Azithromycin-induced rash in infectious mononucleosis

Case Reports 939

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Scand J Infect Dis 34

17. Kuaity J, Lewis FB. Cryptococcosis presenting as an osteolytic rib lesion. Minn Med 1968; 51: 1727 – 30. 18. Scadding JG, Olsen EGJ. A case of sarcoidosis with cryptococcal meningitis. Br Med J 1969; iv: 729 –32. 19. Sarosi GA, Parker JD, Doto II, Tosh FE. Amphotericin B in cryptococcal meningitis. Ann Intern Med 1969; 71: 1079 – 87. 20. Sokolowski JW, Schillaci RF, Motley TE. Disseminated cryptococcosis complicating sarcoidosis. Am Rev Respir Dis 1969; 100: 717 – 22. 21. Brock DJ, Grieco MH. Cryptococcal prostatitis in a patient with sarcoidosis. J Urol 1972; 107: 1017 – 21. 22. Balasubramaniam P, Silva JF. Case of cryptococcosis of spine. Br Med J 1973; ii: 27 – 8. 23. Nottebart HC, McGehee RF, Utz JP. Cryptococcosis complicating sarcoidosis. Am Rev Respir Dis 1973; 107: 1060 – 3. 24. Levinson DJ, Silcox DC, Rippon JW, Thomsen S. Septic arthritis due to nonencapsulated Cryptococcus neoformans with coexisting sarcoidosis. Arthritis Rheum 1974; 17: 1037 – 47. 25. Lord GP. Pulmonary sarcoidosis complicated by cryptococcosis and coccidioidomycosis. J Maine Med Assoc 1974; 65: 236 – 40. 26. Nottebart HC, McGehee RF, Utz JP. Cryptococcus neoformans osteomyelitis: case report of two patients. Sabouraudia 1974; 12: 127 – 32. 27. Belcher RW, Palazij R, Wolinsky E. Immunologic studies in patients with sarcoidosis and cryptococcosis. Arch Dermatol 1975; 111: 711 – 6. 28. Roberts SH, Gault MH, Fardy PW. Occurrence of two cases of cryptococcosis within three months on the same general medical ward. Can Med Assoc J 1976; 115: 537 – 8. 29. Hay RJ, Mackenzie DWR, Campbell CK, Philpot CM. Cryptococcosis in the United Kingdom and the Irish Republic: an analysis of 69 cases. J Infect 1980; 2: 13 – 22. 30. Shaff MI, Berger JL, Green NE. Cryptococcal osteomyelitis, pulmonary sarcoidosis, and tuberculosis in a single patient. South Med J 1982; 75: 225 – 6. 31. Levine AM, Meier P, Dorfman HD. Isolated cryptococcal osteomyelitis of the humerus simulating a neoplasm of bone in a patient with sarcoidosis. Skeletal Radiol 1985; 14: 152 – 6. 32. Allen KS, Glickstein M, Arger PH, Bilaniuk L, Levy DW. Cryptococcosis associated with sarcoidosis: CT and MR ndings. J Comput Assist Tomogr 1988; 12: 420 – 2. 33. Ahmad I, Sharma OP. Sarcoidosis, cysticercosis and cryptococcosis: an unusual association. Sarcoidosis 1989; 6: 57 – 9.

34. Shijubo N, Fujishima T, Ooashi K, Morita S, Shigehara K, Nakata H, Abe S. Pulmonary cryptococcal infection in an untreated patient with sarcoidosis. Sarcoidosis 1995; 12: 71 – 4. 35. Bohne T, Sander A, P ster-Wartha A, Schopf E. Primary cutaneous cryptococcosis following trauma of the right forearm. Mycoses 1996; 39: 457 – 9. 36. Botha RJP, Wessels E. Cryptococcal meningitis in an HIV negative patient with systemic sarcoidosis. J Clin Pathol 1999; 52: 928 – 30. 37. Giner V, Casademont J, Cardellach F. Cryptococcal meningoencephalitis and sarcoidosis. Sarcoidosis 1999; 16: 228– 9. 38. Lauerma AI, Jeskanen L, Rantanen T, Stubb S, Kariniemi AL. Cryptococcosis during systemic glucocorticosteroid treatment. Dermatology 1999; 199: 180 – 2. 39. Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lancaster DJ, et al. Cryptococcosis in HIV-negative patients in the era of effective azole therapy. Clin Infect Dis 2001; 33: 690– 9. 40. Liu PY. Cryptococcal osteomyelitis: case report and review. Diagn Microbiol Infect Dis 1998; 30: 33 – 5. 41. Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, et al. Central nervous system sarcoidosis: diagnosis and management. Q J Med 1999; 92: 103 – 17. 42. Sharma OP. Neurosarcoidosis. Chest 1997; 112: 220 – 8. 43. Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immune de ciency syndrome. N Engl J Med 1986; 321: 794 – 9. 44. Duncan RA, von Reyn CF, Alliegro GM, Toossi Z, Sugar AM, Levitz SM. Idiopathic CD4 » T-lymphocytopenia: four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med 1993; 328: 393 – 8. 45. Pickuth D, Heywang-Kobrunner SH. Neurosarcoidosis: evaluation with MRI. J Neuroradiol 2000; 27: 185 – 8. 46. Miszkiel KA, Hall-Craggs MA, Miller RF, Kendall BE, Wilkinson ID, Paley MN, Harrison MJ. The spectrum of MRI ndings in CNS cryptococcosis in AIDS. Clin Radiol 1996; 51: 842– 50. 47. Dale JC, O’Brien JF. Determination of angiotensin-converting enzyme is not a useful test for the diagnosis of neurosarcoidosis. Mayo Clin Proc 1999; 74: 535. 48. Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practice guidelines for the management of cryptococcal disease. Clin Infect Dis 2000; 30: 710 – 8.

Submitted September 2, 2002; accepted September 25, 2002 DOI: 10.1080:0036554021000026969

Azithromycin-induced Rash in Infectious Mononucleosis GHENWA K. DAKDOUKI, KHALIL H. OBEID and SOUHA S. KANJ From the Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon Antibiotic-induced skin eruption in the setting of infectious mononucleosis is a common and well-documented clinical scenario. The skin lesions are non-speci c and the mechanisms causing them are unclear. Several reports have described this entity with different antibiotic classes, mainly penicillins. Only 1 case of azithromycin-induced skin eruption has previously been described in this setting. Herein, we report the second case. S. S. Kanj, MD, FACP, Division of Infectious Diseases, Department of Medicine, American University of Beirut Medical Center, PO Box 113 -6044, Hamra 110 32090, Beirut, Lebanon (Tel. »961 1 350000, fax. »961 1 370814, e-mail. [email protected])


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Case Reports


INTRODUCTION

sis is not well understood. It is thought to be due to an alteration in the immune status of the host in the setting of a viral infection. In fact, levels of circulating Th1 lymphocytes are increased in patients with EBV infection (16); these lymphocytes produce IL-2, interferon-gamma and tumor necrosis factor-alpha. Interferon-gamma in turn inhibits the function of Th2 and the secretion of interleukins, including IL-10 (17). The absence of IL-10 then leads to loss of tolerance. This may result in a hypersensitivity reaction to an antigen, which in the case of antibiotics could manifest as a drug eruption (18). The occurrence of skin rash following antibiotic intake in the setting of infectious mononucleosis does not appear to indicate an allergic reaction; ampicillin has been safely prescribed to patients who have had a previous cutaneous reaction to ampicillin during an episode of infectious mononucleosis (19). Judicious use of antibiotics in the setting of viral infections is highly recommended. These drugs can have deleterious side-effects and increase the cost of healthcare. There may be no safe antibiotic to prescribe in the setting of infectious mononucleosis.

Infectious mononucleosis is a self-limiting disease occurring most frequently in older children and young adults (1, 2). Penicillin derivatives as well as several other antibiotics are known to induce a rash in patients with mononucleosis and ampicillin (3– 5), amoxicillin, methicillin, pivampicillin, talampicillin (6, 7), cephalexin (8), minocycline (9) and sulfonamides (10) have all been incriminated. Until recently, macrolides had been considered relatively safe in the setting of infectious mononucleosis. However, with the publication of 1 case of erythromycin-induced rash and another of azithromycin-induced rash in infectious mononucleosis, this presumption is no longer valid (11, 12). This report describes a young man with infectious mononucleosis who developed a generalized cutaneous eruption following treatment with azithromycin. CASE REPORT A 19-y-old previously healthy man presented to the American University of Beirut Medical Center with right-sided neck swelling and high-grade fever. He had experienced a sore throat 2 weeks prior to admission for which he received cefuroxime, 500 mg twice daily, for 10 d. He had no history of travel, unprotected sexual activity or any other drug intake. He denied any history of skin lesions or pulmonary, gastrointestinal or urinary symptoms. On admission, his temperature was 38.3°C, with normal vital signs. Physical examination revealed right conjunctival injection as well as multiple, enlarged, movable, tender, anterior and posterior cervical and inguinal lymph nodes. The pharyngeal wall was mildly erythematous with no exudates. The liver edge was palpable 3 cm below the costal margin. Laboratory tests revealed a white blood cell count of 10900 cells:mm3 (47% neutrophils, 40% lymphocytes). Atypical lymphocytes were seen on a peripheral blood smear. The hematocrit level was 39% and the platelet count 257000:mm3 . Liver enzymes were mildly elevated. A monospot test was negative; CMV serology showed negative IgM and positive IgG titers. Epstein – Barr virus (EBV) serology was ordered. On the third day of admission, the patient had a recurrence of sore throat with persistent fever and new tonsillar exudates. A CT scan of the neck revealed multiple, matted, enlarged lymph nodes. Fine-needle aspiration of 1 of the lymph nodes showed a mixture of large and small lymphocytes as well as macrophages, favoring a reactive process. Azithromycin, 500 mg, was started by the otolaryngologist for possible bacterial infection. On the same day, the patient developed a maculopapular, non-pruritic skin rash, which was diffusely scattered over the neck, chest, back and extremities. Blood smear was repeated and again showed atypical lymphocytes. EBV serology revealed EBV VCA titers of 1:140 for IgM and 1:76 for IgG. Azithromycin was stopped and the patient was started on antihistamines. A throat culture failed to grow beta-hemolytic Streptococci. The patient improved slowly and uneventfully over the following 2 weeks.

DISCUSSION The great majority of patients suffering from infectious mononucleosis develop a rash following intake of ampicillin (13, 14). The skin lesions can be maculopapular, scarlatiniform or erythema multiforme-like (15). The mechanism of antibiotic-induced rash in infectious mononucleo-

REFERENCES 1. Horowitz W. What is mononucleosis? Ann Intern Med 1983; 98: 415. 2. Read JT, Helwig FC. Infectious mononucleosis. Arch Intern Med 1945; 75: 376 – 80. 3. Davis RA. The relationship between infectious mononucleosis and ampicillin sensitivity. J Am Coll Health Assoc 1972; 20: 291. 4. Haidar SA. Ampicillin and mononucleosis. Br Med J 1971; 1: 364. 5. Klemola E. Hypersensitivity reactions to ampicillin in cytomegalovirus mononucleosis. Scand J Infect Dis 1970; 2: 29. 6. Shapiro S, Slone D, Siskind V, Lewis GP. Drug rash with ampicillin and other penicillins. Lancet 1969; 8: 969 – 72. 7. Pullen H, Wright N, Murdoch JM. Hypersensitivity reactions to antimicrobial drugs in infectious mononucleosis. Lancet 1967; 2: 1176 – 8. 8. McCloskey GL, Massa MC. Cephalexin rash in infectious mononucleosis. Cutis 1997; 59: 251 – 4. 9. Lupton JR, Figueroa P, Tamjidi P, Berberian BJ, Sulica VI. An infectious mononucleosis-like syndrome induced by minocycline: a third pattern of adverse drug reaction. Cutis 1999; 64: 91 – 6. 10. Lund BMA, Bergan T. Temporary skin reactions to penicillins during the acute stage of infectious mononucleosis. Scand J Infect Dis 1975; 7: 21 – 8. 11. Schissel DJ, Singer D, David-Bajar K. Azithromycin eruption in infectious mononucleosis: a proposed mechanism of interaction. Cutis 2000; 65: 163 – 6. 12. Schmutz JL, Barbaud A, Trechot P. Skin eruption due to azithromycin and infectious mononucleosis. Ann Dermatol Venereol 2001; 128: 579. 13. Nazareth IJ. Ampicillin and mononucleosis. Br Med J 1971; 3: 48. 14. Casey TP, Matthews JRD. Ampicillin and mononucleosis. Br Med J 1972; 30: 827. 15. Knudsen ET. Ampicillin and urticaria. Br Med J 1969; 29: 846– 7.

Case Reports 941


16. McKenna RW, Parkin J, Gajl-Peczalska KJ, Kersey JH, Brunning RD. Ultrastructural, cytochemical, and membrane surface marker characteristics of the atypical lymphocytes in infectious mononucleosis. Blood 1977; 50: 505 –15. 17. Huston DP. The biology of the immune system. JAMA 1997; 278: 1804 – 14.

18. Zeidler R, Eissner G, Meissner P, Uebel S, Tampe R, Lazis S, et al. Downregulation of TAP1 in B lymphocytes by cellular and EBV encoded IL-10. Blood 1997; 90: 2390 – 7. 19. Nazareth I, Mortimer P, McKendrick GDW. Ampicillin sensitivity in infectious mononucleosis – temporary or permanent? Scand J Infect Dis 1972; 4: 229 – 30.

Submitted August 6, 2002; accepted August 16, 2002 DOI: 10.1080:0036554021000026949


Eubacterium Bacteremia and Colon Cancer SOMNUEK SUNGKANUPARPH1 , SIRINTORN CHANSIRIKARNJANA1 and MALAI VORACHIT2 From the Departments of 1 Medicine and 2 Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Eubacterium bacteremia is rare. We report a senile patient who presented with 3 episodes of bacteremia, caused by Clostridium perfringens, Eubacterium limosum and Escherichia coli, respectively, which led to the diagnosis of adenocarcinoma of the colon. A differential diagnosis of colon cancer should be considered in patients with eubacterium bacteremia. S. Sungkanuparph, MD, Division of Infectious Diseases, Department of Medicine, Ramathibodi Hospital, 270 Rama 6 Road, Bangkok 10400, Thailand (Tel. »66 2 2011922, fax. » 66 2 2012107 , e-mail. [email protected])

INTRODUCTION Bacteremia caused by anaerobic bacteria is less common than that caused by aerobic bacteria (1). Eubacterium is a non-sporulating anaerobe that has been recognized as a pathogen in respiratory infections, brain abscess, meningitis and shunt infections, osteomyelitis, peritonitis, urinary tract infections, wound infections and periodontal disease (2– 7). In rare instances this organism can become blood-borne in patients with neutropenia, malignancies or gastrointestinal disorders (2, 8, 9). Herein, we report a case of colon cancer that presented with acute fever, anorexia and 3 episodes of bacteremia, 1 of which was caused by eubacterium. CASE REPORT An 83-y-old woman with underlying diseases of hypertension and atrial brillation presented with a 1-week history of acute fever and anorexia. She had developed abdominal pain 3 d prior to admission and high fever with chills 1 d prior to admission. On admission, body temperature was 38.2°C; pulse rate, respiration and blood pressure were normal. The patient was slightly pale and slightly drowsy. There was no evidence of jaundice, lymphadenopathy or embolic phenomena. The cardiovascular and pulmonary systems were normal. The abdomen was soft and not tender. The liver and spleen were not palpable. Per-rectal examination revealed soft yellow stool and no rectal shelf. The rest of the neurological examination was normal. Laboratory investigations revealed a hemoglobin level of 9.5 g:dl, mild leukocytosis (11,000 white blood cells:mm3 with 85% neutrophils) and a normal platelet level. Stool examination was negative for occult blood, cells and parasites. Other laboratory investigations, including blood glucose, blood urea nitrogen, creatinine, liver function test, serum electrolytes and chest radiography,

were within normal ranges. An ultrasound scan of the abdomen showed a fatty liver and gallstones with chronic cholecystitis. Intravenous ceftriaxone was started. On Day 3 of admission, it was revealed that Clostridium perfringens had been recovered from 1:2 blood cultures taken on admission. The organism was susceptible to penicillin, cefoxitin, clindamycin, erythromycin, chloramphenicol, tetracycline and metronidazole. Ceftriaxone was switched to cefoperazone and metronidazole, which were continued for 2 weeks. The fever subsided and repeat blood cultures were negative. A cholecystectomy was performed on Day 21 of admission. Five d after the operation (Day 26), the patient developed high fever and shock compatible with bacterial sepsis. Ceftazidime, cipro oxacin and metronidazole were given, in addition to hemodynamic support. A repeat ultrasound scan of the abdomen showed only a fatty liver without space-occupying lesions or intra-abdominal uid collection. Eubacterium limosum was recovered from 2 blood cultures. The organism was susceptible to penicillin, clindamycin and erythromycin, and resistant to cefoxitin, chloramphenicol, tetracycline and metronidazole. Antibiotic therapy was switched to amoxicillin– clavulanic acid. The clinical status of the patient improved, with stable vital signs and resolution of fever. On Day 36, the patient had a recurrence of fever and acute abdominal pain, indicating another episode of sepsis. Ceftazidime and amikacin were given and amoxicillin – clavulanic acid was switched to clindamycin. Blood cultures revealed Escherichia coli, which was susceptible to cefuroxime, ceftriaxone, ceftazidime, gentamicin and amikacin, and resistant to amoxicillin– clavulanic acid and trimethoprim – sulfamethoxazole. A gastrointestinal lesion was suspected and colonoscopy was planned following the resolution of fever. However, the patient developed acute peritonitis that night and an exploratory operation was performed. The operative ndings revealed a polypoid tumor in the proximal descending colon with perforation and invasion to the retroperitoneum, and strawcolored ascitic uid. A left-half colectomy with end colostomy and oversewing of the distal stump was performed. The pathological