Cryptococcal Choroiditis

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Disease Entity

Cryptococcal choroiditis. ICD-10: B45.9

Disease

Cryptococcus neoformans infection, an AIDS-defining illness, is a common cause of infectious choroiditis in immunodeficient patients. Choroidal lesions are the initial manifestation of disseminated disease or meningitis secondary to infection with C. neoformans.

Etiology and Incidence

C. neoformans is most commonly found in dried pigeon feces and is transmitted via aerosolization. A study conducted in 2008 showed that there were 957,900 cases of cryptococcal meningoencephalitis cases resulting in more than 600,000 deaths annually.[1][2]

Risk Factors

Risk factors include immunocompromised status (such as CD4 count <100 cells/µL) and exposure to pigeon droppings,[3] unwashed raw fruit,[4] decaying wood, tree hollows, and contaminated soil.[5][6]

Pathophysiology

C. neoformans is an encapsulated yeast organism. Primary infection begins in the lung of an immunocompromised host and subsequently undergoes hematogenous dissemination to the rest of the body including to the choroidal vasculature.[7]

Prevention

Since mortality rates are so high, prevention is essential. Immunodeficient patients should be instructed to avoid contact with people at risk of exposure. Patients with known CD4 counts <100 cells/µL should be promptly placed on prophylactic antimicrobials (discussed under Medical Therapy). They should also be instructed to visit an ophthalmologist at the earliest sign of visual symptoms and/or when their CD4 counts are <200 cells/µL as these patients may develop disseminated disease and systemic complications.[8]

Diagnosis

Cryptococcal choroiditis is an ocular manifestation of a systemic disease. Initial evaluation includes a careful history, neurologic exam, and serum cryptococcal antigen (CrAg) assay. Evaluation should also include a lumbar puncture (LP) to assess for increased intracranial pressure and culture of the cerebrospinal fluid (CSF) to confirm the diagnosis in those with symptoms and/or a positive CrAg. Mucicarmine staining and the India Ink Stain can be used to identify the thick capsule of C. neoformans. Fluorescein angiography (FA) and indocyanine green angiography (ICG) have been used to detect cryptococcal choroiditis. These imaging techniques may show a blockage of choroidal filling (hypofluorescence) in the early stages of infection and lesions associated with decreased filling in the later stages.[9] Findings on optical coherence tomography (OCT), while nonspecific, include choroidal thickening and hyperreflectivity within the photoreceptor layer. Retinal pigment epithelial (RPE) disruption is not typical.[9] While findings on FA, ICG, and OCT in cryptococcal choroiditis are nonspecific, CSF culture is highly sensitive and specific.[10][9][11]

History

Patients should be asked about coexisting conditions associated with immunosuppression such as steroid use, known malignancy, history of transplantation, and HIV infection. Patients should also be asked about possible exposure.

Physical Exam

A comprehensive eye exam should be performed with careful attention to the signs and symptoms described below.

Signs

Cryptococcal choroiditis typically presents with creamy yellow lesions in the choroid together with intraretinal, white-centered hemorrhages. Due to the requisite level of immunocompromise, there are generally no other signs of intraocular inflammation, such as vitritis.[12][13][14][15]

Symptoms

Cryptococcal choroiditis initially presents as mild headaches, fatigue, fever, and nonspecific eye complaints such as intermittent blurring or loss of vision. Symptoms may wax and wane.[16]

Differential Diagnosis

The differential diagnosis for cryptococcal choroiditis in advanced AIDS patients includes toxoplasmosis or infection with pneumocystis carinii, mycobacterium tuberculosis, histoplasma capsulatum, and candida albicans.[17] A detailed history may help narrow this differential. To rule out pneumocystis carinii, a sample of induced sputum of bronchoalveolar lavage fluid should be analyzed for microbiologic identification. Mycobacterium tuberculosis can be ruled out with a chest X-ray. Histopathologic examination of lung or mediastinal lymph node tissue may be necessary to rule out histoplasma capsulatum. A sample of fluid should be analyzed for candida albicans if there is a high clinical suspicion for such an infection.

Management

Medical Therapy

The best medical treatment for cryptococcal choroiditis has not yet been established. In some cases, systemic therapy with amphotericin B and flucytosine has been sufficient to resolve the choroiditis. There is limited literature on successful resolution of the infection with intravitreal flucytosine injection alone or in conjunction with amphotericin B.[18][19]

Medical Follow-up

Patients should be followed closely initially, until a clinical response is seen. Any immunosuppressive therapy should be held for at least 2 weeks after initiation of antifungal therapy. Since recurrences are not uncommon, medical treatments should be tapered very slowly.[19]

Surgical Therapy

Some cases may progress rapidly to endophthalmitis and require aggressive treatment with intravitreal therapy and pars plana vitrectomy.[20][21]

Complications

Postoperative complications after surgical intervention include recurrence of cryptococcal choroiditis as well as others such as infection, glaucoma, cataract, wound leak, and astigmatism.[20][21]

Prognosis

If left untreated, cryptococcal infection may disseminate further and lead to rapid death within weeks[22] from respiratory failure, systemic complications, or central nervous system involvement.

Additional Resources

Visit EyeSmart from the American Academy of Ophthalmology (https://www.aao.org/eye-health) for patient friendly information on choroiditis.

References

  1. Warkentien, T., & Crum-Cianflone, N. F. (2010). An update on Cryptococcus among HIV-infected patients. International Journal of STD & AIDS21(10), 679-684.
  2. Cox, G. M., Perfect, J. R., Bartlett, J. G., & Mitty, J. (2014). Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-infected patients. UpToDate.
  3. Soltani, M., Bayat, M., Hashemi, S. J., Zia, M., & Pestechian, N. (2013). Isolation of Cryptococcus neoformans and other opportunistic fungi from pigeon droppings. Journal of Research in Medical Sciences18(1), 56.
  4. Cryptococcosis. (n.d.). Retrieved from https://rarediseases.org/rare-diseases/cryptococcosis/
  5. Sorrell TC, Ellis DH. Ecology of Cryptococcus neoformans. Rev Iberoam Micol. 1997 Jun;14(2):42-3.
  6. Lazera MS, Salmito Cavalcanti MA, Londero AT, Trilles L, Nishikawa MM, Wanke B. Possible primary ecological niche of Cryptococcus neoformans. Med Mycol. 2000 Oct;38(5):379-83.).
  7. Chang, C. C., Sorrell, T. C., & Chen, S. A. (2015, October). Pulmonary cryptococcosis. In Seminars in Respiratory and Critical Care Medicine. Vol. 36, No. 05, pp. 681-691. Thieme.
  8. Nishijima, T., Yashiro, S., Teruya, K., Kikuchi, Y., Katai, N., Oka, S., & Gatanaga, H. (2015). Routine eye screening by an ophthalmologist is clinically useful for HIV-1-infected patients with CD4 count less than 200/μL. PloS one10(9), e0136747.
  9. 9.0 9.1 9.2 Baillif, S., Delas, J., Asrargis, A., & Gastaud, P. (2013). Multimodal imaging of bilateral cryptococcal choroiditis. Retina33(1), 249-251.
  10. Govender, N. P., Meintjes, G., Bicanic, T., Dawood, H., Harrison, T. S., Jarvis, J. N. & Variava, E. (2013). Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med14(2), 76-86.
  11. Sofia, O., Sridharan, S., & Biswas, J. (2012). Algorithm of Choroiditis. World2(2), 39-45.
  12. Aderman, C. M., Gorovoy, I. R., Chao, D. L., Bloomer, M. M., Obeid, A., & Stewart, J. M. (2018). Cryptococcal choroiditis in advanced AIDS with clinicopathologic correlation. American Journal of Ophthalmology Case Reports10, 51-54.
  13. Govender, P., Hansraj, R., Naidoo, K. S., & Visser, L. (2011). Ocular manifestations of HIV/AIDS: A literature review (Part 2). African Vision and Eye Health70(2), 81-88.
  14. Kestelyn, P., Taelman, H., Bogaerts, J., Kagame, A., Aziz, M. A., Batungwanayo, J., et al. (1993). Ophthalmic manifestations of infections with Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome. American Journal of Ophthalmology116(6), 721-727.
  15. Vrabec, T. R. (2004). Posterior segment manifestations of HIV/AIDS. Survey of Ophthalmology49(2), 131-157.
  16. Andreola, C., Ribeiro, M. P., de Carli, C. R., Gouvea, A. L. F., & Curi, A. L. (2006). Multifocal choroiditis in disseminated Cryptococcus neoformans infection. American Journal of Ophthalmology142(2), 346-348.
  17. de Smet, M. D. (1992). Differential diagnosis of retinitis and choroiditis in patients with acquired immunodeficiency syndrome. The American Journal of Medicine92(2), S17-S21.
  18. Henderly, D. E., Liggett, P. E., & Rao, N. A. (1987). Cryptococcal chorioretinitis and endophthalmitis. Retina (Philadelphia, Pa.)7(2), 75-79.
  19. 19.0 19.1 Friese, G., Discher, T., Füssle, R., Schmalreck, A., & Lohmeyer, J. (2001). Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease. Aids15(17), 2344-2345.
  20. 20.0 20.1 Hiss, P. W., Shields, J. A., & Augsburger, J. J. (1988). Solitary retinovitreal abscess as the initial manifestation of cryptococcosis. Ophthalmology95(2), 162-165.
  21. 21.0 21.1 Essman, T. F., Flynn, H. W., Smiddy, W. E., Brod, R. D., Murray, T. G., Davis, J. L., & Rubsamen, P. E. (1997). Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis. Ophthalmic Surgery, Lasers and Imaging Retina28(3), 185-194.
  22. Jabs, D. A., Green, W. R., Fox, R., Polk, B. F., & Bartlett, J. G. (1989). Ocular manifestations of acquired immune deficiency syndrome. Ophthalmology96(7), 1092-1099.