Baseline Characteristics of Canadian Patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

BACKGROUND: ß-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE. OBJECTIVE: We sought to identify genetic predisposing factors for immediate reactions to ß-lactam antibiotics. METHODS: Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort. RESULTS: Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10-14); this was in linkage disequilibrium with HLA-DRB1∗10:01 (odds ratio, 2.93; P = 5.4 × 10-7) and HLA-DQA1∗01:05 (odds ratio, 2.93, P = 5.4 × 10-7). Haplotype analysis identified that HLA-DRB1∗10:01 was a risk factor even without the HLA-DQA1∗01:05 allele. The association with HLA-DRB1∗10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1∗10:01 increased the risk of immediate hypersensitivity at a genome-wide level (odds ratio, 2.96; P = 4.1 × 10-9). No association with HLA-DRB1∗10:01 was identified in 268 patients with delayed hypersensitivity reactions to ß-lactams. CONCLUSIONS: HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.

Comparative safety and benefit-risk profile of biologics and oral treatment for moderate-to-severe plaque psoriasis: A network meta-analysis of clinical trial data.

BACKGROUND: The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied. OBJECTIVE: To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments. METHODS: A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs). RESULTS: Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. LIMITATIONS: The results may not be generalizable to real-world populations. CONCLUSIONS: Anti-interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term.

Radiation dermatitis assessment tools used in breast cancer: A systematic review of measurement properties.

PURPOSE: This review aimed to assess the quality and efficacy of tools currently used in breast cancer patients to score radiation dermatitis (RD), a common debilitating side effect of radiotherapy (RT). METHODS: A search was conducted through Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials databases on 14 February 2020. English articles that evaluated an instrument's use in assessing RD among breast cancer patients receiving external beam RT were included. Studies that reported on the reliability, validity, or concordance of items between assessment tools were included in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria. RESULTS: Twelve studies were included in this review, with a total of 13 skin toxicity assessment tools discussed. Tools that assessed clinician-reported outcomes (CROs) mostly reported moderate correlation with biophysical parameter (BP) measurements and low correlation with patient-reported outcomes (PROs). Traditionally used CRO scoring tools demonstrated moderate inter-rater reliability between clinicians, likely due to the subjective nature of items on the grading scales. Most commonly used tools were found to be either insufficient or indeterminate in their measurement properties. CONCLUSIONS: Current standardized tools that measure CROs are subject to clinician interpretation and fail to represent the patient experience. Tools designed to assess PROs are promising in their assessments of the impact of RT on patient quality of life; however, most PRO tools are generic to all skin conditions and require further validation for use in breast cancer. Among tools that measure CROs, PROs, and BPs, there is insufficient evidence on their measurement properties to establish a "gold standard" for the assessment of RD in breast cancer patients.

Oral Methotrexate Monotherapy for Severe Alopecia Areata: A Single Center Retrospective Case Series.

BACKGROUND: Although several therapeutic options have been suggested for alopecia areata (AA), none of them are consistently effective, thus making the management of severe or refractory cases challenging. Several studies have recently reported the usage of methotrexate (MTX) in AA; however, the pure effect of MTX monotherapy remains elusive. OBJECTIVE: To evaluate efficacy and safety of oral methotrexate monotherapy for AA. METHODS: We retrospectively reviewed the clinical course of AA patients including pediatric cases treated with MTX monotherapy. Their detailed clinical data including original severity of AA, final treatment outcome, the duration until the maximum response, and side effects, were assessed. Statistical analysis was performed to evaluate if the clinical factors including the duration of current alopecia, age, the presence of body hair loss, and sex were associated with treatment response. RESULTS: All included patients had severe AA and failed standard therapies. Thirteen out of 15 cases demonstrated improvement during the monotherapy, and all responders demonstrated the maximum response within 1 year. Female patients had significantly better outcomes than male patients. Other factors did not significantly influence on the treatment outcome. None of the patients experienced side effects that were severe enough to terminate the treatment. CONCLUSIONS: Our results support MTX monotherapy as a feasible option for severe AA patients who fail other standard therapies or for whom systemic corticosteroids are contraindicated.

Retrospective Study of Patients With SJS/TEN Treated at a Tertiary Burn Unit in Canada: Overview of 17 Years of Treatment.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are adverse drug reactions. OBJECTIVES: To learn about the clinical characteristics of patients with SJS/TEN including treatments provided, outcomes, and mortality. METHODS: We conducted a retrospective chart review of patients who were hospitalized with the diagnosis of SJS/TEN at the Ross Tilley Burn Center between the years 1999 and 2015. RESULTS: A total of 43 patients were identified with a mean age of 54 ± 19 (58, 18-85). The most common offending medications were allopurinol and carbamazepine. The overall mortality rate in our study is 21% with the most common causes of death being multiorgan failure and sepsis. The majority of our patients had oral (84%), ocular (79%), and genital (60%) involvement during hospitalization. Our data revealed that combination treatment involving oral corticosteroids with intravenous immunoglobulin (IVIG) had the highest mortality rate in our study since 55% (6/11) of patients who were treated in this manner passed away compared to 11% (2/18) of patients passing away who were treated with solely IVIG and 33% (1/3) who were treated with only supportive care. Our study also demonstrates the addition of etanercept and cyclosporine treatment in the second time period we studied: 2008-2015 versus the earlier time period of 1999-2007. None of the patients in our study who were treated with therapies including cyclosporine and/or etanercept passed away. CONCLUSIONS: Our study sheds light on a possible beneficial role of cyclosporine and etanercept for the treatment of SJS and TEN and reinforces the necessity of a multidisciplinary care team for patients.

Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis.

Onychomycosis is a difficult to treat condition whose prevalence is increasing. Until recently, there was no FDA approved antifungal agent for the treatment of onychomycosis in children. Although systemic antifungal agents are effective, their use is restricted by the potential adverse events and drug-drug interactions. There is evidence regarding the safety and efficacy of topical antifungal agents for pediatric onychomycosis. We have summarized the results of a recently published study using efinaconazole topical solution 10% to treat onychomycosis in children and discuss management of pediatric onychomycosis. In a multicenter, open-label phase 4 study, efinaconazole 10% solution was applied topically once daily in children aged 6 to 16 years with mild to severe, culture positive, distal and lateral subungual onychomycosis. Treatment was for 48 weeks with a follow-up at week 52. Pharmacokinetics was performed in a subset of patients. There were 62 patients enrolled in the study. At week 52, the efficacy was mycological cure rate 65% and complete cure rate 40%. All treatment-emergent adverse events (TEAE) were mild to moderate in severity with none resulting in study discontinuation. The only treatment-related TEAE was ingrown toenail. Efinaconazole was detected at low levels in plasma. Efinaconazole topical solution 10% is effective and safe in treating onychomycosis in children age 6 to 16 years and was recently FDA-approved for this indication. The on-label use of other topical agents, tavaborole solution 5% and ciclopirox nail lacquer solution 8% is reviewed. We also briefly discuss the use of oral agents, terbinafine, itraconazole, and fluconazole in pediatric onychomycosis.

A network meta-analysis on the efficacy and safety of monotherapies for tinea capitis, and an assessment of evidence quality.

Various monotherapies exist for tinea capitis; however, their relative efficacies have never been determined using a statistical approach which compares treatments' efficacy simultaneously. The goal of this study was to determine the relative efficacy (mycologic and complete cure rates) of monotherapies for the treatment of tinea capitis. On October 5, 2019, searches were performed in Scopus, PubMed, EMBASE, MEDLINE (Ovid), and CINAHL; there were no date restrictions. For the main network meta-analysis, eligible studies were randomized trials that investigated the effect of tinea capitis monotherapies on subjects' mycological and complete cure rates. Network meta-analyses were conducted in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for network meta-analyses. Mycological cure rate was the primary outcome; complete cure rate and adverse events were secondary outcomes. Twelve studies met the eligibility criteria for the main network; five systemic monotherapies were identified, griseofulvin, ketoconazole, terbinafine, itraconazole, and fluconazole. When the causative species was of the Microsporum genus, griseofulvin was most efficacious in terms of mycological cure (SUCRA = 66.1%) and complete cure (SUCRA = 80.6%). For tinea capitis caused by the Trichophyton species, terbinafine was the most efficacious in terms of both mycological and complete cure (SUCRA values of 75.2% and 78.2%, respectively). Risk of adverse events did not significantly differ across the interventions. Our results are congruent with those of previous pairwise meta-analyses; our findings also corroborate clinical experience and anecdotal evidence.

Controversies in drug allergy: Testing for delayed reactions.

Controversies exist with regard to in vivo approaches to delayed immunologically mediated adverse drug reactions, such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruptions. In particular, widespread differences exist between regions and practice on the availability and use of intradermal and patch testing, the standard drug concentrations used, the use of additional drugs in intradermal and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T cell-mediated reactions that have shed light on immunopathogenesis and provided a mechanism of preprescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine Stevens-Johnson syndrome/toxic epidermal necrolysis in Southeast Asian subjects. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches, such as skin testing and patch testing, combined with ex vivo and in vitro laboratory approaches.

Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

PURPOSE: Establishment of causality between drug exposure and adverse drug reactions (ADR) is challenging even for serious ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several causality assessment tools (CAT) exist, but the reliability and validity of such tools is variable. The objective of this study was to compare the reliability and validity of existing ADR CATs on SJS/TEN cases. METHODS: Seven investigators completed three CAT (ALDEN, Naranjo, Liverpool) for 10 SJS/TEN cases. Each CAT categorized the causality of 30 potential drugs as definite/very probable, probable, possible, or doubtful/unlikely. An additional reviewer provided expert opinion by designating the implicated drug(s) for each case. A Kappa score was generated to compare CAT responses both by method (reliability of all 7 reviewers, by CATs) and by reviewer (reliability of the 3 CAT, by reviewer). A c statistic was calculated to assess validity. RESULTS: Inter-rater reliability by CAT was poor to fair: ALDEN 0.22, Naranjo 0.11, and Liverpool 0.12. Reliability was highest when causality classification was definite/very probable (0.16-0.41). Similarly, intra-rater reliability by reviewer was poor. When comparing the validity of the overall CAT to expert reviewer, area under the curve was highest for ALDEN (c statistic 0.65) as compared to Liverpool (0.55) or Naranjo (0.54). CONCLUSION: Available CAT have poor reliability and validity for drug-induced SJS/TEN. Due to the importance of determining ADR causality for research, industry, and regulatory purposes, development of an enhanced tool that can incorporate data from immunological testing and pharmacogenetic results may strengthen CAT usefulness and applicability for drug-induced SJS/TEN.

Correction to: Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

The correct name of the 9th Author is David J. Margolis. The original article was corrected.

What Is the Risk of Harm Associated With Topical Calcineurin Inhibitors?

The topical calcineurin inhibitors (TCIs), tacrolimus (Protopic) and pimecrolimus (Elidel), were approved in the early 2000s and were widely used as a nonsteroid treatment for atopic dermatitis (AD) in adult and pediatric populations. In 2005, the addition of a boxed warning was mandated for TCIs based on a potential risk of malignancy, and there was subsequently a substantial decline in their use. Since then, evidence has mounted to support the safety of this class of medications and suggests that the increased risk of malignancy remains theoretical. This review aims to dispel some of the common myths surrounding the safety of TCIs by evaluating the key evidence regarding their safety and tolerability in adult and pediatric populations. Four major themes are addressed in a practical question-and-answer format: the risk of harm associated with TCIs including common and serious adverse events; warnings and precautions for their use including the risk of systemic absorption, immunosuppression, and malignancy; the comparative safety of TCIs; and suggestions for counselling patients about the risk of harm with TCIs. Based on the available evidence, international professional dermatological organizations and regulatory authorities have concluded that the benefits of TCIs outweigh their potential risks when used in the appropriate patient populations for the recommended duration of time.

Comparison of Management Guidelines for Moderate-to-Severe Plaque Psoriasis: A Review of Phototherapy, Systemic Therapies, and Biologic Agents.

INTRODUCTION:: Many international guidelines for management of psoriasis exist and most have variations in grading evidence quality, strength of recommendations, and dosing. The objective of our review is to compare international guidelines published in the United Kingdom, Canada, Europe, and the United States for the management of moderate-to-severe plaque psoriasis. METHODS:: We conducted a literature review on systemic therapies and phototherapy for moderate-to-severe plaque psoriasis in adult patients. The British, Canadian, European, and American guidelines served as the key comparators in our review. To identify relevant supporting clinical trials not referenced in the guidelines, we conducted literature searches in PubMed and EMBASE. Two authors independently extracted data on indications, dosing, efficacy, evidence grade, and strength of clinical recommendation for each therapy. RESULTS:: Monoclonal antibodies directed toward tumour necrosis factor and interleukin (IL)-12/23 received the strongest recommendations for treatment of moderate-to-severe plaque psoriasis, supported by robust, high-quality randomized controlled trials (RCTs). Newer agents such as IL-17 and IL-23 inhibitors are not referenced in most guidelines. There are fewer RCTs for conventional therapies and few head-to-head comparisons with biologics, making it difficult to draw direct comparisons. Among older agents, methotrexate is most strongly recommended for long-term maintenance and cyclosporine is recommended for short-term control of flares. CONCLUSION:: Physicians should individualize psoriasis-management strategies based on medication tolerance, efficacy, safety, patient comorbidities, availability of the medication, and patient preference.

The Efficacy of Platelet-Rich Plasma in the Field of Hair Restoration and Facial Aesthetics-A Systematic Review and Meta-analysis.

As a promising alternative to traditional treatment, platelet-rich plasma (PRP) is being used to encourage hair growth through the release of growth factors and cytokines. In addition to hair restoration, PRP's multifactorial capabilities can also be used to treat aging skin, facial scarring, and acne. The purpose of this review is to critically examine the success of PRP in the field of dermatology, with specific attention to the role of PRP in hair restoration. Where possible, meta-analyses were used to evaluate the efficacy of PRP. In androgenetic alopecia (AGA) patients, 3 monthly PRP injections (1 session administered every month for 3 months) exhibited greater efficacy over placebo as measured by change in total hair density (hair/cm2) over the treatment period (mean difference: 25.61, 95% CI: 4.45 to 46.77; P = .02). The studies included in the meta-analysis used a half-head design, which may have influenced the results because of the effects PRP can induce. Controlled studies suggest that 2 to 4 sessions of PRP combined with traditional therapies and procedures can help minimize acne scarring and facial burns, improve aesthetic results, and decrease recovery time. However, data for these indications are lacking and are less robust in design. In conclusion, to achieve an improvement in hair restoration in patients with mild AGA, 3 initial monthly PRP injections should be given. Only upon completion of rigorous, randomized, controlled studies can standardized and effective PRP protocols for treating dermatology conditions such as acne scarring, facial burns, and aging skin be determined.

Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials.

BACKGROUND: Injection-site reactions (ISRs) are reported with biologic therapies. The objective of this study was to comprehensively characterize ISRs among moderate-to-severe psoriasis patients treated with ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A.

METHODS: ISRs are presented from UNCOVER-1, UNCOVER-2, and UNCOVER-3 (12 weeks) and all ixekizumab-exposed patients in 11 controlled and uncontrolled trials (156 weeks).

RESULTS: At week 12, reported ISR frequency with 80 mg ixekizumab every 2 weeks (IXE Q2W, 16.8%) was comparable with etanercept twice weekly (16.4%); both were significantly higher than placebo (3.3%). With IXE Q2W, ISRs were mild (12.3%), moderate (3.9%), or severe (0.7%), typically reported in the first 2 weeks (median onset, 6.6 days), and most commonly characterized as nonspecified, erythema, and pain. Generally, erythema onset was delayed, whereas pain occurred around drug administration. Discontinuation from ixekizumab due to ISRs (0.4%) occurred in the first 12 weeks. After 2 weeks, ISR frequency decreased and remained stable (≤4.2%) through week 156. No ISR-related serious adverse events were reported in ixekizumab-treated patients. ISR data were solicited if patients reported injection-associated events. Since nonspecified ISR was the most commonly reported term, specific types might be underreported.

CONCLUSIONS: ISRs have been reported with ixekizumab during clinical trials. These reactions are typically tolerable, manageable, and decrease over time.

Clinicaltrials.gov: NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A); NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ); NCT02561806 (I1F-MC-RHBS); NCT02387801 (I1F-US-RHBO);NCT02513550 (I1F-MC-RHBP); NCT02634801 (I1F-EW-RHBZ)

J Drugs Dermatol. 2018;17(2):200-206.

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Onychomycosis in children: Safety and efficacy of antifungal agents.

Onychomycosis is an uncommon condition in childhood, but prevalence in children is increasing worldwide.The objective was to review the efficacy and safety of systemic and topical antifungal agents to treat onychomycosis in children. Databases (Pubmed, OVID, Scopus, clinicaltrials.gov, Cochrane Library) were searched. Seven studies were selected for inclusion. Only one was a randomized controlled trial. In total, 208 children were administered antifungal agents for the treatment of onychomycosis. Four reports of mild adverse events were documented (1.9% of treated children), one of which discontinued treatment (0.5%). Limitations of this review are the lack of randomized controlled trials available in pediatric onychomycosis. These findings suggest that antifungal therapies used to treat onychomycosis in children are associated with a low incidence of adverse events. Current dosing regimens for antifungal drugs are effective and appear safe to use in children, notwithstanding that the Food and Drug Administration has not approved any of these agents for the treatment of onychomycosis in children. To our knowledge, this review is the most up-to-date, comprehensive summary of pediatric onychomycosis treatment.

Confirmatory Testing Prior to Initiating Onychomycosis Therapy Is Cost-Effective.

BACKGROUND: Onychomycosis can be investigated by sampling. Information gleaned includes nail bed involvement, nail plate penetration, fungal viability, and species identification. Testing samples can confirm a diagnosis. While diagnostic testing is considered useful in directing therapy, a substantial number of clinicians do not confirm diagnosis prior to treatment. OBJECTIVES: The aim of this study is to quantify the benefit of confirmatory testing prior to treating toenail onychomycosis. METHODS: The cost of mycological cure (negative potassium hydroxide and negative culture) and the cost-effectiveness of confirmatory testing were determined using the average cost of potassium hydroxide (KOH), culture, periodic acid-Schiff (PAS), efinaconazole, ciclopirox, terbinafine, and itraconazole. Costs were obtained through literature searches, public domain websites, and telephone surveys to local pharmacies and laboratories. To represent the potential risks of prescribing onychomycosis treatment, the costs associated with liver monitoring, potential life-threatening adverse events, and drug-drug interactions were obtained through public domain websites, published studies, and product inserts. RESULTS: PAS was determined to be the most sensitive confirmatory test and KOH the least expensive. The overall cost of an incorrect diagnosis (no confirmatory test used) ranged between $350 and $1175 CAD per patient for treatment of 3 infected toenails. Comparatively, performing confirmatory testing prior to treatment decreases the overall cost to $320 to $930, depending on the therapy, physician, and test. CONCLUSIONS: It is preferred to diagnose onychomycosis prior to treatment. Furthermore, there are cost savings when confirmatory testing is performed before initiating treatment with both topical and oral antifungals in Canada.

Toxic Epidermal Necrolysis Spectrum Management at Sunnybrook Health Sciences Centre: Our Multidisciplinary Approach After Review of the Current Evidence.

Toxic epidermal necrolysis spectrum (TENS) is a rare yet severe adverse drug reaction associated with a high mortality rate. Beyond supportive care, there is still no established therapy for TENS, although recent meta-analyses and UK guideline recommendations have attempted to offer a review of relevant literature on this difficult topic. As most directed treatments lack clear consensual evidence, care centres often resort to establishing their own strategies. As Canada's largest adult burn centre and the provincial reference centre for most burn patients in Ontario, our team at the Ross Tilley Burn Centre, in collaboration with the Department of Dermatology at Sunnybrook Health Sciences Centre, Toronto, Canada, has managed over 60 confirmed cases of TENS over the past 2 decades. We would like to share our management, experience, and present our treatment protocol that we recently established by a collaborative multidisciplinary team approach to help guide treatment of these complex patients not only in Canada but worldwide.

Onychomycosis and Chronic Fungal Disease: Exploiting a Commensal Disguise to Stage a Covert Invasion.

Onychomycosis is a chronic fungal infection that is recalcitrant to treatment and often results in relapse. New evidence suggests that disease prognosis may be linked to pathogens manipulating host immune responses. Therefore, individuals with specific mutations, including those affecting pattern recognition receptors or the interleukin (IL)-17 and IL-22 pathways, may be more susceptible to infection. Moreover, it is recommended that those with a family history of immune mutations or predisposition to fungal disease be treated aggressively for onychomycosis prior to symptom progression. In addition, incorporating genetic testing and new investigational therapy such as IL-33 and interferon-γ may improve treatment outcome.

Methotrexate in the Treatment of Moderate to Severe Atopic Dermatitis: A Retrospective Study.

BACKGROUND: Atopic dermatitis is a common inflammatory condition of the skin. Moderate to severe cases not responding to topical treatments and lifestyle changes may need second-line therapy. Methotrexate has been suggested as an effective treatment in such cases. OBJECTIVE: This study was done to determine the efficacy, adverse effects, and safety profile of methotrexate therapy in patients with atopic dermatitis. MATERIALS/METHODS: All adult patients with moderate to severe atopic dermatitis seen in the dermatology clinic at this tertiary hospital from January 2015 to December 2015 who were treated with methotrexate were reviewed in a retrospective chart review. RESULTS: Forty-one patients (19 female, 22 male, mean age 45 years, range 19-90 years) were enrolled. Of these, 29% were naive to any systemic treatments in the past, including systemic corticosteroids. Methotrexate treatment resulted in excellent improvement (>75%) in 93% of patients, good (50%-75% improvement) in 5%, and partial (25%-50% improvement) in 2%. Median duration of therapy was 26 months, and 80% of patients were still on treatment at last review. Transient nonsignificant elevation of transaminases was the most common adverse effect noted in 20%, followed by nausea in 12% and fatigue in 7%. A fibroscan was done in 10 patients at cumulative doses ranging from 2 to 11 g methotrexate. No liver fibrosis was seen in these patients. CONCLUSION: Methotrexate is an effective treatment for moderate to severe atopic dermatitis with an acceptable safety profile. A low dose can be used to control the disease for prolonged periods without significant risk.