Hyper-IgD syndrome is a rare autosomal recessive disorder in which recurring attacks of chills and fever begin during the first year of life. Episodes usually last 4 to 6 days and may be triggered by physiologic stress, such as vaccination or minor trauma.

Hyper-IgD syndrome clusters in children of Dutch, French, and other Northern European ancestry and is caused by mutations in the gene coding mevalonate kinase, an enzyme important for cholesterol synthesis. Reduction in the synthesis of anti-inflammatory isoprenylated proteins may account for the clinical syndrome.

In addition to chills and fever, patients may have abdominal pain, vomiting or diarrhea, headache, and arthralgias. Signs include cervical lymphadenopathy, splenomegaly, arthritis, skin lesions (maculopapular rash, petechiae, or purpura), and orogenital aphthous ulcers.

Diagnosis is based on history, examination, and a serum IgD level of > 14 mg/mL. Nonspecific abnormalities include leukocytosis and elevated acute-phase reactants during fever; elevated urinary mevalonic acid during attacks helps confirm the diagnosis. Gene testing is available but is negative in 25% of patients.

There are no proven treatments to prevent attacks. Patients can expect to have recurrent bouts of fever throughout their life, although episodes tend to become less frequent after adolescence. NSAIDs and corticosteroids may help relieve symptoms during attacks.

Last full review/revision February 2013 by Stephen E. Goldfinger, MD

Content last modified March 2013