Background: Juvenile scleroderma (JS) comprises a group of rare chronic autoimmune and fibrosing disorders in children, primarily presenting as juvenile localized scleroderma (jLS) or juvenile systemic sclerosis (jSS). While jLS predominantly affects the skin and subcutaneous tissues, jSS may involve multiple internal organs and is associated with increased morbidity and mortality. Due to the scarcity of pediatric-specific clinical trials, the current treatment strategies are largely empirical and often adapted from adult protocols. Objective: This narrative review aims to provide a comprehensive update on emerging systemic therapies for juvenile scleroderma, focusing on biologics, small molecule inhibitors, and advanced cellular interventions, to support the development of more personalized and effective pediatric treatment approaches. Methods: A literature search was conducted through PubMed and a manual bibliographic review, covering publications from 2001 to 2024. Only English-language studies involving pediatric populations were included, comprising randomized controlled trials, reviews, and case reports. Additional searches were performed for drugs that are specifically used in juvenile scleroderma. Results: Biologic agents such as tocilizumab, rituximab, and abatacept, along with small molecules including Janus kinase (JAK) inhibitors and imatinib, have demonstrated potential in managing refractory cases by reducing skin fibrosis and pulmonary involvement. Novel approaches—such as pamrevlumab, nintedanib, and chimeric antigen receptor (CAR-T) cell therapy—target fibrotic and autoimmune pathways but remain investigational in children. Autologous stem cell transplantation (ASCT) has also been explored in severe, treatment-resistant cases, although data are extremely limited. The overall evidence base is constrained by small sample sizes, a lack of controlled pediatric trials, and reliance on adult extrapolation. Conclusions: While innovative systemic therapies show promise for juvenile scleroderma, their widespread clinical application remains limited by insufficient pediatric-specific evidence. Large, multicenter, long-term trials are urgently needed to establish safety, efficacy, and optimal treatment algorithms that are tailored to the pediatric population.

Pemphigus vulgaris (PV) is a rare, potentially lethal blistering disease typically occurring in adulthood and characterized by autoantibodies directed against mucocutaneous desmosomal proteins. Clinically, flaccid vesicles, bullae and erosions after breakage are the main clinical features. According to the literature, the incidence of PV is rare in the pediatric population, ranging from 1 to 4% of reported cases. We describe an interesting case of a 12-year-old boy with severe PV that was referred to our university hospital for a mucocutaneous disease resistant to anti-infective therapy. Following the appearance of bullous lesions on the skin, antibody screening for autoimmune diseases showed positivity for PV and corticosteroid therapy was started. In view of the numerous adverse effects, we decided to set up biological therapy with rituximab, which was interrupted due to the onset of an urticarial reaction. Further second-line therapies were therefore attempted, with only a partial response. For this reason, a desensitizing therapy with rituximab was decided, thus allowing a clear improvement in the clinical picture and quality of life of the patient. To the best of our knowledge, this is the first report of a child with severe PV resistant to conventional therapies and with an urticarial reaction to rituximab. This case highlights that despite PV being extremely rare in the pediatric population, this diagnosis should not be entirely discounted. In case of severe clinical manifestations, rituximab represents a valid option in children and desensitization tests should be recommended in the presence of hypersensitivity to this drug.

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) are pediatric inflammatory conditions with overlapping mucocutaneous features that may complicate early diagnosis. We performed a narrative review of the literature to characterize and compare cutaneous manifestations reported in children with KD and MIS-C and to assess their diagnostic relevance. Published studies describing dermatologic findings in patients aged 0–18 years were reviewed. The analysis revealed a broad heterogeneity of skin manifestations in both conditions, ranging from classic polymorphous rash and acral erythema to atypical presentations, including annular, psoriasiform, vesiculobullous, urticarial, and erythema nodosum-like lesions. Reactivation at Bacillus Calmette–Guérin vaccination sites and associated mucocutaneous findings, such as conjunctivitis and oral changes, emerged as supportive diagnostic clues, particularly for incomplete KD. Considerable overlap in cutaneous phenotypes between KD and MIS-C was observed, especially in patients with persistent fever and systemic inflammation, highlighting the risk of diagnostic delay. These findings underscore the importance of recognizing atypical dermatologic patterns as part of an integrated diagnostic approach, as delayed identification may increase the risk of cardiovascular complications. Early recognition of cutaneous clues can support timely initiation of immunomodulatory therapy and improve clinical outcomes.

Background: Acute pain in children is frequently under-recognized and undertreated despite validated assessment tools and effective therapies. This systematic review aimed to synthesize recent evidence on assessment and management of acute pediatric pain. Methods: The review followed PRISMA 2020 guidelines. Clinical questions were developed using the PICO framework, and evidence certainty was assessed with GRADE. PubMed and Embase were searched for studies published from 2016 to 2025. Italian pediatric scientific societies and specialists involved in acute pediatric care contributed to the process. Results: A total of 13 studies were included. Validated pain scales showed high reliability and were associated with reduced pain scores after analgesic administration. Paracetamol and ibuprofen showed comparable efficacy for mild-to-moderate pain; evidence suggesting a modest late advantage of ibuprofen was inconsistent. Combination therapy reduced rescue analgesia in individual studies. Non-pharmacological interventions, including virtual reality, distraction, and hospital play, reduced anxiety and procedural distress, although certainty of evidence was low. Evidence on opioids was limited and did not show clear superiority over non-opioid strategies. Intranasal fentanyl appeared comparable to intravenous morphine and more feasible in emergency settings. Overall, evidence for several clinical questions remains limited, and GRADE recommendations were only possible for selected PICOs. Conclusions: Acute pediatric pain management should rely on structured assessment and multimodal strategies. Validated pain scales should be used routinely. Paracetamol and ibuprofen remain first-line treatments for mild-to-moderate pain, with possible context-specific benefits of ibuprofen or combination therapy. Non-pharmacological interventions may be useful adjuncts, especially for anxiety and procedural distress. Further high-quality studies are needed on opioids, intranasal administration, alternating regimens, and inhaled versus topical analgesia.