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Secondary acquired lacrimal duct obstructions or SALDO is a term used to define all the secondary causes of lacrimal obstructions [1–4]. It essentially means that the specific cause of obstructions could be zeroed in on, and therapies targeting the cause may result in relief from obstructions. Bartley GB et al. [1–4] described five categories of secondary obstructions, namely, infectious, inflammatory, traumatic, mechanical, and neoplastic with numerous etiologies for each category. Most of the traumatic and neoplastic etiologies have been covered under specific chapters in this Atlas. Inflammatory SALDO can include endogenous etiologies like Stevens-Johnson syndrome, cicatricial pemphigoid, sarcoidosis, and Wegener’s granulomatosis. Exogenous etiologies include burns, allergies, use of eye drops like antiviral, radiotherapy, and certain chemotherapeutic agents like 5-fluorouracil, paclitaxel, and radioactive iodine (I-131) [4–5]. The term mechanical refers to a lacrimal passage physically obstructed anywhere along its entire course by specific agents. These could be endogenous factors like dacryoliths and migrated punctal plugs or exogenous factors like conjunctivochalasis, sinus mucocele, or caruncular masses. The general principle of treatment for a SALDO is to remove the causative factor or to minimize its influence.

IMPORTANCE: Pneumocystis pneumonia (PCP) is a potentially lethal opportunistic infection that primary prophylaxis can help prevent. The risk of prophylactic therapy must be weighed against the incidence of PCP in the patient population. Prophylaxis most frequently involves trimethoprim-suIfamethoxazole, with second-line therapies, including atovaquone, dapsone, and pentamide. The indication for prophylaxis in immunocompromised patients without HIV is less well defined. Previously, an incidence of at least 3.5% has been proposed as a cutoff to justify prophylaxis.OBJECTIVE: To assess the incidence of PCP in patients with autoimmune blistering diseases receiving no routine prophylaxis.DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of patient medical records to determine the incidence of PCP infections. The multicenter study was performed at tertiary care centers that provide care for patients with autoimmune blistering disease in Germany, Italy, Singapore, Israel, and the Netherlands. Patients had a confirmed diagnosis of pemphigus vulgaris/foliaceus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid/cicatricial pemphigoid, or anti-p200 pemphigoid.MAIN OUTCOMES AND MEASURES: To determine the incidence of PCP defined as patients with the International Classification of Diseases, Ninth Revision (ICD-9), code 136.3, for PCP or free text documentation of PCP occurring based on characteristic radiographic findings with elevated lactate dehydrogenase, or hospitalization for pneumonia with bronchioalveolar lavage demonstrating Pneumocystis jiroveci on confirmatory stains.& para;& para;RESULTS A total of 801 patients with autoimmune blistering diseases were included in this study; their mean (SD) age was 66.5 (17.6) years, and a total of 465 (58%) were female. Only 1 patient developed PCP, resulting in an incidence rate of 0.1%, This incidence significantly fell below the recommended threshold of 3.5% (0.1% vs 3.5%, chi(2)(1) = 27.0; P CONCLUSIONS AND RELEVANCE: Routine Pneumocystis prophylaxis for patients with autoimmune blistering diseases does not seem to be warranted. Patients with autoimmune blistering disease seem to have a lower risk of PCP than the general population of immunosuppressed dermatology patients. Risks of routine prophylaxis include hyperkalemia, hypoglycemia, photosensitivity, thrombocytopenia, and more rare adverse reactions.

The aim of this paper is to gain better understanding of the ocular manifestations of multiple system atrophy (MSA), a neurodegenerative disorder rarely studied in terms of its ophthalmologic features. We performed a retrospective case series (1/1/05–12/31/14) to search for patients seen at Mayo Clinic, Rochester, MN, who had mention of MSA in the medical record and an eye examination, which yielded 285 cases. Of the 285, we identified 39 cases of true MSA. Each of these 39 patients was further reviewed for ocular abnormalities potentially related to MSA. Ocular findings potentially attributable to MSA were found in 64% of patients. Most common were dry eye (N = 14), conjugate eye movement abnormalities (N = 13), and ocular misalignment (N = 7). One patient had dry eye and monocular diplopia from trichiasis due to cicatricial pemphigoid, one had bilateral optic atrophy, and one had Adie’s tonic pupil. Conjugate eye movement abnormalities (33%) and ocular misalignment (18%) were more common in patients with MSA-C. Patients with ocular findings, excluding dry eye, had a significantly shorter lifespan from time of initial neurologic symptoms to death. Our study confirms conjugate eye movement abnormalities and misalignment are common ocular findings in patients with MSA. Bilateral optic atrophy and cicatricial pemphigoid are possibly attributable to the disease. Ocular manifestations in MSA predict a poor prognosis as these patients have a significantly shorter lifespan. Therefore, we recommend patients with MSA have a comprehensive neuro-ophthalmologic exam at time of diagnosis, and thereafter, to screen for eye findings that may indicate a shorter lifespan.

S Journal of the American Academy of Dermatology Q. Desquamative gingivitis is not a disease sui generis but is a reaction pattern. The cause must be ascertained by tissue study. Desquamative gingivitis may be an early presentation of mucous membrane pemphigoid or of other blistering diseases such as pemphigus. Over time, about one half of patients with desquamative gingivitis will develop extragingivaI disease. R. Benign mucous membrane pemphigoid is neither benign (it may cause blindness) nor limited to the mucosa (it may involve the skin). Some prefer to call the disease cicatricial pemphig·oid. Cicatricial pemphigoid responds nicely to dapsone and/or sulfapyridine therapy in the majority of patients. Ketoconazole metamorphosis: An antimicrobial becomes an endocrine drug Stevens DA: Arch Intern Med 145:813-815, 1985 In addition to its antifungal activity, ketoconazole reduces androgen and adrenocorticoid synthesis. The drug has been found useful in treatment of prostatic carcinoma and hyperadrenalism and is under study in breast cancer. Italso reduces serum cholesterol. J. G. S. The effects of a shampoo containing zinc pyrithione on the control of dandruff Marks R, Pearse AD, Walker AP: Br J Dermatol 112:415-422, 1985 In a comparison study of zinc pyrithione shampoo with its base in the same patient, forty-eight patients were studied. Despite the progressive reduction in dandruff on the sides of the head treated with the zinc pyrithione shampoo, there were no significant differences in the labeling index and mean epidermal thickness on the two sides, whereas there was a significant reduction in the number of periodic acid-Schiff staining organisms but not in the number of gram-positive staining organisms. The authors suggest that the improvement in clinical dandruff correlates better with the reduction in numbers of yeast microorganisms in the· scalp area. J. G. S. Steroid sulphatase deficiency in patients initially diagnosed as ichthyosis vulgaris or recessive Xlinked ichthyosis Yoshiike T, Matsui T, Ogawa H: Br J Dermatol 112:431-433, 1985 Steroid sulphatase assay of plantar callus and peripheral leukocytes was carried out on five patients with ichthyosis vulgaris and sixteen cases of recessive X-linked ichthyosis. When deficiency of steroid sulphatase was used as a pathognomonic feature of recessive X-linked ichthyosis, it was found that some cases initially resembling ichthyosis vulgaris were actually recessive X-linked ichthyosis, although it was unlikely that a case initially diagnosed as recessive X-linked ichthyosis will prove to be ichthyosis vulgaris by steroid sulphatase assay. J. G. S.

La Pemphigoide cicatricielle est une dermatose bulleuse sous épithéliale qui atteint essentiellement les muqueuses avec une évolution cicatricielle. Il s'agit d'un homme de 66 ans hospitalisé pour gingivite érosive avec dysphagie, dyspnée et flou visuel. L'examen dermatologique retrouvait des lésions érosives du palais et du pharynx. L'examen ophtalmologique notait des symblépharons, un ectropion et une cataracte bilatérale. La biopsie gingivale avait montré un décollement nécrotique de l'épithélium buccal. L'immunofluorescence directe notait un dépôt linéaire d'Immunoglobuline A à la jonction dermo-épidermique. L'Immunofluorescence indirecte était revenue négative. Le diagnostic de pemphigoide cicatricielle était confirmé. Le Transit oeso-gastro-duodénal a objectivé une double sténose de l'œsophage. L'endoscopie nasale, pharyngée et bronchique retrouvait des ulcérations de l'épiglotte, de l'hypopharynx, du pharynx et de l'arbre bronchique. Le patient a bénéficié d'un bolus de Solumedrol relayé par la Prednisone à la dose de 0.5mg/Kg/j associé à la Disulone à la dose de 100mg/j. L'évolution était favorable au début mais s'est compliquée après 2 mois d'une aggravation de la dysphagie et de la sténose oesophagienne. Notre observation est très particulière par la survenue d'une Pemphigoide cicatricielle chez un sujet de sexe masculin ayant un tableau grave en rapport avec l'extension des lésions à toutes les muqueuses conjonctivale, buccale, nasale, œsophagienne et même bronchique associée à une immunofluorescence directe faite d'un dépôt d'IgA uniquement.

Immune-mediated diseases frequently affect oral mucosa, which may often be the first site of clinical manifestation. In this review, we describe the most important oral lesions related to inflammatory disorders and present their management and novel therapies. The review is based on an open PubMed literature search from 1980 to 2012 with relevant keywords. Pemphigus vulgaris, oral lichen planus, cicatricial pemphigoid, erythema multiforme, Stevens-Johnson syndrome, systemic lupus erythematosus, Sjögren's syndrome, and linear IgA dermatosis are the immune-mediated diseases with oral manifestations discussed. Etiology is unknown in most of these diseases, but recently some of them have been found to share common genes. Modern treatment of these diseases is based on drugs that interfere along the pathogenic mechanisms instead of the still commonly used palliative measures. However, the immunomodulatory drugs may also cause oral side effects, complicating the clinical picture. Therefore, consulting dental or oral medicine specialists can be necessary in some cases with various immune-mediated diseases.

Uncommon bullous skin disorders including mucous membrane pemphigoid can sometimes involve the esophageal mucosa, but are not thought to be associated with esophageal neoplasia. A 57-year-old Caucasian woman with a history of refractory painful oral ulceration due to mucous membrane pemphigoid was found to have esophageal mucous membrane pemphigoid when her dysphagia and acid reflux symptoms were investigated. Repeated endoscopies with esophageal dilatation were performed for her recurrent stricturing esophageal mucous membrane pemphigoid. Five years after esophageal involvement was diagnosed, she developed squamous cell carcinoma of the oesophagus. Chronic inflammation of the squamous esophageal mucosal lining may explain the development of esophageal squamous cell carcinoma in esophageal mucous membrane pemphigoid. Gastroenterologists, endoscopists and dermatologists should be mindful of esophageal involvement in mucous membrane pemphigoid and a possible link with esophageal cancer.

As doenças bolhosas autoimunes incluem dois grandes grupos: aquelas que resultam de autoanticorpos contra proteínas dos desmossomas e as que estão associadas a autoanticorpos contra componentes moleculares da membrana basal. Dentro do primeiro grupo vamos abordar o pênfigo vulgar, o pênfigo foliáceo, o pênfigo paraneoplásico e o pênfigo por IgA. No segundo grupo, falamos do penfigóide bolhoso, do penfigóide cicatricial e do penfigóide gestacional. Para cada uma destas patologias, é descrita a etiologia, a fisiopatologia e as manifestações clínicas. Posteriormente aprofundam-se os tópicos do diagnóstico, tratamento e prognóstico destas sete doenças em conjunto.

Mucous membrane pemphigoid (MMP, formerly cicatricial pemphigoid) is a chronic autoimmune, subepithelial blistering disease usually of middle aged or elderly patients, more common in women. The prevalence is uncertain and the aetiology is still unknown. Target antigens are epithelial basement membrane proteins BPAG-1, BPAG-2, laminin-331, and laminin-332 [1]. Oral and conjunctival membranes are most frequently affected. Oesophageal involvement is rare but may be complicated with persistent dysphagia [2]. Herein, we present a patient with MMP with acute dysphagia evaluated by upper gastrointestinal (GIT) endoscopy. This study is based on a case report of a 75-year-old patient with MMP. Clinical and endoscopic examinations as well as direct immunofluorescence (DIF) of conjunctival biopsy were used as methods in this study. A 75-year-old woman was referred to the Dermatology Clinic in November 2011 due to painful erosions in the oral cavity and dysphagia. Her past medical history was significant for dry-eye sensations with visual disturbances diagnosed as ocular MMP in 2007 confirmed by DIF (IgA+ deposits) and treated with dapsone. On physical examination there were erosions and haemorrhagic blisters on the hard palate (Figure 1 A). Inspection of the eyes revealed bilateral conjunctival hyperaemia and fibrous adhesions between bulbar and palpebral conjunctiva (symblepharon) (Figure 1 B). No laboratory changes were found, and autoantibodies in the blood (indirect immunofluorescence) were negative. An endoscopic examination of the upper GIT was performed and revealed: 1) white fibrin with or without flat erosions on the mucosa of cricopharynx, along the oesophagus, and on the lining of the stomach body and prepyloric region; 2) two flat, linear erosions, about 10 mm long on the lower third of the oesophagus; 3) hiatal hernia with line “Z” 4 cm above the diaphragm; and 4) spastic but passable pylorus and erythematous mucosa of duodenal bulb (Figure 1 C). An endoscopic biopsy from the oesophagus showed separation between epithelium and mucosa (Figure 1 D). Given the final diagnosis of MMP with prominent conjunctival and oro-oesophageal involvement, the patient was started on methylprednisolone 16/8 mg per day, which resulted in resolution of oral lesions and dysphagia. She remains stable on maintenance therapy with low-dose methylprednisolone. At 18-months’ follow-up the patient remains under control. Figure 1 A – Haemorrhagic blister and erosion localised on hard palate. B – Eye involvement – symblepharon (arrow). C – Endoscopic features of oesophageal involvement in a 75-year-old patient (see text). D – An endoscopic ... Most patients (89–100%) manifest with oral involvement [1]. The conjunctival mucosa is the second most frequently involved site (66%) [1]. Mucous membrane pemphigoid typically begins with blisters or erosions on mucous membranes or skin. Symptoms of MPP evolve over several weeks with subsequent exacerbation and remission periods. The primary lesion is a serous or haemorrhagic blister of variable size that ruptures in 24 to 48 h producing erosion or ulceration that heals slowly and usually tends toward scarring [1]. Mucous membrane pemphigoid is characterised by deposits of IgG, IgA, or C3 complement along the basement membrane zone. Antigens of epithelium are regarded as targets for autoantibodies. These autoantigens are basically BPAG-1, BPAg-2, laminin-331, and laminin-332, which belong to epithelial proteins [3]. Oral lesions present as painful erosions on buccal mucosa and the palate or as desquamative gingivitis, which is very typical of MMP [4–6]. When dysphagia is observed, it is usually secondary to the involvement of hypopharynx. Oesophageal affection is present in up to 15% of cases and rarely as first or isolated presentation [4]. Endoscopic features of oesophageal involvement vary at different stages of the disease and include longitudinal folding of the oesophageal mucosa and diffuse nonspecific inflammatory changes (mucosal oedema, areas of inconstant narrowing and spasm, erosions, superficial ulcerations), which heal with scarring, leading to the formation of adhesions, transverse and circumferential webs, and various sizes of strictures. Oesophageal involvement may be completely asymptomatic or complicated with dysphagia and even life-threatening bleeding from upper GIT [7, 8]. It may manifest as various types of lesions including esophagitis dissecans superficialis (EDS), as a most severe but rare form. Typical features of EDS are vertical fissures and sloughing of whitish superficial epithelium, resulting in dysphagia, odynophagia, and heartburn, but haematemesis or vomiting oesophageal casts occurs rarely [7]. Adhesions appear as healing progresses and scar formation develops. Strictures result from recurrent episodes of disease may be single or multiple and of variable length, sometimes requiring endoscopic dilatation or surgery [7]. Bullae are rarely seen because endoscopy is usually performed at a late stage when scarring has already occurred [4]. Upper endoscopy is not a routine method in the investigation of patients with MMP. It should be indicated in patients with odynophagia, epigastric pain, or bleeding of the gastrointestinal tract [8]. The course of MMP is progressive. The disease seldom goes into complete remission spontaneously, and the aim of therapy is to prevent progression. Treatment strategies depend on the extent and severity of the disease [4]. Most patients require systemic therapy, and corticosteroids (prednisone or methylprednisolone) are the drugs of choice. Immunosuppressants and Dapsone have also been used with success [1, 5]. Some studies show promising results with the use of mycophenolate mofetil or etanercept [9, 10]. The presented case shows the importance of endoscopic diagnostics in acute dysphagia, regardless of the underlying disease. It is also worth emphasising that patients with MMP must be followed up because the disease may relapse, often in a different localisation.

Autoimmune mucocutaneous blistering diseases (ABDs) represent a group of conditions that manifest with blisters on the skin and/or mucous membranes. Bullous pemphigoid (BP) is the most common autoimmune mucocutaneous blistering disease. In BP, the location of the blisters is subepidermal and the oral involvement is rare. Variants of BP have been described, including pemphigoid vegetans; however, this disease is not completely characterized. The majority of ABDs have blisters and/or vesicles, that are often pruritic, and manifest autoantibodies to diverse proteins. These proteins include 1) hemidesmosomal plaque proteins(ie, BP230, plectins), 2) transmembrane proteins such as BP180 and α6β4-integrin, which are connected via laminin 332 to type VII collagen and 3) currently uncharacterized 105 kDa and 200 kDa molecules. Other ABDs include drug-induced linear IgA disease, bullous systemic lupus erythematosus (BSLE), dermatitis herpetiformis (DH), cicatricial pemphigoid (CP; also termed mucous membrane pemphigoid), lichen planus pemphigoides (LPP), pemphigoid gestationis (PG), herpes gestationis(HG), chronic bullous dermatosis of childhood (CBDC) and the localized forms of CP, such as Brunsting-Perry pemphigoid. The diagnosis of ABDs requires clinical data; skin biopsies (in 10% buffered formalin) for hematoxylin and eosin (H&E) examination and skin biopsies(in Michel’s transport medium) for direct immunofluorescence (DIF). In many ABDs, the histopathologic findings demonstrate a subepidermal vesicle or bulla with a luminal inflammatory infiltrate of neutrophils, eosinophils and/or lymphocytes. In many ABDs, an extensive perivascular and interstitial inflammatory infiltrate is also noted subjacent to the blister in the upper dermis. Normal skin adjacent to an ABD plaque is often excellent for DIF results. Many ABD biopsies reveal autoantibody deposition at the lesional basement membrane zone (BMZ); IgG, IgM, IgA, other immunoglobulins, complement components and fibrinogen may be detected. Indirect immunofluorescence (IIF) yields antibody titer data; the titers usually correlate with disease activity and with ELISA. Linear epitopes are commonly studied by using an immunoblotting (IB) assay. Topical and systemic corticosteroids remain as mainstays of therapy in ABDs; however, multiple other immunosupressors and/or “steroid sparing agents” such as azathioprine have been demonstrated to be of therapeutic value. In the IgA mediated dermatoses, dapsone is often helpful; in addition, liver and blood testing (including G6PD levels) is indicated. The prognosis depends on each case; rapid diagnosis avoids complications and assists in maintaining a good quality of life for each patient.

Autoimmune bullous skin diseases (ABDs) are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ). These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP), linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA) and dermatitis herpetiformis (DH), loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a „cluster of jewels”-like pattern in childhood (chronic bullous disease of childhood) and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of ABDs is based on histology of lesional skin and direct immunofluorescence (DIF) of perilesional skin, as well as by serologic confirmation of autoantibodies by indirect immunofluorescence (IIF) and recombinant autoantigens. The titers of the autoantibodies may correlate with the disease severity, and can be measured by indirect immunofluorescence and by ELISA testing. Therapeutically, systemic treatment with glucocorticoids is combined with immunosuppressive adjuvants which allow for fast reduction of systemic steroids. A prospective clinical trial in pemphigus showed that adjuvant treatment with azathioprine, mycophenolate mofetil and cyclophosphamide led to a significant reduction of the cumulative dose of systemic steroids until complete clinical remission was achieved. In bullous pemphigoid, topical treatment with clobetasol can help to accomplish a clinical remission without the major side effects seen with systemic steroids. Also, therapeutic depletion of B lymphocytes by rituximab has considerably improved the overall prognosis of pemphigus. Nurses and other paramedical personal caring for patients with these disorders play a critical role in improving the quality of life of the patients and their families. The patients need to be continuously evaluated to avoid secondary infections, especially if they have long term immuosupressive treatment. Abbreviations and acronyms: Bullous pemphigoid (BP), immunohistochemistry (IHC), direct and indirect immunofluorescence (DIF and IIF), hematoxylin and eosin (H&E), antibody (Ab), basement membrane zone (BMZ), intercellular staining between epidermal keratinocytes (ICS), pemphigus vulgaris (PV), cicatricial pemphigoid (CP), subcorneal pustular dermatosis (SCPD), dermatitis herpetiformis (DH), sodium dodecyl sulfate (SDS), SDS polyacrylamide gel electrophoresis(SDS-PAGE), autoimmune blistering skin diseases (ABDs), fogo selvagem (FS), endemic pemphigus foliaceus in El-Bagre, Colombia (El Bagre-EPF), desmogleins 1 and 3 (Dsg1 and Dsg3), nonkeratinizing squamous metaplasia (SM).

The subepidermal immunobullous diseases bullous pemphigoid (BP), cicatricial pemphigoid (CP), pemphigoid gestationis (PG) and linear IgA disease (LAD) are characterized by circulating and in vivo deposition of antibodies to antigens in the cutaneous basement membrane zone (BMZ). Indirect immunofluorescence (IMF) of serum is a routine diagnostic test to detect circulating BMZ antibodies in these diseases. We have compared the titres of IgG and IgA and their subclasses, also of IgM and IgE BMZ antibodies in serum and aspirated blister fluid in 35 adult patients with subepidermal immunobullous diseases: BP (n = 30), PG (n = 2), CP (n = 1), and LAD (n = 2), by indirect IMF on intact and salt-split skin. The antibody titre in blister fluid was the same or one dilution less than serum in most cases and there was no significant difference between these results (P > 0.05). IgG1 and IgG4 were the predominant subclasses in both blister fluid and serum in BP. Indirect IMF of serum and blister fluid was also carried out on trypsinized epidermal cells in a subgroup of patients with BP (n = 19). Typical polar fluorescence was obtained in all 14 cases which had positive indirect IMF on intact and split skin. Our findings demonstrate that blister fluid can be used as an alternative to serum for indirect IMF in subepidermal immunobullous diseases. This avoids the need for venesection and has a practical application in children and those with poor venous access.

Summary Cicatricial pemphigoid is a rare subepidermal blistering disease, mainly of elderly women, that primarily involves mucous membranes. Oral, ocular or genital mucous membranes are most frequently involved and skin involvement is less frequent. We report a case of Cicatricial pemphigoid with extensive cutaneous involvement, including unusual bilateral palmar involvement. Clinical improvement has been achieved with a combination of topical steroids, oral nicotinamide and tetracycline.

BACKGROUND: Class I human leucocyte antigens (HLA) -A, -B, -Cw and class II HLA-DRB1, -DQB1 alleles were determined in 131 British Caucasian patients with mucous membrane pemphigoid (MMP) using serological and DNA-based methods. OBJECTIVES: To analyse the class I and II alleles expressed in well-defined clinical and immunopathological subgroups of MMP, in order to establish whether specific alleles or haplotypes might in part explain disease susceptibility, clinical sites of involvement or disease severity. METHODS: Subgroups of patients were analysed according to the following clinical criteria: age of onset, sex, sites of clinical involvement (oral, ocular, skin, nasal, genital, pharyngeal, oesophageal, laryngeal, perianal), disease severity and history of autoimmune disease. Subgroups were also analysed according to the following immunopathological criteria: autoantibody profile, the presence of circulating antibasement membrane IgG or IgA antibodies and the detection of target basement membrane zone (BMZ) antigens (BP230 and BP180) by IgG autoantibodies. RESULTS: Class I HLA typing showed no significant disease or subgroup associations. Class II DRB1 typing showed a significantly increased allelic frequency in MMP vs. controls for DRB1*11 (RR = 2.08, Pc < 0.0000056). For DQB1, MMP vs. controls, there was a significantly increased allelic frequency for DQB1*0301 (Pc < 0.00000028) in both males and females; all clinical sites of involvement, with the exception of laryngeal, oesophageal and perianal sites and in patients with detectable circulating anti-BMZ IgG compared with those negative for IgG (P < 0.0096, Pc < 0.019). A positive trend was noted in patients with ocular involvement compared with no ocular involvement and in patients with a clinical score > or = 10 compared with < 10. We found no difference in DQB1*0301 allele frequency between subgroups with or without BP180 or BP230 target antigens. Haplotype frequencies showed an increase in DRB1*04, DQB1*0301 (Pc < 0.000066) and DRB1*11, DQB1*0301 (Pc < 0.000002) among patients compared with controls. CONCLUSIONS: The DQB1*0301 allele confers a predisposition to all subgroups of MMP and may have a role in T-cell recognition of basement membrane antigens, resulting in the production of anti-BMZ IgG autoantibodies. The positive trend between increased allelic expression of DQB1*0301 in patients with ocular disease and in those with a higher clinical score, further suggests a role for this allele in disease severity.

Summary Cicatricial pemphigoid is a rare autoimmune blistering disease of the elderly. It predominantly affects the mucosae, causing pain and scarring. The target antigen is within the lamina lucida of the basement membrane zone. Potential complications of systemic steroid and other immunosuppressive therapy have prompted trials of other means of treatment. We describe a series of seven patients treated with minocycline, six of whom derived sustained alleviation of orodynia. Four patients developed hyperpigmentation, and two complained of gastrointestinal discomfort which necessitated cessation of minocycline. Complete steroid withdrawal was achieved in two cases. Neither the disease progression nor the response to treatment was influenced by the immunoglobulin isotype or titre. The role of minocycline as a useful adjunct to therapy is discussed.

Autoimmune blistering diseases are a heterogeneous group of disorders that mostly affect the skin and mucous membranes. Occasionally, other organ systems may be involved, depending on the unique pathophysiology of each disease. Cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus are distinct entities, but all have the potential to have cutaneous and ocular involvement. Awareness and early recognition of ocular involvement in these diseases is important given the increased risk for vision loss and blindness with delay in management. Several skin diseases may be associated with involvement of the external eye. The most common autoimmune diseases are cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus.

In immunobullous disease, the host immune system disrupts adhesive interactions in the skin, typically leading to clinical blister formation. The pathophysiology of these diseases has been an active area of investigation. The mechanisms by which these disorders lead to loss of adhesion are variable and disease dependent; however, general principles have been described. The term ‘‘subepidermal blistering disease’’ applies to several disorders that share the clinical appearance of vesicles and bulla, the histologic finding of subepidermal blistering, and in situ deposition of autoantibodies at the dermal–epidermal junction. This group of diseases includes bullous pemphigoid (BP), cicatricial pemphigoid, herpes gestationis, dermatitis herpetiformis, linear IgA disease, lichen planus pemphigoides, epidermolysis bullosa acquisita (EBA), and bullous systemic lupus erythematosus. Intraepidermal blistering diseases are characterized by acantholysis, loss of adhesion between adjacent epidermal keratinocytes, and deposition of immunoreactants at the keratinocyte cell membrane. The protypical intraepidermal autoimmune blistering diseases are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The autoimmune nature of these disorders began to be appreciated in the late 1960s when Jordon and Beutner used immunofluorescent techniques to demonstrate that BP patients have circulating and tissue-bound autoantibodies directed against antigens of the basement membrane zone. Use of these autoantibodies as a screening tool facilitated the identification of the target autoantigens. Using such an approach, Stanley et al. (1981, 1988) first characterized BP antigens at the molecular level and cloned the BP230 cDNA. Subsequently, cDNAs encoding BP180 (the autoantigen for BP, cicatricial pemphigoid, herpes gestationis, lichen planus pemphigoides, and linear IgA disease), laminin 5 (the autoantigen for cicatricial pemphigoid), and type VII collagen (the autoantigen for EBA and bullous systemic lupus erythematosus) were also cloned and characterized.

The mystery of the association of skin disease with systemic disease has been a matter of fascination to dermatologists for hundreds of years. There are a myriad of articles and case reports linking various cutaneous findings to internal disease. The implication has always been that some soluble or cellular factor is being produced that results in a cutaneous disease. Immunobullous disease associates a particular antibody with a cutaneous disease and so the responsible factor for associating an immunobullous disease with a systemic disease is production of an antibody. We will review the milestones in immunobullous disease that have refined our understanding of these associations and consider possible pathogenic mechanisms. Dermatitis herpetiformis (DH) is a papulovesicular skin disease with gluten-sensitive enteropathy (celiac disease, CD) and a unique HLA type (HLADQ2 and DQ8) associated in virtually all cases. Granular deposition of IgA is the immunopathological hallmark. Marks et al. (1966) are generally credited with describing the association of CD with DH. Marks, Fry, and others established that the skin disease with its IgA deposition as well as the intestinal disorder responded to gluten restriction and recurred with the reinstitution of a gluten-containing diet culminating in a landmark paper on gluten challenge in 1983 (Leonard et al., 1983). Katz and Strober (1978) clarified the association of HLA B8/DR3 with the entire spectrum of CD with DH. Kumar et al. (1987) established the presence of IgA endomysial antibodies in DH and CD patients. The endomysial antigen was found to be tissue transglutaminase, and now testing for IgA tissue transglutaminase antibody has become the standard for the serological diagnosis of CD. The link between the intestine and the skin in genetically predisposed individuals is twofold. First, Hall et al. (2007) have established that cytokines elaborated at the site of intestinal inflammation are likely critical to the inflammatory process in the skin. Second, Sardy et al. (2002) have shown that epidermal transglutaminase is the antigen bound to the IgA stimulated by the intestinal inflammatory process. The association between DH and thyroid disease is even more intricate. In 1983, Cunningham and Zone (Cunningham and Zone, 1985) closely evaluated 50 DH patients, and showed that these patients had a high incidence of thyroid autoantibodies as well as hyperthyroidism, hypothyroidism, and thyroid enlargement. Gaspari et al., 1990. showed that this association was not related to the underlying HLA B8/DR3 genotype but was likely related to a high prevalence of Hashimoto’s thyroiditis manifested by thyroid autoantibodies and was independently associated with DH. Whether or not the intestinal inflammation in DH patients is responsible for stimulating the thyroid autoimmune process by a cellular or humoral mechanism remains to be determined (Gaspari et al., 1990). Since the 1980s, several immunobullous disorders have been linked to inflammatory bowel disease including bullous pemphigoid, epidermolysis bullosa acquisita (EBA), and linear IgA bullous disease in case reports and case series. Of these, EBA appears to have the strongest association with inflammatory bowel disease. EBA, an immunobullous disorder is characterized by autoantibodies to type VII collagen, the major structural protein of anchoring fibrils, and clinical presentations resembling bullous pemphigoid, cicatricial pemphigoid, or epidermolysis bullosa. EBA has been described in patients with both Crohn’s disease and UC, with Crohn’s disease being the predominant association. In a study of 51 EBA patients, Chen et al. (2002) found that 25% (13 of 51) had inflammatory bowel disease: 12 had Crohn’s disease and 1 had UC. They also demonstrated full-length (290 kDa) type VII collagen in normal colonic extracts from four patients and type VII collagen immunoreactivity in the colonic basement membrane. Of 19 patients, 13 patients with Crohn’s disease and 4 of 31 patients with UC were found to have elevated levels of circulating antibodies to the immunodominant NC1 domain of type VII collagen by ELISA. Despite these findings, there is no evidence linking an autoantibody to the pathogenesis of inflammatory bowel disease. The presence of type VII collagen antibodies is thought to represent epitope spreading, resulting from exposure of type VII collagen epitopes due to damage to the overlying colonic mucosa. Immunobullous diseases have also been linked to malignancies. The quintessential disorder is paraneoplastic pemphigus (PNP), described by Anhalt et al. (1990). PNP is characterized by painful mucosal erosions and polymorphous

OBJECTIVE Sub-epidermal bullous disorders belong to immunobullous diseases which develop as a result of autoantibody action against epidermal basement membrane proteins. Clinically, they are tense bullae and do not rupture easily. They are classified into various forms based on histopathology and direct immunofluorescence patterns. This study was undertaken to assess the incidence of various sub-epidermal bullous disorders and the utility of direct immunofluorescence in accurately classifying them, and to study the intensity and pattern of immunofluorescence in various sub-epidermal bullous disorders Material and Method: A 2-year study of 38 cases of sub-epidermal bullous disorders sent for direct immunofluorescence studies formed the study group. The specimens were processed as per standard protocols. The clinical details were obtained from case files and requisition sent for histopathological and direct immunofluorescence studies. RESULTS Thirty-eight patients were diagnosed to have sub-epidermal bullous disorders over the period of 2 years. Twenty five cases of Bullous Pemphigoid, 5 cases of Dermatitis Herpetiformis, 3 cases of Linear IgA Bullous disorder, 2 cases of Bullous Systemic Lupus Erythematoses and 1 case each of Epidermolysis Bullosa Acquisita, Cicatricial Pemphigoid and Pemphigus Gestationis was diagnosed. Positive direct immunofluorescence was seen in 91.3% of the cases. CONCLUSION Histopathology alone cannot classify sub-epidermal bullous disorders and direct immunofluorescence studies are mandatory in all of them. Bullous Pemphigoid needs to be distinguished from Epidermolysis Bullosa Acquisita which requires Salt split direct immunofluorescence studies. Dermatitis Herpetiformis, Bullous Systemic Lupus Erythematosus and Linear IgA Bullous disorder show more or less similar histological picture with neutrophilic microabscess. Direct immunofluorescence studies help in the majority of cases but further testing such as immunoblotting, immunoelectron microscopy or indirect immunofluorescence becomes essential in cases with overlapping features.

Mucous membrane pemphigoid (MMP) is an immune-mediated systemic disease affecting the mucosa of the mouth, eyes, nasopharynx, GI tract, genitalia and skin. Chronic inflammation and subepithelial blisters of the mucosa result in progressive scarring. Ocular MMP is characterized by a chronic cicatrizing conjunctivitis, which leads to symblepharon, entropion, trichiasis, severe dry eye, cornea ulceration and potential blindness when untreated. One of the most effective treatments for ocular MMP is the combination therapy of cyclophosphamide (administered for 12–18 months) and oral corticosteroids (tapered over 3–4 months). This regimen has proven effective in controlling conjunctival inflammation, halting mucosal scarring and preventing potential vision loss, and is typically used for severe disease. Long-term drug-free remission is achievable in patients with this regimen. For all immunosuppressive medications, careful monitoring for drug-related side effects is crucial.

Adjuvant immunosuppressive drugs are widely used to minimize corticosteroid-related adverse effects in the short-term and long-term management of cautoimmune bullous diseases. In bullous pemphigoid and pemphigus vulgaris, azathioprine and mycophenolate mofetil seem to be equally effective when used in combination with oral corticosteroids, but mycophenolate mofetil is less myelosuppressive and hepatotoxic. Due to a better safety profile, mycophenolate mofetil or enteric-coated mycophenolate sodium may gradually replace azathioprine as the first-line adjuvant of choice in the treatment of moderate to severe autoimmune bullous diseases, including epidermolysis bullosa acquisita and cicatricial pemphigoid. Cyclophosphamide still has a place in the treatment of severe relapsing autoimmune bullous diseases. Continuous oral cyclophosphamide provides optimal immunosuppression, but it also produces the highest cumulative dose. Several pulsed cyclophosphamide regimens have, therefore, been developed and are reported to be effective in severe forms of pemphigus. Randomized controlled studies are needed to compare the efficacy and safety of cyclophosphamide with newer treatment options, such as rituximab and immunoapheresis, and to define optimal dose ranges and duration of available immunosuppressive treatments in different stages of autoimmune bullous diseases.

According to Sir William Osler, Mouth is the mirror of the body which reflects systemic -diseases. The oral mucosa may be affected by a variety of mucocutaneous diseases and oral lesions may occur first or very early in several mucocutaneous disorders. The erosive gingival lesions associated with vesiculobullous diseases such as lichen planus, cicatricial pemphigoid, and pemphigus vulgaris have been collectively referred to as "Desquamative gingivitis" (DG). Gingival desquamation is a clinical sign in which the gingiva appears reddish, painful, glazed and friable with destruction of the epithelium. This gingival desquamation is due to various disease processes in gingiva. The disease process may be a localized disease of gingiva or a systemic disease which manifests in the gingiva. It is important to be aware of this rare clinical entity so as to distinguish DG from plaque induced gingivitis which is an extremely common condition, easily recognized and treated daily by the dental surgeon. Accurate diagnosis and effective treatment of these lesions may greatly diminish or reverse disease progression. Here by, we present a case of mucous membrane pemphigoid presenting as gingival desquamation in a 45 year old female. Our patient presented with generalized erythematous gingiva and gingival desquamation involving the free, attached and marginal gingiva of left maxillary and mandibular dentition. However, other mucosal and skin involvement was not appreciated in the present case. Thorough history, clinical examination, histopathology and immunofluorescence studies helped us to arrive at the diagnosis of this rare sub-epithelial blistering disorder.

The immunobullous disorders are a group of autoimmune diseases in which components of the epidermis and basement membrane zone are targeted, resulting in the formation of cutaneous and mucosal blisters. Based on the level of blistering, the autoimmune blistering diseases may be subdivided into intraepidermal and subepidermal. An exhaustive list of immunobullous disorders is beyond the scope of this review, but those involving oral mucosa are taken into consideration. One major group namely the subepidermal immunobullous diseases which includes bullous pemphigoid (BP), mucosal pemphigoid [cicatricial pemphigoid (CP) or (MMP)], epidermolysis bullosa acquisita (EBA) linear IgA bullous disease (LABD) are discussed in this section. The diagnosis of these diseases requires clinicopathological correlation; immunofluorescence methods provide a useful adjunct to light microscopy. These methods entail the use of fluorescein-linked antibodies to immunoglobulins, complement components, or other proteins either in the skin biopsy or sera. In continuation with part I, the immunofluorescence patterns in the above listed immunobullous disorders are reviewed in detail with a summary of pathogenesis and characteristic histopathological findings. How to cite this article Rao RS, Premalatha BR, Mysorekar V. Immunofluorescence in Oral Pathology—Part II: Pathology and Immunofluorescent Patterns in Subepidermal Immunobullous Disorders. World J Dent 2012;3(1):68-73.

Mucous membrane pemphigoid, a heterogeneous group of autoimmune blistering diseases, affects primarily the mucous membranes. Although oral and ocular mucosae can both be affected in a given patient, patients with involvement restricted to oral mucosae tend to have a benign outcome, whereas those with ocular disease commonly face treatment resistance, resulting in scarring and blindness. Diagnosis requires direct immunofluorescence microscopy to demonstrate a linear deposition of immunoglobulin (Ig) G or IgA, or complement component 3 (C3), at the epithelial basement membrane. Although the target antigens vary, subsets of patients affected exclusively by oral and ocular mucosal diseases have autoantibodies targeting α-6 and β-4 integrins, respectively.

Epidermolysis bullosa acquisita (EBA) is a rare, acquired, chronic subepidermal bullous disease of the skin and mucosa characterized by autoantibodies to type VII collagen (C7) structures, a major component of anchoring fibrils, which attach the epidermis to the dermis. EBA patients have tissue-bound and circulating antitype C7 autoantibodies that attack type C7 and result in a reduction or perturbation of normally functioning anchoring fibrils. Patients with EBA have skin fragility, blisters, erosions, scars, milia, and nail loss, all features reminiscent of genetic dystrophic epidermolysis bullosa. These immunoglobulin G antitype C7 antibodies are pathogenic, because when they are injected into mice, the mice develop an EBA-like blistering disease. In addition to the classical mechanobullous presentation, EBA also has several other distinct clinical syndromes similar to bullous pemphigoid, Brunsting-Perry pemphigoid, or cicatricial pemphigoid. Although treatment for EBA is often unsatisfactory, some therapeutic success has been achieved with colchicine, dapsone, plasmapheresis, photopheresis, infliximab, and intravenous immunoglobulin.

Pemphigoid is a group of bullous diseases that have a diversified morphologic presentation and affects skin, oral mucosa and other mucosal membranes alone or in combination. In the literature, the condition has been subclassified into bullous pemphigoid and cicatricial pemphigoid (Mucous membrane pemphigoid) on the basis of primary organ of involvement. Oral pemphigoid, defined as cicatricial pemphigoid limited to the oral cavity, is a clinical subset of cicatricial pemphigoid. Like cicatricial pemphigoid, it occurs mostly in middle-aged women and it is uncommon in children under 20 years of age, with very few cases reported in the medical literature. We present a case of a 14-year-old girl with desquamative gingivitis as the only clinical presentation of this rare disease and lay emphasis on early recognition and clinical awareness.

Epidermolysis bullosa acquisita (EBA) is a rare and acquired autoimmune subepidermal bullous disease of skin and mucosa. EBA includes various distinct clinical manifestations resembling genetic dystrophic epidermolysis bullosa (DEB), Bullous pemphigus, Brunsting-Perry pemphigoid, or cicatricial pemphigoid. These patients have autoantibodies against type VII collagen (C7), an integral component of anchoring fibrils (AFs), which are responsible for attaching the dermis to the epidermis. Destruction or perturbation of the normal functioning AFs clinically results in skin fragility, blisters, erosions, scars, milia, and nail loss, all features reminiscent of genetic dystrophic epidermolysis bullosa. These anti-C7 antibodies are "pathogenic" because when injected into a mouse, the mouse develops an EBA-like blistering disease. Currently, treatment is often unsatisfactory; however, some success has been achieved with colchicine, dapsone, photopheresis, plasmapheresis, infliximab, rituximab, and IVIG.

Antiepiligrin cicatricial pemphigoid (AECP) is a chronic autoimmune subepidermal blistering disease characterized by clinical features of cicatricial pemphigoid and circulating IgG antibasement membrane autoantibodies directed against laminin 332. There is growing evidence of an increased relative risk for solid cancers and lymphomas in AECP patients, especially in the 1 st year after the onset of blisters. However, it is difficult to distinguish patients with initially skin-predominant AECP from similar findings of epidermolysis bullosa acquisita merely based on clinical, histopathologic, and immuno-pathologic examinations. This is a report on a case of AECP confirmed by indirect immunofluorescence of type VII collagen- and laminin 332-deficient skin as substrates to differentiate it from epidermolysis bullosa acquisita.

Autoimmune blistering diseases are a significant cause of morbidity and mortality in the elderly population. Given the advancing age of the population, the incidence of these disorders, particularly bullous pemphigoid, is expected to rise. This contribution reviews autoimmune immunobullous disorders of particular relevance in the elderly population. These include bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, pemphigus, paraneoplastic pemphigus, and linear immunoglobulin A bullous dermatosis. Because therapy and management of individual immunobullous dermatoses differ, establishing the diagnosis is often critically important. An overall approach to bullous diseases in the elderly, as well as key clinical features, appropriate diagnostic tests, microscopic findings, immunofluorescence microscopy patterns, and molecular targets for select disorders are reviewed. Elucidation of antigenic targets at the molecular level has allowed for development of serum enzyme-linked immunofluorescence assays, which have enhanced diagnostic accuracy for several autoimmune blistering disorders. Given the relative rarity of these diseases, large randomized trials evaluating efficacy of various treatments are few, and therapy for most immunobullous disorders in the elderly has not been standardized. Despite this, appropriate therapeutic considerations for each condition are presented and the evidence for them is reviewed.

WOS: 000340080300012, Vulvar cicatricial pemphigoid is a rare variant of bullous pemphigoid, which is characterized by isolated and localized vulvar involvement, observed in childhood. The typical clinical finding is erosive lesions of the vulva healing with scar formation. Ocular involvement may be associated with vulvar disease or may develop during the follow-up. On histopathologic examination of the lesions, subepidermal blister and on direct immunofluorescence study, linear deposition of Ig G and C3 are observed. The differential diagnosis includes lichen sclerosus and, sexual abuse should be considered at first. Topical and systemic steroids and dapsone are the main treatment options. Ophthalmological examination and follow-up should be repeated on every six months for ocular involvement. Here, we report development of vulvar cicatricial pemphigoid in an 11-year-old girl with clinical and histopathological findings.

Mucous membrane pemphigoid describes a rare heterogeneous group of chronic, inflammatory, mucous membrane-dominated, subepithelial blistering diseases that manifest a varying constellation of oral, ocular, skin, genital, nasopharyngeal, esophageal, and laryngeal lesions. Life-threatening airway obstruction and sight-threatening ocular scarring can occur in this condition, which is rarely reported in Indian literature. Vitiligo is another acquired autoimmune disorder characterized by loss of melanocytes. Vitiligo is associated with a number of disorders also considered to be autoimmune. Here we report a very rare coexistence of MMP and vitiligo, the first such report from India.

Desquamative gingivitis (DG) is a clinical descriptive term indicating "peeling gums". DG is usually the result of a disease process that causes separation of the epithelium from the underlying connective tissue in the oral masticatory mucosa. DG may be a manifestation of several mucocutaneous diseases, most commonly cicatricial pemphigoid, pemphigus vulgaris and lichen planus. Correct diagnosis of the underlying disease in DG patients requires careful clinical observation, detailed examination of medical history, biopsy and histopathological examination of the lesions as well as more specialized tests such as direct and indirect immunofluorescence. Treatment of DG consists of treating the underlying disease and often requires the use of immunosuppressive agents, such as corticosteroids. Elimination of local gingival irritants, such as dental plaque and calculus, can significantly improve the treatment outcome.

Intravenous immunoglobulin has been used in the treatment of various dermatological conditions, including toxic epidermal necrolysis, bullous pemphigoid and pemphigus vulgaris. From March 2008, the National Blood Authority has implemented the 'Criteria for the clinical use of intravenous immunoglobulins in Australia'. The new criteria have formalized the eligibility requirements for several dermatological conditions. This may increase access to intravenous immunoglobulin for treatment for these conditions. However, there remain stringent eligibility criteria with which dermatologists need to be acquainted. In some conditions, dermatology review is mandated by these criteria while in other conditions with skin manifestations, referral to other specialists is required. The following article provides a summary of the salient points in relation to the clinical use of intravenous immunoglobulin in dermatology, as well as its production and supply in Australia.

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune subepidermal bullous disease with autoimmunity to the type VII collagen which is the major component of anchoring fibrils. Clinical manifestations of the classical EBA include skin fragility, blisters over the trauma-prone surfaces and milium cysts. Other presentations of EBA have been reported: mucosal predominant appearance reminiscent of cicatricial pemphigoid, bullous pemphigoid-like presentation and IgA-EBA. Making a definitive diagnosis of EBA could be difficult because specialized tests available in only some laboratories are necessary to confirm the clinical suspicion: immunoelectron microscopy demonstrating immune deposits on anchoring fibrils and immunoblotting or enzyme-linked immunosorbent assay (Elisa) detecting autoantibodies recognizing the type VII collagen. EBA frequently is associated with Crohn's disease and an inflammatory bowel disease must be ruled out in patients with EBA and abdominal manifestations. EBA potentially is serious, has usually a chronical evolution and is difficult to treat.There are no guidelines for treatment of EBA, which is adapted to clinical severity and include dapsone, cyclosporine and rituximab.

Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepidermal blistering disease with predominant mucosal involvement. In this article, we report a young patient with mucosal and extensive cutaneous involvement in the form of large erosions mimicking those of pemphigus vulgaris thus leading to diagnostic dilemma. We were unable to find any other previous reports with such extensive cutaneous erosions mimicking those of pemphigus vulgaris. Laminin 5 was the antigen found on knockout substrate testing. Antiepiligrin CP is a distinct subtype of CP with antibodies against laminin 5. This subtype is mostly associated with malignancy but no underlying malignancy was found in our case. Present report also highlights the importance of knockout substrate testing when immunoblot is not available.

Mucous membrane pemphigoid and pemphigus vulgaris are autoimmune blistering disorders in which many similar drugs and therapeutic strategies are utilized. In general, localized disease can be treated with topical agents. In contrast, patients with more severe and progressive disease usually require a combination of systemic corticosteroids and immunosuppressive medications. Oral corticosteroids, adjuvant immunosuppressive agents, antibiotics such as dapsone and immunomodulatory procedures like intravenous immunoglobulin are the main therapeutic agents used in treating these two disorders. Much of the morbidity and mortality associated with these disorders are related to the sites involved and to the drugs used for therapy. Treatment should be individualized based on severity, extent, and rate of progression of disease, comorbidities, and age of the patient. Serum levels of specific autoantibodies and indirect immunofluorescence titers, in certain cases, can be used to monitor response to therapy.

Cicatricial pemphigoid is an extremely rare condition in children, since only 17 cases have been reported in the English literature, so far. We describe a new case in a 20-month-old boy, who is to our knowledge the youngest patient reported yet. The disorder had begun 10 months before he was referred to our department by mucosal crusted erosions of the oral and nasal cavities and conjunctivae. Cutaneous examination showed buccal erosions with limited mouth opening, entropion of the lower eyelids, trichiasis, cicatricial cornea, synechia of the nasal cavities and hypopigmented lesions of the abdomen. There were no anal or genital lesions. Cicatricial pemphigoid was confirmed by positive direct and indirect immunofluorescence on mucous biopsy. Systemic corticosteroids (2 mg/kg/day), maintained for 12 months, had led to complete healing of lesions. But due to cicatrization, synechia of the nasal cavities and corneal opacities, leading to a dramatic visual loss, have occurred. Dapsone 25 mg/day and topical ocular cyclosporine are now maintained to avoid relapse. Our review of the literature of all cases of CP showed that ocular and to a less degree, vulvar lesions are the most severe ones, due to the serious complications with scar formation.

Cicatricial pemphigoid is a rare autoimmune disease with chronic blister and decomposition formation in the membrane leaving scarring. Blistering and decomposition may also be expected in the pharynx, larynx or esophagus. This study began when the subject started showing symptoms from 3 years of age and continued for 10 years as the cicatricial pemphigoid progressed. Breathing difficulty appeared nightly when she was 3 years and 10 months old. It was urgent, requiring endotracheal intubation and a tracheotomy. Rubor of a left main bronchus and strangulation effects were observed from 4 and a half years of age. A keloplasty of the epiglottis was performed and the glottis was closed by cicatricial adhesion. In Japan, the number of cicatricial pemphigoid cases requiring tracheotomies, including this case, was 15. The number of cases whose tracheal gill holes were closed relatively quickly was 3. Medical treatment of the larynx cannot be carried out while the condition is not under control. The girl in this study is now a junior high school student and has the ability for satisfactory everyday conversation as well as functional deglutition. Since steroids are prescribed for ongoing treatment, we think it's important to see and carefully monitor progress. Depending on future progress, it may be that larynx reconstruction among other physical treatments could be indicated.

Background Antilaminin-332 mucous membrane pemphigoid (MMP) is a chronic autoimmune bullous disease that is often associated with internal malignancy. IgG autoantibodies against laminin-332 in patients with MMP are well documented; however, IgA and IgE autoantibodies against laminin-332 have not yet been described. Objectives To characterize IgA and IgE autoantibodies binding to laminin-332 in sera from patients with antilaminin-332 MMP. Methods Sera and skin samples from four patients who met the following criteria were used: (i) subepidermal blistering lesions present on the mucous membranes; (ii) in vivo deposition of IgG along the epidermal basement membrane zone of sampled skin; (iii) circulating IgG antibasement membrane zone antibodies that react with the dermal side of salt-split normal human skin; and (iv) circulating IgG autoantibodies that do not show positivity against type VII collagen or 200-kDa protein (p200 antigen) in immunoblot analysis using dermal extracts. Circulating IgG/IgA/IgE class autoantibodies against laminin-332 were determined by immunoblotting. Results Circulating IgG autoantibodies against the gamma2, alpha3/gamma2, alpha3 and alpha3/beta3/gamma2 subunits of laminin-332 were demonstrated in sera from four patients, respectively. Serum from one of the four patients showed IgA reactivity with the alpha3/beta3/gamma2 subunits of laminin-332. Serum from one of the four patients showed IgE reactivity with the gamma2 subunit of laminin-332. The control sera failed to display IgG/IgA/IgE reactivity to laminin-332. Conclusions In addition to IgG autoantibodies, circulating IgA and IgE autoantibodies against laminin-332 are detectable in a subset of patients with antilaminin-332 MMP.