Hemophagocytic Lymphohistiocytosis in Adults with Intraocular Involvement: Clinicopathologic Features of 3 Cases

Abstract

Background/Aims: Hemophagocytic lymphohistiocytosis (HLH) is an infrequent inflammatory multisystemic syndrome. Only rare cases with ophthalmic involvement describing their pathologic features have been previously reported. Methods: We report 3 cases of adult-onset HLH with bilateral ocular involvement and describe their clinicopathologic features. Results: Three adult males - 2 with a history of viral infection - developed persistent fever, fatigue, bone marrow abnormalities, and irreversible multiorgan failure. Visual impairment was also documented in 2 cases. Complete autopsies were performed. Ophthalmic pathology demonstrated a bilateral histiocytic infiltrate with scant lymphocytes affecting the uvea. Focal extension to the retina, optic nerve, and trabecular meshwork were also identified, as well as hemophagocytosis in 1 case. Macrophages showed strong immunoreactivity for CD163 antibody and lacked BRAF p.V600E mutant protein. Conclusion: HLH is an unusual disorder associated with several systemic conditions. Histologic features in the eye are poorly documented, with prior reports restricted to children. Our 3 adult cases are reported using updated criteria and, despite the difference in age, show changes similar to those observed in the pediatric population.

Hemophagocytic Lymphohistiocytosis After Dengue Fever and Its Ocular Features

“…Visual acuity was 20/20 OU, anterior-segment examination was normal, and fundus examination revealed vitritis, 1+ vitreous haze, nerve fiber layer infarcts, retinal hemorrhages, and whitish outer retinal lesions in the inferior periphery in both eyes (Figure, A). Optical coherence tomography over the whitish lesions revealed subretinal pigment epithelium deposits, which could be the lymphohistiocytic aggregates seen in HLH as described in the literature (Figure, B) . At a recent follow-up visit, visual acuity was stable with resolving fundus lesions.…”

Two Cases of Hemophagocytic Lymphohistiocytosis Associated with Disseminated Histoplasmosis Presented with Transient Pancytopenia

“…Secondary or acquired HLH may result from a malignant, infectious, or autoimmune stimulus in the absence of an identifiable underlying genetic trigger [ 7 ]. Hemophagocytic lymphohistiocytosis is characterized by uncontrolled activation of NK/CTL that provokes the release of large amounts of proinflammatory cytokines such as IFN- γ , TNF- α , GM-CSF, M-CSF, and IL-2, resulting in hyperstimulation and systemic infiltration by macrophages, which in turn phagocytose blood cells, mostly red blood cell precursors, and secrete other cytokines responsible for myelosuppression, endothelial damage with coagulopathy, tissue injury, and NK/CTL incessant activation (IL-1, IL-6, and TNF- α ) [ 6 , 8 ]. The cytokine storm causes vascular endothelium damage and myelosuppression, which, in turn, induces fatal bleeding, infection, and multiorgan failure [ 6 ].…”

Secondary Hemophagocytic Lymphohistiocytosis Causing Hemorrhagic Encephalomyelitis and Spinal Subarachnoid Hemorrhage: A Case Report

“…5 Intracranial SAH has been previously reported in HLH, as a late effect following treatment, or a finding noted on autopsy. 6,7 While one such case was aneurysmal, a mechanism for SAH was not proposed in most reports. 6 Our patient may represent the first reported adult case of hemorrhagic encephalomyelitis with spinal SAH in HLH, although without CNS tissue biopsy we lack 100% diagnostic certainty.…”