A Practical Guide to Using Biologics in Pediatric Dermatology.

Psoriasis, hidradenitis suppurativa (HS), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU), are common, immune-mediated, chronic, inflammatory skin diseases that can affect the pediatric population. While there is adequate evidence supporting the use of biologics in pediatric patients, concerns regarding safety and efficacy amongst healthcare providers are not uncommon. However, new emerging evidence in this population highlights the safety of biologic therapy, making it crucial to review and establish a practical guide for their use. This article describes a methodological framework for initiating biologics in the management of pediatric psoriasis, HS, AD, and CSU, with a special focus on baseline work-up, monitoring, dosing, and considerations in this population.

Reliability, validity and responsiveness of composite finger flexion in patients with traumatic hand injuries: A clinical measurement study.

BACKGROUND: Composite finger flexion (CFF) is proposed to be a convenient alternative to total active motion (TAM) and total passive motion (TPM). Passive CFF (PCFF) may be useful for early monitoring in post-operative rehabilitation of traumatic hand injuries. PURPOSE: To determine whether active and passive CFF are reliable, valid, and responsive measures of hand motion and of higher utility to the tester. STUDY DESIGN: Cross-sectional observational clinical measurement study. METHODS: Fifty hand injury patients were recruited from a hospital-based out-patient clinic. TAM, TPM, repeated measures of active CFF (ACFF) and PCFF, self-reported stiffness, patient reported wrist/hand evaluation (PRWHE) scores, and grip strength were recorded. Intraclass correlation coefficients (ICCs) and standard error of measurement were calculated for inter-rater and test-retest reliability. Criterion and construct validity were assessed using correlation coefficients. Responsiveness was explored by calculating correlation coefficients of change scores, effect sizes, and standardized response means. Time taken to measure CFF and TAM/TPM was recorded to consider utility. RESULTS: The average age of participants was 47 years and 36% were female. Inter-rater and test-retest reliability estimates for ACFF and PCFF were excellent (ICCs = 0.95-98). Standard error of measurement values ranged from 0.21 to 0.33. The correlation coefficient for criterion validity between ACFF and TAM was -0.69; PCFF and TPM was -0.65; and ACFF and PCFF was 0.83. For construct validity, ACFF and TAM were similarly correlated with PRWHE. Correlations between changes in stiffness with ACFF and PCFF were 0.43 and 0.26, respectively. Effect sizes of ACFF and PCFF were small at 0.1 and 0.2. Time taken to measure CFF was much shorter than TAM/TPM. CONCLUSIONS: The results of this study support the use of active and passive CFF as a reliable, valid, and efficient tool in the clinical setting. Further study is required to verify the responsiveness of CFF.

A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections.

BACKGROUND: Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. OBJECTIVE: To summarize injection site reaction data in phase 3 trials of all biologic agents. METHODS: MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. RESULTS: There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). CONCLUSIONS: The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.

Eruptive Seborrheic Keratoses Are Associated With a Co-Occurring Malignancy in the Majority of Reported Cases: A Systematic Review.

BACKGROUND: Eruptive seborrheic keratoses (ESK) is a benign skin condition that has been associated with malignant and nonmalignant diseases. We conducted a systematic review of reported cases of ESK to identify and summarize associated comorbidities. METHODS: MEDLINE and Embase were searched from database inception (1946) to July 31, 2020 for original articles describing ESK with or without a co-occurring condition. Subject demographics, as well as details of ESK and associated diagnoses were extracted from 76 articles (70 case reports, 3 case series, 3 case control studies) representing 92 patients. RESULTS: In total, 76.1% (n = 70/92) of patients with ESK had a co-occurring malignancy, 4.3% (n = 4/92) presented with a nonmalignant condition, 9.8% (n = 9/92) experienced ESK as an adverse drug reaction, and 9.8% (n = 9/92) did not report any underlying medical condition. ESK preceded a cancer diagnosis in 76.1% (n = 70/92) of patients with a mean latency period of 4.0 months (range: 0.25-9 months). The most common malignancies associated with ESK were cutaneous T-cell lymphoma (n = 10/70, 14.3%) and gastrointestinal adenocarcinoma (n = 9/70, 12.9%). ESK preceded nonmalignant conditions or no disease in 14.1% (n = 13/92) of patients with a mean latency period of 3.1 months (range: 0.75-6 months). Drug-induced ESK occurred in 9.8% (n = 9/92) of patients with a mean latency period of 7.1 weeks after changing medication. CONCLUSION: Although the role of ESK as a paraneoplastic cutaneous marker is debated, healthcare providers should consider screening for underlying malignancy in patients presenting with ESK. Larger studies are needed to confirm its role as a marker for disease.

Drugs associated with development of porokeratosis: A systematic review.

Porokeratosis is a rare disorder characterized by atrophic macules or patches, with a well-defined ridge-like hyperkeratotic border called cornoid lamella. Although the exact pathogenesis is unknown, drug associated cases have recently been reported in the literature. As such, we systematically reviewed and identified drugs associated with drug-induced porokeratosis, their resultant effects, and whether there was a casual relationship between the use of a drug and the development of porokeratosis. We searched for articles which reported drug-induced porokeratosis in MEDLINE and Embase in June 2020. After full-text review, 25 studies were included for analysis. We identified 26 patients with drug-induced porokeratosis. The most common therapies associated with development of porokeratosis is biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), which occurred in psoriasis patients undergoing phototherapy, and eruptive disseminated type (24%) which occurred in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. Clinicians should consider drug reactions as possible triggering events for porokeratosis, especially for patients taking biologics, phototherapy, and radiotherapy. Large-scale studies are required to confirm our findings and further explore the pathogenesis for drug-induced porokeratosis.

Atopic dermatitis treated with tralokinumab and upadacitinib combination therapy: A case report.

A patient presented to clinic with atopic dermatitis that had been previously unresponsive to multiple topical and systemic therapies. They were successfully treated with a combination of tralokinumab and upadacitinib, showing significant improvement after 3 weeks and near-resolution after 6 months.

IgA pemphigus following COVID-19 vaccination: A case report.

A patient presented with pruritic lesions on their back and leg after COVID-19 vaccination. Biopsy and direct immunofluorescence were consistent with IgA pemphigus-likely caused by the COVID-19 vaccine.

Incidence of melanoma and non-melanoma skin cancer in patients with celiac disease: a systematic review and meta-analysis.

There is conflicting observational evidence regarding the association between skin cancer and celiac disease (CD). The purpose of this review was to investigate the incidence rate ratio (IRR) of skin cancer incidence between patients with and without CD. MEDLINE and EMBASE databases were searched on October 27th, 2021 and eight articles were identified for review. Quality assessment was conducted using the Newcastle Ottawa Scale. Seven articles were included in meta-analysis for a pooled estimate of IRR across all skin cancers, malignant melanoma (MM), and non-melanoma skin cancers (NMSC). In total, 74,860 CD patients were followed for 710,214 person-years in the meta-analysis. Overall combined incidence was 99.8 cases per 100,000 person-years. Meta-analysis of all skin cancer incidence showed no significant difference in CD patients compared to controls (IRR: 1.06; 95% CI: 0.95, 1.17; p=0.29; I2: 0%). Five studies reported on MM incidence; there was no significant difference in incidence compared to controls (IRR: 0.87, 95% CI: 0.72, 1.06; p=0.22; I2: 9%). Five studies reported on NMSC incidence, revealing a significantly increased risk of NMSC in CD patients (IRR: 1.14; 95% CI: 1.01, 1.28; p=0.04; I2: 0%). Our findings suggest a significantly increased incidence of NMSC in CD patients compared to control data and no significant association between CD and MM incidence. The findings are limited by the quantity and quality of the evidence. Nonetheless, clinicians should emphasize the importance of sun protection, such as sunscreen usage and self-examination for patients with CD.

Squamous cell carcinoma arising within hidradenitis suppurativa: a literature review.

Squamous cell carcinoma (SCC) can present as a rare complication of longstanding hidradenitis suppurativa (HS) lesions. Limited data exist on characteristics and outcomes of SCC development within HS lesions. The purpose of this review is to conduct a literature review of previously reported cases of SCC development in pre-existing HS lesions. EMBASE and MEDLINE searches were conducted in OVID on June 25, 2020, to yield 59 studies. Of the 95 patients (mean age: 52.9 years) who developed a total of 122 SCCs within HS lesions, the majority were males (77.9%, n = 74/95). The most common sites of SCC were the gluteal region (47.5%, n = 58/122), the perianal region (18.9%, n = 23/122), and the genitals (13.9%, n = 17/122). The mean duration between HS onset and SCC development was 25.5 years. Of the patients that had outcomes reported, 54.0% (n = 34/63) experienced SCC metastasis, 43.1% (n = 28/65) experienced SCC recurrences, and 58.7% (n = 44/75) experienced a mortality outcome. The most common documented reasons for death included metastasis (34.1%, n = 15/44) and sepsis (13.6%, n = 6/44). Patients with longstanding HS lesions can develop SCCs with a high rate of metastasis and mortality. Thus, chronic HS lesions, especially in the gluteal, perianal, genital, and perineal regions, should be monitored regularly for timely SCC diagnosis and management.