Ocular cicatricial pemphigoid: is there an association with autoimmune diseases?

PURPOSE: To assess the prevalence of autoimmune diseases (ADs) associated with ocular cicatricial pemphigoid (OCP) and analyze clinical, laboratory, and treatment associations between these entities. METHODS: A multicentre cross-sectional study of patients with an OCP diagnosis. The population was divided into two groups according to their association with other ADs or not. Clinical, laboratory and treatment variables were described and compared between groups. A multivariable logistic regression analysis was performed to identify variables that could suggest the association between OCP and ADs. RESULTS: Eighty-eight patients were recruited, with a mean age at diagnosis of 64.3 years (SD 11.9). Biopsy was performed in 86.8% of the patients. There was a median delay of 2 years from the onset of symptoms to diagnosis. Extraocular involvement was evidenced in 11.5%. The group associated with ADs included 24 patients (27.3%). The most prevalent diagnosis was Sjögren´s syndrome. Hypergammaglobulinemia was associated with ADs and OCP, adjusted for age, sex, smoking, skin and mucosal involvement, and erythrocyte sedimentation rate (OR 8.7; 95%CI 1.6-46.8; p = 0.012). CONCLUSIONS: Due to OCP's autoimmune nature, it could coexist with other ADs. This study observed that more than a quarter of the population presented with this association, and hypergammaglobulinemia could suggest it.

[Refractory esophageal stricture of esophageal mucous membrane pemphigoid after allogeneic hematopoietic stem cell transplantation].

Haploidentical allogeneic hematopoietic stem cell transplantation from her brother was performed on a 41-year-old lady with no prior history of pemphigoid to treat recurrent AML. On day 59 following transplantation, she experienced esophageal stenosis. During immunosuppressive therapy for graft vs. host disease, this condition was controlled with periodic esophageal dilatation (GVHD). Her esophageal stricture, which required periodic dilatation, grew worse after she stopped immunosuppressive therapy because of recurrent AML. The esophageal mucosa was easily hemorrhagic and desquamative. Histologic analysis revealed that the squamous cell layers had been divided. Indirect immunofluorescence was negative for IgG and positive for IgA on the epidermal layers, while direct immunofluorescence showed a linear deposition of IgG on the basement membrane zone. It was determined through immunoblotting utilizing recombinant protein of BP180 C-terminal domain that both IgG and IgA antibodies were present, supporting the diagnosis of mucous membrane pemphigoid with anti-BP180. After allogeneic transplantation, basal epidermal cell destruction by GVHD may result in autoimmune blistering disorders, which expose basement membrane proteins and antigen presentation. A similar mechanism could apply to our situation. For rare GVHD cases, a thorough histological diagnosis is required.

Direct Injection of 5-Fluorouracil Improves Outcomes in Cicatrizing Conjunctival Disorders Secondary to Systemic Disease.

PURPOSE: Conjunctival cicatrizing conditions are vision threatening, with poor outcomes despite aggressive systemic therapy. This study tests the utility of serial injections of 5-fluorouracil (5-FU) into the fornices to treat conjunctival scarring in patients with ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis. METHODS: Retrospective cohort study. Fisher exact test and multivariable logistic regression analyses were used to compare clinical outcomes of patients who were administered 5-FU injections versus patients who were not injected. Model fit was examined for multivariable regression. RESULTS: One hundred twelve eyes (56 patients) met the inclusion criteria. Thirty-eight eyes (34%) had Stevens-Johnson syndrome/toxic epidermal necrolysis, and 74 eyes (66%) were diagnosed with ocular cicatricial pemphigoid. Twenty-five eyes received ≥1 injection of 5-FU. Sixteen eyes received 1-4 injections, while 9 received ≥5. Median follow-up until last encounter was 18 months. Analysis of each disease entity alone and in combination revealed that 5-FU injections were associated with improvement in final visual acuity, corneal scarring, trichiasis, need for/number of mucous membrane graft surgeries, and severity of symblephara. CONCLUSIONS: Serial injection of 5-FU in the affected fornices is a promising treatment for severe vision-threatening conjunctival scarring from ocular cicatricial pemphigoid and Stevens-Johnson syndrome/toxic epidermal necrolysis. Given the excellent safety profile of 5-FU around the eye, the solid biologic foundation for using 5-FU in this setting, and the severe risk of vision loss from these disorders, the authors suggest that serial 5-FU injections be adopted as therapy for conjunctival scarring from ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis despite the limitations of this retrospective study.

Report of two cases of mucous membrane pemphigoid with frontal fibrosing alopecia: a variant of lichen planus pemphigoides or an incidental finding?

Lichen planus pemphigoides (LPP) is a rare autoimmune subepidermal blistering disease characterized by the coexistence of both lichen planus and either bullous pemphigoid or mucous membrane pemphigoid (MMP) features. Frontal fibrosing alopecia (FFA) is a scarring alopecia, generally considered a form of lichen planopilaris. We report two patients with concomitant FFA and MPP. Patient 1 was a 73-year-old woman with the clinical and histological diagnosis of oral lichen planus. In addition, she presented alopecic plaques in the parietal area with blisters, immunohistologically compatible with Brunsting-Perry pemphigoid, a variant of MMP. During follow-up, the patient also developed FFA. Patient 2 was a 70-year-old woman with a history of ocular inflammation and desquamative gingivitis, who was diagnosed with MMP based on a conjunctival biopsy. She also had clinical features of FFA. ELISA and frontal biopsy confirmed the diagnoses of MMP and FFA. In conclusion, we report two patients with MMP associated with FFA, and discuss whether this association is a new variant of LPP or an incidental finding.

Mucous membrane pemphigoid-otorhinolaryngological manifestations: a retrospective cohort study.

INTRODUCTION: Mucous membrane pemphigoid (MMP) refers to a heterogeneous group of rare, chronic, inflammatory, mucous membrane-dominated, sub-epithelial blistering diseases that manifest with a varying constellation of oral, ocular, cutaneous, genital, nasopharyngeal, esophageal, and laryngeal lesions. MMP can progress to scarring in affected areas, which may lead to devastating complications including ocular involvement leading to blindness as well as laryngeal involvement leading to airway obstruction. MATERIALS AND METHODS: A retrospective chart review was conducted for patients that were followed in two tertiary academic centers between 2009 through 2017 for upper aerodigestive tract manifestations of MMP. Patients with significant underlying skin involvement suggestive of bullous pemphigoid as well as MMP with isolated ocular involvement were excluded. RESULTS: Twenty-seven patients were diagnosed with MMP and followed in two tertiary referral medical centers. The most common site of initial presentation was the oral cavity, and all patients had oral cavity involvement at some point. Two-thirds of our patients had complete remission or remission with intermittent relapses disease. Patients with mild to moderate disease showed excellent response to topical steroid treatment. For more severe disease, high-dose prednisone was insufficient, as in most cases relapse occurred at some point of time during tapering down. CONCLUSIONS: MMP is a rare autoimmune disorder that may present with a wide spectrum of head and neck manifestations and, potentially, catastrophic sequelae. This work highlights the experience of two tertiary centers with MMP in an attempt to draw attention to this unusual disorder.

A conjunctival-sparing surgical technique for lower eyelid cicatricial entropion repair in ocular cicatricial pemphigoid.

Purpose: To present five cases of lower eyelid cicatricial entropion secondary to ocular cicatricial pemphigoid (OCP) successfully repaired with a conjunctival-sparing surgical technique.Methods: The records of one surgeon (SKF) were reviewed to identify patients with lower eyelid cicatricial entropion secondary to OCP who underwent repair with a conjunctival-sparing technique between September 1, 2016 and October 18, 2017. The medical records were reviewed and extracted data included: age, gender, past medical history, current medical and OCP status, clinical examination, details of entropion repair surgery, and outcome.Results: Five patients (three female, two male) were included with ages ranging from 44 to 93 years. All had biopsy proven OCP, which was in remission at the time of surgery, and all were currently receiving immunomodulatory medications. All patients were symptomatic from cicatricial entropion secondary to OCP and underwent successful lower eyelid entropion repair with a conjunctival-sparing technique described herein, involving infraciliary rotation with suture fixation of the orbicularis muscle to the tarsus. Other contributing mechanisms of eyelid malposition including horizontal eyelid laxity and orbicularis oculi override were addressed simultaneously with lateral tarsal plication or orbicularis muscle debulking, resulting in 100% anatomic success and relief of symptoms with no cases of OCP reactivation, and with good durability with an average 13.9 months follow up (range 6.5-22 months).Conclusions: Successful repair of lower eyelid cicatricial entropion in immunomodulated patients with OCP can be achieved without disease reactivation using a surgical technique that spares the conjunctiva and lower eyelid retractors.

Mucous membrane pemphigoid-associated paronychia with onychomadesis.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease that is notoriously difficult to treat. Nail involvement in MMP is rare. CASE PRESENTATION: We report on a 58 years old man with severe MMP who presented with onychomadesis. CONCLUSION: To our knowledge, mucous membrane pemphigoid associated paronychia and onychomadesis have not been reported before. We believe it is important for dermatologists to be aware of this entity.

[Pseudopemphigoid Induced by Topical Glaucoma Medications]. / Pseudopemphigoid bei topischer Glaukomtherapie.

Pseudopemphigoid is a chronic disease that causes progressive conjunctival scarring, up to symplepharon formation. Phenotypically, it cannot be distinguished from true mucous membrane pemphigoid with ocular involvement. Possible triggers are ocular surface disorders and/or their therapy. About 50% of all affected patients are glaucoma patients treated with topical antiglaucomatous therapy. Lack of signs of systemic disease, unilateral findings and/or a positive history of glaucoma may be indicative of a pseudopemphigoid. In this review, the two entities will be compared and the diagnostic as well as the therapeutic approach for suspected pseudopemphigoid under topical glaucoma therapy will be presented.

Desquamative gingivitis: Clinical findings and diseases.

Desquamative gingivitis is a clinical finding with several potential etiologies. Among the most common are oral lichen planus, cicatricial pemphigoid, and pemphigus vulgaris, though various other differential diagnoses exist. The presence of desquamative gingivitis often results in poor oral hygiene, which can have downstream consequences, including periodontitis and tooth loss. Though certain mucosal findings may be suggestive of a particular diagnosis, a thorough history, physical examination, and appropriate dermato- and immunopathologic assessment is necessary for narrowing this broad differential diagnosis. This article offers a comprehensive review on the subject, including how to differentiate between the different underlying causes and the best methods for diagnosis (eg, how best to obtain mucosal biopsy specimens). In addition, there is minimal information in the dermatology literature on evaluation of oral hygiene and the consequences of poor oral hygiene not only on disease activity but also overall health. Knowledge on appropriate oral cavity inspection and evaluation of dental hygiene is lacking, and this continuing medical education series discusses methods to evaluate for these consequences so that the dermatologist can be better equipped in managing these patients and recognizing complications early on.

Coexistence of mucous membrane pemphigoid, vitiligo, and hypothyroidism: A second report of a new multiple autoimmune syndrome.

Mucous membrane pemphigoid (MMP) is a rare immunobullous disease affecting the mucous membrane and skin. An association of MMP with other autoimmune disease is uncommon. Multiple autoimmune syndrome (MAS) is a subclass of autoimmune disorders with a coexistence of three or more autoimmune disorder in a single patient. The second report of the association of vitiligo, autoimmune thyroid disease, and MMP shows that this combination can be considered as a new type of MAS, although its mechanism and pathology are unknown.

Oral mucous membrane pemphigoid: A clinical study of 100 low-risk cases.

OBJECTIVE: To analyze the severity of the oral lesions in low-risk oral mucous membrane pemphigoid (OMMP) measured according to the size of the bullous areas and the number of simultaneously affected oral locations. MATERIAL AND METHODS: A total of 100 cases of low-risk OMMP were studied. The symptoms and location of OMMP in the oral cavity were analyzed. The bullous areas were measured, establishing three grades according to the greatest bullous lesion size (grade 1: < 3 cm in size; grade 2: 3-6 cm; and grade 3: > 6 cm). RESULTS: The mean age of the patients was 66.07 ± 13.55 years, with a clear predominance of females (84%). Desquamative gingivitis was the most common presentation (97%). A single oral location was found in 67% of the cases, two in 18% and three in 15%. The most common presentation corresponded to grade 1 (the greatest bullous lesion size < 3 cm; 51.6% of the cases). CONCLUSIONS: Most cases of low-risk OMMP are restricted to a single site in the oral cavity, the gingiva being the most common location-the predominant grade corresponding to the greatest bullous lesion size < 3 cm.

Vegetating erosive cutaneous lesions and pyogenic granuloma in the course of mucous membrane pemphigoid: a case report and review of literature.

Mucous membrane pemphigoid (MMP) is a group of chronic autoimmune sub-epithelial blistering disorders, which mostly affect the oral mucosa and the conjunctiva. MMP is very diverse in terms of both the clinical and immunological features (IgG and IgA autoantibodies may react with different antigens). MMP can be induced by infections and medication, including ophthalmologic medication, which may lead to the development of eye lesions. In contrast, a vegetating variant of MMP is extremely rare. Here, we report an MMP case that demonstrated unusual clinical features, that is, pyogenic granulomas on the conjunctivae and extensive vegetating erosions on the skin of intertriginous regions. All these lesions were considered to be induced by unconventional medication containing arsenic.

Oesophageal involvement in 26 consecutive patients with mucous membrane pemphigoid.

BACKGROUND: Oesophageal involvement of mucous membrane pemphigoid (MMP) has not yet been thoroughly described. OBJECTIVES: To characterize systematically the endoscopic lesions of a series of patients with oesophageal symptoms seen at a referral centre for autoimmune bullous diseases. METHODS: Clinical, endoscopic and immunological findings of consecutively referred patients with MMP with oesophageal involvement, systemic and endoscopic treatments, and follow-up are described. RESULTS: Of 477 consecutive patients with MMP consulting between 2002 and 2012, 26 (5·4%) had symptomatic oesophageal involvement. Dysphagia, observed in 23 (88%) patients, was the most frequent symptom. Oesophageal symptoms could be the first sign of MMP. Patients with oesophageal involvement had a mean of three other involved sites. At initial oesophageal endoscopy, 17 of 26 patients had active lesions (intact bullae, erosions and/or erythema), 15 had stricture(s) and 12 had other cicatricial lesions. Systemic therapy alone achieved oesophageal symptom relief for five patients. Dilatation was combined with systemic therapy for 12 patients and was successful in nine; one perforation occurred. CONCLUSIONS: Symptomatic oesophageal involvement affected 5·4% of patients with MMP. Dermatologists and gastroenterologists should be aware of these mucocutaneous diseases and their oesophageal involvement, as it could lead to earlier diagnosis and better care. Oesophageal dilatation could be a therapeutic option for symptomatic stricture not relieved by optimized systemic therapy alone.

Conjunctival Squamous Cell Neoplasia Associated With Ocular Cicatricial Pemphigoid.

The purpose of this study was to describe a possible causal relationship between ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two middle-aged female patients with already diagnosed OCP were studied in regard to the subsequent onset of conjunctival squamous neoplasia. Their clinical histories, ocular examinations, clinical photographs, and results of biopsies and any ancillary immunofluorescent laboratory evaluation studies were carefully reviewed. One patient had a preinvasive squamous dysplasia and the other an invasive squamous cell carcinoma, both in the unequivocal setting of OCP with bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients had been receiving intensive immunotherapy consisting of some combination of corticosteroids, rituximab, and interferon alpha. Both patients had a positive immunofluorescent study demonstrating immunoreactants at the level of the epithelial basement membrane. Each patient had 2 earlier negative immunofluorescent studies before a third was positive. While rare, there is 1 previous report of an association between OCP and conjunctival squamous neoplasia. The current report provides more data supporting the proposal that this conjunction is more than a random event. Repeat immunofluorescent studies after an initial negative result in a patient with strong clinical signs of OCP are imperative due to the frequency of false negative studies in the context of clinically persuasive disease.

Describing the gingival involvement in a sample of 182 Italian predominantly oral mucous membrane pemphigoid patients: A retrospective series.

BACKGROUND: The oral cavity has been frequently described as the only site of involvement or as the first manifestation of mucous membrane pemphigoid (MMP), being the gingival tissues often involved, but usually this has been effusively detailed in limited case series. This is a retrospective evaluation of the gingival involvement in 182 Italian patients with oral MMP. MATERIAL AND METHODS: The diagnosis of MMP was established by both clinical morphology and direct immunofluorescence finding. Patient information (age, gender, risk factors and medical status) and parameters of manifestation (lesions' distribution, site and type) were detailed. RESULTS: The mean age was 62 years for women (n=137) and 67 years for men (n=45). Patients had several sites of oral involvement; the gingiva was the most common one, affecting 151 patients (82.96%; 119 f - 32 m). Female subjects had more possibilities to develop gingival lesions than male patients (P = 0.005). Sixty-five patients (35.7%; 58 f - 7 m) had pure gingival involvement. Patients with lower gingival involvement statistically had more complaints (P = 0.006). CONCLUSIONS: This report is one of the largest about predominantly oral MMP cases, detailing the very frequent gingival involvement; this could be crucial not only for oral medicine specialists but also for primary dental healthcare personnel and for periodontists.

Long-term rebamipide and diquafosol in two cases of immune-mediated dry eye.

PURPOSE: Two new drugs with mucin-inducing and secretion-promotive effects, rebamipide and diquafosol, were recently approved as topical dry-eye treatments. We report two cases in which the long-term use of mucin-inducing eye drops improved chronic ocular graft-versus-host disease (cGVHD)-related dry eye and ocular cicatricial pemphigoid (OCP)-like disease. CASE REPORTS: Case 1. A 61-year-old woman had cGVHD-related dry eye that resisted traditional medications. Next, we use topical diquafosol in addition to conventional treatments. The patient used diquafosol for 6 months without experiencing any side effects. The symptoms, including dry-eye sensation, ocular pain, foreign body sensation, and photophobia, as well as ocular surface findings including fluorescein and rose bengal scores and tear break-up time (TBUT), partly improved. To further improve the clinical signs and symptoms and decrease chronic inflammation, rebamipide was added to diquafosol. The symptoms, TBUT, and fluorescein and rose bengal scores markedly improved after long-term dual treatment without any side effects for 6 months. Case 2. A 77-year-old woman had OCP-like disease with dry eye. The patient did not improve using the currently available conventional treatments. Next, we use topical rebamipide in addition to conventional treatments. Symptoms including asthenopia, dry-eye sensation, ocular pain, and dull sensation, as well as fluorescein and rose bengal scores and TBUT, partly improved. Specifically, functional visual acuity was markedly improved after commencement of rebamipide. To further improve the clinical signs and symptoms and increase tear film stability and tear film volume, diquafosol was added to rebamipide. The combination of diquafosol and rebamipide worked for the patient. Improvements were seen in several symptoms, fluorescein and rose bengal scores, Schirmer test value, and TBUT without any side effects for 12 months. CONCLUSIONS: Long-term treatment with topical rebamipide and diquafosol can improve dry eye in patients with cGVHD or OCP-like disease.