Snapshot A 26-year-old woman presents to the dermatology clinic for fatigue, weakness, and fevers for the past month. She reports significant weight loss despite eating a normal diet. She reports that she sunburns very easily and has a facial rash that is hard to cover with makeup. On physical exam, she has a butterfly rash with nasolabial sparing on her face, several discoid lesions on her fingers, and a erythematous rash on her chest in a V-neck distribution. On laboratory exam, she has a highly positive antinuclear antibody and positive anti-double-stranded DNA antibody. Introduction Clinical definition systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by acute flares, commonly presenting with rash, joint pain, and fever multiple organ systems are involved, including renal, neurologic, dermatologic, cardiovascular, and hematologic Epidemiology demographics more common in female patients of reproductive age African American, Asian, or Hispanic descent risk factors family history oral contraceptive use hormone replacement therapy other autoimmune diseases Pathogenesis unknown but thought to be an interaction among immune dysfunction, genetic factors, and environmental factors autoantibodies precipitate immune complexes in multiple organs, including kidneys, skin, and brain form of type 3 hypersensitivity reaction polyclonal activation of B-cells with the production of autoantibodies against DNA complement factors and cytokines also play a key role environmental triggers include sunlight (photosensitive rash), infection, and drugs (HIP) Hydralazine Isoniazid Procainamide Associated conditions antiphospholipid syndrome increased risk of thrombosis increased risk of atherosclerosis lupus nephritis anti-DNA immune complexes deposition in glomeruli nephritic or nephrotic syndrome diffuse proliferative is the most common and most severe type drug-induced lupus typically positive for antinuclear antibody and antihistone antibody typically without renal or neurologic involvement complement level is typically normally Libman-Sacks endocarditis (LSE) noninfectious endocarditis characterized by thrombi on the mitral or aortic valves (LSE in SLE) Raynaud phenomenon Prognosis often have recurrent flares Presentation Symptoms constitutional symptoms fatigue, fever, or weight loss arthralgias serositis pericarditis, pleural effusion, or myocarditis Physical exam cutaneous findings malar rash (raised or flat erythematous butterfly rash on cheeks/nose and spares nasolabial fold) discoid lesions (erythematous raised plaques with keratotic scale and follicular plugging) photosensitive rash oral ulcers neurologic findings behavioral changes stroke seizures headaches chance in psychiatric status renal findings hematuria proteinuria hematologic findings anemia of chronic disease leukopenia thrombocytopenia Studies Labs antibodies antinuclear antibody (ANA) best initial test high sensitivity but low specificity anti-double-stranded DNA (dsDNA) antibody often rises during flares high specificity but low sensitivity poor prognostic factor often indicates renal disease anti-Smith antibody (antibody to snRNPs) high specificity (more than anti-dsDNA) but low sensitivity antihistone antibody high sensitivity for drug-induced lupus ↓ complement levels during a flare ↓C3, C4, and CH50 ↑ erythrocyte sedimentation rate pancytopenia leukopenia, thrombocytopenia, or hemolytic anemia elevated partial thromboplastin time (PTT) lupus anticoagulant increases the risk for thrombi and miscarriages associated with antiphospholipid syndrome Urinalysis proteinuria or hematuria may indicate renal disease Making the diagnosis based on clinical presentation and laboratory studies diagnosis confirmed with 4 or more criteria from RASHNIA4 Renal disease Arthralgias Serositis Hematologic abnormalities Neurologic abnormalities Immunologic derangements Antinuclear antibodies 4 types of rashes malar discoid photosensitive oral ulcers Differential Acne rosacea distinguishing factors erythematous papules and pustules on face without nasolabial sparing no other systemic findings Sarcoidosis distinguishing factors adenopathy restrictive lung disease skin findings of lupus pernio, rather than malar rash, discoid lesions, or ulcers Treatment Management approach antimalarials are often used alongside steroids for acute flares management is often dictated by specific organ involvement Conservative use sunscreen and avoid sun exposure indication for all patients Medical non-steroidal anti-inflammatory drugs (NSAIDs) indication arthralgias antimalarials indications dermatologic findings and joint pain often used in conjunction with other medications, including steroids drugs hydroxychloroquine chloroquine side effects risk of retinopathy steroids indication acute flares drugs prednisone immunosuppressants indications patients not responsive to steroids patients unable to tolerate steroid taper lupus nephritis drugs azathioprine methotrexate mycophenolate for patients with lupus nephritis cyclophosphamide for patients with lupus nephritis belimumab indication patients not responsive to steroids or other immunosuppressants mechanism inhibits B-cells Complications Causes of death in SLE infections renal disease cardiovascular disease Lupus nephropathy can be fatal Cardiovascular disease leading cause of death in patients with SLE includes Libman-Sacks endocarditis, hypertension, and cardiac tamponade Thrombosis