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Mucous membrane pemphigoid was diagnosed in a 2.5-year-old male intact foxhound-beagle cross which was presented with an acute onset of non-pruritic, multifocal, slowly progressive erosive-ulcerative dermatitis predominantly affecting the nasal planum, eyelids and muzzle with multiple vesicles on the inner pinnae, oral mucosa and tongue. The diagnosis was based on clinical signs and histological examination of skin biopsies. The patient did not respond to immunosuppressive prednisolone therapy, but went into complete remission with oral doxycycline and niacinamide and stayed in remission on long-term exclusive niacinamide treatment.Bei einem 2,5-jährigen, männlich-intakten Foxhound-Beagle-Mischling mit akuter, multifokaler, langsam fortschreitender, erosiv-ulzerierender Dermatitis ohne Juckreiz wurde basierend auf klinischen Symptomen und histologischer Untersuchung von Hautbioptaten ein mukokutanes Pemphigoid diagnostiziert. Betroffen waren Nasenspiegel, Augenlider und Schnauze. Bläschen fanden sich auch an Ohreninnenseiten, Maulschleimhaut und Zunge. Der Patient sprach nicht auf eine immunsuppressive Therapie mit Prednisolon an. Mit oraler Gabe von Doxycyclin und Niacinamid ließ sich eine vollständige Remission erreichen und die Erkrankung blieb unter langfristiger ausschließlicher Therapie mit Niacinamid in Remission.

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.Das Pseudopemphigoid ist eine chronische Erkrankung, die zu einer fortschreitenden Vernarbung der Bindehaut bis hin zur Symblepharonbildung führt. Phänotypisch lässt es sich kaum vom echten Schleimhautpemphigoid mit okulärer Beteiligung unterscheiden. Mögliche Auslöser sind Erkrankungen der Augenoberfläche und/oder deren Therapie. Circa die Hälfte aller betroffenen Patienten sind Glaukompatienten unter entsprechender Therapie mit topischen Antiglaukomatosa. Fehlende Zeichen einer systemischen Erkrankung, ein einseitiger Befund und/oder eine positive Glaukomanamnese können auf ein Pseudopemphigoid hinweisen. Im Rahmen dieser Übersicht sollen die beiden Entitäten gegenübergestellt und das diagnostische sowie therapeutische Vorgehen bei Verdacht auf Pseudopemphigoid unter topischer Glaukomtherapie dargestellt werden.

A 53-year-old man presented with a 37-year history of erosive and scarring mucosal lesions of several organs. An initial diagnosis of Stevens-Johnson syndrome was maintained for many years. Due to late correct diagnosis of an anti-laminin 332 mucous membrane pemphigoid and the fact that early, targeted, intensified immunosuppressive therapy was not initiated, the disease led to almost complete loss of vision and obstruction of airways.

Autoimmune bullous diseases are characterized by intraepidermal or subepidermal autoantibody deposition that leads to blisters and secondary erosion. Mucous membranes are frequently affected in pemphigus vulgaris and always involved in cicatricial and mucosal pemphigoid. Mucosal lesions are detected less frequently in patients with bullous pemphigoid or epidermolysis bullosa acquisita. The diagnosis of autoimmune bullous disorders is based on determination of the subtype of autoantibodies bound in the skin and the clinical picture. Treatment is based on immunosuppression related to the type of disease and severity of the mucosal symptoms. Ocular involvement in mucosal pemphigoid and pemphigus vulgaris requires systemic treatment.

A detailed medical history and a careful clinical examination are the basis for developing a list of possible differential diagnoses in lesions of the oral mucosa. On this basis, it can be decided whether a lesion can be observed for 14 days after removal of possible causes or the start of a trial treatment, or whether a biopsy for histological examination must be taken immediately. An excisional biopsy is performed for small and presumably benign lesions, an incisional biopsy for large and presumably malignant lesions. If an autoimmune blistering disease is suspected, a second sample for examination by immunofluorescence is taken. Depending on the results of the histological examination further treatment steps are planned or regular appointments for follow-up are arranged.

The oral allergy syndrome is one of the most common form of food allergy and manifests as contact urticaria of the oral mucosa after consumption of cross reacting foods. Whereas allergic contact stomatitis often occurs due to dental materials, allergic contact cheilitis is usually a reaction due to topical therapeutics like herpes ointments or lip care products. As late type reactions are more frequent than immediate type reactions in the anogenital mucosa, contact dermatitis in this area should be identified via epicutaneous testing. In case of contact urticaria at the genital mucosa, a semen allergy or a latex allergy should be given due consideration as a possible cause. Angioedemas, which are mostly common histamine mediated, usually prefer skin areas with loose connective tissue such as the oral or genital mucosa. Fixed drug eruption also occurs preferentially in these areas. Bullous drug-induced skin reactions (e.g., SJS and TEN) are characterized by severe hemorrhagic, erosive affections of mucous membranes.

Mucous membranes are involved in many different inflammatory disorders.We describe the clinical features, diagnostic workup, and therapy of inflammatory diseases of mucous membranes.The diagnostic workup is based on medical history, clinical manifestations, histopathology, and serology. Inadequate dental hygiene is one of the main pathogenetic factors. Treatment options depend on the diagnosis, underlying cause, and disease severity. Both local and systemic immunosuppressive or immunomodulatory strategies may be effective.The diagnostic and therapeutic management of inflammatory mucous membrane disorders is usually more difficult than that of skin diseases and requires interdisciplinary cooperation.

Mucosal lesions occur with different prevalence and severity in all subtypes of hereditary epidermolysis bullosa (EB), a group of rare genodermatoses. They are associated with increased morbidity and mortality, especially in severe junctional and dystrophic subtypes. Despite progress in clinical approaches to curative therapy, the management of these patients is still primarily symptom-oriented. Current recommendations mainly rely on expert opinion and experience from health care professionals of specialized centers, since the rarity of this disease largely limits the availability and feasibility of randomized controlled trials. Accurate preventive and supportive care measures, however, can significantly lessen symptoms, avoid/ameliorate complications, and enhance the quality of life of these patients.

An early diagnosis is crucial for the outcome of mucous membrane pemphigoid (MMP). The sensitivity of the so-called diagnostic gold standard, direct and indirect immune fluorescence (DIF/IIF) ranges from 30 to 80 %, and is thus lower than desirable. Moreover, conjunctival biopsy, mandatory in most cases, entails the risks of exacerbation. The purpose of this study is to establish the contribution of non-invasive in vivo confocal microscopy to the recognition of MMP.We examined the conjunctiva of ten patients and ten control subjects with the confocal microscope Heidelberg Retina Tomograph II/Rostock Cornea Module and checked for differences in qualitative and quantitative structure of the connective tissue.Pemphigoid patients showed an increase and/or aggregation of reticular connective tissue with hyperreflective strands in the substantia propria, as well as an increased subepithelial fibrosis compared to controls. The basal membrane zone was thicker and more hyperreflective than in the healthy subjects.In-vivo confocal microscopy may serve as a useful additional diagnostic method in the detection of MMP.

A 87-year-old woman presented with a three-year history of partially erosive, partially bullous skin and mucosal lesions, symblepharon of both eyelids as well as dysphagia. To date, multiple excisions of the skin lesions, which had been described as "skin tumors" by surgeons, had been performed. The synopsis of histology, direct and indirect immunofluorescence established the diagnosis of anti-p200/anti-laminin γ1 pemphigoid and BP180 NC16A/4575- positive mucous membrane pemphigoid with an unusual "epitope-spreading" phenomenon. Due to the late initiation of therapy, the disease-related loss of vision unfortunately was irreversible.

The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically progressive autoimmune disorders, predominantly affecting mucous membranes (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group of disorders with variable phenotypes that share the unique feature of a subepidermal blistering, through disruption of the adhesion between epidermis and dermis. A key feature is the chronically active inflammation with consecutive fibrosis, leading to a partial or complete loss of function of the affected organ. The ocular disease as a chronic cicatrising conjunctivitis is a common manifestation of the mucous membrane pemphigoid. The identification of the subtle pathology and the prompt initiation of an appropriate therapy are of pivotal importance. One purpose is to prevent further vision loss due to extensive corneal scarring and life-threatening systemic complications, such as the formation of oesophageal or tracheal strictures. So far there are no prospective, randomised studies, regarding the therapy guidelines with an evidence level more than III. The autoimmune nature of the disease implies that systemic immunosuppression is the only effective treatment option, most notably in extended stages. The aim of our study is to give a guideline for a stage adjusted therapy with conventional immunosuppressants and to give a perspective for alternative therapies, especially for recalcitrant disease.

Treatment of mucous membrane pemphigoid (MMP) aims at reduction of conjunctival inflammation by means of systemic immunosuppression. In addition, cicatricial progression and management of the resulting ocular surface disease requires topical conservative or surgical measures. The former includes systemic immunosuppression with steroids and other immunosuppressive agents: dapsone in mild to moderate disease and cyclophosphamide in severe cases have been established in two randomized trials. Other agents such as methotrexate, azathioprine, mycophenolate mofetil or monoclonal antibodies including daclizumab or rituximab were found to be effective in uncontrolled small studies. Surgery is primarily focused on eyelid problems such as entropium and trichiasis. Ocular surface disease and secondary complications, e.g. cataract formation and glaucoma, may need surgical treatment. Any surgery is associated with the risk of a relapse of inflammation and should be postponed until inflammation is controlled by systemic therapy. Management of MMP patients requires close collaboration of a specialized ophthalmologist with specialists from dermatology and internal medicine.

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.

Mucous membrane pemphigoid (MMP) is often accompanied with a chronic cicatrizing conjunctivitis that may eventually lead to loss of vision. The study is intended to investigate the current scientific knowledge on the diagnosis of and therapy for MMP involving the eye. Previous studies published before December 2004 have been systematically reviewed for their level of evidence. Consequently, recommendations for patient management are provided.

Severe ocular surface diseases, such as Stevens-Johnson syndrome, ocular cicatricial pemphigoid or severe ocular burns may result in a significant loss of corneal stem cells, eventually leading to vision impairment or even corneal blindness. In case of unilateral involvement, limbal autografting, by means of transplanting limbal stem cells from the healthy fellow eye, has proved to be an effective procedure for restoring the integrity of the ocular surface. Limbal allografts may be performed in patients with bilateral disease, however, systemic immunosuppression is mandatory in these cases, with a long-term outcome that is frequently reduced compared to limbal autografts due to acute or chronic graft rejection. In recent years, amniotic membrane transplantation has been successfully employed as an additional tool in ocular surface reconstruction. The AlphaCor synthetic cornea, which is made of flexible acrylic may be considered as an alternative in patients with repeated corneal graft failures. Both limbal transplantation and the AlphaCor have been shown to be effective in eyes with an adequate tear film, but are most likely to fail in severe dry eyes or in patients with cicatrising diseases. Such conditions are the domain of keratoprostheses (KPros) with rigid optics, which certainly can be considered as the 'last resort' to restore vision in patients with profound corneal blindness not amenable to conventional corneal and limbal grafting. The osteo-odonto-keratoprosthesis according to Strampelli and modified by Falcinelli makes use of a "biological" support consisting of a longitudinal section of one of the patient's teeth that is also supported by the surrounding alveolar bone tissue. Compared to other devices favourable long-term results have been reported. In patients lacking any usable teeth, implantation of a keratoprosthesis with haptics made of Dacron (Pintucci-KPro) or tibial bone (Temprano-KPro) might be considered.

Ocular cicatrical pemphigoid can lead to severe structural damage or loss of vision at worst. Longterm therapy with dapsone or systemic immunosuppressive therapy, e.g. with cyclophosphamide is often inevitable. Immunosuppression may cause severe side effects in some patients.Data are presented on 5 patients with ocular cicatrical pemphigoid who were treated with mycophenolate mofetil 2 g daily. Criterion of effectiveness was the clinical course of the condition defined as nonprogression of the morphologic alterations. Patients were initially examined and interviewed routinely every four weeks for the first four months, then every eight weeks. Patients were asked about side effects and underwent monthly blood checks.All patients were followed for at least 12 months. Mycophenolate mofetil proved to be effective with respect to the clinical course in 9 out of 10 eyes. All patients showed regression of inflammatory conjunctival alteration and improvement of their complaints. In one eye the inflammatory process restarted after surgery due to excessive symblephara had been performed. Gastrointestinal side effects were reported in the initial phase, e.g. lack of appetite, nausea and mild diarrhoea.Mycophenolate mofetil proved to be an effective immunosuppressant for the treatment of ocular cicatrical pemphigoid. Namely side effects were less severe and frequent compared to those known from other currently administered immunosuppressants. Longterm results and larger case numbers are needed to sustain these early results.

We describe a case of cicatricial pemphigoid in a 92-year-old female with extensive mucocutaneous involvement. She developed extensive hemorrhagic blistering with severely bleeding lesions, that healed with scarring. The conjunctivae showed extensive synechia. The diagnosis was based on clinical and histopathological features as well as immunofluorescence findings and immunoblot analysis. There was no clinical response to topical corticosteroids. The patient was given tetracycline and nicotinamid and showed rapid improvement of the mucocutaneous lesions within a few weeks. The clinical features, differential diagnosis and various treatment modalities of cicatricial pemphigoid are briefly reviewed, whereby the use of tetracycline and nicotinamide is discussed as an alternative effective and safe therapy for this potentially incapacitating condition.

Cicatricial pemphigoid (CP) is a rare autoimmune disease characterized by subepidermal blistering and progressive cicatrization affecting the skin and mucosa. Ocular involvement occurs in approximately 70% of the patients.The course of the disease, complications and putative risk factors in patients with ocular cicatricial pemphigoid (OCP) treated at the Departments of Ophthalmology and Dermatology were analyzed retrospectively from 1986 to 1998.Eighteen of 28 patients (64%) with CP demonstrated ocular involvement. The mean age of patients with OCP was 73 years; 61% were female. At the time of referral to our hospital, all patients had reached advanced stage III (83%) or IV (17%) of OCP. In 38% of patients vision was already reduced to20/200 at first presentation. Twenty-eight percent of patients additionally suffered from glaucoma. Two patients exhibited life-threatening extraocular manifestations of CP (larynx stricture, esophagus stricture). Conjunctival or mucosal biopsies were performed in 15 patients with OCP and showed typical immuno-deposits at the basement membrane zone in 12/15 patients. Therapy with dapsone (12 patients), oral steroids (11 patients), azathioprine (5 patients), cyclophosphamide (4 patients), colchicine (2 patients) and methotrexate (1 patient) was used concomitantly or consecutively. Complications of OCP including entropion, recurrent epithelial erosions, corneal ulcers, keratitis, and corneal perforations required multiple surgical interventions such as entropion surgery (8 patients), tarsorrhaphy (3 patients), mucous membrane grafting (1 patient), amniotic membrane transplantation (1 patient), tectonic keratoplasty (1 patient), keratoprosthesis (1 patient) and enucleation (1 patient). Despite control of the inflammatory process, further visual loss occurred in 53% of eyes. Reading visual acuity could only be maintained in 35% of eyes.Early diagnosis and therapy can prevent ocular complications of OCP. This study indicates that advanced stages of the disease often result in irreversible visual loss despite institution of immunosuppressive therapy. Whether or not the high association of OCP with glaucoma and/or anti-glaucomatous treatment in our patients represents part of the underlying disease process or plays a role in the pathogenesis of OCP must still be clarified.

The basement membrane molecule laminin forms a family of proteins. Laminin-5 was identified as key protein in the anchoring filaments of the basement membrane. The anchoring filaments connect the basement membrane to the epithelial cells and together form the epithelial adhesion complex. Disturbances in the epithelial adhesion complex result in subepithelial blistering dermatosis. Autoantibodies against laminin-5 are found in cicatricial pemphigoid. Mutations in genes of laminin-5 with loss of the protein cause epidermolysis bullosa Herlitz. It can be determined during prenatal genetic diagnostic testing. Laminin-5 supports migration of keratinocytes and forms the basis for migrating keratinocytes in oral wound healing. Positive re-epithelialization via laminin-5 has been the subject of experimental studies. Oral squamous cell carcinomas are found to have a focal loss of laminin-5 in conjunction with a loss of the cellular receptor, and increased synthesis of laminin-5 by budding tumor cells has been observed along with deposition of the protein in the stroma. As a result of these observations laminin-5 has been suggested as a route of invasion. Quantitative assessment of this phenomenon and the modulation of laminin-5-tumor cell interaction offer new and hopeful means of describing and affecting the invasive behaviour of oral squamous carcinoma.

Cicatricial pemphigoid is a chronic autoimmune subepithelial bullous disease that primarily involves mucous membranes and less frequently the skin. The subepithelial blisters characteristically heal with scarring.In seven years, eleven patients (ten female, one male) underwent interdisciplinary treatment in the departments of dermatology, otorhinolaryngology, and ophthalmology of the university of Würzburg. The mean age of onset was 69 (50-76) years. Histopathologic examination and direct immunofluorescence microscopy of skin biopsies and indirect immunofluorescence analysis of sera were performed in all patients. Seven patients were treated with dexamethasone and cyclophosphamide, two patients received dapsone and two patients both therapy schemes.The oral cavity (n = 10) and/or conjunctival mucosa (n = 6) was most frequently involved, less frequently the larynx (n = 4), the nasal mucosa (n = 3), the skin (n = 3), or the pharynx (n = 1). Histopathologic examination of lesional skin biopsies revealed subepithelial blisters accompanied by mixed mononuclear inflammatory cell infiltrates. Direct immunofluorescence microscopy of skin adjacent to the lesion showed linear deposits of IgG and/or C3 along the cutaneous basement membrane zone. Circulating anti-basement membrane zone autoantibodies were detected in six patients, binding on the dermal (n = 3), epidermal (n = 2), or epidermal/dermal (n = 1) side of NaCl-separated human split skin. Though mucosal and skin lesions responded well to treatment, the ocular involvement was frequently progressive under the therapy, even with a combined dexamethasone and cyclophosphamide pulse regimen.The various clinical symptoms may make the diagnosis of cicatricial pemphigoid difficult. A detailed history and physical examination and application of direct and indirect immunofluorescence microscopy are important for the accurate diagnosis. A spontaneous remission of cicatricial pemphigoid is uncommon. Because of treatment limitations in the later stages of the disease, adequate therapy should start early.

Up to now ophthalmologists have only a small number of substances in their therapeutic armamentarium for the treatment of ocular immunological disorders. These are very potent agents, and any rapidly proliferating cells are extremely sensitive to such agents, thus the possibility of severe side effects is great. Mycophenolatemofetil (MMF) has been shown to be effective in preventing acute graft rejection following clinical renal and cardiac transplantation with a low risk of adverse events. Likewise MMF was effective in the treatment of experimental immunological disorders. A review of literature was performed in Medline.We report on the effective use of MMF in a patient with ocular cicatricial pemphigoid, the switch from Cyclosporin A (CSA) therapy to MMF therapy following high-risk keratoplasty due to CSA allergy and about the combination therapy (CSA/MMF) in a patient following high risk keratoplasty, in whom CSA monotherapy was not sufficient to prevent allograft rejection.In these three cases MMF has been shown to be a safe and effective agent for the treatment of ocular immunological disorders. Whether these beneficial casuistic experiences will hold true will be depended on the outcome of longterm studies underway.

Cicatrical pemphigoid (CP) comprises a group of patients with a chronic subepidermal blistering disease which primarily involves mucous membranes; lesions characteristically heal with scarring. Immunofluorescence investigations typically demonstrate deposits of tissue bound and circulating immunoreactants of the IgG and less frequently of the IgA class in a linear pattern along the basement membrane zone. These autoantibodies are thought to play an important role in the blister formation of CP. Most patients show binding to the bullous pemphigoid antigen 2 (BPag2), collagen type XVII, with a molecular-weight of 180 kD. A smaller group of patients with CP have autoantibodies to laminin 5. Animal models confirm that autoantibodies binding to these two adhesion molecules (BPag2 and laminin 5) are important in blister formation. There are other autoantigens described in CP; however, they are only found in small groups of CP patients and most of them are not further characterised. The described molecules are part of the hemidesmosomal adhesion complex. Impaired function of any component of this complex may lead to a separation of the epidermis from the dermis; better knowledge about the single molecules and the exact localisation of epitopes within these molecules may lead to further understanding of the clinical picture.

Cicatricial pemphigoid is an autoimmune subepidermal blistering disease of the skin and mucous membranes. We report on eight patients in whom the clinical diagnosis was confirmed by direct immunofluorescence. The patients' age averaged 69 years; seven were female and one male. Initial symptoms were erosions of the oral mucous membranes in four patients, skin blisters in three patients, and in one patient an ocular involvement was the first manifestation of the disease. Indirect immunofluorescence on NaCl-split human skin revealed circulating IgG antibodies binding to the roof of the artificial blister in three patients. Immunoblotting of epidermal and dermal extracts disclosed binding of IgG antibodies of one of these patients to an epidermal 230-kD protein, whereas IgA-antibodies showed no specific binding. In four of five patients with a strong ocular involvement IgA deposits were found by direct immunofluorescence. These studies were done on biopsies of perilesional skin or oral mucous membranes, and they were positive in one patient even before the first ocular lesions appeared. Therefore, finding of IgA deposits by direct immunofluorescence may be taken as a prognostic criterion allowing selection of the proper treatment. We treated six patients with a dexamethasone-cyclophosphamide pulse therapy, while two patients received dapsone orally. The involvement of skin and oral mucous membrane responded well to both regimens, whereas the ocular lesions were progressive, except in one patient. On the basis of our eight cases, we discuss both options and limitations in the treatment of cicatricial pemphigoid and review new aspects of the pathogenesis of this disease.

BACKGROUND Since it's first description in 1974 by Kristensen and Norn numerous substances have been reported as potential causes for drug-induced pseudopemphigoid. The signs and symptoms are as severe as with ocular cicatricial pemphigoid. It seems to be most important for the visual outcome for how long the inducing drug was applied and how soon it has been stopped after the first signs. PATIENTS Six female patients were investigated. All six patients presented the clinical picture of a cicatricial pemphigoid but this was not confirmed by immunostaining. The average age of these patients was 72.5 +/- 8.1 years. In 5 of these patients topical antiglaucomatous drugs are thought to be the inducing factor. The average interval from the start of medication until the appearance of the first symptoms was 14.8 +/- 5.3 years. CONCLUSIONS. The drug-induced ocular pseudopemphigoid is a serious but rare consequence of long-term topical medication. This potential risk should be carefully balanced against the benefit of long-term topical therapy.

Nine patients (11 eyes) with ocular cicatricial pemphigoid were treated with systemic azathioprine and a syngeneic nasal mucosa transplant from the inferior turbinate. Follow-up was 8-26 months (average 15 months). Grafting was successful in all cases. Treatment ameliorated the symptoms of pain in all patients and double vision in one. In 2 eyes in which simultaneous pannus resection had been performed, neither pannus nor corneal vascularization recurred. Late complications were recurrences with symblephara in two cases when azathioprine was stopped; in one patient with a serpiginous ulcer tectonic penetrating keratoplasty à chaud had to be performed; and in another a trophic ulcer was healed with a therapeutic contact lens.

Chronic progressive conjunctival cicatrization is found in some mucocutaneous disorders (cicatricial pemphigoid, linear IgA disease) and after long-term treatment with certain topical medications (pseudo-pemphigoid). Little is known about the mechanisms of conjunctival shrinkage, and therapy for these conditions remains difficult.To elucidate the immune mechanisms and assess the main factors involved in conjunctival scar tissue formation in patients with chronic progressive conjunctival cicatrization.We examined 14 bulbar conjunctival biopsy specimens from patients with chronic progressive conjunctival cicatrization (8 with benign mucous membrane pemphigoid confirmed by biopsy, 4 with the ocular features of benign mucous membrane pemphigoid and 2 with pseudopemphigoid) and 10 biopsies from matched healthy individuals: 1.5 mm sections of glycol methacrylate embedded tissue were analysed with the aid of a panel of monoclonal antibodies.Cell counts in the subepithelial substantia propria showed a marked increase in T-cells over normal controls (up to 30-fold). Among the T-cell subsets, there were more CD8 than CD4-positive cells observed. Only about 5% of the T-cells were activated (IL-2 receptor-positive). Macrophages were--as in normal tissues--the second most predominant cell. The absolute number was 2-3 times as high in diseased conjunctiva as in controls. There was increased expression of MHC II molecules on macrophages, lymphocytes und fibroblasts. The numbers of B-cells and NK were not increased.The analysis of the cellular infiltrate showed nonspecific immunopathological characteristics. Thus, the cellular infiltrate gives no explanation for the progressive cicatrization. There is evidence that soluble factors, especially fibrogenic cytokines, play an important role.

The problem in the treatment of bullous autoimmune dermatoses with long-term corticosteroids is that the high doses cause side-effects. An alternative form of therapy with high-dose dexamethasone-cyclophosphamide pulses was used to treat 20 patients between 33 and 86 years: 7 patients had bullous pemphigoid, 6 pemphigus vulgaris, 5 pemphigus foliaceus, and 2 cicatricial pemphigoid. On each of days 1-3 100 mg dexamethasone was administered i.v. and on day 1, 500 mg cyclophosphamide i.v. In the therapy interval between the pulses 50 mg cyclophosphamide per day. Initially the pulses were repeated every 2 weeks and later at 10-week intervals. After 6 months of this regimen 13 patients were symptom-free, 4 had improved, and 3 showed no change. The efficacy of treatment was equal in newly diagnosed and previously treated cases. (Side-effects were leucopenia (n = 3), myalgia and arthralgia (n = 2), taste disturbance (n = 2), diffuse hair loss (n = 2), thrombophlebitis (n = 1), herpes zoster (n = 1) and a delayed-type hypersensitivity reaction to mesna. Owing to the rather short follow-up, no conclusions on long-term side-effects of this therapy are possible. However, dexamethasone-cyclophosphamide pulse therapy appears so far to be a good alternative to the standard continuous corticosteroid treatment.

Localized cicatricial pemphigoid of the Brunsting-Perry type is a very rare bullous condition, which has so far been reported in 51 cases. It is characterized by scarring blisters confined to the head, scalp and neck. Diagnosis can be difficult because of the discrete skin lesions, often repeatedly false-negative direct immunofluorescence, and the absence of circulating antibodies. We report on a 87-year-old male patient with the typical clinical feature of a cicatricial pemphigoid of the Brunsting-Perry type and give a review of the 51 cases published in the world literature.

After severe chemical and thermal burns, and in chronic inflammatory conditions of the conjunctiva frequently scarring of the tarsal plate with distortion of the eyelid margin and keratinization of the tarsal conjunctiva could be found. This condition is accompanied with chronic inflammation and malposition of the eyelids resulting in entropion and trichiasis.A surgical procedure is introduced separating the scarred and shortened tarsal plate from the cutis-muscle sheet. After excision of tarsal scar tissue and of the marginal metaplastic tarsus a new eyelid margin is formed by tarso-conjunctival advancement, correcting trichiasis and cicatricial entropion. During the time from August 1984 to December 1991 this surgical procedure was conducted on 16 patients, correcting 18 upper and 4 lower eyelids. 11 patients suffered from severe chemical and thermal burns, 2 patients from Stevens-Johnson-syndrome, 2 patients from ocular pemphigoid and 1 patient from herpes zoster infection.All patients were examined at least once in the first 6 postoperative months, 11 patients are still under continuing outpatient review. The mean follow-up time is 27 months, the minimum follow-up period is 7 months. In 7 patients the surgical procedure prepared conditions for a successful keratoplasty and in 5 other cases the keratopathy healed. In 4 cases a recurrence of the entropion occurred (18% recurrence rate).The presented surgical procedure is a promising alternative to more complicated procedures for correcting cicatricial entropion with keratinization of the marginal tarsus.

Benign mucous membrane pemphigoid (BMMP) is characterized by immunoglobulin deposits along the basal zone of the skin and mucous membranes, leading to blistering erosions of the involved regions. We report the case history of a 72-year old woman, in whom a cicatricial, supraglottic stenosis caused increasing dyspnea. Through immunohistochemical analysis the diagnosis of BMMP was confirmed. Therapy with cyclophosphamide and steroids led to a remission. Clinical, diagnostic and therapeutic aspects of this laryngologic-dermatologic disease are presented and discussed in the context of the available literature.

The authors describe a typical case of a rare disease, disseminated cicatricial pemphigoid. At the site of the subepidermal bulla excessive scarring in seen. Electron microscopic examination reveals elastic fibrin deposition and incipient vacuolation under the basement membrane. The indirect immunoperoxidase study shows increased numbers of positive Langerhans cells, which support their antigen-presenting role.

We present a typical localized bullous pemphigoid (Brunsting-Perry) associated with positive Nikolski sign. To the best of our knowledge, this is the first report on positive Nikolski sign in localized bullous pemphidoid.

1. A case of the very rare "disseminated cicatricial pemphigoid" is presented in a 68-year-old man. Clinically, prurigo-like nodules and keloidiform plaques, tense blisters and tight atrophic scars were disseminated in the occipital region, on the trunk and on the extremities. The mucous membranes were never affected. 2. Histologically, subepidermal blisters were found. The blister roof contained the complete, intact epidermis; in the floor of the blisters, fibroplasia, angioplasia, and a scarce inflammatory infiltrate containing some eosinophils were present. 3. Direct immunofluorescence revealed linear precipitates of IgM and C3 in the basement membrane. Circulating antibodies have not been found. 4. Semithin sections and electron microscopy showed subepidermal microvesicles and fibrin deposits in initial lesion, followed by edema and blister formation within and below the fibrin deposits. 5. Among several trials of treatment, only azathioprine (Imurek) seemed effective.