Disseminated histoplasmosis with cutaneous lesions in an HIV patient

ARTICLE

Auteur(s) : Sophie MAHY¹ sophie.mahy@chu-dijon.fr, Blandine BEL¹, Pascal CHAVANET¹, Fréderic DALLE², Michel DUONG¹, Adeline ERVAIS-WAKOSA¹, Tony PETRELLA³, Lionel PIROTH¹

¹ Department of Infectious Diseases, CHU Dijon, Bd maréchal de Lattre de Tassigny, 21000 Dijon, France

² Parasitology, CHU Dijon, Bd maréchal de Lattre de Tassigny, 21000 Dijon, France

³ Anatomopathology, CHU Dijon, Bd maréchal de Lattre de Tassigny, 21000 Dijon, France

Disseminated histoplasmosis remains rare in metropolitan Europe. We report a case of disseminated histoplasmosis with cutaneous lesions in an HIV positive patient.

A 45-year-old Ghanaian patient was referred to our department for management of HIV infection (heterosexual contamination). He had lived in France for 20 years and returned to Ghana only once, ten years before. He presented with deterioration of his general condition, fever, dry cough and a mild eruption of non pruriginous papules (figure 1A). CD4+ T cell count was 1/mm³ and plasma HIV RNA level was 6.5 log₁₀ copies/mL. Biological assessment showed anaemia, leucopenia and hepatitis. Interstitial infiltrates were seen on thoracic scan. Sputum examinations for tuberculosis were negative whereas PCR diagnosis of Pneumocystis jiroveci was positive. He refused bronchoalveolar lavage. A skin biopsy showed follicular inflammation with PAS and Grocott stainings revealing yeasts of 4 μm, suggesting Malassezia sp. by argument of frequency, but no cultures were done. Cryptococcal antigenemia was negative. The patient was treated with cotrimoxazole for possible pneumocystis pneumonia, oral and topical ketoconazole for Malassezia folliculitis. Then, he started antiretroviral therapy (ART) and his condition progressively improved. However, ten weeks after ART initiation with TDF +3TC + atazanavir, he was re-admitted for fever, odynophagia, a generalized but non-pruriginous papular and erythematous eruption with a leonine appearance face, and ulcerations on the hard palate. Small nodules were seen on a thoracic scan with regression of the interstitial infiltrates. The CD4+ T cell count had increased to 300/mm³ and the HIV RNA level had fallen to 4 log₁₀ copies/mL. A skin biopsy revealed a perivascular infiltrate of lymphocytes, histiocytes and granulocytic cells in the dermis (figure 1B). Pseudo-encapsulated and refringent yeasts were highlighted after Calcofluor white and May-Grünwald Giemsa staining. Mycelial filaments obtained on Sabouraud agar at 30 ̊C and the dimorphic character were evocative of Histoplasma sp. Morphologic characteristics suggested Histoplasma capsulatum. It was confirmed by DNA extraction from the biopsy followed by amplification of the Internal Transcribed Spacer region of the ribosomal fungal DNA. Serologic tests for histoplasmosis were negative, probably because of severe immunosuppression.

Finally, disseminated histoplasmosis (pulmonary histoplasmosis suspected lesions, cutaneous and mucous histoplasmosis lesions) associated with immune reconstitution syndrome (IRS) (atypical clinical manifestations occurring after initiation of efficacy ART) was diagnosed. The patient was treated with amphotericin B (3 weeks) then posaconazole (for 12 months because of low CD4 cell counts) and prednisone for severe IRS. After 2 months, there was a complete regression of symptomatology and cutaneous lesions.

Since the onset of the AIDS epidemic, histoplasmosis has become a more common opportunistic fungal infection in endemic areas (North and Latin America). In Europe, cases of histoplasmosis in AIDS patients essentially concerns people coming from endemic regions such as sub-Saharan Africa and, exceptionally, patients who left endemic areas many years before [1]. During AIDS, the development of histoplasmosis could be due to reactivation of initial pulmonary lesions, primary infection or re-infection. Infection can occur at various sites. Skin involvement has been reported in half of patients in the form of papules, crusting plaques, nodules and ulcers [2]. Folliculitis is an uncommon manifestation of cutaneous histoplasmosis.

IRS associated with histoplasmosis in seropositive patients has rarely been reported [3]. To our knowledge, this is only the second report of an IRS-associated histoplasmosis that has predominantly affected the skin with two characteristics: rapid generalization of the papular lesions and infiltration of the facial skin resulting in a leonine facies [4]. The management of IRS is not well standardized. The use of corticosteroids is usually recommended in severe forms of histoplasmosis [5]. In our patient, the persistence of severe reactions despite antifungal therapy justified the use of systemic corticosteroids for a short duration.

Disclosure

Financial support: none. Conflict of interest: none.

References

1 PY Dietrich, P Pugin, C Regamey, J. Bille Disseminated histoplasmosis and AIDS in Switzerland Lancet 1986; 2: 752.

2 A Bonifaz, P Chang, K Moreno, V Fernandez-Fernandez, G Montes de Oca, J Araiza et al. Disseminated cutaneous histoplasmosis in acquired immunodeficiency syndrome: report of 23 cases Clin Exp Dermatol 2009; 34: 481-486.

3 SA Shelburne 3rd., F Visnegarwala, C Adams, KL Krause, RJ Hamill, A.C. White Jr. Unusual manifestations of disseminated Histoplasmosis in patients responding to antiretroviral therapy Am J Med 2005; 118: 1038-1041.

4 E Sarazin, M Nacher, Y Toure, E Clyti, M El Guedj, C Aznar et al. Dermatologic manifestations associated with immune reconstitution syndrome in HIV+ patients starting HAART: a retrospective study in French Guiana Bull Soc Pathol Exot 2005; 98: 187-192.

5 LJ Wheat, AG Freifeld, MB Kleiman, JW Baddley, DS McKinsey, JE Loyd et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America Clin Infect Dis 2007; 45: 807-825.