American Journal of Clinical Dermatology最新文献

The advent of immune checkpoint inhibition has revolutionized treatment of advanced melanoma. While most patients derive survival benefit from established immunotherapies, notably monoclonal antibodies blocking cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1, a subset does not optimally respond due to the manifestation of innate or acquired resistance to these therapies. Combination regimens have proven efficacious relative to single-agent blockade, but also yield high-grade treatment toxicities that are often dose-limiting for patients. In this review, we discuss the significant strides made in the past half-decade toward expanding the melanoma immunotherapy treatment paradigm. These include newly approved therapies, adoption of neoadjuvant immunotherapy, and studies in the clinical trials pipeline targeting alternative immune checkpoints and key immunoregulatory molecules. We then review how developments in molecular and functional diagnostics have furthered our understanding of the tumor-intrinsic and -extrinsic mechanisms driving immunotherapy resistance, as well as highlight novel biomarkers for predicting treatment response. Throughout, we discuss potential approaches for targeting these resistance mechanisms in rational combination with established immunotherapies to improve outcomes for patients with melanoma.

The growing field of psychodermatology examines the interplay between dermatological and psychiatric comorbidities. While current literature recognizes that cutaneous and psychiatric conditions often coexist within patients, the relationship between dysregulated inflammation and depression in patients with inflammatory skin conditions has not been thoroughly explored. This review seeks to describe the connection between cutaneous disease and depression via shared inflammatory cytokine pathways. A review of current literature was conducted, and studies addressing the co-occurrence of depression and inflammatory skin diseases were included. This review focuses on depression in patients with psoriasis, atopic dermatitis, and hidradenitis suppurativa. Studies that focused on the prevalence of depression in these populations, shared inflammatory pathways, and co-management of cutaneous and psychiatric disorders were chosen. The literature revealed a high prevalence of depression in individuals with inflammatory skin conditions compared with those without cutaneous disease. Recent studies described how proinflammatory cytokines in inflammatory skin diseases can elicit inflammation in the brain, leading to depressive symptoms. Certain subsets of cytokines that mediate inflammatory pathways were associated with both cutaneous inflammation and depression, highlighting shared pathology. Antiinflammatory medications targeting shared cytokines found reductions in both cutaneous and depressive symptoms. Practitioners have emphasized interdisciplinary approaches to treating both conditions, including psychotherapy and pharmacological methods. There is a clear association between inflammatory cutaneous diseases and depression. Co-management of these conditions, including interdisciplinary methods, is essential for patients’ well-being. Future research addressing similar links between other cutaneous and psychiatric conditions could yield new treatment opportunities as well.

Secondary hyperhidrosis is a multifactorial condition that poses unique diagnostic and management challenges. Distinguishing secondary from primary hyperhidrosis remains difficult due to overlapping symptoms. This review consolidates existing evidence on the numerous underlying causes and pathophysiologic mechanisms of secondary hyperhidrosis across various disciplines. Secondary hyperhidrosis typically manifests in the fourth decade of life or later, whereas primary hyperhidrosis usually begins earlier. Generalized hyperhidrosis often suggests a secondary cause, though the distribution can vary, including focal symmetric/asymmetric or regional patterns depending on the underlying condition. Key clinical features such as lack of family history and associated symptoms provide additional clues favoring a secondary etiology. Recognizing these distinct characteristics is crucial for accurate differentiation between secondary and primary hyperhidrosis, thereby guiding appropriate evaluation and management of the underlying cause.

Keratoacanthoma (KA) is a relatively common, fast-growing epithelial tumour, with characteristic behaviour and clinical variability. Although it appears as a solitary lesion in a majority of cases, multiple KAs do occur, secondary to skin exposure to ultraviolet radiation, chemical carcinogens or certain medications, but may also be associated with various genetic syndromes. Thus, multiple KAs may serve as an early clinical alarm sign. Prompt diagnosis of the underlying cause and identification of the mechanism of development are critical for the secondary prevention of associated organ disorders or neoplasias, the improvement of patient quality of life and familial counselling. Although research in this field has seen important progress in the last few years, there are still many pathogenic processes that have not been elucidated. Additionally, the literature on this topic is limited to individual case reports and small case series, making it difficult for clinicians to parse available data and select the essential information. Therefore, this work aims to review current knowledge, summarizing existing studies, with focus on multiple KAs associated with genetic syndromes, and proposes a diagnostic algorithm for these rare cases to help guide clinicians in their practice. Lastly, we aim to highlight the main gaps in understanding the underlying mechanisms and suggest further research avenues.

Graphical Abstract

Background

Atopic dermatitis (AD) is associated with itch, skin pain, sleep disturbances, and diminished quality of life (QoL). Ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream demonstrated efficacy and safety in adults and adolescents with mild-to-moderate AD in two phase III studies (TRuE-AD1/TRuE-AD2). In TRuE-AD1/TRuE-AD2, significant improvements in itch were observed as early as 12 h following application of ruxolitinib cream.

Objective

The aim of this paper was to assess additional patient-reported outcomes (PROs) in the vehicle-controlled (VC) and long-term safety (LTS) periods of TRuE-AD1/TRuE-AD2.

Methods

In the TRuE-AD studies, patients aged ≥12 years with AD were randomized 2:2:1 to apply twice-daily 1.5% ruxolitinib cream, 0.75% ruxolitinib cream, or vehicle cream continuously for 8 weeks (VC period). During the LTS period, patients applied the same ruxolitinib cream strength, but on an as-needed basis; patients who initially applied vehicle were re-randomized to apply 0.75% or 1.5% ruxolitinib cream. Pooled data from both study periods were analyzed. PRO assessments included symptoms (itch [Patient-Oriented Eczema Measure, POEM], skin pain [numerical rating scale], and sleep [POEM and Patient-Reported Outcomes Measurement Information System]) and assessments of disease-specific QoL (Dermatology Life Quality Index [DLQI] and the children’s version [CDLQI]).

Results

A total of 1208 and 1031 patients from the VC and LTS periods, respectively, were included in the analysis. Significant improvements in skin pain were observed within 12 h among patients who applied ruxolitinib cream versus vehicle; improvements continued throughout the VC period. Improvements in patient-reported symptoms (including sleep) were observed within 2 weeks (first assessment) of ruxolitinib cream application. At Week 2, significant improvements in symptom burden and overall QoL were observed with ruxolitinib cream (0.75%/1.5%) versus vehicle in POEM (−8.9/−9.8 vs −2.2; both p < 0.0001), DLQI (mean changes from baseline, −5.8/−6.1 vs −1.2; both p < 0.0001), and CDLQI (−4.3/−5.3 vs −1.3; both p < 0.0001). Further symptom burden and QoL improvements were reported during the VC period and were maintained through the end of the LTS period (Week 52).

Conclusions

Consistent with the previously reported itch response data, ruxolitinib cream improved skin pain within 12 h of application. Ruxolitinib cream improved patient-reported AD symptom burden and overall QoL by Week 2. Improvements continued or were maintained for 52 weeks. (Graphical abstract and plain language summary available).

Trial Registration

ClinicalTrials.gov identifiers, NCT03745638 and NCT03745651 (both studies were registered on November 19, 2018).

Graphical Abstract

Background

Pyoderma gangrenosum (PG) is rare neutrophil skin disease causing painful, progressively enlarging ulcers. Among the treatment options, intravenous immunoglobulin (IVIG) is a therapy of first choice for paraneoplastic PG. Otherwise, it is used in therapy-refractory courses.

Objective

To assess the efficacy and safety of IVIG therapy in patients with PG.

Methods

A retrospective chart review for patients in five dermatologic wound centres in Germany was performed.

Results

Overall, 81 patients were included. IVIG was used as adjunct therapy with (methyl-) prednisolone and/or a steroid sparing therapy in 77 (95.1%) cases. Response to treatment (combined complete and partial, defined as tendency to heal and cessation of lesion progression, respectively) was 49.3% 1 month after initiation of IVIG. In total 18.8% had a complete response after 6 months. Statistically significantly higher response rates were observed in patients with diabetes mellitus and thyroid disease [odds ratio (OR) 3.49, confidence interval (CI) 1.13–10.80 and OR 6.64, CI 1.01–43.57, respectively]. Patients with solid malignancy tended to have better response (OR 4.36, CI 0.79–23.91). A higher IVIG dose was also associated with a tendency towards better response rates (OR 2.70, CI 0.84–8.63). In total, 1 (1.2%) severe adverse event (myocardial infarction with consequent death) was observed as well as three moderate adverse events, with two thromboembolic events (2.5%) and one acute kidney injury (1.2%). Other adverse events were mild or unlikely to be associated with IVIG therapy, with 14 events in 10 patients overall (12.3%).

Conclusions

This multicentre retrospective study shows the important role of adjunctive IVIG therapy in patients with PG with recalcitrant courses. Identifying subgroups with a higher probability of response could improve future response rates and save patients from ineffective treatment and potential adverse events.

Graphical Abstract

Urticarial vasculitis (UV) is a rare and difficult-to-treat, small-vessel leukocytoclastic vasculitis presenting with recurrent long-lasting wheals. So far, no guidelines and treatment algorithms exist that could help clinicians with the management of UV. In this review, we describe evidence on systemic treatments used for UV and propose a clinical decision-making algorithm for UV management based on the Urticarial Vasculitis Activity Score assessed for 7 days (UVAS7). Patients with occasional UV-like urticarial lesions and patients with UV with skin-limited manifestations and/or mild arthralgia/malaise (total UVAS7 ≤7 of 70) can be initially treated using the step-wise algorithm for chronic urticaria including second-generation H1-antihistamines, omalizumab, and cyclosporine A. Patients with UV with more severe symptoms (UVAS7 >7), especially those with hypocomplementemic UV, may require a multidisciplinary approach, particularly if underlying diseases, for example, systemic lupus erythematosus, cancer, or infection, are present. Immunomodulatory therapy is based on clinical signs and symptoms, and the drug availability and safety profile, and includes systemic corticosteroids, dapsone, hydroxychloroquine, anti-interleukin-1 agents, and other therapies. The level of evidence for all UV treatments is low. Prospective studies with current and novel drugs are needed and could provide further insights into UV pathogenesis and treatment.

Background

Disseminated superficial actinic porokeratosis (DSAP) is a disorder of keratinization characterised by small, brown plaques with elevated keratotic rims, typically occurring on sun exposed areas. DSAP poses a risk for malignant transformation, emphasising the need for effective management strategies.

Objective

The aim of this study was to review the current reported management options for DSAP.

Methods

This systematic review was based on a comprehensive search of databases (Cochrane, PubMed, Medline, Embase, Emcare, ProQuest, Web of Science, CINAHL) from inception to 15 March 2024. Studies reporting management of DSAP were included irrespective of study design.

Results

Of 923 citations, 61 studies were included, predominantly comprising case reports and retrospective case series. A limited number of randomized and open-label trials were identified. Various treatment modalities were reported, including topical and systemic agents, photodynamic therapy, and laser therapy.

Conclusion

Multiple management options are available for DSAP, including topical and systemic agents, photodynamic therapy and laser treatments. However, these approaches vary in their balance between efficacy and toxicity. Currently, there is a paucity of high-quality clinical trial data to guide treatment decisions. Further studies are required to determine the most effective and safe management strategies for DSAP.

Prospero registration

CRD42024514558.

Background

The ALLEGRO phase 2b/3 study investigated the efficacy and safety of ritlecitinib in patients with alopecia areata (AA).

Objective

To describe the impact of ritlecitinib on patient-reported hair loss using the Alopecia Areata Patient Priority Outcomes (AAPPO) instrument and evaluate the relationship between clinically meaningful hair regrowth and improvements in patient-reported impacts.

Methods

In ALLEGRO-2b/3, patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg daily loading dose), 10 mg, or placebo for 24 weeks and then continued ritlecitinib or switched from placebo to ritlecitinib 200/50 or 50 mg for 24 weeks. The AAPPO instrument evaluated improvement in hair loss, emotional symptoms (ES), and activity limitations (AL) from weeks 4 to 48 (secondary endpoint). Mean changes in ES and AL domain scores and individual items at weeks 24 and 48 were calculated for Severity of Alopecia Tool (SALT) score ≤ 20 responders and nonresponders (exploratory endpoint).

Results

Overall, 718 patients were randomized. At week 24, 5–36% of patients receiving ritlecitinib 10–200/50 mg reported improvement in scalp hair loss versus 9% receiving placebo. The results for eyebrow, eyelash, and body hair loss were similar. Mean change from baseline in ES and AL scores at weeks 24 and 48 was small and similar between groups. Mean change was larger for individual hair loss and ES items at weeks 24 and 48 in SALT score ≤ 20 responders versus nonresponders.

Conclusions

The AAPPO instrument demonstrated the beneficial impact of ritlecitinib on patient-reported hair growth, which was consistent with improvements in clinician-reported outcomes.

Clinical Trial Registration

NCT03732807.

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