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Hyper-IgD Syndrome


Apostolos Kontzias

, MD, Stony Brook University School of Medicine

Last full review/revision Mar 2020| Content last modified Mar 2020
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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. Diagnosis is mainly clinical but includes serum IgD level and possibly gene testing. Attacks can be prevented with anakinra or canakinumab. Symptoms can be treated with nonsteroidal anti-inflammatory drugs, corticosteroids, and anakinra.

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, symptoms of hyper-IgD syndrome may include abdominal pain, vomiting or diarrhea, headache, and arthralgias. Signs of hyper-IgD syndrome include cervical lymphadenopathy, splenomegaly, arthritis, skin lesions (maculopapular rash, petechiae, or purpura), and orogenital aphthous ulcers (1).

General reference

  • 1. Vladutiu A: Immunoglobulin D: Properties, measurement, and clinical relevance. Clin Diagn Lab Immunol 7(2):131–140, 2000. doi: 10.1128/cdli.7.2.131-140.2000.


  • Clinical evaluation

  • Sometimes gene testing

Diagnosis of hyper-IgD syndrome is based on history, examination, and a serum IgD level of > 100 units/L; however, up to 20% of patients have normal serum IgD levels. 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.


  • For preventing attacks, anakinra or canakinumab

  • For symptoms, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and anakinra

Anakinra (100 mg subcutaneously once a day) and canakinumab (150 mg subcutaneously every 4 weeks) are proved to prevent attacks (1). 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. On-demand treatment of symptoms with anakinra has been used successfully (2).

Treatment references

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