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 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... read more ).
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
Diagnosis
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 (1 Diagnosis reference 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... read more ).
Gene testing is available but is negative in 25% of patients.
Diagnosis reference
1. Gattorno M, Hofer M, Federici S, et al; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO): Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis 78(8):1025–1032, 2019. doi: 10.1136/annrheumdis-2019-215048
Treatment
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 Treatment references 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... read more ). 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 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... read more ).
Treatment references
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
