Disseminated keratoconjunctival epitheliopathy in a patient with systemic lupus erythematosus

Conjunctivocorneal involvement in systemic lupus erythematosus (SLE) is quite infrequent.¹,²,³ We report the impression cytological (IC), immunohistochemical (IHC), and transmission electron microscopic (TEM) features of a case with unusual keratoconjunctival epitheliopathy refractory to medical treatment.

Case report

A 76 year old woman was referred with a long history of bilateral foreign body sensation. She had been on topical antibiotics, artificial tears, corticosteroids, hyaluronate, and aciclovir without improvement. At initial examination, biomicroscopy revealed diffuse, translucent, disseminated peripheral corneal intraepithelial coin lesions with a cystic appearance (fig 1A, B), also in the bulbar conjunctiva over the limbus (fig 1C). Fluorescein staining revealed increased permeability with negative staining. Schirmer's test was normal in both eyes. The patient had systemic and dermatological features diagnosed as SLE and had been taking prednisolone 7.5 mg/day for 1 year. Conjunctival cultures were negative for infectious processes. A thorough systemic evaluation for other systemic diseases and serum antibodies for herpes simplex virus (HSV‐1, HSV‐2), varicella zoster virus (VZV), and Epstein‐Barr virus (EBV) were negative.

Figure 1 Biomicroscopic features of ocular surface in a patient with SLE. (A) Fluorescein staining revealed disseminated, coin‐like epithelial lesions predominantly in the peripheral cornea and bulbar conjunctiva at the initial examination. (B) Retroillumination observation revealed intraepithelial cystic appearances of the lesions. (C) The lesions observed in both the cornea and bulbar conjunctiva cross over the limbus with no apparent differences in morphology. (D) Coin lesions changing to a different location over time. (E) The epitheliopathy attained a vortex phenotype following therapeutic contact lens wear.

The patient was managed with non‐preserved artificial tears, topical corticosteroids and therapeutic lenses with temporary resolution, but on recurrence of the lesions these changed their distribution and shape (fig 1D) attaining vortex morphology (fig 1E). IC revealed inflammatory cells over and in between the epitheliae (fig 2A). Haematoxylin and eosin staining also showed conjunctival epithelial thickening, cystic spaces, and numerous mononuclear cells near the basement membrane and in the stroma (fig 2B). IHC of the conjunctival limbal biopsy showed positive staining for immunoglobulin (IgG, IgA) or complement (C3 and C4) deposition beneath basal epithelial layers and perivascularly (figs 2C, D). Isotype control specimens did not reveal any staining for all markers (fig 2E). Conjunctival TEM from a coin lesion showed decreased cellular cohesion, necrotic cells, and disorganised basement membrane (fig 2F). The epitheliopathy persisted for the next year without complete resolution to date.

Figure 2 Histopathological features of conjunctival specimens obtained from a patient with SLE. (A) IC revealing inflammatory cells over and in between the epitheliae. Magnification, ×200. (B) Haematoxylin and eosin staining also showed conjunctival epithelial thickening, cystic spaces, and numerous mononuclear cells near the basement membrane and in the stroma. Magnification, ×400. (C) Immunohistochemistry showed IgG depositions beneath basal epithelial layers and perivascularly in the stroma. Epithelial thickening, cystic spaces and numerous mononuclear cells near the basement membrane and in the stroma were also shown. Magnification, ×400. (D) Immunohistochemistry also showed depositions of C3 beneath basal epithelial layers and perivascularly in the stroma. Magnification, ×400. (E) Representative isotype control specimen showing lack of stain for IgG deposition. Magnification, ×400. (F) Conjunctival transmission electron microscopy from a coin lesion site showed decreased cellular cohesion, necrotic cells, and disorganised basement membrane. Magnification, ×2500.

Comment

The unusual epitheliopathy of this patient has several different characteristics including (1) diffuse keratoconjunctival involvement, (2) persistence with migratory changes in shape and localisation, (3) association with conjunctival inflammation without involvement of the anterior chamber or posterior segment, (4) unresponsiveness to conventional medical treatments including topical corticosteroids. While histopathological features accorded in part with previous reports,⁴,⁵ a PubMed review revealed no report describing migrating coin lesions combining to form a vortex keratopathy in SLE. Although corneal staining is common in secondary Sjögren's syndrome,⁶ Schirmer's test was normal in our case. Simultaneous conjunctivocorneal lesions suggested infectious, toxic, or immunological aetiologies including viral infections and Thygeson's superior punctate epithelitis. However, repeated laboratory tests were negative for infectious processes, and topical corticosteroids were not effective. It is also unlikely that viral infection of the epithelium could stay active for many years.

Although the exact pathogenesis is unclear, immunological and inflammatory reactions related to SLE may explain the interesting epitheliopathy. Indeed, IC and biopsies revealed an inflammatory process that may have resulted in weakening of cellular cohesion, increased cellular death, and epithelial turnover manifesting with epithelial thickening, cystic spaces corresponding to necrotic cells or areas of increased cellular exfoliation viewed as coin lesions. TEM showed decreased intercellular cohesion and disorganisation of basement membrane, which in part may be responsible for the epitheliopathy. In summary, we reported new clinical conjunctivocorneal features of an unusual disseminated epitheliopathy in SLE which was associated with histopathological evidence of inflammatory and immunological reactions.