Mucocutaneous Histoplasmosis in immunocompetent adult patients

Introduction: Histoplasmosis is a fungal infection caused by the agent Histoplasma capsulatum, a dimorphic fungus. The spectrum of illness ranges from subclinical infection to progressive disseminated disease. The major bulk of histoplasma infections are asymptomatic or pulmonary histoplasmosis. In immune compromised patients it can cause disseminated infections involving different organs of the body. In immune competent individuals it may cause isolated adrenal histoplasmosis. Material and methods: A retrospective study was done to look for mucocutaneous histoplasmosis. The excised tissue samples were cultured and only culture confirmed cases were included in the study. Result: Here, we present five cases of primary mucocutaneous histoplasmosis in immune competent individuals in a tertiary care centre in India. These patients had no other co-morbidities and had only isolated lesions in oral cavity or penis.The tissue on excision was cultured and showed growth of Histoplasma capsulatum. All the patients improved with treatment. There are limited cases of mucocutaneous ulcerated lesions caused by Histoplasma capsulatum in immune competent people in published literature. Conclusion: This study emphasizes the necessity of a vigilant look out and clinical suspicion of fungal causes like histoplasma in chronic non healing ulcers which should be confirmed by the laboratory investigations. Accurate diagnosis helps in specific management of these cases.


Introduction
Histoplasmosis is a fungal disease caused by dimorphic fungi Histoplasma capsulatum. Two varieties of fungi are known to infect humans, namely: H. capsulatum var. capsulatum and H. capsulatum var. Duboisii 1 . Clinical manifestations of histoplasmosis varies from asymptomatic infection, pulmonary histoplasmosis and progressive disseminated disease 2 . The only report of Histoplasma being isolated from soil is from the Gangetic plain of West Bengal as early as in 1975 3 . The first case of histoplasmosis from India was reported in 1954 by Panja and Sen from Calcutta 4 . A number of risk factors can predispose to disseminated histoplasmosis such as AIDS, primary immunodeficiency, long-term immunosuppression as with use of glucocorticoids and post-organ transplantation 2 . Only few cases of primary mucocutaneous histoplasmosis are reported and even fewer in immunocompetent individuals.

Materials and methods
A retrospective study was done for five and half years (July 2011to December 2016) to find out the cases of primary mucocutaneous histoplasmosis in a tertiary care hospital in Eastern India. The clinical features and associated diseases were noted. The excised tissue was sent to the Department of Microbiology. Direct microscopy showed presence of yeast cells on Gram stain preparation and potassium hydroxide preparation. Tissue was then inoculated on Sabouraud's dextrose agar and incubated at 37 0 C and 25 0 C temperature. The growth of the organism was noted and identification was done by lactophenol cotton blue preparation. All the cases included were positive for fungal culture. The samples which had yeast cells on direct microscopy but did not grow in culture were excluded from the study. Ethical clearance: Prior to the submission, the study was approved by the ethics committee of Medical College, Kolkata.

Results
A retrospective study was done in a tertiary care hospital in Eastern India which revealed five cases of primary mucocutaneous histoplasmosis during the period of five and half years (2011 -2016). The age of the patients was between 52 to 71 years (mean = 60.94, SD = 8.35). All the patients were male. All the patients were from rural areas of southern part of West Bengal and farmer by occupation. All these patients were immunocompetent and were negative for HIV test by ELISA, had no history of any medications, transplant etc. None of the patients were diabetic. The patients presented with swelling and ulcer of the affected region. Among these patients four had oral histoplasmosis while one had penile histoplasmosis (Table 1). The lesion was excised and sent for microscopy and culture. On direct microscopy, it showed yeast cells on Gram stain preparation and potassium hydroxide preparation. It was inoculated on Sabouraud's dextrose agar and brain heart infusion agar and incubated at 37 0 C and 25 0 C temperature. The growth of the organism was noted and identification was done by lactophenol cotton blue preparation. The growth from culture at 25 0 C was white cottony growth (Fig 1). On microscopy septate hyaline hyphae with tuberculate macroconidia and small smooth microconidia, corresponding to the structure of Histoplasma capsulatum was seen (fig 2). None of these five cases had any malignant change on histopathology.
The mycelial phase converted to yeast phase on brain heart infusion agar at 37 0 C confirming the isolate as Histoplasma capsulatum. The patients were treated with amphotericin B and improved.  10 . In many instances oral lesions are associated with cutaneous lesions. Such a case has been reported by Harnalikar and group in a 60 year old HIV negative male who presented with asymptomatic swelling of the hard palate and crusted papules and nodules over the extremities, face and trunk which was diagnosed as histoplasma on culture 11 . A similar case was reported by Anza and colleagues with linear erythematous atrophic plaques and oral ulcers in a immunocompetent patient 12 and Vidyanath et al 13 .

Discussion
However, here we present five cases of mucocutaneous histoplasmosis of which four had isolated oral ulceration on presentation. The study shows that it is more common in the older age group with a mean age of 60.94 years which is similar to the findings of Deodhar et al who saw that the mean age of disseminated histoplasmosis was 52.2 years in immunocompetent patients as compared to much lesser age in immunodeficient individuals 2 . In many studies histoplasmosis is diagnosed based on histology alone 14 19 . Another similar case was seen in a renal transplant recipient whose epididymal biopsy revealed histoplasmosis 20 . But in our case, the patient was a healthy immunocompetent male patient who had penile histoplasmosis.

Conclusion
Histoplasmosis may have varied clinical manifestations, ranging from oral ulcer, laryngeal histoplasmosis to penile histoplasmosis in immunocompetent individuals. As the disease mimics other diseases like malignancy and tuberculosis, a constant vigilance is required for clinical suspicion and laboratory diagnosis of these unusual presentations so that the causative agent is identified and appropriate management is given to these patients.