Successful induction of oral tolerance in Netherton syndrome.

We describe the case of a four-year-old girl admitted to our hospital to attend a specific oral tolerance induction (SOTI) to wheat. She was born at term, without perinatal problems. On the second day of life, she developed a perioral dermatitis that worsened during the following days into a scaling eczema localised on face, neck and skin folds. Because of this her diet was changed from cow’s milk to soy formula. Specific IgE result was positive for cow’s milk 6.61 kUA/L, egg white 30.6 kUA/L and wheat 67 kUA/L, so these foods were never introduced into her diet. Later on she experienced two severe allergic reactions, characterised by urticaria, abdominal pain with or without vomiting and bronchospasm, due to accidental ingestion of a very small amount of wheat. When she was first evaluated in our department she presented total alopecia with seborrhoeic dermatitis of the scalp. Her dermatitis was extremely severe involving the entire body (Fig. 1). We decided to treat strongly the skin and then, after a good improvement, to try a SOTI for wheat. On the day of admission she was in good clinical condition; her weight was just below the 3rd percentile, her height in the 10th percentile for age. On physical examination she had downy, short, brittle hair, and sparse eye brows especially laterally. The skin showed good improvement compared to prior evaluation, but an erythematous desquamating eczema was evident on the eyelids, arms, trunk and legs. Teeth, nails and mucous membranes were normal. Laboratory investigations showed high levels of eosinophils (930/ L, normal values 0--3500/ L), high serum level of total IgE (9436 mg/dL, normal values 0--52 UI/mL) with wheat-specific and milk-specific IgE > 100 kUA/L. Based on clinical history and physical signs we hypothesized a Netherton syndrome. Scalp hair examination on light microscopy showed typical bamboo deformity of trichorrhexis invaginata (Fig. 2) suggestive of Netherton syndrome. Genetic analysis established this diagnosis, showing mutations in the gene SPINK5. Wheat SOTI was performed using semolina. The process consisted in a rapid increase of dosage, starting with very low amounts of diluted semolina, as previously described for milk (Table 1). During hospital admission, she was administered an antihistaminic daily (cetirizine, 1 gtt/2 kg per day), she had a venous line placed and a complete emergency kit was always available. At 15 mL of pure semolina she presented bronchospasm and urticaria, with a complete recovery of symptoms using nebulised epinephrine (1 mg/10 kg diluted in 3 mL of saline solution). Semolina dosage was temporarily decreased (8 mL), but on the last day of admission (11th day) she was able to tolerate 20 mL of pure semolina without any allergic reactions occurring. Afterwards the desensitisation treatment continued at home until she was able to take 150 mL of semolina as a single dose, without adverse reactions. An appropriate training to manage adverse reactions, including the use of nebulised and self-injectable epinephrine was provided to the girl’s parents. We recommended avoiding physical exercise for 3 h after semolina intake to minimise the risk of food/exercise-induced anaphylaxis. Antihistamine treatment was continued at home until the 150 mL was reached and then reduced over four weeks. After one year she was able to ingest cereals without any restrictions. On the way, she experienced some mild allergic reactions but never life-threatening events. At this point the girl was newly hospitalised for an attempt to specific oral tolerance induction to cow’s milk