Post-streptococcal small-vessel vasculitis in a 16-month-old with associated intussusception and hypertension: Henoch Schönlein purpura?

Henoch Schönlein purpura (HSP), also known as IgA vasculitis, is a systemic small-vessel vasculitis typically occurring in children 3-15 years of age, with peak incidence at 4-6 years. It is characterized by a constellation of symptoms including palpable purpura, arthralgias or arthritis, abdominal pain including intussusception, and renal involvement. We report a patient with these clinical findings whose IgA immunofluorescence was negative but with a presumptive diagnosis of HSP at 16 months of age, significantly younger than the classic population. This condition rarely affects this age group, and we highlight the importance of considering vasculitis in children of all ages, as a failure to diagnose could lead to insufficient long-term monitoring, particularly regarding renal function.

Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Dyschromatosis symmetrica hereditaria: A clue to early diagnosis of Aicardi-Goutières syndrome.

A 6-year-old female with a history of Aicardi-Goutières syndrome (AGS) presented to dermatology clinic with hypopigmented and hyperpigmented macules and patches consistent with dyschromatosis symmetrica hereditaria (DSH). Previous genetic workup demonstrated a de novo, heterozygous mutation in the adenosine deaminase acting on RNA 1 (ADAR) gene. While the co-occurrence of AGS and DSH has previously been described in mutations of the ADAR gene, our case highlights the potential association between these disorders that may aid in earlier future diagnosis of AGS.

Rapid resolution of diffuse warts following initiation of dupilumab for severe atopic dermatitis.

Cutaneous warts are an exceedingly common cutaneous viral infection for which existing treatment options are often painful, expensive, and only marginally effective. Extensive warts may occur in the setting of primary immunodeficiencies, wherein they can co-occur with other diseases of immune dysfunction, such as atopic dermatitis (AD). Dupilumab, an IL-4 receptor α (IL-4Rα)-blocking monoclonal antibody, is a biologic agent recently approved for the treatment of moderate-to-severe eczema. Here, we report a case of a young girl with both severe AD and diffuse filiform warts, which resolved shortly after initiating treatment for AD with dupilumab.

Widespread keratinocytic epidermal nevus with an associated chylous pericardial effusion.

A 17-year-old male presented for review of a widespread keratinocytic epidermal nevus (KEN) in the setting of a chronic pericardial effusion. Biopsy of the epidermal nevus revealed a KRAS mutation. Pericardiocentesis revealed a chylous effusion and magnetic resonance lymphangiogram demonstrated an underlying lymphatic malformation. There are rare case reports of KEN with an associated KRAS mutation. This case highlights the importance of being alert to epidermal nevus syndrome, particularly in patients with a widespread nevus and seemingly unrelated pathology.

Morphea after initiation of dupilumab in two pediatric atopic dermatitis patients.

Morphea is a rare multifactorial autoimmune disorder characterized by a complex and dynamic interplay between Th1 and Th2 signaling. Active clinical trials are currently investigating the safety and efficacy of dupilumab for the treatment of primary morphea. Here, we present two cases of morphea that developed in pediatric atopic dermatitis patients treated with dupilumab. These findings may support a causal relationship between IL-4 receptor blockade and the development of the early inflammatory phase of morphea.

Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly.

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

Rare airway tumor in a previously healthy adolescent successfully treated with endoscopic resection and oral propranolol.

Airway tumors are rare in children. Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a benign vascular tumor usually found on the skin or in the oral cavity. Rarely, these lesions occur in the airway and cause significant hemoptysis. Most reported airway PGs have occurred in the trachea of adults. Here, we present a case of an adolescent female who presented with hemoptysis and was found to have a PG in the right lower lobe. Per institutional guidelines, this case report was exempt from institutional review board approval.

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease.

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Atopic dermatitis-like graft-versus-host disease treated with dupilumab.

The mainstay of treatment for atopic dermatitis (AD)-like graft-versus-host disease (GVHD) in both pediatric and adult patients includes oral corticosteroids with or without other systemic immunosuppressive therapies. To our knowledge, we report the first case series of dupilumab in the treatment of AD-like GVHD in a pediatric cohort of four patients, where we observed clinical improvement of GVHD as well as a reduction in itch in 3/4 (75%) patients. Our findings suggest that dupilumab is not only effective in treating AD-like GVHD, but also reduces systemic immunosuppression in the pediatric transplant population. The ability to reduce the length and amount of immunosuppression as well as improve quality of life suggest that dupilumab may serve as a safe and effective therapeutic option in our transplant population with GVHD.

Paraneoplastic pemphigus associated with Castleman disease: A multicenter case series.

INTRODUCTION: Paraneoplastic pemphigus (PNP) is a rare, often fatal, autoimmune blistering disease of the skin and mucous membranes. In children, PNP is frequently associated with Castleman disease (CD). This series describes five cases of PNP associated with CD. METHODS: Data were collected retrospectively from the medical records of patients with a diagnosis of PNP and CD from January 2013 to June 2022. Patients ≤22 years old with clinical and immunopathologic evidence of PNP were included; CD was diagnosed histopathologically. RESULTS: Two children, two adolescents, and one young adult (two males, three females) were included. The average age at disease presentation was 11.8 years (range: 7-22 years). Oral (n = 5) and anogenital (n = 3) mucositis were common. Four patients had "unicentric" CD (UCD); one patient had "multicentric" CD (MCD). Castleman tumors were in the retroperitoneum (n = 4) or axilla (n = 1). One patient had myasthenia gravis without thymoma. Three patients had bronchiolitis obliterans (BO). Three patients had complete resection of their CD; two had partial resection. Three patients remain alive with a median follow-up of 13 months (range: 12 months to 13 years); two are clinically stable with resolution of mucocutaneous lesions; one has persistent BO requiring ongoing ventilatory support. Patients who remain alive had UCD with complete resection; all deceased patients had partial resection and BO. CONCLUSION: Most patients had UCD, and the retroperitoneum was the most common location. Patients with MCD, incomplete resection, and BO died; patients with UCD and complete resection remain alive, even in the setting of BO. Consideration of PNP is critical when pediatric patients present with mucositis as PNP may be clinically indistinguishable from more common causes of mucositis.

Management of Bleeding Pyogenic Granulomas in Acute Care Settings.

BACKGROUND: Pyogenic granulomas are acquired, benign growths of capillary blood vessels that are commonly seen in the pediatric population. Patients with these lesions often present to emergency departments and urgent care centers with persistent bleeding after minor trauma. Much of the published literature describing the management of pyogenic granulomas, however, is focused on outpatient or definitive therapies, and there is limited information on the management of acute bleeding. OBJECTIVE: We conducted a narrative review to present and evaluate strategies and therapies available to emergency physicians for managing actively bleeding pyogenic granulomas in acute care settings. DISCUSSION: Multiple options are available to emergency physicians to achieve hemostasis. Direct pressure with a nonadherent dressing remains first-line treatment. Additional therapeutic options, such as dressings impregnated with topical vasoconstrictors or hemostatic dressings or agents, can be used if bleeding persists. Certain approaches-silver nitrate, suture ligation, or electrocautery-may be available to some emergency physicians. These therapies, however, can compromise future histologic analysis of tissue for definitive diagnosis and have potential risks. CONCLUSION: Although there are multiple options to achieve hemostasis in cases of bleeding, some treatments may lead to suboptimal cosmesis or interfere with future management. Many bleeding pyogenic granulomas will become hemostatic with treatments available to emergency physicians. Surgical consultation may be warranted for pyogenic granulomas that are unresponsive to the therapies described in this review.

Safety of dupilumab in a 5-month-old infant with severe atopic dermatitis.

Dupilumab is a fully humanized monoclonal antibody that suppresses Th2-mediated inflammation by inhibiting signaling of interleukin-4 and interleukin-13 through the interleukin-4 alpha receptor subunit, and is approved by the FDA for the treatment of moderate to severe atopic dermatitis (AD) in children 6 years of age and older. While initial data from phase 2 trials in children less than 6 years are promising, dupilumab use in children less than 6 months of age is not well studied. Here we present a case of a 5-month-old boy with severe primary AD, eosinophilia, hypogammaglobulinemia, and poor weight gain, who was successfully treated with dupilumab and experienced no serious adverse effects. To our knowledge, this is the youngest patient to receive dupilumab to date.

Severe recalcitrant hidradenitis suppurativa in a 2-year-old boy with partial trisomy 13.

We report the case of a 2-year-old boy with mosaic trisomy 13 and immunodeficiency who developed severe hidradenitis suppurativa beginning at the age of 18 months. Unresponsive to standard therapies, he exhibited a partial response to immunoglobulin replacement therapy.

Cutaneous mastocytosis in a child with a de novo GNB1 mutation.

In the last few years, de novo mutations in the GNB1 gene have been found to cause a neurodevelopmental disorder typically characterized by global developmental delay and hypotonia. Only 4 cases of maculopapular cutaneous mastocytosis in children with GNB1 mutations have been reported to date. Here, we describe another case of the condition with concomitant cutaneous mastocytosis.

Experience using dupilumab for pediatric atopic dermatitis at a tertiary care c enter: Inadequate response and adverse events.

BACKGROUND/OBJECTIVE: Dupilumab is highly effective in treating atopic dermatitis (AD). However, some patients experience difficulties with dupilumab therapy, such as inadequate clinical response, failure to achieve long-term disease control, or adverse events (AEs). Our objective is to assess inadequate response and AEs occurring in children on dupilumab therapy for AD. METHODS: This is a retrospective cohort study of children on dupilumab for AD. Collected variables included patient demographics, medical histories, and dupilumab therapy characteristics. Response analysis was conducted in those with ≥3 months of dupilumab therapy: primary poor responders were defined as those whose EASI scores did not decrease by >50%, and secondary poor responders were those who initially responded but had significant AD flares while on therapy. RESULTS: We included 200 patients on dupilumab for AD in our cohort; 192 received ≥3 months of therapy and were included in our response analysis. Twelve children experienced inadequate primary response, and 4 were secondary poor responders. Four of these 16 children discontinued therapy due to inadequate response. The most common dupilumab-associated AEs were facial erythema (n = 24, 12.0%) and injection-site reactions (n = 24, 12.0%). Female sex was significantly associated with experiencing injection-site reactions, and prior hospitalization was significantly associated with HSV infection on dupilumab. Eight patients discontinued therapy due to an AE. CONCLUSION: A small but significant number of patients experienced treatment difficulties while on dupilumab. The risk of inadequate response to dupilumab and dupilumab-associated AEs should be discussed thoroughly with patients and their families prior to initiation.

A case of disseminated Lyme disease in a child with skin of color.

Disseminated Lyme disease requires treatment to prevent severe sequelae, particularly neurologic. We report here a case of disseminated Lyme disease in a patient with skin of color. Pediatric dermatologists must maintain a high clinical suspicion for Lyme disease and be aware of how typical cutaneous findings may appear differently in skin of color.

Misdiagnosis of capillary malformations in darker skin phototypes.

In the dermatologic medical literature, there is an underrepresentation of conditions in individuals of color. Due to the lack of representation, it may be harder for clinicians to recognize certain diagnoses in patients with darker skin phototypes leading to misdiagnosis and affecting overall patient management, outcomes, and satisfaction. Here, we present four Black or Indigenous People of Color who were initially referred for hyperpigmentation, hemihyperplasia, or café au lait spots and found to have syndromic capillary malformations.