SHORT REPORT Flutamide-induced cyanosis refractory to methylene blue therapy P ETER A. KOUIDES ,* CAMILLE N. ABBOUD † AND V IRGIL F. FAIRBANKS ‡ *Hematology Unit, Rochester General Hospital and †Strong Memorial Hospital, University of Rochester Medical Center, Rochester, New York, and ‡Mayo ClinicDepartment of Pathology and Laboratory Medicine,Rochester, Minnesota, U.S.A. Received 5 January 1996; accepted for publication 1 April 1996 Summary. Flutamide, an anti-androgen used in prostate cancer therapy, is also a derivative of aniline. Mild, usually asymptomatic, methaemoglobinaemia has been reported. We report a patient receiving flutamide therapy who developed cyanosis, dyspnoea and anaemia, initially attributed to marked methaemoglobinaemia by the CO- Oximeter method. An unsuccessful trial of methylene blue therapy led to the finding of marked sulphaemoglobinaemia. Sulphaemoglobinaemia has not previously been reported with flutamide use. Recognition of this association is important, given the refractorinessof sulphaemoglobinaemia to methylene blue therapy. Keywords: methaemoglobinaemia, sulphaemoglobinaemia, cyanosis, flutamide, methylene blue. Nearly all drugs that cause methaemoglobinaemia or sulphaemoglobinaemia are derivatives of aniline (e.g. anal- gesics, sulphonamides, local anaesthetics) (Lukens, 1993; Fairbanks, 1994). Flutamide, an anti-androgen used in prostate cancer therapy, is also a derivative of aniline.Mild, usually asymptomatic, methaemoglobinaemia has been ascribed to flutamide (Haefliger, 1985; Brodgen & Clissold, 1989). However, we recently encountered a patient who developed dyspnoea and cyanosis on flutamide initially attributed to methaemoglobinaemia, but further evaluation led to the predominant finding of sulphaemoglobinaemia, a more serious toxic haemoglobinopathy. We now report this case and emphasize the potential for the misdiagnosis of sulphaemoglobinaemia with the present widespread method of spectrophotometric assay of whole blood which reveals a falsely elevated methaemoglobin in the presence of sulphaemoglobin (Kneezel & Kitchens, 1976; Park & Nagel, 1984). CASE REPORT A 70-year-old white male presented with a history of progressive cyanosis of his lips and distal extremities as well as 5 d of increasing dyspnoea. Past medical history was notable for prostatic cancer, stage A2, treated with local radiotherapy 5 years previously. He had recurrence confined to the prostate 1 year ago, treated with palladium implants followed by leuprolide (7 . 5 mg i.m. monthly) and flutamide (150 mg t.i.d.) 1 month prior to this presentation. There was a long-standinghistory of constipation and a 5-year history of depression.There was no history of cardiopulmonary disease. Medications on admission were: flutamide, leuprolide, psyl- lium colloid, amoxapine (10 mg q.h.s.), vitamin C, and methylphenidate (10mg b.i.d.), the latter for the past 30 years. He was not ingestingany other aniline derivatives at the time of onset of cyanosis. He was afebrile, BP was 128/90, and respiratory rate was 14/min. There was perioral cyanosis as well as cyanosis of the fingertips and toes. Complete blood count: haematocrit 0 . 31 l/ l (0 . 34 l/l 2 d prior; 0 . 42l/l 3 years prior); haemoglobin concentration (Hb) 10 . 3 g/dl; mean cell volume 98 fl; white blood cell count 8 1 10 12 /l, platelet estimate normal. Peripheral blood smear revealed moderate polychromasia and poikilocytosis with several ‘bite’ cells in the erythrocyte series (a reticulocyte count, lactate dehydrogenase level, Heinz body test, and haptoglobin level were not obtained). Arterial blood gas (while he was breathing room air) showed a pO 2 of 92 mmHg and a pCO 2 39 mmHg with a pH of 7 . 42. Arterial O 2 saturation could not be measured because of colour interference. Methaemoglobin was reported as 32% (normal 0 . 2–2 . 0%). This was determined by CO-Oximeter method (Instrumentation Laboratory model 282). All British Journal of Haematology , 1996, 94, 73–75 73 1996 Blackwell Science Ltd Correspondence: Dr Peter A. Kouides, Hematology Unit, Box 266, Rochester General Hospital, 1425 Portland Ave., Rochester, NY 14621, U.S.A.