Review Note
Last Update: 02/06/2025 03:56 AM
Current Deck: STEP 1::Biochemistry::Molecular Biochemistry
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Anverso
A 54-year-old female presents for evaluation of joint pain and fevers. She has a history of systolic heart failure with a left ventricular ejection fraction of 15% (normal >50). One week ago, she developed pain in her knees, elbows, shoulders, and wrists. She also reports subjective fevers. Review of systems is negative for headache, nausea, vomiting, or diarrhea. On physical exam, she has an erythematous rash on her cheeks. She was started on isosorbide dinitrate and hydralazine six months ago for treatment of heart failure. Antibodies to which of the following are most likely involved in the pathogenesis of this woman's condition?
A H1 histone linker protein
B. U1 ribonucleoprotein
C.DNA topoisomerase
D.Tissue transglutaminase
E. Smith antigen
Reverso
Answer A (correct answer): This is the typical presentation of drug-induced lupus. Most patients present with signs of inflammation such as fever plus arthritis. The arthritis of lupus (drug-induced or otherwise) is usually polyarticular (more than 5 joints) and symmetrical. Drug-induced lupus is a milder form of lupus. Malar rash is less common. Renal failure, CNS involvement or bone marrow suppression are rare.
Drug-induced lupus classically occurs months to years after a patient is exposed to a triggering medication. Medications most associated with drug-induced lupus can be remembered by the mnemonic SHIPPE (Sulfonamides, Hydralazine, Isoniazid, Phenytoin, Procainamide, Etanercept). Drug-induced lupus is an autoimmune reaction involving anti-histone antibodies. One component of histones targeted by the reaction is the H1 histone linker protein which binds to the nucleosome and stabilizes chromatin fibers. Anti-histone antibodies are rarely seen in typical (i.e., non-drug-induced) lupus.
Answer B (incorrect answer): Anti-U1 ribonucleoprotein antibodies are involved in Mixed Connective Tissue Disease (MCTD).
Answer C (incorrect answer): Anti-DNA topoisomerase I antibodies, also known as anti-Scl-70 antibodies, are seen in the diffuse form of scleroderma.
Answer D (incorrect answer): Anti-tissue transglutaminase antibodies are associated with celiac disease.
Answer E (incorrect answer): Anti-Smith antibodies are involved in systemic lupus erythematosus (non-drug-induced). In clinical practice, this patient would likely be evaluated for SLE in addition to drug-induced lupus. However, the time course of symptoms emerging after starting hydralazine (one of the SHIPPE medications) is more consistent with drug-induced lupus.
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