Systemic Lupus NCNP

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Systemic Lupus NCNP

Session 215

Rick Pope MPAS, PA-C, DFAAPA, CPAAPA

Western CT Medical Group Dept of Rheumatology Danbury, CT

[email protected]

Treatment in 2016?

• With modern therapeutic advances, the mortality rate from lupus erythematosus has decreased substantially.

• It is hoped that current research will further improve the prognosis of this disease in the near future.

South Med J. 2007 Sep;100(9):896-8. The history of lupus erythematosus.

Lupus = Latin for Wolf

Term of lupus first used in the Middle Ages to describe skin lesions that were suggestive of a wolf’s bite

1 What is this?

Lupus Types

1. Subacute Lupus Erythematosus 2. Discoid Lupus 3. Drug Induced Lupus* 4. Systemic Lupus Erythematosus 5. Neonatal Lupus*

*Will not be covered in this slide set

Speaker’s disclosures

Nothing to disclose

2 Case 1

47 y.o. African American female with “swelling all over” - Generalized joint pain - Cough with clear sputum production - Occasional pleuritic chest discomfort - Occasional dyspnea - Generalized weakness - Toe numbness - 10-11 hospitalizations with ? Tx per pt. - Rectal bleeding, N/V---Transfused

Case 1

PMHx- HTN, palpitations, COPD, blood transfusions

Surgical Hx -Partial Hyst (2003)

Meds- Norvasc, Altace, Lasix

FH- No CTD, Maternal aunt-? Arthritis

SH- Single, Last worked in 2000.

Tobacco-D/C cigs in “1980’s” X “short period of time”

ETOH- D/C age 31-32—”as much as I could get”

Case 1 ROS

Pertinent (+) Pertinent (-) Fatigue Raynaud’s ?Fever Lymphadenopathy Anorexia Seizure Sleep difficulty 2° “sore” Inflammatory eye sxs “Very light” headache Chest Pain Weak Dysphagia Occasional dry mouth and nose Sun sensitivity Dyspepsia Psoriasis Vaginal discharge Hair loss ? Left Knee rash

3 Case 1

PE- Vital signs-5’4’’, 152lbs, 130/82, 98.7 Chronically ill appearing Thinning of hair in temporal regions Mildly diminished salivary pool Diffuse abd. discomfort without guarding/rebound Diffuse synovitis, small knee effusions Hyperpigmentation—BUE, Left knee, face Generalized decreased motor strength Decrease sensation to touch in feet

Case 1

What would you do next?

Order labs: 1. CBC 2. CMP 3. Inflammatory markers 4. ANA, RF anti-CCP 5. Lyme screen 6. Urinalysis 7. Chest x-ray

Case 1

 ANA (+)≥1:2560 homogeneous  RF negative  CBC- Mild chronic disease anemic MCI wnl  WBC- 3.2 relative leukopenia, lymphopenia  Platelets 97,000  CMP- Creatinine 1.3, eGFR 56ml/min  ESR- 42  CRP- 28 (uln 20)  Urinalysis- 1+ protein  Chest x-ray- no acute process

4 Systemic lupus erythematosus: 1982 classification criteria definitions

Malar rash Fixed erythema, flat or raised, sparing the nasolabial folds

Discoid rash Raised patches, adherent keratotic scaling, follicular plugging; older lesions may cause scarring

Photosensitivity Skin rash from sunlight

Oral or nasopharyngeal Usually painless ulcers

Arthritis Nonerosive, inflammatory in two or more peripheral joints

Serositis Pleuritis or pericarditis

Systemic lupus erythematosus: 1982 classification criteria definitions

Renal disorder Persistent proteinuria or cellular casts

Neurologic disorder Seizures or psychosis

Hermatologic Hemolytic anemia, leukopenia (<4,000/mm3), lymphopenia (<1,500/mm3), or thrombocytopenia (<100,00/mm3)

Immunologic disorder Antibodies to dsDNA or SM or positive antiphospholipid antibodies (IgG or IgM antibodies, lupus anticoagulant, or false-positive serologic test positive serologic test for syphilis)

ANA test Positive

ACR Criteria for Classification of SLE

Rules for using the criteria:

A patient who exhibits any 4 of these 11 criteria is classified as having SLE

Criteria need not be present simultaneously

SLE evolves over time.

5 The 1982 criteria for classification of SLE

 For the purpose of clinical studies: SLE can be diagnosed if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation.

 Sensitivity 96%  Specificity 96% in adults and peds.

Differential diagnosis

 Pt has 3 out of 4 criteria for SLE

 ANA +

 Leukopenia, lymphopenia, thrombocytopenia

 Arthritis of two or more peripheral joints

When Is proteinuria elevated enough to consider a kidney biopsy?

1. Increasing creatinine without any other cause. (hypovolemia, medication etc) 2. Confirmed proteinuria of >1 g per 24 hours 3. Proteinuria >0.5 plus hematuria or cellular casts

Famous people with Lupus who do not have it In 2010, Lady Gaga told Larry King that she tested "borderline positive" for lupus . “But to be diagnosed with lupus, a person must have certain symptoms and a positive blood test for self-attacking antibodies”

And the pop diva told Larry she didn’t.

One in five women test positive for lupus-associated antibodies but a small fraction have the autoimmune disease.

6 Famous people with lupus

Seal The scars on the singer’s face are the result of discoid lupus erythematosus, a type of lupus involving only the skin.

Discoid Lupus

Ten percent of people with discoid lupus will go on to develop systemic lupus.

SLE: A Working Definition

1. Lupus is a systemic autoimmune disease in which the body loses tolerance to self

2. Can affect virtually any organ in the body and initial symptoms are often nonspecific, making it very difficult to diagnose

3. Typical autoantibodies seen are those reacting against nuclear components of the cell

4. Most commonly seen in women of childbearing age but 10% of patients are men

5. Lupus is a clinical diagnosis made by a clinician. Most patients will have four or more ACR criteria.

Systemic Lupus Erythematosus SLE Definition/Diagnosis • Prototype of auto-immune disease • Onset maybe acute, episodic, or insidious • Anything can happen to any organ system at any time. • Antinuclear antibodies are almost always present • Serositis & Immune complexes can be the hallmark and pathogenesis of the disease.

SLE: Average Time to Diagnosis

• Average time of two years between initial symptomatology and definitive diagnosis¹.

1.Cervera, Medicine, 1993; Font, Semin Arthritis Rheum, 2004

The 1982 revised criteria for classification of SLE Revised 1997

1.Malar rash 6. Serositis 2.Discoid rash 7. Renal disorder 3.Photosensitivity 8. Neurologic disorder 4.Oral ulcers 9. Hematologic disorder 5.Arthritis 10. Immunologic disorder 11. Antinuclear antibody

Revised 1997

Malar Rash

1. Photosensitive 2. Spares nasolabial folds 3. Rosacea does not spare nasolabial folds*

8 Malar Rash

• Fixed erythema, flat or raised, over malar eminences

• Tends to spare nasolabial folds

Malar Rash

Erythematous May be hyperpigmented in darker skinned individuals Flat or raised May occur on exposure to sunlight SPARES NASOLABIAL FOLDS

Malar Rash Pathognomic

9 Differential Diagnosis of Malar Rash

Malar rash, flushing or hyperpigmentation of bilateral cheeks and bridge of nose which spares the nasolabial folds, is pathognomic of lupus.

Nevertheless, similar rashes may be present in a variety of other disorders including:

• Rosacea • Glucocorticoid-induced atrophy • Dermatitis • Chloasma/ Melasma • Seborrheic • Benign flushing • Atopic • Contact

Skin and mucosal lesion Patterns

1. Acute - localized or generalized

2. Subacute – Annular or psoriaform

3. Chronic – Discoid localized or generalized

4. Nonspecific rashes (biopsy can be helpful and diagnostic)

• vasculitis • alopecia • livedo reticularis • Raynaud’s • urticaria • lichen planus

Lupus Vasculitis

10 Lupus Alopecia

• Most SLE patients • Localized or generalized • Scalp, eyebrows, eyelashes, body hair • Increased with disease activity

Subsides as disease subsides

Livedo Reticularis

Raynaud’s Phenomenon

• Vascular • Color Changes • Ulcers • Gangrene

11 Urticaria

Lichen Planus

The 1982 revised criteria for classification of SLE

Revised 1997

12 Discoid Lupus Erythematosis (DLE) Subset

• Patients with DLE have a 5 to 10% risk of developing SLE

90-95% do not go on to SLE

• This form of SLE tends to be mild

• The more numerous and widespread the lesions are the higher the risk of developing SLE

Discoid Lupus

Can occur in 25% of SLE patients

Discoid Rash

Erythematous raised patches Adherent keratotic scale Follicular plugging

Atrophic scarring may occur as DLE on arm lesions age

LOOK IN EARS! DLE on arm DLE in ear

DLE in ear

13 Discoid Rash

• Erythematous raised patches with adherent keratotic scaling and follicular plugging

• Atrophic scarring may occur in older lesions

Subacute Cutaneous Lupus Subset of (SCLE)

•Positive anti–Ro (SS-A) and anti–La (SS-B) •Photosensitive •Face usually spared •Non scarring •Fatigue common •Arthralgia and arthritis

•50% of patients with SCLE will have SLE

THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Revised 1997

14 Photosensitivity

• Skin rash as an unusual reaction to sunlight

• By patient history or practitioner observation

This is not easily sun burned Or getting blisters with a 2° sunburn

The 1982 revised criteria for classification of SLE

Revised 1997

Mucocutaneous Ulcers

• Oral or nasopharyngeal ulcerations

• Must be observed by physician health care provider

• Often painless

15 The 1982 Revised Criteria For Classification of SLE

Revised 1997

Arthritis

1. Nonerosive arthritis involving 2 or more peripheral joints

2. Characterized by tenderness swelling, or joint effusion.

Jaccoud’s Arthropathy

Reducible deformities No erosions Peri-articular fibrosis and ligamentous laxity Swan neck deformities

16 Rhupus

• Erosive and symmetric pattern

• Associated erosive pattern on x-ray

• 65% have a positive RF and anti-CCP -

THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Revised 1997

Serositis

Pleuritis - convincing history of pleuritic pain or rub heard by a physician/pratitioner or evidence of pleural effusion.

Pericarditis - documented by ECG or rub or evidence of pericardial effusion. Transthoracic echo, transesophageal echo.

17 SLE Pleuropulmonary disease

• Pleuritis/Pleural effusion • Infiltrates/Atelectasis • Acute lupus pneumonitis • Pulmonary hemorrhage • “Shrinking lung” - diaphragm dysfunction • Subclinical restrictive disease

Left sided pleural effusion in SLE

SLE Cardiac involvement

• Pericarditis • Myocarditis • Endocarditis, Libman-Sacks* • Accelerated atherosclerosis

*Described as non infectious cross between bacterial endocarditis and fibroid non-infectious growth on cardiac valves. Described in 1928 by Libman and Sacks in the American Journal of Pathology and associated with similar lesions in kidney and rash on face.

18 THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Revised 1997

Renal Disorder 1. Persistent proteinuria greater than 0.5 grams/ 24 hr or greater than 3+ if quantitation not performed

Red cell cast 2. Active urinary sediment - Cellular casts - may be red cell, hemoglobin, granular, tubular, or mixed.

SLE Renal involvement

• Usually asymptomatic (Pearl: get UA) • Gross hematuria • Nephrotic syndrome • Acute renal failure • Hypertension • End stage renal failure

19 SLE Nephritis

Nephritis remains the most frequent cause of disease-related death.

THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Revised 1997

Neurologic disorder Psychiatric disorder

1. Seizures - in the absence of offending drugs or known metabolic derangements, e.g., uremia, ketoacidosis, or electrolyte imbalance

2. Psychosis - in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis, or electrolyte imbalance

20 THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Revised 1997

Thrombocytopenic Purpura

• Non blanching • Purplish discoloration • Purpura is not a disease but indicates underlying bleeding disorder • Usually lower extremities • < 1 cm is petechiae

Hematologic Disorder

Hemolytic anemia with reticulocytosis OR Leukopenia—less than 4000/mm 3 total on two separate occasions OR Lymphopenia—less than 1500/m 3 on two or more occasions OR Thrombocytopenia—less than 100,000/m³ in the absence of offending drugs

21 THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Revised 1997

Immunologic Disorder “ANA subsets or ENAs”

1. Anti-dsDNA: antibody to native DNA in abnormal titer or

2. Anti-Sm: presence of antibody to Sm nuclear antigen or

3. Antiphospholipid antibodies by positive IgG or IgM anticardiolipin antibodies (not IgA) or a positive test for lupus anticoagulant, or a false positive test for syphilis (RPR) for 6 months

Immunologic Disorder

3. Antiphospholipid antibodies:

• Anti-ACL by + antibodies

• Lupus anticoagulant +

• False positive test for syphilis RPR for 6 months (Not VDRL)

22 SLE Laboratories

• Antibodies to dsDNA are present in 70% of lupus patients and are >95% specific for lupus • Anti-Sm (Smith) + in up to 30% of lupus patients and is pathognomonic • Decreased C3 and C4 indicate activity • Anti-Ro (SS-A) congenital heart block (refer children of mothers for pediatric evaluation)

THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

Revised 1997

Antinuclear Antibody

1:20 - 1:40 Screening titer is + in most labs: 1: x titer Higher titers Speckled Rim/peripheral likelihood of disease At any point in time (example 1:320, 640,1280, 2560)

Patterns

• Speckled • Rim/peripheral • Homogeneous/Diffuse • Nucleolar

Courtesy ACR slide collection Nucleolar Diffuse/homogeneous

23 Antinuclear Antibodies ANA

•Low titer positive ANA in normal population increases with age

•Patterns of ANA immunofluorescence vary.

-SLE is commonly associated with peripheral or speckled patterns

-Homogeneous patterns are associated with drug induced lupus.

-First degree relatives of patients with SLE are likely to be ANA positive

32% of relatives had antinuclear antibodies, compared with 1.5% of the healthy controls

(Sack, Primer 2001; Van der Linden, J Rheumatol 2001)

+ANA What does it mean

• Sensitivity 95-98%

• Specificity very low

• Positive in many autoimmune diseases

• 10 to 35% of adults aged >65 have + ANAs and do not have Lupus or other autoimmune disease

• Negative ANA occurs in less then 3% of lupus patients

ANAs

1. ANAs do not correlate with disease activity.

2. Do not forget other causes of a positive ANA.

3. A patient with a negative ANA has less than a 3% chance of developing SLE.

24 Other causes positive ANA

Other Collagen Vascular Diseases

• RA, Sjogren’s, Scleroderma, Myositis • Infections (viral, bacterial, spirochetal) • Thyroiditis or Graves • Cancers such as melanoma, breast, lung • GI ( hepatitis, UC, Crohn’s, Primary Biliary Cirrhosis • Lung (pulmonary fibrosis, TB) • Medications

Diagnostic Imaging

• Not valuable for diagnosis of lupus

• Used in detecting specific organ manifestations and in ruling out other disorders.

Diagnostic Imaging

X-ray -Distinguish erosive or deforming arthritis -Check for cardiopulmonary involvement (cardiomegaly, interstitial lung disease, pleural effusion)

Echocardiogram -Identify pericardial effusion -Identify pulmonary hypertension

Pulmonary function test: -Useful for picking up low diffusion capacity (DLCO), suspicious for pulmonary hypertension -Identify restrictive versus obstructive disease

25 SLE

Common manifestations ACR Criteria

1. Arthritis 83% 2. Malar rash 54% 3. Photosensitivity 41% 4. Nephropathy 34% 5. Oral Ulcers 30% 6. Serositis 28% 7. Seizure/Psychosis 12%

SLE Common manifestations not part of ACR criteria

1. Fever and Constitutional Symptoms 42% 2. Raynaud's Phenomenon 22% 3. Alopecia 18% 4. Cutaneous Vasculitis 13%

Clustering of symptoms

1. Cutaneous, articular and renal manifestations tend to appear “together”

2. CNS thrombotic and muscular symptoms also cluster, although to a lesser extent

26 Case 2

• 33 year old Caucasian female is referred for + ANA speckled pattern with + dsDNA. • CC: recent onset of arthritis symptoms in the index finger of the left hand for the past eight months and she describes a sausage shaped swelling making it difficult to make a fist. These symptoms dissipated and then the long finger developed the same symptoms. She also has Raynaud’s phenomenon but denies other symptoms of connective tissue disease. She does complain of Raynaud’s in the cold months of the year

• PMHx: History of cholecystectomy for chronic nausea, MVA in 2004 and 2010 left with recurrent low back pain

Case 2

• PMHx continued:

• 3 episodes of renal stones • ADD Rx with Vyvanse • Depression- Rx on Zoloft

• FMHx: Grandmother has SLE and “arthritis”

Differential Diagnosis of Lupus

• SLE has been termed “the great imitator” for its propensity to mimic various other disorders. • Differential diagnoses to consider when a patient presents with polyarticular joint pain.

• Early Rheumatoid Arthritis • Mixed Connective Tissue Disease- Undifferentiated Connective Tissue Disease • Anti phospholipid antibody syndrome (APLS) • Fibromyalgia with positive ANA • Primary Sjogren’s Syndrome • Vasculitis • Scleroderma • Drug induced lupus

27 Did she meet the SLE criteria?

1. She has ANA and dsDNA 2, She has arthritis

• She has Raynaud’s (not a criteria)

• The answer is no but we treated her as if she has SLE

Case 2

• Chest x-ray was negative • Urinalysis was negative for protein • No hypertension, no hyperlipidemia • HIV and Hep studies were negative. • Child bearing years and worked up for APLS (LAC and cardiolipins were -)

Case 2

• What is the best approach in SLE patients with arthritis who have no internal organ involvement?

• 1st line NSAIDS COX 2s preferred

• Anti-malarials low dose-200mg BID of hydroxychloroquine with benefit of decreased flares and of developing end organ damage

28 Management Goals for SLE for co-management with PCP

• Counseling, education

• Decrease inflammation; prevent end-organ injury/failure

• Provide HBP Rx

• Evaluate for dyslipidemia

• Maintain up-to-date immunizations

Management Goals for SLE for co-management with PCP

• Management of infection

• Identify patients at risk of thrombo- occlusive events

• Family planning/contraceptive issues

• If pregnant refer to maternal/fetal specialist or high risk OB-GYN

Take home points

• Lupus is treatable • Most patients it is an annoyance because they take medication and see the rheumatologist and PCP more often • Educate your patient on maintaining controlled BP and lipids • Vaccinate your patients for infection • Monitor for changes and look for any new symptoms

29 Summary

• Do not order ANAs for broken bones

• Most ANAs do not mean Lupus

• Know what you are going to do with the result of an ordered lab test.

• Lupus patients can live and accomplish goals just like everyone else

Questions? Thank you

Rick Pope MPAS, PA-C, DFAAPA [email protected]

Extra Slides

30 Differential Diagnosis of Fever

Low grade fever is a systemic sign of infection or inflammation. Common diagnoses to consider include: • InfectionTuberculosis, -Malaria, AIDS-associated infections • Malignancy -lymphoma • Drug-induced • Inflammatory and Collagen-vascular disease -Sarcoidosis, SLE, Stills disease, Vasculitis

(Bor DH. Approach to patient with FUO. Up to Date v.14.2 )

Photosensitivity

Pathophysiology Clinical Correlation

• UV light damage 29 lupus patients (Finland)

• Disease activity increased significantly

• epidermal/dermal cells apoptosis in spring and summer

• nuclear autoantigen exposed • Most due to renal disease, low

complements, hematologic • immune system sensitized Flares in “photosensitive” patients • autoantibodies production and in “not-photosensitive” pts

No difference in sun-avoidant behaviors or sun protection use between “photosensitive” pts and malar rash multiorgan flares “not-photosensitive” pts

WORLD HEALTH ORGANIZATION CLASSIFICATION OF LUPUS NEPHRITIS

Class I Normal Class II Mesangial IIA Minimal alteration IIB Mesangial glomerulitis Class III Focal and segmental proliferative glomerulonephritis Class IV Diffuse proliferative glomerulonephritis Class V Membranous glomerulonephritis Class VI Glomerular sclerosis

31 ACR Criteria for Classification of SLE

• Initially published in 1971

Purpose: to provide a standardized definition of SLE for use in research

• Revised in 1982

• Clarifications made in 1997

Revised the immunologic criteria to reflect the growing knowledge and new diagnostic tests available

Criteria as detailed on the following slides are listed almost verbatim from the Primer on Rheumatic Diseases. Original sources: (Tan, 1982; Hochberg, 1997)