A distinction is made between primary, i.e. congenital immunodeficiencies and secondary, acquired immune deficiencies – for example as a result of diseases of the hematopoietic system or adverse drug reactions. There are many different immunodeficiencies, and classifying them can be a challenge.
The main symptom of all immunodeficiencies is the recurrence of infectious diseases, with long or severe courses depending on the severity of the immunodeficiency. Treatment depends on the type and severity of the immunodeficiency. Various drugs are used and, in particularly severe cases, a blood stem cell transplant may be indicated.
What is an immunodeficiency?
An immunodeficiency means that a part of the immune system is not functioning properly. Affected people are unable to defend themselves adequately against infectious pathogens such as bacteria, viruses, fungi or parasites.
Immunodeficiencies – primary or secondary
Imundefects can be categorized as follows:
- Primary immunodeficiency: The disease is congenital, so the predisposition to susceptibility to infection already exists in the newborn. However, the symptoms do not always appear immediately after birth, but often later in life.
- Secondary immunodeficiency: More frequently, a person acquires immunodeficiency in the course of their life. This can be caused, for example, by tumor diseases, infections (e.g. HIV) or drugs that suppress the immune system.
The weakness of the immune system usually manifests itself in the form of repeated, often more persistent and longer than usual infectious diseases. Pathogens have an easy time of it if the body’s immune system is not functioning properly.
Primary immunodeficiencies – many different clinical pictures
The majority of primary immunodeficiencies are inherited. Parents therefore pass on the faulty genes to their children. To date, more than 350 clinical pictures are known that are classified as primary immunodeficiencies. They can affect different parts of the immune system, such as the various subgroups of white blood cells like lymphocytes or phagocytes, antibodies or the complement system.
Some examples:
- Combined T and B cell defects: Severe Combined Immunodeficiency (SCID)
- Immunodeficiencies in which an antibody deficiency is in the foreground: Hypogammaglobulinemia, agammaglobulinemia, variable immunodeficiency syndrome (CVID), IgG subclass deficiency and IgA deficiency
- Defects in phagocyte count and function (phagocytes): Septic/chronic granulomatosis (CGD), Severe chronic neutropenia
- Other immunodeficiencies: e.g. autoinflammatory syndromes, DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia/Louis-Bar syndrome
Treatment varies from immunodeficiency to immunodeficiency. For example, precautionary shielding against infections, for example with antibiotics or other anti-infectives, is used. Immunoglobulin infusions are used in cases of antibody deficiency. A stem cell transplant may be indicated for very severe immunodeficiencies. A blood stem cell transplant is carried out at the USZ by an interdisciplinary team of experts with representatives from the fields of hematology, pediatrics, infectiology and immunology.
Immunodeficiency – frequency and age
Congenital immunodeficiencies are rare. In Switzerland, approximately one in 1,000 people is affected by a milder form of congenital immunodeficiency. A severe form affects around one in 10,000 people. Secondary immunodeficiencies, on the other hand, are more common.
Immunodeficiencies can become noticeable in childhood and adolescence, but can also become manifest in adulthood. In the case of primary immunodeficiencies, up to 50 percent of patients are over 25 years old at the time of diagnosis.
Immunodeficiency: causes are congenital or acquired
The immune system consists of different systems that complement each other in their work. These include white blood cells, phagocytes, antibodies (immunoglobulins) and the complement system. The latter consists of more than 25 proteins that circulate in the blood plasma and are an important part of the innate defense system. The immunodeficiency can affect one or more of these systems.
Primary immunodeficiencies: Causes
The cause of primary immunodeficiencies lies in the genes, so the disease is usually inherited. Sometimes, however, the gene mutation occurs spontaneously in the course of life.
Secondary immunodeficiencies: Causes
In this case, a person is not born with immunodeficiency, but acquires it in the course of their life. The causes can be different:
- Tumor diseases, especially of the hematopoietic system such as leukemia or lymphoma
- Infections (e.g. HIV, measles)
- Medication, e.g. immunosuppressants (drugs that suppress the immune system, e.g. after an organ transplant), cytostatics (chemotherapy for cancer), glucocorticoids (e.g. cortisone, which reduces inflammation and slows down the immune system)
Symptoms: Immunodeficiency causes infections
The symptoms of an immunodeficiency depend on the type of immunodeficiency and how severe it is. Some sufferers only experience mild symptoms or none at all, so that the disease is only suspected in adulthood. In other cases, however, the immunodeficiency becomes apparent at an early stage. They have very severe and serious symptoms that can even be life-threatening.
The most important symptom of primary and secondary immunodeficiency is increased susceptibility to infections. If the immune system’s effectiveness is reduced, pathogens such as bacteria, viruses, fungi or parasites have an easier time of it. They penetrate the body, multiply and cause discomfort. These include, for example, fever, cough, nausea and vomiting or diarrhea.
- A typical feature of immunodeficiency is that infections occur more frequently,
- last longer,
- are more severe and are often associated with complications.
Doctors have developed various criteria for children and adults that are considered alarm signals for a primary immunodeficiency. To make matters worse, immunodeficiencies often do not occur alone, but in combination with autoimmune reactions.
Congenital immunodeficiency in children: Ten warning signs and symptoms
- Two or more pneumonia cases per year
- Two or more severe sinus infections or more than eight middle ear infections per year
- Two or more serious infections per year, e.g. meningitis and bone marrow inflammation
Permanent plaque in the mouth due to fungi or infestation of other skin areas after the first year of life
- Recurrent infection with pathogens that are normally harmless, such as atypical mycobacteria
- Repeated deep skin and organ abscesses (accumulations of pus) or chronic redness on the hands and feet of babies
- Taking antibiotics that do not bring about any significant improvement even after two months
- Primary immunodeficiencies in the family
- Illnesses that occur after live vaccinations, for example against measles, chickenpox, polio or rotaviruses
- Failure to thrive – low growth and body weight
Primary immunodeficiency in adults: Six warning signs and symptoms
- Four or more infections per year that doctors had to treat with antibiotics. Examples: Otitis media, bronchitis, sinusitis or pneumonia
- Recurrent infections or prolonged treatment with antibiotics for an infection
- Two or more serious bacterial infections, e.g. osteomyelitis, meningitis, sepsis
Two or more cases of pneumonia diagnosed by a radiologist within three years
- Infection with an unusual pathogen or at a rare site
- Primary immunodeficiency in the family
Always consult a doctor if you experience such symptoms. This could be due to a primary immunodeficiency.
Immunodeficiency: diagnosis with us
The diagnosis of an immunodeficiency is not easy, even for doctors. This is because primary immunodeficiencies in particular comprise a variety of different manifestations that are not always easy to classify. Added to this is the enormous number of possible causes. In addition, primary immunodeficiencies are comparatively rare. As a result, many doctors hardly ever have to deal with them in their day-to-day practice and have little experience with them. Many sufferers are therefore diagnosed with immunodeficiency at a late stage. With the Department of Immunology, the USZ has the necessary expertise. The first port of call should be an immunologist. Depending on your symptoms, you can also consult your family doctor. Lung specialists, ENT specialists and pediatricians are also eligible.
The diagnosis of an immunodeficiency always begins with the medical history (anamnesis). We ask you or the parents the following questions, for example:
- What are the symptoms?
- How long have the complaints existed?
- How intensively are they pronounced?
- In which parts of the body do the symptoms appear?
- Are more frequent infections known? Which (e.g. middle ear, sinus or lung infection)? How often per year?
- Have you or your child been taking antibiotics for a long time that were not effective enough?
- Are there any known underlying illnesses, for example an allergy, atopic disease or autoimmune disease?
- Are there immunodeficiencies in the family?
- Do you or your child take medication regularly? If yes: Which (e.g. immunosuppressants, glucocorticoids) and since when?
We base your questions on the list of warning signs for children and adults.
Primary immunodeficiencies: Diagnosis using ELVIS and GARFIELD
The abbreviation “ELVIS” also helps us to diagnose an immunodeficiency:
- E = Pathogen: Infections with unusual pathogens, e.g. pneumonia caused by the fungus Pneumocystis jirovecii or the cytomegalovirus (CMV), blood poisoning caused by Candida (yeast fungi), intestinal or biliary tract infection caused by cryptosporidia or microsporidia (both are unicellular parasites)
- L = Localization: Infections that affect different parts of the body or change location more frequently. Atypical localizations also provide clues. Examples: Brain abscess caused by molds (Aspergillus spp.) or liver abscess caused by Staphylococcus aureus.
- V = course: A protracted course of infection or, if treatment with antibiotics does not work, can be important for the diagnosis. Complications following live vaccinations with an attenuated pathogen also provide indications, e.g. a measles-mumps-rubella, chickenpox or rotavirus vaccination.
- I = Intensity: Severe “major infections” are pneumonia and meningitis, blood poisoning or bone and bone marrow inflammation. Minor infections”, on the other hand, include middle ear and sinus infections, bronchitis or superficial skin abscesses. Major infections occur more frequently with a primary immunodeficiency.
- S = sum – number of infections. They must have been diagnosed in an X-ray examination.
The abbreviation “GARFIELD” helps us to diagnose a congenital immunodeficiency if there is no increased susceptibility to infection, but you still suspect it:
- G = Granulomas (nodules in the tissue)
- A = Autoimmunity – the body is unable to recognize its components as “endogenous” and classifies them as “foreign”
- R = recurrent (recurring)
- F = Fever
- E = unusual eczema
- L = Lymphoproliferation (excess of lymphocytes)
- D = chronic intestinal inflammation
Diagnose immunodeficiency: Further examinations
This is usually followed by a physical examination, during which we check the condition of various organ systems. Examples are:
- Skin, mucous membranes
- Hair, nails
- Bones, teeth
- Airways
- Heart and blood vessels
- Gastrointestinal tract
In some cases, molecular genetic testing is helpful to identify altered genes. However, a genetic test is always preceded by a detailed consultation.
Immunodeficiency: prevention, early detection, prognosis
You cannot prevent a congenital immunodeficiency because genes play a major role here. And you cannot influence this. Sometimes the causes are not yet known, which is why preventive measures would not be effective.
Prevention is also virtually impossible in the case of secondary immunodeficiencies. This is because other diseases such as tumors and infections or the intake of medication are often the cause.
Special measures for the early detection of an immunodeficiency are not known. Doctors are discussing newborn screening in order to diagnose and treat particularly severe cases of congenital immunodeficiencies in good time. This includes, for example, severe combined immunodeficiency (SCID), which is quickly fatal without therapy.
Otherwise, the general advice is: always consult a doctor yourself or with your child if frequent infections occur that are also protracted and severe.
Course and prognosis of immunodeficiency
The course and prognosis of an immunodeficiency cannot be generally predicted. The type of immunodeficiency and how severe it is play a role. The course of the disease can vary greatly from person to person, as sometimes residual functions of the immune system remain. In this case, the body can defend itself against pathogens to a certain extent and the course is less severe.
In addition, some immunodeficiencies, such as antibody deficiency, can be treated well. Then the prognosis is favorable. However, primary immunodeficiencies are not yet curable.
Some congenital immunodeficiencies are so severe that they quickly become life-threatening and can be fatal if not treated quickly. The most severe form of congenital immunodeficiency is severe combined immunodeficiency (SCID). Without a bone marrow transplant, babies suffer life-threatening infections and often do not survive the first year of life.
In the case of secondary immunodeficiencies, the underlying disease (e.g. cancer, HIV/Aids) has a significant influence on the course and prognosis. The chances of survival also depend on this.
Immunodeficiency: treatment depends on the type and severity
The treatment of an immunodeficiency depends on the type and severity of the immunodeficiency. It is always important that doctors who have experience with immunodeficiencies treat the disease. With the Department of Immunology, the USZ has the necessary expertise. If necessary, specialists from other disciplines such as internal medicine are consulted. There is currently no cure for congenital immunodeficiency. But there are several treatment options, which we sometimes combine with each other.