Cutaneous Reactions in Pediatric Patients Treated with MEK Inhibitors- A Retrospective Single Center Study.

Introduction MEK inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to describe the spectrum of cutaneous adverse events, its frequency and severity in a cohort of pediatric patients. Methods We reviewed all records of patients in our tertiary treatment center treated with MEK inhibitors between January 2016 and January 2023 for all indications. Results Among 33 patients, 76% reported cutaneous adverse effects. The highest prevalence was in the group of patients treated with trametinib (90%), followed by the group treated with selumetinib (50%) and the group treated with combination of trametinib and BRAF inhibitor (dabrafenib, 34%). Xerosis, dermatitis, paronychia and hair heterochromia were most frequently reported. Severity was graded 1 or 2 for most adverse events, and 237 visits to the dermatology clinic related to these adverse events were recorded. Conclusions Cutaneous adverse events are common in the pediatric population as in adults, but the clinical spectrum is different. Although considered as mild, multiple dermatological consultations reflect the distress caused by these events. Dermatologists have a central role in the multidisciplinary care of pediatric patients receiving these agents.

Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid Papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population is scarce. OBJECTIVES: To characterize epidemiological, clinical, histopathological, and prognostic features of paediatric LyP. METHODS: This was a retrospective, multicentre international cohort study including 87 cases of children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years old at disease onset were included. Diagnosis was made in each centre based on clinical-pathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. The mean age at onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2:1. The mean time between onset of first cutaneous lesions and diagnosis was 1.3 years (range 0-14 years). Initial misdiagnosis concerned 26.4% of patients. Initially, LyP was most often misdiagnosed as Pityriasis lichenoides et varioliformis acuta (PLEVA), insect bites, or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned for 20.7% of patients. The main histological subtype was type A in 55.1% of the cases. If analysed, monoclonal TCR rearrangement was found in 76.5% of the skin biopsies. The overall survival rate was 100% with follow up at 5 years available for 33 patients and at 15 years for 8 patients. A development of associated haematological malignancy (HM) occurred in 9.6% of the cases (7/73), including four mycosis fungoides (MF) cases, one primary cutaneous anaplastic large cell lymphoma (pc-ALCL), one systemic ALCL and one case of acute myeloid leukaemia. If we compare incidence rates of cancer with the world 0-19 years old population from 2001-2010, we estimate a significantly higher risk of associated malignancy in general, occurring before the age of 19 years old with incidence rate ratio of 87.49 (CI 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall the prognosis of the disease is good, with excellent survival rates for all patients. Due to increased risk of associated HM, a long-term follow-up should be recommended for LyP patients.

Hyperhidrosis and Hypermobility Spectrum Disorders Among Adolescents.

This cross-sectional study assesses the prevalence and risk of excessive sweating and joint hypermobility in Israeli adolescents aged 16 to 19 years.

Verrulyse Methionine® as Monotherapy in Children and Adolescents With Common Warts.

BACKGROUND: Common cutaneous non-genital viral warts are a common skin infection with significant morbidity in the pediatric population. Although various therapeutics are available, many of them necessitate recurrent patient visits and may be associated with significant irritation and pain. Verrulyse Methionine® (VM), a nutritional supplement, was previously suggested as a non-invasive treatment option for the disease. OBJECTIVE: To assess the response to oral VM supplement as a monotherapy in a cohort of children and adolescents with multiple, non-genital viral warts after failing previous treatments. METHODS: We reviewed medical records of pediatric patients (<18 y/o) with viral warts treated with VM between 2010 and 2021. RESULTS: Among 25 patients with multiple verrucae vulgaris lesions who failed previous treatments, 14 (56%) had complete or almost-complete response to VM within 4 months, after an average of 18 months of active disease prior to VM treatment initiation. None of the 4 patients with verruca plana had response to VM treatment. Favourable cosmetic results were found in responders, and no adverse events were recorded. CONCLUSION: Response rates in our cohort are comparable to those reported in the literature for destructive local therapeutics for viral warts. Thus, our data suggest that VM may be considered for children with multiple verrucae vulgaris, providing a painless and non-invasive therapeutic option for this common disease.

Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. OBJECTIVE: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. METHODS: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. RESULTS: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1). CONCLUSIONS: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

Treatment with Methotrexate in Infants and Toddlers with Atopic Dermatitis: A Retrospective Multi-Center Study.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of children. Methotrexate (MTX) is used off-label as a systemic treatment for AD patients unresponsive to topical therapies, but limited data exist regarding its safety and efficacy in children, especially in those < 4 years old. To further investigate MTX in younger patients, we screened the medical records of three referral centers between 2016 and 2022 and identified 28 infants and toddlers < 4 years old with AD treated with MTX. Mean age upon MTX initiation was 2.7 ± 1.2 years and mean investigator global assessment (IGA) score was 3.78 ± 0.4. Median duration of MTX treatment was five months. Following 12 and 24 weeks of MTX treatment, the response rate was 50% and IGA 0/1 was achieved in 14.2% and 21.4% of patients, respectively. Most treatment cessations were attributed to a lack of efficacy or parental concern. Although adverse events were reported in 57.1% of patients, MTX was discontinued due to such adverse events only in two patients (7.1%). Taken together, MTX demonstrated a high safety profile in AD patients <4 years old. MTX efficacy was moderate and presumably underestimated by parents who opted for premature treatment cessation due to concerns associated with an immunomodulatory drug.

Pediatric Tinea Capitis: A Retrospective Cohort Study from 2010 to 2021.

Pediatric tinea capitis displays a wide range of prevalence, with significant variability among populations. We retrospectively extracted the medical records of 456 pediatric patients diagnosed with tinea capitis during the years 2010-2021, from the dermatology outpatient clinics in two tertiary medical centers. Three species were isolated in 90% of patients: T. tonsurans, M. canis, and T. violaceum. While T. tonsurans presented a six-fold increase in incidence during the years 2019-2021, M. canis maintained stable incidence rates. Furthermore, terbinafine was the most efficient antifungal agent against T. tonsurans, achieving complete clinical clearance in 95% of patients, as compared to fluconazole (68%) and griseofulvin (38%) (p < 0.001). The mycological cure was recorded in 61/90 (68%) of patients with available data, at an average of 10 weeks. For patients with M. canis, griseofulvin and fluconazole were equally efficient (73% and 66%, respectively) (p = 0.44). Kerion was described in 36% and 14% of patients with T. tonsurans and M. canis, respectively, (p < 0.001). In conclusion, since 2019, there has been a significant increase in the prevalence of T. tonsurans, establishing this pathogen as the most common cause for tinea capitis in our population. Our data suggest that terbinafine is effective and presents high cure rates for tinea capitis in the pediatric population.

Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

Psoriasis and Renal Disorders: A Large-Scale Population-Based Study in Children and Adults.

BACKGROUND: Psoriasis is a systemic disease with associated comorbidities. An association between renal diseases and psoriasis has previously been reported in adult patients, but little is known about renal diseases in pediatric patients. OBJECTIVE: To determine whether there is an association between psoriasis and renal comorbidities in adult and pediatric patients. METHODS: This cross-sectional study analyzed the database of the largest health care maintenance organization in Israel. Logistic regression was used to calculate odds ratios to compare 68,836 psoriatic patients and 68,836 controls with respect to renal comorbidities. RESULTS: In adults, an inverse association emerged between psoriasis and dialysis (OR, 0.69; 95% CI, 0.58-0.83) and kidney transplantation (OR, 0.60; 95% CI, 0.43-0.83), a positive association with other kidney diseases (OR, 1.09; 95% CI, 1.05-1.13), and no association between psoriasis and chronic kidney disease (OR, 1.03; 95% CI, 0.98-1.09). Comparing 9,127 pediatric patients and 9,478 controls, no association was found between psoriasis and renal comorbidities, chronic kidney disease (OR, 0.90; 95% CI, 0.33-2.48), dialysis (OR, 2.06; 95% CI, 0.19-22.69), kidney transplantation (OR, 0.34; 95% CI, 0.04-3.29), or other kidney diseases (OR, 0.98; 95% CI, 0.79-1.23), even after a multivariate analysis adjusting for putative confounders. CONCLUSION: As opposed to adult patients, pediatric patients with psoriasis were not shown at risk of kidney diseases.

Epidemiologic features and risk of scarring in pediatric patients with kerion celsi.

BACKGROUND: Kerion celsi represents the inflammatory extreme of tinea capitis, as a delayed hypersensitivity reaction to the causative dermatophyte. Data regarding prevalence, trends in pathogens, and risk factors for scarring are limited. OBJECTIVE: The main objective of the study is to assess clinical and epidemiologic features of children with kerion celsi and risk factors for scarring. METHODS: We reviewed medical records of pediatric patients with kerion celsi treated between January 2006 and July 2020. RESULTS: Among 80 patients, the prevalence of permanent alopecia was 27.5%. Patients with remaining alopecia presented to our clinic at a mean 1.3 months earlier than those with complete response to treatment (2.2 ± 2.1 and 3.4 ± 4.8, respectively; p < .05). Patients of Ethiopian ethnicity were more represented than in the general population; however, scarring was observed in only 11% (p = 0.08). Outcomes did not differ by pathogen, antifungal treatment prescribed, duration of treatment, or the use of prednisone or antibiotics. CONCLUSIONS: Scarring alopecia is a common complication of kerion celsi. Host innate immune response, pathogen virulence, and treatment timeline should be considered as possible variables affecting risk of scarring in the future studies.

Treating pediatric cutaneous Leishmania tropica with systemic liposomal amphotericin B: A retrospective, single-center study.

Leishmania tropica (L. tropica) cutaneous leishmaniasis (CL) is associated with high morbidity and low response rate to therapy, especially in pediatric patients. Intravenous (IV) liposomal amphotericin B (LAmB) has been used off-label as a treatment for L. tropica CL for many years. However, data regarding its efficacy and safety in children is lacking. In order to evaluate the efficacy and safety of IV LAmB for treating pediatric patients with L. tropica, we retrospectively reviewed electronic medical records of 24 children who were diagnosed with L. tropica CL and treated with IV LAmB during 2014-2020, at a tertiary medical center in Israel. Fourteen (58%) completed the treatment protocol and 10 (42%) experienced an infusion-related adverse event (IRAE) leading to treatment termination. Complete response was noted in 6/14 (43%) patients, while 8/14 (57%) failed to respond. Lower response rate was noted in lesions involving the mid-facial area. The relatively low response rate is speculated to result from a low dose of LAmB, short follow-up period, and difficult to treat anatomic locations. The observation of a lower response rate for mid-facial lesions should be validated in larger cohorts. The highrisk of IRAE should be considered in physician decisions regarding this treatment.

Trametinib for orbital plexiform neurofibromas in young children with neurofibromatosis type 1.

INTRODUCTION: Plexiform neurofibromas (PNF) in neurofibromatosis type 1 (NF1) are usually diagnosed in childhood and can grow rapidly during this period. In 10% of patients, PNF involve the orbital-periorbital area and may cause visual problems including glaucoma, visual loss from amblyopia (deprivational, strabismic, or refractive), optic nerve compression, or keratopathy. Ptosis, proptosis, and facial disfigurement lead to social problems and decreased self-esteem. Complete surgical removal involves significant risks and mutilation, and regrowth after debulking is not uncommon. Inhibitors of the RAS/MAPK pathway have recently been investigated for their activity in PNF. We administered the oral MEK inhibitor trametinib to five young children with NF1 and PNF of the orbital area, with visual compromise and progressive tumor growth; and followed them clinically and by volumetric MRI. METHODS: Treatment was initiated at a mean age of 26.8 months (SD ± 12.8) and continued for a median 28 months (range 16-51). Doses were 0.025 mg/kg/day for children aged > 6 years and 0.032 mg/kg/day for those aged < 6 years. RESULTS: Volumetric MRI measurements showed a reduction of 2.9-33% at 1 year after treatment initiation, with maximal reductions of 44% and 49% in two patients, at 44 and 36 months, respectively. No change in visual function was recorded during treatment. One child reported decreased orbital pain after 2 weeks; and another, with involvement of the masseters, had increased ability to chew food. Toxicities were mostly to skin and nails, grades 1-2. CONCLUSIONS: Trametinib can decrease tumor size in some young children with orbital PNF and may prevent progressive disfigurement.

Cutaneous Leishmaniasis Treated with Miltefosine: A Case Series of 10 Paediatric Patients.

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.

Cutaneous Leishmaniasis Treated with Miltefosine: A Case Series of 10 Paediatric Patients.

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.

Vascular lesions in genital lichen sclerosus in pediatric patients.

BACKGROUND/OBJECTIVES: Lichen sclerosus is a rare, pruritic, mucocutaneous disease affecting mostly the anogenital area. Reports have occasionally associated lichen sclerosus with overlapping vascular lesions. This study explores this association in children. METHODS: A retrospective study was conducted in the dermatology unit of a pediatric tertiary care medical center. Electronic medical records were searched for patients diagnosed with lichen sclerosus from 2006 to 2019. Review of the cases was performed to identify overlapping vascular lesions and review the clinical course of overlap cases. RESULTS: Of 74 children diagnosed with lichen sclerosus during the study period, five (6.75%) had overlapping vascular lesions and genital lichen sclerosus. Four patients presented with reticular telangiectatic macules and patches (n = 4, 5.4%) that appeared at or shortly after disease onset; resolution occurred a few months after treatment initiation. The fifth patient presented with telangiectases that appeared more than 2 years after the onset of the first symptoms of lichen sclerosus (n = 1, 1.3%). CONCLUSION: Vascular lesions in children with genital lichen sclerosus are common and have variable clinical manifestations. Early appearance of reticular macules, patches, and papules is a variant of the disease and is followed by prompt resolution of these lesions. Pathogenesis is attributed to structural changes and repositioning of the papillary vascular plexus. These changes may be alarming to parents and therefore must be recognized by physicians to prevent unnecessary concern and investigations.

Atopic Dermatitis and Celiac Disease: A Cross-Sectional Study of 116,816 Patients.

BACKGROUND: Both atopic dermatitis and celiac disease are often accompanied by other immune-mediated disorders. OBJECTIVE: The objective of this study was to evaluate the potential association between atopic dermatitis and celiac disease in a broad community-based population. METHODS: A cross-sectional observational design was used. Demographic and clinical data were collected for patients enrolled in a large health management organization who were diagnosed with atopic dermatitis by a dermatologist in 2002-17. The presence of celiac disease/celiac disease-related morbidities was recorded for the whole group, for adults (age > 18 years), and for adults with moderate-to-severe atopic dermatitis. Findings were compared with a matched control group without atopic dermatitis. RESULTS: The study group included 116,816 patients of whom 45,157 were adults; 1909 adult patients had moderate-to-severe atopic dermatitis. Compared to the respective control subjects, the prevalence rate of celiac disease in the whole group was 0.6% vs. 0.4%; in the adults, 0.6% vs. 0.3%; and in the adults with moderate-to-severe atopic dermatitis, 0.8% vs. 0.3% (p < 0.001 for all). On multivariate analysis, atopic dermatitis was associated with a significantly higher prevalence of celiac disease (odds ratio = 1.609, 95% confidence interval 1.42-1.82, p < 0.001) in the entire study population and each subgroup. CONCLUSIONS: We observed a significant association between atopic dermatitis and celiac disease. This association emphasizes the need for timely screening of gastrointestinal morbidities in individuals with atopic dermatitis to prevent long-term complications.

The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex.

Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to "ash-leaf like" hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance.

Cutaneous presentations of omphalomesenteric duct remnant: A systematic review of the literature.

BACKGROUND: Disorders of the umbilicus are commonly seen in infancy, including hernias, infections, anomalies, granulomas, and malignancies. Meticulous inspection of the umbilicus at birth might reveal a persisting embryonic remnant, such as an omphalomesenteric duct (OMD), manifested by a variety of cutaneous signs, such as an umbilical mass, granulation tissue, or discharge. OBJECTIVE: To systematically review the available data regarding the presence and management of OMD remnant with cutaneous involvement to suggest a practical approach for diagnosis and treatment. METHODS: A systematic review of the literature evaluating OMD anomalies presenting with cutaneous symptoms was performed. In addition, an index case of an 11-month-old patient is presented. RESULTS: We included 59 publications reporting 536 cases; 97% of the patients whose age was noted were infants (mean age 11 months). In 7.5% of the cases, diagnosis was established only after treatment failure. In 6.4% of patients, nonlethal complications were reported, and in 10.3%, the outcome was death, partly due to delayed diagnosis or mismanagement. LIMITATIONS: Limited quality of the collected data, reporting bias. CONCLUSION: OMD is relatively rare; however, the clinician must consider this remnant while examining patients with umbilical abnormalities because mismanagement could cause severe morbidity and mortality.

Are Biologics Efficacious in Atopic Dermatitis? A Systematic Review and Meta-Analysis.

BACKGROUND: Current systemic treatments for atopic dermatitis (AD) offer limited efficacy and are often restricted by safety concerns. Biologics may address the unmet need for improved AD therapeutics. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of biologic agents in AD. METHODS: A systematic review and meta-analysis of studies evaluating AD patients treated with biologics was performed. The primary outcome was the Eczema Area and Severity Index (EASI)-75 response, while secondary outcomes were SCOring Atopic Dermatitis (SCORAD)-75, EASI-50, SCORAD-50, Investigator Global Assessment 0/1 responses, change in responses from baseline, and adverse events. RESULTS: We included 13 randomized controlled trials (RCTs) and 10 observational studies evaluating nine biologics. High-quality evidence was available for dupilumab, nemolizumab and ustekinumab. Pooling five studies, at weeks 12-16 dupilumab 300 mg every week to every 2 weeks achieved EASI-75 responses of 55%, superior to placebo [relative risk (RR) 3.3, 95% confidence interval (CI) 2.9-3.6]. Nemolizumab had similar EASI-75 responses as placebo, but significantly improved pruritus. In online reports, lebrikizumab demonstrated superior EASI-50 responses versus placebo (RR 1.3, 95% CI 1.04-1.7), while tralokinumab had superior SCORAD-50 responses versus placebo, with borderline significance (RR 1.7, 95% CI 0.97-3.1). In two RCTs each, omalizumab and ustekinumab were comparable with placebo, while antithymic stromal lymphopoietin receptor, infliximab, and rituximab lacked adequate evidence of efficacy. All medications had a comparable safety profile to placebo. LIMITATIONS: Lack of RCTs and the use of variable outcome measures limited conclusions. CONCLUSION: Dupilumab is currently the only biologic with robust evidence of efficacy in AD. Nemolizumab, lebrikizumab, and tralokinumab show promise but further data are needed. Longer follow-up and larger studies will establish their safety profile.

Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study.

INTRODUCTION: Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer-basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). OBJECTIVE: The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. METHODS: This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. RESULTS: Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01-3.82); BCC and ARBs (OR 2.86; 95% CI 2.13-3.83), ACEIs (OR 2.23; 95% CI 1.78-2.81) and TZs (OR 2.11; 95% CI 1.60-2.79); SCC and ARBs (OR 2.22; 95% CI 1.37-3.61), ACEIs (OR 1.94; 95% CI 1.37-2.76), and TZs (OR 4.11; 95% CI 2.66-6.35). CONCLUSIONS: A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.