Severe Henoch-Schönlein Purpura Induced by Cytarabine

TO THE EDITOR: Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis thatprimarily affects children and is characterized by vascular and/ormesangial immunoglobulin A deposition. The majorclinical findings are nonthrombocytopenic palpable purpura, arthritis, abdominal pain, gastrointestinal bleeding,and nephritis.The etiology of HSP remainsobscure,but a variety of antigenicstimuli, including infections, drugs(eg,penicillin, ampicillin, erythromycin, quinine), toxins, systemic diseases,and cancer have beenconsidered. ' Renal involvement ranges from 50% to 85% in adults with HSP and is associatedwith a negative long-term prognosis. ' Drug-associated HSPtypically resolves rapidly after discontinuation of the involveddrug. ' In less severe cases, therapy has consisted of topical corticosteroid products, nonsteroidal antiinflammatorydrugs,and antihistamines. " Hemodialysis, pulsecorticosteroids, cyclophosphamide, and plasmapheresis may be used in severecases.To the bestof our knowledge, this is the first reported case of HSPassociated withthe useof cytarabine. Case Report. A 28-year-old man who was diagnosed with acute myeloid leukemia (MO, MI) wasgivena remission induction regimen of idarubicin(IDA) 12 mg/mz/day for 1-3 days and cytosine arabinoside (ARA-C) 100mg/rnvday for 1-7 days beginningon April 2, 2006. He developed neutropenic feveron day 2 of IDA+ ARA-Ctherapy; empirical antibiotictreatmentwith levofloxacin and sulbactam/cefoperazone was initiated due to suspicion of atypical pneumonia. Persistence of fever3 dayslaterprompted a switch to a combination of teicoplanin and imipenem/cilastin on day 5. On day 6, gentamicin was added.Caspofungin wasaddedto the regimen on day7, due to continuing fever, and was continued fora totalof 20 days. High-resolution computed tomography showedclear lungfields. On May4, he developed an erythematous rash over the lowerextremities(Figure I), associated with bloodydiarrhea. Direct microscopic examination of a stool specimen showed 25-30 leukocyteslhpf and many erythrocytes per high-power field. Oral metronidazole wasbegunon day 32 to treata possible antibiotic-induced pseudomembranous enterocolitis. After 10 days, despite appropriate therapy, hissymptoms werenot improved. Hedeveloped pitting pretibial edema and fever. Laboratory values included hemoglobin 8.9 g/dL, platelets482 cells x IQJ/jlL, erythrocytesedimentation rate 91 (0-20) rnm/h, international normalized ratio4.0, bloodurea nitrogen 13.4 g/dL, creatinine 0.8 g/dL,and serum totalprotein and albumin levels3.2 g/dL and 1.4g/dL, respectively. Stool cultures for ova and parasitesand for ClostridiumdijJicile toxinwerenegative, as weretestsforantinuclear antibody and antineutrophil cytoplasmic antibodies. Urinary protein excretion in 24-hoururinecollection was7550mg/day. Abdominal ultrasonographicfindings were normal.On May 19,a bonemarrowbiopsyafter one cycle of IDNARA-C therapywas normal, indicating completeremission.However, a skin biopsytakenfrom the purpuric plaqueon the patient's lowerextremities that sameday revealedleukocytoclastic vasculitis. Colonoscopic examination demonstrated multiple smallulcers. Histopathologic examination of thecolonicbiopsy specimen revealed mild colitis. Renal biopsy revealed focal mesangial proliferative glomerulonephritis (Figure 2); immunofluorescent staining demonstrated immunoglobulinA and complement 3 deposits. These findings were consistent with HSP. Treatmentwith intravenous methylprednisolone I rug/kg/day for 3 doses, followed by oral prednisolone60 mg/day was initiated on May 23. Oral prednisolone was gradually taperedand then continued at a doseof 20 mg/day duringconsolidation therapy. The skin lesions, diarrhea, and pretibial edemaimproved on the second day of intravenous methylprednisolone therapy. The urinary protein excretion rate in 24-hour urine collectiondecreasedto 3 g/day on the third day. Any one of the agents used prior to the developmentof this clinical picture couldhave been the causeof HSP,and the causative agentcould not be ascertained.