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Isolated conjunctival histoplasmosis in an elderly patient: a rare but important scenario

      Histoplasmosis is a granulomatous infection caused by the dimorphic fungus Histoplasma capsulatum. It has two variants which are known to cause human infection: Histoplasma capsulatum var capsulatum and Histoplasma capsulatum var duboisii. Ocular manifestations are known in the form of involvement of the choroid and retina.
      • Diaz R.I.
      • Sigler E.J.
      • Rafieetary M.R.
      • Calzada J.I.
      Ocular histoplasmosis syndrome.
      Here, we describe the clinical features, diagnosis, and management of an isolated conjunctival histoplasmosis infection as a primary manifestation in an immunocompromised individual.

      Case Description

      A 60-year-old male patient was referred to us for a gradually increasing, painless, light pink, conjunctival mass in the left eye over four months (Fig. 1). Examination revealed a visual acuity of 20/20 in both eyes. Right eye anterior segment examination was essentially within normal limits, whereas the left eye showed a diffuse conjunctival mass extending from the limbus till the fornices without any corneal or orbital involvement. Extra ocular movements were normal in all the gazes. Dilated fundus evaluation revealed a healthy optic nerve and retina in both eyes.
      Fig. 1
      Fig. 1Left-sided temporal conjunctival thickening extending till the fornices (red arrows).
      The deduced differential diagnoses were lymphoma, angiomyxoma, myxoma, lipodermoid, and/or amyloidosis. The B scan ultrasound performed over closed eyelids revealed a temporal ocular coat thickening along the anterior aspect with an underlying hypo echoic muscle tendon; however, ocular coats appeared intact in absence of any orbital extension. Subsequently, the contrast-enhanced MRI of the orbit revealed a variably enhancing diffuse mass along the left epibulbar region, which collaborated with the ultrasound findings. Under local anesthesia, complete excision biopsy of the lesion was performed, with grafting of the residual bed using an amniotic membrane. The light microscopy examination of the specimen revealed sheets of subconjunctival histiocytes with round intracytoplasmic and extracellular organisms measuring approximately 2–4 microns (Fig. 2A). The silver methamine stain demonstrated the black capsule (Fig. 2B) and Periodic Acid Schiff (PAS) stain highlighted the cell wall (Fig. 2C). Based on the findings, a diagnosis of conjunctival histoplasmosis capsulatum var capsulatum was made and the patient underwent thorough dermatological and pulmonary evaluation, which revealed findings suggestive of systemic histoplasmosis. Serology showed reactivity for HIV along with very low CD4 counts. The patient was started on anti-retroviral therapy along with intravenous liposomal Amphotericin B, but, due to a severely compromised immune status, the patient did not survive for more than a few weeks after the clinical diagnosis was established.
      Fig. 2
      Fig. 2(A) Incisional biopsy specimen under light microscopy revealed sheets of subconjunctival histiocytes containing round intracytoplasmic as well as extracellular 2–4 micron organisms (10X). (B) Silver methamine staining the capsule (black) (20X). (C) Periodic Acid Schiff (PAS) stain highlights the organisms (20X).

      Discussion

      Conjunctival involvement due to Histoplasma capsulatum is very unusual in clinical practice. Human infection mainly affects the lungs due to the inhalation of spores which reside in soil with high nitrogen content. Histoplasmosis due to Histoplasma capsulatum var capsulatum, which is mainly found in the United States along the sides of the Ohio and Mississippi river valleys.
      • Shirali A.
      • Kini J.
      • Vupputuri A.
      • Kuruvila M.
      • Venkatraya Prabhu M.
      Disseminated histoplasmosis with conjunctival involvement in an immunocompromised patient.
      • Krakauer M.
      • Prendes M.A.
      • Wilkes B.
      • Lee H.B.H.
      • Fraig M.
      • Nunery W.R.
      A case of orbital histoplasmosis.
      Symptoms include acute or chronic pulmonary histoplasmosis, progressive disseminated histoplasmosis, ocular histoplasmosis, and cutaneous histoplasmosis. The pulmonary manifestations can be asymptomatic in healthy individuals, but, in patients who are immunocompromised, it can be devastating. The second variant is Histoplasma capsulatum var duboisii, also known as African histoplasmosis, as it is mainly prevalent in West Africa. It can be localized to the skin or the disseminated form involving the lymph nodes, bone, and other visceral organs.
      • Ravindran S.
      • Sobhanakumari K.
      • Celine M.
      • Palakkai S.
      African histoplasmosis: the first report of an indigenous case in India.
      Conjunctival involvement is rare and it has been noted previously on two occasions; Knox et al. noted isolated histoplasmosis presenting as an isolated conjunctival granuloma, which was small and successfully managed surgically.
      • Knox D.L.
      • O’Brien T.P.
      • Green W.R.
      Histoplasma granuloma of the conjunctiva.
      Similarly, Shirali et al. described conjunctival involvement associated with diffuse nodular skin lesions in an HIV-infected patient with disseminated histoplasmosis, who was managed initially with intravenous Amphotericin B followed by oral itraconazole 200 mg for life.
      • Shirali A.
      • Kini J.
      • Vupputuri A.
      • Kuruvila M.
      • Venkatraya Prabhu M.
      Disseminated histoplasmosis with conjunctival involvement in an immunocompromised patient.
      Histopathological assessment by an experienced ocular pathologist is of paramount importance to make a final diagnosis. These fungal infections mainly show granulomatous inflammation along with necrosis. Under the microscope, the Histoplasma capsulatum var capsulatum variant shows oval yeasts, measuring 2–4 microns, and their cell walls are usually identified by Gomori Methamine Silver and Periodic Acid Schiff stains. Because these yeasts are ingested by macrophages, they can also be visualized inside the macrophages in a clustered manner.
      • Guarner J.
      • Brandt M.E.
      Histopathologic diagnosis of fungal infections in the 21st century.
      Histoplasma capsulatum var duboisii shows similar clustering inside the macrophages, and it can be differentiated from the former based on the size of the yeasts, which are larger (8 to 15 μm in diameter) than the former. Other modalities to differentiate include lysis centrifugation method, culture, and detection of the antigen in urine.
      • Guarner J.
      • Brandt M.E.
      Histopathologic diagnosis of fungal infections in the 21st century.
      To conclude, isolated conjunctival histoplasmosis was the primary clinical manifestation of a severely compromised immune status in an elderly patient. Thus, cases with unusual conjunctival masses in elderly patients must undergo detailed ocular and systemic evaluation for optimal results.

      Disclosure(s)

      The authors have no proprietary or commercial interest in any materials discussed in this article

      Supplementary data

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