Muckle-Wells syndrome is an inherited metabolic disease that belongs to the amyloidoses and causes an inflammatory reaction in the body. Characteristic symptoms include fever, hives, and later hearing problems. The treatment is drug-based and is primarily aimed at counteracting the chain reaction that causes the inflammatory symptoms.
What is Muckle-Wells Syndrome?
Muckle-Wells syndrome is an autoinflammatory disease that the World Health Organization classifies as nonneuropathic hereditary amyloidosis (E85.0). Medicine describes deposits of proteins that accumulate in the spaces between cells as amyloidosis. See foodezine for Everything about Bloom Syndrome.
In an autoinflammatory disease such as Muckle-Wells syndrome, the body initiates processes that are intended to respond to inflammation. The various symptoms such as fever serve to fight bacteria and other foreign bodies more effectively. However, in Muckle-Wells syndrome, these reactions occur without actual inflammation being present.
Autoinflammatory diseases are therefore similar to autoimmune diseases, in which the body’s defense reaction is directed against the immune system and not against a pseudo-inflammation.
Causes
Muckle-Wells syndrome is an inherited disorder. It is passed from at least one parent to their children via the NLRP3 gene on the first chromosome. Other autoinflammatory diseases can also be based on a change in NLRP3. The altered gene is dominant and therefore leads to the onset of the disease even if it occurs only once in the genetic code. However, not every child of an affected person has to fall ill as well.
Humans have a diploid set of chromosomes: each chromosome is normally present twice. If only one parent has Muckle-Wells syndrome and has a second healthy one in addition to the disease-carrying chromosome 1, the probability of inheritance is about 50 percent. The NLRP3 gene encodes a specific protein called cryopyrin.
Among other things, cryopyrin is involved in the transmission of inflammatory signals and the programmed suicide of cells (apoptosis). In addition, it stimulates the synthesis of interleukin-1β – a messenger substance that promotes inflammation. Interleukin-1β, in turn, stimulates liver cells to produce serum amyloid A protein (SAA).
Medicine today knows three different types of acute-phase SAAs that the body produces in response to inflammatory signals: SAA-1 and SAA-2 play a role primarily in the inflammatory response of the liver, while SAA-3 also in other tissues occurs.
Symptoms, Ailments & Signs
The symptoms of Muckle-Wells syndrome vary greatly from person to person. However, the recurring, interrupted episodes of the disease are characteristic. During the episodes, those symptoms that are indicative of immune and inflammatory reactions are more pronounced. Typically, those affected have a fever during these phases or at least have an elevated temperature.
The fever often occurs together with muscle pain and joint problems. Hives are also very common in Muckle-Wells syndrome. Medicine also refers to this skin reaction as urticaria. It causes wheals, which show up as small bumps in the skin because the tissue beneath them swells. The skin is also often reddened.
As the disease progresses, those affected may lose their ability to hear. As a rule, the hearing ability decreases only slightly at first and then decreases continuously. The progressive amyloidosis damages the organ of Corti between the cochlea and the eardrum and/or the vestibulocochlear nerve. As a result, the functioning of the cochlea in the inner ear decreases.
Medicine also calls the vestibulocochlear nerve the auditory balance nerve – it is also responsible for the sense of balance. Dizziness and nausea are therefore also among the symptoms of Muckle-Wells syndrome. Tiredness, concentration problems and brief periods of unconsciousness occur less frequently.
The progressive damage to the kidneys causes a number of other symptoms: There is an unnatural amount of protein in the urine (proteinuria) and those affected have a significantly increased risk of acute kidney failure.
Diagnosis & course of disease
Muckle-Wells syndrome appears to be very rare, although exact data are lacking. In many cases, it only becomes noticeable in adolescence. As the disease progresses, the symptoms increase and increase in number and severity. Doctors often make the diagnosis after a detailed medical history and after they have been able to rule out other causes for the symptoms.
In the laboratory test, the increased blood sedimentation rate and a high content of C-reactive protein in the blood provide further information. A genetic test can provide definitive clarity as to whether the affected person carries the altered gene NLRP3, which causes Muckle-Wells syndrome. However, the genetic test is not absolutely necessary for the diagnosis.
Complications
First and foremost, Muckle-Wells syndrome causes severe reddening of the skin. The affected regions of the body can also swell and be affected by unpleasant itching. It is not uncommon for those affected to feel ashamed and suffer from inferiority complexes or reduced self-esteem. Mental health problems or depression can also occur.
Muckle-Wells syndrome can also lead to pain in the muscles and joints. Especially at night, this pain can lead to sleep disorders and thus to irritability in the patient. Those affected usually continue to suffer from fever and a weakened immune system. As a result, infections or inflammations occur more often, so that the quality of life of the patients is significantly reduced.
Concentration also decreases and those affected appear exhausted and tired. Muckle-Wells syndrome significantly increases the risk of kidney failure. Complications usually arise when Muckle-Wells syndrome is left untreated. The internal organs fail and the patient dies.
The treatment itself can take place with the help of medication and significantly reduce the symptoms. Whether there will be a reduction in life expectancy due to Muckle-Wells syndrome cannot be universally predicted.
When should you go to the doctor?
If the first signs of Muckle-Wells syndrome are noticed, a doctor should be consulted immediately. Muscle pain, joint problems and reddening of the skin indicate a serious illness that must always be examined by a doctor and then treated. The doctor can determine whether the symptoms are actually caused by the Muckle-Wells syndrome and initiate appropriate treatment in cooperation with various specialists in internal diseases. If this happens early, serious health complications can usually be ruled out.
However, if wheals or even hearing or balance disorders occur, the metabolic disease may already be at an advanced stage. At this point at the latest, a specialist must be consulted, who can clarify the symptoms and, if necessary, initiate treatment. In the event of acute kidney failure, an ambulance must be called. Further therapy takes place in a specialist clinic for metabolic diseases. Those affected can first consult their family doctor or a specialist in internal diseases. Children should be presented to the pediatrician if Muckle-Wells syndrome is suspected.
Treatment & Therapy
Current therapies cannot completely cure Muckle-Wells syndrome because the triggering mutation persists for life; however, the symptoms are mostly treatable. Doctors typically use drugs to stop the inflammatory response. One of these is anakinra. It is an interleukin-1 receptor antagonist.
Anakinra can restore hearing at the symptomatic level and normalize ESR and C-reactive protein. People usually inject it under the skin at about the same time each day. Anakinra reduces the effects of both interleukin-1α and interleukin-1β. Another drug called canakinumab specifically targets interleukin-1β, which mediates the autoinflammatory response in Muckle-Wells syndrome.
Canakinumab stays in the body for some time; Patients receive the injections several weeks apart. Medicine often uses cortisone to alleviate the symptoms of inflammation. In addition, sufferers often take painkillers. Left untreated, Muckle-Wells syndrome leads to progressive disability and organ failure.
Outlook & Forecast
Muckle-Well syndrome has a relatively poor prognosis. The therapy of the genetic disease is purely symptomatic. Early treatment can reduce pain and inflammation. The physical malformations can be treated with an early diagnosis, but not completely eliminated. Affected people always suffer from physical limitations. The poor physical and mental general condition often results in mental problems. The quality of life is generally greatly reduced and well-being continues to decline as the disease progresses.
Prescribed drugs such as cortisone or rilonacept are associated with side effects that further limit well-being. The same applies to any interventions on the joints, which are risky due to the risk of inflammation. Untreated Muckle-Wells syndrome is progressive. The disabilities and malformations increase and cause concomitant diseases. Life expectancy is reduced by infections, amyloidosis and other ailments.
The prognosis of Muckle-Well syndrome is based on other factors such as the type of therapy and any concomitant diseases. The responsible specialist usually gives the patient and their relatives an exact prognosis, on the basis of which further measures can be planned exactly.
Prevention
Since Muckle-Wells syndrome is a genetic disease, prevention is currently not possible. In the future, genetic engineering treatments could eliminate the defect in the NLRP3 gene, thereby preventing the syndrome from being inherited.
Aftercare
In most cases, those affected by Muckle-Wells syndrome have no special or direct follow-up measures available. Ideally, a doctor should be consulted at the first signs and symptoms to prevent other complications or further deterioration of the symptoms. Muckle-Wells syndrome cannot heal itself, so those affected should consult a doctor early on.
Since this is a genetic disease, genetic testing and counseling is advisable if you wish to have children. Most of those affected are dependent on taking various medications. The correct dosage and regular intake of the medication should always be observed. If you have any questions or are unclear, you should always consult a doctor first.
Regular check-ups by a doctor are also very important for Muckle-Wells syndrome, since the internal organs in particular can be negatively affected by the syndrome. A hearing aid should be used if you have hearing problems. In the case of children in particular, parents must ensure that hearing aids are worn correctly and that medication is taken correctly. In many cases, this syndrome significantly reduces the life expectancy of those affected.
You can do that yourself
Muckle-Wells syndrome must first be treated by a doctor. Since the hereditary disease has a very negative effect on general well-being, the most important self-help measure is to counteract the individual symptoms through rest, rest and individual measures.
This can be achieved, for example, by changing your diet. In consultation with the doctor and a nutritionist, a suitable diet can be created. Foods with lots of vitamins and minerals, such as nuts, fruit and vegetables, are recommended as they help with fever, hives and other typical ailments. If the kidneys are involved, alcohol, caffeine and other drinks that put additional strain on the organ should be avoided. Excessively salty or spicy foods should also no longer be eaten, as they put a considerable strain on the kidneys. If the doctor makes specific dietary requirements, the patient should follow them.
After the acute phase, the immune system can be boosted by moderate exercise. There are walks and exercises from yoga or aerobics. Which measures make sense in detail always depends on the individual symptoms of the autoinflammatory disease and must be worked out together with the family doctor.
