Hyper-IgD syndrome clusters in children of Dutch, French, and other Northern European ancestry and is caused by
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).
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.
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).
1. De Benedetti F, Gattorno M, Anton J, et al: Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med 378(20):1908–1919, 2018. doi: 10.1056/NEJMoa1706314.
2. ter Haar NM, Oswald M, Jeyaratnam J, et al: Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis 74(9):1636–1644, 2015. doi: 10.1136/annrheumdis-2015-207546.