Hyper IgD Syndrome: A Complex Case of Recurrent Fevers, Abdominal Pain, and Atypical Skin Rash

Background Hyper immunoglobulin D syndrome (HIDS), also known as mevalonate kinase deficiency, is a rare autosomal recessive autoinflammatory disorder caused by mutations in the MVK gene, characterized by recurrent fevers, abdominal pain, and elevated serum IgD levels. Case Presentation We report the case of a 5-year-old Saudi boy with history of recurrent fever, abdominal pain, and hyperpigmented skin lesions. He started to have recurrent fever episodes with abdominal pain at 4 months of age. His past medical history was notable for failure to thrive and congenital atrioventricular block. His past medical history was notable for failure to thrive and congenital atrioventricular block. Physical examination revealed abdominal distension and multiple hyperpigmented spots on the lower extremities but no lymphadenopathy or organomegaly. His height and weight were below the 3rd and 10th percentiles for age, respectively. Laboratory investigations showed leukocytosis with lymphocytosis. The patient also had thrombocytosis (666 × 103/µL) and elevated inflammatory markers, including ESR (68 mm/h), CRP (15.6 mg/dL), and serum amyloid A (45.1 mg/L). A CT scan demonstrated thickening of the terminal ileum, cecum, and ascending colon with mucosal hyperenhancement. However, stool calprotectin was negative, and a lower GI endoscopy was unremarkable. Skin biopsy showed increased basal cell pigmentation and melanocytes consistent with café-au-lait spot. Whole-exome sequencing revealed a homozygous missense pathogenic variant (c.1129G>A; p.Val377Ile) in the MVK gene, consistent with a diagnosis of HIDS. The patient was initially treated with an interleukin-1 inhibitor (anakinra) and colchicine. However, he continued to experience recurrent fever and abdominal pain. Due to concerns about compliance with daily anakinra injections, treatment was switched to canakinumab. After starting canakinumab, the patient showed significant clinical improvement, with resolution of symptoms and normalization of inflammatory markers. Conclusion This case highlights the diagnostic complexity and therapeutic challenges of HIDS. Café-au-lait spots are typically associated with genetic disorders, such as neurofibromatosis, Legius syndrome, and Noonan syndrome but have not been previously reported in HIDS. While this association cannot be established based on a single case, this report may inspire further research into this potential link.