Garbino, J.

Hirschel, B.

Lambert, J.

Matulionyte, R.

Uçkay, I.

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Eur J Clin Microbiol Infect Dis (2005) 24: 361–363DOI 10.1007/s10096-005-1317-7BRIEF REPORTR. Matulionyte · J. Garbino · I. Uc¸kay ·J. F. Lambert · B. HirschelDisseminated histoplasmosis in an HIV-infected patient discoveredby routine blood smear stainingPublished online: 16 April 2005C© Springer-Verlag 2005Histoplasma capsulatum is a dimorphic fungus of the As-comycetes class. Histoplasmosis is the most common en-demic mycosis in the USA and has emerged as an importantopportunistic infection among patients with HIV living inor visiting endemic areas [1]. While the illness is subclini-cal or presents as a mild self-limited pulmonary infection inhealthy individuals, the majority of cases involving AIDSpatients show signs of a life-threatening disseminated in-fection. Presented here is a case of disseminated histo-plasmosis in an HIV-infected patient living in Switzerland,which was diagnosed by examination of a simple bloodsmear.A 45-year-old man was referred to our hospital in 2003with a 3-week history of fever, cough, shortness of breathand fatigue, a 3-month history of diarrhea (3–4 times a day),and a 5-kg weight loss. The patient had been diagnosedwith HIV 5 years previously but had refused treatment.Originally from Colombia, he had resided in Switzerlandsince 1979. Three months before hospital admission, hehad visited his native country.At the time of hospitalization, the patient was tachycardicand tachypneic, with a temperature of 39.6◦C. Bilateralpulmonary rales and hepatosplenomegaly were noted. Theabnormal laboratory findings were as follows: hemoglobin7.9 g/dl, leukocyte count 9.9 G/l with left deviation of36% and lymphopenia 6% (0.6 G/l), platelet count 17 G/l,C-reactive protein level 221 mg/l, alanine aminotransferase152 U/l, aspartate aminotransferase 301 U/l, and serumR. Matulionyte · J. Garbino () · I. Uc¸kay · B. HirschelDivision of Infectious Diseases, University of Geneva Hospitals,24, rue Micheli-du-Crest,1211 Geneva 14, Switzerlande-mail: jorge.garbino@hcuge.chTel.: +41-22-3729839Fax: +41-22-3729832J. F. LambertDivision of Hematology, University of Geneva Hospitals,24, rue Micheli-du-Crest,1211 Geneva 14, Switzerlandcreatinine 1065 µmol/l. The CD4+ cell count was 16/mm3and HIV RNA level 690,000 copies/ml. Chest radiographshowed diffuse, nodular, interstitial infiltrates. Five daysafter admission the patient developed bilateral pleuraleffusions. Due to gastritis, a gastroscopy was performed,revealing two pyloric ulcers.The diagnosis of histoplasmosis was established by rou-tine direct examination of a blood smear (Fig. 1a) andblood staining with calcofluor. Fungi were also seen inbronchoalveolar lavage (Fig. 1b), pleural liquid and bonemarrow, and cultures of these samples grew H. cap-sulatum. Antimicrobial treatment was started with in-travenous liposomal amphotericin B (250 mg/d for 13days) and then switched to oral itraconazole (200 mg/d).Due to the patient’s renal impairment, hemofiltration wasnecessary during the first 3 days, and his anemia wastreated with transfusions of red blood cells. The pa-tient also had several comorbid conditions, including cy-tomegalovirus chorioretinitis, Kaposi’s sarcoma, oropha-ryngeal candidiasis and giardiasis, for which he receivedtargeted treatment. His clinical evolution was slowly favor-able, and he was transferred to a rehabilitation facility after40 days.At the time of transfer, the patient’s levels of serum cre-atinine, transaminases and platelets had returned to nor-mal, and his anemia had improved. Treatment consistedof itraconazole, valganciclovir, 3TC, tenofovir and cotri-moxazole. At 12-month follow-up, the patient’s CD4+ cellcount had risen to 145/mm3, and no relapse had occurred.The decision was made to continue treating the patient withitraconazole until his CD4+ cell count reached 200/mm3,at which time treatment would be switched to highly activeantiretroviral treatment.Although H. capsulatum has a worldwide distribution, itis more prevalent in certain parts of North America, Centraland South America, Africa, and Asia [1]. Once regarded asa rare disease, it is now the most common endemic mycosisin the USA and one of the most common opportunisticfungal infections in HIV-infected patients living in areas ofhigh prevalence [2], where it occurs in about 5% of AIDSpatients [3].362Fig. 1 a Wright-Giemsa stain of peripheral blood smear. Numerouscircular inclusions with basophilic nuclei are visible in the cytoplasmof neutrophils. A surrounding clear capsule is also visible. In addi-tion, the neutrophils have large granules and vacuoles indicating asevere infection. Elongated pale-blue Do¨hle bodies representing ac-tive rough endoplasmic reticulum can also be seen in the neutrophilson the left and at the bottom (enlargement 1000×). b Bronchoalveolarlavage stain viewed with calcofluor under a fluorescence-microscopeAmong cases of histoplasmosis occurring in Europe,69 cases due to H. capsulatum and 17 cases due to H.dubosii have been reported in the literature from 1980to 1993, one-third of which occurred in AIDS patients[1]. The first case of disseminated histoplasmosis inSwitzerland was diagnosed in 1984 in an HIV-infectedpatient from Zaire [4]. In the subsequent Swiss HIV cohortstudy, histoplasmosis accounted for 0.07% (11 cases) ofall AIDS-defining diseases identified between 1987 and2002. All of these patients had resided in endemic areas.In nearly all reports of histoplasmosis in patients withAIDS, the infection has been disseminated [3, 5], while inthe general population only 1 in 2,000 individuals developsdisseminated infection [6]. An acute, rapidly fatal coursewith diffuse reticuloendothelial involvement characterizesthe infection in these patients, and severity varies withthe degree of immune deficiency [1]. Patients oftenpresent with shock, respiratory distress, hepatic and renalfailure, obtundation, and coagulopathy [5]. Respiratorycomplaints, hepatosplenomegaly or lymphadenopathy arepresent in one- to two-thirds of cases. Skin or mucosallesions are less frequent [5]. Although involvement ofthe gastrointestinal tract is common, gastrointestinalmanifestations are relatively rare [7]. However, in certaincases gastrointestinal and/or hepatic signs and symptomsmay predominate, and these patients may have nopulmonary symptoms [8]. Symptoms of gastrointesti-nal histoplasmosis can mimic other AIDS-associatedpathologies, making the diagnosis difficult. In some cases,kidney lesions result from disseminated histoplasmosis,as shown by renal biopsy [9]. Skin involvement wasfound to be more common in a Brazilian than in a U.S.cohort [10]. Disseminated histoplasmosis with a neuro-logical focus could present with symptoms mimickingcancer [11].Recent guidelines for the treatment of disseminated histo-plasmosis in patients with AIDS recommend a 12-weekinduction therapy, initially starting with intravenous am-photericin B deoxycholate, which can later be switchedto itraconazole to complete the 12-week course [12]. Fur-ther investigation into the pathogenesis of disseminatedhistoplasmosis at the molecular level is necessary in or-der to identify new targets for the development of effectivetherapy to eradicate the infection in immunocompromisedpatients. For patients with AIDS, long-term maintenancetherapy with itraconazole is required after a severe mani-festation of histoplasmosis to prevent relapses. Coadmin-istration with lopinavir/ritonavir led to a strong increase initraconazole concentrations and its dosage must be adaptedwhen used in this combination.Early diagnosis is crucial for the positive outcome of dis-seminated histoplasmosis infection. Without treatment themortality rate is 80%; however, with early diagnosis andantifungal therapy the mortality rate is usually <25% [11].Therefore, it is important to recognize cutaneous histoplas-mosis lesions so that prompt histologic evaluation and cul-ture can be performed in suspected cases of disseminatedfungal infection, thereby expediting diagnosis and treat-ment. Although immunocompromised patients may havea large number of organisms in a lesion with a minimaltissue reaction [8], serologic antigen tests for antibodies toH. capsulatum are positive in about 80% of patients withdisseminated histoplasmosis [2].In conclusion, histoplasmosis is a rare opportunisticinfection in Europe, but it must be included in thedifferential diagnosis of opportunistic infections inHIV-infected patients, mainly if they are returning fromendemic areas. Vigilance concerning the travel history ofpatients must be maintained. Fungal staining of blood andtissue samples, and even routine blood smear staining,point toward the diagnosis of this infection, whichcan be confirmed by the isolation of H. capsulatum inculture.Acknowledgment We thank K. Bouchuigi-Waf for microbiologicallaboratory assistance363References1. Wheat LJ, Kauffman CA (2003) Histoplasmosis. Infect Dis ClinN Am 17:1–192. Manfredi R, Mazzoni A, Nanetti A, Chiodo F (1994) Histoplas-mosis capsulati and dubosii in Europe: the impact of the HIVpandemic, travel and immigration. Eur J Epid 10:675–6813. Cano MVC, Hajjeh RA (2001) The epidemiology of histoplas-mosis. Semin Respir Infect 16:109–1184. McKinsey D, Spiegel RA, Hutwagner L, Stanford J, Driks MR,Brewer J, Gupta MR, Smith DL, O’Connor MC, Dall L (1997)Prospective study of histoplasmosis in patients infected with hu-man immunodeficiency virus: incidence, risk factors, and patho-physiology. Clin Infect Dis 24:1195–12035. Dietrich PY, Pugin P, Regamey C, Bille J (1986) Disseminatedhistoplasmosis and AIDS in Switzerland. Lancet 2:7526. Wheat LJ, Connolly-Stringfield PA, Baker R, Curfman MF, EadsME, Israel KS, Norris SA, Webb DH, Zeckel ML (1990) Dis-seminated histoplasmosis in the acquired immune deficiencysyndrome: clinical findings, diagnosis and treatment, and reviewof the literature. Medicine 69:361–3747. Suh KN, Anekthananon T, Mariuz PR (2001) Gastrointestinalhistoplasmosis in patients with AIDS: case report and review.Clin Infect Dis 32:483–4918. Lamps LW, Molina CP, West AB, Haggitt RC, Scott MA (2000)The pathologic spectrum of gastrointestinal and hepatic histo-plasmosis. Am J Clin Pathol 113:64–729. Burke DG, Emancipator SN, Smith MC, Salata RA (1997) Histo-plasmosis and kidney disease in patients with AIDS. Clin InfectDis 25:281–28410. Karimi K, Wheat LJ, Connolly P, Cloud G, Hajjeh R, Wheat E,Alves K, Lacaz CS, Keath E (2002) Differences in histoplasmo-sis in patients with acquired immunodeficiency syndrome in theUnited States and Brazil. J Infect Dis 186:1655–166011. Nicolas X, Granier H, Laborde JP, Talarmin F, Zagnoli F,Garin A, Le Flohic AM, Moalic E, Quinio D, Klotz F (2003)[Disseminated and central nervous system Histoplasma capsu-latum infection mimicking neoplasm: difficulties in diagnosis,failure in management]. Rev Med Interne 24:389–39312. Wheat J, Sarosi G, McKinsey D, Hamill R, Bradsher R, John-son P, Loyd J, Kauffman C (2000) Practice guidelines for themanagement of patients with histoplasmosis. Infectious diseasessociety of America. Clin Infect Dis 30:688–695

Disseminated histoplasmosis in an HIV-infected patient discovered by routine blood smear staining

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Disseminated histoplasmosis in an HIV-infected patient discovered by routine blood smear staining

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