title: Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome.
abstract: 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.
authors.affiliation: From Departments of General Internal Medicine (JCHvdH, EJD, JWMvdM, AS) and Gastroenterology and Hepatology (JPHD), Radboud University Nijmegen, Medical Centre, Nijmegen; and Departments of General Pediatrics and Pediatric Immunology (JF), Division of Pediatrics, University Medical Center, Utrecht, the Netherlands; and National Institute of Allergy and Infectious Diseases (KSB), National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Jeroen C H
authors.initials: JCH
authors.lastname: van der Hilst
authors.forename: Evelien J
authors.initials: EJ
authors.lastname: Bodar
authors.forename: Karyl S
authors.initials: KS
authors.lastname: Barron
authors.forename: Joost
authors.initials: J
authors.lastname: Frenkel
authors.forename: Joost P H
authors.initials: JPH
authors.lastname: Drenth
authors.forename: Jos W M
authors.initials: JWM
authors.lastname: van der Meer
authors.forename: Anna
authors.initials: A
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D018771:Arthralgia / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D000068800:Etanercept; D005260:Female; D005767:Gastrointestinal Diseases / Q000503:physiopathology; D006306:Health Surveys; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008137:Longitudinal Studies; D008206:Lymphatic Diseases / Q000503:physiopathology*; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012871:Skin Diseases / Q000503:physiopathology; D013163:Splenomegaly / Q000503:physiopathology*; D013577:Syndrome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D000068800:Etanercept