Muckle-Wells Syndrome

Muckle-Wells Syndrome (MWS) is a rare type of genetic disease that is characterized by occasional occurrences of skin rash, fever and joint pain as well as various other problems. Read on to know all about this syndrome, including its causes, symptoms, diagnosis and treatment.

What is Muckle-Wells Syndrome?

It is a rare autosomal dominant disease which causes sensorineural deafness and hives, and can progress to Amyloidosis. It is believed to be a type of Periodic Fever Syndrome. MWS is related to two other syndromes, Familial Cold Urticaria and Neonatal Onset Multisystem Inflammatory Disease. All three of these are linked to mutations in the same gene and colligated under the name cryopyrin-associated periodic syndromes.

The condition is also known as UDA.

Muckle–Wells Syndrome Synonyms

The disease is referred to by various names like:

  • Urticaria, deafness and amyloidosis
  • UDA syndrome
  • Urticaria-deafness-amyloidosis syndrome

Muckle-Wells Syndrome History

This syndrome was described for the first time in the year 1962 by Thomas James Muckle and Michael Vernon Wells. It is for this reason that this medical condition has been named “Muckle- Wells Syndrome”.

Muckle-Wells Syndrome Incidence

MWS is a rare disorder. Although it has been reported in many regions of the world, the exact prevalence of this disorder is not known properly.

Muckle-Wells Syndrome Causes

MWS is caused by a deficiency in the CIAS1 gene. CIAS1 is also known as NLRP3 (nucleotide-binding domain, leucine-rich family [NLR] pyrin domain containing 3). CIAS1 creates the protein Cryopyrin which is partially responsible for the reaction of the body to any damage or infection. Under such circumstances, a chemical called interleukin 1β is developed by an immune cell known as a macrophage. This chemical acts with a receptor on the exterior portion of other immune cells to generate symptoms of inflammation like fever, arthritis and malaise. There is increased activity of Cryopyrin, which finally leads to a growth in interleukin 1β. This results in inflammation all over the body, with associated symptoms.

Muckle-Wells Syndrome Symptoms

People suffering from this syndrome have recurring “flare-ups” which begin during babyhood or among children. These episodes may appear to arise instinctively or be actuated by cold, heat, fatigue or stresses. Individuals getting affected develop non itchy rash, fever which varies from mild to moderate range, swollen or at times painful joints and redness in the white portions of the eyes which is commonly known as Conjunctivitis. Hearing loss and kidney damage are also associated with this disorder.

Individuals affected with MWS generally begin to have its symptoms from birth. Occasionally, the symptoms may occur later in childhood. This condition is generally inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is enough to cause the disorder. In certain cases, the inheritance pattern is not known. This syndrome mostly affects Europeans below 20 years of age. MWS is another cause of Acute Anterior Uveitis.

The overproduction of IL-1β can give rise to inflammation in some parts of the body. The symptoms tend to worsen at night. The problems usually last for one to two days, although there may also be days when these cannot be felt.

  • Rash
  • Joint pain
  • Eye redness/pain
  • Fatigue
  • Fever/chills
  • Hives
  • Pins and Needles sensation
  • Loss of libido
  • limb pain
  • clawfoot
  • skin thickening
  • infertility
  • nephrotic syndrome
  • small kidney
  • glaucoma
  • shriveled kidney
  • polycythemia
  • muscle pain
  • protein deposit in kidney
  • excessive glycine levels in urine
  • atrophy of cochlear nerve

Muckle-Wells Syndrome and Familial Cold Auto Inflammatory Syndrome

MWS is one of the Cryopyrin-associated periodic syndromes (CAPS), caused by mutations in the CIAS1/NLRP3 gene. The syndrome is usually characterized by fever and rashes, along with joint pain. Familial cold autoinflammatory syndrome (FCAS), on the other hand, is a rare, inherited inflammatory disorder. It is also known as Familial Cold Urticaria. The condition is characterized by intermittent episodes of rash, fever, joint pain and other signs and symptoms of systemic inflammation that results from exposure to cold.

The mutation of a new gene encoding a putative pyrin-like protein is the cause of Familial Cold Autoinflammatory Syndrome and Muckle-Wells syndrome. According to doctors, both MWS and Familial Cold Auto Inflammatory Syndrome are simply dissimilar phenotypes of a single disease.

Muckle-Wells Syndrome Diagnosis

The diagnosis of MWS can be done only through careful evaluation of the symptoms and analysis of the medical history of patients. The confirmation of the diagnosis is done through genetic testing and the identification of NLRP3 mutations. Not all patients have a detectable genetic mutation, which makes accurate evaluation of symptoms quite critical.

Muckle-Wells Syndrome Treatment

The treatment of this disorder is basically symptomatic. The medications mainly used for curing the disorder involve:

  • Anakinra – An interleukin 1 receptor antagonist, it helps treat hearing loss caused by the disorder.
  • Rilonacept (Arcalyst) – It is a dimeric fusion protein for the treatment of CAPS. It has been approved for the treatment and has shown remarkable effectiveness against inflammatory symptoms of the syndrome.
  • Canakinumab – A monoclonal antibody, it fights against interleukin-1β and is also used for the treatment of MWS.

There are also FDA-approved therapies which help cure the adverse effects of MWS.

Muscle Wells Syndrome Complications

Quite a few complications arise due to this syndrome. These include:

  • Abdominal pain
  • Peritonitis
  • Urticaria
  • AA amyloidosis
  • Sensorineural hearing loss

Muckle Wells Syndrome Prognosis

The prognosis of MWS depends on the possible outcomes of its symptoms. Deterioration of the health of its sufferers leads to a condition called uremia, an illness resulting from kidney failure. Not much detail is available about the level of incidence and prevalence. In certain cases of MWS, Amyloidosis develops in later part of life of patients. This is a disease in which an unusual buildup of the protein Amyloid takes place in the tissues and organs of sufferers. This accumulation, if not treated in time, can give rise to fatal consequences (including kidney failure). People having fever without Amyloidosis are generally expected to have a normal life expectancy.

Muckle Wells Syndrome Pictures

Check out some pictures of patients suffering from this rare genetic disorder.

Picture 1 – Muckle-Wells Syndrome

Picture 2 – Muckle-Wells Syndrome Image

If you spot symptoms of Muckle-Wells Syndrome in any of your friends or family members, seek medical attention as soon as possible. When timely treated and managed, the condition can be resolved without risk of any major complications.

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