Side effects can be minimized by careful monitoring and use of preventive strategies.59 The duration of glucocorticoid therapy and the glucocorticoid dose should be as low as Rabbit Polyclonal to STA13 possible. and subsequent scarring. The disease severity and distribution is highly variable, from mild cases involving only the oral mucosa, to severe cases involving the ocular, genital and esophageal mucosa. Involvement of the larynx or esophagus can give rise to strictures, which may be life-threatening. Since the consequences of this disease can be severe and limited therapeutic options are available once scarring develops, early diagnosis of this disease is critical.3 However, as the disease is rare and the early presenting symptoms are non-specific, MMP Dimethylenastron is often unrecognized in the early inflammatory stage. Other nomenclatures for MMP include cicatricial pemphigoid, oral pemphigoid, ocular cicatricial Dimethylenastron pemphigoid (OCP), ocular pemphigoid, and benign mucous membrane pemphigoid Autoantibodies to one or several autoantigens in the mucosal or epithelial BMZ have been identified in MMP patients.4C10 The association of MMP with human leukocyte antigen (HLA) major histocompatibility class II HLA-DQB1*0301 has been demonstrated.11C13 The cause is usually unknown, but there are a few reports of MMP triggered by medications such as methyldopa, clonidine and D-penicillamine.14, 15 EPIDEMIOLOGY The true incidence of MMP is unclear. A recent study from the United Kingdom demonstrated that ocular MMP accounted for 61% of the cases of newly diagnosed cicatricial conjunctivitis and the incidence was calculated as 0.8 per million population.16 The incidence of MMP was estimated to be 1.3C2.0 per million per year in France and Germany.17, 18 MMP predominantly affects women more often than men with a male to female ratio of nearly 2:1.19 MMP mainly occurs in the elderly population, commonly observed between 60 and 80 years of age.20 Albeit rare, children may also be affected. Approximately 20 cases of childhood onset MMP have been reported, among whom the youngest one was 10 months old.21C23 There is no known racial or geographic predilection. PATHOGENESIS The pathogenesis of MMP is complex. MMP has been found to be heterogeneous with several different antigens implicated. The pathogenic relevance of autoantibodies in MMP has been demonstrated in vivo and in vitro. Circulating IgG and/or IgA autoantibodies against components of the basement membrane zone found in MMP patients serum indicate MMP is mediated by a humoral immune response. 24, 25 Loss of immunologic tolerance to structural proteins in the BMZ results in development of autoantibodies. By use of immunoblotting and immunoprecipitation techniques, a variety of autoantigens including the bullous pemphigoid antigen 1 (BPAg1) (a 230-kDa protein, BP230), the bullous pemphigoid antigen 2 (BPAg2) (a 180-kDa protein, BP180), 24, 25 integrin subunits 6/4, laminin-332 (also called epiligrin and laminin-5), laminin-6, and collagen type I have been identified (Table 1). BPAg1 is an intracellular protein, whereas BPAg2 and 6/4 integrins are transmembrane proteins. The most frequently targeted autoantigen in MMP is BPAg2. Laminin-5 is thought to be the major ligand between the transmembrane proteins and the anchoring filaments.26 Anchoring fibrils, composed of type VII collagen, are located deeper in the lamina densa (Fig. 1). These autoantigens are not exclusive to MMP. Autoantibodies to both BPAg1 and BPAg2 can be present in BP, although BPAg2 is more common, and autoantibodies to type VII collagen is also found in epidermolysis bullosa acquisita. Open in a separate window Fig. 1 Components of the basement membrane zone. Table 1 Autoantigens identified in MMP demonstrated that Dimethylenastron titers of circulating IgG and IgA autoantibodies determined by the IIF technique using mucosal substrates might be predictors of disease severity.45 IIF performed on 1 mol/L salt-split normal human skin substrate, which is separated at the site of the lamina lucida portion of the BMZ can improve the sensitivity. Dimethylenastron Autoantibodies to BPAg2 and integrin subunits 6/4 bind the epidermal side (upper lamina lucida), whereas, autoantibodies to epiligrin and type VII collagen bind to the dermal side on salt-split tissue (lower lamina lucida). Although distinct subgroups of MMP have been identified by use of the advanced immunopathologic and immunochemical techniques, diagnosis should still be made on the basis of clinical presentation combined with pathologic, immunohistologic, and serum antibody analysis. Subgroups Some investigators attempted to subdivide MMP into four subgroups based on autoantigens and clinical features. For a listing of these groups, please refer to Table 4.46C48 Table 4 Features of MMP subgroups
Pure ocular involvementIntegrin 4 subunitHigh-riskPure oral involvementIntegrin 6 subunitLow-riskMucosal and skin involvementBP180Heterogeneous outcomeMultiple mucosal involvementHeterogenous autoantigensHeterogeneous outcome Open in a separate window Diagnostic dilemmas Diagnosis of MMP Dimethylenastron is often delayed because of the non-specific presentations in.