Objectives Refractory juvenile dermatomyositis (JDM) and idiopathic inflammatory myopathies pose significant therapeutic challenges, with a subset of patients failing to respond to the standard therapy of corticosteroids and immunosuppressants. Anifrolumab, a monoclonal antibody targeting the type I interferon receptor, has demonstrated effectiveness in treatment-resistant pediatric myositis, yet evidence is limited to a recent few case reports.[1] We aimed to detail the efficacy and safety of anifrolumab in treating 4 pediatric cases with refractory inflammatory myositis. Methods We retrospectively and prospectively reviewed the medical records of patients with childhood-onset inflammatory myositis who experienced persistent disease activity and were treated with anifrolumab. This study involved 2 tertiary medical centers: Hospital Sant Joan de Déu in Barcelona and the Hospital for Sick Children in Toronto. Data on demographics, disease manifestations and severity, laboratory findings, treatment details, and responses to therapy were collected. Results Four patients, 3 females and 1 male, aged 3.5 to 10 years at the time of diagnosis, were identified (Table 1). The median time from diagnosis to starting anifrolumab was 12 months (IQR 7.8 to 31). All presented with muscle weakness and cutaneous features, and patient 1 also had ulcerative skin disease, bowel perforation, and pulmonary infections. Patients 1 and 4 were positive for anti-NXP2 antibody, while patients 2 and 3 had positive anti-p155. Prior to commencing on anifrolumab infusions, all patients received prednisone, methylprednisolone pulses, and intravenous immunoglobulins (IVIG), along with 2 or more of methotrexate, tacrolimus, mycophenolate mofetil (MMF), and cyclophosphamide. Patient 1 also needed 3 surgeries due to bowel perforation. Clinical responses were evaluated after 6 anifrolumab infusions (5mg/kg q4 weeks) for patient 1, 3 infusions for patients 2 and 4, and 2 infusions for patient 3. All 4 patients demonstrated clinically meaningful improvement in their skin involvement and overall disease activity. Patient 4 experienced a halt in the progression of the calcinosis lesion, while patient 1 also saw significant improvement in muscle strength and no recurrence of gastrointestinal involvement. The prednisone dosage was substantially reduced in patients 2 and 3, while it was discontinued in case 1. No anifrolumab-related adverse effects were observed. Table 1: Demographics, Clinical Characteristics and Treatment History of Patients Conclusion This study highlights the promising efficacy of anifrolumab in the management of refractory JDM, with clinically meaningful improvement in cutaneous and other involvement, along with a favorable safety profile. These findings provide additional support for the systemic inhibition of type I interferon in managing the disease and emphasize the need for prospective studies. References [1.] Barrutia-Etxebarria A. Pediatr Dermatol 2026;43:116-20.

Darier disease (DD) is a rare autosomal dominant genodermatosis. This comprehensive review, developed by the Darier Disease International Task Force (DDITF), consolidates current knowledge on the genetic basis, molecular pathophysiology, clinical presentation, diagnosis and management of DD, offering a global perspective that unites shared expertise. The disease arises from pathogenic variants in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), leading to disrupted calcium homeostasis and impaired desmosomal integrity. Clinically, DD is classified based on lesion type (classic vs. non-classic) and is often accompanied by significant extracutaneous manifestations. Management remains challenging and requires a multifaceted approach, including topical therapies, systemic retinoids and lifestyle modifications. Emerging treatments that target the underlying molecular mechanisms offer promise for improved outcomes. This review aims to provide an updated reference and practical guidance for clinicians involved in the care and study of DD.

BACKGROUND AND OBJECTIVES:Atopic dermatitis (AD) has a highly variable clinical phenotype and ancestry can contribute to this heterogeneity. This study aims to identify clinical phenotypes of AD in children from diverse ancestry groups, evaluate clinical outcomes and response to treatment, and define phenotypic clusters with potential relevance. PATIENTS AND METHODS:Multicenter, descriptive, observational study of patients with moderate-to-severe AD treated in eight Spanish hospitals. Patient ancestry was based on self-reported parental origin and country of birth. Phenotypic clusters were identified through analysis of demographic, clinical, and morphological variables. Systemic treatment response was assessed using validated AD scales. RESULTS:157 children were categorized into five ancestry groups: American Indian, Asian, Black, Mixed, and White. Three phenotypic clusters were identified. Cluster 1 had varied ancestries and the highest rate of Th2 comorbidities. Cluster 2 patients were mostly Asian with a predominantly non-classic morphologies, and a higher rate of hospital admissions. Cluster 3 were mostly white with fewer Th2 comorbidities. Systemic treatments yielded differential responses across clusters. Cluster 1, slower response; Cluster 2, fastest improvement; Cluster 3, milder disease and consistent improvement. CONCLUSIONS:We propose a clinically based clustering framework to refine pediatric AD phenotypes and support individualized care across diverse ancestries.

As atopic dermatitis signs and symptoms wax and wane, assessing severity scores over time best captures sustained response to treatment. We report that the majority of pediatric patients (6 months to 17 years) had sustained improvements in skin lesions (Eczema Area and Severity Index ≤ 7), itch (SCORING Atopic Dermatitis pruritus Visual Analog Scale [SCORAD Pruritus VAS < 4]), and sleep loss (SCORAD sleep loss VAS < 4) over one year of treatment with dupilumab.

BACKGROUND:Verrucous venous malformation (VVM) is a rare, congenital, slow-flow vascular anomaly, typically involving the dermis and epidermis, with progressive verrucous changes. A recently recognized subcutaneous variant (VVM-SC), which lacks cutaneous involvement, challenges current nomenclature and presents diagnostic difficulties in paediatric patients. OBJECTIVES:To describe the clinical, imaging, histopathological and molecular features of VVM-SC and highlight diagnostic pitfalls and implications for classification. METHODS:This case series includes three paediatric patients (aged 8-16 years), evaluated between 2021 and 2025 at a tertiary referral centre. All presented with well-demarcated, painless subcutaneous nodules without overlying skin changes. Clinical and imaging assessments favoured benign soft tissue tumours, including lipomas and infantile haemangiomas. One patient received pharmacological treatment based on a presumptive diagnosis of haemangioma. All lesions were surgically excised and evaluated using histopathology, immunohistochemistry and targeted next-generation sequencing. RESULTS:All lesions were solitary, skin-coloured or bluish subcutaneous nodules, lacking epidermal alteration. Imaging findings were nonspecific and misleading. Histopathology revealed lobular proliferations of dilated, congested venous channels within fibrous stroma, sparing the dermis and epidermis. One patient exhibited focal perieccrine and subepidermal vascular congestion without epidermal hyperplasia. Immunohistochemical analysis showed diffuse CD31 and CD34 positivity, focal GLUT-1 expression and negativity for D2-40, consistent with a venous phenotype. All cases harboured the recurrent somatic MAP3K3 c.1323C>G (p.Ile441Met) mutation, confirming the diagnosis of VVM-SC. Surgical excision was curative in all patients, with no recurrence observed during follow-up. CONCLUSIONS:Subcutaneous VVM lacks the hallmark superficial features of classical VVM and may mimic other paediatric soft tissue tumours, such as lipomas or haemangiomas, leading to diagnostic error and unnecessary treatment. Despite sharing the same MAP3K3 mutation, these lesions differ in depth, clinical presentation and behaviour. We propose reconsidering the terminology, and suggest 'cutaneous MAP3K3-related slow-flow vascular malformation' to encompass both superficial and subcutaneous variants. Recognition of this phenotype and its defining features, including focal GLUT-1 expression and MAP3K3 mutation, can support accurate diagnosis and reduce the risk of overtreatment. Further studies are needed to determine whether subcutaneous variants differ in recurrence risk, natural history or systemic associations.

This is a summary of the original article “Systemic Treatments in Moderate-to-Severe Atopic Dermatitis in Pediatric Patients up to 12 Years of Age: Real-World Treatment Outcomes from the PEDISTAD Registry.” Atopic dermatitis (AD, or eczema) is a chronic, relapsing skin disease that can cause intense itching and negatively affect the quality of life of patients and their families. An additional burden can be the occurrence of atopic comorbidities, such as asthma, food allergies, or allergic rhinitis (hay fever). This summary of research provides an overview of a previously published article reporting on 3-year results from the PEDISTAD study, a real-world, observational study of patients < 12 years of age with moderate-to-severe AD who received AD treatment with dupilumab, methotrexate, and/or cyclosporine. The results showed that patients treated with dupilumab had greater improvements in AD signs (extent and severity of AD) and symptoms (such as itch) compared with patients treated with methotrexate and cyclosporine. The improvements in quality of life for patients and their families were greater for children in the dupilumab and methotrexate groups than for those in the cyclosporine group. In addition, children treated with dupilumab had fewer side effects and were more likely to continue treatment.

BACKGROUND/OBJECTIVE:The multifactorial disease burden of moderate-to-severe atopic dermatitis (AD) may affect children's growth. We report height, weight, and body mass index (BMI) of children under 12 years old with moderate-to-severe AD in comparison to the general population. METHODS:This was a cross-sectional analysis of enrollment data from PEDISTAD, a global real-world observational study of pediatric patients < 12 years old with moderate-to-severe AD. RESULTS:Among the 1329 children with moderate-to-severe AD, 72% of male children 5 to < 12 years were below the 50th percentile for height, as were 53% of females in this age group. In contrast, the weight of children 5 to < 12 years was above the 50th percentile in 56% of males and 52% of females, resulting in above-average BMI values. In the 0 to < 5 years old age groups, height and weight were above the 50th percentile for 59% and 50% of female children, and 52% and 42% of male children, respectively. CONCLUSIONS:This real-world observational study showed in children 5 to < 12 years old with moderate-to-severe AD that the average height was lower than the US 50th percentile, with a more pronounced reduction in male children. Additionally, higher weight and, as a result, higher BMI were observed in the children included in this analysis. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT03687359.

BACKGROUND:Chronic hand eczema is a multifactorial, inflammatory skin disease associated with itch, pain, and a substantial physical and psychosocial burden. Delgocitinib cream (2%, 20 mg/g), a topical, non-steroidal, pan-Janus kinase inhibitor, is approved for the treatment of moderate to severe chronic hand eczema in adults. We aimed to assess the efficacy and safety of delgocitinib cream in adolescents with moderate to severe chronic hand eczema. METHODS:DELTA TEEN was a double-blind, vehicle-controlled, multicentre, phase 3 randomised controlled trial conducted at 29 trial sites in Australia, Belgium, Canada, France, Poland, Spain, and the UK. Adolescents (aged 12-17 years) with moderate to severe chronic hand eczema were randomly assigned 3:1 via an interactive response technology system to twice-daily application of delgocitinib cream or cream vehicle for 16 weeks. The primary endpoint was the Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as an IGA-CHE score of 0 or 1 (clear or almost clear) with a 2 step or greater improvement from baseline. Efficacy of delgocitinib cream versus cream vehicle was assessed in all randomly assigned patients exposed to trial treatment, and safety was assessed in all patients exposed to trial treatment. This trial is registered with clinicaltrials.gov, NCT05355818, and is complete. FINDINGS:DELTA TEEN was conducted between July 14, 2022, and Dec 17, 2024. Patients (N=98, of whom 58 [59%] were female and 40 [41%] were male, and 89 (91%) patients were White) were randomly assigned to delgocitinib cream (n=74) or cream vehicle (n=24). Superiority of delgocitinib cream to cream vehicle was shown for the primary endpoint (IGA-CHE treatment success at week 16). 47 (64%) of 74 of patients treated with delgocitinib versus seven (29%) of 24 patients treated with the cream vehicle had IGA-CHE treatment success at week 16 (difference 37·9%; 95% credibility interval 13·5-58·2). Adverse events were reported by 37 (50%) patients treated with delgocitinib and eight (33%) patients treated with the cream vehicle. All adverse events with delgocitinib cream were mild or moderate in severity. No serious adverse events were reported in either group. INTERPRETATION:Delgocitinib cream showed superior efficacy compared with cream vehicle and was well tolerated over 16 weeks. The results support delgocitinib cream as a treatment option for adolescents with moderate to severe chronic hand eczema. FUNDING:LEO Pharma.

Capillary malformations are one of most common birthmarks and sometimes they represent a diagnosis challenge for the physician at first sight. New genetic findings during the last decade have allowanced the understanding of these birthmarks and the developing of more accurate treatments, although in most cases the treatment of choice is pulsed-dye laser with some exceptions. This overview will be focused on recognize and point out first assessment of nevus simplex, port-wine stain, reticulated and geographic capillary malformations, Klippel-Trenaunay syndrome, capillary malformations fast flow-arteriovenous malformation and cutis marmorata telagiectatic congenita.

BACKGROUND:5 years have passed since the formation of the multidisciplinary consortium 'Knowing & Treating Kosaki and Penttinen Syndromes', two ultra-rare degenerative multisystem syndromes caused by heterozygous activating variants in PDGFRB. Neurological, orthopaedic and vascular deterioration can occur. Case reports of patients treated with tyrosine kinase inhibitors (TKIs) suggest that these drugs may be a therapeutic option in the future. The bi-annual remote meetings provide an opportunity to share knowledge on these syndromes. MATERIAL AND METHODS:The consortium has validated the communication process, standardised follow-up guidelines, established a database to improve the natural history of these syndromes and evaluated the real-world safety and efficacy profile of TKIs by comparing treated and untreated patients. The regulatory framework is in place. RESULTS:As of November 2024, 18 teams in 13 countries have joined the consortium. More than 25 patients have been identified worldwide, either published or unpublished; 7 of them were treated with a TKI. The guidelines include retrospective and prospective sections for each organ affected by the disease and are based on literature and expert opinion. They also include recommendations to standardise the assessment of the efficacy and safety of treatments prescribed under compassionate use. CONCLUSION:The consortium welcomes new teams on an ongoing basis. Recommendations are especially useful in such ultra-rare degenerative diseases. The real-life observational study seems to be an appropriate model to improve knowledge, including the assessment of treatment efficacy when the prevalence of the disease does not allow the setting up of clinical trials.

Objective:. VASCERN (https://vascern.eu/) is the European Reference Network for Rare Multisystemic Vascular Diseases. VASCERN-VASCA is the working group within VASCERN that focuses on the study of vascular anomalies. One of the objectives of this group is to establish patient pathways to guide physicians toward efficient diagnostic and management measures. The patient pathway presented here is focused on capillary malformations (CMs). Methods:. The Nominal Group Technique, a structured variation of small group discussion was used. Two facilitators were identified: one to propose initial discussion points and draw the pathway and another to chair the discussion. A dermatologist (E. Baselga) was chosen as the first facilitator due to her specific clinical and research expertise. The draft was subsequently discussed within VASCERN-VASCA monthly virtual meetings and biannual face-to-face meetings. Results:. The pathway starts from the clinical recognition of a vascular red stain, describing clinical characteristics and location. Depending on the clinical features, a subsequent workup for associated manifestations or complications is suggested. These steps should enable the establishment of 6 subtypes of CMs: (1) nevus simplex; (2) isolated CM, syndromic or nonsyndromic; (3) CM of microcephaly CM syndrome; (4) CM of CM–arteriovenous malformation syndromes; (5) “pseudo” CM of arteriovenous malformation; (6) cutis marmorata telangiectatica congenita. Management according to the recognized phenotype is detailed in subsequent pages of the pathway. A color code is used to differentiate (1) clinical evaluations, (2) investigations, (3) associated genes, and (4) treatments. Actions relevant to all types are marked in separate boxes, for example, when to perform specific imaging. Conclusion:. The collaborative efforts of VASCERN-VASCA, a European network of the 14 Expert Centers for Vascular Anomalies, have led to a consensus pathway for CMs. This pathway may help clinicians to guide in the diagnosis and management of CMs, as well as to emphasize the crucial role of multidisciplinary expert centers in the management of these patients. This pathway is available on the VASCERN website (http://vascern.eu/).

ABSTRACT The term ‘mosaic skin disorders’ encompasses conditions in which the skin is involved by mosaic mutations, including epidermal nevi, vascular nevi, connective tissue nevi and lipomatous nevi, among others. Mosaic skin abnormalities can present under a segmental pattern or as nonsegmental skin lesions. Nonsegmental mosaicism, which is most common, includes individual point lesions, tumours, hamartomatous lesions, or malformations, such as melanocytic nevi, Spitz tumours, and sporadic trichoepitheliomas. In some autosomal dominant genodermatoses with multiple skin lesions, a nonsegmental disseminated mosaicism emerges, often associated with neurological or multi‐organ involvement. A patchy skin involvement without midline separation is frequently observed in congenital melanocytic nevi. Segmental mosaicism is less common and presents as asymmetric cutaneous lesions in one or more separate body areas, respecting the body's midline. While the precise mechanisms remain uncertain, these segments possibly reflect clonal expansion of cells during prenatal development. In this article, we provide an overview of the types of mosaicism, discussing their patterns, clinical manifestations, and the varying degrees of severity associated with these conditions.

PTEN hamartoma tumor syndrome (PHTS) is a rare tumor risk disorder caused by germline loss-of-function mutations in PTEN. Half of these patients develop vascular malformations, a hamartoma characterized by overgrowth of vessels. In this study, we harness biopsies and patient-derived endothelial cells (EC) to study the genetic etiology of PHTS-related vascular malformations. We discover that these lesions are generated by somatic loss of the PTEN wild-type allele through copy-neutral loss of heterozygosity, leading to somatic uniparental disomy of the PTEN-mutated allele in ECs. We established a mouse model of PHTS-related vascular malformations and identified that the mTOR inhibitor rapamycin and AKT inhibitor capivasertib block vascular lesion growth. As proof-of-concept for clinical activity, off-label treatment with rapamycin of two patients with PHTS reduced vascular overgrowth and abrogated lesion-associated pain. Overall, our results uncover the genetic cause of vascular malformations in patients with PHTS and open new avenues for therapeutic intervention. SIGNIFICANCE:Somatic loss of PTEN in ECs causes vascular malformations in patients with the tumor risk syndrome PHTS. These lesions respond to PI3K signaling inhibition. See related commentary by Del Prior and Toker, p. 1306.

Systemic beta-blockers are highly effective for the management of infantile hemangiomas (IH), but little is known about infants who do not adequately respond. We aimed to describe the characteristics and outcomes of suboptimal responders to standard-dose systemic beta-blockers in infants with IH. This is a multicenter retrospective cohort study to evaluate demographics, IH lesion characteristics, and treatment specifics of infants with IH with suboptimal response to baseline standard-dose propranolol treatment. Clinical response was used to assess the outcome after a therapeutic change. Twenty-five infants were included in this study. Seven (28%) had segmental IH, 16 (64%) focal, and 2 (8%) indeterminate. The IHs were located on the head and neck in 21 (84%) infants, with 24 (96%) having a deep or combined component. Therapy changes after standard-dose propranolol treatment failure, most commonly by escalating propranolol dose to ≥2.5 mg/kg/d (59%) or surgical interventions (29%), were associated with good therapeutic effects. Among suboptimal responders to standard-dose systemic propranolol, IHs with a deep or combined component and located on the head and neck were the most common. This retrospective study was largely descriptive in nature with additional exploratory analyses. However, it is still encouraging that for patients with a suboptimal clinical response, higher propranolol doses of ≥2.5–3 mg/kg/d or second-line treatments with surgical interventions or systemic steroids can be considered as potentially safe and effective alternatives. Level 4 (case series).