The doctor calls Hyper-IgD syndrome – also known as HIDS – a hereditary disease that is mainly characterized by recurring episodes of fever. For this reason, the hyper-IgD syndrome is also one of the so-called periodic fever syndromes.
During the fever episodes, those affected complain of diarrhea, abdominal pain, nausea and vomiting, among other things. There is no causal treatment; however, the prognosis – in terms of patient life expectancy – is good.
What is Hyper IgD Syndrome?
Hyper -IgD syndrome (or HIDS) is a hereditary disease. Characteristic are recurrent episodes of fever as well as gastrointestinal symptoms. Periodic diseases, which include the hyper-IgD syndrome, have been known since the 19th century, but were only redefined and coined in 1948 by the physician Hobart A. Reimann.
Hyper-IgD syndrome was first mentioned in 1984. A Dutch working group described recurring fever in siblings as well as general inflammatory reactions and significantly increased levels of immunoglobulin D and immunoglobulin A. Around 160 diagnoses have been made since 2001; the majority of those affected live in France and the Netherlands. However, it is suspected that the number of unreported cases is higher.
Hyper-IgD syndrome is caused by a change in genetic information – a so-called mutation. The mutation occurs on chromosome 12. Hyper-IgD syndrome is inherited in an autosomal recessive manner. In around 80 percent of all cases, there is a missense mutation in the gene area, which subsequently encodes the MVK (12q12, GeneID 4598 – enzyme mevalonate kinase). This mutation causes a slightly reduced stability of the enzyme’s activity.
So far, however, it is unclear why the reduced mevalonate kinase activity subsequently triggers fever attacks. Due to the unclear cause, there is also no known therapy that sometimes combats the cause. Doctors can therefore only carry out symptomatic treatments that focus primarily on the fever episodes.
Symptoms, Ailments & Signs
Hyper-IgD syndrome already occurs during the first year of life. Recurrent episodes of fever are characteristic; the patient complains of fever and chills that occur very quickly. The triggers of these fever attacks are minor injuries, vaccinations or stress as well as operations.
In many cases, the patients also complain of abdominal pain, nausea and vomiting as well as diarrhea. Sometimes the lymph nodes in the neck can also swell. Other symptoms that are characteristic of Hyper-IgD syndrome: headaches, joint inflammation as well as joint pain and rashes.
The relapses themselves occur at intervals of between four and six weeks. The duration is between three and seven days. However, the duration and frequency of flare-ups can vary significantly depending on the patient. Bouts of fever occur more frequently, especially in childhood; in adulthood, the frequency and intensity decreases.
Diagnosis & disease progression
If there are characteristic symptoms that indicate hyper-IgD syndrome, checking the concentration of immunoglobulin D in the blood can provide information as to whether hyper-IgD syndrome actually exists. If the concentration of immunoglobulin D is over 100 IU/ml, it can be assumed that a hyper-IgD syndrome is present. Sometimes molecular genetic evidence of an existing mutation can also provide information as to whether hyper-IgD syndrome is present or not.
However, in order to secure the diagnosis, the doctor must rule out other diseases that have similar symptoms in advance. The Hyper-Ig-D syndrome is also one of the periodic fever syndromes; Familial Mediterranean fever (FMF) must also be ruled out in advance.
Other diseases that take a similar course and must be ruled out before diagnosing hyper-IgD syndrome are: “Tumor necrosis factor receptor 1-associated periodic syndrome” (also known as TRAPS), cyclic neutropenia, chronic infantile neurological syndrome -cutaneous-articular syndrome (or CINCA syndrome ) and Muckle-Wells syndrome. Diseases that fall under the PFAPA syndrome (periodic fever, canker sores, adenitis syndrome or pharyngitis ) are also included.
Although the treatment of hyper-IgD syndrome is relatively difficult, the prognosis is good. There is no reduction in life expectancy, even if the syndrome is extremely severe. However, the joints can be attacked during flare-ups, so that joint destruction is possible.
Amyloidosis, such as that found in familial Mediterranean fever, has only been documented in isolated cases. In a few cases, neurological abnormalities and limitations in mental abilities were also documented. Epilepsy, coordination and balance disorders are also possible, but also occur only rarely.
Hyper-IgD syndrome causes those affected to suffer from strong episodes of fever that recur after a certain period of time. It is not possible to predict the exact time of the next flare-up. In addition to the fever, the affected person also suffers from abdominal pain and diarrhea. Furthermore, there is also nausea and vomiting.
The quality of life is greatly reduced by the hyper-IgD syndrome and everyday life is made more difficult by the symptoms. As a rule, the patient’s resilience is also reduced and the affected person appears exhausted and tired. Bouts of fever can also have a negative effect on the psyche and lead to depression or other upsets.
There is also pain in the head and joints. It is not uncommon for the skin to be affected by rashes and the lymph nodes to swell. As a rule, children in particular are affected by the frequent bouts of fever. The treatment of hyper-IgD syndrome is symptomatic and limits the symptoms of the fever flare-up. There are no further complications. In most cases, the incidence decreases with age. Life expectancy is also not reduced by hyper-IgD syndrome.
When should you go to the doctor?
In the case of hyper-IgD syndrome, after the child has reached the age of one year, such severe symptoms suddenly appear that a doctor’s consultation is always necessary. Since similar symptoms are also observed in other diseases, an urgent diagnostic clarification of the symptoms is required. This is the only way to initiate effective therapy. A visit to the doctor should take place, among other things, if the one-year-old child suddenly suffers from inexplicable fever attacks, which can also occur at longer intervals.
The fever usually announces itself with the onset of chills. Above all, the doctor should also be consulted if there is a flare-up of fever due to special events such as vaccinations, stress or injuries. Even the accompanying symptoms of fever attacks should be taken as an opportunity to seek medical help. These symptoms include swollen lymph nodes, severe abdominal pain, vomiting and diarrhea.
If the doctor diagnoses hyper-IgD syndrome, he and the parents will discuss the necessary therapy. This consists of the administration of the cholesterol-lowering drug simvastatin and the immunosuppressant etanercept. These drugs relieve symptoms while reducing the risk of rare complications such as joint contractures or abdominal adhesions. Since the disease usually does not limit life expectancy and fever flares become increasingly rare over the course of life, constant medical care is not necessary.
Treatment & Therapy
So far, there is no therapy or treatment that primarily combats or treats the cause of hyper-IgD syndrome. For this reason, the physicians concentrate primarily on the symptomatic treatment of the fever attacks that occur again and again. However, these treatments are also extremely difficult. Not only are they different from patient to patient, but they can also have different intensities depending on the episode.
Classic fever-reducing or anti-inflammatory drugs – such as non-steroidal anti- inflammatory drugs – are completely ineffective. Colchicine, steroids or thalidomide have also proven to be ineffective. However, medical professionals have recognized that simvastatin can help treat any flare-ups of fever.
Positive developments in the context of the “interleukin-1ra analogue anakinra” have also been reported for some time. Sometimes the “tumor necrosis factor-α antagonist etanercept” can reduce the number of fever days and alleviate the intensity. No other treatments are known at this time.
Outlook & Forecast
Hyper-IgD syndrome offers a relatively positive prognosis. Although the disease is associated with severe symptoms such as gastrointestinal disorders, skin rashes, damage to the joints and fever, these health problems can be greatly reduced or even completely eliminated in the long term with comprehensive drug treatment.
Even when the joints are involved, the disease is not always associated with long-term symptoms if treated early. Only in individual cases do permanent joint disorders occur, which permanently impair quality of life and well-being and thus harbor the risk of mental suffering. Amyloidosis, which can affect all organs and the endocrine system, also only occurs in a few patients. However, some patients develop neurological disorders that can impair mental abilities and coordination. In severe cases, epilepsy can develop.
In most cases, those affected can lead a pain-free life, which, however, is always associated with long-term drug treatment and physiotherapeutic measures. Patients also have to repeatedly undergo surgical interventions or suffer from side effects and interactions as a result of the constant administration of medication. Psychological complaints can also occur in chronically ill HIDS patients. Typical mental sequelae are inferiority complexes and depressive moods up to severe depression. Life expectancy is not reduced by hyper-IgD syndrome.
Due to the fact that Hyper-IgD syndrome is a hereditary disease, preventive measures are not known or possible.
The measures or options for aftercare are usually very limited in hyper-IgD syndrome. Since this is also a hereditary disease, a complete cure cannot be achieved. Those affected are therefore dependent on lifelong therapy and treatment in order to permanently relieve the symptoms.
In order to avoid inheritance of the hyper-IgD syndrome to the descendants, genetic counseling should also be carried out if you wish to have children. This is the only way to prevent the inheritance of the disease. Since hyper-IgD syndrome is usually treated by taking medication, those affected should always ensure that they take it regularly and, above all, that it is taken correctly.
Possible interactions should also be taken into account. If you have any questions or are unclear, you should always contact a doctor first. Since hyper-IgD syndrome can also promote tumors, those affected should be examined by a doctor regularly. The support and care of friends and family is also very important and can alleviate the symptoms. Above all, psychological complaints or depression are prevented in this way. The life expectancy of those affected may be reduced by the hyper-IgD syndrome.
You can do that yourself
Unfortunately, since the hyper-IgD syndrome cannot be treated causally and thus causally, only the individual symptoms and complaints can be restricted.
The flare-ups are treated with medication. A general bed rest and taking care of your own body can also have a very positive effect on the course of the disease. Above all, those affected should not easily carry out physical activities. Taking fever-reducing medication or painkillers can also have a negative effect on the stomach, so a doctor should be consulted.
Furthermore, contact with other affected persons can also be helpful in the case of hyper-IgD syndrome. This may make everyday life easier to master. The help of friends and acquaintances can also significantly limit and alleviate the psychological symptoms of the syndrome. Unfortunately, those affected have to come to terms with the disease and should not forget that the fever episodes occur only for a short period of time. However, treatment is still required for epileptic seizures. In particular, driving vehicles or operating heavy machinery should not be carried out if you have epilepsy.