Ischemic retinal vasculitis has varied etiologies and causes inflammation of the retinal blood vessels, with resultant hypoperfusion secondary to vascular occlusions.1 A positive HLA-B27 result and related diseases may also be associated with retinal vasculitis.2
Alopecia areata is a non-scarring patch of hair loss on the scalp. It is thought to have an autoimmune basis with a predilection to certain HLA haplotypes, including HLA-B27.3 Alopecia areata has also been reported in association with HLA-B27-related diseases.3
We describe a patient who presented with alopecia areata and retinal vasculitis in the setting of a positive HLA-B27 result.
A 12-year-old Indian boy presented with sudden and profound painless vision loss in his right eye. The review of systems was positive for the presence of scalp alopecia areata (Figure 1A) and rashes above the right brow and behind the ears. A right afferent pupillary defect was detected. Best-corrected visual acuity (VA) was hand motion in the right eye and 20/20 in the left eye. The anterior segment examination and intraocular pressure were normal in both eyes.
(A) Scalp alopecia areata on presentation. (B) Improved alopecia following 2 weeks of immunosuppression.
The dilated fundus examination of the right eye (Figure 2A) revealed 1+ vitreous cells, optic nerve edema, diffuse retinal hemorrhages, perivascular infiltrates, and severe macular edema. The nasal fundus was relatively spared. The left eye fundus examination was unremarkable.
(A) Color fundus photograph of the right eye showing extensive retinal hemorrhages and perivascular infiltration. (B) Right eye fundus fluorescein angiography (FFA) showing blocked fluorescence, vessel wall staining, and retinal neovascularization nasal to the optic nerve. (C) Color fundus photograph after 1 month shows significantly fewer retinal hemorrhages and improved perivascular infiltration. (D) Right eye FFA shows resolved perivascular staining and retinal neovascularization.
A fundus fluorescein angiography (FFA) of the right eye (Figure 2B) showed blocked fluorescence due to retinal hemorrhages, vessel wall staining, and the presence of retinal neovascularization. The left eye FFA was normal. Optical coherence tomography (OCT) of the right eye (Figure 3) showed an inner retinal hyperreflectivity and intraretinal fluid.
(A) Right eye optical coherence tomography (OCT) on presentation, showing nerve fiber layer edema and the presence of subretinal fluid. (B) Right eye OCT after 4 months.
An extensive inflammatory, infectious, and hypercoagulable workup, including aqueous humor viral PCR, was negative. However, the HLA-B27 test was unequivocally positive and the erythrocytic sedimentation rate was mildly elevated.
Given the extensive negative workup and positive HLA-B27, a diagnosis of hemorrhagic ischemic retinal vasculitis in the setting of positive HLA-B27 was made. The patient was injected with intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) to treat the retinal neovascularization and macular edema. Oral steroids and methotrexate were also initiated in consultation with a rheumatologist.
At a 4-month follow-up visit, the right eye VA improved to counting-finger vision at 3 feet, the retinal neovascularization resolved, and the macular edema significantly improved (Figures 2C and 2D). Retinal thinning was observed on OCT (Figure 3B). The patient's alopecia areata also showed significant improvement (Figure 1B).
The HLA system is genetically encoded in humans by the major histocompatibility complex. It is found on chromosome 6 and plays a crucial role in immunity and self-recognition in virtually all cells and tissues, with the exception of erythrocytes.
HLA-B27 is an antigen found on the surface of white blood cells that increases susceptibility to autoimmune disorders. Retinal vasculitis is multifactorial in origin, including an association with a positive HLA-B27.1,2 Alopecia areata is an autoimmune disease that presents with non-scarring hair loss from some or all hair-bearing areas of the body, typically the scalp. Its reported prevalence in the United States is in the 0.1% to 0.2% range. Hypotheses regarding the pathogenesis of alopecia areata include a lymphocyte-mediated inflammation that suggests an underlying autoimmune etiology, an association with HLA class II antigen alleles, and contribution from environmental factors. Alopecia areata has also specifically been associated with HLA-B27.4
The age-adjusted prevalence of HLA-B27 in the normal U.S. population is 6.1%,5 whereas it is positive in only 3% of control group in subjects of South Asian origin.6
Rodriguez and Yonca detected retinal vasculitis in 24.1% of their patients with a positive HLA-B27 status.2 Braakenburg and Rothova7 noted that less than 35 cases of HLA-B27 associated retinal vasculitis had been reported in literature. However, these patients were not thoroughly investigated. They also described nine similar cases in which the systemic workup, like with our patient, was negative.7
Our patient presented with alopecia areata and retinal vasculitis, both of which are known to be associated with HLA-B27 positivity and related disorders. However, the combination of these two symptoms and an absence of anterior segment inflammation has not been described.
HLA-B27 antigen is an important and under-recognized cause of retinal vasculitis, which could be severe and sight-threatening. It is imperative to consider presence of the antigen when investigating patients with retinal vasculitis and also crucial to perform a review of symptoms to detect any systemic signs which could be related to HLA-B27, such as alopecia areata in our case.
These patients may require the use of aggressive systemic immunosuppressive therapy to control inflammation and preserve vision.
- Talat L, Lightman S, Tomkins-Netzer O. Ischemic retinal vasculitis and its management. J Ophthalmol. 2014;2014:197675. doi:10.1155/2014/197675 [CrossRef]. Epub 2014 Apr 15.
- Rodriguez A, Yonca A, Pedroza-Seres M, Foster CS. Posterior segment ocular manifestations in patients with HLA- B27-associated uveitis. Ophthalmology. 1994;101(7):1267–1274. doi:10.1016/S0161-6420(94)31179-1 [CrossRef]
- Huang K, Mullangi S, Guo Y, Qureshi AA. Autoimmune, atopic, and mental health comorbid conditions associated with alopecia areata in the United States. JAMA Dermatol. 2013;149(7):789–794. doi:10.1001/jamadermatol.2013.3049 [CrossRef]
- Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: A comprehensive review. Autoimmun Rev. 2015;14(2):81–89. doi:10.1016/j.autrev.2014.10.014 [CrossRef]
- Reveille JD, Hirsch R, Dillon CF, Carroll MD, Weisman MH. The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum. 2012;64(5):1407–1411. doi:10.1002/art.33503 [CrossRef]
- Mishra MN, Bharucha KM. HLA-B27 association with uveitis in an Asian Indian population. Iran J Immunol. 2011;8(2):85–89.
- Braakenburg AM, Rothova A. Characteristics of retinal vasculitis in HLA-B27-positive patients. Ocul Immunol Inflamm. 2014;22(3):197–202. doi:10.3109/09273948.2013.835429 [CrossRef]