Hyperimmunoglobulinemia D with periodic fever

Hyperimmunoglobulinemia D with periodic fever (HIDS), also known as mevalonate kinase deficiency (MKD) or Dutch-type periodic fever, is a rare autoinflammatory disorder caused by mutations in the MVK gene, which encodes the enzyme mevalonate kinase involved in the cholesterol biosynthesis pathway. HIDS represents the milder end of the mevalonate kinase deficiency spectrum, with mevalonic aciduria being the more severe form. The disease is characterized by recurrent episodes of high fever lasting 3 to 7 days, typically beginning in infancy or early childhood, often triggered by vaccinations, infections, physical or emotional stress, or surgery. During febrile episodes, patients commonly experience abdominal pain, diarrhea, vomiting, joint pain (arthralgia), skin rashes (including maculopapular and urticarial lesions), cervical lymphadenopathy, hepatosplenomegaly, and headache. A hallmark laboratory finding is persistently elevated serum immunoglobulin D (IgD) levels, though this is not present in all patients. Elevated urinary mevalonic acid during attacks is a more specific diagnostic marker. The disease primarily affects the immune system, gastrointestinal tract, musculoskeletal system, skin, and lymphatic system. Between attacks, patients generally feel well, though the frequency and severity of episodes can vary considerably. There is no definitive cure for HIDS. Treatment is primarily aimed at managing symptoms and reducing the frequency and severity of febrile episodes. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may provide symptomatic relief during attacks. Biologic therapies targeting interleukin-1 (IL-1), particularly anakinra and canakinumab, have shown significant efficacy in reducing attack frequency and severity and represent the current standard of targeted treatment. Anti-TNF agents such as etanercept have also been used with variable success. Colchicine and statins have been tried but generally show limited benefit.

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