DERMATOLOGY FOR THE USMLE AUTOIMMUNE SKIN DISORDERS (1) 1. LUPUS ERYTHEMATOSUS (LE)

DERMATOLOGY FOR THE USMLE

AUTOIMMUNE SKIN DISORDERS (1)

1. LUPUS ERYTHEMATOSUS (LE)

→	General: Complex, multifactorial autoimmune disorder characterized by a chronic relapsing and remitting course and prominent skin involvement  Broadly divided into systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). SLE is the most common and severe type of LE affecting multiple organ-systems. CLE primarily affect the skin although many patients also present with systemic manifestations and go on to develop SLE. SLE is a female predominant disease and more prevalent in African American females Production of autoantibodies and circulating immune complexes are thought to play an important role in the pathogenesis. The important antibodies to consider in SLE are: »Anti-nuclear antibody (ANA): The most sensitive but least specific. May be positive in healthy individuals (eg, elderly) and in many other systemic diseases. »Anti-double-stranded DNA antibody (Anti-dsDNA): Most useful, very sensitive and specific. Correlates with disease activity, exacerbations, prognosis and renal involvement. »Anti-Smith antibody (Anti-Sm): Less sensitive but most specific (if positive, high chance of having lupus). »Anti-phospholipid antibody (aPL): Associated with anti­phospholipid syndrome (APS). APS is characterized by multiple thrombus formation and spontaneous abortions. »Anti-SSA (Anti-Ro) and anti-SSB (Anti-La): Neither specific nor sensitive for lupus. When positive, it is associated with neonatal heart block Anti-SSA and anti-SSB may also be positive in Sjögren syndrome, rheumatoid arthritis (RA), systemic sclerosis and polymyositis.
→	Clinical: Cutaneous lupus erythematosus (CLE) is further subdivided into acute, subacute and chronic CLE. » Acute Cutaneous Lupus Erythematosus (ACLE): This type of cutaneous lupus is characterized by the classic facial malar or “butterfly” rash and a photosensitive, erythematous maculopapular rash predominantly on sun-exposed areas. Oral and nasal mucosal ulcerations are common. Most patients with ACLE will have SLE and also present with systemic symptoms and internal organ involvement, such as: Blood: Leukopenia, anemia and thrombocytopenia. Brain: Seizures and psychosis. Heart: Pericarditis, myocarditis and arrhythmias. Kidney: Renal failure and nephritis. Lung: Pleural effusion and pleuritis. Musculoskeletal: Arthritis and arthralgias. Constitutional symptoms: Fever, fatigue, lymphadenopathy and weight loss. » Subacute Cutaneous Lupus Erythematosus (SCLE): This type of cutaneous lupus typically presents with erythematous annular lesions with raised borders and central clearing or psoriasis-like scaly papules and plaques. Sun-exposed areas such as the upper extremities, chest and face are mainly affected. About half of patients with SCLE have SLE and also present with systemic manifestations. » Chronic Cutaneous Lupus Erythematosus (CCLE): Most commonly presents with erythematous, inflamed and round (discoid) scaly plaques with central atrophy and white patches. Lesions are located above the neck 80% of the time and may heal with scarring. Scalp involvement may lead to permanent alopecia. Patients with CCLE less commonly have SLE or systemic symptoms.
→	Diagnosis » Best initial test: Clinical + CBC (anemia, thrombocytopenia and leukopenia) + urinalysis, BUN and Cr + autoantibody assays to detect anti-nuclear antibody, anti-dsDNA and anti-Sm. If patient has renal involvement, perform a renal biopsy before initiating treatment (biopsy guides treatment). » Most accurate test: Skin biopsy showing epidermal atrophy and inflammation at the DEJ and perivascularly. Direct immunofluorescence (DIF) studies revealing a granular pattern of IgG, IgM, IgA and C3 along the DEJ.
→	Treatment » First line: Avoid and protect from sun + topical steroids and hydroxychloroquine. » Second line: Systemic therapy with steroids, methotrexate, cyclophosphamide or azathioprine for severe disease.
→	USMLE pearls: drug-induced lupus: A subtype of lupus erythematosus induced by drugs. The main culprits are: hydralazine, isoniazid, procainamide, quinidine, diltiazem, minocycline and proton pump inhibitors (PPIs). May arise months to years after drug exposure. Presents similar to SLE but without CNS or kidney involvement. Diagnosis based on clinical features and presence of anti­histone antibody. Treat by discontinuing offending drug.
→	USMLE Pearls: Patients with autoimmune disorders are commonly under chronic systemic corticosteroid therapy. Abruptly discontinuing or insufficient supply of steroids in these patients may lead to an Addisonian crisis secondary to hypothalamic-pituitary-adrenal (HPA) axis imbalance. They present with hypotension, confusion, weakness, muscle and abdominal pain and electrolytes imbalance (high K+ and low Na+). These episodes are usually provoked by stressful situations such as a surgery or systemic infections. Chronic steroid therapy may also lead to important side effects, including: » Infections » Osteoporosis or avascular necrosis of bones (eg, hip, wrist). » Cushing features, high blood glucose and weight gain. » Fatigue, headaches and myalgias. » Depression, insomnia, psychosis and delirium. » Leukocytosis with high neutrophil count.