Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome

Medicine (Baltimore). 2008 Nov;87(6):301-310. doi: 10.1097/MD.0b013e318190cfb7.


The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), one of the autoinflammatory syndromes, is caused by mutations in the gene coding for mevalonate kinase (MVK). We conducted the current study to assess the genetic, laboratory, and clinical features as well as the complications and course of disease in patients with genetically confirmed HIDS. In addition, we studied the quality of life and course of life in a selection of patients. Follow-up data were obtained by a questionnaire sent to all physicians of patients in the International HIDS Database. In addition, we assessed the course of life and quality of life in Dutch patients aged >16 years using validated quality of life instruments. Data were obtained from 103 patients from 18 different countries. The median age of first attack was 6 months (range, 0-120 mo), with a median period of 9.9 years from onset of disease to diagnosis. The most frequent symptoms that accompanied attacks of fever were lymphadenopathy, abdominal pain, arthralgia, diarrhea, vomiting, skin lesions, and aphthous ulcers. Amyloidosis was a severe but infrequent complication (2.9%). The median serum IgD level was 400 U/mL. IgD levels were normal in 22% of patients. The 4 most prevalent mutations (V377I, I268T, H20P/N, P167L) accounted for 71.5% of mutations found. The frequency of attacks decreased with the patient's increasing age, although 50% of patients over the age of 20 years still had 6 or more attacks per year. Many drugs have been tried in HIDS. Some patients responded to high-dose prednisone (24.4% response). Anakinra and etanercept can also be effective (33.3% response). Quality of life was determined in a subgroup of patients (n = 28). Social functioning, general health perception, and vitality were significantly lower in patients with HIDS than in controls, as were autonomy and social development. In addition, HIDS had an adverse impact on educational achievements and employment status. In conclusion, HIDS is an early-onset disease that is accompanied by an array of inflammatory symptoms. Although the frequency of attacks decreases during the patient's life, many patients continue to have frequent attacks. HIDS impairs several aspects of quality of life.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use
  • Arthralgia / physiopathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Disease Progression
  • Etanercept
  • Female
  • Gastrointestinal Diseases / physiopathology
  • Health Surveys
  • Humans
  • Immunoglobulin G / therapeutic use
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Longitudinal Studies
  • Lymphatic Diseases / physiopathology*
  • Male
  • Mevalonate Kinase Deficiency / drug therapy
  • Mevalonate Kinase Deficiency / genetics
  • Mevalonate Kinase Deficiency / physiopathology*
  • Middle Aged
  • Mutation / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Quality of Life*
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Skin Diseases / physiopathology
  • Splenomegaly / physiopathology*
  • Syndrome
  • Young Adult


  • Antirheumatic Agents
  • Immunoglobulin G
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Tumor Necrosis Factor
  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase
  • Etanercept