Charles Lynde

Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial.

Background  Patients with severe chronic hand eczema (CHE) refractory to topical corticosteroids currently have limited treatment options suited for chronic use, and few controlled clinical studies have investigated new therapies in this setting.

The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010-2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.

Onychomycosis in children: Prevalence and treatment strategies

BACKGROUND Onychomycosis is observed less frequently in children than adults. Until recently management of onychomycosis in children included topical formulations, oral griseofulvin, and in some cases deferral of treatment. OBJECTIVE We attempted to determine the prevalence of onychomycosis in North American children 18 years old or younger attending our dermatology offices (three Canadian, two U.S.) and to report the groups experience using fluconazole, itraconazole, and terbinafine for onychomycosis. METHODS We undertook a prospective, multicenter survey in which all children, regardless of presenting complaint, were examined for onychomycosis by a dermatologist. In instances of clinical suspicion appropriate nail samples were obtained for light microscopy and culture. RESULTS A total of 2500 children under age 18 were examined in the five-center survey (1117 males and 1383 females, mean +/- S.E. age: 11.2 +/- 0.1 years). There was one child with fingernail and ten with mycologically confirmed toenail dermatophyte onychomycosis. The overall prevalence of onychomycosis was 0.44%. Considering those children whose primary or referring diagnosis was not onychomycosis or tinea pedis, the prevalence of onychomycosis was 0.16%. Outside the survey we have seen six other children with dermatophyte onychomycosis; these 17 cases form the basis for the remainder of the report. Of the 17 children, eight (47%) had concomitant tinea pedis infection, and in 11 (65%) a sibling, parent, or grandparent had onychomycosis or tinea pedis. Management included topical terbinafine (two patients: one cured, one failed therapy), topical ketoconazole (one patient: clinical improvement), oral fluconazole (two patients: one cured, one had Downs syndrome and was noncompliant), oral itraconazole (four patients: three cured with subsequent recurrence at follow-up in one patient, one lost to follow-up), oral terbinafine (five patients: four cured with subsequent recurrence at follow-up in one patient, one failed therapy). One child received no therapy following discussion with the parents, one was lost to follow-up and one was found to have asymptomatic hepatic dysfunction with hepatitis C at pretherapy bloodwork. CONCLUSION The prevalence of onychomycosis in our sample of North American children 18 years old or younger was 0.44% (n = 2500). In the subset of children whose primary or referring diagnosis was not onychomycosis, the prevalence of onychomycosis was 0.16%. Children with onychomycosis should be carefully examined for concomitant tinea pedis, and their parents and siblings checked for onychomycosis and tinea pedis. The newer oral antifungal agents fluconazole, itraconazole, and terbinafine may be effective and well-tolerated in the treatment of onychomycosis in this age group. These drugs should be carefully evaluated in a larger cohort of children with onychomycosis.

Interleukin 17A: Toward a new understanding of psoriasis pathogenesis

Molecular and cellular understanding of psoriasis pathogenesis has evolved considerably over the last 30 years beginning in the early 1980s when psoriasis was thought to be a skin disease driven by keratinocyte hyperproliferation. During the next 20 years, the role of the immune system and T-helper (Th) cells in psoriasis pathogenesis was recognized. The presence of the interleukin (IL)-12 cytokine in psoriatic lesions led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as proximal regulators of psoriatic skin inflammation. IL-17A, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other proinflammatory mediators thereby enabling IL-17A to bridge the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. Several monoclonal antibodies that inhibit the IL-17 pathway are in clinical development. These agents exhibit promising clinical efficacy and tolerability profiles including immunohistochemical improvement in psoriatic plaques. Results from clinical trials with IL-17 pathway inhibitors are refining our understanding of psoriasis pathogenesis and may provide a new therapeutic approach for patients with moderate to severe psoriasis.

Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa.

BACKGROUND Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa. METHODS PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12. RESULTS We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences. CONCLUSIONS Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

Terbinafine therapy may be associated with the development of psoriasis de novo or its exacerbation: Four case reports and a review of drug-induced psoriasis

Adverse effects may occur in 10.4% of patients receiving terbinafine therapy, with cutaneous reactions in 2.7%. We describe the development of psoriasis in four patients who took oral terbinafine. Two patients had plaque-type psoriasis that flared 12 and 17 days, respectively, after starting terbinafine. Another patient developed pustular-type psoriasis de novo after 27 days of terbinafine therapy. The fourth patient was a psoriatic with stable plaque disease who experienced a pustular flare after taking terbinafine for 21 days. We are aware of only one report in the literature in which a patient developed pustular psoriasis de novo after 5 days of terbinafine therapy. In all patients the psoriasis cleared or lessened after discontinuation of terbinafine and institution of antipsoriatic therapy.

International multicenter psoriasis and psoriatic arthritis reliability trial for the assessment of skin, joints, nails, and dactylitis.

OBJECTIVE Clinical trials in psoriasis and psoriatic arthritis (PsA) involve assessment of the skin and joints. This study aimed to determine whether assessment of the skin and joints in patients with PsA by rheumatologists and dermatologists is reproducible. METHODS Ten rheumatologists and 9 dermatologists from 7 countries met for a combined physical examination exercise to assess 20 PsA patients (11 men, mean age 51 years, mean PsA duration 11 years). Each physician assessed 10 patients according to a modified Latin square design that enabled the assessment of patient, assessor, and order effect. Tender joint count (TJC), swollen joint count (SJC), dactylitis, physicians global assessment (PGA) of PsA disease activity (PGA-PsA), psoriasis body surface area (BSA), Psoriasis Area and Severity Index (PASI), Lattice System Physicians Global Assessment of psoriasis (LS-PGA), National Psoriasis Foundation Psoriasis Score (NPF-PS), modified Nail Psoriasis Severity Index (mNAPSI), number of fingernails with nail changes (NN), and PGA of psoriasis activity (PGA-Ps) were assessed. Variance components analyses were carried out to estimate the intraclass correlation coefficient (ICC), adjusted for the order of measurements. RESULTS There is excellent agreement (ICC >/=0.80) on the mNAPSI, substantial agreement (0.6 >/= ICC < 0.80) on the TJC, PASI, and NN, moderate agreement (0.4 >/= ICC < 0.60) on the PGA-Ps, LS-PGA, NPF-PS, and BSA, and fair agreement (0.2 >/= ICC < 0.40) on the SJC, dactylitis, and PGA-PsA. The only measure that showed a significant difference between dermatologists and rheumatologists was dactylitis (P = 0.0005). CONCLUSION There is substantial to excellent agreement on the TJC, PASI, NN, and mNAPSI among rheumatologists and dermatologists.

Moderate to severe plaque psoriasis with scalp involvement: A randomized, double-blind, placebo-controlled study of etanercept

BACKGROUND Biologic therapies are used to treat moderate to severe psoriasis, but evidence from randomized, controlled studies is lacking regarding scalp-related effectiveness. OBJECTIVE To evaluate the efficacy and safety of etanercept for scalp symptoms (erythema, induration, scale, and percentage of scalp involvement) in patients with moderate to severe plaque psoriasis and scalp involvement. METHODS In this randomized, placebo-controlled study, adult patients with stable plaque psoriasis and significant scalp symptoms received etanercept 50 mg twice weekly (BIW) by subcutaneous injection (SC) for 12 weeks, followed by etanercept 50 mg once weekly (QW) and placebo QW (Group A, n = 62) or SC placebo BIW for 12 weeks, followed by etanercept 50 mg BIW for 12 weeks (Group B, n = 62). The primary end point was percentage change in Psoriasis Scalp Severity Index (PSSI) at week 12. RESULTS Demographics and disease characteristics were balanced: 56% men, 73% white, median age 41 years, median BMI 30.2 kg/m(2). At week 12, mean PSSI improvement was 86.8% (standard deviation [SD], 18.0%) in Group A and 20.4% (SD, 39.3%) in Group B (P < .0001). At week 24, mean PSSI improvements were as follows: Group A, 90.6% (SD 13.1%); Group B, 79.1% (SD 33.6%). At week 12, 51 of 59 (86%) Group A patients and 7 of 61 (11%) Group B patients achieved PSSI 75 (P <.0001). Three patients (2.7%) reported 5 serious adverse events: cholecystitis/cholelithiasis, fall/rib fracture, and metastatic malignant melanoma. LIMITATIONS The study was insufficiently powered to detect rare adverse events potentially associated with etanercept. CONCLUSIONS Etanercept is an effective, well-tolerated treatment for plaque psoriasis involving the scalp.

Itraconazole pulse therapy is effective in the treatment of tinea capitis in children: an open multicentre study

In an open multicentre study we have demonstrated that itraconazole pulse therapy, 5 mg/kg per day, is effective and safe in the management of tinea capitis in 10 children (seven boys, three girls, mean age: 6.6 years, age range 4–11 years). The causative organisms were Trichophyton tonsurans (six cases), T. violaceum (two cases), T. soudanense (one case) and Microsporum gypseum (one case). Each pulse of drug therapy lasted 1 week with 2 weeks off between consecutive pulses. One, two and three pulses produced complete, clinical and mycological, cure in one, six and three patients, respectively. The children tolerated the treatment well and there were no clinical or laboratory adverse effects. This 1‐week pulse therapy regimen resulted in a high degree of compliance. The preliminary results of this study are promising and need to be evaluated in a larger sample of patients.

Development and validation of a comprehensive acne severity scale.

Background: Although more than 25 acne grading systems exist, only 2 are inclusive of truncal acne. There is neither a gold standard nor a consistently used standardized system. Purpose: Our purpose was to develop and validate an acne grading system incorporating severity at the face, chest, and back. Methods: We developed a comprehensive acne severity scale (CASS) by modifying a preexisting facial acne scale, the Investigator Global Assessment, to include truncal acne. The validity and responsiveness of CASS grades were correlated with Leeds scores at baseline and after 6 months of standard acne treatment. Results: Spearman correlations were significant between Leeds and CASS grades for the face (0.823), chest (0.854), and back (0.872), respectively (p < .001). After 6 months of therapy, changes in these scores were also significantly correlated (p < .001) at all three sites. Conclusion: Concurrent validity of CASS is demonstrated by a very strong correlation with Leeds grading. CASS is simpler to use than the Leeds system and more appropriate for translation of research trial results to clinical practice.