Aghazadeh Mohandesi, Nessa

The focus of this review is the clinical and pathologic presentations of hereditary cancer syndromes with cutaneous manifestations, with the goal of providing a reference for the multidisciplinary care teams involved in the diagnosis and management of these conditions. Advancements in genomics have led to newly recognized syndromes and a deeper understanding of established syndromes. We focus on those with the most relevant cutaneous manifestations. Clinical and histopathologic images provide visual context for these findings, many of which are rare. We summarize the established literature and incorporate new research and noteworthy case reports.

ABSTRACT Myhre syndrome is a rare multisystem disorder characterized by distinctive facial features, hearing loss, and progressive fibrosis affecting the skin, joints, lungs, and cardiovascular system. It is caused by heterozygous pathogenic variants in the SMAD4 gene. In this review, we detail the cutaneous manifestations observed in two previously reported patients with genetically confirmed Myhre syndrome. While skin biopsies demonstrated pan‐dermal thickening of collagen bundles, the immunohistochemical staining patterns were distinct from those seen in other inflammatory sclerosing disorders. Additionally, we conducted a comprehensive literature review of the cutaneous features associated with Myhre syndrome, identifying 175 patients with confirmed SMAD4 pathogenic variants. The most reported cutaneous finding was thickened or stiff skin (76%), followed by keratosis pilaris (22%) and impaired wound healing or abnormal scarring (18%). Genotype–phenotype analysis suggested a diagnostic delay in patients with the codon 496 variant, who were more frequently diagnosed in adulthood. This variant may also be associated with a milder cutaneous phenotype, highlighting the clinical heterogeneity of Myhre syndrome. These findings underscore the importance of recognizing cutaneous features as potential early diagnostic clues in patients with suspected Myhre syndrome.

ABSTRACTEpidermolysis bullosa (EB) is a rare genetic disorder requiring intensive and costly care, often diagnosed in infancy when families are unprepared for the financial burden. We analyzed 160 U.S.‐based crowdfunding campaigns for living EB patients, extracting data on demographics and financial needs. 33.8% of patients requested financial support for wound care supplies, 36.9% of patients requested support for travel costs, and 9.4% of patients requested support with special clothing or bedding. These findings highlight persistent, unresolved financial needs for EB‐related care.

ABSTRACTBackgroundBlau syndrome is a rare, autosomal dominant granulomatous disease caused by mutations in the NOD2/CARD15 gene. While the classic triad of arthritis, dermatitis, and uveitis is well known, the full range of cutaneous manifestations remains underexplored.ObjectiveTo expand the understanding of cutaneous findings in Blau syndrome, correlate these findings with NOD2 variants, and evaluate treatment outcomes across organ systems.MethodsA retrospective review of medical records from January 1999 to January 2024 identified 14 patients with Blau syndrome supported by the presence of NOD2 variants. Clinical data on dermatological features, genetics, and treatment responses were analyzed and categorized into specific and non‐specific cutaneous findings.ResultsOf the 14 patients with Blau syndrome, 85% (12/14) demonstrated skin involvement. Specific findings included lichenoid or granulomatous papules and nodules (50%, 6/12), while non‐specific findings (83%, 10/12) were more diverse, including dermatitis (6/10), chronic urticaria (5/10), ichthyosiform eruptions (4/10), vasospastic disorders (5/10), and oral/genital ulcers (2/10). Skin biopsies in three patients with specific findings revealed non‐caseating granulomas. Genetic analysis identified multiple NOD2 variants, though no clear genotype–phenotype correlation was observed. TNF‐alpha inhibitors demonstrated efficacy in controlling ocular and joint disease.ConclusionBlau syndrome presents with a broader spectrum of cutaneous findings than previously recognized. These findings highlight the importance of dermatological evaluation and a multidisciplinary approach to optimize diagnosis and management.

We performed a retrospective review of patients with lichen planus pemphigoides (LPP) over almost a 23-year period to gather clinical, histopathological, immunological and treatment-related information and to compare idiopathic LPP with drug-induced LPP. This study represents the largest single-institution case series of LPP to date and includes novel findings related to mucosal involvement, autoantibody profiles and the value of monitoring bullous pemphigoid (BP) autoantibodies in predicting treatment response. This study also includes characteristic histopathological findings that can aid in the diagnosis and differentiation of LPP from BP, in addition to comparisons between idiopathic LPP and drug-induced LPP.

ABSTRACTBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory condition. While obesity is linked to increased HS severity in adults, data on its impact in pediatric HS remain limited. This study investigates the relationships between obesity, HS severity, HS‐related comorbidities, and therapeutic management in pediatric patients.MethodsThis is a retrospective cohort analysis on patients diagnosed with HS before 18 years of age. Data were collected on disease severity, comorbidity development, and treatments. Trends were compared between HS patients with and without obesity and with healthy controls for comorbidity development.ResultsThere was no difference in disease severity using Hurley staging between patients with and without obesity (p = 0.679). Patients with obesity were more likely to be prescribed biologics (p = 0.012), but not other treatments. The risk of developing dyslipidemia, anxiety, depression, and thyroid disease was elevated in pediatric HS patients, even after controlling for BMI (p < 0.001).ConclusionsIn this study, obesity was not associated with HS disease severity in children. However, children with obesity were more likely to be prescribed biologics. HS may independently increase the risk of dyslipidemia, anxiety, depression, and thyroid disease.

Objectives: 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. Methods: 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. Results: 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. Conclusion: 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 of evidence: Level 4 (case series).

ABSTRACTRubinstein‐Taybi syndrome (RTS) is a rare genetic disorder featuring craniofacial abnormalities, intellectual disability, and multi‐organ involvement, including increased risk of keloid formation, pilomatricomas, and hypertrichosis. Hidradenitis suppurativa (HS), a chronic inflammatory skin condition characterized by recurrent abscess formation and draining tunnels, has never been described in a patient affected by RTS. In this report, we detail the history of a 32‐year‐old male with RTS and refractory Hurley stage III HS and discuss the important considerations and risks of managing this unique patient population.