- D1.341 - Severe Atopic Features with Prematurity and Ichthyosis: Ichthyosis Prematurity Syndrome

Introduction:Ichthyosis Prematurity Syndrome (IPS) is a rare autosomal recessive disorder caused by biallelic variants in SLC27A4, which encodes FATP4. Defective fatty-acid uptake in keratinocytes disrupts the epidermal barrier, enabling allergen and microbe entry and driving epithelial cytokine release (TSLP, IL-33, IL-25),  activation of Th2 and ILC2 responses, IL-4/IL-13–driven IgE elevation, and IL-5–mediated eosinophilia. Clinically, IPS combines prematurity with neonatal respiratory distress,  hyperkeratosis, erythroderma, ichthyosis, hypereosinophilia, markedly elevated IgE, and persistent atopic dermatitis.

Case:A male infant born at 29 weeks to consanguineous parents exhibited diffuse xerosis, erythema, and hyperkeratosis at birth. He required NICU care due to respiratory distress syndrome and bronchopulmonary dysplasia. Despite emollients and topical antiinflammatory therapy, cutaneous findings progressed. At five months, he was referred for evaluation of suspected primary immunodeficiency. On examination, he had generalized erythroderma and xerosis, crusted and eczematous scalp and eyebrow lesions, and bilateral crackles and rhonchi. Laboratory findings showed anemia (Hb 8.8 g/dL), eosinophilia (8100/mm³), high IgE (2242 IU/ml), low IgG (253 mg/dl). Skin prick testing showed sensitization to cow’s milk and egg white. Lymphocyte subsets, lymphocyte activation, and DOCK8 expression were normal by flow cytometry. Chest CT revealed fibroatelectatic changes, and echocardiography demonstrated aortic root dilatation.Throughout childhood, the patient experienced frequent upper and lower respiratory tract infections, requiring repeated hospitalizations. The Hyper IgE Syndrome (HIES) score was 46. Based on clinical and laboratory features, he was followed for possible HIES and combined immunodeficiency, receiving antibiotic prophylaxis and monthly IVIG replacement therapy.Whole-exome sequencing initially detected no pathogenic variant. During follow-up, dermatopathic lymphadenopathy developed in cervical, axillary, and inguinal regions. Hypereosinophilia, elevated IgE, food allergies, and ichthyotic dermatitis persisted, whereas infections gradually decreased under prophylaxis.At 13 years of age, repeat WES identified a homozygous pathogenic SLC27A4 variant, establishing the diagnosis of IPS.  IVIG and prophylaxis were discontinued.

Conclusion:In patients with hypereosinophilia, elevated IgE levels, and recurrent infections, Hyper IgE Syndrome should be considered in the differential diagnosis. When prematurity and ichthyosis coexist with these features, IPS must be suspected. Genetic confirmation is critical not only for reducing morbidity but also for guiding appropriate management.