When white blood cells are severely damaged as a side effect of a medication, the body’s immune system can break down as a result. This opens the door to both bacterial and viral infections, which in extreme cases can have fatal consequences. This is then referred to as agranulocytosis.
What is agranulocytosis?
Agranulocytosis is said to occur when the percentage of granulocytes falls below 500 cells per microliter of blood. Granulocytes belong to the white blood cells. Agranulocytosis occurs when the percentage of granulocytes falls below 500 cells per microliter of blood. Granulocytes belong to the white blood cells and are found wherever the body comes into contact with pathogens, for example on mucous membranes. They are produced in the bone marrow and are mainly responsible for the defense against bacteria and fungi, i.e. they are crucial for maintaining the immune system. If granulocytes are no longer produced in the bone marrow, for example as a result of taking a drug, there is a severe reduction or even complete absence of granulocytes in the blood. Forms of agranulocytosis:
Generally, a distinction is made between allergy-related and congenital agranulocytosis. Congenital agranulocytosis is rather rare. One example is the Kostmann syndrome. More frequent, however, is agranulocytosis triggered by drugs, whereby two types are distinguished here. Type I of allergic agranulocytosis is triggered by drugs. The immune reaction to the drug, in which the granulocytes are damaged, happens both time- and dose-independently. Type II is also called toxic agranulocytosis because the drug triggers toxic bone marrow damage. Characteristically, type II is both drug dose and time dependent. The difference between type I and type II is that in type I granulocytes are produced, but they are destroyed. In type II, the production of granulocytes in the bone marrow is already prevented.
Causes
Unless it is hereditary, agranulocytosis can be caused both by an immune response to certain drugs and by toxic influences affecting the bone marrow. The most common cause of agranulocytosis is intolerance to certain drugs, which severely damage the granulocytes. Drugs with which agranulocytosis has been frequently observed are:
- Analgesics, e.g., metamizole, acetaminophen.
- Antipyretics, e.g., phenylbutazone.
- Antibiotics, e.g. metronidazole, penicillin.
- Neuroleptics, psychotropic drugs
- Thyrostatic drugs, e.g. thiamazole, carbimazole
- Sulfonamides
- Others, e.g., antihistamines, antidiabetics
Drugs that induce type II agranulocytosis directly damage bone marrow cells. An example of such a drug is chlorpromazine. It should be noted that the drug inducing agranulocytosis can be reintroduced here at an appropriately low dose over time without causing such a reaction. This is different in the case of type I. Here, the allergic reaction usually persists throughout life, and even the smallest amounts of the drug cause agranulocytosis again.
Symptoms, complaints, and signs
Agranulocytosis is initially manifested by nonspecific symptoms. At the beginning of the disease, headache, muscle pain, fever, and a general feeling of malaise occur. In the further course, high fever with chills and gastrointestinal complaints may occur. Nausea and vomiting are typical, and diarrhea is usually added in later stages. The loss of fluids can lead to deficiency symptoms, which become apparent in the form of dizziness, fatigue and impaired physical and mental performance. Furthermore, agranulocytosis can cause swelling of the lymph nodes, necrosis of the mucous membranes in the mouth and throat, and infections of the respiratory tract. The anal area may also become inflamed, resulting in severe pain, itching, and bleeding. The weakened immune system can no longer fend off any pathogens, resulting in increased infections. The mucous membranes are particularly affected, leading to herpes or tonsillitis, for example.If agranulocytosis is due to an immune reaction to a drug, the symptoms mentioned above occur immediately after ingestion. Toxic agranulocytosis, on the other hand, progresses insidiously and only causes major symptoms in the later stages of the disease. An external feature of affected individuals is pale skin, sometimes associated with sweating and skin irritation.
Diagnosis and course
The onset of agranulocytosis initially manifests nonspecifically with a general malaise, headache, muscle pain, and fever. Subsequently, high fever with chills, nausea, swelling of the lymph nodes, and further mucosal necrosis of the mouth and throat, infections of the respiratory tract, and the anal area occur. Pneumonia or diarrhea may also occur. In general, there is a severe feeling of illness. Since the immune system collapses, infections, especially of the mucous membranes, occur in particular. Examples are herpes or tonsillitis. If it is an immune reaction to a drug, the symptoms occur immediately, often after the first dose. In the case of toxic agranulocytosis, the first symptoms may not become apparent for weeks. The question of whether or not agranulocytosis is present can be answered very easily by examining the granulocytes in the blood (blood count). In addition, a physical examination is performed, during which the lymph nodes and mucous membranes in particular are examined in detail. The course of the disease and the medication taken are also reviewed with the patient. There are no methods with which the triggering drug could be determined. Therefore, it must be thoroughly investigated which drug could be the trigger. Another way to diagnose agranulocytosis is by bone marrow biopsy, in which samples of the bone marrow are taken by needle and examined.
Complications
Agranulocytosis is an allergic intolerance reaction to certain drugs. It acts directly in the bone marrow and causes an acute deficiency of granulocytes. These white blood cells are in effect the body’s police force and have the ability to destroy pathogens as well as fungi, parasites and bacteria. If this endogenous defense fails, serious complications are the result. The symptom is considered a side effect of preparations such as: antibiotics, analgesics, neuroleptics, thyreostatics and cytostatics. Affected persons, whose physical condition worsens when taking described medications, need medical assistance. In the worst case, there is a risk of mucosal necrosis or life-threatening toxic reaction. Thorough history taking can analyze the sensitivity but cannot cure it. If patients are on long-term medication that causes agranulocytosis, they are subject to regular medical monitoring. In addition to making the diagnosis, attempts are made to stabilize the patient’s immune balance. In some cases, the patient is isolated if infection-like symptoms with fever are already apparent and the lymph nodes are swollen. To restore the physical balance, a broad-spectrum antibiotic is administered. Depending on the condition, the individual may be given an indication of granulocyte growth factors. In order to minimize the risk of complications, agranulocytosis patients should emphasize accurate hygiene of all body orifices in addition to the therapeutic measure. Due to the increased risk of infection, places where crowds of people gather closely together should be avoided.
When should you go to the doctor?
Agranulocytosis must definitely be examined and treated by a physician. If treatment is not received, the patient may die in the worst case scenario. For this reason, a weakened immune system must be treated and strengthened again in any case. The affected person should then consult a doctor if fever and general exhaustion occur. This may indicate agranulocytosis. Not infrequently, there is also a foul and putrid mouth odor and a very severe headache. These complaints may also indicate the disease. If it is not possible to visit the doctor, an emergency doctor can also be called if, for example, the patient has difficulty breathing or loses consciousness. Furthermore, pneumonia can also be a symptom of agranulocytosis. Treatment can usually be provided by a general practitioner.If further symptoms occur, these can be treated by a specialist physician. As a rule, agranulocytosis does not result in a reduced life expectancy. A physician must also be consulted if the agranulocytosis is triggered by a specific medication. However, discontinuing or changing the medication should be done only after consultation with the physician.
Treatment and therapy
If agranulocytosis is suspected, the triggering drug must be discontinued immediately. If it is unclear which drug is involved in the specific case, the use of all nonessential drugs must be stopped. The production and number of granulocytes in the blood then increases again and regulates itself. Growth can be supported by the administration of granulocyte growth factors. To help the body’s defense system, antibiotics are given in case of infections and fever. Rapid administration of a broad-spectrum antibiotic can usually prevent a fatal effect of the disease due to sepsis that has developed. If severe symptoms develop, hospitalization is required. To minimize the risk of infection, isolation of the affected person is advisable. In general, special attention should be paid to personal hygiene and crowds should be avoided due to the increased possibility of infection. Since agranulocytosis is a rather rare disease, many physicians and pharmacists underestimate the risk. Because some triggering medications are used precisely for the initial, flu-like symptoms of agranulocytosis, a downward spiral can occur here if administered. Therefore, if the above symptoms occur, it is imperative to consult a physician rather than to combat the symptoms with self-medication or by selling an influenza drug through a pharmacist. In the absence of or delayed diagnosis by a physician, conditions resulting from agranulocytosis can be life-threatening.
Outlook and prognosis
Agranulocytosis can be well treated if detected early. However, symptoms such as fever, nausea, chills, malaise, and loss of appetite are so nonspecific that the critical death of granulocytes as a component of leukocytes is often not detected in time. Rather, other causes for these symptoms are often suspected initially. Patients taking medications such as certain neuroleptics or analgesics are potentially at risk. If the symptoms of protracted influenza appear in those affected, the leukocytes in the blood should be measured. If their number reaches a critical lower limit, agranulocytosis is present. This can lead to a complete breakdown of the immune system and be fatal. However, agranulocytosis is rare. Therapeutically, all drugs that can trigger agranulocytosis are first discontinued. The number of leukocytes then quickly rises again. In addition, drugs are started that temporarily take over the functions of the immune system until it has stabilized again. The chances of recovery are then good. Because the symptoms of agranulocytosis are so nonspecific, patients taking medications such as the neuroleptic clozapine should go for regular blood checks. If the leukocyte count is checked continuously, intervention can be rapid. If left untreated, agranulocytosis is very severe in most cases.
Prevention
It is important to keep in mind the problem of self-medication. Taking medications on one’s own can lead to severe illness in the event of hypersensitivity to one of the ingredients. Therefore, any medication should be discussed with a physician in advance. If medications causing agranulocytosis are administered, regular monitoring of the blood of the affected person can prevent serious consequences. If agranulocytosis exists, special attention should be paid to appropriate personal hygiene, especially in the oral cavity, pharynx, and anal region, to exclude any risk of infection.
Follow-up
As a rule, the options for follow-up care in agranulocytosis are severely limited. In this case, the patient is always dependent on medical treatment. Without treatment, this can also lead to the death of the affected person in the worst case.Early diagnosis and treatment always have a very positive effect on the further course of the disease and can prevent further complications. In agranulocytosis, the patient is dependent on taking medication. These should be taken regularly. Likewise, possible interactions with other medications must be taken into account. Parents must also ensure that their children take their medication regularly. However, should the agranulocytosis show severe symptoms, a stay in a hospital is necessary. The affected person should be careful to take it easy so as not to put unnecessary strain on the immune system. For example, the affected person should not spend time in high-risk areas. In general, a healthy lifestyle also has a positive effect on the course of agranulocytosis. Above all, a healthy diet and avoidance of nicotine and alcohol can alleviate the symptoms. Furthermore, contact with other people affected by agranulocytosis is also recommended.
What you can do yourself
In agranulocytosis, the most important self-help measure is to carefully observe the effect of the prescribed medication and to report the results to the responsible family doctor or cardiologist. Often, a change to another drug is sufficient to correct the reduction in granulocytes. Occasionally, however, side effects and interactions occur, which can lead to other complaints. Patients should also pay attention to a healthy diet that supports white blood cell production. Foods rich in vitamin B12 and folic acid, such as bananas, nuts and low-fat fish, have proven particularly effective. An adapted diet and medication are usually sufficient to reduce and eventually resolve agranulocytosis. Since the condition may also cause physical and psychological discomfort, further therapeutic measures may be necessary depending on the symptom picture, which the patient can often support by resting and taking it easy. The most important self-help measure in agranulocytosis is to pay attention to the body’s own signals. If a deficiency of granulocytes becomes apparent again, for example, through fatigue or lassitude, a visit to the physician is recommended.
