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AIDS:
doi: 10.1097/01.aids.0000432448.53110.e3
Correspondence

A case of immune reconstitution inflammatory syndrome related to a disseminated histoplasmosis in an HIV-1 infected patient

Mambie, Adelinea; Pasquet, Armellea; Melliez, Huguesa; Bonne, Severinea; Blanc, Anne-Laurea; Patoz, Pierreb; Ajana, Faizaa

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aService des maladies infectieuses

bLaboratoire de microbiologie, Hospital Dron, Tourcoing, France.

Correspondence to Adeline Mambie, Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing (Faculté de Médecine de Lille), 59200 Tourcoing, France. Tel: +33 3 20 69 46 16; fax: +33 3 20 69 46 15

The immune reconstitution inflammatory syndrome (IRIS) is a set of clinical and laboratory findings, related to the expression of opportunistic infections or of cancers. IRIS occurs in two ways: revelation (unmasked disease) or deterioration of a known infection or neoplasic disease (paradoxical reaction) [1]. It may be associated with many different opportunistic pathogens such as Mycobacterium tuberculosis, Cryptococci, JC polyomavirus, and hepatitis C and B virus [2]. This syndrome is usually characterized by an increased CD4 cell count and a rapid decrease in viral load [1]. The pathogenesis is speculative and seems to be caused by a recovery of pathogen-specific T cells responses and perturbations of innate immune responses [2].

Histoplasma capsulatum var. capsulatum is endemic in central regions of sub-Saharian Africa and in the USA (Ohiao and Mississipi River valley) [3], and is an opportunistic fungal infection in HIV-infected patients with a CD4 low cell count of less than 50 cells/μl [3]. The pathogenesis remains unclear and seems to be related to airborne contamination from the soil (bird ant bat excrements) [4].

We report a case of IRIS related to a disseminated histoplasmosis infection in an African HIV-1-infected patient living in France.

A 28-year-old woman with a history of tuberculosis was diagnosed with HIV-1 after her childbirth in 2002 in Ivory Coast, and then she was lost to follow-up. In October 2011, she consulted for weight loss and fatigue. Her physical examination was unremarkable, her CD4 cell count was 3 cells/μl and viral load was 62 976 copies/ml (4.8 log). The patient started her antiretroviral therapy (ART) with tenofovir/emtricitabine, atazanavir and ritonavir, but she stopped it 1 month later because of a digestive intolerance and came back to the hospital.

Abdominal computed tomography (CT) scan found mesenteric and retroperitoneal adenopathies without necrosis (the largest one measured 23 × 12 mm). The patient refused further investigations and a new ART regimen was started in November with abacavir/lamivudine, darunavir and ritonavir. Two months later, she presented with fever, night sweats and multiple cervical adenopathies. CD4 cell count was 10 cells/μl, viral load was 235 copies/ml (3.37 log) and C-reactive protein was less than 5. Sputum and blood testing did not find any fungal, bacterial or viral infection. The second tomography revealed multiple mesenteric, cervical and retroperitoneal adenopathies with central necrosis, with an increase of the latero aortic one, which measured 36 mm. The biopsy of a cervical adenopathy revealed a necrotizing lymphadenitis with typical yeast bodies of Histoplasma sp. (Fig. 1). Liposomal Amphotericin B treatment (3 mg/kg) has been infused for 3 weeks and switched to itraconazole (200 mg × 2) for several weeks. The patient slowly felt well. Histoplasmosis was considered cured as the patient continued ART with a favourable immunovirological status.

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We described a disseminated histoplasmosis after reintroduction of ART, probably related to an unmasked IRIS because of a more than 50% increase in CD4 cell count and a more than 1 log10 decrease in viral load. This is rarely described in the literature [5], and histoplasmosis is rare outside disease-endemic areas [6], although our patient was born in the Ivory Coast but did not return to Africa since 2000. Because of the lack of compliance of this patient, the diagnosis of IRIS could be discussed. Marc De Lavaissière et al.[5] reported a case of IRIS related to H. capsulatum in an HIV-infected patient born in French Guyana, who did not travel to South America or Africa. This case was associated with a haemophagocytic syndrome, which was not the case of our patient. Breton et al.[7] have already reported four cases of patients infected with HIV-1 from Surinam, Ivory Coast, Congo and French Guyana who were showing different clinical signs due to disseminated histoplasmosis (Histoplasma variety capsulatum and duboisii), after initiation of ART. They found granulomas with caseation in the three cases, which are typically associated with immunocompetent patients and attributed to IRIS [7].

In our patient, the histological analysis revealed a necrotizing lymphadenitis, which had been described in a immunocompetent patient with a cervical localization as an unusual presentation in chronic-disseminated histoplasmosis [8]. Finally, histoplasmosis is a differential diagnosis of tuberculosis [9] and even lymphoma, in an immunocompromized patient coming from endemic areas, and presenting with fever, asthenia, weight loss, sweats and lymph nodes such as in our patient [10].

In conclusion, histoplasmosis is an opportunistic infection that can be revealed by an unmasked IRIS in HIV-infected patients on ART and should be suspected in case of fever, alteration of general conditions and lymphadenitis, even outside disease-endemic areas.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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References

1. Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients. New York State Department of Health AIDS Institute, New York, August 2009. http://www.hivguidelines.org

http://www.hivguidelines.org


2. Martyn AH. Immune reconstitution inflammatory syndrome: immune restoration disease 20 years on. MJA. 2012; 196:318–321.

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4. Wheat LJ, Freifeld AG, Kleiman MN, Baddley JW, McKinsey DS, Loyd JE, Kauffman CA. Practice guidelines for the management of patients with histoplasmosis. Clin Infect Dis. 2000; 30:688–695.

5. De Lavaissière M, Manceron V, Bourée P, Garçon L, Bisaro F, Delfraissy J-F, et al. Reconstitution inflammatory syndrome related to histoplasmosis, with a hemophagocytic syndrome in HIV infection. J Infect. 2009; 58:245–247.

6. Peigne V, Dromer F, Elie C, Lidove O, Lortholary O. the French Mycosis Study Group Imported acquired immunodeficiency syndrome-related histoplasmosis in metropolitan France: a comparison of pre-highly active anti-retroviral therapy and highly active anti-retroviral therapy eras. Am J Trop Med Hyg. 2011; 85:934–941.

7. Breton G, Adle-Biassette H, Therby A, Ramanoelina J, Choudat L, Bissuel F, et al. Immune reconstitution inflammatory syndrome in HIV-infected patients with disseminated histoplasmosis. AIDS. 2006; 20:119–132.

8. Meijer JA, Sjögren EV, Kuijper E, Verbist BM, Visser LG. Necrotizing cervical lymphadenitis due to disseminated Histoplasma capsulatum infection. Eur J Clin Microbiol Infect Dis. 2005; 248:574–576.

9. Mandengue CE, Lindou J, Mandeng N, Takuefou B, Nouedoui C, Atangana P, Fonkoua MC. Fatal military tuberculosis in an HIV-infected Cameroon woman: disseminated histoplasmosis due to Histoplasma capsulatum capsulatum. Med Trop. 2011; 71:615–617.

10. Pervez MM, Cobb B, Matin N, Shahrin L, Ford ER, Pietroni M. Disseminated histoplasmosis in a patient with advanced HIV disease: lessons learnt from Bangladesh. J Health Popul Nutr. 2010; 28:305–307.

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