Muckle Wells Syndrome

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

The Muckle-Wells syndrome (MWS) is a rare autosomal dominant inherited autoinflammatory disease. It is named after Thomas James Muckle and Michael Vernon Wells , who first described it in 1962. The prevalence is unknown, but about 135 cases have been described. MWS is one of the cryopyrin-associated periodic syndromes (CAPS) .

Symptoms

Symptoms include intermittent episodes of fever , hives (urticaria) , joint and muscle pain, and increasing sensorineural numbness . Often, AA amyloidosis develops in the kidneys and other organs . The consequences of kidney involvement are proteinuria , nephrotic syndrome and chronic kidney failure . Blood sedimentation and C-reactive protein are increased.

Many other symptoms, some of which are not or only poorly documented, are possible. In acute attacks, pain behind the eyes , warm skin areas and often a greatly reduced ability to concentrate can also be observed. Strong phases of fatigue of different lengths are also common.

Dizziness , nausea and periods of brief loss of consciousness may occur.

Most patients present to rheumatologists , immunologists or paediatricians with the first symptoms of the disease . Kidney involvement occurs later.

Pathogenesis

The cause of the Muckle-Wells syndrome is a missense mutation in the NLRP3 gene (also called the CIAS1 gene) on chromosome 1 . The gene codes for the protein cryopyrin , a component of the inflammasome that is involved in apoptosis and inflammation signaling pathways. Cryopyrin leads to an increased formation of interleukin-1β (IL-1β) . IL-1β, in turn, stimulates the synthesis of serum amyloid A protein by liver cells (hepatocytes) during the acute phase reaction . Mutations in the NLRP3 gene not only lead to Muckle-Wells syndrome, but can also cause other autoinflammatory diseases.

In contrast to autoimmune diseases , autoinflammatory diseases are not directed against the body's own immune system . Rather, the unspecific immune defense is activated, although no pathogens such as viruses or bacteria attack the body. Scavenger cells (e.g. macrophages ) are particularly active in this case and the same immunological processes take place as in the fight of the immune system against infection with pathogens. This leads to an inflammatory reaction that affects the whole body (in such cases one speaks of "systemic"). Those affected then notice this as a flare-up of illness with typical symptoms such as fever, pain and fatigue.

therapy

The treatment is carried out with anakinra (Kineret ® , Swedish Orphan Biovitrum AB ), a recombinant interleukin -1- receptor - antagonists . Anakinra leads to a competitive inhibition of the binding of IL-1α and IL-1β to the IL-1 receptor type 1 and neutralizes its biological activity . The safety and efficacy has been demonstrated in CAPS patients with varying degrees of disease severity. The active ingredient significantly reduces the manifestations of CAPS, including the reduction of common symptoms such as fever, rash , joint pain, headache , fatigue and red eyes. A rapid and sustained decrease in the concentration of inflammatory biomarkers and a normalization of the inflammatory haematological changes were observed during therapy .

Canakinumab (Ilaris ® , Novartis ) is another active ingredient used to treat MWS . Canakinumab is a monoclonal antibody (interleukin-1β inhibitor) and is usually injected subcutaneously every eight weeks . Recently canakinumab also for other diseases approvals obtained.

Drugs that work against other forms of CAPS (e.g. colchicine ) will not help MWS and are therefore not indicated.

literature

Individual evidence

  1. ^ Orpha.net: Muckle-Wells syndrome. In: https://www.orpha.net/ . July 2014, accessed December 19, 2019 .
  2. ↑ S. Stojanov, P. Lohse: Autoinflammatory diseases as important differential diagnoses in rheumatology - an update . In: Current Rheumatology . tape 36 , no. 04 , August 2011, ISSN  0341-051X , p. 226-235 , doi : 10.1055 / s-0031-1277186 ( thieme-connect.de [accessed December 19, 2019]).
  3. ↑ sobi Germany: Summary of the characteristics of the drug Kineret. In: https://sobi-deutschland.de . Swedish Orphan Biovitrum AB, March 2019, accessed December 19, 2019 .
  4. ↑ Novartis: Summary of Product Characteristics Ilaris. In: https://www.fachinfo.de/ . Novartis Pharma GmbH, June 2019, accessed December 19, 2019 .