710.0 – Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease of unclear etiology characterized by immune abnormalities and multisystem involvement. Patients can present with marked constitutional symptoms, fever, fatigue, weight loss, arthralgias, and skin findings. In some individuals, psychiatric disturbances, pericarditis, pleurisy, or abdominal pain can be prominent.

The disease affects women more often than men, and it is more common in blacks than whites. It is found worldwide. Genetic factors play a role, and a family history of SLE or lupus erythematosus in any form is a risk factor for developing the disease.

There are drug-induced forms of the disease, with a differing pattern of autoimmunity and clinical profile (discussed separately as drug-induced SLE). Other findings in lupus erythematosus include lymphadenopathy, conjunctivitis, episcleritis, normocytic normochromic anemia, (sometimes hemolytic anemia), and leukopenia.

The classic cutaneous finding in SLE is the malar or "butterfly" blush. Erythema covering the nose and medial cheeks can occur after sun-exposure and precede the systemic symptoms by weeks. The erythema often develops into fine, scaling coalesced papules. The erythema can become intense, and small infarcts and necrosis can develop in fulminant cases. A rash can develop in a photo distribution with prominence on the dorsa of the hands and digits. This rash can involve the arms and trunk. Nail fold erythema and even necrosis often occurs. Small mucous membrane ulcers, especially on the palate, can develop. Livedo reticularis is common. Discoid lupus lesions can be seen. If systemic lupus does not start within the first few (often 2) years of the disease, there is a low probability of systemic lupus. Variants also include bullous lupus erythematosus. Purpura can occur secondary to vasculitis and is usually found on the extremities. Lupus profundus is a panniculitis rarely seen in patients with SLE. Some patients with systemic lupus will have psoriasiform or annular lesions in a photo distribution (subacute cutaneous lupus).

Sometimes multiple dermatofibroma may be present. Look for periungual telangiectasias, erythema and scaling between the finger joints, and temporal hair thinning in addition to the clinical lesions.

Dermatomyositis – Characteristic heliotrope rash (violaceous plaques surrounding eyes), photodistributed cutaneous eruption, and nailfold changes. Look for elevated serum CK levels and proximal symmetric extremity weakness.
Rosacea – ANA negative.
Stevens-Johnson syndrome – Characteristic target lesions, prominent systemic symptoms, but ANA and DIF negative.
Antiphospholipid antibody syndrome / lupus anticoagulant – Can overlap with SLE; associated with recurrent thromboses and spontaneous abortions, elevated PT time.
Polymorphous light eruption (PMLE) – Most lesions resolve within several days; skin lesions are located primarily on sun-exposed areas (SLE can occur on sun-exposed and sun-protected areas). Note that previous studies have shown that up to 19% of patients with PMLE can be ANA positive. Hence, an ANA alone may not be sufficient in differentiating PMLE from SLE.
Phototoxic / photoallergic drug eruptions
CREST syndrome – Can have overlap with dermatomyositis. Refers to a subset of patients with limited scleroderma.
Seborrheic dermatitis – No systemic findings. Erythema and scale in sebaceous distribution.
Systemic amyloidosis
Contact dermatitis
Pityriasis rubra pilaris
Sarcoidosis
Scleroderma – Check for anticentromere antibodies and anti-Scl-70 antibodies. Typified by sclerotic changes in skin not seen in dermatomyositis.
Graft-versus-host disease – Occurs after allogeneic stem-cell transplantation
Mixed connective tissue disease – Check for anti-U1RNP antibody. Most patients are positive for this in mixed connective tissue disease.
Generalized morphea – Asymmetric induration, no Raynaud's phenomenon, no systemic involvement.
Polymyositis – Without cutaneous findings.
Acute lesions of erythropoietic protoporphyria may have similar locations, especially on the dorsum of the hands, but usually there is no weakness.
Tinea faciei – Check KOH; will also be ANA negative.

ANA and anti-DNA antibodies are found in a majority of patients. Diagnosis is made on clinical and serologic grounds, using the ARA (American Rheumatologic Association) criteria for diagnosis. Skin biopsy can be diagnostic for lupus, as well as biopsy of uninvolved skin for direct immunofluorescence. Check BUN/Cr, liver urinalysis, function tests, and serum complement (CH50). Slight elevations in PTT and PT might suggest the presence of the lupus anticoagulant. Patients with the lupus anticoagulant are at higher risk for stroke and thrombosis. ARA criteria (at least 4 of the following): malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder, and presence of anti-nuclear antibody.

Consultation with multiple specialists is mandatory for patients with SLE.

The patient should avoid sunlight (especially at noon and at high altitudes), photosensitivity drugs (antihistone antibody), and exogenous estrogens.

Treatment should be commensurate with the severity of the disease.

Antimalarials

• Hydroxychloroquine: 200–400 mg p.o. daily
• Chloroquine: 125–250 mg p.o. daily

Glucocorticoids

• Prednisone: 5–60 mg p.o. daily or divided 2–4 times daily; taper over 2 weeks

Immunosuppressives

• Cyclophosphamide: 10–20 mg/kg IV every 3–4 weeks or 1.5–2.5 mg/kg p.o. daily
• Azathioprine: 1.5–3 mg/kg p.o. daily, maintenance dose of 1–2 mg/kg/day
• Mycophenolate mofetil: 500 mg p.o. twice daily, increase over several weeks to 1,500 mg p.o. twice daily
• Arthritis, arthralgias, and myalgias can be managed with nonacetylated salicylates (choline magnesium trisalicylate 500 mg to 1.5 g p.o. 2–3 times daily) and NSAIDs (ibuprofen 400–600 mg p.o. every 4–6 hours, as needed)

Rhodes B, Vyse TJ. The genetics of SLE: an update in the light of genome-wide association studies. Rheumatology (Oxford). 2008 Nov;47(11):1603-11. PubMed Id: 18611920

Hiraki LT, Benseler SM, Tyrrell PN, Hebert D, Harvey E, Silverman ED. Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. J Pediatr. 2008 Apr;152(4):550-6. PubMed Id: 18346514

Bertsias G, Ioannidis JP, Boletis J, Bombardieri S, Cervera R, Dostal C, Font J, Gilboe IM, Houssiau F, Huizinga T, Isenberg D, Kallenberg CG, Khamashta M, Piette JC, Schneider M, Smolen J, Sturfelt G, Tincani A, van Vollenhoven R, Gordon C, Boumpas DT, Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis. 2008 Feb;67(2):195-205. PubMed Id: 17504841

Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008 Feb 28;358(9):929-39. PubMed Id: 18305268

Bertsias G, Gordon C, Boumpas DT. Clinical trials in systemic lupus erythematosus (SLE): lessons from the past as we proceed to the future--the EULAR recommendations for the management of SLE and the use of end-points in clinical trials. Lupus. 2008;17(5):437-42. PubMed Id: 18490423

Costner ML, Sontheimer RD. Lupus Erythematosus. In: Fitzpatrick TB, Wolff K, eds. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008:1515-1535.

Munoz LE, van Bavel C, Franz S, Berden J, Herrmann M, van der Vlag J. Apoptosis in the pathogenesis of systemic lupus erythematosus. Lupus. 2008;17(5):371-5. PubMed Id: 18490410

Macdermott EJ, Adams A, Lehman TJ. Systemic lupus erythematosus in children: current and emerging therapies. Lupus. 2007;16(8):677-83. PubMed Id: 17711907

Tucker LB. Making the diagnosis of systemic lupus erythematosus in children and adolescents. Lupus. 2007;16(8):546-9. PubMed Id: 17711886

Petri M. Review of classification criteria for systemic lupus erythematosus. Rheum Dis Clin North Am. 2005 May;31(2):245-54, vi. PubMed Id: 15922144

Majeski C, Ritchie B, Giuffre M, Lauzon G. Pincer nail deformity associated with systemic lupus erythematosus. J Cutan Med Surg. 2005 Jan;9(1):2-5. PubMed Id: 16208437

Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999 Sep;42(9):1785-96. PubMed Id: 10513791

Appearance
No Acute Distress
Patient Appears Ill

Body Location
Cheek
Face
Finger Nails
Periungual Fingers
Superior Chest
Upper Back

Configuration
Reticular

Distribution
Acral
All Twenty Nails or Distal Digits
Photodistributed (Sun-Exposed)

Laboratory
ANA Positive
Anti-Double Stranded DNA
Anti-Sm Antibodies
Blood Urea Nitrogen (BUN) Elevated
Creatinine Elevated
Erythrocyte Sedimentation Rate (ESR) Elevated
Hematocrit Decreased (Anemia)
Hemolytic Anemia
Leukopenia
Microscopic Hematuria
Partial Thromboplastin Time (PTT) Prolonged
Proteinuria
Prothrombin Time (PT) Prolonged
RBC Casts
Thrombocytopenia

Lesion
Buccal Mucosa Ulcer
Conjunctival Injection (Redness, Bloodshot Eyes)
Diffuse Black
Diffuse Blue
Diffuse Brown
Erythema and Edema
Hair Loss (Alopecia)
Hyperkeratotic Cuticle
Koebner Phenomenon
Longitudinal Pigmented Bands
Nail Fold Telangiectasia
Oil Spots
Onycholysis - Lifting Nail
Palpable Purpura
Papule
Petechiae
Pincer Curvature
Pleural Effusion
Pterygium
Reticular - Netlike
Scaly Plaque
Subungual Hyperkeratosis
Tongue Ulcer
Transverse White Lines

Medications
Clopidogrel
Hydralazine
Isoniazid
Procainamide
Ticlopidine

Signs and Symptoms
Abdominal Pain
Arthralgia (Joint Pain)
Cardiac Dysrhythmia (Arrhythmia)
Fatigue (Lethargy, Weariness)
Fever (Febrile)
Generalized Weakness (Asthenia)
Headache
Hepatomegaly
Hypertension (High Blood Pressure, Elevated Blood Pressure)
Joint Swelling
Joint Tenderness
Lung Exam - Decreased Breath Sounds
Lung Exam - Dullness to Percussion
Lung Exam - Pleural Rub
Lymphadenopathy
Mental Status Alteration
Muscle Atrophy
Myalgia (Muscle Pain)
Nail Pain
Nausea
Oral Ulcers
Photosensitivity
Pleuritic Chest Pain
Sclerodactyly
Seizures
Weight Loss

Temporal
Developed Acutely Over Days to Weeks
Developed Steadily Over Weeks to Months

Medical History
Nephritis