Dermatologic Effects of Selumetinib in Pediatric Patients with Neurofibromatosis Type 1: Clinical Challenges and Therapeutic Management.

Background: Plexiform neurofibromas (pNFs) are benign neoplasms, primarily originating from Schwann cells, posing challenges in patients with type 1 neurofibromatosis (NF1) due to pain, disfigurement, compression of vital structures and potential for malignancy. Selumetinib, a MEK1/2 inhibitor, has shown promising results in treating inoperable pNFs, with clinical trials demonstrating tumor volume reduction and improved patient-reported outcomes. Despite its efficacy, dermatologic toxicities may impact the quality of life and treatment adherence. Evaluating the frequency and spectrum of such effects is crucial for effective management. Methods: In a four-year retrospective and prospective study, pediatric NF1 patients with symptomatic, inoperable plexiform neurofibromas (pNFs) were treated with selumetinib. Eligibility criteria included significant morbidity, pNF size exceeding 3 cm or surgical inoperability, and performance status >70%. Hematological, liver, lung and cardiac assessments established baseline health. Selumetinib, orally administered at 25 mg/m2 twice, was administered for two years unless a response warranting extension occurred. Cutaneous AEs were documented and graded by severity according to CTCAE v5.0, with evaluations every three to six months. The impact on symptoms and pNF size was systematically recorded, and biopsies characterized histopathological features in those patients requiring surgery. Results: Twenty patients were enrolled, with an average age at therapy initiation of 11.6 years. Cutaneous side effects were common, with all patients experiencing at least one and a median of two per patient. Xerosis, paronychia and acneiform rash were prevalent. Notably, pre-pubertal individuals were more susceptible to xerosis. Acneiform rash had a higher incidence in older patients and those with skin phototypes II and III. Successful management involved tailored approaches, such as clindamycin for acneiform rash and topical agents for paronychia. Hair abnormalities, including color changes and thinning, occurred, with female patients at higher risk for the latter. Paronychia presented challenges, necessitating various interventions, including surgical approaches. AEs led to treatment suspension in 20% of patients, with tumor rebound observed in 75%. Conclusions: According to our experience, successful management of selumetinib-induced cutaneous AEs requires tailored strategies including surgery. AEs might indirectly determine pNF regrowth due to therapy suspension. We thus emphasize the pivotal role of addressing cutaneous reactions for effective selumetinib management in pediatric patients.

Corticophobia among Parents of Children with Atopic Dermatitis: Assessing Major and Minor Risk Factors for High TOPICOP Scores.

Corticophobia, fear of applying topical corticosteroids (TCSs), is a rising issue in industrialized countries, despite the actual safety of TCSs for atopic dermatitis (AD). Patients attending the Pediatric Dermatology Unit for skin examination were screened for AD. AD patients were included, and data were collected. Parental corticophobia was evaluated through the Topical Corticosteroid Phobia (TOPICOP) questionnaire. The χ2 test and logistic regression were used to analyze statistical associations between parental corticophobia (mild/moderate vs. severe) and patients' and parents' characteristics. Overall, 100 patients were included (53 females; 47 males; mean age 5.9 years): 44 had mild/moderate AD (EASI ≤ 21), and 56 had severe AD (EASI > 21) (mean EASI 19.7). Of the patients, 33 never consulted healthcare providers for AD, and 67 did. Parental education was low/intermediate in 60 cases and high (gymnasium/university degree) in 40. Mean parental DLQI was 10.7. Mean parental TOPICOP was 39.1%: 51 had mild/moderate corticophobia (TOPICOP ≤ 50%), and 49 had severe corticophobia (TOPICOP > 50%). At the χ2 test, corticophobia was associated with mild/moderate AD (OR 20.9487; 95% CI 7.2489-60.5402; p < 0.001), older age of patients (OR 4.1176; 95% CI 1.7880 to 9.4828; p < 0.001), early disease onset (OR 9.8925; 95% CI 2.7064-36.1596; p < 0.001), and previous healthcare professional consultations (OR 4.9279; 95% CI 1.9335-12.5597; p < 0.001). Also, severe parental corticophobia was very significantly associated with severe parental involvement of life quality (OR 33.3333; 95% CI 10.9046-101.8937; p < 0.001) and with high education of parents (gymnasium or university degree) (29/49) (OR 5.2727; 95% CI 2.1927-12.6790; p < 0.001). At logistic regression, high parental DLQI (p < 0.0001), high parental education (p < 0.0338), older age of patients (p = 0.0015), and early disease onset (p < 0.0513) accounted for major risk factors influencing severe parental corticophobia. Assessing risk factors for corticophobia is essential for addressing groups of parents at higher risk for corticophobia using educational programs, to overcome unfounded fears and augment treatment adherence.

Skin manifestations help identifying different phenotypes of paediatric SAPHO syndrome.

OBJECTIVES: to evaluate whether the heterogeneous skin manifestations might influence the disease presentation and outcome of a cohort of SAPHO children. METHODS: the clinical, serological, imaging and therapeutic data of 14 SAPHO patients, followed between 2001 and 2022 at the Unit for Autoinflammatory diseases at the Gaslini Hospital, were reviewed. According to their cutaneous manifestations, patients were divided into 2 groups: the acne-hidradenitis suppurativa (HS) and the Palmo-Plantar Pustulosis (PPP) group. Data were retrieved from the Eurofever database. RESULTS: all patients presented bone involvement characterized by Chronic Recurrent multifocal Osteomyelitis (CRMO): 8 patients presented acne-HS while 6 patients had PPP. In the PPP group, all patients were female, characterized by a prepuberal disease onset with osteoarticular manifestations, followed by the appearance of PPP in the following 6 months. This group responded well to the treatments. In the acne-HS group, 7/8 patients were male: the disease onset was characterized by skin manifestations in pubertal age, followed by osteoarticular manifestations in the following year. This group presented a severe refractory skin disease that required in most cases the addition of biological therapies. A literature review confirmed our data highlighting the association males-acne-puberal age and female-PPP-prepuberal age. CONCLUSION: paediatric SAPHO patients should be mainly stratified according to their skin involvement. In fact, our data suggest that two different skin phenotypes may be identified in SAPHO: the first is constituted by prepuberal females with PPP and a prevalent osteoarticular involvement, while the second by puberal males with a difficult-to-treat acne-HS.

Facial pruritic skin rash in a Nigerian boy with atopic dermatitis.

We present the case of a 4-year-old boy with annular, pruritic macules on the face who did not respond to the application of topical immunosuppressive therapy for atopic dermatitis. In this case report, we emphasize how pruritic annular macules that are not responsive to immunosuppressants should always be suspected of being tinea incognita.

Childhood vitiligo developing after COVID-19 infection.

Both COVID-19 and vaccinations against it have been related to immune cutaneous manifestations. Here, we present a case of childhood vitiligo, developed after a COVID-19 infection.

Pediatric spitzoid lesions of the ear: a single-center experience and review of the literature.

Spitzoid lesions are challenging melanocytic lesions comprising benign, intermediate, and malignant lesions. In this study, we aimed to analyze the diagnostic accuracy of clinical and dermatoscopical evaluations of pediatric spitzoid ear lesions. We collected and analyzed, clinically, dermatoscopically, and histologically, pediatric spitzoid ear lesions. We also conducted a systematic review of the literature. At the Pediatric Hospital Gaslini, excision and histopathological evaluation were performed on eight cases: 87.5% of the lesions were consistent with Spitz nevus (SN), and 12.5% with atypical Spitz tumor (AST). Notably, multiple (≥2) dermatoscopical irregularities were present in 5 of 7 SN (71%), yet none were found in AST (0%, 0/1) (Fisher's exact test, P=0.375). From systematic research in the literature, 9 patients were included in this review. At histology, 88.9% were SN and 11% AST. Remarkably, also in the literature, multiple dermatoscopical irregularities were present in most SN (75%, 6/8), but not in the identified AST (0%, 0/1) (P=0.3333). We present a monocentric study on pediatric spitzoid ear lesions. Importantly, dermatoscopical irregularities were not significantly associated with AST, neither in our series nor in the reviewed literature (respectively P=0.375 and P=0.3333), supporting the fact that relying only on the dermatoscopical aspect of spitzoid lesions is not accurate enough for the special site of the ear, where dermatoscopy could actually be misleading.

Paediatric Spitzoid Neoplasms: 10-Year Retrospective Study Characterizing Histological, Clinical, Dermoscopic Presentation and FISH Test Results.

INTRODUCTION: Spitzoid lesions are a wide tumour class comprising Spitz nevus (SN), atypical Spitz tumour (AST) and Spitz melanoma (SM). MATERIALS AND METHODS: We conducted a single-centre-based retrospective survey on all histologically diagnosed spitzoid lesions of paediatric patients (1-18 years) of the last 10 years (2012-2022). Histopathological reports and electronic records of patients were used to retrieve relevant data regarding patients' features, clinical and dermatoscopical aspects of lesions when recorded, and FISH tests when present. RESULTS: Of 255 lesions, 82% were histologically benign, 17% atypical, 1% malignant. Clinically, 100% of SM were large (≥6 mm) and raised; AST were mainly large (63%), raised (98%), pink (95%). Small (≤5 mm), pigmented, flat lesions correlated with benign histology (respectively 90%, 97%, 98% SN) (p < 0.0001). Dermatoscopical patterns were analysed in 100 patients: starburst pattern correlated with benign histology (26% SN (p = 0.004)), while multicomponent pattern correlated with atypical/malignant lesions (56% AST, 50% SM (p = 0.0052)). Eighty-five lesions were subjected to fluorescence in situ hybridization (FISH): 34 (71% AST; 29% SN) were FISH-positive; 51 (63% SN; 37% AST) were FISH-negative (p = 0.0038). DISCUSSION: This study confirmed predominant benign histology (82%) of paediatric spitzoid lesions, thus detecting 17% AST and 1% SM, highlighting the need for caution in handling spitzoid lesions. CONCLUSION: Until AST are considered potentially malignant proliferations and no reliable criteria are identified to distinguish them, the authors suggest a prudent approach, especially in children.

Treatment of Pediatric Anogenital Warts in the Era of HPV-Vaccine: A Literature Review.

Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see approach is often adopted in asymptomatic immunocompetent children, with spontaneous clearing in almost 90% of cases within two years, persistent or symptomatic lesions can be reasonably treated. However, few studies have been conducted on children. Consequently, most treatments on patients under age 12 are not approved by the Food and Drug Administration. Herein, we review possible therapies for pediatric use in AW and report an illustrative case of a two-year-old boy with atopic skin and symptomatic, persistent AWs who was successfully treated with topical podophyllotoxin, without adverse effects or recurrence. Among available therapies for AWs, topical therapies, such as immunomodulating-agents (topical imiquimod 5% and 3.75% cream, sinecatechins 15% ointment) and cytotoxic agents (podophyllotoxin and cidofovir) are considered manageable in children because of their low aggressiveness. In particular, podofillotoxin gel 5% and imiquimod 5% cream have been reported to be safe and efficacious in children. Currently, HPV vaccination is not recommended as a treatment for established HPV infection and AWs, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and deserves mention.

Disseminated life-threatening viral skin rash in a child with atopic dermatitis.

We report the case of a toddler, with a history of mild atopic dermatitis (AD) since early infancy, presented to the Giannina Gaslini, a pediatric polyclinic hospital, 14 days after measles-mumps-rubella (MMR) vaccination, for the occurrence of a disseminated vesico-pustular rash, accompanied by general malaise, fever, restlessness, and anorexia. Eczema herpeticum (EH) was diagnosed clinically and confirmed by laboratory examinations. The exact pathogenesis of EH in AD is still debated and possibly involves an inter-play between altered cell-mediated and humoral immunity, failure to up-regulate antiviral proteins, and exposure of viral binding sites through the dermatitis and an epidermal barrier failure. We hypothesize that in this particular case, MMR vaccination might have played an additional important role in the alteration of innate immune response, facilitating the manifestation of herpes simplex virus type 1 in the form of EH.

Cutaneous Disorders Masking Celiac Disease: Case Report and Mini Review with Proposal for a Practical Clinical Approach.

Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including damage to cutaneous and connective tissue. We report a rare case of chronic severe dermatitis involving connective tissue and cutaneous vascular vessels as the main clinical presentation of undiagnosed seronegative gluten disorder. A gluten-free diet dramatically improved the intestinal and cutaneous clinical damage in the patient. Pitfalls and the steps of differential diagnosis are described. We also review the literature regarding studies of CD and connective tissue diseases to extend the knowledge of these rare associations. We propose a practical diagnostic approach in suspected CD in autoimmune cutaneous disorders.