Pemphigus represents a group of rare and severe autoimmune intra-epidermal blistering diseases affecting the skin and mucous membranes. These painful and debilitating diseases are driven by the production of autoantibodies that are mainly directed against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). The search to define underlying triggers for anti-Dsg-antibody production has revealed genetic, environmental, and possible vaccine-driven factors, but our knowledge of the processes underlying disease initiation and pathology remains incomplete. Recent studies point to an important role of T cells in supporting auto-antibody production; yet the involvement of the myeloid compartment remains unexplored. Clinical management of pemphigus is beginning to move away from broad-spectrum immunosuppression and towards B-cell-targeted therapies, which reduce many patients’ symptoms but can have significant side effects. Here, we review the latest developments in our understanding of the predisposing factors/conditions of pemphigus, the underlying pathogenic mechanisms, and new and emerging therapies to treat these devastating diseases.

Introduction: Atopic dermatitis is a common, chronic pruritic condition affecting both children and adults, which has a negative impact on the quality of life. These guidelines were developed by an expert workgroup appointed by the Dermatological Society of Singapore, to provide doctors with information to assist in the management of their patients with atopic dermatitis. The workgroup members are experienced dermatologists with interest and expertise in eczemas. Materials and Methods: Workgroup members arrived at a consensus on the topics to be included. Relevant studies from the literature were assessed for best evidence, supplemented by the collective experience of the workgroup. Results: For mild atopic dermatitis, emollients, mild potency topical steroids and topical calcineurin inhibitors are recommended. For moderate-to-severe atopic dermatitis, the use of emollients, moderate-to-potent topical steroids, topical calcineurin inhibitors, wet dressings, antimicrobials for secondary skin infection, phototherapy, and systemic therapy (e.g. prednisolone, cyclosporine, azathioprine or methotrexate) may be warranted. Patients with moderate-to-severe atopic dermatitis should be managed in conjunction with a dermatologist. Conclusion: Good outcomes can be achieved with an individualised therapeutic approach combined with adequate patient and parental education. Key words: Antimicrobials, Calcineurin inhibitors, Corticosteroids, Eczema, Moisturisers

Introduction: This study aimed to assess the frequency of anxiety and depression in a cohort of adult patients with atopic dermatitis (AD) in a tertiary dermatological centre, using the Hospital Anxiety and Depression Scale (HADS). We looked for any correlation between anxiety and depression with skin disease severity. Materials and Methods: Patients with AD were recruited from the National Skin Centre, Singapore, from 2008 to 2009 for a prospective cross-sectional study. The scoring atopic dermatitis (SCORAD) grade was determined and the HADS was administered via interviews. Results: A total of 100 patients (78 males, 22 females) were enrolled (92% Chinese, 4% Malays and 4% Indians). Their average age was 25.7 years. Sixty-five percent used topical steroids, 14% had previously taken oral prednisolone for the control of disease flares, and 20% were on concurrent systemic therapy. The mean SCORAD was 55.0, with 99% of patients having moderate or severe AD. The mean HADS anxiety score was 7.2 and the mean depression score was 5.0. The level of anxiety correlated well with that of depression (Spearman’s rank correlation coefficient, ρ = 0.59, P <0.05); 18% were considered as cases of anxiety and 5% as cases of depression. These patients also had higher SCORAD values compared to other patients with lower scores for anxiety or depression (P <0.05). Linear regression demonstrated a statistically significant positive relationship between anxiety and depression scores, and SCORAD scores. Conclusion: Our study identified, by means of the HADS, the frequency of anxiety and depression amongst a cohort of Singaporean patients with AD. More severe skin disease correlated to greater psychological burden. The HADS is a useful screening tool that can constitute part of the overall holistic management of patients with AD so as to improve patient care. Key words: Eczema, HADS, Mood disorders, SCORAD

The Health Sciences Authority launched a pharmacogenetics initiative in 2008 to facilitate evaluation of pharmacogenetics associations pertinent for Chinese, Malays and Indians in Singapore. The aim was to reduce the incidence and unpredictability of serious adverse drug reactions, with a focus on serious skin adverse drug reactions. This paper describes the gathering of evidence and weighing of factors that led to different genotyping recommendations for HLA-B*15:02 with carbamazepine and HLA-B*58:01 with allopurinol, despite both having strong genetic associations. Translation of pharmacogenomics at a national level requires careful deliberation of the prevalence of at-risk allele, strength of genetic associations, positive predictive value, cost-effectiveness and availability of alternative therapies. Our experience provides a perspective on translating genomic discoveries in advancing drug safety.

Background: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans.Objectives: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. Results: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. Conclusions: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.