Hyperimmunoglobulin D syndrome: Clinical manifestations and diagnosis
- Yoram C Padeh, MD
Yoram C Padeh, MD
- Instructor in Clinical Medicine
- Mount Sinai Medical Center
- Arye Rubinstein, MD
Arye Rubinstein, MD
- Professor of Pediatrics Microbiology and Immunology
- Albert Einstein College of Medicine and Montefiore Hospital Medical Center
- Section Editors
- Jordan S Orange, MD, PhD
Jordan S Orange, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Professor of Pediatrics
- Chief of Immunology, Allergy, and Rheumatology
- Baylor College of Medicine
- Texas Children's Hospital
- Robert Sundel, MD
Robert Sundel, MD
- Section Editor — Pediatric Rheumatology
- Associate Professor of Pediatrics
- Harvard Medical School
Hyperimmunoglobulin D syndrome (HIDS, MIM #260920) is a rare, autosomal recessive genetic disorder characterized by recurrent febrile episodes typically associated with lymphadenopathy, abdominal pain, and an elevated serum polyclonal immunoglobulin D (IgD) level. Classic HIDS is due to compound heterozygous or homozygous mutation in the mevalonate kinase (MVK) gene. The underlying genetic defect is not known in variant HIDS.
Recurrent fever that is not due to infection is a clinical feature of several disorders that are collectively referred to as autoinflammatory diseases. HIDS is one of the major periodic fever syndromes, which is a subset of autoinflammatory diseases. An overview of periodic and recurrent fevers and other autoinflammatory diseases is presented separately. (See "Periodic fever syndromes and other autoinflammatory diseases: An overview".)
The clinical manifestations, laboratory features, and diagnosis of HIDS are reviewed here. Pathophysiology and management of HIDS are presented separately. (See "Hyperimmunoglobulin D syndrome: Pathophysiology" and "Hyperimmunoglobulin D syndrome: Management".)
HIDS typically presents during the first year of life . The median age of onset of symptoms was six months in one series (range one week to 10 years of age) . Most patients experienced their first attack within the first year of life (78.1 percent).
HIDS is equally common in males and females. More than 60 percent of patients are of Dutch or French ancestry, although HIDS cases have been reported around the world, including in the United Kingdom, Germany, Italy, Turkey, the Czech Republic, the United States, Japan, and the Arabian peninsula [1,3-6]. An internet-based registry has been created to catalog and follow known patients with HIDS.
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- CLINICAL MANIFESTATIONS
- Abdominal pain
- Mucocutaneous manifestations
- Other manifestations
- HIDS during pregnancy
- Variant HIDS
- Overlap syndromes
- LABORATORY FINDINGS
- Immunoglobulin D level
- Immunoglobulin A level
- Acute phase reactants
- Urinary mevalonic acid
- Urinary LTE4
- Genetic testing
- DIFFERENTIAL DIAGNOSIS
- Causes of recurrent or periodic fever
- - Familial Mediterranean fever (FMF)
- - Tumor necrosis factor receptor-1 associated periodic syndrome (TRAPS)
- - Periodic fevers with aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
- - Muckle-wells syndrome
- - Familial cold autoinflammatory syndrome (FCAS)
- - Mevalonic aciduria (MEVA)
- Causes of recurrent severe abdominal pain
- - Hereditary or acquired angioedema
- - Acute intermittent porphyria
- Causes of elevated immunoglobulin D
- SUMMARY AND RECOMMENDATIONS