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Maloprlm-Induced Pulmonary Eosinophilia
Maloprlrn-lnduced Pulmonary Eoslnophilla* Stephen Begbie, M.B., B.S. ; and Keith R. Burgess, M.B., B.S., M.Sc., F.C.C.P.
A 47-year-old woman developed pulmonary eosinophilia from the use of maloprim as malaria prophyluis. The diagnosis was confirmed by broocboalveolar lavage (BAL) and transbronchial lung biopsy. Her condition improved with drug withdrawal and steroid therapy. With the increased use of pyrimetbamine and dapsone in the treatment of human immunode6ciency syndrome (HIV) infection, this form of drug allergy may become more common. (Chut 1993; l03:30S-06)
P
ulmonary eosinopbilia due to drug allergy is an uncommon clinical problem that may have wider importance in the future because of the increasing use of dapsone and pyrimethamine in the treatment of opportunistic infection in patients with human immunodeficiency virus (HIV). CASE REPORT
A 47-year-old previously well woman presented in June 1991, after returning from a ten-day vacation in Thai1and. For malaria prophylaxis, she bad commenced weekly chloroquine and maloprim (dapsone and pyrimetbamine) therapy just prior to departure. After an uneventful hip, she returned to Sydney, Australia, where, after her third dose of prophylaxis, she experienced sudden onset of fever, rigors, malaise, and nausea. These resolved within a few days. Similar symptoms, with the addition of cough and headache, developed after a fourth dose. After exclusion of malaria by the patient's family physician, the patient was referred to hospital. Examination revealed a low-grade fever of 37 .S°C and mild tachypnea, with normal auscultatory findings. Initially, a diagnosis of "atypical pneumonia" was made on the basis of a chest roentgenogram showing patchy bilateral opacification (Fig 1), a white blood cell count of 2.5.4 x l
FIGURE I. Chest roentgenogram at the time of hospital admission. bomogenous antinuclear antibody (ANA) (1:10), with negative antiScl-70, ANCA, and anti-GBM antibodies. The patient responded well to high-dose steroids and oxygen supplementation. Her examination results, chest roentgenogram, and blood eosinopbil count returned to normal by one month. Pulmonary function studies performed seven weeks after commencement of steroid therapy showed normal spirometry and lung volumes but a reduced Keo (60 percent predicted). DISCUSSION
There can be little doubt that our patient's lung disease
FIGURE 2. Chest roentgenogram four days after cballenge with maloprim in hospital. CHEST I 103 I 1 I JANUARY. 1993
305
was due to pulmonary drug allergy. The symptoms were exacerbated by rechallenge in hospital, there was marked
eosinophilia in both blood and BAL fluid, and the lung biopsy specimen showed a focal process consistent with an allergic reaction. Finally, the chest roentgenogram returned to normal with drug withdrawal and corticosteroid therapy, and has not relapsed. The transfer factor was reduced at seven weeks, suggesting some residual interstitial reaction or damage to the capillary bed. Pulmonary eosinophilia has been a well-described side effect of many drugs, classically presenting 10 to 14 days after drug commencement, relapsing with rechallenge and resolving following withdrawal. u Sulfonamides have a strong association, 1·3 including reports in combination with pyrimethamine (Fansidar) ..., . Respiratory reactions to dapsone (a sulfone) are less common, 7 despite their widespread use at high dose in leprosy, with no reports of pulmonary eosinophilia. Until recently, pyrimethamine was believed to be an innocent bystander in Fansidar hypersensitivity. However, a recent report of noncardiogenic pulmonary edema with peripheral eosinophilia due to higher doses of pyrimethamine suggests otherwise.• In addition, pyrimethamine has been implicated in four patients with antimalarial pulmonary eosinophilia, three of whom took weekly maloprim/cbloroquine, and one who took pyrimethamine/cbloroquine.• As there are no reports (to our knowledge) of chloroquineinduced pulmonary eosinophilia, the maloprim was almost certainly to blame. The absence of specific reports of either component alone causing pulmonary eosinophilia suggests a synergistic effect. With the spread of acquired immunodeficiency syndrome (AIDS), dapsone and pyrimethamine are finding new roles in the treatment ofopportunistic infection-dapsone proving effective against Pneumocysffs carinii10 and pyrimethamine against toxoplasmosis. 11 Prescribers of pyrimethamine or dapsone in AIDS units (in addition to those using this combination for malaria prophylaxis) should be aware of this important side effect, which may mimic pulmonary infection as it did in our patient. REFERENCES
1 Feinmann L. Lung parenchymal changes due to ingested substances. Proc R Soc Med 1975; 68:440-41 2 Murphy RL, Phair JP. Systemic reaction to pyrimethamine and sulfadoxine. J Fam Pract 1986; 22:375-76 3 Leader. Sulphasalazine induced lung disease [editorial]. Lancet 1974; 2:504-05 4 Koch-\\\lser J, Hodel C, Leimer R, Style S. Adverse reactions to pyrimethamine/sulfadoxine. Lancet 1982; 2:1459 5 Svanbon M, Rombo L, Gustafl'son L. Unusual pulmonary reaction during short term prophylaxis with pyrimethamine sulfadoxine (Fansidar). BMJ 1984; 9.88:1876 6 McCormack D, Morgan WKC. Fansidar hypersensitivity pneumonitis. Br J Dis Chest 1987; 81:194-96 7 Grayson ML, Yung AP, Doherty RR. Severe dapsone syndrome due to weekly maloprim. Lancet 1988; 1:531 8 Pang JA. Non-cardiogenic pulmonary oedema associated with pyrimethamine. Respir Med 1989; 83:247-48 9 Davidson AC, Bateman C, Shovlin C, Marnnan M, Burton GH, Cameron IR. Pulmonary toxicity of malaria prophylaxis. BMJ 1988; 297:1240-41 10 Leoung GS, Mills J, Hopewell PC, Hughes W, Wofsy C.
308
Dapsone-trimethoprim for Pneumocy"'8 carlnti pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105:45-8 11 Leport C, Raffi F, Matheson S, Katlama C, Regnier B, Sainot AG, et al. Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome: efficiency of long-term continuous therapy. Am 1Med1988; 84:94-100
Disseminated Pneumocystosis Presenting as a Pleural Effusion* Robert L. Jayes, M.D.; Harry N. Kamerou\ M.D.; Susan M. HasselquiBt, M.D.; Morgan D. Delaney, M.D.; and
Daoid M. lbnmti, M.D.
Extrapulmonary pneumocystosis recently has been reported in a number of tissues. Most cases occurred in patients receiving aerosoli7.ed pentamidine prophylaxis. We report a case of disseminated pneumocystosis presenting as a large pleural effusion withoot apparent lung involvement where Pneurnocystil carinii was the only pathogen identi&ed. The absence of parenchymal lesions on chest x-ray film, the lack of hypoxemia and the minimal uptake of gallium all argue against significant lung involvement. The patient was successfully treated with chest tube drainage, intravenous and inhaled pentamidine and orally administered dapsone and trimethoprim. The addition of inhaled pentamidine to intravenously administered pentamidine may have increased pleural fluid levels substantially and its use coincided with the patient's improvement. (Chat 1993; 103:306-08)
P
neumocysffs carinii pneumonia is a common opportunistic infection in AIDS, but pleural effusions occur rarely and typically are small.1.1 Extrapulmonary pneumocystosis has been reported in a number of tissues including kidney, bone marrow, spleen, lymph node, and liver. 3 •4 Most cases occur in patients receiving aerosolized pentamidine prophylaxis3·4 and probably result from the poor systemic absorption. We report a case of disseminated pneumocystosis in such a patient who presented with a large pleural effusion without apparent lung involvement. We discuss the roles of intravenously administered and inhaled pentamidine in his successful treatment. CASE REPORT
A 27-year-old man was successfully treated 18 months earlier for
P carlnii pneumonia with dapsone and trimethoprim, since he was intolerant of trimethoprim-sulfamethoxizole. He began receiving zidovudine and inhaled pentamidine (300 mg/month). Eight weeks prior to admission, he developed cryptococcal meningitis which *From the Divisions of General Internal Medicine (Dr. Jayes), and InfecPulmonary Diseases (Ors. Hasselquist and Delaney~ tious Diseases (Dr. Parenti), Department of Medicine, and the Department of Pathology (Dr. Kamerow), the George Washington University Medical Center, Washington, DC. Ors. Jayes, Hasselquist, Delaney and Parenti currently are with Medical Faculty Associates, Washington, DC. Dr. Kamerow currently is at Centre Community Hospital, State College, Pa. Olssaminatad Pneumocyslollls '~.,al)
A 47-year-old woman developed pulmonary eosinophilia from the use of maloprim as malaria prophyluis. The diagnosis was confirmed by broocboalveolar lavage (BAL) and transbronchial lung biopsy. Her condition improved with drug withdrawal and steroid therapy. With the increased use of pyrimetbamine and dapsone in the treatment of human immunode6ciency syndrome (HIV) infection, this form of drug allergy may become more common. (Chut 1993; l03:30S-06)
P
ulmonary eosinopbilia due to drug allergy is an uncommon clinical problem that may have wider importance in the future because of the increasing use of dapsone and pyrimethamine in the treatment of opportunistic infection in patients with human immunodeficiency virus (HIV). CASE REPORT
A 47-year-old previously well woman presented in June 1991, after returning from a ten-day vacation in Thai1and. For malaria prophylaxis, she bad commenced weekly chloroquine and maloprim (dapsone and pyrimetbamine) therapy just prior to departure. After an uneventful hip, she returned to Sydney, Australia, where, after her third dose of prophylaxis, she experienced sudden onset of fever, rigors, malaise, and nausea. These resolved within a few days. Similar symptoms, with the addition of cough and headache, developed after a fourth dose. After exclusion of malaria by the patient's family physician, the patient was referred to hospital. Examination revealed a low-grade fever of 37 .S°C and mild tachypnea, with normal auscultatory findings. Initially, a diagnosis of "atypical pneumonia" was made on the basis of a chest roentgenogram showing patchy bilateral opacification (Fig 1), a white blood cell count of 2.5.4 x l
FIGURE I. Chest roentgenogram at the time of hospital admission. bomogenous antinuclear antibody (ANA) (1:10), with negative antiScl-70, ANCA, and anti-GBM antibodies. The patient responded well to high-dose steroids and oxygen supplementation. Her examination results, chest roentgenogram, and blood eosinopbil count returned to normal by one month. Pulmonary function studies performed seven weeks after commencement of steroid therapy showed normal spirometry and lung volumes but a reduced Keo (60 percent predicted). DISCUSSION
There can be little doubt that our patient's lung disease
FIGURE 2. Chest roentgenogram four days after cballenge with maloprim in hospital. CHEST I 103 I 1 I JANUARY. 1993
305
was due to pulmonary drug allergy. The symptoms were exacerbated by rechallenge in hospital, there was marked
eosinophilia in both blood and BAL fluid, and the lung biopsy specimen showed a focal process consistent with an allergic reaction. Finally, the chest roentgenogram returned to normal with drug withdrawal and corticosteroid therapy, and has not relapsed. The transfer factor was reduced at seven weeks, suggesting some residual interstitial reaction or damage to the capillary bed. Pulmonary eosinophilia has been a well-described side effect of many drugs, classically presenting 10 to 14 days after drug commencement, relapsing with rechallenge and resolving following withdrawal. u Sulfonamides have a strong association, 1·3 including reports in combination with pyrimethamine (Fansidar) ..., . Respiratory reactions to dapsone (a sulfone) are less common, 7 despite their widespread use at high dose in leprosy, with no reports of pulmonary eosinophilia. Until recently, pyrimethamine was believed to be an innocent bystander in Fansidar hypersensitivity. However, a recent report of noncardiogenic pulmonary edema with peripheral eosinophilia due to higher doses of pyrimethamine suggests otherwise.• In addition, pyrimethamine has been implicated in four patients with antimalarial pulmonary eosinophilia, three of whom took weekly maloprim/cbloroquine, and one who took pyrimethamine/cbloroquine.• As there are no reports (to our knowledge) of chloroquineinduced pulmonary eosinophilia, the maloprim was almost certainly to blame. The absence of specific reports of either component alone causing pulmonary eosinophilia suggests a synergistic effect. With the spread of acquired immunodeficiency syndrome (AIDS), dapsone and pyrimethamine are finding new roles in the treatment ofopportunistic infection-dapsone proving effective against Pneumocysffs carinii10 and pyrimethamine against toxoplasmosis. 11 Prescribers of pyrimethamine or dapsone in AIDS units (in addition to those using this combination for malaria prophylaxis) should be aware of this important side effect, which may mimic pulmonary infection as it did in our patient. REFERENCES
1 Feinmann L. Lung parenchymal changes due to ingested substances. Proc R Soc Med 1975; 68:440-41 2 Murphy RL, Phair JP. Systemic reaction to pyrimethamine and sulfadoxine. J Fam Pract 1986; 22:375-76 3 Leader. Sulphasalazine induced lung disease [editorial]. Lancet 1974; 2:504-05 4 Koch-\\\lser J, Hodel C, Leimer R, Style S. Adverse reactions to pyrimethamine/sulfadoxine. Lancet 1982; 2:1459 5 Svanbon M, Rombo L, Gustafl'son L. Unusual pulmonary reaction during short term prophylaxis with pyrimethamine sulfadoxine (Fansidar). BMJ 1984; 9.88:1876 6 McCormack D, Morgan WKC. Fansidar hypersensitivity pneumonitis. Br J Dis Chest 1987; 81:194-96 7 Grayson ML, Yung AP, Doherty RR. Severe dapsone syndrome due to weekly maloprim. Lancet 1988; 1:531 8 Pang JA. Non-cardiogenic pulmonary oedema associated with pyrimethamine. Respir Med 1989; 83:247-48 9 Davidson AC, Bateman C, Shovlin C, Marnnan M, Burton GH, Cameron IR. Pulmonary toxicity of malaria prophylaxis. BMJ 1988; 297:1240-41 10 Leoung GS, Mills J, Hopewell PC, Hughes W, Wofsy C.
308
Dapsone-trimethoprim for Pneumocy"'8 carlnti pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105:45-8 11 Leport C, Raffi F, Matheson S, Katlama C, Regnier B, Sainot AG, et al. Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome: efficiency of long-term continuous therapy. Am 1Med1988; 84:94-100
Disseminated Pneumocystosis Presenting as a Pleural Effusion* Robert L. Jayes, M.D.; Harry N. Kamerou\ M.D.; Susan M. HasselquiBt, M.D.; Morgan D. Delaney, M.D.; and
Daoid M. lbnmti, M.D.
Extrapulmonary pneumocystosis recently has been reported in a number of tissues. Most cases occurred in patients receiving aerosoli7.ed pentamidine prophylaxis. We report a case of disseminated pneumocystosis presenting as a large pleural effusion withoot apparent lung involvement where Pneurnocystil carinii was the only pathogen identi&ed. The absence of parenchymal lesions on chest x-ray film, the lack of hypoxemia and the minimal uptake of gallium all argue against significant lung involvement. The patient was successfully treated with chest tube drainage, intravenous and inhaled pentamidine and orally administered dapsone and trimethoprim. The addition of inhaled pentamidine to intravenously administered pentamidine may have increased pleural fluid levels substantially and its use coincided with the patient's improvement. (Chat 1993; 103:306-08)
P
neumocysffs carinii pneumonia is a common opportunistic infection in AIDS, but pleural effusions occur rarely and typically are small.1.1 Extrapulmonary pneumocystosis has been reported in a number of tissues including kidney, bone marrow, spleen, lymph node, and liver. 3 •4 Most cases occur in patients receiving aerosolized pentamidine prophylaxis3·4 and probably result from the poor systemic absorption. We report a case of disseminated pneumocystosis in such a patient who presented with a large pleural effusion without apparent lung involvement. We discuss the roles of intravenously administered and inhaled pentamidine in his successful treatment. CASE REPORT
A 27-year-old man was successfully treated 18 months earlier for
P carlnii pneumonia with dapsone and trimethoprim, since he was intolerant of trimethoprim-sulfamethoxizole. He began receiving zidovudine and inhaled pentamidine (300 mg/month). Eight weeks prior to admission, he developed cryptococcal meningitis which *From the Divisions of General Internal Medicine (Dr. Jayes), and InfecPulmonary Diseases (Ors. Hasselquist and Delaney~ tious Diseases (Dr. Parenti), Department of Medicine, and the Department of Pathology (Dr. Kamerow), the George Washington University Medical Center, Washington, DC. Ors. Jayes, Hasselquist, Delaney and Parenti currently are with Medical Faculty Associates, Washington, DC. Dr. Kamerow currently is at Centre Community Hospital, State College, Pa. Olssaminatad Pneumocyslollls '~.,al)