Identification of ocular cicatricial pemphigoid antibody binding site(s) in human beta4 integrin

PURPOSE: To identify specific site(s) on human ss4 molecule to which sera from ocular cicatricial pemphigoid (OCP) patients bind and to determine its role in the process of blister formation. METHODS: Clone the fragments representing the extracellular and intracellular domain of ss4 molecule from normal human conjunctival mRNA into an expression vector; map the region to which sera from OCP patients bind by Western blot analysis. Determine the role of the immunodominant region in pathogenesis by demonstrating the ability of the rabbit antibody to the immunodominant region to produce separation of basement membrane zone (BMZ) from the basal epithelial layer when incubated with normal human conjunctiva in an in vitro organ culture model. RESULTS: Majority of the OCP sera tested bound to the C-terminal end of the intracellular domain (IC3.0) of the human ss4 integrin. Further subcloning of IC3.0 demonstrated that a smaller fragment extending from 1489 aa to 1572 aa (IC3.4) was responsible for this binding. This region may have multiple antibody binding sites. Antibody to human IC3.0 and IC3.4 produced in rabbit, resulted in BMZ separation, histologically identical with that observed when normal human conjunctiva was cultured with OCP sera in an human conjunctival organ culture model. CONCLUSIONS: These observations identify IC3.4 as the antibody binding site for sera of OCP patients and suggest a possible role for it in blister formation. Indirectly it highlights certain important aspects of the structural and functional dynamics of the biology of the hemidesmosomes and basement membranes.     

Influence of intravenous immunoglobulin therapy on serum levels of anti-beta 4 antibodies in ocular cicatricial pemphigoid. A correlation with disease activity. A preliminary study

PURPOSE: To determine any correlation between activity of ocular cicatricial pemphigoid and titer of anti-beta 4 antibodies, and any effect of intravenous immunoglobulin (IVIg) therapy on serum levels of anti-beta 4 antibodies followed over a 12 month period, using the specific immunoblot assay (IBA). PATIENTS AND METHODS: Eight patients diagnosed with OCP and treated with IVIg as monotherapy were included in the study. Each patient was treated with at least two immunosuppressive agents prior to the institution of IVIg. The presence of anti-beta 4 antibodies in the patients' sera was detected by IBA using bovine gingival lysate (BGL) or tumor cell line lysate (TCL) as substrates. The activity of OCP was graded based on the conjunctival injection using a scale of zero to four in increments of 0.5 at monthly intervals. To determine the correlation between serum levels of circulating autoantibody and the patients' conjunctival disease activity, the titer of anti-beta 4 antibodies was determined at monthly intervals during the course of IVIg therapy. Blood samples were drawn prior to administration of IVIg infusion. The titer was determined by IBA, using serial dilutions of the patients' sera. The highest dilution at which the binding was visible was considered the titer. The dose of IVIg administered was approximately 2-3 g/kg/cycle. The infusion cycles were initially given at monthly intervals, approximately 70 grams daily over four hours for three consecutive days. As clinical improvement was observed, the interval between the cycles was increased, but the dose of IVIg remained the same for each cycle. To study whether the IVIg has an effect on other antibodies, monthly serum levels of antibodies to tetanus toxoid were measured by ELISA. RESULTS: We observed a continuous decrease in mean monthly titer of circulating anti-beta 4 antibodies in the patients' sera during IVIg therapy. A decrease in conjunctival inflammation during the course of IVIg was documented by monthly examination in every patient and paralleled the decrease in titer of anti-beta 4 antibodies. Since the fifth month of IVIg therapy, the mean conjunctival inflammation remained less than 0.5, suggesting a clinical remission of OCP. Titers of antibodies to tetanus toxoid remained unchanged during the study period. CONCLUSIONS: This preliminary study demonstrates a correlation between serum titers of anti-beta 4 antibodies and clinical disease activity in patients with OCP. In addition, the study shows that the use of IVIg is associated with a decrease in the serum titer of anti-beta 4 antibodies.     

Immunophenotypic analysis of the inflammatory infiltrate in ocular cicatricial pemphigoid. Further evidence for a T cell-mediated disease

Ocular cicatricial pemphigoid (OCP) is characterized by the deposition of immunoglobulin and complement along the conjunctival epithelial basement membrane zone (BMZ). In order to further elucidate the cellular populations of the local inflammatory infiltrates, the authors used a panel of monoclonal antibodies in cryostat tissue sections to delineate T cell subsets, B lymphocytes, dendritic cells, and macrophages in six patients with OCP. In comparison with matched controls of the epibulbar conjunctiva, the authors discovered a threefold increase in T lymphocytes within the epithelium and a 20-fold increase within the substantia propria. In contrast with the normal-standing population of conjunctival T lymphocytes, there were activated interleukin 2 receptor (IL-2R)-positive lymphocytes in both the epithelium and the substantia propria. Macrophages were the second most common cells in the substantia propria, accounting for 12.7% of the mononuclear population--a threefold increase over the normal percentage. B cells and plasma cells, normally absent from epibulbar conjunctiva, were the next most prominent populations, constituting 6.9 and 4.6%, respectively, of all mononuclear cells. Dendritic cells which process antigen locally constituted only 1.2% of the mononuclear cell population, but were increased 25-fold over normal controls. By elaborating cytokines that promote fibroplasia, the T cells in OCP may be effector cells along with macrophages and other inflammatory cells in bringing about scarification of the substantia propria, and may furthermore be responsible for an immunoregulatory defect that allows local B lymphocytes to produce autoantibodies to the BMZ.     

Biology of interleukin-5 in ocular cicatricial pemphigoid

BACKGROUND: Ocular cicatricial pemphigoid (OCP) is an autoimmune disease characterized by the presence of autoantibodies, T-cell dysregulation, and abnormal serum levels of cytokines such as interleukin-6, interleukin-1, and tumor necrosis factor-alpha. The purpose of the present study was to investigate levels of interleukin-5 (IL-5) in the sera, eosinophil counts in the peripheral blood, and eosinophil and mast cell counts in the inflamed conjunctivae of patients with active OCP. METHODS: Seven patients diagnosed in the active phase of OCP presenting with chronic cicatrizing conjunctivitis were studied. The serum levels of IL-5 were compared to a group of seven age-, race-, and sex-matched normal human subjects. Eosinophil and mast cell counts in the patients' conjunctivae were compared to those in normal conjunctivae harvested during cataract surgery from seven normal individuals. In addition, eosinophil counts in peripheral blood of patients with active OCP were compared to those in normal individuals. RESULTS: The mean serum level of IL-5 in patients with active OCP was higher (67.23 pg/ml, range 46.33-98.26 pg/ml) than that in normal individuals (12.18 pg/ml, range 7.66-18.86). The difference was statistically significant ( P<0.001). On light microscopy the biopsied conjunctivae stained with hematoxylin and eosin revealed statistically significant differences ( P<0.001) in the mean numbers of eosinophils in the substantia propria between the patients with active OCP (6.8 cells/cm(2), range 4.8-8.2 cells/cm(2)) and normal controls (0.91 cells/cm(2), range 0.4-1.8 cells/cm(2)). The average number of mast cells found in the substantia propria of the biopsied conjunctivae was statistically significantly higher in patients with OCP (13.79 cells/cm(2), range 6.6-19.4) than in normal individuals (4.34 cells/cm(2), range 3.2-7.8; P<0.01). The average number of eosinophils in the peripheral blood of patients with active OCP (6.6x10(7)/l, range 2.9 - 9.3x10(7)/l) was statistically significantly higher ( P<0.01) than in normal controls (2.09x10(7)/l, range 0 - 4.5x10(7)/l). CONCLUSIONS: The results suggest that IL-5 may play an important role in the pathogenesis of OCP.     

Linear IgA bullous disease limited to the eye: a diagnostic dilemma: response to intravenous immunoglobulin therapy

PURPOSE: To report on a diagnostic dilemma and treatment challenge in a patient with chronic cicatrizing conjunctivitis without involvement of skin and other mucous membranes persisting for 6 years and not responding to topical and systemic steroids. DESIGN: Interventional case report. METHODS: We performed direct immunofluorescence of the conjunctiva with fluorescein-conjugated rabbit antihuman antibodies against immunoglobulin A, G, and M, complement 3 component, and fibrinogen. To investigate the presence of circulating antibodies in patient's serum, indirect immunofluorescence using normal human conjunctiva, normal human skin, and monkey esophagus as substrate was done. In addition, we did immunoblot analysis using normal human epidermis as substrate to determine the molecular weight of an antigen. The patient was treated with intravenous immunoglobulin (IVIg). The correlation between the titer of circulating antibodies and the activity of conjunctival inflammation at various intervals during the course of IVIg therapy was demonstrated by immunoblot assay with serial dilutions of the patient's serum. The highest dilution at which the binding was visible was considered the titer. RESULTS: Direct immunofluorescence of the conjunctiva and indirect immunofluorescence with both salt split skin and conjunctiva as substrate disclosed linear deposition of immunoglobulin A (IgA) at the epithelial basement membrane. Immunoblot analysis demonstrated the presence of IgA circulating antibodies in patient's serum directed against a 97kDa protein in human epidermis. A continuous decrease in the titer of these antibodies correlating to improvement of clinical symptoms was observed during IVIg therapy. CONCLUSIONS: Use of a nonconventional diagnostic tool (immunoblot analysis), in addition to conventional immunohistologic studies, might be helpful in establishing the diagnosis of patients with chronic cicatrizing conjunctivitis. On the basis of results of these laboratory tests and clinical presentation, we believe that this patient has linear IgA bullous disease limited to the eye. IVIg therapy decreased the titer of circulating antibodies and induced a remission in this patient.     

Integrins in human corneal epithelium.

Monoclonal antibodies (Mabs) were used for immunohistochemical location of integrin beta- (beta 1,3, and 4) and alpha subunits (alpha 1-6 and alpha v) in the epithelium of both normal and tissue-cultured human cornea. Immunoreaction for the beta 1 integrin subunit was the most intense at the membranes of the basal epithelial cells and weaker at the superficial cell membranes. Anti-beta 4 immunofluorescence appeared in the basal part of the epithelium only, apposing the basement membrane. Both anti-alpha 2 and anti-beta 3 Mabs showed an immunoreaction with distribution similar to the beta 1 integrin subunit. Immunoreaction for the alpha 6 integrin subunit resembled the distribution of the beta 4 subunit. Anti-alpha v showed a faint immunoreaction at the basal and lateral aspects of the basal cell layer. Antisera against beta 3, alpha 1, alpha 4, and alpha 5 integrin subunits showed no specific reactions. The present results suggest that both the normal and tissue-cultured human corneal epithelium contain alpha 2 beta 1, alpha 3 beta 1, and probably also alpha v beta 1 and alpha 6 beta 4 integrin dimers or complexes. We discuss their role as possible receptors for some known ligands.     

Ocular rosacea can mimic trachoma: a case of cicatrizing conjunctivitis

PURPOSE: To report the case of a patient with upper eyelid chronic cicatrizing conjunctivitis and entropion, presumably secondary to ocular rosacea. METHODS: Case report and review of medical literature. RESULTS: The patient has a history of chronic cicatrizing conjunctivitis since 1999. Despite an extensive workup for other possible causes, the patient's known history of acne rosacea is the most substantive explanation for her ocular disease. CONCLUSION: The presence of chronic cicatrizing conjunctivitis affecting mainly the upper eyelids, previously thought to be unique to trachoma, can be associated with ocular rosacea.     

Laminin synthesis and the adhesion characteristics of immortalized human corneal epithelial cells to laminin isoforms

We have studied the synthesis of laminins (Ln) and determined the specific integrins mediating the adhesion of immortalized human corneal epithelial cells to mouse Ln-1, and human Lns-5 and -10. Immunofluorescence microscopy of the cells demonstrated integrin alpha(2), alpha(3), alpha(6), beta(1)and beta(4)subunits, integrins alpha(6)and beta(4)being found in a typical 'leopard-skin' like manner. Immunoprecipitation studies showed that the cells produced alpha 3, beta 3 and gamma 2 chains of Ln-5, but not Lns-1 or -10. In culture Ln-5 was found as small plaques beneath the adhering cells within 1 hr, while in 4 hr widely spread Ln-5 plaques were observed in colocalization with beta(4)integrin subunit. By using a quantitative cell adhesion assay and function-blocking monoclonal antibodies we showed that integrin beta(1)subunit plays a role in mediating corneal epithelial cell adhesion to mouse Ln-1. However, none of the available function-blocking antibodies to integrin alpha-subunits inhibited the adhesion. Integrin alpha(3)beta(1)complex mediated the adhesion of corneal epithelial cells to human Lns-5 and -10. Integrin complex alpha(3)beta(1), as well as laminin alpha(3)chain, was also shown to mediate cell adhesion to newly produced endogenous Ln-5. The present results show that integrin alpha(3)beta(1)complex mediates the adhesion of corneal epithelial cells to Lns-5 and -10, while a yet unknown integrin alpha subunit appears to play a role in the adhesion to Ln-1. The results also show that among corneal basement membrane laminins, Ln-5 is synthetized by epithelial cells while Ln-10 may be a product of keratocytes.     

Mucous membrane pemphigoid with ocular involvement. Part I: Clinical manifestations, pathogenesis and diagnosis

Mucous membrane pemphigoid is a subepidermal blistering autoimmune disorder characterized by predominant involvement of mucous membranes and the presence of autoantibodies against proteins of the dermal-epidermal junction. Lesions most frequently develop in the oral cavity followed, in descending order of frequency, by conjunctiva, nasopharynx, the anogenital region, skin, larynx, and oesophagus. When the lesions are restricted to the conjunctiva, the term ocular pemphigoid may be applied. Cicatrization of the plica is considered a pathognomonic sign in early disease. Recurrent conjunctival inflammation results in subepithelial fibrosis, which leads to fornix shortening, symblepharon formation and subsequent trichiasis and entropion. Even in the absence of conjunctival inflammation, ankyloblepharon may occur. In end stage disease, limbal stem cell deficiency, tear deficiency, and lid malpositions may occur and result in a total keratinization of the ocular surface. The diagnosis is based on clinical findings and the detection of linear deposits of IgG and/or IgA and/or C3 at the dermal-epidermal junction by direct immunofluorescence microscopy of a perilesional biopsy. Autoantibodies (against type XVII and VII collagen, laminin 5 and 6, alpha6beta4 integrin, BP230) have been detected in patient serum. In the case of ocular involvement, preferential reactivity against beta4 integrin has been described.     

The effect of integrin antibodies on the attachment and proliferation of human Tenon's capsule fibroblasts

The integrins are protein heterodimers consisting of noncovalently associated alpha and beta subunits. The adhesive interactions mediated by integrins are necessary for cellular survival and proliferation. In this study we investigated the effects of three different integrin antibodies on the proliferation of human Tenon's capsule fibroblasts in tissue culture. Human Tenon's capsule fibroblasts were cultured into 96 well plates and treated with different concentrations (ranging from 10(-6) to 1 microg ml(-1)) of three different integrin antibodies: human integrin alpha-2 antibody, human integrin alpha-3 antibody and human integrin alpha-5/FnR (fibronectin receptor) antibody. Coulter counter, hexosaminidase, and 3H-thymidine assays were used to determine the inhibitory effects of these integrin antibodies on ocular fibroblasts on days 0 (attachment), 1,3 and 7 following antibody treatment. The concentration of each antibody required to produce a proliferation 50% less than the control (ID50) was calculated for each assay. With respect to attachment, all three antibodies studied displayed some inhibitory activity. All three antibodies also displayed dose-dependent antiproliferative properties, especially at the highest concentration tested after 7 days of exposure. The integrin alpha-2 antibody was the most potent of the inhibitors, followed by the integrin alpha-3 antibody, with the integrin alpha-5 antibody being the least potent antibody tested. In addition, the anti-proliferative activities of the integrin alpha-2 and integrin alpha-3 antibodies increased with increasing incubation time. In conclusion, these integrin antibodies demonstrated some inhibitory effects on the attachment and proliferation of human Tenon's capsule fibroblasts in culture. Further investigation will be required to determine whether integrin antibodies can significantly limit scar formation in vivo without significant toxicity.     

Cicatrizing conjunctivitis associated with paraneoplastic lichen planus

PURPOSE: To report two cases of cicatrizing conjunctivitis associated with paraneoplastic lichen planus. METHODS: Case reports. RESULTS: Two patients were examined because of redness and discomfort in both eyes. A 63-year-old woman with follicular, small-cleaved cell lymphoma had cicatrizing conjunctivitis, stomatitis, vulvitis, and skin lesions. A 25-year-old man with malignant thymoma had cicatrizing conjunctivitis, erosive stomatitis, and penile papules. Histopathologic studies of conjunctiva and skin biopsy specimens in the first patient and labial biopsy specimens in the second revealed lichen planus. CONCLUSION: Paraneoplastic lichen planus is a possible cause of cicatrizing conjunctivitis associated with inflammatory skin and mucous membrane disease.     

Cicatrizing conjunctivitis as an uncommon manifestation of primary Sjögren's syndrome

PurposeTo report occurrence of cicatrizing conjunctivitis as an extraglandular ocular manifestation of primary Sjögren's syndrome (SS).MethodsMedical charts of all patients with SS evaluated at two tertiary ophthalmological referral centers were reviewed. Patients who demonstrated clinical findings of cicatrizing conjunctivitis were included in this review. Patient and disease-related data including ocular complications, therapies and outcomes were collected.ResultsEight patients with a diagnosisis of SS were noted to have cicatrizing conjunctivitis findings over a period of 11 years (between 2009 and 2020). Mean age of patients was 79. All patients had a negative immunoreactant deposition in conjunctival biopsy. Mean follow-up time was 6 years (range, 18–197 months). Three patients had progression of conjunctival scarring. Worsening of vision occurred in 4 patients due to corneal complications, including ulceration, perforation and scarring.ConclusionsSS is an under-recognized etiology of severe progressive cicatrizing conjunctivitis that can lead to ocular morbidity and loss of vision without appropriate management.     

Cicatrizing Conjunctivitis

Cicatrizing conjunctivitis is a clinical sign found mainly in autoimmune disorders affecting the skin and mucus membranes. It may also arise from topical medications, infectious agents, or ionizing, chemical and physical trauma. Rarely, cicatrizing fibrosis may be the harbinger of an occult malignancy. This article reviews the major causes of cicatrizing conjunctivitis in its acute and chronic forms. Clinical symptoms and signs, immu-nopathology, and therapeutic modalities will be emphasized.     

Conjunctival cicatrizing disease presenting with lacrimal obstruction

Patients with conjunctival cicatrizing disease may develop lacrimal obstruction. Little is published on lacrimal obstruction as the presenting feature of otherwise asymptomatic cicatrizing conjunctival disease. The records of all patients presenting between 1994 and 2015 with lacrimal obstruction found to have cicatrizing conjunctival disease were reviewed. Demographic details, clinical findings, disease progression and treatment were analyzed. Thirty-five patients (25 female), aged 43–91 years (median 74, mean 71.3 years) had epiphora and a mild conjunctival cicatrizing process. Nine patients had onset of epiphora after cataract surgery. All except one patient had obstruction of the proximal lacrimal system (punctum and/or canaliculus). In 14 cases, the obstruction was unilateral (both puncta or canaliculi), with one progressing to bilateral obstruction after 11 years. In 19, all 4 puncta or canaliculi were obstructed. Two patients had unilateral nasolacrimal duct obstruction; one developed contralateral canalicular obstruction 2 years later. Conjunctival biopsies were obtained in 19 of 35 cases (54%), and OCP immunohistochemistry was positive in 7/19 (37%). All other biopsies showed chronic inflammation. Two patients had lichen planus. In follow-up (range 0.1–11 years, mean 3.2 years), 2 patients’ conjunctival disease progressed mildly, and 3 progressed moderately, with 2 of these 5 having positive OCP immunohistochemistry, and 1 having lichen planus. Patients with conjunctival cicatrization may present with lacrimal obstruction, usually punctal or canalicular. Conjunctival disease is usually mild and non-progressive, but patients should be monitored for disease progression.     

Prevalence of Chlamydia trachomatis pooled serotypes BDE and FGK in children with chronic follicular conjunctivitis

PURPOSE: To evaluate type-specific antichlamydial antibody IgG in children with chronic follicular conjunctivitis. METHODS: A total of 90 serum samples from juvenile patients with chronic follicular conjunctivitis were collected in the Southeastern Anatolian region of Turkey where trachoma is still endemic. These samples were investigated regarding Chlamydia trachomatis pooled serotype-specific IgG by using the micro-immunofluorescence test. A titer of 1/32 or higher was considered positive. RESULTS: Specific IgG seropositivity to Chlamydia trachomatis titer was found in 33 (36.1%) of the 90 subjects. A higher titer was observed frequently in the serotypes pooled in BDE (21 subjects), CHIJ (10 subjects), and FGK (2 subjects), respectively. CONCLUSIONS: The presence of antichlamydial antibodies in blood should always be interpreted in accordance with the history of the patient, the clinical picture, and the course of the disease. In the diagnosis of Chlamydia trachomatis infections in a patient with chronic follicular conjunctivitis, not only genus-specific antibodies but also the presence of the subspeciespecific antibodies should be investigated.     

Linear IgA disease

PURPOSE: A case of linear IgA disease is reported to alert ophthalmologists and physicians to this unusual cause of chronic cicatrizing conjunctivitis. METHODS: Clinical records of a patient suffering from linear IgA disease were reviewed. RESULTS: A 65-year-old woman with a complicated medical history experienced rapidly progressive chronic cicatrizing conjunctivitis leading to corneal perforation. Undiagnosed gingivitis and palatal ulceration had been present for 5 years prior to the onset of ocular symptoms and vitamin C deficiency had followed the consequent dietary restrictions. A diagnosis of linear IgA disease was made on conjunctival biopsy, which demonstrated linear deposits of IgA along the epithelial basement membrane. The perforation was managed successfully with a conjunctival pediculate flap. Control of the inflammation was achieved with systemic prednisolone and cyclophosphamide but at the expense of serious systemic side-effects. CONCLUSIONS: Linear IgA disease causes progressive conjunctival cicatrization in many affected individuals.Although dapsone generally controls the inflammation, heavier systemic immunosuppression was required in this case. Involvement of skin or other mucosal surfaces may become symptomatic before the conjunctivitis, and physicians must be educated to refer patients for ophthalmological review on diagnosis. Conversely, ophthalmologists encountering ocular linear IgA disease should be aware of the possibility of other mucosal involvement requiring physician intervention.     

Linear IgA disease

Purpose: A case of linear IgA disease is reported to alert ophthalmologists and physicians to this unusual cause of chronic cicatrizing conjunctivitis. Methods: Clinical records of a patient suffering from linear IgA disease were reviewed. Results: A 65-year-old woman with a complicated medical history experienced rapidly progressive chronic cicatrizing conjunctivitis leading to corneal perforation. Undiagnosed gingivitis and palatal ulceration had been present for 5 years prior to the onset of ocular symptoms and vitamin C deficiency had followed the consequent dietary restrictions. A diagnosis of linear IgA disease was made on conjunctival biopsy, which demonstrated linear deposits of IgA along the epithelial basement membrane. The perforation was managed successfully with a conjunctival pediculate flap. Control of the inflammation was achieved with systemic prednisolone and cyclophosphamide but at the expense of serious systemic side-effects. Conclusions: Linear IgA disease causes progressive conjunctival cicatrization in many affected individuals. Although dapsone generally controls the inflammation, heavier systemic immunosuppression was required in this case. Involvement of skin or other mucosal surfaces may become symptomatic before the conjunctivitis, and physicians must be educated to refer patients for ophthalmological review on diagnosis. Conversely, ophthalmologists encountering ocular linear IgA disease should be aware of the possibility of other mucosal involvement requiring physician intervention.     

Mucous membrane pemphigoid and pseudopemphigoid

PURPOSE: To describe the clinical characteristics of patients with mucous membrane pemphigoid (MMP) and pseudopemphigoid. DESIGN: Retrospective cohort study. PARTICIPANTS: Two hundred eighty consecutive patients referred for the evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001. METHODS: Information on patients presenting for evaluation of possible MMP was entered prospectively into a database, which was supplemented by a retrospective chart review. Mucous membrane pemphigoid was diagnosed in patients with a compatible clinical picture by the linear deposition of antibodies to the basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous membrane biopsy specimen or by the presence of circulating autoantibodies to epithelial BMZ. MAIN OUTCOME MEASURES: Demographic and clinical characteristics of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with extraocular MMP without ocular disease. RESULTS: Among patients with ocular MMP, extraocular disease was common (82.4% of patients). The risk of ocular involvement among patients with MMP seen without ocular disease was approximately 5% per year over the first 5 years of follow-up (cumulative risk at 5 years, 22%). Although immunohistologic confirmation of the diagnosis was obtained in all patients, the initial conjunctival biopsy was positive for MMP in 80% of the patients diagnosed with ocular MMP. The most frequent presumed causes of pseudopemphigoid were topical glaucoma medications (28.3%), rosacea blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and conjunctival lichen planus (8.3%). CONCLUSIONS: Patients with ocular MMP typically have other systemic manifestations of MMP. Patients who are initially seen with extraocular MMP without ocular involvement are at risk for ocular disease developing. The clinical characteristics of ocular MMP and pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied tissue is needed to confirm the diagnosis of MMP.     

Chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and fatal Wegener granulomatosis

PURPOSE: To describe a case of chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and Wegener granulomatosis. METHODS: Observational case report. A retrospective study. RESULTS: An 80-year-old man presented with chronic cicatrizing conjunctivitis, peripheral corneal thinning, and Wegener granulomatosis, which were diagnosed by his referring physician based on clinical (recurrent epistaxis, sinus congestion) and histopathologic features of nasal mucosa (granulomatous inflammation, vasculitis). A conjunctival biopsy performed by us disclosed features of active Wegener granulomatosis and ocular cicatricial pemphigoid, which indicate lack of control of both diseases with methotrexate treatment. The patient died of pulmonary complications from Wegener granulomatosis 1 week after our evaluation. CONCLUSION: Ocular cicatricial pemphigoid and Wegener granulomatosis are both potentially fatal autoimmune diseases. Ocular involvement in Wegener granulomatosis indicates poor control of the underlying systemic condition and is a marker for active vasculitis, which indicates the need for treatment with cyclophosphamide.