Hemophagocytic lymphohistiocytosis (HLH) is a high-mortality primary immunologic or genetic disorder that rarely presents with ocular symptoms. This is a case report of a 30-year-old Asian female with quiescent HLH in whom retinal lesions were identified during the third trimester of pregnancy. Multimodal imaging, including the first use of optical coherence tomography angiography (OCTA) in HLH, was used to characterize these lesions. OCTA was useful for distinguishing chronic ocular HLH from other uveitic syndromes affecting the retina.
[Ophthalmic Surg Lasers Imaging Retina. 2019;50:653–655.]
Hemophagocytic lymphohistiocytosis (HLH) is a high-mortality disorder of hyperactive macrophages and lymphocytes with either a primary genetic etiology or a reactive etiology secondary to malignancy or infection.1 HLH with concurrent ocular symptoms is very rare. Herein, we present an especially unusual case of a woman with retinal lesions presumed secondary to HLH who underwent a chemotherapy induction protocol and subsequently complained of blurry vision during pregnancy. To our knowledge, there are no prior reports of spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) being used to characterize retinal lesions from HLH.
A 30-year-old Asian female presented to our hospital with fever, scleral icterus, diffuse anasarca, and numerous skin lesions. She reported several months of recurring fevers that were unsuccessfully treated with faith healing in the Philippines. Labs were notable for pancytopenia, disseminated intravascular coagulation, and transaminitis with a negative infectious and autoimmune workup. She was diagnosed with HLH based on previously established criteria.1 Two months after completing a chemotherapy protocol with dexamethasone and etoposide to induce remission of HLH, the patient had an unplanned pregnancy. At 33 weeks and 3 days gestational age, several retinal lesions less than 1 disc diameter in size were identified in each eye using non-mydriatic SD-OCT and OCTA (Figure 1). The patient reported blurry vision gradually developing in her right eye starting 4 months prior. Dilated eye exam was deferred given her high-risk pregnancy status and stability of visual symptoms. Four days later, labor was induced due to premature, preterm rupture of membranes and the patient delivered a 2,400-gram male via normal spontaneous vaginal delivery. The remainder of the hospital course was unremarkable. The patient returned to clinic for follow-up 2 months after giving birth for a dilated exam and fluorescein angiography (Figure 1). The retinal lesions remained unchanged.
Imaging studies of the right eye. Red dashed circles all correspond to the same lesion in the posterior pole. (A) Optos shows yellow/grey hyperpigmented lesions less than 1 disc diameter in size. (B) Spectral-domain optical coherence tomography (OCT) of the largest corresponding lesion shows outer retinal atrophy, severe ellipsoid disruption, and dropout of the outer retinal layers deep into the choroid. (C–E) OCT angiography reveals mild hypoperfusion associated with the yellow/grey lesions in the superficial vascular plexus, intermediate capillary plexus, and the deep capillary plexus, respectively. (F) In the choriocapillaris, diffuse hypoperfusion is noted extending well beyond the borders of the lesion. (G) Fundus autofluorescence reveals hypoattenuation of signal overlying the lesions. (H) Early phase fluorescein angiography (FA) reveals hypofluorescence of the lesions. (I) Late phase FA reveals staining.
Given the relatively late age of onset, this patient likely had an acquired secondary form of HLH classically caused by immunologic activation after an unknown viral infection.1 Blurry vision is the most common ophthalmic complaint from adult patients with HLH (Table 1).2–6 Although the patient did not complain of visual symptoms during her active HLH episode, this is likely because she presented with devastating multi-organ dysfunction and subsequent altered mental status.
Reported Cases of Adult-Onset Hemophagocytic Lymphohistiocytosis With Ocular Symptoms
There are only four prior case reports of eye exams in adults with ocular HLH. They were described presenting as Vogt-Koyanagi-Harada, unilateral panuveitis, acute posterior multifocal placoid pigment epitheliopathy, and bilateral serous pigment epithelial detachments (Table 1).2–6 A separate case series describing postmortem ocular pathology in three patients found choroidal infiltrates with macrophages and rare lymphocytes suggestive of hemophagocytosis.5 Our case resembles punctate inner chorioretinopathy. SD-OCT demon strated severe ellipsoid zone disruption with dropout of outer retinal layers. OCTA showed choroidal hypoperfusion and confirmed the absence of secondary choroidal neovascularization (Figure 1).
In addition to the rarity of ocular HLH, this case is particularly unique given the patient's pregnancy status and the use of SD-OCT and OCTA to characterize scars resulting from posterior uveitis secondary to HLH (Figure 1). The eye exam, SD-OCT, and OCTA were performed during pregnancy without dilation or dye injection to confirm absence of choroidal neovascularization. This is one of the first reports of using OCTA as an alternative to fluorescein dye in pregnancy, which has a Category C rating and should be used only if clearly indicated.
In conclusion, ocular symptoms secondary to HLH are rare and most commonly manifest as unusual inflammatory syndromes. Multimodal imaging was helpful to characterize and diagnose this patient with eye manifestations of HLH. SD-OCT and OCTA were able to assess the macula during pregnancy without the use of dilating eye drops or fluorescein dye. The clinical overlap with PIC highlights the complexity of immune-mediated uveitis.
- Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–131. https://doi.org/10.1002/pbc.21039 PMID: doi:10.1002/pbc.21039 [CrossRef]
- Lee EW, Mieler WF. Ocular findings in a patient with hemophagocytic syndrome. Arch Ophthalmol. 2006;124(11):1656–1658. https://doi.org/10.1001/archopht.124.11.1656 PMID: doi:10.1001/archopht.124.11.1656 [CrossRef]17102019
- Li X, Ma Y, Tang J, Chen T, Ma X. A Hemophagocytic Lymphohistiocytosis Patient that Presented with Unilateral Panuveitis. Ocul Immunol Inflamm. 2017;25(2):275–277. https://doi.org/10.3109/09273948.2015.1107593 PMID: doi:10.3109/09273948.2015.1107593 [CrossRef]
- Suzuki S, Mizota A, Adachi-Usami E. A case of hemophagocytic syndrome with retinal changes resembling acute posterior multifocal placoid pigment epitheliopathy. Retina. 2002;22(2):219–222. https://doi.org/10.1097/00006982-200204000-00015 PMID: doi:10.1097/00006982-200204000-00015 [CrossRef]11927858
- Vizcaino MA, Eberhart CG, Rodriguez FJ. Hemophagocytic Lymphohistiocytosis in Adults with Intraocular Involvement: Clinicopathologic Features of 3 Cases. Ocul Oncol Pathol. 2017;4(1):1–11. https://doi.org/10.1159/000475551 PMID: doi:10.1159/000475551 [CrossRef]
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Reported Cases of Adult-Onset Hemophagocytic Lymphohistiocytosis With Ocular Symptoms
|First Author, Year, [Ref]||Age||Gender||Ocular Findings||Ocular Symptoms||Survival€|
|Lee, 20162||31||Female||Resembled Vogt-Koyonagi-Harada disease: Multiple bilateral serous pigment epithelial detachments with macular edema. Corresponding early phase pinpoint leakage with late staining at the level of the pigment epithelium.||Blurry vision||7 months|
|Li, 20163||53||Male||Unilateral panuevitis and serous pigment epithelial detachments with macular edema.||Blurry vision||1 month|
|Suzuki, 20024||55||Male||Resembled acute posterior multifocal placoid pigment epitheliopathy: Bilateral dotlike hemorrhages and cotton-wool spots around optic disc. White placoid lesions associated with vascular arcades with early phase hypofluorescence and late phase hyperfluorescence. Some attenuation of retinal vessels.||None reported||Patient death not reported|
|Yao, 20126||51||Male||Unilateral progressing to bilateral multiple serous pigment epithelial detachments with macular edema and scattered hemorrhages. Early phase pinpoint leakage with late staining at the level of the pigment epithelium.||Blurry vision||<1 month|
|Current reported case||30||Female||Resembles punctate inner choroidopathy: Scattered yellow/gray hyperpigmented lesions <1 disc diameter in size. Early phase hypoperfusion with late phase staining.||Blurry vision||Currently alive (22 months to date)|