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To evaluate the efficacy and safety of oral alendronate sodium therapy once daily in preventing glucocorticoid-induced bone loss in patients with immunobullous skin diseases treated with long-term glucocorticoid therapy.A 12-month randomized, double-blind, placebo-controlled trial.A tertiary referral dermatology center in Singapore.Patients newly diagnosed as having an immunobullous disease and deemed to require at least 6 months of systemic glucocorticoid therapy.The patients were randomized to receive either oral alendronate sodium (10 mg/d) or a matching placebo for 12 months. All patients also received concurrent calcium with vitamin D, 2 tablets daily.Percent change in bone mineral density (BMD) at the lumbar spine and the femoral neck at 12 months.A total of 29 patients (alendronate [n = 15], placebo [n = 14]) were evaluated. The percent change in BMD in the alendronate group was +3.7% and +3.5% at the lumbar spine and the femoral neck, respectively, whereas in the placebo group, it was -1.4% and -0.7% at the lumbar spine and the femoral neck, respectively. The increase in BMD observed in the alendronate group compared with the placebo group was statistically significant at both the lumbar spine (P = .01) and the femoral neck (P = .01). There was also a statistically significant decrease in serum heat-labile alkaline phosphatase levels after 12 months (-32.6%, P.01) in the alendronate group but not in the placebo group. Adverse events were generally minor, and the frequency of occurrence did not differ significantly between both treatment groups (P = .59).There were statistically significant increases in BMD at both the lumbar spine (P = .01) and the femoral neck (P = .01) with alendronate therapy. It is imperative to use bisphophonate therapy in patients with immunobullous disorders who are receiving oral corticosteroids because it largely prevents the morbidity associated with low BMD.

D ESQUAMATIVE GINGIVITIS CAN RESULT from various pathogenetic factors, including mucous membrane pemphigoid (MMP). Adequate gingival sampling for immunopathologic evaluation is mandatory for the diagnosis of MMP. The gingival mucosal “peeling” biopsy technique (Figure 1) yields sufficient epithelium samples for histologic analysis and direct immunofluorescence (DIF). Hemidesmosomal proteins (BPAG1-2 and 6 4-integrin) are the most common MMP autoantigens, resulting in a “capping hemidesmosomal” linear IgG DIF pattern on the gingival epithelial undersurface (Figure 2). To circumvent false-negative DIF results, related to less common, deeper basement membrane zone autoantigens (laminin5/6 and collagenVII), serologic evaluation for anti–basement membrane zone autoantibodies (eg, indirect immunofluorescence and enzyme-linked immunosorbent assay) should be performed. If the findings of DIF and serologic studies are nondiagnostic and a high index of clinical suspicion for MMP remains, an appropriate mucosal punch or incisional biopsy should be performed. Gingival lesions in patients with MMP may deter clinicians from performing sampling owing to technical difficulty. Mucosal peeling can provide adequate immunopathologic samples for the diagnosis of desquamative gingivitis– associated MMP.

Background Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid, is a serious, autoimmune, blistering disorder that can result in blindness and other complications as a result of scarring of the mucous membranes. Effective treatment modalities are often toxic. Herein, we describe a novel therapeutic approach that is based on 2 reports in the literature of the successful use of etanercept to treat MMP. Observations Three patients with MMP were treated with subcutaneous injections of 25 mg of etanercept twice weekly. All 3 patients had oral mucosal involvement, and 1 had severe, recalcitrant, ocular disease. Oral mucosal disease improved in all 3 patients. The patient with ocular involvement experienced stabilization of progression. Conclusions Effective treatment modalities for MMP are often toxic. Etanercept may be an effective treatment option for MMP of the oral and ocular mucous membranes. This therapy should be considered as an alternative treatment option for patients who would require other aggressive systemic treatments, such as cyclophosphamide, corticosteroids, azathioprine sodium, and intravenous immunoglobulin.

Our patient was diagnosed with cicatricial pemphigoid (CP) in 2001. She demonstrated classic clinical findings and underwent biopsies that supported this diagnosis. She unfortunately experienced severe CP involving both of her eyes, oral mucosa, pharyngeal mucosa, and esophagus. Her left eye was seriously affected early in the course of her disease. She experienced significant scarring of the cornea of her left eye as well as of both its upper and lower eyelids, resulting in symblepharon and complete blindness of this eye. She has also endured considerable disease in her right eye and has undergone multiple corneal transplants of this eye (in March 2001, September 2004, January 2005, and April 2005). The most recent corneal transplant in April 2005 was performed emergently for a ruptured corneal ulcer. Our dermatology team was consulted during the patient’s hospitalization for this event. At our initial encounter with the patient, she had complete blindness of her left eye and had recently undergone emergent corneal transplant surgery on her right eye. The right eye was sutured closed and bandaged. On examination, we observed multiple erosions of her soft palate and buccal mucosa (Figure 1). She reported difficulty eating for the past several years. This difficulty had progressed to the point where she could tolerate only soft, bland foods, and her pain significantly affected her oral intake and nutrition. Our patient had previously received multiple therapies to treat her CP, including prednisone, cyclophosphamide, and dapsone. She had received one 5-day course of intravenous immunoglobulin; however, she had no response to this treatment and was also felt to be a poor candidate for it given her risk of congestive heart failure. Her comorbid medical problems included diabetes mellitus, coronary artery disease requiring stent placement, and high blood pressure. None of the treatments for her CP resulted in substantial improvement, and her disease continued to progress.

Objective To develop a practical technique to distinguish autoimmune subepidermal bullous diseases. Design A prospective study. Setting Academic referral center—the Department of Dermatology, Medical University of Warsaw. Patients Forty-two patients fulfilling clinical, immunological, and/or immunoelectron microscopic criteria for bullous pemphigoid (n = 31), mucous membrane pemphigoid (n = 6), or epidermolysis bullosa acquisita (n = 5), diagnosed as having disease and treated from January 1, 1997, to December 31, 2002. Main Outcome Measures We applied laser scanning confocal microscopy to determine the localization of in vivo–bound IgG at the basement membrane zone in biopsy specimens taken from patients' skin to compare the localization of basement membrane zone markers: antibody against β 4 integrin, antibody against laminin 5, and antibody against type IV collagen. In vivo–bound IgG was visualized by labeling with fluorescein isothiocyanate–conjugated anti–human IgG antibody, whereas basement membrane zone markers were labeled with anti–mouse Cy5-conjugated antibodies. Results In patients with bullous pemphigoid, in vivo–bound IgG was localized on the epidermal side of laminin 5 and co-localized with β 4 integrin. In patients with mucous membrane pemphigoid, IgG was in vivo bound to the dermal-epidermal junction between localization of laminin 5 and type IV collagen. In patients with epidermolysis bullosa acquisita, in vivo–bound IgG was present on the dermal side of type IV collagen. Conclusions Laser scanning confocal microscopy allows precise localization of in vivo–bound IgG in patients' skin and, thus, it is a rapid method for the differentiation of mucous membrane pemphigoid from bullous pemphigoid and epidermolysis bullosa acquisita. This tool is suitable for the routine diagnosis of individual patients and for retrospective studies. This method is of special value in those patients in whom circulating autoantibodies are not detectable.

OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

Objective To identify and critically evaluate evidence from randomized controlled trials for the efficacy of treatments for mucous membrane pemphigoid (MMP)/cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA). Search Strategy Review of MEDLINE from 1966 through March 2000, EMBASE from 1980 through March 2000, and the Cochrane Controlled Trials Register (February 28, 2001) to identify randomized controlled trials for the efficacy of treatments in MMP/CP and EBA. Selection Criteria All randomized controlled trials of therapeutic interventions that included patients with MMP/CP or EBA confirmed by immunofluorescence study findings. All age groups were included. Results We found 2 small randomized controlled trials of MMP/CP, both conducted in patients with severe eye involvement. We were not able to identify a randomized controlled trial of therapeutic interventions in EBA. Conclusions There is evidence from 2 small trials that severe ocular CP responds best to treatment with cyclophosphamide, and mild to moderate disease seems effectively suppressed by treatment with dapsone. No treatment recommendations can be made for EBA because to our knowledge no randomized controlled trials are published. Even though systemic corticosteroids are regarded as the gold standard in the treatment of MMP/CP and EBA, there is poor evidence from the literature that they are the best treatment for these diseases.

Context Mucous membrane pemphigoid has a wide clinical spectrum. The clinical context was to determine whether pemphigoid disease that initiates in the oral cavity progresses to involve other mucosae and to determine the influence of systemic therapy on such progression. Objective To determine the clinical outcomes and disease progression in patients with oral pemphigoid for whom dapsone therapy was impossible. Design Retrospective analysis of a cohort of 20 patients with immunopathologic-proven oral pemphigoid studied between September 1, 1994, and October 31, 2000. Twelve patients received conventional therapy that consisted of a combination of oral prednisone with an immunosuppressive agent. Eight patients in whom such therapy was contraindicated received intravenous immunoglobulin therapy. Patients were followed up for 33 to 62 months (mean follow-up, 47.5 months). Setting Patients were treated in an ambulatory tertiary medical care facility of a university-affiliated hospital. Patients The 20 patients had pemphigoid disease limited to the oral cavity only at the initial clinical presentation and when enrolled in the study. Main Outcome Measures The following variables were compared between the 2 groups of patients: (1) duration of treatment, (2) frequency of relapses, (3) induction of remission, (4) adverse effects of therapy, (5) extra oral involvement, and (6) quality of life. Results Using the aforementioned factors, the group treated with intravenous immunoglobulin had statistically significant shorter treatment duration, fewer relapses, higher remission rate, fewer adverse effects, no extraoral involvement, and a better quality of life compared with the group who received conventional therapy. Conclusions Intravenous immunoglobulin is a safe and effective modality to treat mucous membrane pemphigoid. It seems to be a good option for patients who cannot be treated with dapsone and in whom conventional therapy is contraindicated or results in the development of serious adverse effects. In patients with progressive mucous membrane pemphigoid, intravenous immunoglobulin therapy may arrest disease progression.

Background Antiepiligrin cicatricial pemphigoid (AECP) is a chronic autoimmune subepidermal blistering disease characterized by autoantibodies to laminin 5 and clinical features of cicatricial pemphigoid. Only a few patients with AECP have been described to date. The aim of the present study was to analyze the relative frequency of AECP among patients with the clinical phenotype of cicatricial pemphigoid. Observations Serum from 16 consecutive patients with the clinical phenotype of cicatricial pemphigoid were included in this study. Nine patients had circulating IgG autoantibodies by indirect immunofluorescence on sodium chloride–split skin; patients' IgG bound to the epidermal side (n=2), dermal side (n=5), or both sides (n=2) of this test substrate. Interestingly, all 5 cases with dermal binding immunoprecipitated laminin 5 from extracts and media of cultured keratinocytes, and 4 of these serum samples reacted with the α3 subunit of laminin 5 by immunoblotting. None of the patients with dermal binding of IgG demonstrated autoantibodies to type VII collagen. Conclusion Our data suggest that, among patients with the clinical phenotype of cicatricial pemphigoid, AECP may be more frequent than previously assumed.

Background Cicatricial pemphigoid (CP) is a scarring subepithelial mucocutaneous blistering disease characterized by anti–basement membrane zone autoantibodies. Anti-epiligrin CP is an uncommon variant that has been recently characterized. Severe laryngeal involvement is infrequently observed in all forms of CP and has been documented in only 2 patients with anti-epiligrin CP. Observations We report a case of CP exhibiting extensive laryngeal and ocular involvement. Histological, immunofluorescence, and immunoprecipitation studies confirmed the diagnosis of anti-epiligrin CP. Immunoblotting studies demonstrated the presence of antibodies against the α3 and the γ2 subunit of laminin 5. Conclusion This article expands the diversity of the clinical and immunopathologic features of this newly characterized variant of CP.

• A patient with severe cicatricial pemphigoid demonstrated both in vivo bound and circulating anti-basement membrane zone antibodies of the IgA and IgG classes. Complement component 3 (C3) was also deposited in the basement membrane zone of lesional skin as well as in normal-appearing buccal mucosa of the patient. However, C1q was absent, while granular deposits of two factors of the alternative complement activating pathway, properdin and properdin factor B, were present only in the basement membrane zone of lesional skin, but not in normal buccal mucosa. Deposition of alternative complement pathway reactants in the lesion suggests that complement activation by IgA was associated with lesion development. Western blot analysis of the patient's serum on electrophoresed cultured keratinocyte antigens identified two distinct sets of epidermal antigens. While IgG bound antigens of 230, 205, 140, and 90 kd, the patient's IgA antibodies bound a distinct set of antigens, 180 and 130 kd. The potential pathogenic role of IgA in cicatricial pemphigoid is discussed. (Arch Dermatol.1990;126:1466-1468)

Background: In 1979, Provost described two patients with the clinical features of disseminated cicatricial pemphigoid for the first time. Until now, only four additional cases of disseminated cicatricial pemphigoid have been described. Existence of diagnosis of disseminated cicatricial pemphigoid has been discussed controversially because in four cases investigated by electron microscopy the blister formation was found below the lamina densa, which is indicative of an epidermolysis bullosa acquisita. Observation: A 78-year-old woman is presented with a generalized eruption of blisters leaving behind scars that developed after a 7-year-long history of mild circumscribed recurrent blisters and scarring eruptions that had been diagnosed previously as Brunsting-Perry type of cicatricial pemphigoid. Immunofluorescence antigen mapping disclosed the blister formation above the lamina densa. Electron and immunoelectron microscopy using a preembedding immunogold technique revealed blister formation and antibody binding within the lamina lucida, predominantly below the subbasal dense plate. Conclusions: The clinical features of disseminated blistering followed by scarring, the immunofluorescence antigen mapping, and the electron and immunoelectron microscopic findings in our case for the first time clearly prove the existence of a disseminated cicatricial pemphigoid. (Arch Dermatol. 1995;131:580-585)

Epiligrin is a glycoprotein complex deposited in extracellular matrix by cultured human keratinocytes that serves as the major integrin ligand of these cells. In human skin, epiligrin is found at the interface of the lamina lucida and lamina densa in epidermal basement membrane where it is believed to be associated with anchoring filaments and plays an important role in keratinocyte adhesion.We have identified six patients with a subepithelial bullous disorder of mucous membranes and skin who have IgG anti-basement membrane autoantibodies that immunoprecipitate epiligrin from human keratinocyte extracts and culture media. These patients' IgG autoantibodies also bind epiligrin in human keratinocyte extracellular matrix and epidermal basement membrane as determined by immunofluorescence and immunoelectron microscopy. Studies of 10 patients who are clinically indistinguishable from subjects with anti-epiligrin autoantibodies (ie, cicatricial pemphigoid patients) found that while seven had anti-basement membrane autoantibodies, the latter are directed exclusively against a region of epidermal basement membrane that does not contain epiligrin, are present in low titer (ie,or = 1:10), do not react with keratinocyte extracellular matrix, and do not bind epiligrin (or any other specific antigen) in immunoprecipitation studies of human keratinocyte extracts or media. Antiepiligrin autoantibodies were also not detected in studies of 36 additional patients with bullous diseases or six normal volunteers.Cicatricial pemphigoid is a disease phenotype in which patients' autoantibodies may target different constituents of epidermal basement membrane. Antiepiligrin autoantibodies are a specific immunologic marker for a group of patients with a disease entity that we propose to designate antiepiligrin cicatricial pemphigoid.

Background Mucous membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. In a subset of patients with severe MMP, conventional immunosuppressants are ineffective or contraindicated. Observations Twenty-five patients with severe refractory MMP, including 5 with mucous membrane –dominant epidermolysis bullosa acquisita, received 1 or 2 cycles of rituximab (375 mg/m 2 weekly for 4 weeks). Twenty-one of the patients were receiving concomitant therapy with dapsone and/or sulfasalazine therapy, which was maintained during rituximab cycles. Complete responses in all affected sites (ocular and/or extraocular) were obtained in 17 patients (68%) by a median time of 12 weeks after the first cycle, and 5 additional patients responded completely after a second cycle, yielding an 88% complete response rate. In all but 1 of the 10 patients with ocular lesions, their eyes became noninflammatory within a mean of 10 weeks. Among the 3 patients (12%) who developed severe infectious complications, 2 (8%) died; they had been receiving concomitant conventional immunosuppressants and high-dose corticosteroids and were hypogammaglobulinemic. Treatment with immunosuppressants was discontinued for all other patients, and no other infection was observed. Ten patients experienced relapse after a mean of 4 (range, 1-16) months after achieving complete responses. Conclusions Rituximab appears to have rapid and dramatic efficacy in patients with severe, refractory MMP. The occurrence of severe infections in patients receiving concomitant conventional immunosuppressants supports using rituximab without other immunosuppressants. Controlled prospective studies are warranted to define an optimal treatment protocol.

The full spectrum of bullous diseases associated with underlying cancers remains to be fully defined.We describe a patient with a mixed bullous disease exhibiting combined features of cicatricial pemphigoid and pemphigus and associated with a B-cell lymphoma producing an IgM paraprotein to intercellular antigens in human skin. The patient had the clinical features of cicatricial pemphigoid and the histologic and immunofluorescence abnormalities of both cicatricial pemphigoid and pemphigus. These included oral and cutaneous erosions; ocular scarring; subbasal and acantholytic intraepidermal bullae; and circulating and tissue-fixed basement membrane zone and intercellular antibodies. The antibodies were directed to a 140-kd antigen in dermal extracts of skin split with 1 mol/L of sodium chloride and to antigens with approximate molecular weights of 150, 180, 230, and 285 kd in the dermal extract. In contrast to paraneoplastic pemphigus, the intercellular antibodies did not react to mammalian bladder. The intercellular antibodies were of the IgM class and were associated with the paraprotein produced by the malignant B cells.We believe that this condition represents a novel bullous disease, which we refer to as paraneoplastic mixed bullous disease. This condition illustrates that distinct bullous diseases are associated with paraneoplastic syndromes and that at least one possible mechanism for such eruptions is the production of anti-skin antibodies by malignant B cells.

There is much confusion in the clinical classification of immune-mediated subepithelial blistering diseases of mucous membranes. We conducted a 6-year comprehensive study to better classify this heterogeneous disease group. Indirect immunofluorescence was performed on a salt-split-skin substrate to detect circulating antibasement membrane antibodies (n = 47). Serologic reactivity against cultured keratinocyte antigens was examined by immunoblots (n = 38) and immunoprecipitation (n = 15). The results were correlated with the clinical features and direct immunofluorescence data of the entire patient group (n = 87) without preassignment of clinical diagnoses. chi 2 Statistical analyses compared these results with those of the classic bullous pemphigoid group (n = 36).When compared with the bullous pemphigoid patients, a subset of patients with combined oral mucosal and skin lesions demonstrated marked similarity in direct and indirect immunofluorescence findings and in serologic reactivity to bullous pemphigoid antigens. By contrast, a subset of patients with only ocular lesions exhibited significantly lower in vivo deposits of IgG and C3, higher deposits of fibrin, virtual absence of circulating antibodies, and negative serologic reactivity to bullous pemphigoid antigens.Ocular patients without skin or mouth lesions, in particular those with negative indirect immunofluorescence, should be distinctively classified as ocular cicatricial pemphigoid, a unique clinical and immunopathologic entity. Patients with mucous membrane involvement who also demonstrate skin lesions and antibodies to the root of salt-split-skin substrate should be classified as anti-BP Ag mucosal pemphigoid, even though they may exhibit severe oral and/or ocular diseases. The remaining mucous membrane patients are heterogeneous. Some can be classified on the basis of autoantibodies to other basement membrane determinants, or if serum autoantibody negative, on the basis of clinical features (ie, pure oral mucosal pemphigoid or overlapping mucosal involvement).

The nature of skin antigens defined by antibodies in patients with cicatricial pemphigoid was studied with use of the 1 mol/L of sodium chloride split skin technique and Western immunoblot analysis. Antibodies in the serum samples of three of seven patients with cicatricial pemphigoid reacted to the epidermal side of 1 mol/L of sodium chloride split skin, and antibodies in the serum sample of one patient reacted to the dermal side. With Western immunoblot analysis, three patients had antibodies to antigens in the epidermal extracts of skin. The antibodies reacted in all patients to a 160-kd antigen and in one patient to an additional 230-kd antigen. These two antigens are similar in molecular weight to the 230-kd major bullous pemphigoid antigen and to the 160-kd minor bullous pemphigoid antigen. However, while the basement membrane zone antibodies present in cicatricial pemphigoid were most often directed to the 160-kd antigen, those present in 38 patients with bullous pemphigoid reacted most often (in 34 patients [89%]) to the 230-kd antigen. None of the serum samples reacted to antigens in dermal extracts that contained the epidermolysis bullosa acquisita antigen. These results indicate that the basement zone membrane antibodies present in cicatricial pemphigoid are directed in part to epidermal antigens that are similar in molecular weight to bullous pemphigoid antigens. However, the frequency of reactions to different basement membrane zone antigens differs in the two diseases, which may account for the clinical differences between the two conditions.

• A 56-year-old woman with the typical clinical feature of cicatricial bullous pemphigoid of the Brunsting-Perry type was studied. Histologic examination of a lesional skin biopsy specimen demonstrated a subepidermal blister. Direct immunofluorescence microscopy revealed linear deposits of IgG, IgM, and C3 located on both the roof and the floor of the blister. Immunofluorescence antigen mapping using cryostat sections of a spontaneous blister and antisera against defined basement membrane components localized the bullous pemphigoid antigen and type IV collagen in the roof of the blister. This dermal type of blister formation was confirmed by electron microscopy, which showed the cleavage level below the lamina densa. In direct immunoelectron microscopy, granular deposits of C3 and IgG were found attached to and just beneath the lamina densa in a pattern identical to the distribution of anchoring fibrils. These findings are diagnostic of acquired epidermolysis bullosa, a blistering disease that has much more clinical heterogeneity than previously suggested. ( Arch Dermatol. 1991;127:391-395)

Normal skin was transplanted into a cicatricial plaque in a patient affected with localized, benign pemphigoid of the Brunsting-Perry type. Eight weeks later, the transplanted tissue was removed and found to have IgG at the basement membrane zone on immunofluorescence microscopy. Subepidermal bullae developed at the graft-donor site. Local factors and trauma may be important in the pathogenesis of this variant of cicatricial pemphigoid.

Three patients are described with cicatricial pemphigoid and positive immunofluorescence findings in the basement membrane zone of mucous glands of the pharynx, mouth, and nose. These findings appear to be unique to cicatricial pemphigoid.

Three years after the onset of lupus erythematosus, blisters, erosions, and erythema of the gingivae developed in a 31-year-old man. A diagnosis of cicatricial pemphigoid was established by routine and immunofluorescence microscopy studies. An association between cictricial pemphigoid and other autoimmune disorders seems to be rare. This case demonstrates the importance of performing immunofluorescence microscopy studies, as well as routine histologic assessments, of conditions that resemble desquamative gingivitis.

Benign mucous membrane pemphigoid, in the form of desquamative gingivitis, occurred in a 57-year-old woman. The disease then developed in her 59-year-old husband 16 months later. The clinical manifestations were mild and similar in both cases. Direct immunofluorescence microscopy tests were consistent with the diagnosis. Sequential occurrence of this disease in spouses suggests the possibility that it is transmissible.

Lever (1951, 1953) first clearly differentiated ocular pemphigus, which he renamed benign mucous membrane pemphigoid and, more recently, cicatricial pemphigoid, from pemphigus vulgaris. He pointed out the benign course, the subepidermal position of the bullae, and, most important of all, the tendency for the bullae to form scars on mucosae and skin. Church and I (1953) drew attention to the lesions on mucous membranes other than the conjunctiva and confirmed (1956) Lever's observations that there were 2 types of skin lesions. The most common is a generalized bullous eruption of short duration which is similar to the bullous eruption of pemphigoid. The second is a localized erythematous plaque, the site of recurring bullae, which may become scarred or ulcerated. Such ulceration is superficial, moist, and with little evidence of epithelialization. The localized skin lesions occur near affected mucous surfaces and are not unusual on the scalp. Lortat-Jacob (1958) stressed that