Muckle-Wells syndrome is a hereditary metabolic disease that belongs to the amyloidoses and causes an inflammatory reaction in the body. Characteristic symptoms are fever, hives and later hearing problems. Treatment is by medication and is directed primarily against the chain reaction that causes the inflammatory symptoms.
What is muckle-wells syndrome?
Muckle-Wells syndrome is autoinflammatory disease that the World Health Organization classifies as nonneuropathic heredofamilial amyloidosis (E85.0). Amyloidosis is the medical term for deposits of proteins that accumulate in the spaces between cells. In an autoinflammatory disease such as Muckle-Wells syndrome, the body sets in motion processes that are actually intended as a response to inflammation. The various symptoms, such as fever, serve to fight bacteria and other foreign bodies more effectively. However, in Muckle-Wells syndrome, these responses run without actual inflammation being present. Autoinflammatory diseases thus resemble autoimmune diseases, but in which the body’s defensive response is directed against the immune system rather than against a mock inflammation.
Causes
Muckle-Wells syndrome is an inherited disorder. It is passed from at least one parent to children via the gene NLRP3 on the first chromosome. Other autoinflammatory diseases may also be due to an alteration of 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. Nevertheless, not every child of an affected person must also develop the disease. Humans have a diploid chromosome set: each chromosome is normally present twice. If only one parent suffers from Muckle-Wells syndrome and has a second healthy chromosome in addition to the disease-bearing chromosome 1, the probability of inheritance is about 50 percent. The gene NLRP3 encodes a specific protein called cryopyrin. Among other things, cryopyrin participates 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). Medical science now recognizes 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, whereas SAA-3 also occurs in other tissues.
Symptoms, complaints, and signs
Symptoms of muckle-wells syndrome vary widely from person to person. However, recurrent, intermittent episodes of the disease are characteristic. During the episodes, those symptoms that are indicative of immune and inflammatory responses become more pronounced. Typically, affected individuals fever or at least have an elevated temperature during these episodes. The fever often occurs together with muscle pain and joint complaints. Hives are also very common in muckle-wells syndrome. Medicine also refers to this skin reaction as urticaria. It results in wheals, which appear as small bumps in the skin because the tissue underneath them swells. The skin is also frequently reddened. In the later course of the disease, affected individuals may lose their hearing. As a rule, hearing ability decreases only slightly at first and then steadily decreases. Progressive amyloidosis damages the organ of Corti between the cochlea and the tympanic membrane and/or the vestibulocochlear nerve. As a result, the functional capacity 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. Therefore, dizziness and nausea are also among the symptoms of muckle-wells syndrome. Less frequently, fatigue, concentration problems and brief loss of consciousness occur. Progressive damage to the kidneys causes a number of other signs of the disease: There is an unnatural amount of protein in the urine (proteinuria), and affected individuals have a significantly increased risk of acute kidney failure.
Diagnosis and course of the disease
Muckle-Wells syndrome appears to occur very rarely, although accurate data are not available. It does not become apparent until adolescence in many cases.As the disease progresses, the symptoms increase in number and severity. Doctors often make the diagnosis after taking a detailed medical history and ruling out other causes of the symptoms. In laboratory tests, the increased sedimentation rate and a high level of C-reactive protein in the blood provide further clues. 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 essential for diagnosis.
Complications
First and foremost, Muckle-Wells syndrome causes severe redness on the skin. Likewise, the affected regions on the body may swell and be affected by an unpleasant itching sensation. It is not uncommon for those affected to feel ashamed as a result and also suffer from inferiority complexes or reduced self-esteem. Psychological complaints or depression may also occur. Furthermore, Muckle-Wells syndrome can lead to pain in the muscles and joints. Especially at night, this pain can lead to sleep problems and thus to irritability of the patient. Those affected usually also continue to suffer from fever and a weakened immune system. As a result, infections or inflammations occur more often, so that the patient’s quality of life is significantly reduced. Concentration also decreases and those affected appear fatigued and tired. Muckle-Wells syndrome significantly increases the risk of kidney failure. Complications usually occur if Muckle-Wells syndrome is not treated. In this case, the internal organs fail and the affected person dies. The treatment itself can take place with the help of medication and significantly reduce the symptoms. Whether there is a reduction in life expectancy due to Muckle-Wells syndrome cannot be universally predicted.
When should you see a doctor?
When the first signs of muckle-wells syndrome are noticed, a doctor should be consulted immediately. For example, muscle pain, joint discomfort, and redness of the skin indicate a serious condition that should always be evaluated by a physician and subsequently treated. The physician can determine whether the complaints are actually based on Muckle-Wells syndrome and initiate appropriate treatment in cooperation with various specialists for internal diseases. If this is done at an early stage, serious health complications can usually be ruled out. However, if wheals or even disturbances of the sense of hearing or balance appear, the metabolic disease may already be far advanced. In this case 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, the emergency physician must be called. Further therapy takes place in a specialist clinic for metabolic diseases. Affected persons 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 and therapy
Therapies to date cannot completely cure Muckle-Wells syndrome because the triggering mutation remains for life; however, symptoms are mostly treatable. Doctors usually use drugs to interrupt the inflammatory response. One of these is anakinra. This is a receptor antagonist of interleukin-1. Anakinra can restore hearing at a symptomatic level and normalizes blood sedimentation rate and C-reactive protein. Affected individuals usually inject it under the skin at approximately the same time each day. Anakinra reduces both interleukin-1α and interleukin-1β effects. Another agent called canakinumab focuses specifically on interleukin-1β, which mediates the autoinflammatory response in muckle-wells syndrome. Canakinumab persists in the body for some time; patients receive injections several weeks apart. To relieve the symptoms of inflammation, medicine often uses cortisone. In addition, sufferers often take painkillers. If left untreated, Muckle-Wells syndrome leads to progressive disability and organ failure.
Outlook and prognosis
Muckle-Wells syndrome offers a relatively poor prognosis. Therapy for the genetic disorder is purely symptomatic. Early treatment can reduce pain and inflammation.The physical malformations can be treated if diagnosed early, but they cannot be completely eliminated. Affected individuals always suffer from physical limitations. The poor physical and mental general condition often also results in psychological complaints. Quality of life is generally greatly reduced and well-being continues to decline as the disease progresses. Prescribed medications such as cortisone or rilonacept are accompanied by 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 deformities 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 specialist in charge usually gives patients and relatives an accurate prognosis, which can be used to plan further measures precisely.
Prevention
Because Muckle-Wells syndrome is a genetic disorder, prevention is not currently possible. In the future, genetic treatments could eliminate the defect in the NLRP3 gene, thereby preventing inheritance of the syndrome.
Follow-up
In most cases, affected individuals do not have any special or direct measures of follow-up care available for Muckle-Wells syndrome. However, a physician should ideally be consulted at the first signs and symptoms to prevent other complications or further worsening of symptoms. Muckle-Wells syndrome cannot heal itself, so those affected should see a doctor early on. Since it is a genetic disease, genetic testing and counseling is advisable if the patient wishes 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. In case of questions or uncertainties, a doctor should always be consulted first. Likewise, regular checks by a doctor are very important in Muckle-Wells syndrome, because especially the internal organs can be negatively affected by the syndrome. Hearing aids should be used in case of hearing difficulties. Especially in children, parents must pay attention to the correct wearing of hearing aids and also to the correct taking of medications. In many cases, this syndrome significantly limits the life expectancy of those affected.
What you can do 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 by resting, taking it easy and taking individual measures. This can be achieved, for example, by changing the diet. In consultation with the physician and a nutritionist, a suitable diet can be established. Foods with many vitamins and minerals are recommended, for example nuts, fruits and vegetables, as these help with fever, hives and other typical symptoms. If the kidneys are involved, alcohol, caffeine and other drinks that put additional strain on the organ should be avoided. Excessively salty or strongly spiced foods should also no longer be consumed, as they represent a considerable burden for the kidneys. If the doctor gives special instructions regarding diet, the patient should follow them. After the acute phase, the immune system can be boosted by moderate exercise. Walks and exercises from yoga or aerobics are suitable. Which measures are useful in detail always depends on the individual symptoms of the autoinflammatory disease and must be worked out together with the family doctor.
