Morphea as an isotopic response to pigmented purpuric dermatosis and lichen striatus.

Morphea is an uncommon inflammatory and fibrosing disorder that has a polymorphous clinical presentation. We report two cases of morphea developing as an isotopic response after a preceding benign skin disease, accompanied by a review of the literature. This case series highlights the importance of return to care recommendations for benign skin conditions such lichen striatus and pigmented purpuric dermatoses due to the rare possibility of subsequent morphea development.

Dermatologic complications in pediatric patients after hematopoietic stem cell transplantation for sickle cell disease.

Dermatologic complications are common following allogeneic hematopoietic stem cell transplantation, but dermatologic complications among pediatric patients undergoing hematopoietic stem cell transplantation for the treatment of sickle cell disease have been poorly characterized. In this case series of 17 patients (<21 years old) with sickle cell disease who underwent hematopoietic stem cell transplantation, 16 (94.1%) experienced one or more dermatologic complications after transplant, with the most common complications including acute or chronic mucocutaneous graft-versus-host disease (GVHD) (34.1% of complications), skin eruptions of unknown origin (15.9% of complications), infections (15.9% of complications), and chemotherapy-related pigmentary changes (11.4% of complications). Patients who developed acute or chronic skin GVHD were significantly older at the time of hematopoietic stem cell transplantation. These findings highlight the need to closely monitor for dermatologic complications in pediatric patients who undergo hematopoietic stem cell transplantation for sickle cell disease and underscore the importance of involving dermatology early on when skin complications occur, although further research with a larger multicenter study could help clarify the risk for dermatologic complications and help identify potential ways to mitigate this risk.

A survey assessment of combined pediatric dermatology-rheumatology clinics.

The expertise of both dermatology and rheumatology may be beneficial when managing autoimmune conditions with cutaneous and systemic manifestations in children. This survey study was directed to pediatric dermatologists who participate in combined pediatric dermatology-rheumatology clinics; 13 sites in North America responded. The results provide information regarding clinic operations, benefits, and barriers to establishment. These findings have the potential to help institutions establish or modify combined pediatric dermatology-rheumatology clinics, although further research is needed to determine their impact.

Presenting characteristics and progression of pediatric-onset morphea: Interim analysis of a prospective registry.

Morphea is a rare fibrosing disorder with a highly variable disease course, which can complicate management. Here, we present a prospective cohort study describing the current treatments used in the management of pediatric-onset morphea and assessing responses to systemic and topical therapies. Most patients demonstrated inactive disease by 1 year, regardless of treatment, though recurrences were common in our cohort overall (39%). Our results support the need for continuous monitoring of all children with morphea following the completion of treatment, including topical treatment, due to high rates of disease relapse.

Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines.

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.

Body site distribution of pediatric-onset morphea and association with extracutaneous manifestations.

BACKGROUND: The distribution of pediatric-onset morphea and site-based likelihood for extracutaneous complications has not been well characterized. OBJECTIVE: To characterize the lesional distribution of pediatric-onset morphea and to determine the sites with the highest association of extracutaneous manifestations. METHODS: A retrospective cross-sectional study was performed. Using clinical photographs, morphea lesions were mapped onto body diagrams using customized software. RESULTS: A total of 823 patients with 2522 lesions were included. Lesions were more frequent on the superior (vs inferior) anterior aspect of the head and extensor (vs flexor) extremities. Linear morphea lesions were more likely on the head and neck, whereas plaque and generalized morphea lesions were more likely on the trunk. Musculoskeletal complications were more likely with lesions on the extensor (vs flexor) extremity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.4), whereas neurologic manifestations were more likely with lesions on the anterior (vs posterior) (OR, 2.8; 95% CI, 1.7-4.6) and superior (vs inferior) aspect of the head (OR, 2.3; 95% CI, 1.6-3.4). LIMITATIONS: Retrospective nature and the inclusion of only patients with clinical photographs. CONCLUSION: The distribution of pediatric-onset morphea is not random and varies with body site and within individual body sites. The risk stratification of extracutaneous manifestations by body site may inform decisions about screening for extracutaneous manifestations, although prospective studies are needed.

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy.

Cancer remains a leading cause of morbidity and mortality among children. Targeted therapies may improve survivorship; however, unique side-effect profiles have also emerged with these novel therapies. Changes in hair, skin, and nails-termed dermatologic adverse events (AEs)-are among the most common sequelae and may result in interruption or discontinuation of therapy. Though dermatologic AEs have been detailed in adults, these findings are not well described in the pediatric population. We reviewed the literature to characterize dermatologic AEs to anticancer targeted therapies available as of July 2020 and summarized the spectrum of clinical findings as well as treatment recommendations for children. Dermatologic AEs are among the most common AEs reported in pediatric patients receiving targeted therapy, but morphologic and histologic descriptions are often lacking in current publications. Pediatric dermatologists are uniquely poised to recognize specific morphology of dermatologic AEs and make recommendations for prevention and treatment that may improve quality of life and enable ongoing cancer therapy.

Pediatric maculopapular cutaneous mastocytosis: Retrospective review of signs, symptoms, and associated conditions.

BACKGROUND/OBJECTIVES: Though maculopapular cutaneous mastocytosis is the most common form of pediatric mastocytosis, it remains unclear which patients will experience severe symptoms. We sought to better define the presentation and the cutaneous and systemic signs and symptoms in patients with maculopapular cutaneous mastocytosis. METHODS: We analyzed retrospective data on 227 patients diagnosed with maculopapular cutaneous mastocytosis prior to age 15 years from five US clinical sites. We collected data on signs, symptoms, age of onset, and laboratory testing. RESULTS: Median age of onset of maculopapular cutaneous mastocytosis was 3 months, with 94% of patients presenting prior to age 2 (range 0-15 years). Patients presenting before age 2 had significantly lower serum tryptase level (P = .019). Greater number of skin lesions (P = .006), number of reported skin signs and symptoms (P < .001), and higher tryptase levels (P < .001) were associated with more systemic symptoms. CONCLUSION: Children with maculopapular cutaneous mastocytosis, who have greater skin involvement, higher serum tryptase level, and more skin signs and symptoms, are more likely to have systemic symptoms.

The geographic distribution of the US pediatric dermatologist workforce: A national cross-sectional study.

BACKGROUND /OBJECTIVES: Although 82% of pediatricians report that their patients have difficulty accessing pediatric dermatologists, the regions with greatest need for the specialty are not well-defined. We aimed to determine the geographic distribution of pediatric dermatologists relative to the number of children and pediatric generalists. METHODS: We performed a cross-sectional study of all US board-certified pediatric dermatologists, generalists (defined as pediatricians and family medicine physicians), and children in 2020. Data were obtained from the Society for Pediatric Dermatology, American Board of Pediatrics, Centers for Medicare and Medicaid, and US Census Bureau. Number of children, pediatric dermatologists, and pediatric generalists were tabulated in each county and state, and the distributions of pediatric dermatologists and generalists relative to the population of children were quantified with the Gini coefficient. RESULTS: Of 317 pediatric dermatologists, 243 (76.7%) were women and 311 (98.1%) worked in a metropolitan county. A pediatric dermatologist was present in 41/50 (82%) states and 142/3228 (4.4%) counties. Not a single pediatric dermatologist was found in 54/92 (58.7%) counties with 100 000-199 999 children, 15/53 (28.3%) counties with 200 000-499 999 children, and 4/13 (30.8%) counties with ≥500 000 children. The Gini coefficient for the state-level distribution of pediatric dermatologists relative to population of children was 0.488 compared to 0.132 for that of pediatric generalists. CONCLUSION: There is a maldistribution of pediatric dermatologists, resulting in children with unmet dermatologic needs in nine states and 96 heavily populated counties. These results can inform initiatives to recruit pediatric dermatologists and to expand telehealth access to specific high-density areas.

A retrospective study: Impact of consensus treatment plans on systemic therapy of pediatric morphea.

BACKGROUND: Morphea is an inflammatory and fibrosing condition that affects the skin and subcutaneous structures. Morphea is managed by dermatologists, rheumatologists, or both. Prior studies have suggested there is significant variability in approach to treatment. In 2012, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) for pediatric morphea to develop more standardized treatment plans for patients requiring systemic therapy. We aimed to assess whether the publication of CTPs has impacted care of patients with morphea at our institution. METHODS: Data were collected via a retrospective review of medical records of 61 pediatric patients diagnosed with morphea at Seattle Children's Hospital (SCH) from January 1, 2005, to December 12,2017. RESULTS: Prior to the publication of CTPs, 2 out of 24 patients (8.3%) were treated with a regimen that matched a subsequent CTP. After publication of CTPs, 29 out of 37 patients (78.4%) were treated with a regimen that matched a CTP (P < 0.001). A subanalysis was performed to assess the number of patients who needed second- or third-line therapies. Of those who followed a CTP therapy plan (n = 26), 3 patients (11.5%) needed a second-line therapy compared with 11 patients (44%) in the no-CTP followed group (n = 25), (P = 0.012). CONCLUSIONS: The publication of CTPs led to a significant change in treatment approach for patients with morphea requiring systemic therapy at SCH. Patients treated with one of the treatment plans recommended by the CTPs were less likely to need second-line systemic therapy.

Hypergammaglobulinemic purpura of Waldenström in children.

BACKGROUND: Hypergammaglobulinemic purpura of Waldenström (HGPW), a rare cutaneous eruption characterized by the triad of recurrent episodes of lower extremity petechiae, symptoms of stinging and burning, and lower extremity edema, is poorly described in children. Some children have been reported to follow a benign course, while others are eventually diagnosed with fulminant rheumatologic disease. OBJECTIVES: To determine the distinguishing features of HGPW including the spectrum of disease manifestations and clinical outcomes. METHODS: This is a multicenter, retrospective case series of six children with HGPW combined with a literature review of 45 previously published pediatric cases. RESULTS: Most children were eventually diagnosed with systemic disease (63%) or developed autoantibody accumulation suggestive of evolving disease (71%). The most common diagnoses were Sjogren's syndrome and systemic lupus erythematosus. The mean duration between onset of cutaneous eruption and diagnosis of systemic disease was 5.6 years, underscoring that HPGW patients often present with a rash that precedes the development of systemic symptoms. CONCLUSIONS: Diagnosis of HGPW should prompt initial screening for rheumatologic disease with long-term rheumatology follow-up, as the majority of patients present with evolving manifestations of systemic disease.

Systemic immunosuppressive therapy for inflammatory skin diseases in children: Expert consensus-based guidance for clinical decision-making during the COVID-19 pandemic.

BACKGROUND/OBJECTIVES: The COVID-19 pandemic has raised questions about the approach to management of systemic immunosuppressive therapies for dermatologic indications in children. Change to: Given the absence of data to address concerns related to SARS-CoV-2 infection and systemic immunosuppressive therapies in an evidence-based manner, a Pediatric Dermatology COVID-19 Response Task Force (PDCRTF) was assembled to offer time-sensitive guidance for clinicians. METHODS: A survey was distributed to an expert panel of 37 pediatric dermatologists on the PDCRTF to assess expert opinion and current practice related to three primary domains of systemic therapy: initiation, continuation, and laboratory monitoring. RESULTS: Nearly all respondents (97%) reported that the COVID-19 pandemic had impacted their decision to initiate immunosuppressive medications. The majority of pediatric dermatologists (87%) reported that they were pausing or reducing the frequency of laboratory monitoring for certain immunosuppressive medications. In asymptomatic patients, continuing therapy was the most popular choice across all medications queried. The majority agreed that patients on immunosuppressive medications who have a household exposure to COVID-19 or test positive for new infection should temporarily discontinue systemic and biologic medications, with the exception of systemic steroids, which may require tapering. CONCLUSIONS: The ultimate decision regarding initiation, continuation, and laboratory monitoring of immunosuppressive therapy during the pandemic requires careful deliberation, consideration of the little evidence available, and discussion with families. Consideration of an individual's adherence to COVID-19 preventive measures, risk of exposure, and the potential severity if infected must be weighed against the dermatological disease, medication, and risks to the patient of tapering or discontinuing therapies.

Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis.

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectual disability can be present, although affected individuals without seizures and with normal intellect have also been reported. Given the patchy and asymmetric nature of the malformations, ECCL has been hypothesized to be due to a post-zygotic, mosaic mutation. Despite phenotypic overlap with several other disorders associated with mutations in the RAS-MAPK and PI3K-AKT pathways, the molecular etiology of ECCL remains unknown. Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each. These two residues are the most commonly mutated residues in FGFR1 in human cancers and are associated primarily with CNS tumors. Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of individuals with ECCL identified one additional individual with a c.1638C>A (p.Asn546Lys) mutation in FGFR1. Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling. In addition to identifying the molecular etiology of ECCL, our results support the emerging overlap between mosaic developmental disorders and tumorigenesis.

Cutaneous polyarteritis nodosa in pediatric patients successfully treated with TNF-α inhibitor and methotrexate: Case series and literature review.

Cutaneous polyarteritis nodosa (CPAN) is a rare necrotizing vasculitis affecting small- to medium-sized arteries. Reported treatments include oral corticosteroids alone or in combination with non-steroidal antiinflammatory drugs, intravenous immunoglobulins, cyclophosphamide, azathioprine, colchicine, or dapsone. However, some patients with CPAN do not respond to such treatments and continue to experience exacerbations over prolonged periods. This series provides support for the use of TNF-α inhibitors in the treatment of recalcitrant CPAN in pediatric patients.

Pediatric dermatology workforce in the United States.

Studies have suggested there is a shortage of pediatric dermatologists in the United States, but the workforce has not been well defined. The Society for Pediatric Dermatology (SPD) Workforce Committee sought to characterize the US pediatric dermatology workforce with a nine-question survey, sent to all 484 US SPD members in December 2016. The response rate was 30%. Most pediatric dermatologists were practicing in major metropolitan markets, seeing an average of 80 patients a week with an average 6-week wait time. These findings indicate that geographic maldistribution and long wait times for new patient appointments remain substantial hurdles for adequate access to subspecialty pediatric dermatology care.

Characterization of a severe case of PIK3CA-related overgrowth at autopsy by droplet digital polymerase chain reaction and report of PIK3CA sequencing in 22 patients.

PIK3CA-related overgrowth spectrum (PROS) refers to a group of disorders of segmental overgrowth of a wide variety of tissues as well as venous and lymphatic malformations. Clinical and molecular diagnosis can be challenging due to phenotypic heterogeneity and difficulties detecting low-level mosaicism using standard methods. Here, we report a patient with a severe presentation of PIK3CA-related overgrowth with analysis of 27 posthumously collected tissues by droplet digital polymerase chain reaction (PCR) at autopsy. This patient had a complicated medical course, with coagulopathy, ischemic brain injury, and sepsis resulting in multi-organ failure and death at age 2 months despite sirolimus therapy. Five of the 27 tissues analyzed possessed a mosaic PIK3CA mutation (p.E545K), with mutation levels ranging from 3 to 20% across affected tissues. We found no correlation between tissue-specific disease severity and mutation levels, likely reflecting sampling limitations. We also tested a series of 22 individuals with somatic overgrowth and/or vascular-lymphatic malformations using a targeted next generation sequencing panel and found PIK3CA mutations in nine individuals, identifying three novel PIK3CA variants. This report expands the clinical and molecular spectrum of PROS, emphasizes that different molecular methods can be complimentary in the diagnosis of these disorders, and highlights the risk of coagulopathy in a subset of patients with PIK3CA-related overgrowth.

An atypical presentation of herpes simplex virus infection in Harlequin ichthyosis.

We present an atypical presentation of herpes simplex virus infection in a patient with Harlequin ichthyosis, which we attribute to abnormal cornification.

Discordance of pediatric morphea treatment by pediatric dermatologists.

BACKGROUND/OBJECTIVES: Studies describing treatment efficacy in pediatric morphea are lacking. Subspecialists have reached no consensus on how to optimally treat pediatric morphea. The objective of the current study was to describe the most common treatment practices of pediatric dermatologists worldwide who care for children with morphea. METHODS: A survey regarding topical treatment practices of pediatric morphea, with representative case-based scenarios, was distributed to pediatric dermatologists and results were tallied. RESULTS: The survey response rate was 13.4%, with 110 respondents in the final analysis. The majority of respondents agreed on red violaceous rim (99%), increased local warmth (75%), raised borders (69%), and dermal thickening (64%) as signs of disease activity. Respondents had less agreement on sclerotic lesions (41%), scaling (43%), dyspigmentation (19%), and atrophy (13%) as signs of disease activity. Ninety-two percent of respondents used primary therapy or monotherapy with topical medications, including 45% in linear morphea of the limbs and 37% in linear morphea of the head or neck. High-potency topical corticosteroids were most commonly used (80%), although respondents did not agree on specific regimens. Sixteen different treatment regimens were selected as first-line therapy for one case scenario of active disease. CONCLUSION: The survey found large variation in how pediatric dermatologists treat pediatric morphea. Consensus treatment guidelines developed by pediatric dermatologists and pediatric rheumatologists are urgently needed regarding the efficacy of therapies for pediatric morphea. Prospective studies of treatment efficacy in pediatric morphea are urgently needed as well.