Faisal R. Ali

Genetic susceptibility to psoriasis and psoriatic arthritis: implications for therapy

The era of genome‐wide association studies has revolutionized the search for genetic susceptibility loci in complex genetic conditions such as psoriasis. There are currently 16 loci with confirmed evidence for association with psoriasis susceptibility but there is the potential for more to be discovered as the genetic heritability of the disease has not yet been fully explained. Many of the associated loci overlap with those for psoriatic arthritis. In contrast to psoriasis susceptibility, few studies have been performed to identify predictors of drug response in psoriasis. As large‐scale collaborations and registries for psoriasis and psoriatic arthritis are established, it is likely that a genome‐wide approach may be used as a more effective method of searching for genetic predictors of treatment response. However, candidate gene studies will still have a role; for example, it is likely that some disease susceptibility genes will also be markers of treatment response, based on evidence from other diseases. This review summarizes recent advances in investigating the role genetics plays in psoriasis susceptibility and contrasts these to advances made in psoriatic arthritis. Further, it describes the genetics of treatment response in the two diseases and indicates how susceptibility loci could be used to identify drug response in the future.

Impact of Psychological Factors on Subjective Disease Activity Assessments in Patients With Severe Rheumatoid Arthritis

The Disease Activity Score in 28 joints (DAS28), used to assess disease activity in rheumatoid arthritis (RA), is a composite score comprising clinical, biochemical, and patient self‐report measures. We hypothesized that psychological factors (cognitions and mood) would be more strongly associated with patient‐reported components of the DAS28 than clinical or biochemical components.

Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort

Objective A number of rheumatoid arthritis (RA) susceptibility genes have been identified in recent years. Given the overlap in phenotypic expression of synovial joint inflammation between RA and psoriatic arthritis (PsA), the authors explored whether RA susceptibility genes are also associated with PsA. Methods 56 single nucleotide polymorphisms (SNPs) mapping to 41 genes previously reported as RA susceptibility loci were selected for investigation. PsA was defined as an inflammatory arthritis associated with psoriasis and subjects were recruited from the UK and Ireland. Genotyping was performed using the Sequenom MassArray platform and frequencies compared with data derived from large UK control collections. Results Significant evidence for association with susceptibility to PsA was found toa SNP mapping to the REL (rs13017599, ptrend=5.2×104) gene, while nominal evidence for association (ptrend<0.05) was found to seven other loci including PLCL2 (rs4535211, p=1.7×10−3); STAT4 (rs10181656, p=3.0×10−3) and the AFF3, CD28, CCL21, IL2 and KIF5A loci. Interestingly, three SNPs demonstrated opposite effects to those reported for RA. Conclusions The REL gene, a key modulator of the NFκB pathway, is associated with PsA but the allele conferring risk to RA is protective in PsA suggesting that there are fundamental differences in the aetiological mechanisms underlying these two types of inflammatory arthritis.

Telemedicine for Peer-to-Peer Psychiatry Learning Between U.K. and Somaliland Medical Students

ObjectiveThe proportion of U.K. medical students applying for psychiatry training continues to decline, whereas, in Somaliland, there are no public-sector psychiatrists. This pilot study assessed the usefulness and feasibility of online, instant messenger, peer-to-peer exchange for psychiatry education between cultures.MethodsTwenty medical students from King’s College, London, and Hargeisa University (Somaliland) met online in pairs every 2 weeks to discuss prearranged psychiatric topics, clinical cases, and treatment options, completing online evaluations throughout.ResultsAverage ratings of the enjoyment, academic helpfulness, and interest of sessions were 4.31, 3.56, and 4.54 (of a maximum of 5), respectively; 83% would recommend the partnership to a friend.ConclusionsThis partnership enabled students on both sides to exploit psychiatry-learning resources at the other’s disposal, outside the standard medical education context, illustrating the benefits to medical students in dramatically different locations of partnership through telemedicine. This pilot study presents an innovative, cost-effective, under-used approach to international medical education.

Escalating methylisothiazolinone/methylchloroisothiazolinone allergy probably attributable to methylisothiazolinone in leave-on body cosmetics

Faisal R. Ali1, Elizabeth L. Shepherd2, Laura C. Yell2, Deirdre A. Buckley3 and Jason D. L. Williams1 1Contact Dermatitis Investigation Unit, Dermatology Centre, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, University of Manchester, Stott Lane, Manchester, M6 8HD, UK, 2University of Manchester Medical School, Stopford Building, Oxford Road, Manchester, M13 9PT, UK, and 3Dermatology Department, Royal United Hospital Bath NHS Trust, Combe Park, Bath, BA1 3NG, UK

Systemic treatments for basal cell carcinoma (BCC): the advent of dermato-oncology in BCC

Basal cell carcinoma (BCC) is the most common cancer in the U.K. and its incidence is increasing. Vismodegib, a hedgehog pathway inhibitor, has recently been licensed by the U.S. Food and Drug Administration for treatment of advanced BCC. Phase 2 trials have demonstrated efficacy in cases of locally advanced and metastatic BCC, as well as cases of hereditary basal cell naevus (Gorlin) syndrome. Side‐effects are frequent and considerable and include myalgia, taste disturbance, alopecia, weight loss and fatigue. Further research is needed to investigate means of circumventing these side‐effects, and longitudinal data are required to assess the long‐term benefits of, and the nature of resistance to, this novel class of agents. Alternative hedgehog inhibitors are currently in clinical development. We review the current data pertaining to this novel treatment modality and discuss its likely future role in the management of BCC.

An investigation of rheumatoid arthritis loci in patients with early-onset psoriasis validates association of the REL gene.

Background  Phenotypically diverse autoimmune conditions share common genetic susceptibility loci and underlying molecular pathways.

Guttate psoriasis is associated with an intermediate phenotype of impaired Langerhans cell migration.

An episode of guttate psoriasis can be an isolated event, can recur as guttate episodes, or develop into chronic plaque psoriasis (CPP). A previous study revealed that early‐onset (before age 40 years) CPP is associated with inhibition of epidermal Langerhans cell (LC) migration.

Psoriasis and susceptibility to other autoimmune diseases: An outline for the clinician

Psoriasis is a chronic inflammatory disease affecting 2% of the adult population. Common cutaneous manifestations include well-defined red plaques with a silvery-white scale, typically distributed symmetrically on extensor surfaces [1]. The multisystem nature of psoriasis, namely its association with a seronegative arthropathy and the metabolic syndrome, is now well established. During the last decade, it has become increasingly recognized that psoriasis is part of an autoimmune spectrum in which diverse diseases share common underlying genetic susceptibility loci, molecular mechanisms and treatment modalities. We will review existing evidence and explore the implications this may have to the practicing clinician.

Tacrolimus toxicity following topical treatment of perianal Crohn's disease: An admonitory anecdote

Dear Sir, A 23 year old female with a 12 year history of Crohns disease had received a variety of systemic and biologic therapies, all of which were either of poor efficacy or had been poorly tolerated. Most recently an end ileostomy and rectal stump had been formed, with a view to ileal pouch formation at a later date. However, our patient continued to develop deep ulceration of the anal verge and distal rectum, despite daily application of superpotent topical corticosteroid ointment. A trial of once daily topical application of 1 g tacrolimus …