Hyper-IgD syndrome

Classification according to ICD-10
E85.0	Heredofamily non-neuropathic amyloidosis
ICD-10 online (WHO version 2019)

The Hyper-IgD syndrome ( HIDS ) is a hereditary -related disease associated with recurrent bouts of fever accompanied and to the periodic fever syndromes counts. Abdominal pain , diarrhea and vomiting are usually present during the fever episodes . There is no causal treatment. However, the prognosis for life expectancy is quite good.

root cause

The Hyper-IgD syndrome is caused by a change of the genetic information ( mutation caused), which on the long arm of chromosome 12 is located. The inheritance is autosomal - recessive . In more than 80% of the cases there is a missense mutation in the area of ​​the gene that codes for the enzyme mevalonate kinase , MVK (12q24, GeneID 4598 ). The change leads to a slightly reduced stability and catalytic activity of the enzyme. How the reduced mevalonate kinase activity is linked to the recurring fever is still unclear.

Symptoms

Hyper-IgD syndrome usually begins in the first year of life. It is characterized by recurring attacks of fever, in which an abrupt increase in fever is heralded by chills. The attacks can be provoked by vaccinations, minor injuries, surgery or stress. Most episodes are accompanied by swelling of the cervical lymph nodes , abdominal pain, and vomiting, diarrhea, or both. Headaches, joint pain, or inflammation of the large joints and skin rashes are also common. The flare-ups usually occur about every four to six weeks and last for three to seven days. However, the frequency can vary greatly from patient to patient. It is greatest in childhood and adolescence and decreases in adulthood.

Diagnosis and differential diagnosis

If characteristic clinical symptoms exist, a determination of the immunoglobulin D content in the blood can corroborate the diagnosis. If this is above 100 IU / ml, it is confirmed by a determination of the activity of the mevalonate kinase in white blood cells ( leukocytes ). This is reduced to around 5–15% in patients with hyper-IgD syndrome. Molecular genetic evidence of the mutation is also possible. Hyper-Ig-D syndrome must be differentiated from other periodic fever syndromes that are also rare, such as familial Mediterranean fever (FMF), cyclic neutropenia , tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS), chronic infantile neurological Cutaneous articular syndrome (CINCA syndrome), Muckle-Wells syndrome or PFAPA syndrome (periodic fever, aphthous ulcers, pharyngitis, adenitis syndrome).

therapy

A causal treatment is not possible. The symptomatic treatment of the individual fever episodes is also difficult. Common anti-inflammatory and antipyretic drugs ( non-steroidal anti-inflammatory drugs ) have proven to be just as ineffective as steroids , colchicine and thalidomide . Simvastatin , on the other hand, is probably helpful . The positive effects of the interleukin- 1 receptor antagonist anakinra have recently been reported. The tumor necrosis factor -α antagonist etanercept can also reduce the number of febrile days in individual cases.

forecast

Although hyper-IgD syndrome is difficult to treat, the overall prognosis is good . Life expectancy is not restricted. Even if the joints are involved during the relapses, permanent joint destruction only occurs in exceptional cases. The development of amyloidosis , as it is feared in familial Mediterranean fever, is observed in hyper-IgD syndrome, if at all, only in isolated cases. In adulthood, however, a subgroup of patients can also develop neurological abnormalities such as impaired intellectual abilities, balance and coordination disorders ( ataxia ) or even epilepsy . This shows the close connection between the disease and mevalonate aciduria, a likewise hereditary metabolic disease in which there is also a genetic defect in the area of ​​the mevalonate kinase with a restriction of activity below 5%.

history

Periodic diseases were described variously as early as the 19th century. It was not until 1948 that Hobart A. Reimann coined the term as such. After a distinction had been made over the years in addition to familial Mediterranean fever, a Dutch working group headed by Jos van der Meer described a syndrome with recurring, debilitating fever attacks, general inflammatory reactions of the body and increased immunoglobulin for the first time in 1984 using three patients, two of whom were siblings -D and -A concentrations in the blood. Since then, up to 2001, around 160 patients, the majority of them in the Netherlands and France , have been discovered.

Individual evidence

1. ↑ ^{a b c d} G. F. Hoffmann, D. Haas: Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome. In: Orphanet Journal of Rare Diseases. 2006; 1, p. 13.
2. ^ S. Stojanov et al.: Periodic fever syndromes. In: Monthly Pediatrics. 2003, 151, pp. 91-106.
3. ↑ EJ Bodar et al .: Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. In: Neth J Med. 2005, 63, pp. 260-264. PMID 16093577 pdf (English)  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.  
4. ^ HA Reimann: Periodic disease. Probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia. In: JAMA. 1948; 141, pp. 239-244.
5. ^ J. Van der Meer et al.: Hyperimmunoglobulinemia D and periodic fever: a new syndrome. In: Lancet. 1984; i, pp. 1087-1090. ( PMID 6144826 )

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !