L. Puig

Efficacy of biologics in the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials with different time points

Differences in response rates of biologics for the treatment of moderate‐to‐severe plaque psoriasis have been reported in several meta‐analyses published to date. However, the usefulness of these meta‐analyses is limited as they do not reflect currently approved recommendations in the Summaries of Product Characteristics (SmPCs) and clinical practice.

Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management.

The recognition of the central role of interleukin (IL)‐17A in the pathogenesis of psoriasis has led to the development of several monoclonal antibodies targeting this cytokine or its receptors for therapeutic purposes. IL‐17A also plays an important role in immunological protection against infections, especially those due to Candida spp., as evidenced by findings in patients with genetic defects in IL‐17‐related immune responses. To assess the potential of anti‐IL‐17 treatment to promote Candida infections, here we have systematically reviewed published clinical trials of patients with psoriasis or psoriatic arthritis. Candida infections were reported in 4·0% of patients treated with brodalumab, 1·7% with secukinumab and 3·3% with ixekizumab vs. 0·3%, 2·3% and 0·8% of those assigned to placebo, ustekinumab or etanercept, respectively. Although the incidence of Candida infection was found to be increased by only a small degree during anti‐IL‐17 therapy, patients undergoing such treatment should be monitored for fungal infection and treated as necessary. We propose adoption of the recently updated recommendations for the practical management of Candida infection in patients administered IL‐17 inhibitors.

Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double‐blind, phase III NAVIGATE trial

Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials.

Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long‐term management with anti‐inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti‐inflammatory treatment of AD. Pimecrolimus 1% is approved for second‐line use in children (≥2 yr old) and adults with mild‐to‐moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long‐term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short‐ and long‐term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long‐term intermittent use. Unlike topical corticosteroids, long‐term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post‐marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.

Enzyme‐linked immunosorbent assay (ELISA) and indirect immunofluorescence testing in a bullous pemphigoid and pemphigoid gestationis

Enzyme‐linked immunosorbent assay (ELISA) is an excellent tool for detection of circulating antibodies against the NC16A portion of BP180 antigen. We compared the sensitivity and specificity of a commercially available BP180‐NC16a domain ELISA with that of an indirect immunofluorescence (IIF) testing in the evaluation of bullous pemphigoid (BP) and pemphigoid gestationis (PG), and analyzed the relationship between ELISA results and the presence of IgG deposition, in an epidermal or combined pattern, on direct immunofluorescence (DIF) testing of salt‐split skin. ELISA was performed on serum from 28 patients (24 BP, 4 PG) and 50 controls. IIF testing was performed on serum from 27 patients and 98 controls. For the group of 28 patients with BP or PG, ELISA had a sensitivity of 93% and specificity of 96% (P < 0.001), while sensitivity was 74% and specificity 96% (P < 0.001) for IIF testing. In these patients, ELISA has a higher sensitivity than IIF testing, but similar specificity. Evaluation of controls who had IgG deposition on the dermal side of salt‐split skin on DIF testing showed specificity for the ELISA of 100% (all four cases negative) and 80% for IIF testing (one of five positive). Positive ELISA correlated with a diagnosis of BP or PG only in patients who had IgG at the basement membrane zone (BMZ) by DIF testing. Overall, ELISA appears to have greater sensitivity and specificity for BP or PG than does IIF testing.

Consensus document on the evaluation and treatment of moderate-to-severe psoriasis: Psoriasis Group of the Spanish Academy of Dermatology and Venereology

Psoriasis is a highly prevalent disease with a major impact on quality of life; therefore, appropriate patient management is mandatory. Given that many issues in psoriasis are controversial and not clearly defined by evidence‐based medicine, management of psoriasis is very variable. Expert consensus can generate practical guidelines for optimization of patient care. Much has changed since 2009, when the Consensus Document on the Evaluation and Treatment of Moderate to Severe Psoriasis was published by the Spanish Psoriasis Group (GEP) of the Spanish Academy of Dermatology and Venereology (AEDV). The objective of the present consensus document is to provide the dermatologist with updated recommendations for the evaluation and treatment of patients with moderate‐to‐severe plaque psoriasis. All active members of the GEP of the AEDV were invited to participate in the survey. The final group comprised 46 members from various areas of Spain and with substantial experience in managing psoriasis. A 3‐round Delphi process was used to reach consensus. Consistent agreement and consistent disagreement (consensus) required the achievement of at least two of the following three criteria: Criterion 1, which was based on the position occupied by the mean on a scale of 1–9 and an SD <2; Criterion 2, which was based on the median and interquartile range (IQR) on a scale of 1–9; Criterion 3, which considered the percentage of the voting experts on a scale of 1–9. The items studied were definition of severity, therapeutic objectives, indications for systemic treatment and biologic therapy, induction and maintenance periods, therapeutic failure, loss of response, relapse and rebound, continuous and intermittent therapy, screening of patients before treatment, adherence to therapy, follow‐up of treatment outcome, combination of drugs, transitioning and associated comorbidities. Consistent agreement or disagreement (consensus) was achieved for 198 items (agreement, 3 criteria 146 items, 2 criteria 43 items; disagreement, 3 criteria 9 items, 2 criteria 0 items) based on the criteria described above. Completion of the Delphi consensus process enabled a broad and experienced group of Spanish psoriasis experts to provide useful and practical guidelines for the management and treatment of patients with moderate‐to‐severe psoriasis, particularly in areas where evidence is lacking.

Psoriasis beyond the skin: an expert group consensus on the management of psoriatic arthritis and common co-morbidities in patients with moderate-to-severe psoriasis.

Psoriatic arthritis (PsA) and co‐morbidities of psoriasis represent a significant clinical and economic burden for patients with moderate‐to‐severe psoriasis. Often these co‐morbidities may go unrecognized or undertreated. While published data are available on the incidence and impact of some of them, practical guidance for dermatologists on detection and management of these co‐morbidities is lacking.

Long-term study of infliximab for psoriasis in daily practice: drug survival depends on combined treatment, obesity and infusion reactions.

Infiximab has been shown to be highly effective in phase III clinical trials, but limited information is available regarding drug survival and maintenance of efficacy beyond 1 year in real‐life clinical setting.

One‐year safety and efficacy of ustekinumab and results of dose adjustment after switching from inadequate methotrexate treatment: the TRANSIT randomized trial in moderate‐to‐severe plaque psoriasis

There are limited long‐term, ‘real‐world’ data on ustekinumab, or the effect of dose adjustment in suboptimal responders.

Grover Disease: A Reappraisal of Histopathological Diagnostic Criteria in 120 Cases

Grover disease (GD) is a rather common papular pruritic dermatosis that can be transient, persistent, or asymptomatic. The microscopic diagnosis of clinically suspected lesions can be challenging because GD can adopt different patterns, and involved areas are generally admitted to be mostly focal. The histopathologic hallmark of the disease is acantholysis, frequently combined with dyskeratosis, which confers the lesions an appearance similar to Darier disease, Hailey-Hailey disease, or pemphigus. Eczematous features can be observed as well. In this study of 120 consecutive cases of GD, we have found a sex and age incidence similar to what has been previously described, with no obvious seasonal influence, but careful evaluation of their microscopic features suggests that the histopathological diagnostic criteria of GD should be expanded. Specifically, in addition to the commonly described GD findings, we have detected cases with porokeratosis-like oblique columns of parakeratosis, lesions showing a nevoid or lentiginous silhouette, intraepidermal vesicular lesions, lichenoid changes with basal vacuolization and dyskeratosis, and dysmaturative foci with keratinocyte atypia. Moreover, quite often the dermal infiltrate was composed not only of lymphocytes intermingled with eosinophils, but also of neutrophils. In many cases, the capillary vessels showed hints of vascular damage including endothelial tumefaction due to cytoplasmatic edema and erythrocyte extravasation. Finally, because involved areas were larger than 2 mm in more than 50% of our cases, we should assume that GD lesions are not always as small as commonly claimed. Awareness of the patterns newly described herein may be important to avoid underdiagnosis of GD and may contribute to understand the pathogenesis of this acantholytic disease.