Cryopyrin-associated periodic syndrome is the name given to three autoinflammatory diseases that result from the same mutation. The diseases are among the periodic fever syndromes and progress in episodes. To date, all three syndromes can only be treated symptomatically and with medication.
What is cryopyrin-associated periodic syndrome?
In autoimmune diseases, patients’ immune systems turn against their own bodies. The disease group of autoimmune diseases includes several subcategories, such as autoinflammatory diseases with activation of nonspecific immune defenses. The most important characteristic of this disease group is inflammation caused by the immune system. The cryopyrin-associated periodic syndrome includes several autoinflammatory diseases that arise from the same cause. Three different diseases belong to the CAPS group of diseases: FCAS, MWS and NOMID. There are well under 1000 known patients worldwide. The prevalence is estimated at one to two cases per million people. It is estimated that there is probably a high number of unreported cases. All diseases from the cryopyrin-associated periodic syndrome group belong to the periodic fever syndromes. These fever syndromes are rare, monogenically inherited diseases that cause episodes of fever at irregular intervals due to immune system factors. The course of the disease varies from mild to lethal.
Causes
Cryopyrin-associated periodic syndrome does not appear to occur sporadically in all cases. Familial clusters have been observed in the cases documented to date, most notably for the FCAS group of the disease. Heritability characterizes most periodic fever syndromes. Presumably, autosomal dominant inheritance underlies the inheritance of CAPS. The primary cause of the syndrome is a genetic mutation. Thus, based on the results of research to date, science assumes a genetic defect in the NLRP3 gene. This gene codes for cryoporin in human DNA. This substance is an element of IL-1 inflammasome and thus an important part of protein complexes of the non-specific immune system. The defective gene initiates an overproduction of IL-1b and thus causes systemic inflammatory reactions. Because the cause of CAPS is a genetic defect, the disease group can also be classified as immunodeficiencies instead of autoimmune diseases.
Symptoms, complaints, and signs
The symptomatic manifestation type of CAPS depends on the subtype. Urticaria is among the core symptoms of the three disorders, along with fever, fatigue, hearing loss, arthralgias, and myalgias. FCAS manifests as a familial cold-induced disease. This is the mildest form, causing an episode two to three hours after exposure to cold. The episode appears flu-like and is accompanied by fever, headache, and chills. Muckle-Wells syndrome (MWS), which usually first manifests in early childhood, should be distinguished from this. The episodes last longer than 24 hours and occur more frequently than in FCAS. Not only cold, but also stress and fatigue cause relapses. Systemic amyloidosis is observed in a quarter of patients during the relapses, which can lead to renal failure if left untreated. The last disease from the CAPS group is chronic infantile neuro-cutaneo-articular syndrome and corresponds to the most severe CAPS expression. The manifestation takes place already in the infant. Symptoms may progress from relapsing to persistent chronic form. Symptomatically, CNS involvement makes up the clinical picture. In addition to aseptic meningitis, increased intracranial pressure or seizures, joint involvement may also occur. Lymph node swelling, high fever, and hepatosplenomegaly accompany the symptoms. Patients with this form have additional growth retardation and sometimes suffer from sensorineural hearing loss or inflammatory eye involvement that can lead to blindness.
Diagnosis
For CAPS, the most certain way to diagnose the disease is by molecular genetic analysis. If one of the three disorders is suspected, the physician has the patient’s DNA tested for the genetically typical change. If the mutation can be detected, the diagnosis is considered proven.Prognosis is highly dependent on the severity and course in individual cases and is most favorable for FCAS patients.
Treatment and therapy
CAP syndromes are not curable to date, as gene therapy interventions have not yet reached the clinical phase. Therapy is symptomatic and is usually equivalent to drug therapy when conventional treatment is used. The drugs serve as relapse prophylaxis and at the same time attenuate the symptoms when a relapse occurs. NSAIDs/NSAIDs, for example, are used to alleviate the symptoms and belong to the group of analgesics and antipyretics. Antihistamines are only suitable for FCAS patients. Steroids are suitable for all three groups and include, for example, cortisone treatment. Many patients with autoimmune diseases are also prescribed immunosuppressants. In the case of CAPS, their use is most appropriate for MWS or NOMID patients. In patients with the mildest form, suppression of the immune system is usually not necessary. Patients with FCAS or MWS are also encouraged to prevent relapses as much as possible. This can include warm drinks, warm baths, multiple layers of clothing, and reducing physical as well as psychological stress. Depending on the symptoms, patients with the severe form of NOMID may need further treatment. This may include, for example, provision of hearing aids. Ophthalmologic procedures may also be required for inflammatory reactions in the eye area.
Outlook and prognosis
The prognosis of cryopyrin-associated periodic syndrome is unfavorable. The disease is genetic and is not curable according to current legal as well as medical guidelines. The treatment plan is individualized and is aimed at alleviating symptomatic symptoms. The cryopyrin-associated periodic syndrome consists of a total of three disorders, which vary in their occurrence as well as their respective manifestations in each patient. The intensity of the syndrome is largely responsible for the prospect of improvement of the existing symptoms. Since the course of the disease is usually intermittent, the patient may experience phases of complete remission. In the mild form of the syndrome, the episode remains for 24 hours. Subsequently, the symptoms gradually regress completely. The moderate form of the syndrome can, in addition to many other impairments, end in the worst case in a disturbance of the kidney function. This threatens the patient with organ failure. This represents a life-threatening situation. In the most severe form of cryopyrin-associated periodic syndrome, there is usually no further complete relief of the symptoms. The symptoms that have occurred no longer completely regress, but remain permanently present. This represents a considerable reduction in the quality of life and can lead to further illnesses. In addition to the physical impairments, there is a threat of psychological disorders, which contribute to a further deterioration of the prognosis.
Prevention
The diseases from the CAPS group are genetic diseases. External factors for the development of the disease are not yet known. For this reason, no preventive measures exist to date. Only genetic counseling during family planning can be described as a preventive measure in the broadest sense.
Follow-up
In this syndrome, the further measures of aftercare depend very much on the exact nature and severity of the symptoms, so that no general prediction can be made in this regard. However, early detection of the symptoms in this disease has a very positive effect on the further course and can also prevent or limit further complications and complaints. The sooner the syndrome is detected, the better is usually the further course of the disease, so that the affected person should see a doctor at the first symptoms and complaints. In most cases the intake of various medications is necessary. Care must always be taken to ensure that the correct dosage is taken and that the medication is taken regularly in order to permanently limit the symptoms. Often the affected persons are still dependent on the support and help of their own family or friends in order to prevent psychological upsets or depression. Regular visits to a doctor are also necessary to permanently check the condition of the disease.There may be a decreased life expectancy for the patient due to this condition.
What you can do yourself
Cryopyrin-associated periodic syndrome comprises three autoinflammatory diseases due to the same genetic defect. There are no conventional medical or alternative procedures that treat the disease causally. What the patient himself can do to improve his condition depends on how severe the disease is. The mildest form is the so-called familial cold-induced autoinflammatory syndrome (FCAS). As the name suggests, the symptoms of FCAS are triggered by hypothermia. Here, the patient can take mainly preventive measures. Sufferers should get into the habit of always studying the weather prognosis and, as a precaution, always keep a scarf and a warm jacket in the office or in the car. A dry pair of shoes should also always be handy. As soon as the outside temperatures drop into the minus range, thermal clothing is helpful. If possible, a hot drink, preferably tea, should be consumed after acute exposure to cold. If possible, hot baths should also be taken. Many patients also react negatively to fatigue, stress, and severe physical exertion. In these cases, it is important for sufferers to have an orderly daily routine. Sports should only be done moderately. Since stress cannot always be avoided, relaxation techniques such as yoga or autogenic training should be learned.