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drug-induced lupus erythematosus

Etiology: 1) general a) low levels of hepatic acetyltransferase may play a role. b) drugs that are metabolized by acetylation are most commonly involved 2) antiarrhythmic agents a) procainamide* - almost all patients develop anti-histone antibodies - antibodies of IgM class in asymptomatic patients - IgG antibodies to H2A-H2B dimer in symptomatic patients (also IgM) - 50% of patients treated with procainamide develop anti-nuclear antibody (ANA) after 1 year b) quinidine c) practolol 3) antihypertensive agents a) hydralazine* - anti-nuclear Ab (ANA) - anti-histone Ab - antibodies to H2A-H2B dimer - antibodies to H3-H4 complex - IgM > IgG b) methyldopa (Aldomet) c) beta-blockers d) calcium channel blockers, diltiazem* [3] - anti-nuclear Ab (ANA), anti-SSA/Ro Ab, anti-histone Ab (rare) e) thiazide diuretics - anti-nuclear Ab (ANA), anti-SSA/Ro Ab, anti-histone Ab (rare) f) ACE inhibitors [3] - anti-nuclear Ab (ANA), anti-SSA/Ro Ab, anti-histone Ab (rare) 4) antibiotics a) nitrofurantoin b) penicillin c) sulfonamides d) tetracycline - minocycline** - anti-nuclear Ab (ANA), ANCA, anti-dsDNA e) cephalosporins f) griseofulvin g) terbinafine [3] 4) anticonvulsive agents a) phenytoin b) mephenytoin c) carbamazepine d) ethosuximide 6) antituberculous agents a) isoniazid* b) streptomycin c) para-aminosalicylic acid 7) phenothiazines a) chlorpromazine b) promethazine 8) thyroid medications a) anti-nuclear Ab (ANA), ANCA, anti-histone Ab b) propylthiouracil, methimazole, iodide 9) biologicals a) interferon-alpha - anti-nuclear Ab (ANA) in 23-57% - anti-dsDNA (common) - anti-histone Ab (rare) b) interleukin-2 c) TNF-alpha inhibitors* [3,5,6] - etanercept - infliximab - adalimumab 10) chemotherapy a) 5-fluorouracil b) capecitabine [3] 11) others a) D-penicillamine b) methysergide 3) oral contraceptives c) phenylbutazone d) statins - anti-nuclear Ab (ANA), anti-dsDNA, anti-histone Ab e) tolazamide f) sulfasalazine g) zafirlukast h) ticlopidine i) L-dopa * common causes ** minocycline appeared twice in MKSAP questions [3] Epidemiology: more common in older white patients Clinical manifestations: 1) arthralgias & arthritis (90%) 2) fever & malaise (40%) 3) pleural effusion (50%) 4) pulmonary infiltrates (30%) 5) serositis 6) non-blanching purpuric rash [3] 7) renal disease is rare - low-grade proteinuria [3] - microscopic hematuria, few WBC in urine; described as active urine sediment [3] - may be more common with TNF-alpha inhibitor 8) neurologic & cutaneous involvement may be more common with TNF-alpha inhibitor [11] 9) clinical improvement upon withdrawing the drug Laboratory: 1) complete blood count: anemia, leukopenia 2) erythrocyte sedimentation rate elevated 3) positive antinuclear antibody (ANA) is positive in 100% - almost all have anti-histone antibodies with older agents - more variable with newer agents [3] - anti-histone antibodies less common with TNF-alpha inhibitor [11] 4) lupus erythematous (LE) cell clot (75%) 5) low complement levels in 70%; complement levels normal [4] 6) antinuclear antibody, anti-histone Ab & anti-ssDNA Ab is typical 7) anti-double-stranded DNA (anti-dsDNA) is uncommon, unless caused by TNF-alpha inhibitor 9) rheumatoid factor (RF) is positive in 33% 10) anti-RNP Ab is uncommon a) anti-Sm Ab is uncommon b) anti-U1 RNP Ab is uncommon 11) anti-SSA, anti-SSB uncommon - anti-SSA, anti-SSB common according to [3] Management: 1) identify & stop offending agent 2) symptoms resolve 4-6 weeks after stopping offending agent [3]

Related

anti-histone antibody

General

systemic lupus erythematosus

References

  1. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 1017-18
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 760-61
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
  5. Wetter DA and Davis MDP. Lupus-like syndrome attributable to anti-tumor necrosis factor therapy in 14 patients during an 8-year period at Mayo Clinic. Mayo Clin Proc 2009 Nov; 84:979. PMID: 19880688
  6. Williams EL, Gadola S, Edwards CJ. Anti-TNF-induced lupus. Rheumatology (Oxford). 2009 Jul;48(7):716-20 PMID: 19416947
  7. Sontheimer RD, Henderson CL, Grau RH. Drug-induced subacute cutaneous lupus erythematosus: a paradigm for bedside-to-bench patient-oriented translational clinical investigation. Arch Dermatol Res. 2009 Jan;301(1):65-70 PMID: 18797894
  8. Katz U, Zandman-Goddard G. Drug-induced lupus: an update. Autoimmun Rev. 2010 Nov;10(1):46-50. Review. PMID: 20656071
  9. Chang C, Gershwin ME. Drug-induced lupus erythematosus: incidence, management and prevention. Drug Saf. 2011 May 1;34(5):357-74 PMID: 21513360
  10. Lowe GC, Henderson CL, Grau RH, Hansen CB, Sontheimer RD. A systematic review of drug-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2011 Mar;164(3):465-72 PMID: 21039412
  11. NEJM Knowledge+ Rheumatology