Prevalence of and risk factors for nutritional deficiency and food allergy in a cohort of 21 patients with Netherton syndrome.

BACKGROUND: Netherton syndrome (NS; OMIM: 256500) is a rare autosomal recessively inherited disease due to SPINK5 mutations. Hair and inflammatory skin involvement are variable along with allergies. Morbidity and mortality are high, particularly in infancy. A detailed clinical analysis of a NS patient cohort should broaden the understanding of nutritional challenges and allergic comorbidities. METHODS: In this retrospective monocentric cohort study, medical and dietetic records of pediatric NS patients, presenting between 1999 and 2018, were reviewed. The severity of skin involvement was assessed according to the extent of the body surface area (BSA) affected by erythema. RESULTS: We identified 21 patients with NS (median age 11.6 years). Within the first 6 months of life, requirements for fluid and kcals/protein were high for all patients (average 228 ml/kg/day) and infants had an average of 1.9 feed changes (range 0-4) due to food intolerance. Clinical evidence for IgE-mediated food allergy was present in 84.2% (16/19 children, 2 no data) with a range of 1-12 food allergies per patient. In 75%, more than one food had to be avoided. Specific IgE levels were falsely positive in 38.3% and 8/18 patients (44.4%). One-third (5/15; 6 no data) of patients, all with severe disease, had anaphylactic reactions following ingestion of fish (n = 2), sesame (n = 1), cow's milk (n = 1), and both peanut and egg (n = 1). CONCLUSIONS: Our data emphasize feeding difficulties in children with NS and reveal an unexpectedly higher prevalence of food allergies that gives evidence to the importance of early coordinated multidisciplinary care for overcoming these challenges in NS.

The natural history of laryngo-onycho-cutaneous syndrome: A case series of six pediatric patients and literature review.

BACKGROUND/OBJECTIVES: Laryngo-onycho-cutaneous syndrome (LOC) is a rare subtype of junctional epidermolysis bullosa (JEB), featuring aberrant granulation tissue formation in the skin, larynx, and eyes. So far, three mutations including the specific (founder) mutation in exon 39 of LAMA3 (c.151dup) have been identified, but sparse data exists regarding the natural history, the genotype-phenotype correlation, and its differentiation from other JEB types. METHODS: We reviewed our pediatric EB database to identify English children with clinical and genetically diagnosed LOC within the last 15 years. Their demographic, clinical, and laboratory data were examined. We searched three databases for case reports of LOC between January 1986 and November 2020 and extracted clinical and molecular details. RESULTS: We identified 6 LOC patients, all female (mean age 5.4 years). Periungual hypergranulation and skin fragility were the earliest presenting signs (0-3 months), followed by laryngeal stenosis, symblepharon (mean onset 10.7 and 11.8 months, respectively), and dental abnormalities. Five children developed anemia at an average of 19.2 months. We identified 22 published studies in English with 31 cases. CONCLUSIONS: This study delineates the disease course of LOC and highlights the overlap with some forms of JEB. Classical signs/symptoms including anemia appear early in life. Genetic analysis revealed three new LOC-associated variants and underscores the finding that interpretation of skin immunolabeling and molecular diagnostics can be challenging. We provide recommendations on management of this complex syndrome.