P J Shirlaw

Immunodiagnosis of pemphigus and mucous membrane pemphigoid

Pemphigus and pemphigoid are two of a group of bullous diseases affecting oral mucosa and skin. Mucous membrane pemphigoid (MMP) comprises a heterogeneous group of disorders characterized by subepithelial separation and the deposition of immunoglobulins and complement along the basement membrane zone (BMZ). The target antigens in the epithelium and BMZ determine the nature of the condition, and recently there have been considerable improvements in our understanding of the BMZ antigenic composition. Pemphigus vulgaris (PV) is characterized by autoantibodies of the IgG isotype to the desmosomal glycoprotein desmoglein (Dsg) 3, whereas pemphigus foliaceus targets Dsg1, although at least 50% of PV patients have additional autoantibodies to Dsg1. The clinical phenotype appears to be determined by the relative amounts of Dsg1 and Dsg3. Patients with oral or mucosal PV have predominantly Dsg3 autoantibodies. The most frequently targeted antigen in MMP is bullous pemphigoid antigen 180 (BP180), although bullous pemphigoid antigen 230 (BP230), laminin 5, and beta 4 integrin are also involved. Circulating IgG and IgA antibodies may bind to different epitopes of BP180 - namely the NC16A domain or COOH-terminal domain. Pure ocular disease has been associated with IgA antibodies to a 45-kDa antigen and IgG antibodies to the 205-kDa antigen b4 integrin. The use of salt-split skin substrate enables differentiation between epidermal and dermal binders. Since both the specificity and the antibody titer appear to have direct relationships with the disease severity, and a combination of clinical score and antibody titer provides valuable prognostic data, these investigations should be carried out on a more routine basis.

Cicatricial pemphigoid: serial titres of circulating IgG and IgA antibasement membrane antibodies correlate with disease activity.

We have recently shown in a cohort of patients (nu2003=u200367) with mucous membrane pemphigoid, 63 of whom had cicatricial pemphigoid (CP), that the presence of both IgG and IgA circulating antibasement membrane zone antibodies was associated with a more severe and persistent disease. In this study we sought to ascertain whether in CP, serial titres of IgG and IgA might provide a reliable marker of disease activity. Serum titres for IgG and IgA antibodies were assayed at 6‐ to 12‐monthly intervals in 56 patients over 32.2u2003±u200320.3 (meanu2003±u2003SD) months. Antibody titres were correlated with the clinical score recorded at each follow‐up visit. Sequential titres for both IgG (Pu2003<u20030.001) and IgA (Pu2003=u20030.015) were significantly associated with variations in disease activity. Greatest improvement was seen in patients with the greatest change in either IgG or IgA antibody titre. We suggest that serial antibody titres may therefore be useful in the assessment and management of CP.

Pyoderma gangrenosum associated with severe oropharyngeal involvement and IgA paraproteinaemia

We report a patient with combined cutaneous and oropharyngeal pyoderma gangrenosum in association with an IgA λ paraproteinaemia. The differential diagnosis of oral pyoderma gangrenosum is discussed.

Paraneoplastic cicatricial pemphigoid

We report a 39‐year‐old woman with antiepiligrin cicatricial pemphigoid (CP) in association with non‐small cell carcinoma of the lung. At presentation, mucosal lesions showed minimal response to combined systemic immunosuppressive agents. Following the diagnosis of non‐small cell lung carcinoma and subsequent treatment with gemcitabine (a second‐line chemotherapeutic agent), a significant reduction in both tumour mass and mucosal blistering was observed. Metastatic disease was subsequently associated with recurrent oral erosions. We believe this patient represents the first reported case of paraneoplastic CP.

Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease

Orofacial granulomatosis (OFG) is a condition of unknown aetiology with histological and, in some cases, clinical association with Crohns disease (CD). However, the exact relationship between OFG and CD remains uncertain. The aim of this study was to determine whether OFG could be distinguished immunologically from CD by comparing non‐specific and specific aspects of humoral immunity in serum, whole saliva and parotid saliva in three groups of patients: (a) OFG only (nu2003=u200314), (b) those with both oral and gut CD (OFGu2003+u2003CD) (nu2003=u200312) and (c) CD without oral involvement (nu2003=u200322) and in healthy controls (nu2003=u200329). Non‐specific immunoglobulin (IgA, SigA, IgA subclasses and IgG) levels and antibodies to whole cells of Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans were assayed by enzyme‐linked immunosorbent assay (ELISA) in serum, whole saliva and parotid saliva. Serum IgA and IgA1 and IgA2 subclasses were raised in all patient groups (Pu2003<u20030·01). Salivary IgA (and IgG) levels were raised in OFG and OFGu2003+u2003CD (Pu2003<u20030·01) but not in the CD group. Parotid IgA was also raised in OFG and OFGu2003+u2003CD but not in CD. The findings suggest that serum IgA changes reflect mucosal inflammation anywhere in the GI tract but that salivary IgA changes reflect involvement of the oral cavity. Furthermore, the elevated levels of IgA in parotid saliva suggest involvement of the salivary glands in OFG. Serum IgA antibodies to S. cerevisiae were raised markedly in the two groups with gut disease while serum IgA (or IgG) antibodies to C. albicans were elevated significantly in all three patient groups (Pu2003<u20030·02). No differences were found with antibodies to S. mutans. Whole saliva IgA antibodies to S. cerevisiae (and C. albicans) were raised in the groups with oral involvement. These findings suggest that raised serum IgA antibodies to S. cerevisiae may reflect gut inflammation while raised SIgA antibodies to S. cerevisiae or raised IgA or IgA2 levels in saliva reflect oral but not gut disease. Analysis of salivary IgA and IgA antibodies to S. cerevisiae as well as serum antibodies in patients presenting with OFG may allow prediction of gut involvement.

Patient preferences in a preliminary study comparing an intra-oral lubricating device with the usual dry mouth lubricating methods

Objective: To compare an intra-oral device to relieve oral dryness with the other methods of lubricating the mouth at night.Design: Multidisciplinary single blind randomised cross over study.Setting: The subjects were drawn from patients attending a dry mouth clinic.Materials and methods: Thirty-four dentate subjects attended on five occasions at intervals of 4 weeks. At the first visit the teeth were scaled and impressions were recorded. The device was fitted either on the second or the fourth visit. At all visits samples were taken of the resting and stimulated saliva for volumetric analysis and the dry mouth score recorded. Data were collected from the lubrication timings and the questionnaire.Results: Ten water, nine saliva substitute and ten sugar-free chewing gum lubricators completed the study. There were 27 female and two male subjects with an average age of 62 years. Nine out of 10 of those lubricating with chewing gum preferred wearing the device (P = 0.037). After the device wearing period the subjects self assessment of mouth dryness (P = 0.056), speech (P = 0.009) and swallowing (P = 0.031) were more favourable when compared with the alternative lubrication with 66% preferring the intra-oral device to their alternative method of lubrication.Conclusions: The majority of the subjects preferred wearing the device at night compared with their normal method of lubrication. Subjects perception of dryness, speech and swallowing became closer to the clinicians assessment after wearing the device.

Pyostomatitis vegetans associated with asymptomatic ulcerative colitisA case report

Pyostomatitis vegetans, a rare pustular disorder of the oral mucosa, is a highly specific marker for inflammatory bowel disease and may be difficult to treat. A case of pyostomatitis vegetans in a patient with long-standing asymptomatic ulcerative colitis is presented. Complete remission was achieved with topical steroids; no systemic treatment was required.

Clinicopathological cases - Case 1 - Mucous membrane pemphigoid, epidermolysis bullosa acquisita and linear immunoglobulin A (Iga) disease.

A 71-year-old male was referred in 1997 with a 1-year history of recurrent oral ulceration. When questioned further, he admitted to skin problems in the groin and on the penis. He also had a history of peri-anal problems dating back to 1991, and in 1994 this was treated with a defunctioning colostomy. This was followed by a peristomal dermatitis and in 1995 the colostomy was reversed. The clinical appearance in 1997 is shown in Fig. 1a–c. A skin biopsy is shown in Fig. 2.