Long-Term Follow-Up, Clinical Features, and Quality of Life in a Series of 103 Patients With Hyperimmunoglobulinemia D Syndrome

  title={Long-Term Follow-Up, Clinical Features, and Quality of Life in a Series of 103 Patients With Hyperimmunoglobulinemia D Syndrome},
  author={Jeroen C H van der Hilst and Evelien J. Bodar and Karyl S. Barron and Joost Frenkel and Joost P. H. Drenth and Jos W. M. van der Meer and Anna Katharina Simon},
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… 

Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children

A prospective active surveillance was conducted in Germany during a period of 3 years to determine the incidence of HIDS and report clinical and genetic characteristics together with the underlying MVK genotypes in German children.

Effects of Anakinra on Health-Related Quality of Life in a Patient with 1129G>A/928G>A Mutations in MVK Gene and Heterozygosity for the Mutation 2107C>A in CIAS1 Gene

The patient’s quality of life showed an overall improvement of 27%; results showed a better improvement in role limitations due to physical health (50%).

Different clinical presentation of the hyperimmunoglobulin D syndrome (HIDS) (four cases from Turkey)

The phenomenon of “later-onset HIDS” should shed light into unresolved clinical problems of patients with periodic fever, especially in countries that FMF is more frequent such as Turkey, even though the symptoms start later than classic cases.

A Case of Hyperimmunoglobulinemia D Syndrome Successfully Treated with Canakinumab

Treatment with canakinumab in a final single dose of 4 mg/kg every 4 weeks resulted in the disappearance of febrile attacks and a considerable improvement of patients' quality of life during a 12-month follow-up period.

Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience

The accumulating evidence on the efficacy and safety of biological drugs in pediatric HIDS suggests that the anti-interleukin-1 agent anakinra is the drug of choice for HIDS in children.

Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review

In the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL- 1 inhibitors.

Overlap of Familial Mediterranean Fever and Hyper-IgD Syndrome in an Arabic Kindred

An Arabic girl presenting since the age of 8-years with two patterns of recurrent episodes of fever, and associated with a spectrum of clinical features suggestive of overlap between familial Mediterranean fever (FMF) and HIDS, is reported.

Hyperimmunoglobulinemia D and periodic fever syndrome in children. Review on therapy with biological drugs and case report

Four children have been successfully treated with etanercep, TNF‐alpha inhibitor, and three children with anakinra, IL‐1 receptor antagonist, and currently, there is no established treatment for HIDS.

Long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency: results from the randomised Phase 3 CLUSTER trial.

Canakinumab proved effective to control disease activity and prevent flares in MKD during the 72-week study period and showed no new or unexpected adverse events.

The patient journey to diagnosis and treatment of autoinflammatory diseases

Experiences in patients with AIDs including tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS), and familial Mediterranean fever (FMF) are described to improve the quality of life of patients and families.



Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome.

The clinical relevance of the IgD measurement for the diagnosis of MKD in the population appears as poor, as reflected by likelihood ratios which are both close to 1.79.

Hyperimmunoglobulinemia D and Periodic Fever Syndrome: The Clinical Spectrum in a Series of 50 Patients

The hyper-IgD syndrome is distinct from other periodic fever syndromes like systemic-onset juvenile rheumatoid arthritis, adult-onsets Still disease, and familial Mediterranean fever and treatment is supportive.

First report of systemic reactive (AA) amyloidosis in a patient with the hyperimmunoglobulinemia D with periodic fever syndrome.

This is the first report to describe the occurrence of renal AA amyloidosis causing severe nephrotic syndrome in a young Italian man affected with the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS).

Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features.

The main clinical features distinguishing FMF from HIDS were lymphadenectomy, skin eruption, and symmetrical oligoarthritis in HIDS, and monoarthritis, peritonitis, and pleuritis in FMF.

The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome.

TRAPS is an underdiagnosed cause of recurrent inflammatory syndrome and its presence in the population of persons of Mediterranean ancestry and the short duration of the attacks of inflammation can lead to a fallacious diagnosis of FMF.

Hyper IgD syndrome (HIDS) associated with in vitro evidence of defective monocyte TNFRSF1A shedding and partial response to TNF receptor blockade with etanercept

A 3‐year‐old boy in whom genetic screening revealed a rare combination of two MVK mutations producing clinical HIDS as well as a TNFRSF1A P46L variant present in about 1% of the population is described.

Quality of life of patients with familial Mediterranean fever.

The QOL of FMF patients was found to be impaired compared to healthy controls, and further studies are needed to determine the exact factors affecting the quality of life ofFMF patients.

Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model.

It is proposed that this vaccination model will allow evaluation of treatment-on-demand in a controlled setting, and the IL-1ra analogue anakinra was more successful in aborting the inflammatory attack than etanercept.

Autoinflammatory gene mutations in Behçet’s disease

This study could not demonstrate any significant increases in MVK, CIAS1 or PSTPIP1 mutations in patients with BD as compared with controls, and it is unclear whether this is a polymorphism rather than a true mutation.