Mooren's ulcer of the cornea after immune reconstitution

Abstract

Mooren's ulcer is an uncommon idiopathic form of peripheral ulcerative keratitis (PUK), which, to our knowledge, has never been described in a patient with HIV infection. Although the pathogenesis is poorly understood, Mooren's ulcer is currently considered a T-cell-mediated auto-immune phenomenon [1]. Sustained T-cell-dependent immune activation of inflammatory cells in the peripheral cornea occurs in Mooren's ulceration [1]. Immune reconstitution inflammatory syndrome (IRIS) encompasses a group of disorders that follow after immune recovery on highly active antiretroviral therapy (HAART). Auto-immune diseases occurring as part of IRIS have been described previously [2–5]. We describe the first case of an HIV-positive patient who developed bilateral Mooren's ulcers soon after commencement of HAART. A 40-year-old man presented to our eye clinic with a 3-month history of bilateral red, painful eyes. The onset was insidious and he had no history of previous ocular injuries or surgery. He was known with HIV infection and had commenced treatment with efavirenz, lamivudine and tenofovir 4 months prior to presentation when his CD4+ cell count nadir was 187 cells/μl. Systemic examination revealed no abnormalities. On ocular examination, he had normal visual acuity and mild conjunctival injection in both eyes. His right eye revealed a grey white, crescent-shaped peripheral corneal ulcer concentric to the corneoscleral junction extending from 6 o’clock to 9 o’clock. The edge closest to the pupil was undermined and de-epithelialized (Fig. 1a). A lesion with similar morphology was noted in his left eye, extending from 7 o’clock to 10 o’clock, with the base of the ulcer showing early vascularization (Fig. 1b). Because Mooren's ulcer is a diagnosis of exclusion, we performed a number of special investigations to search for a possible systemic cause of this PUK. These included a complete blood count with differential erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, syphilis serology, hepatitis C serology, chest radiograph examination, as well as sputum cultures for tuberculosis and stool microscopy for hookworms. None of these investigations produced a positive result. In addition, his CD4+ cell count was 503 cells/μl and his CD8+ cell count was 1668 cells/μl, with a CD4+/CD8+ ratio of 0.30. The serum HIV viral load was undetectable.Fig. 1: Ocular examination.(a) The right eye demonstrates a gutter-like ulceration of the peripheral cornea with undermining of the central edge of the lesion. (b) The left eye demonstrates a similar peripheral ulcerating process with significant thinning of the cornea and undermining of the central wound edge.Treatment was commenced with hourly 0.1% dexamethasone drops and 6-hourly hydroxypropyl methylcellulose drops to both eyes. The patient experienced rapid resolution of symptoms and signs in both eyes and has remained asymptomatic on low-dose topical corticosteroid therapy for 6 months. An extensive literature search was performed and we were unable to find any description of Mooren's ulcer in an HIV-infected patient. A possible explanation for this is the fact that CD4+ cells play an important role in the pathogenesis of Mooren's ulcer and patients with low CD4+ cell counts are therefore unable to develop this condition unless HAART-induced immune reconstitution takes place. Other auto-immune diseases such as Graves’ disease, sarcoidosis, Guillain–Barré syndrome and Alopecia Universalis have all previously been described to occur as an IRIS [2–5]. It is therefore likely that our patient, who had experienced immune recovery with an increase in CD4+ cell count from 187 to 503 cells/μl falls into this category of IRIS-related auto-immune disorders. Another interesting facet of this case is the finding of a high CD8+ cell count and a low serum CD4+/CD8+ ratio in our patient. This is contrary to previous findings which showed both serological and histopathological evidence of high CD4+/CD8+ ratios in cases of Mooren's ulcer [1,6,7]. Further investigation is required to determine whether this is a consistent and significant finding in similar cases. The study not only describes the first case of Mooren's ulcer in an HIV-positive patient, but also adds Mooren's ulcer to the ever-increasing list of autoimmune phenomena occurring as part of HAART-induced IRIS. Acknowledgements Conflicts of interest There are no conflicts of interest. Source of funding: No grant or funding process was involved in the present study.