Safe and effective use of alitretinoin in children with recalcitrant hand eczema and other dermatoses - a retrospective analysis

BACKGROUND Alitretinoin is a systemic retinoid licensed for use in adult patients suffering from chronic hand eczema recalcitrant to potent topical steroids. Experience with its use in childhood is lacking. OBJECTIVES To report on the efficacy and safety of alitretinoin treatment in a cohort of children and adolescents with chronic hand eczema (CHE) and other inflammatory skin diseases. METHODS We performed a retrospective chart review of all consecutive patients under the age of 18 years treated with alitretinoin at our paediatric skin centre. Physician's Global Assessment (PGA) was used as the primary outcome measure. RESULTS Thirteen children (9 girls and 4 boys) were enrolled in this study. The median age at start of treatment with alitretinoin was 11.5 years (range 5.8-15.8 years). Nine children were diagnosed with CHE, two with severe atopic dermatitis (AD), and two with inherited ichthyosis [netherton syndrome (NS), autosomal recessive congenital ichthyosis (ARCI)]. Moderate to excellent response (PGA decrease of ≥1 point) was observed in 7 (78%) of the nine patients with CHE, one of the two patients with extensive AD and in the one patient with ARCI. In the remaining four subjects, no convincing effect was documented. Tolerability was overall very good. The most common adverse event was headache in 10 patients (77%) during the initiation of treatment, leading to interruption of therapy in one subject. CONCLUSIONS Alitretinoin seems to be highly effective and safe for the treatment of paediatric CHE and should thus be considered in children with refractory disease under topical therapy. Larger studies are required to corroborate these findings

Natural history of growth and anaemia in children with epidermolysis bullosa: a retrospective cohort study

BACKGROUND Impaired growth and anaemia are major extracutaneous complications of epidermolysis bullosa (EB), but data on their development are lacking. OBJECTIVES To determine the clinical course of growth and anaemia in children with EB and clarify the impact of nutritional compromise, inflammation and genetic factors. METHODS A retrospective study was conducted of 200 children, 157 with recessive dystrophic EB (RDEB) and 43 with junctional EB (JEB)-generalized intermediate, followed at the main referral centre in Germany. Growth charts were calculated using the modified LMS method and were correlated with parameters of anaemia, nutrition, inflammation and the molecular defect in a linear model. RESULTS In our cohort of patients with RDEB, weight impairment started at 12-18 months old; by the age of 10 years, 50% showed wasting. The predicted median weight at age 20 years was 35·2 kg for men and 40·1 kg for women. In JEB, growth resembled that of healthy children. Anaemia was present from the second year of life onwards in RDEB and JEB. Low levels of haemoglobin, iron, vitamin D, zinc and albumin, high levels of C-reactive protein, and absence of collagen VII correlated significantly with low weight in RDEB. No correlation was observed in JEB. CONCLUSIONS The results highlight that nutritional compromise occurs early in children with RDEB and therefore may require interventions as of the first year or two of life. What's already known about this topic? Children with epidermolysis bullosa (EB) suffer from failure to thrive and anaemia as major extracutaneous complications. The course of growth and the development of anaemia in EB are poorly characterized. What does this study add? A molecularly well characterized cohort of 200 children with EB was followed with regard to anthropometrics, anaemia and inflammation. We demonstrate early onset of growth failure and anaemia, most pronounced in the subset of recessive dystrophic EB. Awareness of early growth delay and nutritional deficiencies will improve EB care in daily practice

Case Report: Pansclerotic Morphea-Clinical Features, Differential Diagnoses and Modern Treatment Concepts.

Pansclerotic morphea (PSM) is a rare skin disease characterized by progressive stiffening of the skin with or without the typical superficial skin changes usually seen in morphea (localized scleroderma). Standard therapy, consisting of a combination of systemic glucocorticoids and methotrexate or mycophenolate mofetil, does rarely stop disease progression, which may lead to severe cutaneous sclerosis and secondary contractures. Little is known about the efficacy of newer biologicals such as abatacept, a fusion protein antibody against CTLA-4, or tocilizumab, a fully humanized IL-6R antibody, in the treatment of this pathology. We present the case of an 8 years old girl with an unusual, progressive stiffening of the skin, which was eventually diagnosed as pansclerotic morphea. A treatment with systemic glucocorticoids and methotrexate combined with tocilizumab led to a good clinical response within 2 months after initiation. In this paper, we discuss differential diagnoses to be considered and this new promising treatment option based on a case review of the literature

Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility

Background: Several new genes and clinical subtypes have been identified since the publication in 2014 of the report of the last International Consensus Meeting on Epidermolysis Bullosa (EB). Objectives: We sought to reclassify disorders with skin fragility, with a focus on EB, based on new clinical and molecular data. Methods: This was a consensus expert review. Results: In this latest consensus report, we introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Other disorders with skin fragility, where blisters are a minor part of the clinical picture or are not seen because skin cleavage is very superficial, are classified as separate categories. These include peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility. Because of the common manifestation of skin fragility, these ‘EB-related’ disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. Conclusions: The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and genetic features of EB. What is already known about this topic?. Epidermolysis bullosa (EB) is a group of genetic disorders with skin blistering. The last updated recommendations on diagnosis and classification were published in 2014. What does this study add?. We introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Clinical and genetic aspects, genotype–phenotype correlations, disease-modifying factors and natural history of EB are reviewed. Other disorders with skin fragility, e.g. peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility are classified as separate categories; these ‘EB-related’ disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. Linked Comment: Pope. Br J Dermatol 2020; 183:603