The WHIM syndrome stands for warts-hypogammaglobulinemia-immunodeficiency-myelokathexis syndrome and represents a hereditary and very rare immune deficiency disease. The disease is based on the so-called cytokine receptor defect, which affects the immune system. WHIM syndrome is inherited in an autosomal dominant or recessive manner.
What is WHIM Syndrome?
The main feature of WHIM syndrome is an immunodeficiency characterized by recurrent bacterial and viral infections. The airways are always affected. Here, in the course of the disease, inflammation of the paranasal sinuses, lungs and tonsillitis occur. For definitions of hyperkeratosis, please visit lawfaqs.net.
If left untreated, the disease can have serious consequences. Those affected also often suffer from infections with human papillomaviruses. These cause warts to form, usually on the hands and feet. Furthermore, patients with Whim syndrome have a high risk of developing viral tumors such as cervical carcinoma.
Low IgG concentrations are often found in the blood serum, which is referred to as hypogammaglobulinemia. In the histology, the bone marrow of those affected by the WHIM syndrome shows an excessive number of T-progenitor cells. In contrast, there is often a so-called neutropenia, which is due to defective release and retention of the neutrophilic granulocytes of the bone marrow. This is called myelocathexis.
Causes
The causes of the WHIM syndrome lie in a genetic defect. It is a so-called antibody deficiency syndrome, which can occur sporadically or in families. However, the latter is more likely to be the case. and occurs in about half of those affected. An autosomal dominant or recessive inherited pattern is almost always found in the hereditary disposition.
In most cases, the disease is transmitted from one generation to the next, with an even gender distribution. Therefore, an autosomal dominant inheritance is also spoken of. Various studies of twins have shown that siblings are both concordant and discordant in the occurrence of WHIM syndrome.
According to the current state of knowledge, various environmental influences or epigenetic factors also represent a possible cause of the WHIM syndrome if a predisposing gene that triggers the WHIM syndrome is present at the same time.
Symptoms, Ailments & Signs
The WHIM syndrome is an autosomal dominant hereditary disease. In over 90 percent of those affected, the cause is a mutation of the gene at gene locus 2q21. This is responsible for decoding the so-called chemokine receptor CXCR4.
The mutation, which is found in the intracellular region of the membrane-bound receptor for the cytokine CXCL12, causes the appearance of a truncated receptor protein. This is unable to internalize after activation. In this way, all mechanisms that cause negative self-regulation are permanently blocked.
The receptors are thus permanently stimulated. The reduced expression of the CXCR4 is also required for the release of the T-progenitor cells of the bone marrow. The mutations and the lack of internalization of the CXCR4 remain superficially on the TZ progenitor cells. Therefore, they are unable to leave the bone marrow.
They are therefore the cause of histological findings in the blood and bone marrow of the patients. However, WHIM syndrome can also occur in rare cases with a non-mutated chemokine receptor. This is usually based on a malfunction of the proteins involved in the internalization of the CXCR4.
A disturbed immune defense also occurs here because the CXCR4 receptor is also involved in other migration processes. The sometimes severely reduced immune defense of those affected is the main feature of the WHIM syndrome.
Diagnosis & course of disease
If the WHIM syndrome is detected, an exact medical history should be taken to rule out a drug-induced disease. This can occur, for example, after the administration of antibiotics. If the WHIM syndrome is isolated without any clinically detectable symptoms occurring, regular blood count checks, including a differential blood count, and clinical examinations should be carried out.
In some cases, a spontaneous remission of the disease could also be observed, which occurred after about five to six weeks. However, the WHIM syndrome usually takes a chronic course. Thanks to modern genetic research, it is now possible to identify most hereditary diseases before they break out. However, since the genetic information is very different for each person, the genetic analyzes are still very imprecise.
Complications
THE WHIM syndrome is associated with a whole range of symptoms and complications. Typical sequelae include warts and respiratory infections. Warts in particular can cause psychological problems in those affected, because the cosmetic blemish represents a significant psychological burden.
People who suffer from WHIM syndrome therefore often develop mental illnesses, such as social anxiety, depression or an inferiority complex. Pneumonia can also occur as part of the disease. If pneumonia is not treated promptly, serious complications such as high fever, shortness of breath, and cyanosis occur. In the worst case, the pneumonia ends fatally. WHIM syndrome can also cause infections in the ear and nasopharynx.
In the later stages of the disease, due to weakened immune defenses, sinusitis, otitis and other infectious diseases develop, each of which is fraught with serious complications. The treatment of warts-hypogammaglobulinemia-immunodeficiency-myelokathexis syndrome usually proceeds without incident.
However, the use of immunoglobulins can lead to undesirable side effects and interactions. Allergic reactions rarely occur. Anaphylactic shock or serious circulatory reactions occur very rarely. Accidental administration into the veins can cause tissue damage and circulatory problems.
When should you go to the doctor?
The person affected should always contact a doctor with WHIM syndrome, as self-healing cannot occur and the symptoms continue to worsen if no doctor is consulted. Early detection and treatment of the disease has a very positive effect on its further course. Since this is a genetic disease, it cannot be completely cured. However, if you want to have children, you should also consult a doctor for genetic counseling.
A doctor should also be consulted for WHIM syndrome if the person affected suffers from a very weak immune system and therefore becomes ill very often. Warts often form all over the body and the affected person repeatedly suffers from inflammation of the lungs or tonsils. If these symptoms occur over a longer period of time and do not go away on their own, a doctor should always be consulted. The diagnosis of WHIM syndrome can be made by a general practitioner. Further treatment depends on the exact symptoms and their severity.
Treatment & Therapy
The current therapy for patients affected by WHIM syndrome is to try to reduce their susceptibility to infections, since this is the main problem of the disease. In order to support the immune system of those affected, substitutions with immunoglobulins are often used.
Furthermore, it is necessary to normalize the release of neutrophilic granulocytes of the bone marrow. In order to achieve this, the GM-CSF or G-CSF is usually used. The use of the so-called CXCR4 antagonists, which also include plerixafor, is already being analyzed in multiple clinical studies. However, it is not yet part of the standard therapy for WHIM syndrome. Lifelong medication is indicated to treat the disease, since the genetic defect cannot be cured.
Prevention
Since the so-called WHIM syndrome is a genetic disease, it cannot be cured. For this reason, prevention is not possible. It is an autosomal dominant hereditary disease. Gene mutations and lack of internalization of CXCR4 remain on the surface of the TZ progenitor cells. This means that they cannot escape from the bone marrow and are the cause of histological blood and bone marrow findings. The WHIM syndrome cannot therefore be prevented.
Aftercare
Affected people with WHIM syndrome usually only have limited and only a few measures of direct aftercare available. For this reason, those affected by this disease should ideally consult a doctor very early on and also initiate treatment so that complications or other symptoms do not occur later on. Self-healing cannot occur in this case.
Since the WHIM syndrome is a hereditary disease, a genetic examination and counseling should be carried out in any case if you wish to have children, so that the syndrome cannot recur in the children. Those affected with WHIM syndrome are usually dependent on taking various medications.
Care should always be taken to ensure that the dosage is correct and that it is taken regularly. If you have any questions or are unclear, you should always contact a doctor first. In many cases, the help and support of one’s own family is also very important.
This can prevent or limit depression. In some cases, contact with other people affected by WHIM syndrome can be useful and make everyday life easier for the person affected. The syndrome can significantly reduce the life expectancy of those affected.
You can do that yourself
Patients with WHIM syndrome suffer from an immune deficiency. For this reason everything should be done throughout life to support and stabilize the immune system as best as possible. A balanced and healthy diet is particularly important. A diet rich in vitamins helps to reduce susceptibility to pathogens.
At the same time, it is important to ensure that the consumption of harmful substances, nicotine or drugs, is avoided completely. The ambient air should always be rich in oxygen to prevent breathing disorders. Regular, adequate exercise outdoors is therefore highly recommended. As soon as shortness of breath occurs, the person concerned should leave the area or consult a doctor. Wearing warm clothing is particularly important when the seasons change. Temperatures are often underestimated, which increases the risk of catching a cold.
Direct physical contact with other people suffering from an infection or a cold should be avoided. It is advisable to carry disinfectant for hands or feet with you at all times. This can be used preventively if there are people in the immediate vicinity who are showing the first signs of a cold. In public facilities, care must also be taken to avoid areas where there are many germs. It is advisable to wear appropriate protective clothing.
