Jane Setterfield

Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50 patients with cicatricial pemphigoid.

In this study we investigated sera from 50 typical cicatricial pemphigoid (CP) patients. By indirect immunofluorescence on 1 M NaCl-split human skin sections, IgG of 17 sera and IgA of 22 sera reacted with the epidermal side of the split, while IgG of two sera reacted with the dermal side. These latter two sera were later confirmed to be anti-epiligrin CP. By immunoblotting of epidermal extracts, IgG of 14 sera reacted with the 230 kD bullous pemphigoid (BP) antigen (BP230). IgG of 15 sera and IgA of 11 sera reacted with the 180 kD BP antigen (BP180). Interestingly, a bacterial fusion protein containing the BP180 NC16a domain was recognized by IgG of 18 sera but not by IgA of any sera. Fusion proteins containing the C-terminal region of BP180 were recognized by IgG of 20 sera, but it was detected by IgA of only two sera. Our results suggest that, although CP sera show very low titers of autoantibodies, a considerable number of sera contain IgG antibodies to BP180 (either NC16a or C-terminal domain), confirming previous studies. In addition, we showed that greater numbers of IgA antibodies react with BP180, seemingly with different types of epitopes from those for IgG antibodies. Because the specificity of IgG antibodies is not very different from those in BP, IgA antibodies may play a specific role for the development of characteristic clinical features in CP. Future studies should elucidate the pathogenic role of the IgA antibodies in CP.

Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity

Background  Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically.

The management of oral lichen planus

Oral lichen planus is a relatively common inflammatory disease affecting between 0.5% and 2.2% of the population in epidemiological studies. In contrast with cutaneous lichen planus (LP), in which the clinical course is often mild and resolves within 2 years, mucosal LP tends to follow a more chronic course often punctuated by acute exacerbations. Furthermore, although distinct clinical subtypes such as reticular, atrophic, hypertrophic and erosive forms are well recognized, more than one clinical phenotype may be seen at a time. The rare association with oral neoplasia should always be considered and high‐risk patients must be kept under close observation. Thus the management of this disorder will vary widely both between patients, and for individual patients, with fluctuations in disease activity. Here we discuss the therapeutic options available and review the evidence for their use.

An evaluation of the usefulness of mycophenolate mofetil in pemphigus

Summary Background Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term.

A scoring system for mucosal disease severity with special reference to oral lichen planus

Background  To date, there is only weak evidence for the superiority of any interventions over placebo for the palliation of symptomatic oral lichen planus (LP). Further research involving large placebo‐controlled, randomized clinical trials is needed. These will require carefully selected and standardized outcome measures.

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 (n = 67) 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 32.2 ± 20.3 (mean ± SD) months. Antibody titres were correlated with the clinical score recorded at each follow‐up visit. Sequential titres for both IgG (P < 0.001) and IgA (P = 0.015) 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.

U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016.

U.K. guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults 2016 D. Creamer, S.A. Walsh, P. Dziewulski, L.S. Exton, H.Y. Lee, J.K.G. Dart, J. Setterfield, C.B. Bunker, M.R. Ardern-Jones, K.M.T. Watson, G.A.E. Wong, M. Philippidou, A. Vercueil, R.V. Martin, G. Williams, M. Shah, D. Brown, P. Williams, M.F. Mohd Mustapa and C.H. Smith Department of Dermatology, King’s College Hospital NHS Foundation Trust, London SE5 9RS, U.K. St Andrews Centre for Plastic Surgery and Burns, Mid Essex Hospital Services NHS Trust, Chelmsford CM1 7ET, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. Dermatology Unit, Singapore General Hospital, Singapore Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, U.K. Mucosa and Salivary Biology, Dental Institute, King’s College London, Guy’s Campus, Great Maze Pond, London SE1 9RT, U.K. University College Hospital, London NW1 2BU, U.K. Clinical Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, U.K. Department of Dermatology, Orpington Hospital, Orpington, Kent BR6 9JU, U.K. Department of Dermatology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, U.K. Department of Histopathology and Intensive Care Medicine, King’s College Hospital NHS Foundation Trust, London SE5 9RS, U.K. Late of the Burns Centre, Chelsea and Westminster NHS Foundation Trust, London SW10 9NH, U.K. Department of Burns and Plastic Surgery, University Hospitals of South Manchester, Southmoor Road, Wythenshawe, Manchester M23 9LT, U.K. St John’s Institute of Dermatology, Guy’s and St Thomas NHS Foundation Trust, London SE1 9RT, U.K.

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.

Efficacy of mycophenolate mofetil in severe mucocutaneous lichen planus: a retrospective review of 10 patients

Summary Background  Ulcerative lichen planus is an uncommon and severe subtype of lichen planus primarily affecting the oral mucosal surfaces. It may be associated with significant morbidity and often requires immunosuppressive therapy to achieve disease control. There have been no previous reports in which objective outcome measures have been used to assess the efficacy of mycophenolate mofetil (MMF) in severe ulcerative lichen planus.