A review of JAK and IL-23 inhibitors to treat vitiligo.

Vitiligo is an autoimmune skin disorder resulting in the depigmentation of skin characterised by patches of varying sizes and shapes. A common disorder of pigmentation that affects 0.5%-2% of the global population. Despite its well-understood autoimmune pathogenesis, the targets for effective cytokine intervention remain unclear. Current first-line treatments include oral or topical corticosteroids, calcineurin inhibitors and phototherapy. These treatments are limited, have varying efficacies, and are associated with significant adverse events or can be time-consuming. Therefore, biologics should be explored as a potential treatment for vitiligo. There are currently limited data for the use of JAK and IL-23 inhibitors for vitiligo. A total of 25 studies were identified in the review. There is promising evidence regarding the use of JAK and IL-23 inhibitors for the treatment of vitiligo.

Psoriasis and osteoporosis: a literature review.

Psoriasis is a chronic inflammatory skin disease with complex comorbidities. Recent evidence has revealed how the inflammatory nature of psoriasis affects bone mineral density and may lead to osteoporosis. This review outlines the current understanding and advances on the association between psoriasis and osteoporosis. The current literature suggests an increased risk of osteopenia and osteoporosis in patients with extensive and chronic psoriasis, compounded by other lifestyle and genetic factors. It suggests that prophylactic measures such as vitamin D supplementation and increasing weight-bearing exercises can help, but in patients with extensive psoriasis, prolonged systemic inflammation may require long-term management. Although there have been many short-term RCTs on the efficacy and safety of biologics in psoriasis, clinical studies looking at the long-term effects of biologics, such as whether they might improve bone mineral density in these patients with psoriasis are yet to be conducted.

Probiotics for treating eczema.

BACKGROUND: Eczema is a common chronic skin condition. Probiotics have been proposed as an effective treatment for eczema; their use is increasing, as numerous clinical trials are under way. This is an update of a Cochrane Review first published in 2008, which suggested that probiotics may not be an effective treatment for eczema but identified areas in which evidence was lacking. OBJECTIVES: To assess the effects of probiotics for treating patients of all ages with eczema. SEARCH METHODS: We updated our searches of the following databases to January 2017: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, the Global Resource of Eczema Trials (GREAT) database, MEDLINE, Embase, PsycINFO, the Allied and Complementary Medicine Database (AMED), and Latin American Caribbean Health Sciences Literature (LILACS). We searched five trials registers and checked the reference lists of included studies and relevant reviews for further references to relevant randomised controlled trials (RCTs). We also handsearched a number of conference proceedings. We updated the searches of the main databases in January 2018 and of trials registries in March 2018, but we have not yet incorporated these results into the review. SELECTION CRITERIA: Randomised controlled trials of probiotics (live orally ingested micro-organisms) compared with no treatment, placebo, or other active intervention with no probiotics for the treatment of eczema diagnosed by a doctor. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. We recorded adverse events from the included studies and from a separate adverse events search conducted for the first review. We formally assessed reporting bias by preparing funnel plots, and we performed trial sequential analysis for the first primary outcome - eczema symptoms at the end of active treatment.We used GRADE to assess the quality of the evidence for each outcome (in italic font). MAIN RESULTS: We included 39 randomised controlled trials involving 2599 randomised participants. We included participants of either gender, aged from the first year of life through to 55 years (only six studies assessed adults), who had mild to severe eczema. Trials were undertaken in primary and secondary healthcare settings, mainly in Europe or Asia. Duration of treatment ranged from four weeks to six months, and duration of follow-up after end of treatment ranged from zero to 36 months. We selected no standard dose: researchers used a variety of doses and concentrations of probiotics. The probiotics used were bacteria of the Lactobacillus and Bifidobacteria species, which were taken alone or combined with other probiotics, and were given with or without prebiotics. Comparators were no treatment, placebo, and other treatments with no probiotics.For all results described in this abstract, the comparator was no probiotics. Active treatment ranged from six weeks to three months for all of the following results, apart from the investigator-rated eczema severity outcome, for which the upper limit of active treatment was 16 weeks. With regard to score, the higher the score, the more severe were the symptoms. All key results reported in this abstract were measured at the end of active treatment, except for adverse events, which were measured during the active treatment period.Probiotics probably make little or no difference in participant- or parent-rated symptoms of eczema (13 trials; 754 participants): symptom severity on a scale from 0 to 20 was 0.44 points lower after probiotic treatment (95% confidence interval (CI) -1.22 to 0.33; moderate-quality evidence). Trial sequential analysis shows that target sample sizes of 258 and 456, which are necessary to demonstrate a minimum mean difference of -2 and -1.5, respectively, with 90% power, have been exceeded, suggesting that further trials with similar probiotic strains for this outcome at the end of active treatment may be futile.We found no evidence suggesting that probiotics make a difference in QoL for patients with eczema (six studies; 552 participants; standardised mean difference (SMD) 0.03, 95% CI -0.36 to 0.42; low-quality evidence) when measured by the participant or the parent using validated disease-specific QoL instruments.Probiotics may slightly reduce investigator-rated eczema severity scores (24 trials; 1596 participants). On a scale of 0 to 103 for total Severity Scoring of Atopic Dermatitis (SCORAD), a score combining investigator-rated eczema severity score and participant scoring for eczema symptoms of itch and sleep loss was 3.91 points lower after probiotic treatment than after no probiotic treatment (95% CI -5.86 to -1.96; low-quality evidence). The minimum clinically important difference for SCORAD has been estimated to be 8.7 points.We noted significant to extreme levels of unexplainable heterogeneity between the results of individual studies. We judged most studies to be at unclear risk of bias; six studies had high attrition bias, and nine were at low risk of bias overall.We found no evidence to show that probiotics make a difference in the risk of adverse events during active treatment (risk ratio (RR) 1.54, 95% CI 0.90 to 2.63; seven trials; 402 participants; low-quality evidence). Studies in our review that reported adverse effects described gastrointestinal symptoms. AUTHORS' CONCLUSIONS: Evidence suggests that, compared with no probiotic, currently available probiotic strains probably make little or no difference in improving patient-rated eczema symptoms. Probiotics may make little or no difference in QoL for people with eczema nor in investigator-rated eczema severity score (combined with participant scoring for eczema symptoms of itch and sleep loss); for the latter, the observed effect was small and of uncertain clinical significance. Therefore, use of probiotics for the treatment of eczema is currently not evidence-based. This update found no evidence of increased adverse effects with probiotic use during studies, but a separate adverse events search from the first review revealed that probiotic treatment carries a small risk of adverse events.Results show significant, unexplainable heterogeneity between individual trial results. Only a small number of studies measured some outcomes.Future studies should better measure QoL scores and adverse events, and should report on new probiotics. Researchers should also consider studying subgroups of patients (e.g. patients with atopy or food allergies, adults) and standardising doses/concentrations of probiotics given.

Clinical application of a molecular assay for the detection of dermatophytosis and a novel non-invasive sampling technique.

The dermatophytoses are the most common superficial fungal infections worldwide. Clinical diagnosis is not reliable as there are many differentials, and laboratory diagnosis is required to gain access to treatment in more severe disease. Traditional diagnostic methods are limited by suboptimal sensitivity, specificity and prolonged turnaround times. Molecular methods are being used increasingly in the diagnostic algorithm in the clinical microbiology laboratory. The aim of this study was to evaluate a real-time polymerase chain reaction (RT-PCR) targeting the chitin synthase 1 gene (CHS1) of dermatophytes for analytical specificity, and to assess its clinical application by comparing it to the current methods of microscopy and culture. We also assessed a novel non-invasive sample collection technique involving adhesive tape impressions of suspected lesions. The PCR was highly specific, being able to discern between cultures of dermatophytes and other microorganisms. It also proved to be more sensitive than traditional methods at detecting dermatophytes in clinical samples. Similar sensitivities were seen on the samples assessed by the adhesive tape technique. An internal control system allowed for the detection of inhibition in certain culture and clinical specimens. This rapid and cost-effective technique could be incorporated into the initial diagnostic algorithm for dermatophytosis in Australian laboratories.

Itch Management: Physical Approaches (UV Phototherapy, Acupuncture).

BACKGROUND: Physical therapies refer to non-medical treatment strategies, including surgery, cryotherapy, UV phototherapy, and acupuncture. Most physical approaches are inappropriate in the context of itch. UV phototherapy and acupuncture may be effective in the management of itch. METHODS: A literature search was performed using MEDLINE and EMBASE. Bibliographies were reviewed for relevant articles. RESULTS: Narrowband UVB (311-313 nm) and UVA1 (340-400 nm) are equally effective in managing atopic dermatitis and associated itch. The efficacy of broadband UVB in reducing uraemic itch has been demonstrated in a series of randomised controlled trials, but more recent studies have failed to reproduce these results. Non-randomised, uncontrolled studies and case series suggest that UV is effective in managing itch associated with cholestasis, chronic urticaria, prurigo, cutaneous T-cell lymphoma, aquagenic itch, and scleroderma. UV phototherapy is well tolerated, and no significant relationship between UVB therapy and skin cancer has been found. Experimentally, acupuncture has been shown to reduce allergen-related itch, although this finding has been limited by the small number of studies, inconsistency in agreement on acupuncture sites and study design, small sample sizes, and limited follow-up. CONCLUSIONS: UV phototherapy is an effective treatment for itch associated with atopic dermatitis. UVB may be effective in managing itch associated with end-stage kidney disease, cholestasis, chronic urticaria, prurigo, cutaneous T-cell lymphoma, aquagenic itch, and scleroderma. Phototherapy should be combined with standard first-line therapies. Insufficient evidence exists to justify acupuncture as a physical therapy for itch. Further well-designed studies are required to establish the effectiveness of physical therapies in managing itch.

Evidence-based treatments in pemphigus vulgaris and pemphigus foliaceus.

Treatment modalities in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are many and varied, although level 1 evidence supporting their use is limited. To date, only 2 systematic reviews exist to support the use of different treatment modalities to control this group of conditions. Overall, within the literature, the quality of trials comparing treatment modalities is poor. Cohort sizes are small, methodologies are varied, and standardized outcome measurements are lacking. The authors aim to present a comprehensive view of the level 1 evidence that exists for common treatment modalities used in PV and PF.

The yin and the yang of keratin amino acid substitutions and epidermolysis bullosa simplex.

Mutations that change the same amino acid can result in different clinical phenotypes. Through in silico modeling and keratin filament assessment of genetically engineered HaCaT cells, Natsuga et al., as reported in this issue, have demonstrated how changes in charge and structure of a replacement amino acid in keratin 14 can cause disease (KRT14pA413P, EB simplex) or no clinical effect (KRT14pA413T, polymorphism).

A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus.

BACKGROUND: A range of interventions has been described for the treatment of pemphigus; however, the optimal therapeutic strategy has not been established. OBJECTIVE: We sought to evaluate the safety and efficacy of interventions for pemphigus vulgaris and pemphigus foliaceus. METHODS: We undertook a systematic review and meta-analysis according to the methodology of the Cochrane Collaboration. We selected randomized controlled trials including participants with the diagnosis of pemphigus vulgaris or pemphigus foliaceus confirmed with clinical, histopathological, and immunofluorescence criteria. All interventions were considered. Primary outcomes studied were remission and mortality. Secondary outcomes included disease control, relapse, pemphigus severity score, time to disease control, cumulative glucocorticoid dose, serum antibody titers, adverse events, and quality of life. RESULTS: Eleven studies with a total of 404 participants were identified. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor, and traditional Chinese medicine. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. LIMITATIONS: Many interventions for pemphigus have not been evaluated in controlled trials. All studies were insufficiently powered to establish definitive results. CONCLUSIONS: There is inadequate evidence available at present to ascertain the optimal therapy for pemphigus vulgaris and pemphigus foliaceus. Further randomized controlled trials are required.

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005. OBJECTIVES: To assess treatments for bullous pemphigoid. SEARCH STRATEGY: In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers. SELECTION CRITERIA: Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: At least two authors evaluated the studies for the inclusion criteria, and extracted data independently. MAIN RESULTS: We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12). AUTHORS' CONCLUSIONS: Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.

Dilated cardiomyopathy in epidermolysis bullosa: a retrospective, multicenter study.

Dilated cardiomyopathy (DC) has been reported in severe epidermolysis bullosa (EB) subtypes. Poor nutritional status, low carnitine levels, selenium deficiency, chronic iron overload, drugs and viral etiology have been proposed as potential contributors. This was a retrospective, descriptive, multicenter study describing EB patients that developed DC, and determining potential pre-disposing risk factors. Fifteen patients were enrolled in the study; 11 of them were male subjects (73%). Eighty-seven per cent of the participants had dystrophic EB and 13% had junctional EB. Mean age at diagnosis of DC was 12.18 +/- 4.99 years. Chronic anemia was diagnosed in 13 of 15 patients (86.7%). Sixty per cent of patients had prior red blood cell transfusions. At diagnosis, selenium levels were low in 55% of the patients (n = 11) and total carnitine levels were low in 45% of the patients (n = 11). Systolic function was moderately impaired, with a mean shortening fraction of 19.38% (SD = 5.04, n = 8). After a mean follow-up period of 6.3 +/- 4.8 years, six patients were alive without being on any medications (40.0%), two were alive on medications (13.3%) and seven had died (46.7%). Limitations of the study was that it was a retrospective chart review with relatively small sample size. Retrospective chart review, relatively small sample size. This study substantiates the association between DC and EB. Currently, there is no single risk factor identified in EB patients that leads to DC. Further prospective studies are needed.

Interventions for pemphigus vulgaris and pemphigus foliaceus.

BACKGROUND: A range of interventions have been described for treatment of pemphigus, however the optimal therapeutic strategy has not been established. OBJECTIVES: To assess the efficacy and safety of all interventions used in the management of pemphigus vulgaris and pemphigus foliaceus. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (October 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (2003 to October 2008), EMBASE (2005 to October 2008), LILACS (1981 to October 2008), Ongoing Trials Registers, reference lists of articles, conference proceedings from international pemphigus meetings and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials of any intervention in pemphigus vulgaris or pemphigus foliaceus. DATA COLLECTION AND ANALYSIS: Two authors independently assessed quality and extracted data from studies. All investigators were contacted for further information. Adverse events were identified from included studies. MAIN RESULTS: Eleven studies with a total of 404 participants (337 pemphigus vulgaris, 27 pemphigus foliaceus and 40 not specified ) were identified. The quality of included studies was not high, the majority of studies did not report allocation concealment, and power was limited by very small sample sizes. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. Ten studies included participants with newly diagnosed or newly active recurrent disease, and one trial included participants in maintenance phase.There was sufficient data for 4 meta-analyses, each pooling results of two studies only. For the majority of interventions, results were inconclusive. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Mycophenolate was more effective in achieving disease control than azathioprine (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD -3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone. Topical epidermal growth factor decreased time to control (1 study; n=20; HR 2.35; 95% CI 1.62 to 3.41). AUTHORS' CONCLUSIONS: There is inadequate information available at present to ascertain the optimal therapy for pemphigus vulgaris or pemphigus foliaceus. Further research is required, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.