What is CINCA Syndrome used for?

When infantile chronic neuro-kutaneo-articular syndrome (CINCA syndrome) is an autoinflammatory disease that causes erroneous inflammatory response in the body. The syndrome manifests itself in infancy, including fever, pain and neurological symptoms. Treatment is with drugs that reduce the protein interleukin-1β.

What is the CINCA Syndrome?

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

In the case of an autoinflammatory disease, the body reacts like an inflammation – but in reality this is not there. Autoinflammatory diseases are thus similar to autoimmune diseases, in which the body turns against its own immune system.

All three forms of cryopyrin-associated periodic syndrome share their genetic basis: a genetic defect interferes with the normal inflammatory response and triggers it, although there is no real cause. The CINCA syndrome first occurs in infancy.

Causes

The CINCA syndrome is an inherited disease that is responsible for 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 person affected. Whether an affected parent passes the disease on to a child depends largely on 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 no damage to the body. Cryopyrin stimulates the synthesis of interleukin-1β. This is an inflammation-promoting messenger substance.

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. Medical researchers found SAA-3 in other tissues as well; it seems to trigger the inflammatory reactions there.

Symptoms, ailments & signs

Symptoms of CINCA syndrome are more severe than the other two forms of cryopyrin-associated periodic syndrome. In the case of CINCA syndrome, the symptoms can show up in attacks or continuously. Typical symptoms include fever, rash or hives, hearing loss, joint pain (arthralgia) and muscle pain (myalgia).

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

The disease also has the potential to cause seizures and increase incranial pressure. This is the pressure that exists 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, fatigue, restlessness, bradycardia, headaches and vigilance disorders.

Advanced signs of intracranial pressure include quantitative disturbances of consciousness such as somnolence, which manifests itself primarily as being very drowsy and unusually sleepy. With stupor, those affected are difficult to wake up and only react to strong pain stimuli.

The CINCA syndrome can also trigger the most severe quantitative disturbance of consciousness: the coma. The disease also has the potential to cause lymph node swelling, kidney damage, and blindness.

Diagnosis & course

The CINCA syndrome begins in infancy. Medicine therefore also calls it a systemic inflammatory disease beginning neonatal. When diagnosing, doctors detect inflammation markers in the blood that form a specific pattern. Using this pattern, you can differentiate the CINCA syndrome from other inflammatory diseases.

Complications

CINCA syndrome causes various symptoms. These can mainly occur in episodes, so that the person affected does not have any particular complaints in between. In most cases this will result in a rash and a fever. Furthermore, pain in the muscles and extremities also occurs, which complicates the everyday life of the person concerned. The joints can also be painful and hearing loss can result.

In the worst case, this hearing loss leads to complete hearing loss. Without treatment, the CINCA syndrome leads to meningitis, which can lead to paralysis and other sensory disorders. This also results in convulsions and epileptic seizures. The person concerned generally feels tired and exhausted and no longer takes an active part in life.

The constant pain and discomfort often lead 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 alleviate the symptoms. As a rule, however, the treatment has to be repeated more often.

When should you go to the doctor?

If the 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, as well as hives and hearing loss.

Anyone who experiences any of these symptoms should seek medical advice immediately. If signs of meningitis appear, the hospital must be visited. Seizures, severe headaches and impaired consciousness must also be clarified immediately and treated if necessary. Emergency medical help is required in the event of a stupor or coma.

If possible, the person affected should receive first aid and then treated immediately by a specialist. A longer hospital stay is necessary in any case after such a severe course. Depending on the symptoms that follow, other doctors may need to be called in. If you are hard of hearing, you should consult an audiologist, while blindness should be treated by an eye disease specialist and, later, by an ophthalmologist. If psychological moods and depression occur, a visit to a therapist is recommended.

Treatment & Therapy

Since drugs and other therapies cannot influence the causative mutation in the NLRP3 gene, the treatment of CINCA syndrome is directed against the chain reaction that causes the symptoms of inflammation. 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 and normalize the sedimentation rate and the amount of C-reactive protein in the blood. It is taken at about the same time each day. People 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 dosages. Doctors sometimes treat acute inflammatory symptoms of the CINCA syndrome with drugs containing cortisone. It is often necessary for those affected to take pain relievers for joint and muscle ailments.

Outlook & forecast

As a rule, the treatment for CINCA syndrome is always carried out against the inflammation, with the aim of limiting the chain reaction of the inflammation.

A causal treatment is not possible with this syndrome. With the help of medication, however, the symptoms can be limited relatively well. The hearing loss is also alleviated as this does not occur due to damage to the ear.

There are also no particular complications, although those affected are dependent on lifelong therapy in order to permanently alleviate the symptoms. The pain in the muscles and joints in the CINCA syndrome is relieved with the help of painkillers, although no causal therapy is possible and the patients are dependent on permanent treatment.

If the CINCA syndrome is not treated, the inflammation spreads over the entire body of the patient and can lead to severe complications and in the worst case to death of the person concerned. Treatment is therefore necessary as early as 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 preventing genetic diseases such as the CINCA syndrome. Since the disease already occurs in infancy, there is less room for measures that affect general health. Eating a healthy diet and coping well with stress 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 illness that has a drastic impact on the way we live, children often benefit from psychosocial measures as well.

Aftercare

In most cases, the patient with CINCA syndrome has no follow-up options available. This disease is a congenital disease that cannot 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 passing the syndrome on to the children.

Usually the syndrome itself is treated with the help of medication. There are no particular complications and the symptoms can be alleviated relatively well. However, the person concerned is dependent on the regular use of these drugs. Furthermore, the interactions with other drugs should also be considered.

Not infrequently, the CINCA syndrome also leads to psychological complaints or depressive moods. If these complaints also occur, talking to friends or family can be very helpful. However, a visit to a psychologist is essential if you have serious psychological problems.

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

You can do that yourself

People with CINCA syndrome usually suffer from a variety of ailments. The most important self-help measure is to take the prescribed medication regularly and to carry out the therapeutic measures prescribed by the doctor.

Accompanying this is a therapeutic counseling useful. Especially in the case of serious illnesses, it can help to speak to a specialist who, under certain circumstances, can also establish contact with other people affected. Furthermore, the diet has to be changed in the case of CINCA syndrome.

An individual diet is required to prevent typical symptoms such as rash, joint pain, hives and fever. For this purpose, those affected should turn to a specialist or a nutritionist. Finally, patients need a lot of bed rest and rest.

The disease places enormous strain on the entire body, and therefore greater exertion and stress should be avoided. Moderate exercise and coordinated occupational therapy are allowed, which is best implemented together with a professionally trained doctor. The CINCA syndrome always requires close medical supervision. Especially in the case of unusual symptoms or acute complaints, you should speak to the responsible doctor as soon as possible.

CINCA Syndrome