGE OF RHEUMATOLOGY PRELIMINARY DEFINITION OF IMPROVEMENT IN RHEUMATOID ARTHRITIS (ACR20) (continued)

DISEASE ACTIVITY MEASURE METHOD OF ASSESSMENT

5. Physician’s global assessment of disease A horizontal visual analog scale (usually 10 cm) or Likert scale measure of the physician’s activity assessment of the patient’s current disease activity.

6. Patient’s assessment of physical Any patient self-assessment instrument which has been validated, has reliability, has function been proven in RA trials to be sensitive to change, and which measures physical function in RA patients is acceptable. Instruments which have been demonstrated to be sensitive in RA trials include the AIMS, the HAQ, the Quality (or Index) of Well Being, the MHIQ, and the MACTAR.

7. Acute-phase reactant value A Westergren ESR or a CRP level.

SOURCE: Reprinted from Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology preliminary deﬁ nition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727–735, with permission of the American College of Rheumatology. ABBREVIATIONS: ACR, American College of Rheumatology; AIMS, Arthritis Impact Measurement Scales; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; MACTAR, McMaster Toronto Arthritis Patient Preference Disability Questionnaire; MHIQ, McMaster Health Index Questionnaire; RA, rheumatoid arthritis.

CRITERIA FOR THE CLASSIFICATION OF SPONDYLOARTHROPATHYa

Inﬂ ammatory spinal pain or Synovitis Asymmetric or Predominantly in the lower limbs and one or more of the following Positive family history Psoriasis

Inﬂ ammatory bowel disease

Urethritis, cervicitis, or acute diarrhea within 1 month before arthritis

Buttock pain alternating between right and left gluteal areas

Enthesopathy

Sacroiliitis

VARIABLE DEFINITION

Inﬂ ammatory spinal pain History or present symptoms of spinal pain in back, dorsal, or cervical region, with at least four of the following: (a) onset before age 45, (b) insidious onset, (c) improved by exercise, (d) associated with morning stiffness, (e) at least 3 months’ duration

Synovitis Past or present asymmetric arthritis or arthritis predominantly in the lower limbs

Family history Presence in ﬁ rst-degree or second-degree relatives of any of the following: (a) ankylosing spondylitis, (b) psoriasis, (c) acute uveitis, (d) reactive arthritis, (e) inﬂ ammatory bowel disease

Psoriasis Past or present psoriasis diagnosed by a physician

Inﬂ ammatory bowel disease Past or present Crohn’s disease or ulcerative colitis diagnosed by a physician and conﬁ rmed by radiographic examination or endoscopy

Alternating buttock pain Past or present pain alternating between the right and left gluteal regions

Enthesopathy Past or present spontaneous pain or tenderness at examination of the site of the insertion of the Achilles tendon or plantar fascia

Acute diarrhea Episode of diarrhea occurring within 1 month before arthritis APPENDIX I ) cation continued ( n Cardiovascular rst carpometacarpal a for the classifi or and two minor manifesta- . JAMA 1992;268:2069–2073, cation and reporting of osteo- cation and reporting of osteo- IP), and the fi ankylosis = cation criteria follow. a a ) city of 87%. SUPPORTING EVIDENCE OF PRECEDING SUPPORTING EVIDENCE STREPTOCOCCAL INFECTION moderate, and 4 moderate, continued = ( a minimal, 3 minimal, 3 = a nition of the variables used in classifi city of 89.6%. When radiographic evidence of sacroiliitis was included, the sensitivity evidence of sacroiliitis was included, the sensitivity city of 89.6%. When radiographic city of 91%. possible, 2 possible, 2 = ndings city to 86.7%. Defi ndings rapid streptococcal antigen test Positive throat culture or normal, 1 = Erythrocyte sedimentation rate C-reactive protein Prolonged PR interval Bilateral grade 2–4 or unilateral grade 3–4, according to the following radiographic grading system: to the following radiographic grade 3–4, according 2–4 or unilateral Bilateral grade 0 cation method yields a sensitivity of 94% and a specifi : ESR, erythrocyte sedimentation rate (Westergren). : MCP, metacarpophalangeal. cation method yields a sensitivity of 78.4% and a specifi cation method yields a sensitivity cation method yields a sensitivity of 89% and a specifi 20 mm/hour 20 ≤ : classifi Reprinted from Altman R, Alarcon G, Appelrouth D, et al. The American College of Rheumatology criteria for the : classifi Reprinted from Altman R, Alarcon G, Appelrouth D, et al. The American College of Rheumatology criteria for the : Fever, Endocarditis, and Kawasaki Disease of the Council o Reprinted from Special Writing Group of the Committee on Rheumatic : Study Group preliminary criteri S, Juhlin R, et al. The European Spondylarthropathy Reprinted from Dougados M, Van Der linden CRITERIA FOR THE CLASSIFICATION AND REPORTING OF OSTEOARTHRITIS OF THE HAND, HIP, AND KNEE CRITERIA FOR THE CLASSIFICATION AND CRITERIA FOR THE DIAGNOSIS OF RHEUMATIC FEVER CRITERIA FOR THE CRITERIA FOR THE CLASSIFICATION OF SPONDYLOARTHROPATHY THE CLASSIFICATION FOR CRITERIA BBREVIATION BBREVIATION OURCE OURCE OURCE OURCE This classifi The 10 selected joints are the second and third distal interphalangeal (DIP), the second and third proximal interphalangeal (P The 10 selected joints are the second and third distal If supported by evidence of preceding group A streptococcal infection, the presence of two major manifestations, or of one maj supported by evidence of preceding group A streptococcal infection, the presence of two major manifestations, If This classifi arthritis of the hip. Arthritis Rheum 1991;34:505–514, with permission of the American College of Rheumatology. arthritis of the hip. Arthritis Rheum 1991;34:505–514, with permission of the American College A arthritis of the hand. Arthritis Rheum 1990;33:1601–1610, with permission of the American College of Rheumatology. arthritis of the hand. Arthritis Rheum 1990;33:1601–1610, with permission of the American College A S a femoral or acetabular osteophytes Radiographic joint space narrowing (superior, axial, and/or medial) Radiographic Hip pain and At least two of the following three features: ESR CLASSIFICATION CRITERIA FOR OSTEOARTHRITIS OF THE HIP, TRADITIONAL FORMAT S a Hard tissue enlargement of 2 or more DIP joints than three swollen MCP joints Fewer of at least 1 of 10 selected joints Deformity Hand pain, aching, or stiffness and Three or four of the following features: joints Hard tissue enlargement of 2 or more of 10 selected CLASSIFICATION CRITERIA FOR OSTEOARTHRITIS OF THE HAND, TRADITIONAL FORMAT CLASSIFICATION CRITERIA FOR OSTEOARTHRITIS tions indicates a high probability of acute rheumatic fever. tions indicates a high probability of acute rheumatic S a Subcutaneous nodules Elevated acute phase reactants ChoreaErythema marginatum Laboratory fi Fever CarditisPolyarthritis fi Clinical Arthralgia Elevated or rising streptococcal antibody titer MAJOR MANIFESTATIONS MINOR MANIFESTATIONS S a Urethritis Sacroiliitis arthritis urethritis or cervicitis occurring within 1 month before Nongonococcal VARIABLE DEFINITION VARIABLE Disease in the Young, American Heart Association: guidelines for the diagnosis of rheumatic fever: Jones criteria, updated 1992 Disease in the Young, American Heart Association: with permission. of spondylarthropathy. Arthritis Rheum 1991;34:1218–1227, with permission of the American College of Rheumatology. Rheum 1991;34:1218–1227, with permission of spondylarthropathy. Arthritis (CMC) joints of both hands. This classifi improved to 87.0% with a minor decrease in specifi improved to 87.0% with 674 APPENDIX I

CRITERIA FOR THE CLASSIFICATION AND REPORTING OF OSTEOARTHRITIS OF THE HAND, HIP, AND KNEE (continued)

CRITERIA FOR CLASSIFICATION OF OSTEOARTHRITIS (OA) OF THE KNEE

Clinical and laboratory Knee pain plus at least ﬁ ve of nine: Age >50 years Stiffness <30 minutes Crepitus Bony tenderness Bony enlargement No palpable warmth ESR <40 mm/hour RF <1 : 40 SF OA 92% sensitive 75% speciﬁ c

Clinical and radiographic Knee pain plus at least one of three: Age >50 years Stiffness <30 minutes Crepitus + Osteophytes 91% sensitive 86% speciﬁ c

Clinicala Knee pain plus at least three of six: Age >50 years Stiffness <30 minutes Crepitus Bony tenderness Bony enlargement No palpable warmth 95% sensitive 69% speciﬁ c

SOURCE: Reprinted from Altman R, Asch E, Bloch G, et al. Development of criteria for the classifi cation and reporting of osteoarthritis: classifi cation of osteoarthritis of the knee. Arthritis Rheum 1986;29:1039–1049, with permission of the American College of Rheumatology. ABBREVIATIONS: ESR, erythrocyte sedimentation rate (Westergren); RF, rheumatoid factor; SF OA, synovial fl uid signs of OA (clear, viscous, or white blood cell count <2000/mm3). a Alternative for the clinical category would be four of six, which is 84% sensitive and 89% specifi c.

CRITERIA FOR THE CLASSIFICATION OF ACUTE GOUTY ARTHRITIS

A. The presence of characteristic urate crystals in the joint ﬂ uid, or

B. A tophus proved to contain urate crystals by chemical means or polarized light microscopy or the presence of 6 of the following 12 clinical, laboratory, and x-ray phenomena listed below: 1. More than one attack of acute arthritis 2. Maximal infl ammation developed within 1 day 3. Attack of monarticular arthritis 4. Joint redness observed 5. First metatarsophalangeal joint painful or swollen 6. Unilateral attack involving fi rst metatarsophalangeal joint 7. Unilateral attack involving tarsal joint 8. Suspected tophus 9. Hyperuricemia 10. Asymmetric swelling within a joint (radiograph) 11. Subcortical cysts without erosions (radiograph) 12. Negative culture of joint fl uid for microorganisms during attack of joint infl ammation

SOURCE: Adapted from Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classiﬁ cation of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895–900, with permission of the American College of Rheumatology. CRITERIA FOR THE CLASSIFICATION AND DIAGNOSIS 675

CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOSUSa

CRITERION DEFINITION

1. Malar rash Fixed erythema, ﬂ at or raised, over the malar eminences, tending to spare the nasolabial folds

2. Discoid rash Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions

3. Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

4. Oral ulcers Oral or nasopharyngeal ulceration, usually painless, observed by a physician

5. Arthritis Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion

6. Serositis (a) Pleuritis-convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion OR (b) Pericarditis-documented by ECG or rub or evidence of pericardial effusion

7. Renal disorder (a) Persistent proteinuria greater than 0.5 g per day or greater than 3+ if quantitation not performed OR (b) Cellular casts—may be red cell, hemoglobin, granular, tubular, or mixed

8. Neurologic disorder (a) Seizures—in the absence of offending drugs or known metabolic derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance OR (b) Psychosis—in the absence of offending drugs or known metabolic derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance

9. Hematologic disorder (a) Hemolytic anemia with reticulocytosis OR (b) Leukopenia, less than 4000/mm3 total on two or more occasions OR (c) Lymphopenia, less than 1500/mm3 on two or more occasions OR (d) Thrombocytope- nia, less than l00,000/mm3 in the absence of offending drugs

10. Immunologic disorderb (a) Anti-DNA: antibody to native DNA in abnormal titer OR (b) Anti-SM: presence of antibody to SM nuclear antigen OR (c) Positive fi nding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for at least 6 months and confi rmed by Treponema pallidum immobilization or fl uorescent treponemal antibody absorption test

11. Antinuclear antibody An abnormal titer of antinuclear antibody by immunoﬂ uorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with “drug-induced lupus” syndrome

SOURCE: Adapted from Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classifi cation of systemic lupus erythematosus (SLE). Arthritis Rheum 1982;25:1271–1277, with permission of the American College of Rheumatology. SOURCE: Adapted from Hochberg ME. Updating the American College of Rheumatology revised criteria for the classifi cation of systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725, with permission of the American College of Rheumatology. a This classifi cation is based on 11 criteria. For the purpose of identifying patients in clinical studies, a person must have SLE if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation. b The modifi cations to criterion number 10 were made in 1997. APPENDIX I

CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC SCLEROSIS (SCLERODERMA)a

A. Major criterion Proximal scleroderma: Symmetric thickening, tightening, and induration of the skin of the ﬁ ngers and the skin proximal to the metacarpophalangeal or metatarsophalangeal joints. The changes may affect the entire extremity, face, neck, and trunk (thorax and abdomen).

B. Minor criteria 1. Sclerodactyly: Above-indicated skin changes limited to the fi ngers 2. Digital pitting scars or loss of substance from the fi nger pad: Depressed areas at tips of fi ngers or loss of digital pad tissue as a result of ischemia 3. Bibasilar pulmonary fi brosis: Bilateral reticular pattern of linear or lineonodular densities most pronounced in basilar portions of the lungs on standard chest roentgenogram; may assume appearance of diffuse mottling or “honeycomb lung.” These changes should not be attributable to primary lung disease.

SOURCE: Adapted from Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Pre- liminary criteria for the classiﬁ cation of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:581–590, with permission of the American College of Rheumatology. a For the purposes of classifying patients in clinical trials, population surveys, and other studies, a person shall be said to have systemic sclerosis (scleroderma) if the one major or two or more minor criteria are present. Localized forms of scleroderma, eosinophilic fasciitis, and the various forms of pseudoscleroderma are excluded from these criteria. 676 APPENDIX I

CRITERIA FOR THE DIAGNOSIS OF POLYMYOSITIS AND DERMATOMYOSITISa

CRITERION DEFINITION

1. Symmetrical weakness Weakness of limb-girdle muscles and anterior neck ﬂ exors, progressing over weeks to months, with or without dysphagia or respiratory muscle involvement

2. Muscle biopsy evidence Evidence of necrosis of type I and n fi bers, phagocytosis, regeneration with basophilia, large vesicular sarcolemmal nuclei and prominent nucleoli, atrophy in a perifascicular distribution, variation in fi ber size, and an infl ammatory exudate, often perivascular

3. Elevation of muscle enzymes Elevation in serum of skeletal muscle enzymes, particularly creatine phosphokinase and often aldolase, serum glutamate oxaloacetate, and pyruvate transaminases, and lactate dehydrogenase

4. Electromyographic evidence Electromyographic triad of short, small, polyphasic motor units, ﬁ brillations, positive sharp waves, and insertional irritability, and bizarre, high-frequency repetitive discharges

5. Dermatologic features A lilac discoloration of the eyelids (heliotrope) with periorbital edema, a scaly, erythematous dermatitis over the dorsum of the hands (especially the metacarpophalangeal and proximal interphalangeal joints, Gottron’s sign), and involvement of the knees, elbows, and medial malleoli, as well as the face, neck, and upper torso

Data from Bohan A, Peter JB. Polymyositis and dermatomyositis (fi rst of two parts). N Engl J Med 1975;292:344–347, with permission. a Confi dence limits can be defi ned as follows: For a defi nite diagnosis of dermatomyositis, three of four criteria plus the rash must be present. For a defi nite diagnosis of polymyositis, four criteria must be present without the rash. For a probable diagnosis of dermatomyositis, two criteria plus the rash must be present. For a probable diagnosis of polymyositis, three criteria must be present without the rash. For a possible diagnosis of dermatomyositis, one criterion plus the rash must be present. For a possible diagnosis of polymyositis, two criteria must be present without the rash. The following fi ndings exclude a diagnosis of dermatomyositis or polymyositis. • Evidence of central or peripheral neurologic disease, including motor-neuron disorders with fasciculations or long-tract signs, sensory changes, decreased nerve conduction times, and fi ber-type atrophy and grouping on muscle biopsy. • Muscle weakness with a slowly progressive, unremitting course and a positive family history or calf enlargement to suggest a muscular dystrophy. • Biopsy evidence of granulomatous myositis such as with sarcoidosis. • Infections, including trichinosis, schistosomiasis, trypanosomiasis, staphylococcosis, and toxoplasmosis. • Recent use of various drugs and toxins, such as clofi brate and alcohol. • Rhabdomyolysis as manifested by gross myoglobinuria related to strenuous exercise, infections, crush injuries, occlusions of major limb arteries, prolonged coma or convulsions, high-voltage accidents, heat stroke, the malignant-hyperpyrexia syndrome, and envenomation by certain sea snakes. • Metabolic disorders such as McArdle’s syndrome. • Endocrinopathies such as thyrotoxicosis, myxedema, hyperparathyroidism, hypoparathyroidism, diabetes mellitus, or Cushing’s syndrome. • Myasthenia gravis with response to cholinergics, sensitivity to d-tubocurarine, and decremental response to repetitive nerve stimulation.

CRITERIA FOR THE CLASSIFICATION OF SJÖGREN’S SYNDROMEa

1. Ocular symptoms Deﬁ nition. A positive response to at least one of the following three questions: (a) Have you had daily, persistent, troublesome dry eyes for more than 3 months? (b) Do you have a recurrent sensation of sand or gravel in the eyes? (c) Do you use tear substitutes more than three times a day?

2. Oral symptoms Deﬁ nition. A positive response to at least one of the following three questions: (a) Have you had a daily feeling of dry mouth for more than 3 months? (b) Have you had recurrent or persistently swollen salivary glands as an adult? (c) Do you frequently drink liquids to aid in swallowing dry foods?

3. Ocular signs Deﬁ nition. Objective evidence of ocular involvement, determined on the basis of a positive result on at least one of the following two tests: (a) Schirmer-I test (≤5 mm in 5 minutes) (b) Rose bengal score (∼ 4, according to the van Bijsterveld scoring system)

4. Histopathologic features Defi nition. Focus score ∼ 1 on minor salivary gland biopsy (focus defi ned as an agglomeration of at least 50 mononuclear cells; focus score defi ned as the number of foci per 4 mm2 of glandular tissue) CRITERIA FOR THE CLASSIFICATION AND DIAGNOSIS 677

CRITERIA FOR THE CLASSIFICATION OF SJÖGREN’S SYNDROMEa (continued)

5. Salivary gland involvement Deﬁ nition. Objective evidence of salivary gland involvement, determined on the basis of a positive result on at least one of the following three tests: (a) Salivary scintigraphy (b) Parotid sialography (c) Unstimulated salivary ﬂ ow (≤ 1.5 mL in 15 minutes)

6. Autoantibodies Deﬁ nition. Presence of at least one of the following serum autoantibodies: (a) Antibodies to Ro/SS-A or La/SS-B antigens (b) Antinuclear antibodies (c) Rheumatoid factor

Exclusion criteria: preexisting lymphoma, acquired immunodeﬁ ciency syndrome, sarcoidosis, or graft-versus-host disease

SOURCE: Reprinted from Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classifi cation of Sjögren’s syndrome. Arthritis Rheum 1993;36:340–347, with permission of the American College of Rheumatology. a For primary Sjögren’s syndrome, the presence of three of six items showed a very high sensitivity (99.1%), but insuffi cient specifi city (57.8%). Thus, this combination could be accepted as the basis for a diagnosis of probable primary Sjögren’s syndrome. However, the presence of four of six items (accepting as serologic parameters only positive anti–Ro/SS-A and anti–La/SS-B antibodies) had a good sensitivity (93.5%) and specifi city (94.0%), and therefore may be used to establish a defi nitive diagnosis of primary Sjögren’s syndrome.

CRITERIA FOR THE CLASSIFICATION OF POLYARTERITIS NODOSAa

CRITERION DEFINITION

1. Weight loss ≥4 kg Loss of 4 kg or more of body weight since illness began, not due to dieting or other factors

2. Livedo reticularis Mottled reticular pattern over the skin of portions of the extremities or torso

3. Testicular pain or tenderness Pain or tenderness of the testicles, not due to infection, trauma, or other causes

4. Myalgias, weakness, or leg Diffuse myalgias (excluding shoulder and hip girdle) or weakness of muscles or tenderness of leg tenderness muscles

5. Mononeuropathy or Development of mononeuropathy, multiple mononeuropathies, or polyneuropathy polyneuropathy

6. Diastolic BP >90 mm Hg Development of hypertension with the diastolic BP higher than 90 mm Hg

7. Elevated BUN or creatinine Elevation of BUN >40 mg/dL or creatinine >1.5 mg/dL, not due to dehydration or obstruction APPENDIX I

8. Hepatitis B virus Presence of hepatitis B surface antigen or antibody in serum

9. Arteriographic abnormality Arteriogram showing aneurysms or occlusions of the visceral arteries, not due to arteriosclerosis, ﬁ bromuscular dysplasia, or other non-inﬂ ammatory causes

10. Biopsy of small or Histologic changes showing the presence of granulocytes or artery containing medium-sized polymorphonuclear leukocytes and mononuclear leukocytes in the artery wall

SOURCE: Reprinted from Lightfoot RW Jr, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classifi cation of polyarteritis nodosa. Arthritis Rheum 1990;33:1088–1093, with permission of the American College of Rheumatology. ABBREVIATIONS: BP, blood pressure; BUN, blood urea nitrogen. a For classifi cation purposes, a patient shall be said to have polyarteritis nodosa if at least 3 of these 10 criteria are present. The presence of any three or more criteria yields a sensitivity of 82.2% and a specifi city of 86.6%. 678 APPENDIX I

CRITERIA FOR THE CLASSIFICATION OF HENOCH–SCHONLEIN PURPURAa

CRITERION DEFINITION

1. Palpable purpura Slightly raised “palpable” hemorrhagic skin lesions, not related to thrombocytopenia

2. Age at disease onset Patient 20 years or younger at onset of ﬁ rst symptoms

3. Bowel angina Diffuse abdominal pain, worse after meals, or the diagnosis of bowel ischemia, usually including bloody diarrhea

4. Wall granulocytes on biopsy Histologic changes showing granulocytes in the walls of arterioles or venules

SOURCE: Reprinted from Mills JA, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classifi cation of Henoch–Schonlein purpura. Arthritis Rheum 1990;33:1114–1121, with permission of the American College of Rheumatology. a For purposes of classifi cation, a patient shall be said to have Henoch–Schonlein purpura if at least two of these four criteria are present. The presence of any two or more criteria yields a sensitivity of 87.1% and a specifi city of 87.7%.

CRITERIA FOR THE CLASSIFICATION OF CHURG–STRAUSS SYNDROMEa

CRITERION DEFINITION

1. Asthma History of wheezing or diffuse high-pitched rales on expiration

2. Eosinophilia Eosinophilia >10% on white blood cell differential count

3. Mononeuropathy or polyneuropathy Development of mononeuropathy, multiple mononeuropathies, or polyneuropathy (i.e., glove/stocking distribution) attributable to a systemic vasculitis

4. Pulmonary infi ltrates, nonfi xed Migratory or transitory pulmonary infi ltrates on radiographs (not including fi xed infi ltrates), attributable to a systemic vasculitis

5. Paranasal sinus abnormality History of acute or chronic paranasal sinus pain or tenderness or radiographic opaciﬁ cation of the paranasal sinuses

6. Extravascular eosinophils Biopsy including artery, arteriole, or venule, showing accumulations of eosinophils in extravascular areas

SOURCE: Adapted from Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classifi cation of Churg–Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094–1100, with permission of the American College of Rheumatology. a For classifi cation purposes, a patient shall be said to have Churg–Strauss syndrome if at least four of these six criteria are positive. The presence of any four or more of the six criteria yields a sensitivity of 85% and a specifi city of 99.7%.

CRITERIA FOR THE CLASSIFICATION OF WEGENER’S GRANULOMATOSISa

CRITERION DEFINITION

1. Nasal or oral inﬂ ammation Development of painful or painless oral ulcers or purulent or bloody nasal discharge

2. Abnormal chest radiograph Chest radiograph showing the presence of nodules, ﬁ xed inﬁ ltrates, or cavities

3. Urinary sediment Microhematuria (> 5 red blood cells per high power ﬁ eld) or red cell casts in urine sediment

4. Granulomatous inﬂ ammation Histologic changes showing granulomatous inﬂ ammation within the wall of an artery or in on biopsy the perivascular or extravascular area (artery or arteriole)

SOURCE: Reprinted from Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classifi cation of Wegener’s granulomatosis. Arthritis Rheum 1990;33:1101–1107, with permission of the American College of Rheumatology. a For purposes of classifi cation, a patient shall be said to have Wegener’s granulomatosis if at least two of these four criteria are present. The presence of any two or more criteria yields a sensitivity of 88.2% and a specifi city of 92.0%. CRITERIA FOR THE CLASSIFICATION AND DIAGNOSIS 679

CRITERIA FOR THE CLASSIFICATION OF GIANT CELL ARTERITISa

CRITERION DEFINITION

1. Age at disease onset ≥50 years Development of symptoms or ﬁ ndings beginning at age 50 or older

2. New headache New onset of or new type of localized pain in the head

3. Temporal artery abnormality Temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries

4. Elevated erythrocyte sedimentation rate Erythrocyte sedimentation rate ≥ 50 mm/hour by the Westergren method

5. Abnormal artery biopsy Biopsy specimen with artery showing vasculitis characterized by a predominance of mononuclear cell inﬁ ltration or granulomatous inﬂ ammation, usually with multinucleated giant cells

SOURCE: Reprinted from Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classifi cation of giant cell arteritis. Arthritis Rheum 1990;33:1122–1128, with permission of the American College of Rheumatology. a For purposes of classifi cation, a patient shall be said to have giant cell (temporal) arteritis if at least three of these fi ve criteria are present. The presence of any three or more criteria yields a sensitivity of 93.5% and a specifi city of 91.2%.

CRITERIA FOR THE CLASSIFICATION OF TAKAYASU ARTERITISa

CRITERION DEFINITION

1. Age at disease onset ≤40 years Development of symptoms or ﬁ ndings related to Takayasu arteritis at age ≤ 40 years

2. Claudication of extremities Development and worsening of fatigue and discomfort in muscles of one or more extremity while in use, especially the upper extremities

3. Decreased brachial artery pulse Decreased pulsation of one or both brachial arteries

4. BP difference >10 mm Hg Difference of >10 mm Hg in systolic blood pressure between arms

5. Bruit over subclavian arteries or aorta Bruit audible on auscultation over one or both subclavian arteries or abdominal aorta

6. Arteriogram abnormality Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities, not due to arteriosclerosis, ﬁ bromuscular dysplasia, or similar causes; changes usually focal or segmental

SOURCE: Reprinted from Arend WP, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classifi cation of Takayasu arteritis. Arthritis Rheum 1990;33:1129–1132, with permission of the American College of Rheumatology. ABBREVIATIONS: BP, blood pressure (systolic; difference between arms). APPENDIX I a For purposes of classifi cation, a patient shall be said to have Takayasu arteritis if at least three of these six criteria are present. The presence of any three or more criteria yields a sensitivity of 90.5% and a specifi city of 97.8%.

CRITERIA FOR THE CLASSIFICATION OF HYPERSENSITIVITY VASCULITIS.a

CRITERION DEFINITION

1. Age at disease onset >16 years Development of symptoms after age 16

2. Medication at disease onset Medication was taken at the onset of symptoms that may have been a precipitating factor

3. Palpable purpura Slightly elevated purpuric rash over one or more areas of the skin; does not blanch with pressure and is not related to thrombocytopenia

4. Maculopapular rash Flat and raised lesions of various sizes over one or more areas of the skin

5. Biopsy including arteriole and venule Histologic changes showing granulocytes in a perivascular or extravascular location

SOURCE: Reprinted from Calabrese LH, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classifi cation of hypersensitivity vasculitis. Arthritis Rheum 1990;33:1108–1113, with permission of the American College of Rheumatology. a For purposes of classifi cation, a patient shall be said to have hypersensitivity vasculitis if at least three of these fi ve criteria are present. The presence of any three or more criteria yields a sensitivity of 71.0% and a specifi city of 83.9%. DIAGNOSTIC GUIDELINES FOR KAWASAKI SYNDROME.a

1. Fever lasting >5 days:

Plus four of the following criteria:

2. Polymorphous rash

3. Bilateral conjunctival injection

4. One or more of the following mucous membrane changes: Diffuse injection of oral and pharyngeal mucosa Erythema or ﬁ ssuring of the lips Strawberry tongue

5. Acute, nonpurulent cervical lymphadenopathy (one lymph node must be >1.5 cm)

6. One or more of the following extremity changes: Erythema of palms and/or soles Indurative edema of hands and/or feet Membranous desquamation of the ﬁ ngertips

SOURCE: Reprinted from Kawasaki T, Kosaki T, Okawa S, et al. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 1974;54:271–276, with permission. a Other illnesses with similar clinical signs must be excluded.

CRITERIA FOR THE DIAGNOSIS OF BEHÇET’S DISEASE.a

CRITERION DEFINITION

1. Recurrent oral ulceration Minor aphthous, major aphthous, or herpetiform ulceration observed by physician or patient, which recurred at least three times in one 12-month period

Plus two of

2. Recurrent genital ulceration Aphthous ulceration or scarring, observed by physician or patient

3. Eye lesions Anterior uveitis, posterior uveitis, or cells in vitreous on slit lamp examination; or retinal vasculitis observed by ophthalmologist

4. Skin lesions Erythema nodosum observed by physician or patient, pseudofolliculitis, or papulopustular lesions; or acneiform nodules observed by physician in postadolescent patients not on corticosteroid treatment

5. Positive pathergy test Read by physician at 24–48 hours

SOURCE: Reprinted from International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990;335:1078–1080, with permission. a Findings applicable only in the absence of other clinical explanations. The presence of recurrent oral ulceration and any two of the remaining criteria yields a sensitivity of 91% and a speciﬁ city of 96%.

PRELIMINARY CLASSIFICATION CRITERIA FOR ANTIPHOSPHOLIPID SYNDROME.a

Vascular thrombosis (a) One or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ and (b) Thrombosis confi rmed by imaging or Doppler studies or histopathology, with the exception of superfi cial venous thrombosis and (c) For histopathologic confi rmation, thrombosis present without signifi cant evidence of infl ammation in the vessel wall.

Pregnancy morbidity (a) One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus or (b) One or more premature births of a morphologically normal neonate at or before the 34th week of gestation because of severe pre-eclampsia or severe placental insufﬁ ciency or (c) Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.

Laboratory criteria (a) Anticardiolipin antibody of IgG and/or IgM isotype in blood, present in medium or high titer on two or more occasions at least

6 weeks apart, measured by standard enzyme-linked immunosorbent assay for beta2 glycoprotein l–dependent anticardiolipin antibodies or (b) Lupus anticoagulant present in plasma on two or more occasions at least 6 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Hemostasis.

SOURCE: Adapted from Wilson WA, Gharavi AE. Koike T, et al. International consensus statement on preliminary classifi cation criteria for defi nite antiphospholipid syndrome. Report of an International Workshop. Arthritis Rheum 1999;42:1309–1311 with permission of the American College of Rheumatology. a Defi nite APS is considered to be present if at least one of the clinical and one of the laboratory criteria are met. CRITERIA FOR THE CLASSIFICATION AND DIAGNOSIS 681

WORLD HEALTH ORGANIZATION CRITERIA FOR THE DIAGNOSIS OF OSTEOPENIA AND OSTEOPOROSIS.

Normal BMC or BMD not more than 1 standard deviation below peak adult bone mass T score >−1

Osteopenia BMC or BMD that lies between 1 and 2.5 standard deviations below peak adult bone mass T score between −1 and −2.5

Osteoporosis BMC or BMD value more than 2.5 standard deviations below peak adult bone mass T score ≤−2.5

Severe Osteoporosis BMC or BMD value more than 2.5 standard deviations below peak adult bone mass and the presence of one or more fragility fractures T score ≤−2.5 plus fragility fracture

SOURCE: Adapted from Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO study group. World Health Organ Techn Rep Ser 1994;843:1–129. a World Health Organization criteria for the diagnosis of osteoporosis based on bone mineral content (BMC) or bone mineral density (BMD) measurements. These criteria can be applied to either the central or peripheral skeletal measurement sites.

CRITERIA FOR THE DIAGNOSIS OF JUVENILE RHEUMATOID ARTHRITIS (JRA).

I. General The JRA Criteria Subcommittee in 1982 reviewed the 1977 Criteria (1) and recommended that juvenile rheumatoid arthritis be the name for the principal form of chronic arthritic disease in children and that this general class should be classifi ed into three onset subtypes: systemic, polyarticular, and pauciarticular. The onset subtypes may be further subclassifi ed into subsets as indicated below. The following classifi cation enumerates the requirements for the diagnosis of JRA and the three clinical onset subtypes and lists subsets of each subtype that may be useful in further classifi cation.

II. General criteria for the diagnosis of juvenile rheumatoid arthritis A. Persistent arthritis of at least 6 weeks’ duration in one or more joints B. Exclusion of other causes of arthritis (see list of exclusions)

III. JRA onset subtypes The onset subtype is determined by manifestations during the fi rst 6 months of disease and remains the principal classifi cation, although manifestations more closely resembling another subtype may appear later. A. Systemic onset JRA: This subtype is defi ned as JRA with persistent intermittent fever (daily intermittent temperatures to 103°F or more) with or without rheumatoid rash or other organ involvement. Typical fever and rash will be considered probable systemic onset JRA if not associated with arthritis. Before a defi nite diagnosis can be made, arthritis, as defi ned, must be present. B. Pauciarticular onset JRA: This subtype is defi ned as JRA with arthritis in four or fewer joints during the fi rst 6 months of disease. Patients with systemic onset JRA are excluded from this onset subtype. C. Polyarticular JRA: This subtype is defi ned as JRA with arthritis in fi ve or more joints during the fi rst 6 months of disease. Patients with systemic JRA onset are excluded from this subtype. D. The onset subtypes may include the following subsets: 1. Systemic onset a. Polyarthritis b. Oligoarthritis APPENDIX I 2. Oligoarthritis (pauciarticular onset) a. Antinuclear antibody (ANA)–positive chronic uveitis b. Rheumatoid factor (RF) positive c. Seronegative, B27 positive d. Not otherwise classifi ed 3. Polyarthritis a. RF positivity b. Not otherwise classifi ed

IV. Exclusions A. Other rheumatic diseases 1. Rheumatic fever 2. Systemic lupus erythematosus 3. Ankylosing spondylitis 4. Polymyositis or dermatomyositis 5. Vasculitic syndromes 6. Scleroderma 7. Psoriatic arthritis 8. Reiter’s syndrome 9. Sjögren’s syndrome 10. Mixed connective tissue disease 11. Behçet’s syndrome

(continued) 682 APPENDIX I

CRITERIA FOR THE DIAGNOSIS OF JUVENILE RHEUMATOID ARTHRITIS (JRA). (continued)

IV. Exclusions B. Infectious arthritis C. Inﬂ ammatory bowel disease D. Neoplastic diseases including leukemia E. Nonrheumatic conditions of bones and joints F. Hematologic diseases G. Psychogenic arthralgia H. Miscellaneous 1. Sarcoidosis 2. Hypertrophic osteoarthropathy 3. Villonodular synovitis 4. Chronic active hepatitis 5. Familial Mediterranean fever

V. Other proposed terminology Juvenile chronic arthritis (JCA) and juvenile arthritis (JA) are new diagnostic terms currently in use in some places for the arthritides of childhood. The diagnoses of JCA and JA are not equivalent to each other, nor to the older diagnosis of juvenile rheumatoid arthritis or Still’s disease. Hence reports of studies of JCA or JA cannot be directly compared with one another nor to reports of JRA or Still’s disease. Juvenile chronic arthritis is described in more detail in a report of the European Conference on the Rheumatic Diseases of Children (2) and juvenile arthritis in the report of the Ross Conference (3).

1. JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Current proposed revisions of the JRA criteria. Arthritis Rheum 1977;20(Suppl):195–199. 2. Ansell BW. Chronic arthritis in childhood. Ann Rheum Dis 1978;37:107–120. 3. Fink CW. Keynote address: Arthritis in childhood. Report of the 80th Ross Conference in Pediatric Research. Columbus, OH: Ross Laboratories; 1979:1–2. APPENDIX II Guidelines for the Management of Rheumatic Diseases

Practice guidelines represent a recent and important practice and serve a valuable educational function for development in rheumatology. Guidelines, which are students of the rheumatic diseases. Moreover, because developed by a panel of experts, address a broad range in very few instances have guidelines been tested in of clinical issues from the approach to diagnosis of mus- clinical settings, they present an opportunity to study culoskeletal signs and symptoms to patient manage- whether they result in efﬁ ciencies or improvements in ment. Guidelines provide a framework for clinical diagnosis and patient management.

INITIAL EVALUATION OF THE ADULT PATIENT WITH ACUTE MUSCULOSKELETAL SYMPTOMS.

FEATURE DIFFERENTIAL DIAGNOSIS

History of signiﬁ cant trauma Soft tissue injury, internal derangement, or fracture

Hot, swollen joint Infection, systemic rheumatic disease, gout, pseudogout

Constitutional signs and symptoms Infection, sepsis, systemic rheumatic disease (e.g., fever, weight loss, malaise)

Weakness Focal Focal nerve lesion (compartment syndrome, entrapment neuropathy, mononeuritis multiplex, motor neuron disease, radiculopathya) Diffuse Myositis, metabolic myopathy, paraneoplastic syndrome, degenerative neuromuscular disorder, toxin, myelopathy,a transverse myelitis

Neurogenic pain (burning, numbness, paresthesia) Asymmetric Radiculopathy,a reﬂ ex sympathetic dystrophy, entrapment neuropathy Symmetric Myelopathy,a peripheral neuropathy

Claudication pain pattern Peripheral vascular disease, giant cell arteritis (jaw pain), lumbar spinal stenosis

SOURCE: Reprinted from American College of Rheumatology Ad Hoc Committee on Clinical Guidelines: guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. Arthritis Rheum 1996;39:1–8, with permission of the American College of Rheumatology. a Radiculopathy and myelopathy may be due to infectious, neoplastic, or mechanical processes.

RECOMMENDED MONITORING STRATEGIES FOR DRUG TREATMENT OF RHEUMATOID ARTHRITIS.a

TOXICITIES MONITORING REQUIRING BASELINE SYSTEM DRUGS MONITORINGb EVALUATION REVIEW/EXAMINATION LABORATORY

Salicylates, nonsteroidal Gastrointestinal CBC, creatinine, AST, Dark/black stool, CBC yearly, LFTs, creatinine anti-inﬂ ammatory drugs ulceration and ALT dyspepsia, nausea or testing may be requiredc bleeding vomiting, abdominal pain, edema, shortness of breath

Hydroxychloroquine Macular damage None unless patient is Visual changes, — over age 40 or has funduscopic and previous eye visual ﬁ elds every disease 6–12 months

(continued) 683 684 APPENDIX II

RECOMMENDED MONITORING STRATEGIES FOR DRUG TREATMENT OF RHEUMATOID ARTHRITIS.a (continued)

TOXICITIES MONITORING REQUIRING BASELINE SYSTEM DRUGS MONITORINGb EVALUATION REVIEW/EXAMINATION LABORATORY

Sulfasalazine Myelosuppression CBC, and AST or ALT Symptoms of CBC every 2–4 weeks for in patients at risk, myelosuppression,d ﬁ rst 3 months, then every G6PD photosensitivity, rash 3 months

Methotrexate Myelosuppression, CBC, chest Symptoms of CBC, platelet count, AST, hepatic fi brosis, radiography within myelosuppression,d albumin, creatinine every cirrhosis, pulmonary past year, hepatitis shortness of breath, 4–8 weeks infi ltrates or fi brosis B and C serology in nausea/vomiting, high-risk patients, lymph node swelling AST or ALT, albumin, alkaline phosphatase, and creatinine

Gold, intramuscular Myelosuppression, CBC, platelet count, Symptoms of CBC, platelet count, urine proteinuria creatinine, urine myelosuppression,d dipstick every 1–2 weeks dipstick for protein edema, rash, oral for ﬁ rst 20 weeks, then at ulcers, diarrhea the time of each (or every other} injection

Gold, oral Myelosuppression, CBC, platelet count, Symptoms of CBC platelet count, urine proteinuria urine dipstick for myelosuppression,d dipstick for protein every protein edema, rash, 4–12 weeks diarrhea

D-penicillamine Myelosuppression, CBC, platelet count, Symptoms of CBC, urine dipstick for proteinuria creatinine, urine myelosuppressiond, protein every 2 weeks dipstick for protein edema, rash until dosage stable, then every 1–3 months

Azathioprine Myelosuppression, CBC, platelet count, Symptoms of CBC and platelet count every hepatotoxicity, creatinine, AST or myelosuppressiond 1–2 weeks with changes lymphoproliferative ALT in dosage, and every 1–3 disorders months thereafter

Corticosteroids (oral ≤ Hypertension, BP, chemistry panel, BP at each visit, Urinalysis for glucose yearly 10 mg of prednisone or hyperglycemia bone densitometry polyuria, polydipsia, equivalent) in high-risk patients edema, shortness of breath, visual changes, weight gain

Agents for refractory RA or severe extra-articular complications

Cyclophosphamide Myelosuppression, CBC, platelet count, Symptoms of CBC and platelet count every myeloproliferative urinalysis, myelosuppression,d 1–2 weeks with changes disorders, creatinine, AST or hematuria in dosage, and every 1–3 malignancy, ALT months thereafter, hemorrhagic cystitis urinalysis and urine cytology every 6–12 months after cessation

Chlorambucil Myelosuppression, CBC, urinalysis, Symptoms of CBC and platelet count every myeloproliferative creatinine, AST or myelosuppressiond 1–2 weeks with changes disorders, ALT in dosage, and every 1–3 malignancy months thereafter

Cyclosporin A Renal insufﬁ ciency, CBC, creatinine, uric Edema, BP every 2 Creatinine every 2 weeks anemia, acid, LFTs, BP weeks until dosage until dose is stable, then hypertension stable, then monthly monthly; periodic CBC, potassium, and LFTs GUIDELINES FOR THE MANAGEMENT OF RHEUMATIC DISEASES 685

ANTIRHEUMATIC DRUG THERAPY IN PREGNANCY AND LACTATION, AND EFFECTS ON FERTILITY.

FDA USE-IN- MAJOR PREGNANCY CROSSES MATERNAL FETAL DRUG RATINGa PLACENTA TOXICITIES TOXICITIES LACTATION FERTILITY

Aspirin C; D in third Yes Anemia, Premature Use cautiously; No data trimester peripartum closure of excreted at low hemorrhage, ductus, concentration; prolonged pulmonary doses >1 tablet labor hypertension, (325 mg) result in ICH high concentration in infant plasma

NSAIDs B; D in third Yes As for aspirin As for aspirin Compatible No data trimester according to AAP

Corticosteroids Prednisone B Dexamethasone Exacerbation IUGR 5% to 20% of and beta- of diabetes maternal dose methasone and excreted in breast hyperten- milk; compatible, sion, PROM but wait 4 hours if dose >20 mg Dexamethasone C As above

Hydroxychloroquine C Yes: fetal Few Few Contraindicated No data concentration (slow elimination 50% of rate, potential for maternal accumulation)

Gold C Yes No data 1 report of cleft Excreted into breast No data palate and milk (20% of severe CNS maternal dose); abnormalities rash, hepatitis, and hematologic abnormalities reported, but AAP considers it compatible

D-penicillamine D Yes No data Cutis laxa No data No data connective tissue abnormalities APPENDIX II Sulfasalazine B; D if near Yes No data No increase in Excreted into breast Females: no term congenital milk (40% to 60% effect; males: malformation, maternal dose); signiﬁ cant kernicterus if bloody diarrhea in oligospermia administered 1 infant; AAP (2 months to near term recommends return to caution normal)

Azathioprine D Yes No data IUGR (rate up to No data; hypotheti- Not studied; can 40%) and cal risk of interfere with prematurity, immunosuppres- effectiveness of transient sion outweighs IUD immunosup- beneﬁ t pression in neonate, possible effect on germlines of offspring

(continued) 686 APPENDIX II

ANTIRHEUMATIC DRUG THERAPY IN PREGNANCY AND LACTATION, AND EFFECTS ON FERTILITY. (continued)

FDA USE-IN- MAJOR PREGNANCY CROSSES MATERNAL FETAL DRUG RATINGa PLACENTA TOXICITIES TOXICITIES LACTATION FERTILITY

Chlorambucil D Teratogenic No data Renal Contraindicated No data effects angiogenesis potentiated by caffeine

Methotrexate X No data Spontaneous Fetal Contraindicated; Females: abortion abnormalities small amounts Infrequent (including excreted with long-term cleft palate potential to effect; males: and accumulate in reversible hydrocephalus) fetal tissues oligospermia

Cyclophosphamide D Yes: 25% of No data Severe abnor- Contraindicated; has Females: age maternal malities; case caused bone >25 years, level report: male marrow concurrent twin devel- depression radiation, and oped prolonged papillary exposure cancer at increase risk of 11 years and infertility; neuroblas- males: dose- toma at dependent 14 years oligospermia and azoosper- mia regardless of age or exposure

Cyclosporin A C Yes No data IUGR and Contraindicated due No data prematurity; to potential for 1 case report: immunosuppression hypoplasia of right leg; not an animal teratogen and unlikely to be a human one

SOURCE: Reprinted from American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723–731, with permission of the American College of Rheumatology. ABBREVIATIONS: AAP, American Academy of Pediatrics; CNS, central nervous system; ICH, intracranial hemorrhage; IUD, intrauterine device; IUGR, intrauterine growth retardation; PROM, premature rupture of membranes. a Food and Drug Administration (FDA) use-in-pregnancy ratings are as follows: A, controlled studies show no risk. Adequate, well-controlled studies in pregnant women have failed to demonstrate risk to the fetus. B, No evidence of risk in humans. Either animal fi ndings show risk but human fi ndings do not, or, if no adequate human studies have been performed, animal fi ndings are negative. C, Risk cannot be ruled out. Human studies are lacking and results of animal studies are either positive for fetal risk or lacking as well. However, potential benefi ts may justify the potential risk. D, Positive evidence of risk. Investigational or post-marketing data show risk to the fetus. Nevertheless, potential benefi ts may outweigh the potential risk. X, Contraindicated in pregnancy. Studies in animals or humans, or investigational or postmarketing reports, have shown fetal risk which clearly outweighs any possible benefi t to the patient. GUIDELINES FOR THE MANAGEMENT OF RHEUMATIC DISEASES 687

MONITORING DRUG THERAPY IN SYSTEMIC LUPUS ERYTHEMATOSUS.

TOXICITIES MONITORING REQUIRING DRUG MONITORING Baseline evaluation System review Laboratory

Salicylates, NSAIDs Gastrointestinal bleeding, CBC, creatinine, Dark/black stool, CBC yearly, creatinine yearly hepatic toxicity, renal urinalysis, AST, ALT dyspepsia, nausea/ toxicity, hypertension vomiting, abdominal pain, shortness of breath, edema

Glucocorticoids Hypertension, hyperglyce- BP, bone densitometry, Polyuria, polydipsia, Urinary dipstick for glucose mia, hyperlipidemia, glucose, potassium, edema, shortness of every 3–6 months, total hypokalemia, osteopo- cholesterol, triglycer- breath, BP at each cholesterol yearly, bone rosis, avascular necrosis, ides (HDL, LDL) visit, visual changes, densitometry yearly to cataract, weight gain, bone pain assess osteoporosis infections, ﬂ uid retention

Hydroxychloroquine Macular damage None unless patient is Visual changes Fundoscopic and visual ﬁ elds over 40 years of age every 6–12 months or has previous eye disease

Azathioprine Myelosuppression, CBC, platelet count, Symptoms of CBC and platelet count every hepatotoxicity, lympho- creatinine, AST or myelosuppression 1–2 weeks with changes in proliferative disorders ALT dose (every 1–3 months thereafter), AST yearly, Pap test at regular intervals

Cyclophosphamide Myelosuppression, CBC and differential Symptoms of myelo- CBC and urinalysis monthly, myeloproliferative and platelet count, suppression, urine cytology and Pap test disorders, malignancy, urinalysis hematuria, infertility yearly for life immunosuppression, hemorrhagic cystitis, secondary infertility

Methotrexate Myelosuppression, hepatic CBC, chest radiograph Symptoms of myelo- CBC and platelet count, AST fi brosis, cirrhosis, within past year, suppression, or ALT, and albumin every pulmonary infi ltrates, hepatitis B and C shortness of breath, 4–8 weeks, serum fi brosis serology in high-risk nausea/vomiting, creatinine, urinalysis patients, AST, oral ulcer albumin, bilirubin, creatinine APPENDIX II

SOURCE: Reproduced from Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum 1999;42:1785–1796, with permission of the American College of Rheumatology. ABBREVIATIONS: ALT, alanine transaminase; AST, aspartate transaminase; BP, blood pressure; CBC, complete blood cell count; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Pap, Papanicolaou. 688 APPENDIX II

GUIDELINES FOR CLINICAL USE OF THE ANTINUCLEAR ANTIBODY TEST: CONDITIONS ASSOCIATED WITH POSITIVE IF- ANA TEST RESULTS.a

DISEASE FREQUENCY OF POSITIVE ANA RESULT (%)

Diseases for which an ANA test is very useful for diagnosis SLE 95–100 Systemic sclerosis (scleroderma) 60–80

Diseases for which an ANA test is somewhat useful for diagnosis Sjögren’s syndrome 40–70 Idiopathic inﬂ ammatory myositis (dermatomyositis or polymyositis) 30–80

Diseases for which an ANA test is useful for monitoring or prognosis Juvenile chronic oligoarticular arthritis with uveitis 20–50 Raynaud’s phenomenon 20–60

Conditions in which a positive ANA test result is an intrinsic part of the diagnostic criteria Drug-induced SLE ∼100 Autoimmune hepatic disease ∼100 MCTD ∼100

Diseases for which an ANA test is not useful in diagnosis Rheumatoid arthritis 30–50 Multiple sclerosis 25 Idiopathic thrombocytopenic purpura 10–30 Thyroid disease 30–50 Discoid lupus 5–25 Infectious diseases Varies widely Malignancies Varies widely Patients with silicone breast implants 15–25 Fibromyalgia 15–25 Relatives of patients with autoimmune diseases (SLE or scleroderma) 5–25

Normal personsa ≥1 : 40 20–30 ≥1 : 80 10–12 ≥1 : 160 5 ≥1 : 320 3

ABBREVIATIONS: ANA, antinuclear antibody; IF, immunoﬂ uorescent; MCTD, mixed connective tissue disease; SLE, systemic lupus erythematosus. a Values are titers. Prevalence of positive ANA test result varies with titer. Female sex and increasing age tend to be more commonly associated with positive ANA. GUIDELINES FOR THE MANAGEMENT OF RHEUMATIC DISEASES 689

FLOW CHART FOR CLINICAL ANTINUCLEAR ANTIBODY TESTING.

Clinician suspects LE or other rheumatic condition in table

ANA testing is YES NO not indicated Perform ANA test

Test positive Test negative

How should a positive No further autoantibody testing is indicated. result be interpreted? Follow patient clinically, and consider repeat testing if indicated clinically. Does the patient have one of the conditions listed in table? Further testing for other autoantibodies is driven by specific clinical findings/impressions Is further testing indicated?

Clinician SLE has been Sjogren’s¨ has been Clinician suspects Clinician suspects Clinician suspects Clinician sus- suspects LE diagnosed diagnosed polymyositis or scleroderma or mixed connective pects drug- but the dermatomyositis or has established this tissue disease induced LE diagnosis has established this diagnosis needs to be diagnosis confirmed Information regarding Consider Consider Consider No further Consider Consider prognosis is testing for testing for testing for testing is testing for testing for desired anti-Ro/SSA anti-Jo-1 anti-Scl-70 indicated anti-RNP anti-dsDNA and anti-La/ and anti-Sm SSB

Consider anti-dsDNA Consider testing for testing anti-Ro/SSA Correlate with clinical findings

SOURCE: Reprinted from Kavanaugh A, Tomar R, Reveille J, et al. Guidelines for clinical use of the antinuclear antibody test and tests for speciﬁ c autoantibodies APPENDIX II to nuclear antigens. Arch Pathol Lab Med 2000;124:71–81, with permission of the College of American Pathologists. ABBREVIATIONS: LE, lupus erythematosus; RNP, ribonucleoprotein. 690 APPENDIX II

RECOMMENDATIONS FOR THE MEDICAL RECOMMENDATIONS FOR THE PREVENTION AND MANAGEMENT OF OSTEOARTHRITIS OF THE HIP AND TREATMENT OF GLUCOCORTICOID-INDUCED KNEE. OSTEOPOROSIS.

Nonpharmacologic therapy for patients with osteoarthritis Patient beginning therapy with glucocortocoid (prednisone Patient education equivalents of ≥5 mg/day) with plans for treatment Self-management programs (e.g., Arthritis Foundation Self- duration of ≥3 months Management Program) Modify lifestyle risk factors for osteoporosis Personalized social support through telephone contact Smoking cessation or avoidance Weight loss (if overweight) Reduction of alcohol consumption if excessive Aerobic exercise programs Instruct in weight-bearing physical exercise Physical therapy Initiate calcium supplementation Range-of-motion exercises Initiate supplementation with vitamin D (plain or activated form) Muscle-strengthening exercises Prescribe bisphosphonate (use with caution in premenopausal Assistive devices for ambulation women) Patellar taping Appropriate footwear Patient receiving long-term glucocorticoid therapy Lateral-wedged insoles (for genu varum) (prednisone equivalent of ≥5 mg/day) Bracing Modify lifestyle risk factors for osteoporosis Occupational therapy Smoking cessation or avoidance Joint protection and energy conservation Reduction of alcohol consumption if excessive Assistive devices for activities of daily living Instruct in weight-bearing physical exercise Initiate calcium supplementation Pharmacologic therapy for patients with osteoarthritisa Initiate supplementation with vitamin D (plain or activated form) ORAL Prescribe treatment to replace gonadal sex hormones if defi cient Acetaminophen or otherwise clinically indicated COX-2–specifi c inhibitor Measure bone mineral density (BMD) at lumbar spine and/or hip Nonselective NSAID plus misoprostol or a proton pump If BMD is not normal (i.e., T score below −1), then inhibitorb Prescribe bisphosphonate (use with caution in premenopausal Nonacetylated salicylate women) Other pure analgesics Consider calcitonin as second-line agent if patient has Tramadol contraindication to or does not tolerate bisphosphonate Opioids therapy INTRA-ARTICULAR If BMD is normal, follow-up and repeat BMD measurement Glucocorticoids either annually or biannually. Hyaluronan Topical SOURCE: Reprinted from American College of Rheumatology Ad Hoc Capsaicin Committee on Glucocorticoid-Induced Osteoporosis. Recommendations Methylsalicylate for the prevention and treatment of glucocorticoid-induced osteoporosis. 2001 update. Arthritis Rheum 2001;44:1496–1503, with permission of the American College of Rheumatology. SOURCE: Reprinted from American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 2000;43:1905– 1915, with permission of the American College of Rheumatology. ABBREVIATIONS: COX-2, cyclooxygenase-2; NSAID, nonsteroidal anti-infl ammatory drug. a The choice of agent(s) should be individualized for each patient. b Misoprostol and proton pump inhibitors are recommended in patients who are at increased risk for upper gastrointestinal adverse events. APPENDIX III Supplement and Vitamin and Mineral Guide

SUPPLEMENTS ASU (Avocado Soybean Unsaponiﬁ ables)

Originally published in Arthritis Today, September– Origin: A natural vegetable extract made from avocado October 2006, reprinted by permission of the Arthritis and soybean oils. Foundation. Dosage: Softgel; take 300 mg daily. Claims: Slows the progression of osteoarthritis (OA).

Supplements by Condition Black Currant Oil (Ribes nigrum; see GLA) or Symptom Origin: Black currant seed oil is obtained from seeds of Cartilage Degeneration: ASU, Chondroitin, Glucos- the black currant. Black currant seed oil contains amine, SAM-e 15% to 20% gamma-linolenic acid (GLA). Do not Decreased Mobility: Chondroitin, DMSO, Flax, GLA, confuse with black currant berry. Glucosamine, Indian frankincense, MSM, SAM-e Dosage: Liquid and capsules; typical dosage ranges Depression: St. John’s wort, SAM-e from 360 mg to 3000 mg daily. Infl ammation: Bromelain, Cat’s claw, Chondroitin, Devil’s claw, DMSO, Fish oil, Flax, Ginger; GLA, Caution: Black currant oil may increase immune MSM, SAM-e, Stinging nettle, Thunder god vine, response in elderly. Turmeric Pain: Bromelain, Chondroitin, Devil’s claw, DMSO, Borage Oil (Borago offi cinalis; see GLA) Ginger, GLA, Glucosamine, Indian frankincense, MSM, SAM-e, Stinging nettle, Thunder god vine, Origin: Oil from the seeds of the borage plant. Borage Turmeric seed oil contains about 20% to 26% GLA. Sleep Diffi culties: Melatonin, Valerian Dosage: Liquid and capsules; take 1300 mg (oil) daily. Ankylosing spondylitis: DHEA, Melatonin Fibromyalgia: SAM-e, St. John’s wort, Valerian Boswellia Gout: Devil’s claw, Stinging nettle Lupus: DHEA, Fish oil, Flax, Thunder god vine See Indian Frankincense Osteoarthritis (OA): ASU, Bromelain, Cat’s claw, Chondroitin, Devil’s claw, DMSO, Ginger; Bromelain (Pineapple, Ananas comosus) Glucosamine, Indian frankincense, MSM, SAM-e, Stinging nettle, Turmeric Origin: Group of enzymes found in pineapple that break Psoriasis: Fish oil down protein. Raynaud’s phenomenon: Evening primrose, Flax, Dosage: Capsules and tablets; take 500 to 2000 mg three Ginger, Ginkgo, GLA times a day between meals. Rheumatoid arthritis (RA): Black currant oil (or seed), Claims: Decreases pain and swelling of rheumatoid Borage oil (or seed), Bromelain, DMSO, Evening arthritis (RA) and OA, and increases mobility. primrose, Fish oil, Flax oil (or seed), Ginger, GLA, Indian frankincense/boswellia, Thunder god vine, Caution: Bromelain can cause stomach upset and diar- Turmeric rhea and should be avoided if the patient is allergic Scleroderma: DMSO to pineapples. It can also increase the effect of blood- Sjögren’s Syndrome: GLA thinning medicine. 691 692 APPENDIX III

Cat’s Claw (Uncaria tomentosa) Claims: Relieves pain and inﬂ ammation. May help lower uric acid levels in people with gout. Acts as a Origin: Dried root bark of a woody vine that grows in digestive aid and appetite stimulant. the Amazon rain forests in Peru and other South American countries. Caution: Devil’s claw should not be taken in patients Dosage: Capsules, tablets, liquid, and tea bags; 250 who are pregnant, have gallstones or ulcers, or are to 1000 mg daily. Buy only products that contain taking an antacid or blood thinners. It can affect Uncaria tomentosa. Another plant (Acacia heart rate and may interfere with cardiac, blood- greggi), which also has the name cat’s claw, is thinning, and diabetes medications. It may also cause highly toxic. diarrhea. Claims: Believed to have anti-inﬂ ammatory properties; may stimulate immune system. DHEA (Dehydroepiandrosterone)

Caution: Cat’s claw can cause headache, dizziness, and Origin: An androgen steroid hormone naturally pro- vomiting, and can lower blood pressure, should be duced in the body by the adrenal glands. Do not avoided with anti-hypertensive medications or blood confuse 7-Keto DHEA with DHEA. thinners. Dosage: Capsule and tablets available both as prescription (200 mg) and nonprescription (10, 15, or 25 mg) Chondroitin Sulfate products; typically 200 mg for lupus. Effects of long- term use are unknown. Origin: Chondroitin is a component of human connec- Claims: Helps control lupus fl ares; increases the blood tive tissues found in cartilage and bone. In supple- level of DHEA. ments, chondroitin sulfate usually comes from bovine trachea or pork byproducts. Caution: DHEA side effects include stomach upset, Dosage: Capsules, tablets, and powder; 800 to 1200 mg abdominal pain, and high blood pressure, as well as daily in two to four divided doses. Often combined acne. It also decreases levels of good cholesterol (high- with glucosamine. Allow up to 1 month to notice density lipoprotein, or HDL) and may cause facial hair effect. growth, voice deepening, and changes in menstrual Claims: Reduces pain and infl ammation, improves joint pattern. DHEA can also increase insulin resistance for function and slows progression of OA. people with diabetes, and exacerbate liver disease. Use is contraindicated in men with prostate cancer and Caution: Some chondroitin tablets may contain high women with uterine fi broids. levels of manganese, which may be problematic with long-term use. Because chondroitin is made from DMSO (Dimethyl Sulfoxide; see MSM) bovine products, there is the remote possibility of con- tamination associated with mad cow disease. Chon- Origin: A colorless, sulfur-containing organic byprod- droitin taken with blood-thinning medications or uct of wood pulp processing. NSAIDs may increase the risk of bleeding. In patients Dosage: Cream, gel; topically, 25% DMSO solution; who are allergic to sulfonamides, start with a low dose take internally, only if prescribed by a physician. of chondroitin sulfate and watch for any side effects. Claims: Relieves pain and infl ammation, improves joint Other side effects include diarrhea, constipation, and mobility in OA, RA, juvenile rheumatoid arthritis abdominal pain. (JRA), and scleroderma, and manages amyloidosis. Increases blood fl ow to skin. Curcumin Studies: Controlled studies as a topical application for DMSO and OA have yielded confl icting results. Few See Turmeric human studies.

Devil’s Claw (Also known as Devil’s Claw Root, Caution: Side effects of DMSO taken internally include Grapple Plant or Wood Spider; Harpagophytum headache, dizziness, drowsiness, nausea, vomiting, procumbens) diarrhea, constipation, and anorexia. Topical DMSO also can cause skin irritation and dermatitis. Avoid Origin: A traditional herb used in South Africa. in patients with diabetes, asthma, or liver, kidney, or heart conditions. Never take industrial-grade DMSO. Dosage: Capsules, tincture, powder, and liquid; take 750 Wash off any lotions or skin products before applying to 1000 mg three times a day. DMSO. SUPPLEMENT AND VITAMIN AND MINERAL GUIDE 693

Evening Primrose (Also known as Evening Primrose fl our; 30 g (1 ounce) daily. Capsules, available in Oil or Primrose; Oenothera biennis and other Oeno- 1000 mg to 1300 mg, no typical dosage. Oil, 1 to 3 thera species; see GLA) tablespoons daily. Claims: Eases symptoms of RA, lupus, and Raynaud’s Origin: The seeds of a native American wildfl ower, phenomenon. Lubricates joints and lessens stiffness containing 7% to 10% gamma-linolenic acid and joint pain. Lowers total cholesterol and reduces (GLA). risk of heart disease and some types of cancer. Dosage: Capsules, oil, and softgel; generally fi ve 500-mg Improves hot fl ashes and dry skin. capsules per day. For RA, 540 mg daily to 2.8 g daily in divided doses. Evening primrose oil may take up Caution: Fiber in fl axseed can impair absorption of to 6 months to work. some medications, and as fl axseed acts as a blood thinner, should be avoided in patients taking blood thin- Fish Oil ners, aspirin, or other NSAIDs. Flaxseed should be avoided in hormone-sensitive breast or uterine cancer, Origin: Oil from cold-water fi sh such as mackerel, and used with caution with the use of hypercholesterol- salmon, herring, tuna, halibut, and cod. emia and cholesterol-lowering drugs. Dosage: Fish, capsules, or chewable tablets. For general health, two 3-ounce servings of fi sh a week are rec- Ginger (Zingiber offi cinale) ommended. However, it’s diffi cult to get a therapeutic dose of fi sh oil from food alone. To treat Origin: The dried or fresh root of the ginger plant. arthritis-related conditions, use fi sh oil capsules with Dosage: Powder, extract, tincture, capsules, and oils; up at least 30% EPA/DHA, the active ingredients. For to 2 g in three divided doses per day or up to 4 cups lupus and psoriasis, 2 g EPA/DHA three times a day. of tea daily. For Raynaud’s phenomenon, 1 g four times a day. Claims: Decreases joint pain and reduces infl ammation For RA, up to 2.6 g fi sh oil (1 .6 g EPA) twice a in people with OA and RA. Increases circulation in day. people with Raynaud’s phenomenon. Claims: Reduces infl ammation and morning stiffness. Studies: A recent study showed that ginger extract Treats RA, lupus, psoriasis, depression, and inhibited infl ammatory molecules, including TNF- Raynaud’s phenomenon. Important for brain func- alpha and cyclooxygenase-2 (COX-2). A 2005 tion and may inhibit RA development. study reinforced the anti-infl ammatory effects of Studies: An analysis of nine studies of people with RA ginger. Another 2005 study showed ginger killed taking omega 3 showed a reduction in the number of Helicobacter pylori, a bacterium that causes stomach tender joints but no reduction in joint damage. In six ulcers. studies, people with RA were able to reduce their dosages of NSAIDs or corticosteroids. A 2005 study Caution: Ginger can interfere with medications for of people with RA showed enhanced positive effects blood thinning and should be avoided in the presence when fi sh oil supplements were used in combination APPENDIX III of gallstones. with olive oil.

Caution: Women who are pregnant or hoping to con- Ginkgo (Ginkgo biloba) ceive should avoid shark, swordfi sh, king mackerel, and tilefi sh, and should eat no more than 8 ounces of alba- Origin: Leaf of the ginkgo biloba tree, native to East core tuna each month, due to potentially dangerous Asia. levels of mercury. Fish oil supplements at normal doses Dosage: Liquid, tablet, softgel, capsule, and extract; are safe. Look for brands that follow good manufactur- typically 120 mg to 240 mg extract daily. Choose sup- ing practices and contain fi sh oils without mercury. plements standardized to 5% to 7% terpene lactones and 24% fl avonol glycosides, the active ingredients Flaxseed (Flax, Raxseed Oil, Linseed Oil; Linum in ginkgo. usitatissimum) Claims: Increases blood fl ow and circulation in Raynaud’s phenomenon and claudication. Origin: Seed of the fl ax plant, containing omega 3 and omega 6 fatty acids and lignans (benefi cial plant com- Caution: Ginkgo’s side effects include stomach upset, pounds, similar to fi ber). dizziness, or headaches. Avoid ginkgo with blood- Dosage: Whole seeds, ground meal or fl our, capsules, thinning medication like aspirin, epilepsy, diabetes, or or oil. Whole seeds must be ground into meal or prior to surgery. 694 APPENDIX III

GLA (Gamma-Linolenic Acid) Indian Frankincense (Frankincense, Boswellia, Boswellin, Salai Guggal; Boswellia serrata) Origin: A type of omega 6 fatty acid found in evening primose oil, black currant oil, and borage oil. Origin: Gum resin from the bark of the Boswellia tree Dosage: Capsules or oil; 2 g to 3 g daily. found in India. Claims: Lessens joint pain, stiffness, and swelling associ- Dosage: Capsule or pill; typically 300 mg to 400 mg three ated with RA. Eases symptoms of Raynaud’s phe- times per day. Look for products with 60% boswellic nomenon and Sjögren’s syndromes. acids, the active ingredient. Studies: One of the most promising studies was a Claims: Reduces infl ammation and treats RA, OA, placebo-controlled trial of 56 patients with active and bursitis symptoms. Indian frankincense may RA who received 2.8 g GLA for 6 months. Partici- treat symptoms of ulcerative colitis and Crohn’s pants showed signifi cant improvements related to disease. joint pain, stiffness, and grip strength. GLA doses Studies: In a 2004 study, Indian frankincense was tested at this level were found to be safe and effective for as a treatment for knee OA. Researchers recruited RA. A 2005 study showed that people with Sjögren’s 30 people with knee OA and gave half the group a syndrome who took GLA and linolenic acid had daily supplement containing 333 mg of Indian frank- signifi cant improvement in eye discomfort and tear incense; others got placebo. People who took Indian production. frankincense reported less knee pain, better mobility, and an ability to walk longer distances than those Glucosamine (Glucosamine sulfate, glucosamine taking placebo. hydrochloride, N-acetyl glucosamine) Melatonin Origin: Major component of joint cartilage. Supple- Origin: A hormone produced by the pineal gland, which ments are derived from the shells of shellfi sh such as is located at the base of the brain. shrimp, lobster, and crab. Dosage: Capsules or tablets; 1 mg to 5 mg at bedtime for Dosage: Capsules, tablets, liquid, or powder (to be insomnia, for no longer than 2 weeks. mixed into a drink); 1500 mg per day for all forms. Claims: Aids sleep and treats jet lag. Often combined with chondroitin. May take 1 month Studies: A systematic review of studies shows no evi- to notice effect. dence that melatonin effectively treats sleep disor- Claims: Slows deterioration of cartilage, relieves OA ders or is useful for altered sleep patterns, such as pain, and improves joint mobility. from shift work or jet lag. However; there is evidence Studies: The NIH Glucosamine/Chondroitin Arthritis that it is safe with short-term use. Another review Intervention Trail (GAIT) concluded that glucos- of studies showed that melatonin reduced the onset amine may be benefi cial. The study of 1583 people of sleep by 4 minutes and increased the duration of with knee OA showed that the supplements were sleep by nearly 13 minutes; another showed that more effective when combined, but that they did people taking melatonin slept almost 30 minutes not work signifi cantly better than placebo or the longer than people taking placebo. NSAID celecoxib in people with mild pain. However; a subgroup of people in the study who had moder- Caution: Certain medications interact with melatonin, ate-to-severe pain did show signifi cant benefi t, even including NSAIDs, beta-blockers, antidepressants, more than with the NSAID. Half of the study diuretics, and vitamin B12 supplements. Melatonin participants will continue to be evaluated for 18 should be avoided in patients with autoimmune disease, months to see if glucosamine and chondroitin can depression, kidney disease, epilepsy, heart disease, or slow or stop the progression of knee OA. A 2005 leukemia. Cochrane review of glucosamine analyzed the outcomes of 20 studies comprising 2570 patients. Glu- MSM (Methylsulfonyfmethane) cosamine was found to be safe, but not superior to placebo in reducing pain and stiffness and improv- Origin: Organic sulfur compound found naturally in ing function. fruits, vegetables, grains, animals, and humans. Dosage: Tablets, liquid, capsule, or powder, topical and Caution: Glucosamine may cause mild stomach upset, oral. Typically 1000 mg to 3000 mg daily with meals. nausea, heartburn, diarrhea, and constipation, as well Claims: Reduces pain and infl ammation. as increased blood glucose, cholesterol, triglyceride, Studies: A 2006 pilot study of 50 men and women with and blood pressure. Glucosamine should be avoided in knee OA showed that 6000 mg of MSM improved individuals allergic to shellfi sh. symptoms of pain and physical function without SUPPLEMENT AND VITAMIN AND MINERAL GUIDE 695

major side effects. No large, well-controlled human prescription antidepressants. St. John’s wort can cause studies have been performed. insomnia, restlessness, anxiety, irritability, stomach upset, fatigue, dry mouth, dizziness, or increased sensi- Caution: MSM may cause stomach upset or diarrhea and tivity to sunlight. It should be avoided in patients with should be avoided in patients taking blood thinners. Alzheimer’s disease, human immunodefi ciency (HIV) infection, depression, schizophrenia, infertility, or SAM-e (S-adenosyl-L-methionine) bipolar dis order. It may also reduce effectiveness of oral contraceptives. Origin: A naturally occurring chemical in the body. Dosage: Tablets; 600 mg to 1200 mg daily for OA; Stinging Nettle (Urtica dioica) 1600 mg daily for depression. Because of possible interactions, SAM-e should not be taken without Origin: The leaves and stem of the stinging nettle plant, doctor’s supervision. a stalk-like plant found in the United States, Canada, Claims: Treats pain, stiffness, and joint swelling; and Europe. improves mobility; rebuilds cartilage and eases symp- Dosage: Tea, capsule, tablet, tincture, extract, or whole toms of OA, fi bromyalgia, bursitis, tendinitis, chronic leaf; capsules, up to 1300 mg daily; tea, 1 cup, three low back pain, and depression. times a day; tincture, 1 mL to 4 mL three times a day; Studies: Over the last two decades, multiple clinical nettle leaf applied directly to the skin. trials involving thousands of people have shown Claims: Reduces infl ammation, aches, and pains of OA. SAM-e to improve joint health and treat OA. It has Studies: A German study shows that hox alpha, a new been found to be equal to NSAIDs in clinical studies. extract of stinging nettle leaf, contains an anti- Most of this research has been done in Europe, where infl ammatory substance that suppressed several cyto- SAM-e is sold as a drug. A double-blind study of 61 kines in infl ammatory joint diseases. In a Turkish adults with knee OA done in the United States shows study, stinging nettle extract showed anti microbial that SAM-e had a slower onset of action but was as effects against nine microorganisms, as well as anti- effective as celecoxib in reducing pain and improving ulcer and analgesic activity. Stinging nettle root extract joint function. A 2002 analysis of 14 SAM-e studies combined with sabal fruit extract was shown to be showed it is effective for reducing pain and improv- superior to placebo for treating prostate hyperplasia ing mobility in people with OA. (a precancerous condition), and was well tolerated.

Caution: High doses of SAM-e can cause ﬂ atulence, Caution: Nettle may interfere with blood thinners, dia- vomiting, diarrhea, headache, and nausea. SAM-e may betes, and heart medications, and lower blood pressure. interact with antidepressive medications and should be avoided in patients with bipolar disorder or who are Thunder God Vine (Tripterygium wilfordii) taking monoamine oxidase inhibitors (MAOIs). It may also worsen Parkinson’s disease. Origin: Root of a vinelike plant from Asia.

Dosage: Extract; 30 mg daily. APPENDIX III St. John’s Wort (Hypericum perforatum) Claims: Reduces pain and infl ammation and treats symptoms of RA, lupus, and other autoimmune Origin: The yellow fl ower, leaves, and stem of the St. diseases. John’s wort plant is native to Europe and grows wild Studies: A 2006 review of randomized clinical trials in the United States. shows that thunder god vine improved symptoms of Dosage: Extract in the form of powder (dried), liquid RA but serious side effects occurred. (10 to 60 drops one to four times per day) or tablet, capsules, and tea; extract, typically 900 mg daily. Caution: This root can cause stomach upset, skin reac- Claims: Acts as an antidepressant drug and reduces tions, temporary infertility in men, and amenorrhea in infl ammation and pain. women. It should not be used in patients taking immu- Studies: No scientifi c evidence shows that St. John’s nosuppressive drugs or prednisone. wort is effective for reducing infl ammation. A Cochrane review of studies on St. John’s wort for Tumeric (Curcuma longa, Curcuma domestica) depression showed that current evidence is inconsis- tent. A study also found that the herb is not effective Origin: A yellow-colored powder ground from the roots for social anxiety disorder. of the lilylike turmeric plant. It is a common ingredient in curry powder. The turmeric plant grows in Caution: Although St. John’s wort taken alone is con- India and Indonesia and is related to the ginger sidered safe, it is potentially dangerous if taken with family. 696 APPENDIX III

Dosage: Capsules or spice. Capsule, typically 400 mg to Vitamin A 600 mg three times per day; or 0.5 g to 1 g of powdered root up to 3 g per day. Other names: Beta-carotene, retinal, retinol, and reti- Claims: Reduces pain, infl ammation, and stiffness noic acid. Vitamin A palmitate and vitamin A acetate related to RA and OA; treats bursitis. Known as a are retinol forms. “Retinoids” collectively refers to cleansing agent, tumeric often is used as a digestive different forms of vitamin A. aid in India. Why: Maintains the immune system; protects eyesight; Studies: Several recent studies show that curcumin or keeps skin and tissues of the mouth, stomach, turmeric has anti-infl ammatory properties and modi- intestine, and respiratory system healthy; acts as an fi es immune system responses. A 2006 study showed antioxidant. turmeric was more effective at preventing joint How much: RDA = 3000 IU for men; 2333 IU for infl ammation than reducing joint infl ammation. women. Too much: UL = 10,000 IU from retinol. Caution: High doses of turmeric can act as a blood thinner and cause stomach upset. It should be avoided High levels are associated with bone fractures, liver in patients with gallstones or who are taking blood- abnormalities, and birth defects. Other signs: head- thinning medications. aches; dry, itchy skin; hair loss; bone and joint pain; and vomiting and appetite loss. Valerian (Valeriana offi cianalis) Too little: Rare; symptoms include night blindness and Origin: The dried root of the perennial herb valerian. weakened immune system. Dosage: Capsules, tablets, tincture, softgel, or tea; Foods: Beta-carotene: apricots, cantaloupe, carrots, 300 mg to 500 mg of valerian extract daily (maximum dark leafy greens, and sweet potato. Retinol: cheese, dose is 15 g of root per day). For insomnia and muscle liver, eggs, and fortifi ed milk. soreness, take 1 teaspoon of liquid extract diluted in Supplements: Supplements often contain vitamin A. water or a 400-mg to 450-mg capsule, tablet, or softgel Interactions: Cholestyramine (Questran), colestipol, 30 to 45 minutes before bedtime or as needed. For a and mineral oil can reduce vitamin A absorption, milder effect, drink a cup of valerian tea before bed. while oral contraceptives can increase levels. Supple- Avoid powdered valerian root. ments combined with isotretinoin (Accutane) can Claims: Treats insomnia and eases pain; has antispas- increase drug’s toxicity. modic and sedative effects. Research note: Researchers found that high levels of Studies: A randomized, placebo-controlled trial of 184 vitamin A from retinol (not beta-carotene) signifi - adults showed two tablets per night for 28 nights cantly increased bone fractures among men, con- produced signifi cant improvements in sleep and fi rming research showing that high levels of vitamin quality of life. A from retinol raised the risk of hip fractures in women. Caution: Valerian may cause headache, excitability, uneasiness, and insomnia. Patients should be advised to Vitamin D limit driving or operating machinery while taking it. Patients should avoid or limit alcohol, barbiturates, Other names: Cholecalciferol, calciferol, ergocalciferol, tranquilizers, or other sedative-type drugs or herbs. dihydroxy vitamin D-2 or D-3. Valerian should not be used longer than 1 month, or in Why: Builds and maintains strong teeth and bones; patients with liver disease. protects against osteoporosis; aids in calcium absorption; helps utilize phosphorus. Both calcium VITAMIN AND MINERAL GUIDE and phosphorus are important for bone mineralization. = Originally published in Arthritis Today, September– How much: RDA 200 IU for adults through age October 2005, reprinted by permission of the Arthritis 50; 400 IU from 51 to 70 years of age; 600 IU over Foundation. age 70. Too much: UL = 2000 IU: nausea, vomiting, poor appetite, constipation, weakness, and weight loss; increases Fat-Soluble Vitamins blood levels of calcium, causing confusion, heart Getting suffi cient doses of vitamins is important, but rhythm abnormalities, or calcinosis and deposits of make sure diet and supplements don’t exceed recom- calcium in soft tissues. mendations. Excesses of these vitamins are stored, Too little: A high risk of osteoporosis. Low levels lead rather than excreted. to muscle weakness. SUPPLEMENT AND VITAMIN AND MINERAL GUIDE 697

Foods: Fortiﬁ ed milk and breakfast cereals are good Too little: Too little vitamin K increases blood clotting sources of vitamin D; small amounts also are in egg time and can cause bruises beneath skin and bleeding yolks, butter, salmon, tuna, and sardines. gums. Supplements: Because vitamin D needs increase with Foods: Leafy greens. age, many experts recommend as much as 800 IU for Supplements: Multivitamins often contain amounts seniors. Just 10 to 15 minutes of sun exposure two to lower than the RDA because vitamin K may have a three times a week (without sunscreen) is sufﬁ cient blood-clotting effect. to meet daily requirements. Interactions: Antibiotics can decrease vitamin K pro- Interactions: Corticosteroids, such as prednisone, duction. Excess vitamin K intake may decrease effec- antacids that contain magnesium, cholestyramine tiveness of blood-thinning drugs. (Questran), and mineral oil can interfere with vitamin Research note: A study of more than 72,000 women D absorption. found a link between low dietary vitamin K intake Research note: In a study of 221 people with knee and an increased risk of hip fracture. Women who osteoarthritis (OA), those who increased their daily ate iceberg or romaine lettuce one or more times vitamin D intake gained muscle strength and daily were 45% less likely to break a hip than those improved physical function. who ate lettuce once a week or less.

Vitamin E Water-Soluble Vitamins Other names: Alpha-tocopherol, gamma-tocopherol, During digestion, these vitamins are absorbed into the tocopherol acetate, and tocopherol succinate. blood and transported around the body. The body uses Why: Acts as a scavenger, cleaning up free radicals; also them quickly, however, and excretes—rather than aids in the formation of red blood cells, reproduction, stores—what it doesn’t need. and growth.

How much: RDA = 15 mg for adults. Vitamin B1 Too much: UL = 1000 mg daily. May cause increased bleeding time. Other names: Thiamine and thiamin. Too little: Associated with fat malabsorption diseases Why: Converts glucose to energy; essential for normal like Crohn’s disease. functioning of the heart, brain, nervous system, and Foods: Peanut butter, almonds, sunfl ower seeds, marga- muscles. rine, wheat germ, corn oil, soybean oil, and turnip How much: RDA = 1.2 mg for men; 1.1 mg for women. greens. Too much: No known symptoms, but an allergic reac- Supplements: Supplements should include mixed tion may result in fl ushing, itching, or swelling. tocopherols, natural vitamin E, generally labeled Too little: Defi ciency is associated with abnormal carbo- “D.” The synthetic form “D,L” is only half as hydrate metabolism. Prolonged defi ciency can affect active. the nervous and cardiovascular systems.

Interactions: Blood-thinning medications, aspirin, Foods: All plant and animal foods contain thiamine, APPENDIX III NSAIDs, and drugs for schizophrenia or especially whole wheat, brown rice, ﬁ sh, and lentils. chemotherapy. Enriched pasta, bread, cereals, and rice. Research note: A 2004 review of 19 clinical studies Supplements: Multivitamins generally provide 100% or sparked a debate about the safety of vitamin E sup- more of the daily requirements. plementation. However; a closer look showed most Interactions: Research links long-term use of the diuretic

of the people who experienced negative effects were furosemid (Lasix) to vitamin B1 deﬁ ciency. Regular elderly and had chronic illnesses. A study of 136 use of antacids also may interfere with thiamine’s people with knee OA found that supplemental absorption. vitamin E didn’t have any beneﬁ cial effect.

Vitamin B2 Vitamin K Other names: Riboﬂ avin. Other names: Phylloquinone (K-1), menaquinone Why: Promotes healthy development; helps produce (K-2), menadione (K-3) and dihydophylloquinone. skin and red blood cells; helps convert glucose to Why: Aids blood clotting and activates osteocalcin, a energy. protein that builds and strengthens bones. How much: RDA = 1.3 mg daily for men; 1.1 mg daily How much: RDA for vitamin K = 90 mcg for women; for women. 120 mcg for men. Too much: UL not determined. High doses are believed Too much: No UL set. harmless, but may turn urine orange or yellow. 698 APPENDIX III

Too little: Absorption is decreased in people with hyper- Suboptimal levels are linked to high levels of homo- thyroidism. Symptoms can include dry, cracked skin cysteine, which can increase the risk of stroke and and sensitivity to light. heart disease. Foods: Organ meats, eggs, milk; fortifi ed cereals and Foods: Beans, meat, poultry, and fi sh. grains. Ribofl avin is easily destroyed by light. Supplements: Found in multivitamins, B complex, and

Supplements: Generally contained in B complex or vitamin B6 supplements. multivitamins, which provide 100% or more of the Interaction: Too much vitamin B6 can decrease the DV for riboﬂ avin. effects of drugs for epilepsy and Parkinson’s disease.

Interactions: None known. Vitamin B6 should be taken along with drugs for

Research note: A diet rich in vitamin B2 may help ward tuberculosis. off or slow the progression of cataracts and may help Research note: A study showed that low blood levels

prevent migraine headaches. of vitamin B6 decreased as the activity, severity, and pain of RA increased. Researchers suggest

Vitamin B3 that inﬂ ammation may decrease the level of vitamin B6. Other names: Niacin, nicotinic acid, and nicotinamide.

Why: Helps with producing energy from food (sugars Vitamin B12 and fats); keeps skin, nerves, and digestive system healthy. Other names: Cobalamin, cyanocobalamin, and How much: RDA = 16 mg for men; 14 mg for women. methylcobalamin. Too much: UL = 35 mg, though some doctors prescribe Why: Helps make red blood cells, nerve cells, and higher doses as a treatment to reduce cholesterol and genetic material; converts folate to its active form. triglyceride levels. Flushing of the face, neck, and How much: RDA = 2.4 mcg. ears; itching, nausea, and headache; can aggravate Too much: UL not determined; negative side effects gout. More serious effects include insomnia, palpita- may include rash.

tions, and liver damage. Too little: Because vitamin B12 converts folate to its Too little: Rare; symptoms include dermatitis, diarrhea, active form, too little B12 can lead to a folate defi - and dementia. ciency, resulting in pernicious anemia causing Foods: Chicken, tuna, turkey, fi sh, beef, beans, yeast, fatigue, weakness, nausea, loss of appetite, and peanut butter, and salmon. weight loss. Supplements: Typically in B complex and multivitamins, Foods: Found only in foods of animal origin: organ which generally provide 100% or more of the daily meats, egg yolks, yams, and salmon. Fortifi ed foods requirements. such as cereal, pasta, and bread may contain syn- Interactions: Taking niacin and diabetes medications thetic versions. may interfere with blood glucose control. Some cho- Supplements: Recommended for strict vegetarians, lesterol medications can reduce niacin absorption. those who’ve had gastric surgery, or those who have

Pregnant women should avoid taking more than the a malabsorption disease. Because vitamin B12 absorp- RDA. Take with food. tion declines with age, it is recommended that people

Research note: Studies link diets rich in vitamin B3 with older than 50 get most of their B12 from fortiﬁ ed a decreased risk of Alzheimer’s disease. foods and supplements. Most multivitamins and B complex supplements contain 100% or more of

Vitamin B6 the daily requirements. Interaction: Antacids, drugs for indigestion and reﬂ ux Other names: Pyridoxine, pyridoxal, pyridoxamine, and disease, cholesterol-lowering medication, and the pyridoxine hydrochloride diabetes medication metformin can decrease the

Why: Needed in more than 100 chemical reactions in absorption levels or production of B12. the body and for forming amino acids, red blood Research note: Maintaining a healthy level of vitamins

cells, and antibodies; important for nerve and brain B12, B6, and folic acid may protect bones by keeping function and energy production. blood levels of the amino acid homocysteine from How much: RDA = 1.3 mg for all adults up to age 50; elevating. High homocysteine levels affect the heart over age 50, 1.7 mg for men, 1.5 mg for women. and the skeleton.

Too much: UL = 100 mg. Long-term high doses of B6 can lead to nerve damage, resulting in pain and Vitamin C numbness of the extremities. Too little: Rare; symptoms include skin inﬂ ammation, Other names: Ascorbic acid, L-ascorbic acid, and calcium sore tongue, depression, confusion, and convulsions. ascorbate. SUPPLEMENT AND VITAMIN AND MINERAL GUIDE 699

Why: Builds and maintains collagen and connective Supplements: Multivitamins and B complex vitamin tissue; enhances iron and folic acid absorption; acts supplements generally provide 100% of the RDA. as an antioxidant; aids wound healing. Interactions: Antacids, alcohol, antibiotics, aspirin, car- How much: RDA = 90 mg daily for men; 75 mg for bamazepine (Tegretol), some cholesterol-lowering women; smokers and people with arthritis should drugs, indomethacin (Indocin), oral contraceptives, aim for an additional 35 mg daily. methotrexate, and sulfasalazine (Azulfi dine) can Too much: UL of vitamin C is 2000 mg daily. Can lead decrease absorption levels or production of folic to diarrhea, nausea, and risk of kidney stones. acid. Too little: Weight loss; fatigue; infl amed or bleeding Research note: Methotrexate hinders absorption of gums; slower healing times; repeated infections and folate. Patients taking methotrexate can safely use colds. folate supplements. In a double-blind, placebo-con- Foods: Peppers, orange juice, pineapple and other citrus trolled trial of more than 400 people with RA, folate fruits, strawberries, papaya, broccoli, Brussels supplements helped curb the side effects of metho- sprouts, cabbage, caulifl ower, kale, and kiwi. Cooking trexate, including liver infl ammation with no loss of destroys vitamin C activity. effi cacy. A double-blind study published in the Supplements: Daily intake of 200 to 500 mg is frequently Journal of the American Medical Association reports

recommended for all adults because many experts stroke patients who took folate and vitamin B12 had think the RDA for vitamin C is too low. Some studies a lower risk of hip fracture compared to those taking suggest nearly 1000 mg are needed to maintain plasma placebo. levels at high concentrations. Natural and synthetic vitamin C react the same in the body. Additional ingredients, such as rose hips or biofl avonoids, have not been shown to improve benefi t. Minerals Interactions: Regular use of nonsteroidal anti-infl amma- Minerals are found naturally in the soil and become part tory drugs (NSAIDs), aspirin, antibiotics, nicotine, of the fruits, vegetables, and other plant foods you eat. oral contraceptives, or corticosteroids increases the Minerals requirements are fulfi lled in persons who eat need for vitamin C. plenty of fruits, vegetable greens, and grains. Research note: In a recent study of vitamin C consump- The mineral chart does not contain listings for boron, tion and arthritis, people whose diets contained the iodine, manganese, molybdenum, or potassium because least amount of the vitamin were three times more people need such small amounts of these minerals, and likely to be diagnosed with arthritis than those who the amount in foods usually meet the needs. ate the most fruits and vegetables rich in vitamin C. Calcium Folate Other names: Calcium carbonate, calcium lactate, Other names: Folic acid and folacin. calcium citrate, calcium gluconate, and calcium citrate

Why: Promotes healthy cell growth and reproduction, malate. APPENDIX III formation of DNA; regulates homocysteine levels. Why: Builds and maintains strong teeth and bones; How much: RDA = 400 mcg for adults; 600 mcg for regulates muscle contractions; transmits nerve pregnant women. At least half of this intake (200 mcg) impulses and monitors cell permeability. Calcium should come from the folic acid found in fortiﬁ ed needs phosphorus and vitamin D present to be foods and supplements. effective. Too much: UL = 1000 mcg daily, or 1 mg. Doses higher How much: AI = 1000 mg daily for adults under age 50; than 1500 mcg (1.5 mg) may cause minor discomfort 1200 mg daily for adults older than 50. Some experts such as nausea, appetite loss, and gas, and can mask recommend as much as 1500 mg daily for adults with

a vitamin B12 defi ciency, resulting in nerve and brain infl ammatory conditions and postmenopausal women damage. Folic acid may be prescribed at levels higher not taking hormone-replacement therapy. than the UL for people taking methotrexate. Too much: UL = 2500 mg. Too much causes bloating, Too little: Increases the toxic effects of methotrexate, constipation, impaired kidney function, and kidney can increase homocysteine level. Low levels in preg- stones. nant women increase the risk of neural tube defects Too little: Contributes to bone loss, tooth loss, muscle in their babies. Increased risk for certain cancers, cramps, and hypertension. depression, heart disease, and Alzheimer’s disease. Foods: Milk, yogurt, cheese, ice cream, canned sardines Foods: Spinach, kale, collards, turnip greens, broccoli, and canned salmon (with bones), broccoli, kale, garbanzo beans, lentils, peas, pinto beans, oranges, turnip greens and bok choy, plus calcium-fortifi ed liver, and fortifi ed breads, cereals, and juices. orange juice, cereal, and soy products. 700 APPENDIX III

Supplements: Infl ammatory arthritis accelerates bone Too little: Rare; anemia and osteoporosis. loss, so getting the optimal intake daily is critical. Foods: Organ meats, seafood, cashews, semisweet choc- Supplement with 500-mg doses one or more times olate, peanut butter, lentils, and mushrooms. a day with meals but avoid taking after eating foods Supplements: Not necessary or recommended; a containing oxalic or phytic acid, such as spinach, multivitamin, typically provides the RDA. parsley, beans, and whole cereals. Calcium may inter- Interactions: High levels of zinc, iron, and possibly fere with absorption of iron, magnesium, and zinc, so vitamin C can block copper absorption. take it separate from a multivitamin. Avoid supple- Research note: Although copper does have anti- ments containing coral calcium, bone meal, oyster infl ammatory properties, there currently is no shell, or dolomite; they may be contaminated with research to support dietary copper or supplementa- lead. tion as a treatment for arthritis. Interactions: Calcium may decrease absorption or effectiveness of some bone drugs, antibiotics, and calcium Fluoride channel blockers. Aluminum-containing antacids, anticonvulsants, corticosteroids, diuretics and laxa- Why: Necessary for strong bones and teeth (especially tives may reduce calcium levels. tooth enamel). Research note: A review of fi ve studies shows the com- How much: AI = 4 mg for men; 3 mg for women. bination of calcium and vitamin D supplements sig- Too much: UL = 10 mg daily: mottled and brown nifi cantly prevented bone loss in people taking teeth. corticosteroids. In another study of 65 people with Too little: Tooth decay. RA, those who took calcium (1000 mg) and vitamin Foods: Fluoridated water, tea, and canned salmon and D (500 IU) supplements not only reversed steroid- sardines (with bones). induced bone loss but also gained bone mass. Supplements: By prescription only for infants and children without access to fl uoridated water. Chromium Interactions: Calcium supplements and calcium- and aluminum-containing antacids. Why: Helps body use insulin, protein, fat, and Research note: Doesn’t prevent osteoporosis. Safety carbohydrates. concerns related to joint pain and stress fractures How much: AI = 35 mcg for men age 14 to 50; 30 mcg from taking extremely high doses. for men over age 50; 25 mcg for women age 14 to 50; 20 mcg for women over age 50. Too much: No known symptoms. Iron Too little: Impaired glucose utilization. Food: Black pepper, brewer’s yeast, brown sugar, mush- Other names: Ferrous fumarate, ferrous gluconate, and rooms, whole grains, and wheat germ. ferrous sulfate. Supplements: Not necessary or recommended. Why: Necessary for production of hemoglobin. Research note: There is no conclusive evidence that How much: RDA = 8 mg daily for men; 18 mg daily for chromium supplements can prevent or treat diabetes, women until menopause; 8 mg daily for women after but research continues. Using chromium and beta- menopause. blockers modestly increases levels of high-density Too much: UL = 45 mg per day: nausea, vomiting, diar- lipoprotein (HDL) levels. Chromium may add to rhea or constipation, and dark-colored stools. Iron effects of diabetes medications. Antacids, corticoste- builds up in body tissues and vital organs, leading to roids, H2-blockers, and proton pump inhibitors may cirrhosis, diabetes, heart disease, and arthritis (par- decrease chromium levels. ticularly in the knuckles). High levels also lower zinc absorption. Copper Too little: The most common form of nutritional defi - ciency, mostly affecting young children, female teen- Other names: Cupric oxide, copper gluconate, copper agers, and women of childbearing years. Symptoms sulfate, and copper citrate. of mild defi ciency include tiredness, shortness of Why: Helps build red blood cells, transport iron, and breath, decreased mental performance, poor appe- make connective tissue; keeps immune system, tite, unstable body temperature, and decreased nerves, and blood vessels healthy; and removes free immunity. radicals. Foods: Heme iron comes from beef, lamb, chicken, How much: RDA = 900 mcg daily for adults. turkey, veal liver, ham, bologna or tuna, and is well Too much: UL = 10,000 mcg: nausea, vomiting, diar- absorbed by the body. Non-heme iron comes from rhea, abdominal pain, headache, or death. plant sources and fortifi ed grains, such as raisins, SUPPLEMENT AND VITAMIN AND MINERAL GUIDE 701

peas, lentils, fi gs, oatmeal, and grits, and is not as well Research note: There is no scientifi c evidence showing absorbed. that phosphorus, namely in soft drinks, contributes Supplements: Men and postmenopausal women should to bone loss. However, drinking soft drinks in lieu of take multivitamins or other supplements with little milk may contribute to osteopenia or osteoporosis. or no iron. Interactions: Calcium. High doses of vitamin C, meat, Selenium fi sh, poultry, citric acid, and cream of tartar enhance absorption of iron from plant sources. Coffee, tea, Other names: Sodium selenite (inorganic, supplement wine, tofu, legumes, grains, and rice inhibit absorp- form) and selenomethionine (organic form found in tion of iron from plant sources. food). Why: Works with vitamins C and E as an antioxidant; Magnesium essential for proper function of immune system and thyroid gland. Other names: Magnesium chloride, gluconate, oxide, How much: RDA = 55 mcg daily. citrate (supplement forms); magnesium hydroxide Too much: UL = 400 mcg daily. Too much may cause (antacid) and magnesium sulfate (Epsom salt). hair and nail loss, fatigue, and mild nerve damage. Why: Needed for more than 300 biochemical reactions Too little: Rare; impaired immunity and heart damage. in the body. Maintains muscle and nerve function, Foods: Brazil nuts, walnuts, wheat germ, organ meats, keeps heart rhythm regular, strengthens teeth and shrimp, crab, tuna, turkey, and garlic. bones. Supplements: Not recommended beyond a multivitamin How much: RDA = 420 mg for men older than 31; unless under a doctor’s supervision. 320 mg for women older than 31. Research note: Supplementation of 200 mcg daily may Too much: UL = 350 mg, supplements only; no upper lower the risk of prostate cancer in men, but further limit via diet. Too much causes diarrhea, confusion, studies must be done before scientists make any re- muscle weakness, nausea, irregular heartbeat, and commendations. Although people with RA tend to low blood pressure. have low selenium levels, there is no evidence that Too little: Symptoms include loss of appetite, nausea, selenium supplements are benefi cial. vomiting, fatigue, and weakness. Foods: Kelp, wheat germ, soy beans, almonds, cashews, Sodium sunfl ower seeds, beans, potatoes, peanut butter, and hard (high mineral) water. Other names: Sodium chloride (table salt), sodium Supplements: Diet usually adequate, but supplementing citrate, monosodium glutamate (MSG), sodium is OK. nitrate, sodium bicarbonate (baking soda), Interactions: May reduce effects or absorption of some sodium phosphate (baking powder), and sodium diuretics, bone drugs, antibiotics, and iron. Chemo- saccharin. therapy may decrease magnesium level. Fiber may Why: Regulates body fl uids and blood pressure and

increase absorption. helps nerve impulse function and muscle APPENDIX III contraction. Phosphorus How much: AI = 1.5 g for adults 19 to 50; 1.3 g for adults 51 to 70. DV is 2.4 g (2 g sodium = 1 teaspoon Why: Strengthens teeth and bones; also involved in table salt). Average daily intake in the United States energy production. is 5 g. How much: RDA = 700 mg. Too much: No UL determined; excess may cause high Too much: UL = 4000 mg daily before age 70; 3000 mg blood pressure, stomach cancer, kidney stones, and daily after age 70. Too much may cause diarrhea and osteoporosis. upset stomach. Chronic overdose may cause kidney Too little: Less than 0.5 g daily leads to headache, nausea, damage. dizziness, fatigue, muscle cramps, and fainting. Too little: Rare; symptoms could include weak bones Foods: Salt (75% percent of our salt intake comes and muscles, fatigue, loss of appetite, bone pain, and from sodium added to seasonings or processed increased susceptibility to infection. foods). Foods: Milk, yogurt, cheese, eggs, whole wheat bread, Supplements: Not necessary or recommended. soft drinks, turkey, salmon, halibut, peanuts, almonds, Interactions: Diuretics, NSAIDs, opiates, and tricyclic and lentils. antidepressants. People taking corticosteroids should Supplements: Not necessary or recommended. stay below 3 g daily. Interactions: Aluminum-containing antacids, potassium Research note: One study found women who consumed supplements, and potassium-sparing diuretics. a high salt diet (9 g daily) lost 33% more calcium and 702 APPENDIX III

23% more of a bone protein than those on a low salt Too little: Mild defi ciency impairs immunity, leading to diet (2 g/day). poor wound healing and infection. Foods: Oysters, mussels, lobster, beef, pork, lamb, Zinc chicken, turkey, milk, cheese, yogurt, maple syrup, peanuts, peanut butter, beans, and lentils. Other names: Zinc gluconate and zinc acetate. Supplements: Multivitamins with no more than 100% Why: Involved in wound healing, cell reproduction, DV recommended. tissue growth, sexual maturation, and taste and smell; Interactions: Antibiotics may bind with zinc, decreasing also associated with more than 100 enzymatic reac- both drug and nutrient absorption. Take multivita- tions in the body. mins and antibiotics separately. Calcium can decrease How much: RDA = 11 mg daily for men; 8 mg daily for absorption of zinc supplements. women. Research note: Zinc may protect against age-related Too much: UL = 40 mg daily: immune suppression macular degeneration. (same as defi ciency), diarrhea, abdominal cramps and vomiting, and copper defi ciency. INDEX

A outcome, 457 localized, 539–540 Abatacept, 139–140 pathogenesis, 455 myeloma-associated, 534 in PsA, 189 radiographic fi ndings in, 455–456 pathogenesis, 534 Abciximab, 449 treatment, 457–458 precursors, 536 ACD. See Amplitude color Doppler acute disease, 457–458 proteins, 536 ACE. See Angiotensin-converting chronic disease, 457–458 secondary, 534 enzyme Advanced glycation endproduct (AGE), treatment, 537 Achilles tendon 539 Amyopathic dermatomyositis, 363 rupture, 82 Aerobic exercise, for fi bromyalgia, 92 ANA. See Antinuclear antibodies tendinitis, 81–82 AFQUIP. See Arthritis Foundation Anakinra, 139 Achondroplasioas, 561 Quality Indicators Project Analgesic drugs, opioid, 622–623 aCL. See Anticardiolipin AGE. See Advanced glycation Anaplasma phagocytophilum, 287 Acne fulminans, 501 endproduct ANCA. See Antineutrophil cytoplasmic ACR. See American College of Alanine aminotransferase (ALT), 375 antibody Rheumatology Alcohol, gout and, 252–253 Anesthesia, in arthrocentesis, 22–23 ACR20, 139 Alefacept, in PsA, 189 Angiitis, primary, 439–441 Acrocyanosis, 430 Alendronate, 574, 594 clinical manifestations of, 439–440 Acrodermatitis chronica atrophicans, Alkaptonuria, 525–527 Angiofi broblastic tendinosis, 73 285 clinical features, 525–526 Angiogenesis, 129 Acromegaly, 482–483 laboratory features, 526–527 Angiography, 28, 39–40 rheumatological manifestations of, radiographic features, 526 Angioimmunoblastic T-cell lymphoma- 482 Allergic reactions, 641 associated arthritis, 476 ACTD. See Autoimmune connective Allopurinol, 260 Angiopathy, benign, 441 tissue disease Alopecia, 307 Angiotensin-converting enzyme (ACE), ACTH. See Adrenocorticotropic Alprazolam, 624 352 hormone ALPS. See Autoimmune Ankle Acupuncture, 625, 665 lymphoproliferative syndrome examination of, 13–14 Acute febrile neutrophilic dermatosis, ALT. See Alanine aminotransferase palpation, 14 492 Alzheimer’s disease, 534 Ankylosing spondylitis Adalimumab AMA. See American Medical anti-TNF agents and, 213–214 ankylosing spondylitis and, 213 Association arthritogenic peptides, 202–203 in PsA, 188 Amblyomma americanum, 284 biologic agents, 212–213 Addison’s disease, 483 American College of Rheumatology adalimumab, 213 Adenosine monophosphate, 387 (ACR), 88, 136 etanercept, 212 Adherence, in JIA American Medical Association infl iximab, 213 assessment of, 166 (AMA), 4 bone formation in, 207 factors impacting, 166 Amplitude color Doppler (ACD), 38 classifi cation criteria for, 198, improving, 166 Amyloid arthropathy, 476 672–673 Adhesive capsulitis, 72 Amyloid fi brillogenesis, 534 clinical assessment of, 209–210 Adiposity, in gout, 253–254 Amyloidosis, 56, 533–541 clinical features of, 194 Adrenocorticotropic hormone (ACTH), clinical features, 535–540 cytokine expression in, 207 in gout treatment, 259 AA, 537–538 diagnosing, 197–198 Adult Still’s disease, 455–458 AL, 535–537 disease activity, 209–210 clinical fi ndings in, 455–456 ATTR, 538–539 epidemiology of, 193

clinical manifestations, 456 Aβ2M, 539 etiology of, 193–193 diagnosis, 456–457 localized, 539–540 exercise and, 210 criteria for, 457 diagnosis, 540–541 gut microbes in, 204 differential diagnosis of, 457 histopathology, 541 histopathology in, 206–207 disease course, 457 imaging, 540 HLA-B27 and, 201–203 laboratory ﬁ ndings in, 455–456 epidemiology, 535 aberrant cell surface heavy chains, laboratory tests in, 456 hematologic abnormalities in, 536 203 703 704 INDEX

Ankylosing spondylitis (cont.) Antimalarials, in SLE, 330–331 in SLE, 341 arthritogenic peptides, 202–203 In RA XXX thrombosis, 341 as disease factor, 203 Antineutrophil cytoplasmic antibody Apatite, 267 endoplasmic reticulum stress, 203 (ANCA), 17–19, 410 clinical features, 268–269 enhanced bacterial survival, 203 assay, 423 acute arthritis, 269 protein misfolding in, 203 This entire section needs to be calcifi c periarthritis, 269 imaging in, 196–197 moved to a separate heading calcinosis, 269 MHC genes in, 205 titled Vasculitis large joint destructive arthritis, MTX treatment, 212 antigens, 422 268–269 non-MHC genes in, 206 in blood, 420 Milwaukee shoulder syndrome, pathogenesis, 200–207 in bronchi, 419 268–269 pathology, 200–207 classifi cation criteria, 417 ARAMIS. See Arthritis, Rheumatism, patient education in, 210 clinical features of, 418–420 and Aging Medical Information pharmacologic modalities, 211–212 clinical testing for, 422 System glucocorticoids, 211 clinical utility of, 422 Arterial wall, immune response in, muscle relaxants, 211 course, 425 399–400 NSAIDs, 211 defi nitions of, 417 Arteritis, giant cell, 398–404 pamidronate, 211–212 differential diagnosis, 423, 424 Arthritis. See also specifi c types SSZ, 212 epidemiology, 417 diagnosis of, 2 thalidomide, 211–212 in eyes, 419 public health accomplishments, 3–4 tricyclic antidepressants, 211 in GI tract, 420 public health initiative for, 1–2 physical therapy for, 210 in heart, 420 Arthritis Foundation Quality Indicators Move all of the headings below to in kidneys, 419–420 Project (AFQUIP), 4 Clinical features of above in nervous system, 420 Arthritis, Rheumatism, and Aging cardiovascular involvement, 196 nonmedical interventions, Medical Information System enthesitis, 194 424–425 (ARAMIS), 639 eye lesions, 195 pathology, 421 Arthritis Self-Management Program IBD, 195–196 pathophysiology, 423 (ASMP), 237, 614–615 neurologic involvement, 196 prognosis, 425 Arthrocentesis, 21–23 pulmonary involvement, 196 in skin, 420 indications for, 21–22 renal consequences, 196 in trachea, 419 local anesthesia in, 22–23 sacroiliitis, 194–195 treatment, 424 sterile procedures, 22 skin involvement, 196 in upper respiratory tract, techniques, 22 synovitis, 195 418–419 Arthrochalasia type EDS, 552–553 uveitis, 195 cytoplasmic, 17 Arthrography, 28, 38–39 surgical intervention, 214 perinuclear, 17 Arthus, Maurice, 427 – Need to double treatment guidelines, 213–214 testing, 422 check this one – no clue what operative, 655 Antinuclear antibodies (ANA), 17, 52, this means. Anserine bursitis, 80 89, 345 ASCT. See Autologous stem-cell Anterior chest wall, disorders of, immunopathogenesis of, 321–322 transplantation 84–85 patterns, 17 ASMP. See Arthritis Self-Management Anterior interosseous nerve syndrome, in RA, 119 Program 75–76 in SLE, 321 Aspartate aminotransferase (AST), 375 Anteroposterior (AP) radiography, 29 specifi city of, 324 Aspiration standing, 32 testing, 688 anatomic approach to, 23t Anti-Beta 2 glycoprotein, 340 Antiphospholipid antibody syndrome, image-guided, 40 Anticardiolipin (aCL), 340 316 Aspirin, 637, 638 ANTI-CCP. See Anti-cyclic citrullinated classifi cation criteria, 340 AST. See Aspartate aminotransferase peptide antibodies classifi cation of, 680 Asthma, 641 Anticoagulants, NSAID interactions clinical features of, 339–340 Autoantibodies, 18 with, 642 epidemiology of, 339 B cell, 126 Anti-cyclic citrullinated peptide laboratory features, 340 in idiopathic infl ammatory antibodies (ANTI-CCP), 16–17, pathogenesis, 340–341 myopathies, 366–367, 377, 378 126 pathology, 340 in polymyositis, 378 Antidepressants, 623–624. See also primary, 339 in RA, 125–127 Selective serotonin reuptake secondary, 339 in Sjogren’s syndrome, 390–391 inhibitors; Tricyclic treatment, 341 in SLE, 312–313 antidepressants asymptomatic, 341 in systemic sclerosis, 345 Antigen presentation, 98–99 catastrophic, 341 Autoimmune exocrinopathy, 390 Antihypertensives, NSAID interactions experimental, 341 Autoimmune lymphoproliferative with, 642 pregnancy loss, 341 syndrome (ALPS), 102 INDEX 705

Autoimmunity, 106 Bioenergetics, skeletal muscle, 384 Bursitis B cell, 126 Biofeedback, 664–665 anserine, 80 in RA, 125–127 Bisphosphonates, 574 cubital, 74 T cell, 126–127 in osteoporosis treatment, iliopsoas, 78–79 Autologous stem-cell transplantation 594–595 ischial, 79 (ASCT) duration of, 596 olecranon, 73 in JIA treatment, 158 tolerability of, 595–596 prepatellar, 80 in systemic sclerosis treatment, 361 Black currant oil, 691 retrocalcaneal, 82 Avocado Soybean Unsaponifi ables Blastomyces dermatitidis, 294 septic, 275–276 (ASU), 691 Blastomycosis, 294 subcutaneous, 82 Axial arthritis, 221 B lymphocytes, 98, 104–106, 125 trochanteric, 78 Azathioprine, in SLE treatment, 331 activation, 104–105 Buspirone, 624 autoantibodies, 126 B autoimmunity, 126 C Babinski’s sign, 66 depletion, 335 Calcifi c periarthritis, 269 Bacillus Calmette-Guerin, 292–293 development, 104 Calcifying panniculitis, 496 Back pain, 58–66 differentiation, 104–105 Calcinosis, 269 disorders affecting, 59 inhibition of, 335 in systemic sclerosis, 347 fever and weight loss and, 60 specifi c tolerogen, 335 Calcitonin, in osteoporosis treatment, initial evaluation of, 58–60 BMD. See Bone mineral density 596 mechanical, 61 BMP. See Bone morphogenetic Calcium, 699–700 recumbency, 60 proteins homeostasis, 587 stiffness and, 60 Bone and joint dysplasias, 559–564 Calcium oxalate crystals, 26 Back strain, 61 Bone calcium phosphate crystals, 56 Calcium pyrophosphate dehydrate Baker’s cysts, 79–80 Bone densitometry, 28, 39 deposition disease (CPPD), 35, BAL. See Bronchoalveolar lavage Bone destruction, 130 49, 56, 259, 263–267 BASDAI. See Bath Ankylosing Bone dysplasias, 559–564 clinical features, 265–266 Spondylitis Index Bone formation lanthanic, 266 _ ???? Basic calcium phosphates (BCP), 267 in ankylosing spondylitis, 207 pseudogout, 265 clinical features, 268–269 markers, 582 pseudo-neuropathic arthropathy, acute arthritis, 269 Bone mineral density (BMD), in 266 calcifi c periarthritis, 269 osteoporosis, 577 pseudo-OA, 265 calcinosis, 269 Bone morphogenetic proteins (BMP), pseudo-RA, 265–266 large joint destructive arthritis, 181, 207 conditions associated with, 264 268–269 Bone remodeling diagnostic criteria, 266 Milwaukee shoulder syndrome, cellular basis of, 585–586 pathogenesis of, 264–265 268–269 in PsA, 180–181 crystal deposition, 265 osteoarthritis, 268 Bone resorption markers, 582 radiographic features, 266–267 crystal identifi cation, 267–268 Bone structure, 584–586 treatment, 267 Bath Ankylosing Spondylitis Index Bone turnover CAM. See Complementary and (BASDAI), 209 biochemical markers of, 582 alternative medicine BBK32, 285 – No clue what this means in osteoporosis, 580–581, 590 Cancer ?? formation markers in, 582 musculoskeletal symptoms and, BCP. See Basic calcium phosphates resorption markers in, 582 474–477 Behavioral Risk Factor Surveillance Bone types, 584–585 rheumatic diseases and, 474 INDEX System (BRFSS), 3 Bony abnormalities, 35–36 Candidiasis, 392 Behçet’s disease, 56, 435–439 BOOP. See Bronchiolitis obliterans Capsaicin, 624 brainstem involvement in, 437 organizing pneumonia Capsulitis, adhesive, 72 classifi cation of, 680 Borage oil, 691 Carbamazepine, 624 clinical manifestations, 436–438 Borrelia burgdorferi, 44, 52, 282–283 Carcinomatous polyarthritis, 477 diagnosis, 438 Boswellia, 691 Cardiovascular system disease activity, 438–439 Brachialgia, 65 ANCA and, 420 international study group criteria for, Brachial plexopathy, 72 in ankylosing spondylitis, 196 436 Brachyolmia, 563 glucocorticoids and, 647 management of, 439 BRFSS. See Behavioral Risk Factor in idiopathic infl ammatory pathogenesis, 439 Surveillance System myopathies, 365, 366 ulcers in, 436 Bromelain, 691 NSAIDs, 641 Benign angiopathy, 441 Bronchiolitis obliterans organizing in SLE, 310–311 Bicipital tendon pneumonia (BOOP), 118, 370 in systemic sclerosis, 348 rupture of, 71–72 Bronchoalveolar lavage (BAL), 377 Carnitine palmitoyltransferases (CPT), tendinitis, 71–72 Bunionette, 83 386 706 INDEX

Carpal tunnel syndrome, 630 CINCA. See Chronic infantile in SLE treatment, 328–330 Carpometacarpal (CMC) joint, 49, 75 neurological cutaneous in RA XXXX Cartilage arthropathy Costimulatory interactions, 101, destruction, 130 CK. See Creatine kinase 335–336 enzymes in degradation of, 231 Clobetasol, 330 Costochondritis, 84 MRI of, 35 Clonazepam, 624 COX-2. See Cyclooxygenase-2 in OA, 229–230 Clubbed fi nger, 505 CPM. See Continuous passive motion Cartilaginous loose bodies, 545 CMC joint. See Carpometacarpal joint CPPD. See Calcium pyrophosphate Caspar criteria, 172 Coccidioides immitis, 294 dehydrate deposition disease Cat’s claw, 692 Coccidioidomycosis, 294 CPT. See Carnitine Cauda equina compression, 58 Coccydynia, 79 palmitoyltransferases CCP. See Cyclic citrullinated peptide Codfi sh vertebrae, 554 CRASP gene, 285 CDC. See Centers for Disease Control Cogan’s syndrome, 441–442 C-reactive protein (CRP), 16, 52 CDSMP. See Chronic Disease Self localized corneal edema in, 441 Creatine kinase (CK), 375, 385 Management Program Cognitive behavioral therapy, for CRP. See C-reactive protein Cell migration, 129 fi bromyalgia, 92 CRPS. See Complex regional pain Centers for Disease Control (CDC), 3 Colchicine, 44 syndrome Cerebrospinal fl uid (CSF), 90, 437 in gout treatment, 259 Cryoglobulinemic vasculitis, 429–431 Cervical disc herniation, 65 Cold clinical presentation, 430 Cervical spine in pain management, 625 defi nition, 429 mechanical disorders of, 64–66 in rehabilitation, 602–604 diagnosis, 430–431 operative treatment, 661–662 Common variable immunodefi ciency prognosis, 431 radiograph of, 197 (CVID), 105, 517 therapy, 431 Cervical spondylosis, 65 Complement, 19, 98 Cryoglobulins, 19 CHAQ. See Childhood Health in SLE, 312–313 Cryopyrinopathies, 465–466 Assessment Questionnaire Complementary and alternative clinical fi ndings, 466 Charcot’s joints, 227 medicine (CAM), 625–626, laboratory fi ndings, 466 CHB. See Congenital heart block 664–667 treatment, 466 Cheiralgia paresthetica, 76 miscellaneous, 667 Cryptococcosis, 294–295 Childhood Health Assessment resources on, 667 Cryptococcus neoformans, 294 Questionnaire (CHAQ), 160 Complex regional pain syndrome Crystal disease, 486 Children, septic arthritis in, 275 (CRPS), 509–511 Crystalline arthritis, 54 Chlamydia, 218 clinical features of, 509–510 Crystals Cholesterol crystals, 26 epidemiology of, 509 deposition, 265 Chondrocalcinosis, 267 in hands, 510 oxalate, 269 in hand, 35 laboratory features in, 510–511 pathogenic, 269 Chondrocytes, activation by catabolic mechanisms of, 511 in synovial fl uid analysis, 25–26 pathways, 233 pathophysiology of, 511 urate, 255–256 Chondrodysplasias, 559–561 treatment, 511–512 CSF. See Cerebrospinal fl uid classifi cation, 559 Computed tomography (CT), 28, 32–33 CT. See Computed tomography achondroplasias, 561 of hip, 33 Cubital bursitis, 74 diagnosis, 559–560 of osteonecrosis, 567 Curcumin, 692 features of, 560 of tarsal coalition, 33 Cushing’s syndrome, 483 management of, 564 Congenital heart block (CHB), 315 Cutaneous extravascular necrotizing pathogenesis, 559 Continuous passive motion (CPM), 662 granulomas, 502 punctata, 563 Conventional radiography, 28–29 Cutaneous leukocytoclastic angiitis, rhizomelic, 563 Copper, 700 428 Chondroitin sulfate, 237, 692 Core decompression, 570 CVID. See Common variable Chondromalacia patellae, 81 Corticosteroids, 23 immunodefi ciency Chondromatosis, synovial, 545 in idiopathic infl ammatory myopathy Cyclic citrullinated peptide (CCP), 133 Chondrosarcomas, synovial, 547 treatment, 379 Cyclooxygenase-2 (COX-2), 134, 238, Christmas disease, 470, 471 injections 256, 634–636 Chromium, 700 complications, 631 Cyclophosphamide Chronic Disease Self Management diluting, 630 in SLE treatment, 332–333 Program (CDSMP), 614–615 dose in, 628 in systemic sclerosis treatment, 361 Chronic infantile neurological cutaneous effi cacy, 628, 629 Cyclosporine, 138, 157 arthropathy (CINCA), 151, 460 gloves, 630–631 PsA treatment with, 187–188 Chronic pain of complex etiology, 621 needle length in, 628–629 in SLE treatment, 332 Churg-Strauss syndrome, 416–425, 420 preparations, 628, 630 Cysts classifi cation criteria for, 417 reactions to, 631 Baker’s, 79–80 classifi cation of, 678 in JIA treatment, 155–156 popliteal, 79–80 INDEX 707

Cytokines Disc herniation EMG. See Electromyography in ankylosing spondylitis, 207 cervical, 65 Endocrine factors, 165 blockade, 336 diagnosing, 36 Endoplasmic reticulum (ER), stress, 203 fi broblast, 127–129 lumbar, 61–62 Enteropathic arthritis, 55 in idiopathic infl ammatory Disease-modifying antirheumatic drugs Enteropathic spondyloarthritis, 220–221 myopathies, 373 (DMARDs), 134, 135–137, 287 axial, 221 macrophage, 127–129 in JIA treatment, 157 diagnostic studies on, 221 networks, 127, 128 DISH. See Diffuse idiopathic skeletal genetics, 221 in OA, 231–233 hyperostosis peripheral, 220 cartilage repair, 232–233 Disodium etidronate, 574 treatment, 221 lipid mediators, 231 Distal biceps insertion, rupture of, 74 Enthesitis matrix degradation products, 232 Distal interphalangeal (DIP) joints, 49 in ankylosing spondylitis, 194 mechanical stress, 232 in RA, 115 juvenile idiopathic arthritis and, reactive oxygen species, 231–232 Distal renal tubular acidosis (dRTA), 146–147, 152 oligoarthritis and infl ammatory, 150 393 in PsA, 174 in PsA, 180 DMARDs. See Disease-modifying Environmental factors, in PsA, 179–180 T cell-derived, 127 antirheumatic drugs Enzyme-linked immunofl uorescent Cytophagic histiocytic panniculitis, 496 Dowager’s hump, 578 assay (ELISA), 16, 19, 118 Drug-induced lupus, 55 Eosinophilic fasciitis, 350 D Drug-related lupus, 316–317 clinical features, 468 Dactylitis, 9, 14, 146 Drugs, osteoporosis and, 590 laboratory features, 468 in PsA, 173 Dry mouth symptoms, differential Eosinophilic synovitis, 468 Dapsone, in SLE treatment, 331 diagnosis, 392 Epicondylitis DC. See Dendritic cells Dual-energy x-ray absorptiometry lateral, 73 Deep venous thrombosis (DVT), 438 (DXA), 3, 39 medial, 73–74 Dehydroepiandrosterone, 692 in osteoporosis, 578–579, 581 Epidemiology, of fi bromyalgia, 88 Deletion/insertion polymorphisms Dupuytren’s contracture, 78 Epididymitis, 438 (DIPs), 110 DVT. See Deep venous thrombosis Epstein-Barr virus (EBV), 53, 124, 390 Dendritic cells (DC), 97, 202 DXA. See Dual-energy x-ray Erythema elevatum diutinum, 442 Deposition diseases, 523–531 absorptiometry Erythema migrans, 283 Depot corticosteroid-induced iatrogenic Erythema nodosum, 495 infl ammation, 269 E Erythrocyte sedimentation rate, 15–16, De Quervain’s tenosynovitis, 10, 75, 630 EBV. See Epstein-Barr virus 52 Dermatologic disorders, 492–503 Echinococcus granulosus, 295 Estrogen, in osteoporosis treatment, 596 Dermatomyositis, 9, 55, 368 Echocardiogram, in Kawasaki disease, Etanercept amyopathic, 363 447 ankylosing spondylitis, 212 diagnosis of, 676 ECM. See Extracellular matrix PsA, 188 humoral and endothelial mechanisms EDS. See Ehlers-Danlos syndrome RA, XXXX in, 372–373 Education, self-management, 614–615 Juvenile Polyarthritis, XXXX juvenile, 363 Efalizumab, in PsA, 189 Ethnic differences, 111 Dermatosparaxis type, 553 Efferocytosis, 323 Etidronate, 595 Desert rheumatism, 294 Ehlers-Danlos syndrome (EDS), Evening primrose, 693 Desmopressin, 472 551–553 Examination Devil’s claw, 692 arthrochalasia type, 552–553 ankle, 13–14 Diabetes mellitus, 479–480 classical type, 551 elbow, 10 INDEX neuropathic arthropathy in, 489–490 dermatosparaxis type, 553 forefoot, 14 rheumatologic manifestations of, 480 hypermobility type, 551 hand, 9–10 Diastrophic dysplasia, 562 kyphoscoliosis type, 552 hindfoot, 13–14 Diet, 666–667 types of, 552 hip, 11–12 Diffuse idiopathic skeletal hyperostosis vascular type, 551–552 in JIA, 163 (DISH), 227, 480 Elbow knee, 12–13 Digital radiography, 29 disorders of, 73–74 midfoot, 14 Digital tip pitting scars, 346 examination of, 10 monarticular joint disease, 43 Dimethyl sulfoxide, 692 operative treatment, 660 in OA, 225 DIP joints. See Distal interphalangeal Electrical stimulation, in rehabilitation, polyarthritis, 51–52 joints 603 principles, 7–8 DIPs. See Deletion/insertion Electromyography (EMG), 62 in RA, 116–118 polymorphisms in idiopathic infl ammatory shoulder, 10–11 Disability, 599–600 myopathies, 365, 375 SI joint, 12 examples of, 600 ELISA. See Enzyme-linked spine, 12 prevention, 615 immunofl uorescent assay wrist, 9–10 708 INDEX

Exercise therapy, 603–604, 665 Fish oil, 692 GERD. See Gastroesophageal refl ux Extracellular matrix (ECM), damage, Flaxseed, 693 disease 130 Fluoride, 700 Giant cell arteritis (GCA), 398–404 Eyes Folate, 699 classifi cation of, 679 ANCA and, 419 Forefoot, examination of, 14 clinical features of, 401–403 in ankylosing spondylitis, 195 Foreign body reactions, monarthritis cranial, 401–402 glucocorticoids and, 648 and, 45 fever, 402 JIA and, 166 Fractures large vessel, 403 sarcoidosis and, 515–516 hip, 576–577 spectrum of, 402 in Sjogren’s syndrome, 391 risk for, 577 diagnosis of, 403–404 treatment of, 395 vertebral, 577 imaging studies, 403–404 in SLE, 312 wrist, 577 laboratory testing, 403 Frozen shoulder, 72 epidemiology, 398–399 F Functional losses, 7 histomorphology of, 399 Fabry’s disease, 529–530 Functioning, 599–600 pathogenesis, 399–400, 400–402 clinical features, 529 artery in, 400–401 treatment, 529–530 G immune response in, 399–400 Familial cold autoinfl ammatory GAIT. See Glucosamine-Chondroitin schematic diagram of, 400 syndrome (FCAS), 460 Arthritis Intervention Trial systemic infl ammatory response, Familial Mediterranean fever, 54, 96, Gait, Arms, Leg, Spine (GALS) 401 460–463 system, 8 prognosis, 404 clinical features of, 462–463 GALS system. See Gait, Arms, Leg, risk factors for, 401 laboratory features of, 462–463 Spine system treatment, 404 treatment, 463 Gamma-linolenic acid (GLA), 694 vasculitic lesions, 399 Farber’s disease, 530 Ganglion, 74–75 Giant cell tumor, 547–548 Fat-soluble vitamins, 696 Gastric antral venous ectasia Giardia lamblia, 295 Fertility, 685–686 (GAVE), 362 Ginger, 693 Fever, GCA manifesting as, 402 Gastroesophageal refl ux disease Gingko, 693 Fibrinoid necrosis, 413 (GERD), 347 GLA. See Gamma-linolenic acid Fibroblastlike synoviocytes, 129–130 Gastrointestinal (GI) tract Glenohumeral joint, motion, 11 Fibroblasts, cytokines, 127–129 ANCA and, 420 Glucocorticoids, 483, 644–649 Fibrodysplasia ossifi cans progressiva, glucocorticoids and, 648 adverse effects of, 647–648 555 in idiopathic infl ammatory cardiovascular, 647–648 Fibromyalgia, 8, 87 myopathies, 365, 366 dermatological, 648 classifi cation criteria of, 88 infl ammation, 147 endocrine, 647 clinical features of, 88 microbes in, 204 gastrointestinal, 648 etiology and pathogenesis of, 90–91 NSAIDs and, 639–640 infectious, 648 environmental infl uences, 90 in SLE, 312 musculoskeletal, 647 genetic infl uences, 90 in systemic sclerosis, 347 ophthalmological, 648 hypothalamic-pituitary and Gaucher’s disease, 528–529 psychological, 648 autonomic dysfunction, 90 clinical features, 528 in ankylosing spondylitis treatment, psychological and behavioral laboratory features, 528–529 211 factors, 91 radiographic features, 528 crystals, 26 sensory processing, 90 treatment, 529 mechanisms of action, 644–645 evaluation and treatment for, 91 GCA. See Giant cell arteritis on immune cells, 644, 645 pharmacologic management of, Generalized pustular psoriasis, 500 molecular, 644–645 624 Genetics osteoporosis induced by, 690 treatment, 91–93 determining components, 111–112 in PsA management, 187 aerobic exercise for, 92 disease cause and, 108–109 receptor ligands, 648–649 cognitive behavioral therapy, 92 enteropathic spondyloarthritis, standardized nomenclature on, 646 complementary therapies, 93 221 therapeutic use, 645–647 diagnosis label, 91 in idiopathic infl ammatory in daily practice, 646 education, 91–92 myopathies, 370–371 infl ammation inhibition, 645 pharmacologic therapies, 92 ?? in JIA, 150 radiographic progression and, Curious why page numbers for in osteoporosis, 588–589 646 ‘Pharmacologic Management in PsA, 179 resistance, 647 of above are different? in RA, 123 Glucosamine, 237, 694 Fibrosing diseases, 496–499 in sarcoidosis, 514 Glucosamine-Chondroitin Arthritis dermatological conditions in SLE, 323–324 Intervention Trial (GAIT), 666 associated with, 497–498 in systemic sclerosis, 352 Glycogenoses, muscle, 381–385 Fibrosis, systemic sclerosis, 357–358 terminology, 109 Gonococcal (GC) joint disease, 275 INDEX 709

Gout, 477 Granuloma annulare, 501–502 Heparin, 25 acute intermittent, 242–243 on dorsal hands, 502 Hepatitis B, 53 clinical associations, 246–247 subcutaneous, 502 viral arthritis, 279–280 hyperlipidemia, 247 Growth, in JIA, 163–166 Hepatitis C, 55, 120, 390 hypertension, 247 Growth hormone (GH), JIA therapy, 165 autoimmune conditions associated obesity, 247 Gut-associated lymphoid tissue with, 279 renal disease, 246–247 (GALT), 95 serologic abnormalities in, 279 diagnosis, 247–248 GVHD. See Graft versus host disease viral arthritis and, 278–279 early-onset, 244–245 Herbs, 666 epidemiology, 250–251 H Heritable disorders of connective tissue, in hands, 242 Hallux valgus, 83 549–557 laboratory features of, 247–248 Hammer toe, 83 Ehlers-Danlos syndrome, 551 management of, 258–262 Hand fi brodysplasia ossifi cans progressiva, ACTH, 259 chondrocalcinosis in, 35 555 asymptomatic, 261 CRPS in, 510 ??? What is this ? homocystinuria, 550–551 colchicine, 259 disorders, 74–78 joint instability syndromes, 553 glucocorticosteroids, 259 examination, 9–10 Marfan syndrome, 549–550 NSAID, 258–259 global function of, 9 mucopolysaccharidoses, 555–557 pharmacologic antihyperuricemic gout in, 242 osteogenesis imperfecta syndromes, treatments, 259–260 neutrophilic dermatosis of, 494 553–555 prophylactic, 259 operative treatment, 659–660 pseudoxanthoma elasticum, 555 uric acid lowering, 259–260 Haplotypes, 110 stickler syndrome, 551 MRI of, 244 Haversian system, 585 HGPRT. See Hypoxanthine-guanine in MTP joints, 243 hCMV. See Human cytomegalovirus phosphoribosyltransferase normouricemic, 245–246 HCQ. See Hydroxychloroquine Hidradenitis suppurativa, 500 in organ transplantation patients, 245, HDCT. See Heritable disorders of Highly active antiretroviral therapy 261 connective tissue (HAART), 280 pathogenesis of, 251–254 Health Plan Employer Data and Hindfoot, examination of, 13–14 adiposity, 253–254 Information Set (HEDIS), 3, 4 Hip alcohol and, 252–253 Healthy People 2010, 4 CT scan of, 33 dietary infl uences, 252 Heat disorders, 78–79 insulin resistance, 253–254 in pain management, 625 examination of, 11–12 urate metabolism, 251–252 in rehabilitation, 602–604 fractures, 576–577 urate production pathways, 252 Heat shock protein (HSP), 439 in operative treatment, 656–657 urate solubility, 251 HEDIS. See Health Plan Employer radiograph, 656 pathology of, 255 Data and Information Set Histoplasma capsulatum, 295 provocative factors of acute attacks, HELLP syndrome, 339 Histoplasmosis, 295 246 Hemangiomas, synovial, 547 History, 6–7 pseudo, 265 ?? Not sure what this Hemarthrosis, 25 family, 7 means ? At fi rst I assumed it monarthritis and, 45 functional losses, 7 referred to pseudogout – which Hematologic disorders, nonmalignant, in idiopathic infl ammatory makes sense – but then note that 470–474 myopathies, 367 there is a listing for that but with Hemochromatosis, 56, 523–525 infl ammation and weakness in, 7 different page numbers ?? clinical features, 523–524 location and symmetry in, 6 radiographic features of, 247 laboratory features of, 524–525 in OA, 225 INDEX refractory, 261–262 radiographic features of, 524 onset and chronology in, 6–7 in sickle cell disease, 473–474 treatment of, 525 in polyarthritis, 47–50 stages of, 241–244 Hemoglobinopathy-associated distribution of, 49–50 advanced, 243–244 musculoskeletal manifestations, extra-articular symptoms, 50 asymptomatic hyperuricemia, 472–474 family, 50 241–242 Hemophilia, 57, 470–472 pain characteristics, 49 unusual presentations of, 244–246 operative treatment, 655 pattern of, 48–49 in women, 245 radiographs in, 472 time course of, 48 Gouty arthritis, 54 ?? Not sure what treatment, 471–472 questions in, 6 this refers to ? There is a whole Henoch-Schönlein purpura, 431–432 systemic features, 7 section on Gout which is where classifi cation of, 678 HIV. See Human immunodefi ciency this belongs but page numbers clinical presentation, 431 virus don’t seem to jive. defi nition, 431 HLA. See Human leukocyte antigens classifi cation of, 674 diagnosis, 431–432 HOA. See Hypertrophic Graft versus host disease (GVHD), prognosis, 432 osteoarthropathy 499 therapy, 432 Homocystinuria, 550–551 710 INDEX

Hormonal therapy, in SLE treatment, pathogenesis of, 251–254 genetic factors, 370–371 333 adiposity, 253–254 mechanisms, 371 HPA. See Hypothalamic-pituitary- alcohol and, 252–253 MHC in, 373–374 adrenal insulin resistance, 253–254 pathology, 368–370 Human cytomegalovirus (hCMV), 352 urate metabolism, 251–252 prognosis, 367 Human immunodefi ciency virus (HIV), urate production pathways, 252 treatment of, 378–380 50, 53, 390 urate solubility, 251 extramuscular manifestations of, viral arthritis, 280 pharmacologic treatments, 260–261 380 Human leukocyte antigens (HLA), 98, urate-lowering agents and, 254 general measures, 378–379 112, 120, 154 Hypochondroplasia, 561 pharmacologic, 379 B27, 218 Hypocomplementemic urticarial IFN. See Interferon in ankylosing spondylitis, 201–203 vasculitis syndrome, 432–433 IL-1. See Interleukin 1 crystallized, 204 clinical presentation, 432–433 IL-6. See Interleukin 6 evolutionary pathway of, 205 defi nition, 432 Iliopsoas bursitis, 78–79 host immune responses and, 219 diagnosis, 433 Imaging, 28–40. See also specifi c host-pathogen interactions, 219 prognosis, 433 techniques subtypes, 204–205 therapy, 433 in amyloidosis, 540–541 shared epitope hypothesis and, 123 Hypogonadism, osteoporosis and, 589 decisions, 40 Hyaluronan, 24 Hypoparathyroidism, 482 in GCA, 403–404 Hyaluronates, intra-articular, 631–632 Hypopyon, 437 HOA, 506 Hydrotherapy, 603 Hypothalamic-pituitary-adrenal (HPA), in osteoporosis, 578–579 Hydroxyapatite, 26 609 Immune cells, 95 Hydroxychloroquine (HCQ), 135, 138 Hypothyroidism, 481 glucocorticoids and, 644, 645 Hyperbaric oxygen, 569 Hypoxanthine-guanine innate, 97–98 Hypercholesterolemia, 486 phosphoribosyltransferase in SLE, 324–325 HyperIgE syndrome (HIES), 102 (HGPRT), 245 Immune complex-mediated vasculitis, Hyperimmunoglobulinemia D with 427–433 period fever syndrome (HIDS), I clinical syndromes, 428–433 460, 463–464 Ibandronate, 595 cryoglobulinemic vasculitis, clinical fi ndings, 463–464 IBD. See Infl ammatory bowel disease 429–431 laboratory fi ndings, 463–464 ICAM-1. See Intercellular adhesion hypersensitivity vasculitis, Hyperlipidemia molecule 1 428–429 classifi cation of, 485 Idiopathic infl ammatory myopathies hypocomplementemic urticarial in gout, 247 assessment of, 375–378 vasculitis syndrome, 432–433 Hyperlipoproteinemia, 54, 485 tools, 375–378 pathophysiology, 427–428 management, 486 clinical features of, 363–365 Immune system, 94–96 Hyperparathyroidism, 481–482 constitutional, 363–364 Immunoablation Hypersensitivity vasculitis, 428–429 GI tract, 365 with stem cell transplantation, in SLE classifi cation of, 679 heart, 365 treatment, 334 clinical presentation, 428–429 joints, 364 without stem cell transplantation, in defi nition, 428 lungs, 364–365 SLE treatment, 334 diagnosis, 429 malignancy, 365 Immunoglobulins, 104–106 prognosis, 429 myositis, 365 gene rearrangement, 104–106 purpura in, 428 skeletal muscle, 364 Immunological diseases, 94–106 therapy, 429 skin, 364 Immunopathogenesis, of ANAs, Hypertension, in gout, 247 immunopathology, 368–370 321–322 Hyperthyroidism, 481 investigations, 365–367 Impingement test, 71 Hypertrophic osteoarthropathy electromyography, 365, 376 Inclusion body myositis, cytotoxic (HOA), 57 heart, 366 mechanisms in, 372 classifi cation of, 505 intestine, 366 Indian frankincense, 694 clinical features, 505–506 lung, 366 Infections diagnosis, 507 muscle biopsy, 365–366, 376 identifying bone, 36 imaging, 506 radiography, 376 monarthritis, 44–45 laboratory features, 506 serum autoantibodies, 366–367, Infectious arthritis, 54, 56 pathogenesis, 504 377, 378 Infl ammation, 7 theoretical, 506 serum muscle enzymes, 365 depot corticosteroid-induced pathology, 504 skin, 366, 376 iatrogenic, 269 radiographs in, 507 natural history, 367 GI, 147 treatment, 507 pathogenesis, 370–374 glucocorticoids and, 645 Hyperuricemia chemokines in, 373 in monarthritis, 43 asymptomatic, 241–242 cytokines in, 373 ocular, 437 management, 261 environmental factors, 371–372 pathogenesis of, 264–265 INDEX 711

in systemic sclerosis, 353 classifi cation criteria for, 143 coronary and peripheral aneurysms, urate crystal-induced, 255–256 clinical features, 142–144 445 Infl ammatory bowel disease (IBD), 50 enthesitis, 146–147, 152 cutaneous manifestations of, 446 in ankylosing spondylitis, 195–196 epidemiology, 142 diagnosis of nonarticular complications of, 221 examination, 163 principle criteria for, 445 Infl iximab eye disease and, 166 revised guidelines, 447 ankylosing spondylitis and, 213 growth in, 163–166 echocardiogram criteria, 447 in PsA, 188 general, 164 epidemiology, 447 in RA, XXX local, 164 etiology, 447–448 Injections, image-guided, 40 nutrition, 165 pathogenesis, 448 Innate immunity, 96–98 osteopenia, 164 peripheral aneurysms in, 445 cells, 97–98 osteoporosis, 164 recommended therapy, 447 Insulinlike growth factor 1, 165 thyroid disease, 165 strawberry tongue in, 446 Insulin resistance, in gout, 253–254 meta-analysis of, 148 treatment, 448–449 Intercellular adhesion molecule 1 ocular involvement in, 147–148 Kidneys (ICAM-1), 355, 373 oligoarthritis, 145–146, 149–150 ANCA and, 419–420 Interferon (IFN), 400 cause of, 150 in ankylosing spondylitis, 196 Interleukin 1 (IL-1), 128–129 genetic predisposition, 150 in gout, 246–247 receptor antagonist protein, 129 infl ammatory cytokines, 150 NSAIDs and, 640 Interleukin 6 (IL-6), 129, 165 joint damage, 150 in SLE, 308–310 Intermittent hydrarthrosis, 467–468 laboratory fi ndings, 149 in systemic sclerosis, 348–349 clinical features, 467–468 synovium in, 149 transplantation, 309 laboratory features, 467–468 treatment, 158 Killer immunoglobulinlike receptors Interphalangeal (IP) joints uveitis, 149–150 (KIR), 179 swelling of, 116 outcomes, 160–161 Klebsiella aeruginosa, 194 ultrasound of, 38 pain in, 168 Klebsiella pneumoniae, 218 Intersection syndrome, 75 polyarthritis, treatment, 158 Knee Intravenous immunoglobulin (IVIg) polyarthritis RF negative, 145 arthroscopic view of, 658 in idiopathic infl ammatory myopathy polyarthritis RF positive, 145 disorders, 79–81 treatment, 379 polyarticular, 151–152 examination of, 12–13 in JIA treatment, 158 psoriatic, 146, 152 OA treatment, 236 in SLE treatment, 334 treatment, 159 operative treatment, 657–659 Iron, 700–701 psychosocial and educational issues, palpation, 13 Ischial bursitis, 79 167–168 radiographs, 658 IVIg. See Intravenous immunoglobulin systemic arthritis, treatment, 158 Kniest dysplasia, 562 Ixodes scapularis, 282 systemic category, 145, 150–151 Kyphoscoliosis, 552 laboratory fi ndings in, 150–151 J pathogenesis, 151 L Jansen metaphyseal chondrodysplasias, treatment Labial salivary gland, 393 562–563 anti-IL-6 receptor antibody, 158 Laboratory evaluation, 15–19 JIA. See Juvenile idiopathic arthritis biologic-modifying medications, in alkaptonuria, 526–527 Joint destruction, in RA, 129–130 157–158 CRPS, 510–511 ??? What is this ?? Joint dysplasias, 559–564 corticosteroid, 155–156 in Gaucher’s disease, 528–529 Joint instability syndromes, 553 DMARDs, 157 in GCA, 403 c-Jun N-terminal kinases (JNKs), 232 enthesitis-related, 159 in gout, 247–248 INDEX Juvenile Arthritis Damage Index future research, 161 of hemochromatosis, 524–525 (JADI), 161 IL-1 receptor antagonists, 158 HOA, 506 humoral and endothelial mechanisms IVIg, 158 in monarticular joint disease, 44 in, 372–373 lefl unomide, 157 in multicentric reticulohistiocytosis, Juvenile Arthritis Functional Assessment MTX, 156–157 531 Report (JAFAR), 160 NSAIDs, 155 in ochronosis, 526–527 Juvenile Arthritis Self-Report Index physical therapy in, 159 polyarthritis, 52 (JASI), 160 rationale, 154 in RA, 118–119 Juvenile dermatomyositis (JDM), 363, SSZ, 157 in septic arthritis, 272–273 375 uveitis, 159 in systemic juvenile idiopathic Juvenile idiopathic arthritis (JIA), 56, undifferentiated, 147 arthritis, 150–151 142–149 Juvenile osteochondroses, 563–564 in Wilson’s disease, 527 adherence and, 166–167 Lactate dehydrogenase (LDH), 375 assessment of, 167 K Lactation, 685–686 factors impacting, 166 Kawasaki’s disease, 444–449 Lateral epicondylitis, 73 improving, 167 classifi cation of, 680 Lateral stenosis, 63 category characteristics, 144 clinical features of, 444–445 LDH. See Lactate dehydrogenase 712 INDEX

LE. See Lupus erythematosus treatment, 287–288 muscle glycogenoses, 381–385 Lefl unomide, 137–138 recommended, 288 myoadenylate deaminase in JIA treatment, 157 Western blot interpretation, 286 defi ciency, 387 PsA treatment with, 188 Lymphoma, 476 secondary, 387 in SLE treatment, 333 Lyzosomal granule enzymes, 18 Metacarpophalangeal (MCP) joints, 9, Leprosy, 293 49, 76, 77 Leukemia, 54 M in RA, 115 Leukemic arthritis, 475–476 Macrophage activation syndrome subluxation of, 116 Lichen planus, 502, 503 (MAS), 448 ulcers, 345 Lichen sclerosus, 496 Macrophages, cytokines, 127–129 ultrasound of, 38 Lidocaine, 22, 624 Magnesium, 701 Metaphyseal chondrodysplasias, 562 Lifestyle issues, in osteoporosis, Magnetic resonance imaging (MRI), 28, Jansen, 562–563 593–594 33–36, 63 McKusick, 563 Linkage disequilibrium (LD), 110 in bone infection identifi cation, 36 Schmid, 563 Lipid, 26 in bony abnormality detection, 35–36 Metastatic carcinomatous arthritis, 475 metabolism disorders, 385–386 of cartilage, 35 Metatarsalgia, 83 Lipochrome histiocytosis, 530 in disc herniation diagnosis, 36 Metatarsophalangeal (MTP) joints, 14, Lipodermatosclerosis, 495–496, 496 of gout, 244 49 Lipoma, intra-articular, 546 in idiopathic infl ammatory gouty arthritis in, 243 Lipopolysaccharide (LPS), 96 myopathies, 366 in RA, 115 Livedoid vasculopathy, 501 muscle abnormalities and, 36 Metatropic dysplasia, 563 Liver, in SLE, 312 in muscular neoplasm evaluation, 36 Methotrexate (MTX), 135, 137, 140, 379 Localized bone pain, 60 of osteonecrosis, 567 in ankylosing spondylitis treatment, Long thoracic nerve paralysis, 72 in osteonecrosis diagnosis, 36 212 Lorazepam, 624 in PVNS, 544 in JIA treatment, 156–157 LPS. See Lipopolysaccharide Major histocompatibility complex NSAID interactions with, 642 Lumbar disc herniation, 61–62 (MHC), 98–99, 112–113, 194 In PsA treatment, 187 Lumbar spine in ankylosing spondylitis, 205 in RA treatment, XXXX radiograph of, 197 class I, 99 in SLE treatment, 331–332 stenosis, 63 class II, 99 in systemic sclerosis treatment, 362 Lumbosacral spine, mechanical disease associations with, 113 Methylsulfonylmethane (MSM), 666, disorders of, 61–64 in idiopathic infl ammatory 694–695 Lumbosacral spondylosis, 62–63 myopathies, 373–374 MHC. See Major histocompatibility Lungs MALT. See Mucosa-associated complex ANCA and, 418–419 lymphoid tissue Microaneurysms, 411 in ankylosing spondylitis, 196 MAPK. See Mitogen-activated protein Microscopic polyangiitis, 416–425 in idiopathic infl ammatory kinases alveolar hemorrhage in, 419 myopathies, 364–365, 366 Marfan’s disease, 354 Midfoot, examination of, 14 sarcoidosis and, 515, 518, 519 Marfan syndrome, 549–550 Migration inhibitory factor (MIF), 151 in SLE, 311–312 MAS. See Macrophage activation Milwaukee shoulder syndrome, 268–269 in systemic sclerosis, 347–348 syndrome Minerals, 699–702 Lupus anticoagulant (LA), 340 Massage, 625, 665–666 Minimally invasive surgery (MIS), 657 Lupus erythematosus (LE), 25 Matrix metalloproteinases (MMPs), Minor allele frequency (MAF), 109 classifi cation of, 309 178 Mitogen-activated protein kinases Lupus nephritis McArdle’s disease, 381 (MAPK), 129–130 active, 320 McKusick metaphyseal Mixed connective tissue disease, 55 immune deposits in, 320 chondrodysplasias, 563 MMF. See Mycophenolate mofetil WHO classifi cation of, 308 Medial epicondylitis, 73–74 MMPs. See Matrix metalloproteinases Lupus panniculitis, 495 Medial plica syndrome, 80 Molecular mimicry, 124 Lyme disease, 56, 282–289 Medical model, public health model reactive arthritis and, 219–220 clinical manifestations of, 283–285 and, 2 Monarthritis, 120 early disseminated infection, 284 Meditation, 664–665 crystal-induced, 45 early localized, 283–284 Melatonin, 694 diagnosis of, 42–43 late disease, 284–285 Meniscus tears, 35 foreign body reactions, 45 diagnosis, 286–287 Meralgia paresthetica, 79 hemarthrosis and, 45 epidemiology, 282–283 Metabolic myopathies, 381–387 infection in, 44–45 erythema migrans in, 283 primary, 381–387 infl ammatory causes of, 43 pathogenesis, 285–286 key features of, 382–383 initial treatment, 44 in pregnancy, 287 lipid metabolism disorders, laboratory tests in, 44 prevention, 288–289 385–386 non-infl ammatory causes of, 43 prognosis, 287–288 mitochondrial, 386–387 osteoarthritis and, 45 INDEX 713

osteonecrosis, 45 Myeloma, multiple, 476 Neuropathic pain, 621 physical examination, 43 Myelopathy, 65–66 Neuropathy, suprascapular neuropathy, specifi c types of, 44–45 Myeloperoxidase (MPO), 18 72 synovial fl uid analysis, 43–44 Myoadenylate deaminase defi ciency, Neutrophilic dermatoses, 492–495 systemic rheumatic diseases, 45 387 associations with, 493 trauma and, 45 Myopathy. See also Idiopathic of dorsal hands, 494 Monocyte chemoattractant protein infl ammatory myopathies; rheumatoid, 494 (MCP), 314 Metabolic myopathies Neutrophils, 256 Mononeuritis multiplex, 412 in scleroderma, 349 NK cells. See Natural killer cells Monosodium urate crystals, 26 Myositis Nociceptive pain, 620–621 Morning stiffness, 60 in idiopathic infl ammatory NOMID. See Neonatal-onset Mortality, in PsA, 175 myopathies, 365, 375, 377–378 multisystem infl ammatory disease Morton’s neuroma, 83–84 sarcoidosis and, 517 Nonspecifi c interstitial pneumonitis MSM. See Methylsulfonyl methane in scleroderma, 349 (NSIP), 370 MTP joints. See Metatarsophalangeal in hyperlipoproteinemia management, joints N 486 Mucin clots, 24 Nail pitting, 146 Nonsteroidal anti-infl ammatory drugs Muckle Wells syndrome (MWS), 151, National Arthritis Act, 3 (NSAIDs), 44, 61, 63, 65, 71, 76, 460 National Arthritis Action Plan 154, 634–642 Mucopolysaccharidoses, 555–557 (NAAP), 3 adverse effects of, 638–639 Mucosa-associated lymphoid tissue National Committee on Quality allergic reactions, 641 (MALT), 95 Assurance (NCQA), 3 asthma, 641 Multicentric reticulohistiocytosis, 55 National Health Interview Survey cardiovascular, 641 clinical features, 530–531 (NHIS), 4 gastrointestinal, 639–640 fi ngers in, 530 Natural killer (NK) cells, 125, 179 hepatic, 640–641 laboratory features, 531 NCQA. See National Committee on renal, 640 synovium in, 530 Quality Assurance in ankylosing spondylitis treatment, treatment, 531 Neck pain, 58–66 211 Multifocal sterile recurrent fever and weight loss and, 60 clinical pharmacology, 637 osteomyelitis, 492 initial evaluation of, 58–60 drug interactions, 641–642 Multiple epiphyseal dysplasia (MED), mechanical, 64 anticoagulants, 642 562 recumbency, 60 antihypertensives, 642 Multiple myeloma, 476 stiffness and, 60 MTX, 642 Muscle biopsy, in idiopathic Neck strain, 65 salicylates, 641–642 infl ammatory myopathies, Neisseria gonorrhoeae, 44, 45, 120 in gout treatment, 258–259 365–366, 375 Neonatal lupus, 315 in JIA treatment, 155 Muscle glycogenoses, 381–385 Neonatal-onset multisystem list of, 636 Muscle relaxants, 211 infl ammatory disease (NOMID), mechanism of action, 636–637 in pain management, 623 96, 460 in OA treatment, 238–239 Muscle strength testing, 601 Neoplasms, joint, 534–548 prostaglandin biology, 634–636 Musculoskeletal system primary, 543–547 in PsA, 186–187 bioenergetics, 384 secondary, 547–548 in RA treatment, 654 cancer and, 474–477 Neoplasms, musculoskeletal, evaluating, in reactive arthritis treatment, 220 evaluation of, 683 36 in SLE treatment, 328 glucocorticoids and, 647 Nephelometry, 19 therapeutic actions, 637–638 INDEX in idiopathic infl ammatory Nephrogenic fi brosing dermopathy, Nonsyphilitic interstitial keratitis, 441 myopathies, 364 499 Nonvascularized bone grafting, 570 sarcoidosis and, 516–517 Nephrogenic systemic fi brosis (NSF), NSAIDs. See Nonsteroidal in SLE, 307–312 349 anti-infl ammatory drugs in systemic sclerosis, 349 Neuroma, Morton’s, 83–84 Nutritional factors, osteoporosis and, MWS. See Muckle Wells syndrome Neuropathic arthropathy, 227, 488–491 589 Mycobacterial infections, 56, 290–293 clinical features, 489–490 Mycobacterium avium, 293 diagnosis of, 490 O Mycobacterium bovis, 292–293 epidemiology of, 488 OA. See Osteoarthritis Mycobacterium kansasii, 293 of foot, 489, 490 Obesity, in gout, 247 Mycobacterium leprae, 293 management of, 491 Occlusive vasculopathy, 320 Mycobacterium marinum, 293 pathology of, 488–489 Ochronosis, 56, 525–527 Mycobacterium tuberculosis, 26, 290–291 pathophysiology of, 489 clinical features, 525–526 Mycophenolate mofetil (MMF) prevention of, 491 laboratory features, 526–527 in SLE treatment, 333 pseudo, 266 radiographic features, 526 in systemic sclerosis treatment, 362 synovial fl uid in, 490 Olecranon bursitis, 73 714 INDEX

Oligoarthritis differential diagnosis, 227 pathology, 567 acute infl ammatory, 54 erosive infl ammatory, 56 PET scans of, 567 chronic infl ammatory, axial fungal, 291 radiographic staging, 567–568 involvement and, 55–56 initiation of, 233 risk factors, 565–567 juvenile idiopathic, 145–146, 149–150 hypothetical model of, 234 in sickle cell disease, 473 cause of, 150 joints in, 230 treatment genetic predisposition, 150 phase 1, 230 algorithm, 570–571 infl ammatory cytokines in, 150 phase 2, 230 nonoperative, 569 joint damage, 150 phase 3, 230 operative, 569–570, 655 laboratory fi ndings in, 149 localized, 56 prognosis, 570–571 synovium in, 149 menopausal, 226–227 resurfacing arthroplasty, 570 treatment, 158 monarthritis and, 45 total joint replacement, 570 uveitis, 149–150 mycobacterial, 291 Osteopenia management of, 486 operative treatment, 652–653 hip fractures, 576–577 Omenn syndrome, 100 outcomes, 227–228 incidence of, 576–577 Onycholysis, 146 pathogenesis, 230–231 JIA and, 164 Operative treatment, 651–663 enzymes involved in, 231 prevalence, 576–577 disease-related factors, 652–656 pathology, 229–230 Osteoporosis, 3, 483, 592 ankylosing spondylitis, 655 normal to aging cartilage in, additional laboratory evaluation, 582 hemophilic arthropathy, 655–656 229–230 bone structure and function in, juvenile RA, 654 primary generalized nodal, 56 584–586 osteoarthritis, 652–653 prognosis, 227–228 remodeling in, 585–576 osteonecrosis, 655 pseudo, 265 types of bone, 584–585 psoriatic arthritis, 655 radiographic fi ndings in, 29, 226 calcium homeostasis in, 587 PVNS, 656 rapidly progressing, 227 classifi cation of, 681 RA, 653–654 risk factors for, 225 clinical assessment of, 578–582 synovial chondromatosis, 656 treatment, 690 bone mass measurement in, new, 663 knee, 236 580–581 perioperative, 662 localized pharmacologic, 239 bone turnover measurement, postoperative, 662–663 narcotic analgesic medication, 238 581–582 preoperative evaluation, 651–652 non-narcotic analgesic medication, history, 578 preparation for, 652 238 physical examination, 578 sites of intervention, 656–662 nonpharmacologic, 235–237 skeletal imaging for, 578–579 ankle, 659 NSAIDs, 238–239 DXA in, 578–579, 581 cervical spine, 661–662 surgery, 239 epidemiology of, 576–577 elbow, 660 systemic pharmacologic, 237–239 bone mineral density criteria in, 577 foot, 659 Osteoblasts, 585 glucocorticoid-induced, 690 hand, 659–660 Osteocalcin, 165 JIA and, 164 hip, 656–657 Osteochondroses, juvenile, 563–564 lifestyle issues and, 593–594 shoulder, 660–661 Osteoclasts, 585, 586 pathophysiology of, 587–588 wrist, 659–660 Osteocytes, 585 mechanical properties of bone, OPG. See Osteoprotegerin Osteogenesis imperfecta syndromes, 587–588 Opioid analgesics, 622–623 553–555 pharmacologic treatment, 594–597 Organ transplantation, gout and, 245, natural history, 553–555 bisphosphonates, 594–595 261 type I, 553 calcitonin, 596 Orthotic devices, 605 type II, 553 combination therapy, 597 Osteoarthritis (OA), 6, 56 type III, 553 estrogen, 596 classifi cation of, 673–674 type IV, 553 future of, 597 clinical features of, 224–228 Osteolysis, 349 raloxifene, 596 disease patterns, 226–227 Osteomyelitis teriparatide, 596–597 epidemiology, 224 multifocal sterile recurrent, 492 postmenopausal, 594 history, 225 radionuclide imaging of, 37 QCT in, 579–580 investigations, 225–226 in sickle cell disease, 473 radiography in, 578–579 physical examination, 225 Osteonecrosis, 483, 565–571 risk factors, 588–590 course, 227–228 clinical presentation, 567 bone turnover, 590 cytokines in CT of, 567 drugs and, 590 cartilage repair, 232–233 direct causes of, 566 falls, 590 lipid mediators, 231 indirect causes of, 566–567 genetic infl uences, 588–589 matrix degradation products, 232 monarthritis and, 45 hypogonadism, 589 mechanical stress, 232 MRI diagnosis of, 36, 567 nutritional factors, 589 reactive oxygen species, 231–232 pathogenesis, 565–567 physical activity, 589 INDEX 715

Osteoprotegerin (OPG), 130 Palpation idiopathic intermittent, 466–468 Osteotomy, 570, 657 ankle, 14 palindromic rheumatism, 466–467 Otorhinolaryngeal relapsing knee, 13 Perioperative management, 662 polychondritis, 451 sternoclavicular joint, 11 Peripheral aneurysms, in Kawasaki’s Oxalate crystals, 269 of wrist, 9 disease, 445 Oxalosis, 26 Pamidronate, 574, 595 Peripheral arthritis, 220 in ankylosing spondylitis treatment, Peripheral tolerance, 102 P 211 Peroneal nerve palsy, 81 Paget’s disease of bone, 573–575 PAN. See Polyarteritis nodosa Peroneal tendon diagnosis, 573–574 Pancreatic disease-associated dislocation, 82–83 symptoms, 573 arthropathy, 57 tendonitis, 82–83 therapy, 574–575 Panniculitides, 495–496 Pes cavus, 83 alendronate, 574 calcifying, 496 Pes planus, 83 bisphosphonate, 574 cytophagic histiocytic, 496 PET. See Positron emission disodium etidronate, 574 PAPA syndrome, 500 tomography pamidronate, 574 Paracoccidioides brasiliensis, 295 Phalen’s test, 76 plicamycin, 574 PA radiography. See Posterior-anterior Pharmacologic therapy, for risedronate, 574 radiography fi bromyalgia, 92 synthetic salmon calcitonin, 574 Paraneoplastic rheumatic syndromes, Phosphatidylinositol-3′-kinase (PI-3K), tiludronate, 574 476–477 232 zoledronate, 574 Parasites, 295 Phosphorus, 701 Pain, 611. See also Back pain; Parathyroid disease, 481–482 Physical activity, 616 Complex regional pain rheumatological manifestations of, 482 osteoporosis and, 589 syndrome; Neck pain; Parvovirus B19, 277–278 Physical therapy Regional rheumatic pain PAS. See Periodic acid-Schiff for ankylosing spondylitis, 210 syndromes Patellar tendon in JIA, 159 assessment, 622 rupture of, 81 in pain management, 625 back, 58–66 tendinitis, 81 exercise in, 625 categories of, 620–621 Patellofemoral pain syndrome, 81 heat and cold in, 625 in children, 626 Pathergy, 437 PI-3K. See chronic, of complex origin, 621 Pathogen-associated molecular patterns Phosphatidylinositol-3′-kinase control in rehabilitation, 602 (PAMPs), 96 Pigmented villonodular synovitis diffuse, 88 Patient-controlled analgesia (PCA), 662 (PVNS), 543–545 in JIA, 168 Patient evaluation, 6–14 MRI in, 544 localized bone, 60 ANAs in, 17 operative treatment, 656 management, 620–626 arthrocentesis, 21–23 Pineapple, 691 antidepressants, 623–624 complement in, 19 PIP joints. See Proximal interphalangeal antiepileptic drugs, 624 CRP in, 16 joints fi bromyalgia, 624 cryoglobulins in, 19 Piriformis syndrome, 79 general approach to, 621–622 erythrocyte sedimentation rate in, Plantar fasciitis, 82 muscle relaxants and, 623 15–16 Plasmapheresis, in SLE treatment, 334 opioid analgesics, 622–623 examination, 7–14 Platelet-derived growth factor (PDGF), pharmacologic, 622–624 history, 6–7 355 physical therapy, 625 imaging, 28–40 Plexopathy, brachial, 72 procedure-based, 626 RF in, 16 Plicamycin, 574 INDEX psychological and behavioral Pattern recognition receptors (PRRs), 96 PMNs. See Polymorphonuclear approaches to, 624–625 PDGF. See Platelet-derived growth leukocytes topical agents, 624 factor Pneumocystis jirovecii, 331 nature of, 620–621 Pellegrini-Stieda syndrome, 80–81 Polyarteritis nodosa (PAN), 410–414 neck, 58–66 Pentoxifylline, 449 classifi cation of, 677 neuropathic, 621 Peptidylarginine deiminases, 119 clinical features, 411–412 nociceptive, 620–621 Periodic acid-Schiff (PAS), 27 cutaneous ulcerations in, 412 in older persons, 626 Periodic syndromes diagnosis, 412–413 in polyarthritis, 49 hereditary, 460–466 biopsy, 413 psychogenic, 621 clinical features, 462–463 classifi cation, 413 visceral, 60 cryopyrinopathies, 465–466 features of, 411 Palindromic rheumatism, 114, familial Mediterranean fever, imaging, 413 466–467 460–463 laboratory, 413 clinical fi ndings, 466–467 hyperimmunoglobulinemia D with pathology of, 412 laboratory fi ndings, 466–467 period fever syndrome, 463–464 prognosis of, 414 treatment, 467 laboratory features, 462–463 treatment of, 414 716 INDEX

Polyarticular joint disease Pregnancy outcome measures in, 186 acute infl ammatory, 53–54 in antiphospholipid syndrome, 341 pathogenesis, 179–183 carcinomatous, 54, 477 drug therapy in, 685–686 cytokine pathways in, 180 chronic infl ammatory, 54–55 Lyme disease in, 287 dysregulated bone remodeling in, classifi cation of, 47 SLE in, 314–315 180–181 infl ammatory, 48 Preoperative evaluation, 651–652 environmental factors, 179–180 non-infl ammatory, 49 Prepatellar bursitis, 80 of extra-articular, 182–183 demographics in, 50 Prevention, 2–3 genetic basis of, 179 diagnostic approach to, 47–53 Primary angiitis of central nervous pathology of, 178 history, 47–50 system (PACNS), 439–441 patterns of, 173 laboratory studies, 52 cerebral angiogram in, 440 QOL in, 175 physical examination in, 51–52 clinical manifestations of, 439–440 skin disease in, 174 radiographic studies, 52–53 diagnosis of, 440 spondyloarthritis, 172–173 differential diagnosis, 53 management and outcome, 440–441 SSZ and, 187 diseases causing, 53–57 Probenecid, 261 Psychogenic pain, 621 distribution of, 49–50 Proliferative glomerulonephritis, 430 Psychological factors extra-articular symptoms, 50 Proliferator-activated receptor-gamma affective components, 610 juvenile idiopathic, 145 receptor (PPAR), 256 cognitive components, 610–611 treatment, 158 Pronator teres syndrome, 75 in fi bromyalgia, 91 non-infl ammatory, 56 Prostaglandin biology, 634–636 glucocorticoids and, 648 pain in, 49 biosynthetic pathway, 635 Psychosocial factors, 609–612 systemic involvement in, 50, 51 Protein tyrosine kinases (PTKs), 100 PTKs. See Protein tyrosine kinases Polymorphonuclear leukocytes (PMNs), Proximal interphalangeal (PIP) joints, 9, PTSD. See Post-traumatic stress disorder 25, 285 49, 77 Public health Polymyalgia rheumatica, 54, 398, in RA, 115 history of, 1 404–406 PsA. See Psoriatic arthritis rationale for arthritis initiative, 1–2 clinical features, 405–406 Pseudoachondroplasia, 562 medical model and, 2 epidemiology of, 405 Pseudogout, 54 prevention and, 2–3 pathogenesis of, 405 Pseudo-rheumatism, 90 Pulmonary arterial hypertension prognosis, 406 Pseudoxanthoma elasticum, 555 (PAH), 348, 359–360 treatment, 406 Psoriasis vascular therapy for, 360–361 Polymyositis, 55, 363 generalized pustular, 500 Purpura cytotoxic mechanisms in, 372 management of, 186 Henoch-Schönlein, 431–432 diagnosis of, 676 NSAIDs in, 186–187 in hypersensitivity vasculitis, 428 serum autoantibodies in, 378 Psoriatic arthritis (PsA), 6, 55 Pustular conditions, 500–501 Poncet’s disease, 292 abatacept, 189 PVNS. See Pigmented villonodular Popliteal cysts, 79–80 adalimumab, 188–189 synovitis Popliteal tendinitis, 80 alefacept, 189 Pyoderma gangrenosum (PG), 493–494, Population structure, 111 articular manifestations of, 173–174 494 Positron emission tomography (PET), dactylitis, 173–174 atypical, 494 of osteonecrosis, 567 enthesitis, 174 Pyrin, 106 Postchemotherapy rheumatism, 477 tenosynovitis, 174 Posterior-anterior (PA) radiography, 29 assessment of, 185–186 Q standing, 32 clinical features of, 171–173 QCT. See Quantitative computed Posterior interosseous nerve syndrome, peripheral arthritis in, 172 tomography 76 course of, 175 QOL. See Quality of life Posterior tibialis tendon rupture, 82 cyclosporine, 187–188 Quadriceps tendon, rupture of, 81 Posterior tibial tendinitis, 82 diagnosing, 174–175 Quality of life (QOL) Postoperative treatment, 662–663 DMARDs in, 187–188 in JIA treatment, 161 Poststreptococcal reactive arthritis efalizumab, 189 in PsA, 175 (PSRA), 300–301 epidemiology of, 170–171 Quantitative computed tomography clinical fi ndings in, 301 classifi cation criteria, 171 (QCT), 39 diagnostic criteria, 301 prevalence of, 170–171 in osteoporosis, 579–580 treatment, 301 etanercept in, 188 Post-traumatic stress disorder (PTSD), extra-articular features of, 174 R 609 infl iximab in, 188 RA. See Rheumatoid arthritis Pott’s disease, 291 juvenile idiopathic, 146, 152 Radial nerve palsy, 76 PPAR. See Proliferator-activated management, 186–189 Radicular symptoms, 62 receptor-gamma receptor glucocorticoids in, 187 Radiography PR3. See Serine protease-3 mortality in, 175 in alkaptonuria, 526 Pramipexole, 624 MTX and, 187 AP, 29, 32 Prayer, 665 operative treatment, 655 conventional, 28–29 INDEX 717

in CPPD, 266–267 patient assessment in, 601–602 prognosis, 300 digital, 29 physical modalities in, 602–604 special tests for, 299 in Gaucher’s disease, 528 electrical stimulation, 603 treatment, 299–300 glucocorticoids and, 646 exercise therapy, 603 Rheumatic sequelae, 479–483 in gout, 247 heat and cold, 602–604 diabetes mellitus, 479–480 in hemophilia, 472 hydrotherapy, 603 thyroid disease, 480–481 hip, 656 rest, 603 Rheumatoid arthritis (RA), 6, 52, 55, 89 in HOA, 507 setting, 600–601 ANA in, 119 in idiopathic infl ammatory team, 600–601 assessment of, 133–134 myopathies, 376 upper extremity aids, 604–605 disease activity indices, 134 knee, 658 orthotic devices, 605 laboratory studies, 133–134 of lateral cervical spine, 197 vocational, 606–607 autoimmunity and autoantibodies in, of lateral lumbar spine, 197 Relapsing polychondritis, 56 125–127 in monarticular joint disease, 44 cardiovascular, 452 cell count in, 24 in OA, 29, 226 clinical manifestations of, 452 classifi cation, 670 in ochronosis, 526 diagnosis of, 453 classifi cation of, 115 of osteonecrosis, 567–568 features of, 453 clinical remission in, 671 in osteoporosis, 578 management, 453 comorbidities, 140 PA, 29, 32 musculoskeletal, 452–453 differential diagnosis of, 120–121 polyarthritis, 52–53 ocular, 452 DIP joints in, 115 in RA, 119–120, 134 otorhinolaryngeal, 451 epidemiology and risk factors of, in sarcoidosis, 518 respiratory, 451–452 122–124 shoulder, 661 Relapsing seronegative synovitis with bacteria as, 124 in synovial chondromatosis, 546 pitting edema (RS3PE), 53–54 sex as, 123–124 in Wilson’s disease, 527 Relative risk (RR), 111 tobacco as, 124 Radionuclide imaging, 28 Renal dialysis, in SLE treatment, 334 viruses as, 124 of osteomyelitis, 37 Renal system. See Kidneys functional status in, 671 Raloxifene, in osteoporosis treatment, Replication, 112 genetic factors, 123 596 Resilience, 612 improvement in, 671–672 Range of motion, 68 Resolution joint destruction in, 129–130 shoulder, 11 high contrast, 28 juvenile, 654 Raynaud’s phenomenon, 361 high spatial, 28 classifi cation of, 681–682 in systemic sclerosis, 344–345 Respiratory relapsing polychondritis, laboratory fi ndings in, 118–119 Reactive arthritis, 54, 217–220 451–452 macrophage and fi broblast cytokines clinical features of, 218 Rest, 603 in, 127–129 epidemiology of, 217–218 Resurfacing arthroplasty, 570 MTP joints in, 115 HLA-B27 and Retrocalcaneal bursitis, 82 nongenetic factors, 123–124 host immune responses RF. See Rheumatoid factor operative treatment, 653–654 interactions, 219 Rheumatic diseases, 53–54, 54 organ systems involved in, 117 host-pathogen interactions, 219 cancer and, 474 patient history in, 114–116 molecular mimicry and, 219–220 rehabilitation in patients with, physical examination in, 116–118 pathogenesis of, 218–219 599–607 extra-articular, 117–118 poststreptococcal, 300–301 ambulatory aids, 604 joint examination, 116–117 diagnostic criteria, 301 classifi cations in, 599–600 PIP joints in, 115 treatment, 301 lower extremity orthoses, 605–606 progression of, 670 INDEX therapy for, 220 pain control in, 602 pseudo, 265–266 NSAIDs, 220 patient assessment in, 601–602 radiological fi ndings in, 119–120, 134 Refl ex sympathetic dystrophy, 509 physical modalities in, 602–604 synovial fl uid in, 125 Regional rheumatic pain syndromes, setting, 600–601 synovial pathology, 124–125 68–85 team, 600–601 synovium in, 125 causative factors, 68–69 upper extremity aids, 604–605 treatment, 134–137, 683–684 management of, 69 vocational, 606–607 abatacept, 139–140 drug therapy, 69 Rheumatic fever, 53, 673 biologics for, 137 guidelines for, 69 clinical fi ndings, 297–298 DMARD, 135–137 intralesional injections, 69 diagnostic criteria, 297 HCQ, 138 physical therapy, 69 major clinical criteria, 297–298 NSAID, 654 Rehabilitation, 599–607 minor clinical criteria, 298 rituximab, 139–140 ambulatory aids, 604 diagnostic tests, 298, 673 SSZ, 138 classifi cations in, 599–600 differential diagnosis, 299 Rheumatoid factor (RF), 16, 126 lower extremity orthoses, 605–606 epidemiology of, 297 IgM, 119 shoeware, 606 modifi ed Jones’ criteria for, 298 Rheumatoid neutrophilic dermatoses, pain control in, 602 pathogenesis, 299 494 718 INDEX

Rhizomelic chondrodysplasia punctata, treatment, 520–521 Severe combined immunodefi ciency 563 clinical course, 520 (SCID), 100, 130 Risedronate, 574, 595 prognosis, 520 Sex, as RA risk factor, 123–124 Risk factors steroid-sparing agents, 520–521 Shared epitope hypothesis, 123 fractures, 577 therapy, 520 Shoeware, 606 of GCA, 401–403 Sarcoma, synovial, 547 Short tau inversion recovery (STIR), osteonecrosis, 565–567 Schober test, 12 197 osteoporosis, 588–590 SCID. See Severe combined Shoulder genetic infl uences, 588–589 immunodefi ciency arthrogram of, 38 hypogonadism, 589 Scintigraphic techniques, 36–37 disorders of, 70–73 nutritional factors, 589 imaging agents, 36–37 examination of, 10–11 physical activity, 589 SCLE. See Subacute cutaneous lupus frozen, 72 of RA, 122–124 erythematosus operative treatment, 660–661 bacteria as, 124 Scleredema, 350 passive range of motion, 11 genetic, 123 Scleroderma, 9, 17 radiography, 661 nongenetic, 123–124 dermatological conditions associated SI. See Sacroiliac sex as, 123–124 with, 497–498 Sickle cell disease, 57, 472–474 tobacco as, 124 disorders like, 349–350 gout in, 473–474 for renal toxicity, 640 forms of, 344 osteomyelitis in, 473 Rituximab, 105, 139–140 limited, 343 osteonecrosis in, 473 Rotator cuff linear, 499 vertebra in, 473 tear, 71 localized, 343, 496 Single nucleotide polymorphisms tendinitis, 70–71 myopathy in, 349 (SNPs), 109, 352 RS3PE. See Relapsing seronegative myositis in, 349 Sjogren’s syndrome, 389–396 synovitis with pitting edema renal crisis, 348–349, 361 classifi cation of, 676–677 Rubella, 278 Scleromyxedema, 350, 496 clinical features of, 391–394 Sclerosing, 496–499 extraglandular, 393–394 S Scoliosis, 64 laboratory features of, 394 SAA. See Serum amyloid A Screening musculoskeletal exams, 8 ocular, 391 Sacroiliac (SI), examination of, 12 Scurvy, 501 oral salivary, 391–392 Sacroiliitis, in ankylosing spondylitis, Selective serotonin reuptake inhibitors diagnosis of, 394–395 194–195 (SSRIs), 361, 623 classifi cation criteria, 394–395 Salicylates, NSAID drug interactions, Selenium, 734 epidemiology of, 389–390 641–642 Self-management strategies, 614–618 etiology of, 390 Salivary glands education, 614–615 immunopathology of, 390–391 bilateral enlargement, 393 fi ve A’s model, 617–618 autoantibodies, 390–391 eosinophilic infi ltration of, 421 advise, 617 cellular, 390 hypofunction, 391 agree, 617 histopathology of, 390 Salmonella typhimurium, 218 arrange follow-up, 618 prognosis, 396 SAM-e, 695 assess, 617 treatment, 395–396 SAPHO syndrome, 500 assist, 618 extraglandular, 396 Sarcoid arthritis, 54 support, 617–618 ocular, 395 Sarcoidosis, 56 Septic arthritis, 271–276 oral, 395–396 abdominal, 517 in children, 275 Skin acute, 515 clinical features, 272 ANCA and, 420 chronic cutaneous, 515 laboratory fi ndings, 272–273 biopsy in idiopathic infl ammatory clinical features, 514–517 microbiology, 272 myopathies, 375 epidemiology, 514 outcome, 274 glucocorticoids and, 648 familial associations, 514 pathogenesis, 271 in idiopathic infl ammatory genetic associations, 514 prevention, 274 myopathies, 364, 366 laboratory features, 518 pseudo, 272 in PsA, 174 musculoskeletal, 516–517 risk factors, 271 SLE. See Systemic lupus erythematosus bone, 517 therapy, 273–274 SLEDAI. See Systemic Lupus joint, 516–517 antibiotic, 273 Erythematosus Disease Activity myositis, 517 Septic bursitis, 275–276 Index ocular, 515–516 Serine protease-3 (PR3), 18 SLICC. See Systemic Lupus osseous, 517 Serum amyloid A (SAA), 537 Erythematosus International pathogenesis, 519–520 Serum muscle enzymes, in idiopathic Cooperating Clinics pathology, 518 infl ammatory myopathies, 365, SNPs. See Single nucleotide pulmonary, 515, 518, 519 375–376 polymorphisms radiographic features of, 518 Serum sickness, 428 Social factors, 611–612 INDEX 719

Sodium, 701–702 Synovial chondromatosis, 545–546 nervous system in, 310 Soluble endothelial protein C receptor operative treatment, 656 novel therapies, 334–336 (sEPCR), 314 radiograph of, 546 cytokine blockade, 336 Somatic hypermutation, 105 treatment of, 546 targets for, 335 Speed’s test, 72 Synovial fl uid ocular system in, 312 Spinal tuberculosis, 291 analysis, 23–26 organ systems in, 305–307 Spine, examination of, 12 blood in, 25 mucocutaneous, 305–307 Spirituality, 665 cell count, 24–25 pleura in, 311–312 Spondyloarthropathy. See Ankylosing crystals in, 25–26 in pregnancy, 314–315 spondylitis diagnosis by class, 24 renal system in, 308–310 Spondyloepiphyseal dysplasias, 561–562 gross examination, 24 therapy, 328–334, 687 congenita, 561–562 in monarticular joint disease, 43–44 antimalarial, 330–331 late-onset, 562 classes of, 23 azathioprine, 331 Spondylolisthesis, 64 detection of, 13 B cell depletion, 335 Sporotrichosis, 294 in neuropathic arthropathy, 490 B cell-specifi c tolerogen, 335 SSRIs. See Selective serotonin reuptake in RA, 125 B cell survival inhibition, 335 inhibitors Synovitis, 7 corticosteroids, 328–330 SSZ. See Sulfasalazine in ankylosing spondylitis, 195 costimulatory interaction inhibition, Staphylococcus aureus, 44 eosinophilic, 468 335–336 Statistical power, 111–112 infl ammatory, 349 cyclophosphamide in, 332–333 Stem cell transplantation, in SLE Synovium cyclosporine in, 332 treatment, 334 in juvenile idiopathic oligoarthritis, dapsone, 331 Sterile procedures, in arthrocentesis, 23 149 hormonal, 333 Sternoclavicular joint, 84–85 in multicentric reticulohistiocytosis, immunoablation, 334 palpation of, 11 530 IVIg, 334 Sternocostoclavicular hyperostosis, 84 normal, 125 lefl unomide, 333 Stickler dysplasia, 562 in RA, 125 MMF, 333 Stickler syndrome, 551 Synthetic salmon calcitonin, 574 MTX, 331–332 Stiffness, 7 Systemic diseases, 54 novel, 334–336 back pain and, 60 back and neck pain and, 60 NSAID, 328 morning, 60 Systemic lupus erythematosus (SLE), 9, plasmapheresis, 334 neck pain and, 60 43, 53, 55, 89, 109, 303–317 renal dialysis, 334 Still’s disease, 53 ANAs in, 321 thalidomide, 333–334 Stinging nettle, 695 antiphospholipid antibody syndrome topical agents in, 330 STIR. See Short tau inversion recovery in, 316, 341 triggering events, 325 St. John’s wort, 695 cardiovascular system in, 310–311 Systemic Lupus Erythematosus Disease Storage diseases, 523–531 cell count in, 24 Activity Index (SLEDAI), 315 Streptococcal reactive arthritis, 53 classifi cation of, 675 Systemic Lupus Erythematosus Stress, 609–610 course of, 305 International Cooperating Clinics reduction, 664–665 cutaneous manifestations of, 306 (SLICC), 307 Stress-activated protein kinases diagnosis criteria, 304 Systemic rheumatic diseases, 55 (SAPKs), 232 disease susceptibility, 322–323 monarthritis and, 45 Strongyloides stercoralis, 295 drug-related, 316–317 Systemic sclerosis, 55 Subacute cutaneous lupus drug toxicity in, 329 animal models of, 354 erythematosus (SCLE), 306 epidemiology of, 319 assessment of, 359–360 INDEX Sulfasalazine (SSZ), 135, 138 fatigue in, 327 autoantibodies in, 345 in ankylosing spondylitis treatment, general management, 327–328 calcinosis in, 347 212 genetics of, 323–324 cardiac involvement in, 348 in JIA treatment, 157 GI tract, 312 cellular autoimmunity in, 356–357 PsA treatment with, 187 immune cell disturbances in, 324–325 classifi cation of, 675 Superfi cial radial neuropathy, 76 immunopathology of, 319–320 diffuse cutaneous disease, 343, 345 Supplements, 666, 691–696 infections in, 327–328 environmental factors, 352–353 Suprascapular neuropathy, 72 laboratory features in, 312–314 epidemiology, 351–352 Surgery complement in, 312–313 fi broblast activation in, 356 ankylosing spondylitis, 239 hallmark autoantibodies in, fi brosis in, 357–358 OA, 239 312–313 genetic factors, 352 Swan neck deformity, 307 hematologic abnormalities in, 312 in GI tract, 347 Sweet’s syndrome, 492 liver in, 312 humoral autoimmunity in, 356–357 histopathological fi ndings in, 493 lungs in, 311–312 infl ammation in, 353 Synovial biopsy, 26–27 musculoskeletal system in, 307–312 key clinical features of, 346 in monarthritis, 44 neonatal, 315 limited cutaneous disease, 343, 345 720 INDEX

Systemic sclerosis (cont.) Therapeutic injections, 628–632 Trigger fi nger, 77–78 musculoskeletal disease in, 349 corticosteroid, 628–631 injections, 630 pathogenesis, 354 complications, 631 Trigger point injections, 625 pathology, 353–354 diluting, 630 Trochanteric bursitis, 78 pulmonary disease in, 347–348 dose in, 628 Trophermyma whippleii, 56 renal disease in, 348–349 effi cacy of, 628, 629 Tuberculosis, spinal, 291 schematic representation of, 355 gloves, 630–631 Tuberculous arthritis, 291–292 skin manifestations of, 346–347 needle length in, 628–629 Tumeric, 695–696 TGF in, 357 preparations in, 628, 630 Tumor necrosis factor (TNF), 128, 135, treatment of, 360–362 reactions to, 631 448, 449, 460, 654 antifi brotic, 362 Thoracic outlet syndrome, 72–73 alpha, 232, 256 anti-infl ammatory, 361–362 Thrombosis, in antiphospholipid ankylosing spondylitis treatment and, vascular, 360–361 syndrome, 341 213–214

vasculopathy in, 343–346, 354–355 Thromboxane A2 (TXA2), 635 antagonists, 138–139 Thunder god vine, 695 in PsA, 188–189

T Thyroid disease, 480–481 TXA2. See Thromboxane A2 Takayasu’s arteritis (TA), 398, in JIA, 165 406–408 Tietze’s syndrome, 84 U classifi cation of, 679 TIMP. See Tissue inhibitors of UIP. See Usual interstitial pneumonitis clinical features of, 407 metalloproteinases Ulnar deviation, 116 spectrum, 407 Tinel’s sign, 76 Ulnar nerve entrapment, 74 diagnosis of, 408 Tissue inhibitors of metalloproteinases at wrist, 77 epidemiology, 406 (TIMP), 130 Ultrasound, 28, 37–38 pathogenesis, 406–407 TLR. See Toll-like receptors of IP joints, 38 prognosis, 408 T lymphocytes, 98, 99–104, 125 of MCP joints, 38 treatment, 408 autoimmunity, 126–127 Urates Tarsal coalition, CT scan of, 33 CD8+, 103–104 crystal-induced infl ammation, 255–256 Tarsal tunnel syndrome, 84 derived cytokines, 127 lowering agents, 254 T-cell receptors (TCR), 98, 99–100 development, 101–102 metabolism, 251–252 signal transduction, 100–101 differentiation, 102 production pathways, 252, 253 TCR. See T-cell receptors receptors, 202 renal transport of, 254–255 Telangiectasia, in systemic sclerosis, regulatory, 102 solubility of, 251 346 subsets, 127 Urticarial vasculitis, 432 Temazepam, 624 TNF. See Tumor necrosis factor Usual interstitial pneumonitis (UIP), Tendinitis, 68 TNF receptor-associated periodic 370, 421 bicipital tendinitis, 71–72 syndrome (TRAPS), 460, Uveitis, 149–150 patellar, 81 464–465 in ankylosing spondylitis, 195 popliteal, 80 clinical features, 464–465 treatment, 159 posterior tibial, 82 laboratory features, 464–465 rotator cuff, 70–71 treatment, 465 V triceps, 74 Tobacco, as RA risk factor, 124 Valerian, 696 Tendinopathy, 74 Toll-like receptors (TLR), 96, 324, 399 Valley fever, 294 Tendinosis, 68 Topical agents, 624 Variants, relationships between, 110 angiofi broblastic, 73 Total joint replacement, 275, 570 Vascular cell adhesion molecule Tendonitis, peroneal tendon, 82–83 Toxoplasma gondii, 295 (VCAM-1), 373 Tenosynovitis Transcutaneous electrical nerve Vascular endothelial growth factor De Quervain’s, 75 stimulation (TENS), 625 (VEGF), 181, 355–356, 401, 504 in PsA, 174 Transforming growth factor (TGF), 181 Vascularized bone grafting, 570 volar fl exor, 77–78 in systemic sclerosis, 357 Vasculitic lesions, 399 of wrist, 75 Transient ischemic attacks (TIAs), 440 Vasculitis, 307 TENS. See Transcutaneous electrical Transrepression, 645 Vasculopathy, in systemic sclerosis, 343, nerve stimulation Transthyretin (TTR), 535, 538 354–355 Teriparatide, in osteoporosis treatm TRAPS. See TNF receptor-associated VCAM-1. See Vascular cell adhesion ent, 596–597 periodic syndrome molecule TGF. See Transforming growth Trauma, monarthritis and, 45 VEGF. See Vascular endothelial growth factor Treponema pallidum, 45 factor Thalassemia, 474 Triceps Vertebral bodies, 587 Thalidomide tendinitis, 74 Vertebral fractures, 577 in ankylosing spondylitis treatment, tendon rupture, 74 Viral arthritis, 53, 277–281 211–212 Trichomonas vaginalis, 295 chronic, 277 in SLE treatment, 333–334 Tricyclic antidepressants, 211, 623 common, 278 INDEX 721

hepatitis B, 279–280 Weber-Christian disease, 495 examination, 9–10 hepatitis C, 278–279 Wegener’s granulomatosis, 416–425 fractures, 577 HIV, 280 classifi cation criteria for, 417 operative treatment, 659–660 latent, 277 classifi cation of, 678 palpation of, 9 parvovirus B19, 277–278 multifocal cavitary nodules in, 419 tenosynovitis, 75 rubella, 278 saddle-nose deformity in, 418 ulnar nerve entrapment at, 77 self-limited, 277 Weight control, 616–617 Virchow, Rudolph, 533 Westergren method, 15–16 X Viscosupplementation, 631–632 Western blot, in Lyme disease Xanthomas, 484–485 Vitamin A, 696 confi rmation, 286 osseous, 485 Vitamin B, 697–698 Whiplash, 66 tuberous, 485 Vitamin C, 237, 666, 698–699 Whipple’s disease, 56 Xiphodynia, 84 Vitamin D, 237, 593, 666, 696–697 WHO. See World Health Organization Xiphoid cartilage syndrome, 84 Vitamin E, 697 Wilson’s disease, 527–528 X-linked agammaglobulinemia, Vitamin K, 697 clinical features, 527 105 Vitamin supplements, 666 laboratory evaluation, 527–528 Volar fl exor tenosynovitis, 77–78 radiographic features, 527 Y treatment, 528 Yergason’s sign, 72 W World Health Organization (WHO), Waldenstrom’s macroglobulinemia, lupus nephritis classifi cation, 308 Z 476 Wrist Zinc, 702 Water-soluble vitamins, 697–699 disorders, 74–78 Zoledronate, 574 Weakness, 7 dorsum of, 10 Zoledronic acid, 595 INDEX