What's new in dermatology

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ACNE AND ROSACEA

Risk for acne relapse after isotretinoin therapy (April 2025)

Studies assessing rates and risk factors for acne relapse after isotretinoin therapy have yielded varied results. In a retrospective study of data from over 19,000 patients treated with isotretinoin in the United States, 23 percent of patients relapsed after treatment; higher cumulative dose was associated with a reduced risk for relapse, while female sex was associated with an increased risk for relapse [1]. The daily dose did not influence the risk for relapse among patients treated with at least a conventional cumulative dose (120 mg/kg). Major limitations of the study included the use of prescription data to identify relapse and the use of population-based weight data to estimate weight-based dosing of isotretinoin. The findings support cumulative dose as a risk factor for relapse and suggest that individualizing the daily dose to support drug tolerability may be reasonable in patients who will receive at least a conventional cumulative dose of isotretinoin. (See "Oral isotretinoin therapy for acne vulgaris", section on 'Outcomes'.)

ATOPIC DERMATITIS AND OTHER DERMATITIS

Nemolizumab for children with atopic dermatitis (May 2025)

Nemolizumab, a humanized monoclonal antibody against the interleukin (IL)-31 receptor, is approved in the United States for the treatment of moderate to severe atopic dermatitis (AD) in patients ≥12 years, but data on long-term efficacy and safety in younger children are lacking. In a small Japanese trial, 88 children aged 6 to 12 years, previously randomly assigned to nemolizumab or placebo for 16 weeks, were enrolled in an extension study in which all received nemolizumab [2]. At 68 weeks, all patients, irrespective of the group to which they were assigned during the randomized trial, experienced a sustained reduction in pruritus and improvement of cutaneous symptoms from baseline. Adverse effects (most frequently exacerbation of AD and upper respiratory infections) were generally mild. These results suggest that nemolizumab is a potentially useful addition to the treatment for AD in children, but larger studies involving more diverse populations are needed for confirmation. (See "Management of severe, refractory atopic dermatitis (eczema) in children", section on 'Nemolizumab'.)

Topical roflumilast for atopic dermatitis (February 2025)

Roflumilast is a selective, highly potent phosphodiesterase-4 inhibitor with anti-inflammatory properties. In two identical randomized trials including over 1300 patients with mild or moderate atopic dermatitis (AD), more patients assigned to roflumilast cream 0.15% once daily achieved the primary endpoint of Investigator Global Assessment (IGA) clear/almost clear at four weeks compared with those assigned to a vehicle control [3]. Treatment-emergent adverse effects were mild or moderate and included headache, nausea, application site pain, and nasopharyngitis. Based on these data, topical roflumilast cream 0.15% was approved by the United States Food and Drug Administration for the treatment of mild to moderate AD in adults and children ≥6 years. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical roflumilast'.)

AUTOIMMUNE AND SYSTEMIC DISEASES

Additional rituximab for relapse prevention in pemphigus (May 2025)

A repeat dose of rituximab after six months is proposed to reduce pemphigus relapse in patients with rituximab-induced complete remission, but the indications for this approach have been unclear. In a multicenter cohort study of 87 patients with pemphigus treated with rituximab and prednisone, the presence of at least one predictive factor for relapse (severe disease at baseline or specified desmoglein 1 or desmoglein 3 serum antibody levels at month three) was used to determine which patients in complete remission (n = 77) would receive an additional dose of rituximab at month six [4]. At month 12, no relapses had occurred among 30 patients given an additional dose of rituximab, and only two relapses had occurred among 47 patients not given additional rituximab; overall, 3 percent of patients relapsed, compared with 18 percent of patients in a previous study. Eight rituximab-related serious adverse events occurred. Although additional study is necessary to confirm these results, the findings suggest a benefit of additional rituximab at month six for patients at increased risk for relapse. (See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'After achievement of disease control'.)

Pathogenicity of antibodies against anti-laminin beta-4 in anti-p200 pemphigoid (April 2025)

Anti-p200 pemphigoid is a rare, cutaneous autoimmune blistering disease for which the major target autoantigen has been uncertain. An in vitro and ex vivo study suggests a pathogenic role for antibodies against laminin beta-4 based on a dose-dependent association between laminin beta-4 immune complexes and increased leukocyte-derived reactive oxygen species release and the detection of anti-laminin beta-4 immunoglobulin G (IgG)-induced dermal-epidermal separation in normal skin [5]. Although further study is necessary to confirm clinical relevance, the findings suggest that laminin beta-4 may be an important target autoantigen in anti-p200 pemphigoid. (See "Epidemiology and pathogenesis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Role of pathogenic antibodies'.)

Dazukibart for dermatomyositis (January 2025)

Dazukibart is an investigational monoclonal antibody directed against interferon-beta, which has been implicated in the pathogenesis of dermatomyositis. In a randomized trial of 75 patients with active skin-predominant or muscle-predominant dermatomyositis, patients assigned to monthly treatments with intravenous dazukibart (either 150 or 600 mg monthly) had a greater reduction in skin disease after 12 weeks of therapy compared with those assigned to placebo [6]. In an analysis of the muscle-predominant dermatomyositis group, dazukibart at the higher dose was also associated with greater improvements in several muscle parameters, including serum creatine kinase, muscle strength, and patient global assessment, compared with patients treated with placebo. These results imply that interferon-beta blockade may be a new option for patients with dermatomyositis. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Rationale and selection of DMARD'.)

HAIR AND SCALP DISEASE

Epistatic interaction between ERAP1 and MHC class I alleles in frontal fibrosing alopecia (March 2025)

The pathogenesis of frontal fibrosing alopecia (FFA), a form of cicatricial (scarring) alopecia, is not fully understood. A meta-analysis of four genome-wide association studies of female patients with FFA supported an association between FFA and select major histocompatibility complex (MHC) class I alleles and identified a new association with endoplasmic reticulum aminopeptidase 1 (ERAP1), which encodes a protein involved in antigen presentation to MHC class I molecules [7]. Genetic variation at the ERAP1 locus augmented FFA risk only among individuals carrying one or more MHC class I risk alleles. The findings suggest that epistatic interaction between MHC class I risk alleles and ERAP1 may contribute to FFA. (See "Frontal fibrosing alopecia: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pathogenesis'.)

Oral metformin for central centrifugal cicatricial alopecia (March 2025)

Central centrifugal cicatricial alopecia (CCCA) is an inflammatory scalp disorder resulting in follicular destruction, scalp fibrosis, and permanent hair loss. In a case series of 12 patients given adjunctive oral metformin (a drug with antifibrotic properties) for CCCA, eight had symptom improvement and six had partial hair regrowth [8]. Transcriptional analysis of scalp biopsies demonstrated downregulation of fibrosis-related pathways and upregulation of pathways related to hair regrowth. These findings do not confirm efficacy of metformin but add to case reports of hair regrowth in CCCA with topical metformin and support further evaluation of metformin therapy. (See "Central centrifugal cicatricial alopecia", section on 'Other therapies'.)

Oral brepocitinib for cicatricial alopecia (March 2025)

Cicatricial forms of alopecia result in permanent hair loss and are often challenging to treat. In a trial in which patients with central centrifugal cicatricial alopecia, lichen planopilaris, or frontal fibrosing alopecia were randomly assigned to the investigational tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) inhibitor brepocitinib (n = 37) or placebo (n = 12), those receiving brepocitinib had reduced inflammatory biomarkers in lesional skin as well as clinical improvement compared with placebo [9]. The most common adverse effects with brepocitinib were acne, COVID-19 infection, anemia, and elevated serum creatinine levels; two patients stopped the drug due to adverse effects (anemia and pneumonia with gastroenteritis). Although further study is necessary to confirm the efficacy and safety of brepocitinib, these findings suggest benefit for cicatricial alopecia. (See "Central centrifugal cicatricial alopecia", section on 'Other therapies'.)

PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS

Axial spondyloarthritis in patients with psoriasis, uveitis, or inflammatory bowel disease (January 2025)

Axial spondylarthritis (axSpA) often goes unrecognized in patients with chronic back pain who also have psoriasis, acute anterior uveitis, or inflammatory bowel disease. In two prospective cohort studies of over 350 such patients with undiagnosed chronic back pain, axSpA was present in approximately 25 percent of patients with psoriasis or inflammatory bowel disease and 60 percent of patients with acute anterior uveitis [10]. However, musculoskeletal symptoms, response to nonsteroidal anti-inflammatory drugs, and family history (which are commonly used to identify axSpA) did not help discriminate axSpA from other causes of chronic back pain. This study implies that axSpA is common in patients with psoriasis, acute anterior uveitis, or inflammatory bowel disease, but may be challenging for a nonexpert to distinguish from other causes of chronic back pain. (See "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'History'.)

URTICARIA AND ANGIOEDEMA

Withdrawal pruritus with cetirizine and levocetirizine (May 2025)

Cetirizine and levocetirizine are effective nonsedating antihistamines that are commonly recommended for urticaria, seasonal allergies, and various pruritic conditions. However, the US Food and Drug Administration (FDA) issued a safety communication that rare patients may experience increased itching that is sometimes disabling when reducing or discontinuing these medications, particularly after three or more months of regular administration [11]. Restarting the medication and slowly tapering down the dose may help in some cases, and the problem is generally self-limited. (See "Chronic spontaneous urticaria: Standard management and patient education", section on 'Withdrawal pruritus with cetirizine and levocetirizine'.)

Investigational remibrutinib for refractory chronic spontaneous urticaria (May 2025)

Chronic spontaneous urticaria (CSU) can be a debilitating condition that is treated with oral antihistamines and, if refractory, with injectable biologics. Remibrutinib is an oral Bruton tyrosine kinase inhibitor (TKI) that blocks signaling through the high-affinity immunoglobulin E (IgE) receptor on mast cells and basophils. It was studied in two identical phase 3 randomized trials of over 400 adults each with CSU refractory to one to four doses of a nonsedating antihistamine [12]. For the primary endpoint of lowered Urticaria Activity Scores (UAS7) from baseline to week 12, remibrutinib reduced scores by approximately 20 points, with a minimal important difference of 10 points, and responses were seen as early as one week. Therapy was well tolerated, although transient petechiae were noted in some participants receiving remibrutinib. This promising agent would offer an oral treatment for refractory CSU. (See "Chronic spontaneous urticaria: Treatment of refractory symptoms", section on 'Investigational agents'.)

Dupilumab for refractory chronic spontaneous urticaria (May 2025)

Dupilumab is a monoclonal antibody that binds to the alpha subunit of the interleukin (IL)-4 receptor and inhibits the activity of IL-4 and IL-13, type 2 cytokines involved in allergic inflammation. In April 2025, it was approved for use in chronic spontaneous urticaria (CSU) in patients ≥12 years who remain symptomatic despite H1 antihistamines [13]. Prior to this approval, omalizumab was the only biologic agent available for the management of this disorder. Although head-to-head studies comparing the two agents are lacking, dupilumab appears to have a somewhat slower onset of action and didn't perform well in most patients who did not benefit from or tolerate omalizumab [14]. Thus, its role in therapy will likely be as a primary alternative to omalizumab in select patients who have concomitant conditions that could also be treated with dupilumab, or those who prefer it to omalizumab for other reasons. (See "Chronic spontaneous urticaria: Treatment of refractory symptoms", section on 'Dupilumab'.)

OTHER DERMATOLOGY

Topical birch triterpenes for inherited epidermolysis bullosa (June 2025)

Topical birch triterpenes 10% gel, which promotes wound healing by modulating inflammation and keratinocyte migration and differentiation, is approved in the United States, Europe, and the United Kingdom for the treatment of wounds in patients with dystrophic epidermolysis bullosa (DEB) or junctional epidermolysis bullosa (JED). In a large international trial, over 200 patients with DEB or JEB were randomly assigned to apply topical birch triterpenes or vehicle to partial thickness wounds for 90 days, followed by a 24-month extension phase in which all patients applied topical birch triterpenes at least every four days [15]. At 3, 12, and 24 months, the mean Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) showed a clinically significant, sustained decrease from baseline; adverse events (most frequently wound complications, wound infection, and gastrointestinal disorders) occurred in 77 percent of patients and were generally mild or moderate. These findings confirm that topical birch triterpenes are a useful adjunct to the routine wound care for patients with severe epidermolysis bullosa. (See "Overview of the management of epidermolysis bullosa", section on 'Birch triterpenes (oleogel-S10)'.)

Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa (June 2025)

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of epidermolysis bullosa caused by mutations in the type VII collagen gene (COL7A1); topical gene therapy (with unmutated COL7A1) may be a safe and effective treatment option for patients with this condition. Previously published studies demonstrated that prademagene zamikeracel, a gene-corrected autologous keratinocyte graft, transplanted onto chronic wounds in patients with RDEB achieved ≥50 percent wound healing in 90 and 70 percent of grafted sites at six months and at five years, respectively. Based on these findings, prademagene zamikeracel was approved in April 2025 by the US Food and Drug Administration for the treatment of wounds in adults and children with RDEB [16]. (See "Overview of the management of epidermolysis bullosa", section on 'Prademagene zamikeracel'.)

Compression therapy for mixed arterial and venous leg ulcers (May 2025)

The optimal management of mixed arterial and venous leg ulcers (MAVLU) is uncertain. Compression therapy, which is the mainstay of management of venous leg ulcers, can aggravate ischemia and is generally contraindicated for patients with severe peripheral artery disease (PAD). However, modified compression therapy (MCT) may successfully treat MAVLU and moderate PAD. In a meta-analysis, among patients with an ankle-brachial index of 0.5 to 0.85, the pooled rate of ulcer healing using initial MCT was 75 percent [17]. However, 25 percent required rescue revascularization for complete ulcer healing. While these results support initial MCT for MAVLU and moderate PAD, these patients should be referred to a vascular specialist for further evaluation and possible intervention. (See "Compression therapy for the treatment of chronic venous insufficiency", section on 'Contraindications'.)