Dermatology

Ammar, M., C. T. Jordan, L. Cao, E. Lim, C. Bouchlaka Souissi, A. Jrad, I. Omrane, S. Kouidhi, I. Zaraa, H. Anbunathan, M. Mokni, N. Doss, E. Guttman-Yassky, A. B. El Gaaied, A. Menter and A. M. Bowcock (2016). “CARD14 alterations in Tunisian patients with psoriasis and further characterization in European cohorts.” Br J Dermatol 174(2): 330-337.

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BACKGROUND: Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. OBJECTIVES: To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. METHODS: CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-kappaB signalling. RESULTS: Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-kappaB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-kappaB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. CONCLUSIONS: These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.

Pascoe, V. L., A. Z. Fenves, J. Wofford, J. M. Jackson, A. Menter and A. B. Kimball (2016). “The spectrum of nephrocutaneous diseases and associations: Inflammatory and medication-related nephrocutaneous associations.” J Am Acad Dermatol 74(2): 247-270.

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There are a significant number of dermatoses associated with renal abnormalities and disease, and dermatologists need to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations and recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae. Part II of this 2-part continuing medical education article addresses inflammatory and medication-related nephrocutaneous associations.

Wofford, J., A. Z. Fenves, J. M. Jackson, A. B. Kimball and A. Menter (2016). “The spectrum of nephrocutaneous diseases and associations: Genetic causes of nephrocutaneous disease.” J Am Acad Dermatol 74(2): 231-244.

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There are a significant number of diseases and treatment considerations of considerable importance relating to the skin and renal systems. This emphasizes the need for dermatologists in practice or in clinical training to be aware of these associations. Part I of this 2-part continuing medical education article reviews the genetic syndromes with both renal and cutaneous involvement that are most important for the dermatologist to be able to identify, manage, and appropriately refer to nephrology colleagues. Part II reviews the inflammatory syndromes with relevant renal manifestations and therapeutic agents commonly used by dermatologists that have drug-induced effects on or require close consideration of renal function. In addition, we will likewise review therapeutic agents commonly used by nephrologists that have drug-induced effects on the skin that dermatologists are likely to encounter in clinical practice. In both parts of this continuing medical education article, we discuss diagnosis, management, and appropriate referral to our nephrology colleagues in the context of each nephrocutaneous association. There are a significant number of dermatoses associated with renal abnormalities and disease, emphasizing the need for dermatologists to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations with recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae.

Bhushan, R., M. G. Lebwohl, A. B. Gottlieb, K. Boyer, E. Hamarstrom, N. J. Korman, R. S. Kirsner, A. J. Sober and A. Menter (2016). “Translating psoriasis guidelines into practice: Important gaps revealed.” J Am Acad Dermatol. 74(3): 544-551.

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BACKGROUND: There is a well-established lack of adherence to evidence-based clinical guidelines. The American Academy of Dermatology (AAD) developed educational sessions entitled Translating Evidence into Practice based on the published guidelines for psoriasis and psoriatic arthritis. OBJECTIVE: We sought to determine the effectiveness of Translating Evidence into Practice sessions in improving patient care. METHODS: Pre- and post-session surveys were administered at Translating Evidence into Practice sessions. A follow-up was administered 6 months after completion of the most recent session, which was 2.5 years after the first session. RESULTS: At both post-session and follow-up, more than 92% of participants believed the sessions had improved their knowledge. The proportion of participants that self-reported assessing disease severity, comorbidities, and quality of life increased at follow-up. Participants’ self-reported counseling of patients and confidence in treating psoriasis and psoriatic arthritis also increased at post-session and follow-up. Greater than 97% of participants thought the sessions would have a positive impact on their practice whereas 50% reported making a change in practice. LIMITATIONS: Lack of a control group, the self-reported nature of the data, and potential participant bias are limitations. CONCLUSION: The AAD’s Translating Evidence into Practice sessions are effective and well received for improving knowledge and practice and can be useful to determine self-reported practice gaps.

Papp, K., M. A. Menter, M. Raman, D. Disch, D. E. Schlichting, C. Gaich, W. Macias, X. Zhang and J. M. Janes (2016). “A Randomized Phase 2b Trial of Baricitinib, an Oral JAK1/JAK2 Inhibitor, in Patients with Moderate-to-Severe Psoriasis.” Br J Dermatol. Jan 22. doi: 10.1111/bjd.14403. [Epub ahead of print]

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BACKGROUND: The safety and efficacy of baricitinib, an oral JAK1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis was evaluated in a randomized, double-blind, placebo-controlled, dose-ranging phase 2b study. METHODS: Patients were randomized (n=271) to receive placebo or oral baricitinib at 2, 4, 8, or 10 mg once daily for 12 weeks (Part A). Dose adjustment for 12 additional weeks was based on percentage improvement in Psoriasis Area and Severity Index (PASI) score. OBJECTIVES: Primary endpoint was PASI-75 at 12 weeks for North American patients (n=238); secondary were safety and efficacy measures in the entire population. RESULTS: At week 12, more North American patients in 8-mg (43%) and 10-mg (54%) baricitinib groups than in placebo group (17%; p<0.05) achieved PASI-75. All baricitinib-treated groups had greater mean changes from baseline in PASI score (p<0.05) at 12 weeks and (except 2 mg) had higher rates of PASI-50 than placebo group; statistically significant PASI-90 responses were achieved in the 8-mg and 10-mg groups at 8 and 12 weeks. More than 81% of PASI-75 responders maintained their scores through 24 weeks. During Part A, study discontinuations due to adverse events (AEs) were 0%, 0%, 2.8%, 6.3%, and 5.8% and treatment-emergent AE rates were 44%, 50%, 47%, 58%, and 64% for placebo and 2-, 4-, 8-, and 10-mg baricitinib groups, respectively. No opportunistic infections were observed in any treatment group. Dose-dependent changes in laboratory values were observed. CONCLUSION: Patients with moderate-to-severe psoriasis treated with baricitinib for 12 weeks achieved significant improvements in PASI-75.