American Journal of Clinical Dermatology最新文献

A subset of patients with moderate-to-severe psoriasis show long-term remission after drug withdrawal lasting well beyond several half-life times of the drug, particularly following effective treatment with modern biologics such as interleukin-23 inhibitors. Furthermore, evidence suggests that the development of comorbidities, including psoriatic arthritis, a key comorbidity causing irreversible damage, can be prevented or delayed in a subgroup of patients with psoriasis receiving these therapies. This implies that psoriasis treatments may alter the underlying disease mechanisms in some individuals, extending beyond their direct pharmacological effects. However, this concept of disease modification remains controversial, as predicting the natural clinical course of an individual patient with psoriasis is challenging, and typically, no permanent clinically detectable changes occur in psoriatic skin inflammation. This article aims to provide an overview of the current evidence on disease modification in psoriasis and discusses clinical and molecular markers that could be used to predict or monitor disease modification in psoriasis.

Background

Inflammatory nail disorders can have a significant impact on patients’ quality of life owing to aesthetic and functional concerns. They are also challenging to treat because the therapeutic armamentarium is quite limited. This systematic review aims to report the efficacy and safety of Janus kinase and Tyrosine kinase 2 inhibitors in treating these conditions.

Methods

We conducted a comprehensive search on PubMed, Cochrane, and Embase Library to find eligible case reports, case series, single-arm clinical trials, and randomized controlled trials. We used the following search terms from inception until 15 December, 2024: “nail” AND “jak inhibitors” OR “tofacitinib” OR “baricitinib” OR “abrocitinib” OR “ruxolitinib” OR “deuruxolitinib” OR “upadacitinib” OR “ritlecitinib” OR “deucravacitinib” (nine searches in total).

Results

Of 441 articles found, 31 were included in this study. The most extensively studied drug was tofacitinib, followed by baricitinib, deucravacitinib, upadacitinib, and abrocitinib. Janus kinase/Tyrosine kinase 2 inhibitors demonstrated improvements in inflammatory nail conditions, with generally mild adverse events (nasopharyngitis and transient laboratory abnormalities being most common). The topical formulation of tofacitinib, the only one studied in these nail diseases, also demonstrated promising results with minimal systemic absorption and no side effects.

Conclusions

This review highlights Janus kinase/Tyrosine kinase 2 inhibitors as a valuable addition to the therapeutic arsenal for inflammatory nail disorders while emphasizing the importance of safety assessments and tailored treatment approaches. The long-term safety of Janus kinase/Tyrosine kinase 2 inhibitors still needs further investigation and the potential for adverse events emphasizes the need for tailored therapeutic strategies, including more studies on topical formulations.

Cellulitis, a bacterial skin infection most frequently caused by group A streptococci (Streptococcus pyogenes) and less so by Staphylococcus aureus, commonly occurs in pediatric patients. The non-specific clinical presentation of poorly demarcated, expanding erythema, and warmth is common to a multitude of similarly presenting conditions, contributing to challenges in accurate diagnosis. There is also no gold standard diagnostic test for cellulitis, as laboratory assessments, tissue and blood cultures, and imaging studies have not been helpful. These adjunctive studies may be useful, however, for ruling out mimickers or more serious or complicating conditions, such as osteomyelitis, necrotizing fasciitis, or abscess. Diagnosis remains largely clinical and evaluation by a dermatologist and/or infectious disease specialist continues to be the clinical gold standard. As a result, access to specialty care and further research into helpful adjunctive measures, such as thermal imaging, are imperative for accurate diagnosis and management to prevent inappropriate antibiosis. Multidrug resistance has continued to evolve since the initial emergence of community-associated methicillin-resistant Staphylococcus aureus, with more recent studies showing an overall decline of methicillin-resistant S. aureus in the community and highest rates remaining in the Southern region of the USA. Despite changing resistance patterns, inappropriate prescribing patterns have persisted and contribute to rising rates of resistance to antibiotics such as trimethoprim-sulfamethoxazole and clindamycin. Therefore, accurate diagnosis and subsequent management with the narrowest possible antimicrobial therapy is ideal both for individual patient outcomes and for public health.

Background

Psoriatic disease is a lifelong chronic illness for which there is no cure. It is well established that psoriasis leads to a major impairment of health-related quality-of-life and wellbeing. Most people with psoriasis live together with partners, bringing along a major burden for them. The FamilyPso was created to measure this burden in psoriasis.

Objective

The aim of the FamilyPso international study was to validate this tool and to show feasibility for the use of the FamilyPso across multiple countries.

Methods

A prospective cohort study was conducted in 11 centers in Austria, Canada, Germany, Italy, Spain, and Turkey. The factor structure of the FamiliyPso was examined by confirmatory factor analysis (CFA) including tests of measurement invariance for gender and language. Subgroups (e.g., countries and gender) were tested for significant differences, and the relationship between the severity of illness and FamilyPso scores was tested for differences between countries using a mixed regression model. Descriptive statistics for items and scores are presented herein.

Results

The cohort consisted of 556 people with psoriasis and their partners. Patients agreed that their partners would answer the questionnaire in their absence and return the forms to the centers. The mean age of patients and partners was 51 years. Psoriasis severity was mild in 57.6%, moderate in 31.5%, and severe in 10.9% of cases, and 91.3% received treatment. The results of the CFA confirmed the original factor structure with minor modifications. Self-assessed high severity of psoriasis was a predictor for a higher burden in 4/5 FamilyPso domains. There was an increased burden to partners related to the severity of psoriasis particularly in the domain “general emotional strain,” including items such as a “feeling of helplessness.” The results of the study showed that the FamilyPso could assess the burden of partners of people with psoriasis and can be used across different countries.

Conclusions

The data can improve management of psoriatic disease and should be considered in shared decision-making.

Background

Patients with dystrophic epidermolysis bullosa have pathogenic variants in COL7A1, leading to skin fragility. Beremagene geperpavec-svdt (B-VEC) is a modified, herpes simplex virus type 1-based gene therapy vector that topically delivers COL7A1 to dystrophic epidermolysis bullosa wounds. In a phase III study, B-VEC significantly improved wound healing at 3 and 6 months compared with placebo.

Objective

We aimed to evaluate the safety and tolerability of B-VEC beyond 6 months in patients with dystrophic epidermolysis bullosa.

Methods

An open-label extension study was conducted with 47 subjects (24 rollover from phase III; 23 treatment naïve) receiving B-VEC weekly to target wound areas for up to 112 weeks (median 81 weeks). Safety was assessed by adverse events. Treatment satisfaction and quality of life were assessed with patient-reported outcomes as exploratory measures of efficacy. Selected wounds from phase III rollover subjects were assessed for closure.

Results

Thirty-five subjects (74.5%) reported one or more adverse events; most were mild or moderate in severity. Fourteen subjects experienced 17 serious adverse events and ten experienced 14 severe adverse events; none was considered treatment related. No adverse events led to treatment or study discontinuation. Patient-reported outcomes indicated high levels of treatment satisfaction, but were inconclusive with regard to quality of life. Among rollover subjects, wounds that received B-VEC during phase III maintained high closure rates during the open-label extension (range 61.1–89.5%, assessed baseline to month 12).

Limitations

This was an open-label design, with a variable follow-up.

Conclusions

Patients undergoing extended B-VEC treatment maintained high satisfaction and continued to respond to treatment with no new safety signals detected in the open-label extension study, supporting the continuous use of B-VEC.

Clinical Trial Registration

NCT04917874 (date of trial registration: 8 June, 2021).

Background

We report pooled safety data for baricitinib treatment of severe alopecia areata in patients in BRAVE-AA1 (phase II/III) and BRAVE-AA2 (phase III), including data from the long-term extension and bridging extension periods.

Methods

Data are reported from the extended dataset (patients receiving continuous baricitinib 2 mg or 4 mg) and the all-baricitinib dataset (all patients receiving any dose of baricitinib at any time during the trials). Safety outcomes include treatment-emergent adverse events, adverse events of special interest, and abnormal changes in laboratory test results. Incidence rates (IRs) per 100 patient-years were calculated based on time at risk. Data cutoff dates were 22 May, 2023, for BRAVE-AA1 and 8 May, 2023, for BRAVE-AA2 and included follow-up through at least 152 weeks.

Results

Data were collected for 1303 patients treated with baricitinib, reflecting 2789.7 patient-years of exposure (median, 825 days; maximum, 1460 days). Most treatment-emergent adverse events were mild to moderate in severity. Incidence rates of serious adverse events (IR = 2.6) and treatment discontinuations because of adverse events (IR = 1.7) were generally low and remained similar to data presented through at least 104 weeks of follow-up. In an additional 1 year of follow-up, no new cases of serious infections, opportunistic infections, major adverse cardiovascular events, deep vein thromboses, or pulmonary embolisms were observed. The IRs for non-melanoma skin cancer (IR = 0.1) and other malignancies (IR = 0.2) remained stable over time. The IR of herpes zoster was comparable to previously reported IRs (IR = 1.9). Laboratory changes were generally consistent over time. No deaths were reported in either study.

Conclusions

Long-term safety data from BRAVE-AA1 and BRAVE-AA2 are consistent with previously reported data from the baricitinib alopecia areata clinical trial program and demonstrate no new safety concerns or signals for baricitinib through a maximum exposure of 4 years.

Clinical Trial Registration

BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) were registered on 18 June, 2018, and 1 April, 2019, respectively.

Management of hidradenitis suppurativa (HS) can be challenging and often requires a multimodal approach with use of on- and off-label medications. There has been a rapid expansion of available HS treatments in the years since the 2019 North American HS (NAHS) clinical management guidelines. Herein we present an up-to-date practical management algorithm based on the diagnosis and management strategies set forth by the 2019 NAHS guidelines using newly available literature. Evaluation and diagnosis of HS disease involves assessment of severity, extent of disease, and impact on patient quality of life. Initial diagnosis of HS should be shortly followed by comorbidity screening. The multimodal approach to HS treatment typically involves use of treatment stacking of topical therapies, systemic and topical antibiotics, retinoids, hormonal and metabolic therapies, biologics and small molecule inhibitors, systemic immunosuppressants, surgical treatment, pain management, lifestyle modifications, adjunctive treatment, wound care, and flare therapy. Thus, the proposed algorithm aims to guide clinicians in their implementation of treatment stacking in HS.

Radiation therapy (RT) is a crucial modality in cancer treatment, functioning through direct DNA damage and immune stimulation. However, RT's effects extend beyond targeted cells, influencing neighboring cells through the bystander effect (ByE) and distant sites via the abscopal effect (AbE). The AbE, first described by Mole in 1953, encompasses biological reactions at sites distant from the irradiation field. While RT can enhance antitumor immune responses, it may also contribute to an immunosuppressive microenvironment. To address this limitation, combining RT with immune checkpoint inhibitors (ICIs) has gained renewed interest, aiming to amplify antitumor immune responses. Evidence of AbEs has been observed in various metastatic or advanced cutaneous cancers, including melanoma, basal cell carcinoma, cutaneous lymphoma, Merkel cell carcinoma, and cutaneous squamous cell carcinoma. Clinical studies suggest combining RT with ICIs targeting CTLA-4 and PD-1/PD-L1 may enhance AbE incidence in these cancers. This review primarily explores the current understanding of AbEs in skin cancers, briefly acknowledging the ByE focusing on combining RT with immunomodulation. It focuses on proposed mechanisms, preclinical and clinical evidence, challenges in clinical translation, and future directions for harnessing AbEs in managing advanced skin malignancies. Alternative modalities for inducing abscopal-like responses are also explored. While promising, challenges remain in consistently reproducing AbEs in clinical practice, necessitating further research to optimize treatment combinations, timing, and patient selection.