NEMO-NDAS: A Panniculitis in the Young Representing an Autoinflammatory Disorder in Disguise

A 15-month-old full-term boy of African descent with an asymptomatic sickle cell trait presented with episodes of transient erythematous subcutaneous nodules involving the entire body except the face, since 2 weeks of age. The skin lesions evolved to areas of lipoatrophy and hyperpigmentation. An initial skin biopsy, studied at a different department at 2 months, was initially misinterpreted as subcutaneous fat necrosis of the newborn, despite the lack of the typical radiated crystals and needle-shaped clefts characterizing that entity. At 4 months of age, he developed systemic inflammatory manifestations, including fever, a new rash, significant periorbital edema, and failure to thrive. An extensive workup showed leukocytosis, hypercalcemia, elevated inflammatory markers, hypertriglyceridemia, and transaminitis. A new skin biopsy of the eyelid was diagnosed as neutrophilic lobular panniculitis with necrotic adipocytes. An initial whole-exome sequencing did not identify any causative mutations, but a WES reanalysis focused on autoinflammatory disorders was requested based on additional clinicopathologic data and revealed a mosaic intronic mutation in IKBKG c. 671+3 G > C. This mutation encodes an mRNA missing exon 5 resulting in NF-kB essential modulator (NEMO) Delta-exon 5-autoinflammatory syndrome (NDAS). NEMO-NDAS is one of the systemic autoinflammatory diseases that may appear as an unexplained panniculitis in young children, who should be monitored for immunodeficiency and/or autoinflammatory diseases. The differential diagnosis of autoinflammatory disorders should be considered in such cases incorporating the use of the whole-genome/exome sequencing in the investigation. The inhibitor of kappa-B kinase regulatory subunit gamma (IKBKG) is located on chromosome Xq28 and encodes the NEMO, a critical molecule upstream of NF-kB activation.

Automated summary

This is a case report about a 15-month-old boy of African descent with asymptomatic sickle cell trait. He presented with erythematous subcutaneous nodules which evolved into lipoatrophy and hyperpigmentation. After extensive investigations and sequencing, he was diagnosed with NEMO Delta-exon 5 autoinflammatory syndrome. This case highlights the importance of considering autoinflammatory disorders in young children with unexplained panniculitis.