Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid Papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population is scarce. OBJECTIVES: To characterize epidemiological, clinical, histopathological, and prognostic features of paediatric LyP. METHODS: This was a retrospective, multicentre international cohort study including 87 cases of children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years old at disease onset were included. Diagnosis was made in each centre based on clinical-pathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. The mean age at onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2:1. The mean time between onset of first cutaneous lesions and diagnosis was 1.3 years (range 0-14 years). Initial misdiagnosis concerned 26.4% of patients. Initially, LyP was most often misdiagnosed as Pityriasis lichenoides et varioliformis acuta (PLEVA), insect bites, or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned for 20.7% of patients. The main histological subtype was type A in 55.1% of the cases. If analysed, monoclonal TCR rearrangement was found in 76.5% of the skin biopsies. The overall survival rate was 100% with follow up at 5 years available for 33 patients and at 15 years for 8 patients. A development of associated haematological malignancy (HM) occurred in 9.6% of the cases (7/73), including four mycosis fungoides (MF) cases, one primary cutaneous anaplastic large cell lymphoma (pc-ALCL), one systemic ALCL and one case of acute myeloid leukaemia. If we compare incidence rates of cancer with the world 0-19 years old population from 2001-2010, we estimate a significantly higher risk of associated malignancy in general, occurring before the age of 19 years old with incidence rate ratio of 87.49 (CI 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall the prognosis of the disease is good, with excellent survival rates for all patients. Due to increased risk of associated HM, a long-term follow-up should be recommended for LyP patients.

Idiopathic calcinosis cutis in an infant: The importance of a wait-and-see approach.

A healthy 2-year-old girl presented with multiple asymptomatic subcutaneous nodules on both legs. Histologically demonstrated calcium deposition within the dermis and subcutaneous tissue consistent with calcinosis cutis. Laboratory abnormalities, underlying genetic conditions, and potential triggering factors were ruled out. The lesions resolved over an 18-month period without treatment, emphasizing the importance of the wait-and-see approach in idiopathic cases of calcinosis cutis.

Conradi-Hünermann-Happle syndrome with minimal signs.

A 4-year-old girl presented with congenital patches of scalp alopecia, which on physical examination, was consistent with blaschkolinear alopecic patches with mild epidermal atrophy. Similar atrophic hypopigmented patches were seen on the trunk and proximal extremities. With the clinical suspicion of Conradi-Hünermann-Happle syndrome, genetic testing was performed and revealed a mutation in the EBP gene. Despite characteristic cutaneous findings, no skeletal, ocular, or other anomalies were found on further evaluation.

Suspected COVID-19-related reticulated purpura of the soles in an infant.

A growing number of skin lesions during the COVID-19 pandemic are being recognized. Acral ischemic lesions identical to chilblains are most typical in children and young adults. We report an infant girl, aged 1 month and 29 days, with a peculiar reticulated purpuric eruption on her soles, with positive immunohistochemistry for SARS-CoV-2 in the endothelia of dermal blood vessels. The patient had an excellent outcome without specific therapy.

A case of mid-face toddler excoriation syndrome (MiTES).

The term mid-face toddler excoriation syndrome (MiTES) has been proposed to describe a rare condition that arises in infancy as is characterized by self-inflicted excoriations. It is considered to be a milder variant of hereditary sensory-autonomic neuropathy (HSAN) type VIII. We present an 8-year-old boy with lesions on the mid-face that were admittedly self-induced and associated with an abnormally high pain threshold. The diagnosis and management of MiTES is reviewed.

Papillary hemangioma in a child and sonographic characterization.

Papillary hemangioma (PH) is a rare, benign, vascular tumor that usually appears on the scalp and face and is reported most frequently in adults. We present a pediatric case of PH and provide sonographic features that may assist in establishing the diagnosis.

Chilblains in children in the setting of COVID-19 pandemic.

BACKGROUND: Different skin manifestations of COVID-19 are being reported. Acral lesions on the hands and feet, closely resembling chilblains, have been recognized during the peak incidence of the COVID-19 pandemic. MATERIAL AND METHODS: A retrospective review of 22 children and adolescents with chilblain-like lesions seen over a short period of time in the Emergency Department of a children's hospital during the peak incidence of COVID-19 in Madrid, Spain. RESULTS: All patients had lesions clinically consistent with chilblains of the toes or feet, with three also having lesions of the fingers. Pruritus and mild pain were the only skin symptoms elicited, and only 10 had mild respiratory and/or GI symptoms. None had fever. Coagulation tests, hemogram, serum chemistry, and lupus anticoagulant were normal in all patients tested. One out of 16 tested cases had elevated D-dimer results, but without systemic symptoms or other laboratory anomalies. SARS-CoV-2 PCR tested in 19 cases was positive in just one case. Skin biopsies obtained in six patients were consistent with chilblains. On follow-up, all cases showed spontaneous marked improvement or complete healing. CONCLUSION: Acute chilblains were observed during COVID-19 pandemic in children and teenagers. It is a mildly symptomatic condition with an excellent prognosis, usually requiring no therapy. Etiopathogenesis remains unknown.

Erythema multiforme-like lesions in children and COVID-19.

During examination of cases of chilblains in children and adolescents, we identified four patients who also showed skin lesions similar to erythema multiforme (EM). They had no other known triggers for EM. One of them had a positive PCR for SARS-CoV-2, while the other three were negative. Skin biopsies from two patients showed features not typical of EM, such as deep perivascular and perieccrine infiltrate and absence of necrosis of keratinocytes. Immunohistochemistry for SARS-CoV/SARS-CoV-2 spike protein showed granular positivity in endothelial cells and epithelial cells of eccrine glands in both biopsies. All patients had an excellent outcome, and had minimal or no systemic symptoms. The coincidence of EM, a condition commonly related to viruses, and chilblains in the setting of COVID-19, and the positivity for SARS-CoV/SARS-CoV-2 spike protein by immunohistochemistry strongly suggest a link between EM-like lesions and SARS-CoV-2.

Use of topical rapamycin in the treatment of superficial lymphatic malformations.

BACKGROUND: The superficial lymphatic component of vascular malformations poses a significant treatment challenge. It is responsible for the majority of symptoms presented, and to date, there is no consensus regarding treatment. OBJECTIVE: To evaluate the effectiveness of topical rapamycin in treating superficial lymphatic malformations (LM). METHODS: A case series study was performed of patients with superficial LM, treated with topical rapamycin. The clinical characteristics of patients and the concentration and application mode of the drug were recorded. The changes in the signs and symptoms observed and associated adverse effects were noted and analyzed. RESULTS: The study population consisted of 11 patients of an average age of 10.5 years. All were treated with topical rapamycin: 6 patients with a 1% concentration, 1 with a 0.8% concentration, and 4 with a 0.4% concentration. Changes in the clinical appearance of the lesions were observed in all patients. The associated symptoms, present in 9 of 11 patients, improved in every case. The mean follow-up time was 16.1 months. LIMITATIONS: This study is retrospective, with a small sample size and considerable heterogeneity of lesions and treatment approaches. CONCLUSION: Treatment with topical rapamycin modifies the clinical appearance and alleviates symptoms of superficial LM.

Cutaneous Mastocytosis With Predominant Infiltration of Promastocytes.

Mastocytosis is a heterogeneous group of disorders with a variable clinical course, ranging from indolent disease with normal life expectancy to highly aggressive disease. In the skin, mast cells may show a spindle-shape appearance or appear as round cells with wide, polygonal cytoplasm. In this study, we present a case series of 4 patients with cutaneous childhood-onset mastocytosis in whom skin mast cells showed striking nuclear pleomorphism with bilobed and multilobed nuclei. Such finding does not seem to represent a malignant phenotype of the disease in the skin, although the true biological significance and the potential prognostic impact remain to be determined.

Methotrexate for severe nummular eczema in children: Efficacy and tolerability in a retrospective study of 28 patients.

BACKGROUND/OBJECTIVES: Nummular eczema in children is a chronic condition characterized by pruritic coin-shaped eczematous lesions that affect any part of the body and often become exudative. Mid- to high-potency topical corticosteroids are considered the mainstay treatment, but there are limited data on the use of systemic therapy for nummular eczema in children. The objective of the current study was to evaluate the efficacy and safety of methotrexate in children with severe nummular eczema. METHODS: A retrospective review was undertaken of children with nummular eczema treated with methotrexate between January 2007 and May 2017. RESULTS: The records of 28 patients (24 male, 4 female) with a mean age at the beginning of treatment of 7.8 ± 1.6 years (95% confidence interval (CI) = 6.1-9.4 years) were reviewed. The median duration of treatment was 12.6 ± 3.3 months (95% CI = 9.2-16 months), and 14 patients were still undergoing methotrexate therapy at the time of last review. Ten patients (35.7%) had complete or almost complete clearance of eczema (> 90% improvement), 13 (46.4%) had marked improvement (50%-89%), four had mild improvement (< 50%), and one failed methotrexate therapy. Gastrointestinal intolerance (21.4%) and a nonsignificant increase in liver enzymes (17.9%) were the most frequent side effects. No serious adverse events were noted. CONCLUSION: Methotrexate is an effective, well-tolerated treatment in children with moderate to severe nummular eczema that has failed to respond to conventional topical therapy.

Superimposed linear atopic dermatitis.

Superimposed linear atopic dermatitis is rarely manifested in polygenic disease as a counterpart to type 2 segmental mosaicism of monogenic skin diseases. Linear arrangement following Blaschko lines represents more severe disease on a generalized background of atopic dermatitis, perhaps reflecting clonal loss of heterozygosity. Only three cases of superimposed linear atopic dermatitis have been reported; we describe three additional cases.

Ultrasound findings in idiopathic facial aseptic granuloma: Case series and literature review.

Idiopathic facial aseptic granuloma is an inflammatory nodule commonly located on the cheeks and eyelids in young children. Despite its prolonged course, it tends toward spontaneous resolution, so invasive diagnostic procedures should be avoided. Cutaneous ultrasound is a noninvasive modality that has been found to improve the diagnostic accuracy of nodular skin lesions. We report five children with idiopathic facial aseptic granuloma in whom high-resolution ultrasound examination provided distinctive findings.

Omeprazole-induced hypertrichosis in two children.

Omeprazole significantly increases duodenal prostaglandin E2 synthesis. Prostaglandins are involved in hair growth regulation: prostaglandin E2 and prostaglandin F2 alpha stimulate hair growth, and prostaglandin D2 has an inhibitory effect. The use of omeprazole can cause acquired generalized hypertrichosis by increasing prostaglandin E2 levels.

Chronic urticaria in infants as the first manifestation of autoinflammatory disease.

We report two unrelated infants in whom chronic urticaria was the first clinical manifestation of cryopyrin-associated periodic syndrome, which should be suspected in infants with early-onset chronic urticaria, especially if there is a neutrophil-rich infiltrate in the skin biopsy. Early diagnosis of cryopyrin-associated periodic syndrome may lead to early and successful treatment with anti-interleukin-1 medications.

Identical COL71A1 heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes.

Dystrophic epidermolysis bullosa is a rare blistering condition caused by mutations in the COL7A1 gene. Different clinical variants have been described, with dominant and recessive inheritance, but no consistent findings have been elucidated to establish a genotype-phenotype correlation. We present three unrelated patients with two identical pathogenic compound heterozygous mutations in the COL7A1 gene that developed different clinical forms of dystrophic epidermolysis bullosa-epidermolysis bullosa pruriginosa and mild recessive non-Hallopeau-Siemens-raising the possibility of other genetic or environmental modifying factors responsible for the phenotype of the disease.

Cutaneous and Systemic Findings in Mosaic Neurofibromatosis Type 1.

BACKGROUND/OBJECTIVES: Mosaic neurofibromatosis type 1 (MNF1) is a variant of neurofibromatosis type 1 (NF1) in which clinical manifestations are limited to one or several body segments. The objective was to characterize the cutaneous features and associated systemic findings in a cohort of children with MNF1. METHODS: We performed a retrospective study of 40 children diagnosed with MNF1 at the Department of Dermatology, Hospital Infantil Niño Jesús, Madrid, Spain, from January 1, 1986, to October 31, 2015. RESULTS: All patients had pigmentary changes, alone (n = 39) or in combination with neurofibromas (n = 1). Twenty-four cases fulfilling the definition of MNF1 had six or more café au lait spots with or without freckling within the affected segment. They all lacked any other National Institutes of Health criteria of NF1. No patient had juvenile xanthogranuloma (JXG) or nevus anemicus (NA). Two children with MNF1 had epilepsy and two others developed malignancy (Hodgkin's lymphoma and ganglioneuroblastoma). CONCLUSIONS: Pigmentary changes are the most frequent presentation of MNF1 in children. MNF1 must be considered with segmentary distribution of freckling and café au lait spots. Other frequent cutaneous findings in NF1, such as JXG or NA, seem to be exceptional in MNF1. Although the possibility of systemic complications and cancer risk seem to be low, patients must be followed up.

A Case with Juvenile Xanthogranuloma and Progressive Nodular Histiocytosis Overlap.

A patient with overlap between juvenile xanthogranuloma and progressive nodular histiocytosis is presented. He had progressive, superficial, small, yellow-reddish papules and large dermal nodules, consistent with progressive nodular histiocytosis. Histopathology showed distinctive features of juvenile xanthogranuloma. Our patient reinforces the view that progressive nodular histiocytosis is not a distinct clinical entity, but an evolutionary form of juvenile xanthogranuloma.