Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management NGUYET-CAM VU LAM, MD; MARIA V. GHETU, MD; and MARZENA L. BIENIEK, MD, St. Luke’s University Hospital, Bethlehem, Pennsylvania Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskel- etal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treat- ment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body sys- tems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient’s family physician to improve chronic care as well as preventive health services. (Am Fam Physician. 2016;94(4):284- 294. Copyright © 2016 American Academy of Family Physicians.) ▲ See related Close-Up ystemic lupus erythematosus (SLE) is well-coordinated, multidisciplinary health on page 304. an autoimmune disease that affects care teams including subspecialists and fam- CME This clinical content the skin and musculoskeletal, renal, ily physicians to improve chronic care and conforms to AAFP criteria neuropsychiatric, hematologic, car- preventive health services for these patients.7 for continuing medical Sdiovascular, pulmonary, and reproductive A committee of the American College of education (CME). See CME Quiz Questions on systems. Its course is typically recurrent, Rheumatology (ACR) recommended that page 270. with periods of relative remission followed the role of primary care physicians is under- Author disclosure: No rel- by flares. SLE can be fatal and significantly standing the manifestations of SLE to aid evant financial affiliations. increases the risk of cardiovascular disease. in early diagnosis, treating and monitor- ▲ Patient information: SLE affects about 300,000 persons in the ing patients with mild disease, recognizing 1 A handout on this topic, United States. It is twice as prevalent in black warning signs to refer to a rheumatologist written by the authors of persons as in white persons, and it is 10 times appropriately, and helping to monitor dis- this article, is available more common in females than in males.2 ease activity and treatment in patients with at http://www.aafp.org/ 8 afp/2016/0815/p284-s1. Over the past decade, the five-year survival moderate to severe disease. html. rate of patients with SLE has improved to more than 95% because of more effective Diagnosis recognition and treatment of infectious and SLE is difficult to diagnose in primary care renal complications.3,4 Because patients with because many of the symptoms (e.g., fatigue, SLE are living longer, the focus of care should rash, joint pain) are nonspecific and over- be comprehensive, including preventive ser- lap with those of more common conditions. vices in addition to treatment.5 Furthermore, biomarkers are often negative or normal early in the course of the illness. Role of the Primary Care Physician The most common presenting symptoms are A qualitative study in the United Kingdom constitutional, such as fatigue, weight loss, noted a lack of detailed knowledge about SLE and fever without a focal infection, occurring by family physicians and the need for more in up to 90% of patients.9 Other common cohesive health care.6 There is a need for presenting symptoms include arthralgia and 284Downloaded American from the Family American Physician Family Physician website at www.aafp.org/afp.www.aafp.org/afp Copyright © 2016 American AcademyVolume of Family 94, Physicians. Number For 4 the◆ August private, 15,noncom 2016- mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Lupus Table 1. Differential Diagnosis of Systemic Lupus Erythematosus Differential diagnosis Distinguishing features Diagnostic approach Adult-onset Still Arthralgia, fever, lymphadenopathy, Tests for elevated ESR, leukocytosis, and anemia disease splenomegaly Behçet syndrome Aphthous ulcers, arthralgia, uveitis Recurrent oral ulcers plus two of the following: eye lesions, genital ulcers, skin lesions Chronic fatigue Persistent and unexplained fatigue that Tests to rule out other diseases: complete blood count, ESR, CRP, syndrome significantly impairs daily activities complete metabolic panel, TSH, urinalysis Endocarditis Arterial emboli, arthralgia, fever, heart Positive echocardiography findings with vegetation on heart valve; murmur, myalgia positive blood culture Fibromyalgia Poorly localized pain above and below 11 of 18 sites (bilateral) perceived as painful. Posteriorly, the sites waist on both sides, involving neck, back, are: occiput, trapezius, supraspinatus, gluteal, greater trochanter. and chest Anteriorly, they are: low cervical, second rib, lateral epicondyle, knee HIV infection Arthralgia, fever, lymphadenopathy, malaise, Western blot assay for detection of HIV antibodies myalgia, peripheral neuropathy, rash Inflammatory Diarrhea, peripheral arthritis, rectal Colonoscopy to assess disease activity; measure CRP level, platelets, bowel disease bleeding, tenesmus and ESR; test for anemia Lyme disease Arthritis, carditis, erythema migrans, Serologic testing for Lyme disease neuritis Mixed connective Arthralgia, myalgia, puffy fingers, Raynaud Tests for elevated ESR and hypergammaglobulinemia, positive anti- tissue disease phenomenon, sclerodactyly U1RNP antibodies Psoriatic arthritis Psoriasis before joint disease, nail changes Inflammatory articular disease and more than three of the following: in fingers and toes psoriasis, nail changes, negative rheumatoid factor, dactylitis, radiographic evidence of new bone formation in hand or foot Reactive arthritis Acute nonpurulent arthritis from infection Clinical diagnosis to identify triggers; serologic findings of recent elsewhere in the body infections may be present Rheumatoid Morning joint stiffness lasting more than Positive tests for rheumatoid factor and anticyclic citrullinated arthritis one hour; affected joints are usually antibodies; synovial fluid reflects inflammatory state symmetric, tender, and swollen Sarcoidosis Cough, dyspnea, fatigue, fever, night Chest radiography, bilateral adenopathy with biopsy revealing non- sweats, rash, uveitis caseating granuloma, elevated angiotensin-converting enzyme level Systemic sclerosis Arthralgia, decreased joint mobility, Tests for specific autoantibodies myalgia, Raynaud phenomenon, skin induration Thyroid disease Dry skin, fatigue, feeling cold, weakness Measure TSH CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; HIV = human immunodeficiency virus; TSH = thyroid-stimulating hormone. Information from reference 12. myalgia, which occur in up to 95% of patients with SLE.10 hematologic, cardiac, pulmonary, gastrointestinal, or Less common presenting symptoms include malar rash reticuloendothelial.8 Specific symptoms are listed in (31%), photosensitivity (23%), pleuritic chest pain (16%), Table 2.8,13 Discoid rash (positive likelihood ratio [LR+] new-onset Raynaud phenomenon (16%), and mouth sores = 18), malar rash (LR+ = 14), unexplained seizures or (12.5%).11 Table 1 lists the differential diagnosis.12 psychosis (LR+ = 13), and photosensitivity (LR+ = 11) provide the strongest evidence in favor of SLE.14 INITIAL EVALUATION Once SLE is suspected, the initial evaluation should SLE should be suspected in a patient with symptoms include an antinuclear antibody (ANA) test.15 This in at least two of the following organ systems: consti- is a highly sensitive test, with positive results in about tutional, musculoskeletal, skin, renal, neuropsychiatric, 94% of patients with SLE.15 SLE is unlikely in a patient August 15, 2016 ◆ Volume 94, Number 4 www.aafp.org/afp American Family Physician 285 Lupus Table 2. Diagnostic Criteria for Systemic Lupus Erythematosus System ACR criteria* SLICC criteria† Cardiac/ Pleuritis (pleuritic pain or rub, or pleural Serositis (pleurisy for more than one day, pleural effusion, or pulmonary effusion), or pericarditis (documented by pleural rub; pericardial pain more than one day, pericardial electrocardiography, rub, or pericardial effusion, pericardial rub, or pericarditis) effusion) Hematologic Hemolytic anemia, or leukopenia (< 4,000 cells Hemolytic anemia 3 per mm ), or lymphopenia (< 1,500 cells per Leukopenia (< 4,000 cells per mm3) more than once or 3 mm ), or thrombocytopenia (< 100,000 cells lymphopenia (< 1,000 cells per mm3) more than once per mm3) Thrombocytopenia (< 100,000 cells per mm3) Immunologic Positive ANA result