Diseases

CINCA Syndrome – Causes, Symptoms & Treatment

CINCA-Syndrom

Chronic infantile neuro-cutaneous-articular syndrome ( CINCA syndrome ) is an autoinflammatory disease that causes an incorrect inflammatory reaction in the body. The syndrome already manifests itself in infancy, including in the form of fever, pain and neurological symptoms. Treatment is with drugs that reduce the protein interleukin-1β.

What is CINCA Syndrome?

The term chronic infantile neuro-cutaneous-articular syndrome (CINCA syndrome) stands for a form of the cryopyrin-associated periodic syndrome . Medicine summarizes several autoinflammatory diseases under this term; Muckle-Wells syndrome and familial cold-induced autoinflammatory syndrome (FCAS) also belong to this group.

In the case of an autoinflammatory disease, the body reacts as if it were inflamed – but in reality it is not there. Autoinflammatory diseases are similar to autoimmune diseases , but in which the body attacks its own immune system.

All three forms of cryopyrin-associated periodic syndrome share their genetic basis: a genetic defect interferes with and triggers the normal inflammatory response, despite no actual cause. CINCA syndrome first appears in infancy.

causes

CINCA syndrome is an inherited disease that is caused by the NLRP3 gene. The NLRP3 gene is located on chromosome 1 and is dominant. This means that a single mutated allele is sufficient for the CINCA syndrome to manifest itself in the affected person. However, whether an affected parent passes the disease on to a child is largely a matter of chance; the probability of inheritance is 50 percent.

The NLRP3 gene encodes the protein cryopyrin, which transmits inflammatory signals. In addition, cryopyrin also plays a role in the self-destruction of cells ( apoptosis ) – it ensures that damaged cells disappear and do not cause any damage in the body. Cryopyrin stimulates the synthesis of interleukin-1β. This is an inflammatory messenger.

Interleukin-1β stimulates liver cells to produce serum amyloid A protein (SAA). There are three different variants of the acute phase SAAs known to medicine today. These SAAs are responsible for the acute inflammatory response and trigger the symptoms of CINCA syndrome. SAA-1 and SAA-2 are involved in the inflammatory response of the liver. Doctors also found SAA-3 in other tissue during examinations; it seems to trigger the inflammatory reactions there.

Symptoms, Ailments & Signs

The symptoms of CINCA syndrome are more severe than those of the other two forms of cryopyrin-associated periodic syndrome. In the case of CINCA syndrome, the symptoms can appear both in episodes and continuously. The typical symptoms include fever , skin rash or hives , hearing loss , joint pain (arthralgia) and muscle pain (myalgia).

These signs of disease can also manifest themselves in other autoinflammatory diseases. However, the CINCA syndrome differs from them, among other things, in its early onset: even infants can suffer from it. In addition to the general symptoms of cryopyrin-associated periodic syndromes, other symptoms appear. CINCA syndrome can affect the central nervous system (CNS) and lead to meningitis , which becomes chronic.

In addition, the disease potentially causes seizures and increases intracranial pressure . This is the pressure that prevails in the brain. Normally it is 5 to 15 mm Hg. If the incranial pressure increases, those affected initially suffer from symptoms such as nausea , vomiting , tiredness , restlessness , bradycardia , headaches and impaired vigilance.

Advanced signs of intracranial pressure include quantitative disturbances of consciousness such as somnolence , which manifests itself primarily in severe drowsiness and unusual sleepiness. Those affected by stupor are difficult to wake up and only react to strong pain stimuli.

CINCA syndrome can also trigger the most severe quantitative disorder of consciousness: coma . The disease also potentially leads to swollen lymph nodes , kidney damage and blindness .

Diagnosis & History

CINCA syndrome begins in infancy. Medicine therefore also calls it a neonatal inflammatory systemic disease. During diagnostics, doctors detect inflammatory markers in the blood that form a specific pattern. Using this pattern, they can differentiate CINCA syndrome from other inflammatory diseases.

complications

CINCA syndrome causes various symptoms. These can mainly occur in flare-ups, so that the person affected does not have any particular symptoms in between. In most cases, there is a rash and fever. Pain in the muscles and extremities also occurs, which makes everyday life difficult for those affected. The joints can also hurt and hearing loss can occur.

In the worst case, this deafness can lead to complete hearing loss. Without treatment, CINCA syndrome leads to meningitis, which can lead to paralysis and other sensory disturbances. Convulsions and epileptic seizures also occur. The person affected generally feels tired and exhausted and no longer actively participates in life.

The constant pain and discomfort often leads to psychological upsets and depression. Furthermore, blindness or renal insufficiency can occur if the CINCA syndrome is not treated. The treatment itself does not lead to further complications and can relieve the symptoms. As a rule, however, the treatment must be repeated more often.

When should you go to the doctor?

If CINCA syndrome is suspected, the doctor should be consulted immediately. Typical warning signs that require medical clarification include fever, skin rash, joint and muscle pain, hives and hearing loss.

Anyone who notices one or more of these symptoms should seek medical advice immediately. If signs of meningitis appear, the hospital must be visited. Seizures, severe headaches and disturbances of consciousness must also be clarified immediately and treated if necessary. In the case of a stupor or a coma, emergency medical help is required.

If possible, the affected person should receive first aid and then be treated immediately by a specialist. A longer hospital stay is necessary after such a severe course. Depending on the subsequent symptoms, other doctors must be consulted. Hearing impairment requires consultation with an audiologist , while blindness requires treatment by an eye disease specialist and later by an ophthalmologist . If mental upsets and depression occur, a visit to a therapist is recommended.

Treatment & Therapy

Since drugs and other therapies cannot influence the triggering mutation in the NLRP3 gene, treatment of CINCA syndrome is directed against the chain reaction that causes the inflammatory symptoms. Anakinra is often used for this. This drug is an interleukin-1 receptor antagonist and affects both interleukin-1α and interleukin-1β.

Anakinra can reduce hearing loss, normalize the blood sedimentation rate and the amount of C-reactive protein in the blood. It is taken at about the same time every day. Patients can inject it themselves. Another drug that may be used in CINCA syndrome is canakinumab. This is an active ingredient that is only directed against the protein interleukin-1β and thus has a more specific effect.

In contrast to anakinra, those affected only have to repeat the canakinumab injection at longer intervals. As a rule, there are several weeks between two doses. Doctors sometimes treat acute inflammatory symptoms of CINCA syndrome with medication containing cortisone. It is often necessary for those affected to take painkillers for joint and muscle problems.

Outlook & Forecast

As a rule, treatment of CINCA syndrome is always anti-inflammatory, with the aim of reducing the chain reaction of inflammation.

A causal treatment is not possible for this syndrome. With the help of medication, however, the symptoms can be limited relatively well. Hearing loss is also alleviated because it is not caused by damage to the ear.

There are no particular complications, although those affected are dependent on lifelong therapy in order to permanently relieve the symptoms. The pain in the muscles and joints in CINCA syndrome is relieved with the help of painkillers, although causal therapy is also not possible and the patients are dependent on permanent treatment.

If the CINCA syndrome is not treated, the inflammation will spread throughout the patient’s body and can lead to serious complications and, in the worst case, to the death of the person concerned. Treatment is therefore necessary in infancy so that the child can survive. However, it cannot be predicted whether CINCA syndrome will negatively affect life expectancy if treated.

prevention

There is currently no effective way of causally preventing genetic diseases such as CINCA syndrome. Since the disease occurs in infancy, there is less room for measures that affect general health. Eating a healthy diet and managing stress well may help limit complications.

Recognized relaxation methods such as progressive muscle relaxation or autogenic training potentially reduce individual symptoms such as pain. Children can learn such techniques from about preschool age. Since the CINCA syndrome is a serious chronic disease that has a drastic impact on life, children often also benefit from psychosocial measures.

aftercare

In most cases, patients with CINCA syndrome have no options for aftercare. This disease is a congenital disease, which can therefore not be treated causally, but only symptomatically. If the person affected by the CINCA syndrome wishes to have children, genetic counseling can be carried out beforehand in order to avoid the syndrome being inherited by the children.

As a rule, the syndrome itself is treated with the help of drugs. There are no particular complications and the symptoms can be alleviated relatively well. However, the affected person is dependent on the regular intake of these drugs. Interactions with other medications should also be taken into account.

Not infrequently, the CINCA syndrome also leads to psychological problems or depressive moods. If these symptoms also occur, talking to friends or family can be very helpful. In the case of serious psychological problems, however, a visit to a psychologist is essential.

Furthermore, contact with other patients of the CINCA syndrome can often turn out to be very useful, since this often leads to an exchange of information. The life expectancy of the patient is not negatively affected by the CINCA syndrome.

You can do that yourself

Individuals with CINCA syndrome typically suffer from a variety of ailments. The most important self-help measure is to take the prescribed medicines regularly and to carry out the therapy measures prescribed by the doctor.

Accompanying this, a therapeutic consultation is useful. In the case of serious illnesses in particular, it can help to speak to a specialist who may also be able to put you in touch with other people who are affected. Furthermore, the diet must be changed in CINCA syndrome .

To prevent typical symptoms such as skin rash, joint pain, hives and fever, an individual diet is necessary. It is best for those affected to contact a specialist or a nutritionist. Finally, patients require a lot of bed rest and rest.

The disease puts an enormous strain on the entire body, and therefore excessive exertion and stress should be avoided. Moderate exercise and coordinated ergotherapy are permitted , which is best implemented together with a professionally trained doctor. The CINCA syndrome always requires close medical monitoring. In the event of unusual symptoms or acute complaints in particular, the doctor responsible should be spoken to as soon as possible.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.