Non-infectious complications of PIDs

The human immune system has many overlapping layers of defences. These include a diverse collection of cells, proteins, tissues and organs. Normally these all interact in a complex and intricately balanced way to maintain health and fight off infection. However, the genetic abnormalities that cause primary immune deficiency disorders (PIDs) can, in certain circumstances, upset this delicate balance. When this happens, parts of the immune system can become overactive, poorly regulated or directed, which can lead to development of complications (see below) such as inflammation, allergy, autoimmune disease or, rarely, cancer.

So, having a PID does not just cause an increased risk of infections; it can result in other health problems. These include where a person’s immune system:

  • Starts attacking the body’s own cells and tissues. Disorders, where this happens, are known as autoimmune diseases. One example of this is the abnormal production by the body of antibodies that can attack and kill red blood cells. This would cause a person to have anaemia.

Read our section on autoimmunity and PID.

  • Reacts to normally harmless substances that surround us every day. These are called allergies but can also be referred to as hypersensitivities. A common allergy that many people have heard of is an allergy to pollen. This causes hay fever.

Read our section on allergy and hypersensitivity.

  • Produces unusual forms of inflammation by forming organised clumps or nodules of immune cells in tissues or organs of the body. This is known as granulomatous disease. The nodules may cause discomfort and pain, and/or interfere with the working of the body’s organs and tissues.

Read our section on granulomatous disease and PID.

  • Is poorly regulated or directed and does not deal effectively with specific kinds of triggers which can, in some circumstances, lead to development of a range of cancers.

Read our section on cancer and PID.

In summary, disease and tissue damage in PIDs can happen as a result of infections, an unbalanced immune system or a combination of both. The sections below take you through how these complications are diagnosed and treated.

This page was reviewed by the Medical Advisory Panel, April 2018.

The earlier the non-infectious complications, such as autoimmunity, allergy, granulomatous disease and cancer, in primary immunodeficiency are picked up and diagnosed the better. This ensures appropriate and timely treatment is given, and helps to improve health outcomes. So an awareness and understanding of these conditions is important. You can do your part by alerting your healthcare team to any worsening of your health or any new problems you may have developed.

When you see the doctor he/she will want to know what your symptoms are and how they affect your health. This is referred to as taking a clinical history. The doctor will be particularly interested in any newly developing symptoms. These provide useful clues for doctors to help in their investigations and diagnosis. The doctor will also want to carry out a full physical examination. Depending on the particular disease complication you may have, the doctor may decide to do some further tests.

Some of the tests you may expect can include:

  • Culture of sputum or fluids. This is important because the doctor needs to first of all rule out if the problems are caused by an underlying infection or not
  • Blood tests
  • Urine/stool tests
  • Imaging/radiology. These include X-rays, ultrasound, CT/MRI scans
  • Biopsy of affected tissues
  • Pulmonary function tests. These are breathing tests that help find out if your lungs are working well
  • Skin tests. These are most useful for the diagnosis of allergy.

The treatment your doctor gives will depend on the condition you have, how severe it is and if there are special, individual reasons for choosing a particular kind of treatment. This may depend on the type of primary immunodeficiency (PID) you have, the kinds of complications you have developed and any problems you have had in the past with previous drugs or treatments.

Some conditions such as simple allergies like hay fever, or relatively straightforward autoimmune diseases can be managed quite easily. For example, anti-histamine drugs can be used to treat hay fever or allergic skin disease, or thyroid hormone replacement can be used for autoimmune thyroid disease. In many cases the treatments given will be the same as those for people who don’t have a PID.

Use of immunosuppressant drugs

Complicated health problems associated with granulomatous disease or more severe autoimmune diseases might need medicines that reduce the strength of the immune system. These medicines are called immunosuppressants. They help shut down the unwanted immune response that is causing the problem. Some examples of these drugs are corticosteroids and azathioprine.

It is a difficult balancing act for the doctor to get the dose, or amount, of these medicines just right to treat people with PIDs. This is because those affected already have immune systems that are not working properly. The doctor has to choose a dose that will work and not cause unwanted side effects from the drugs, at the same time as not putting the individual at more risk of getting infections. This means it can take some time to find the right dose which balances the best outcomes with the least risk of side effects.

Who takes care of these complications?

An immunologist working with doctors from other specialist teams will often make the decisions on what treatments are best. These multi-disciplinary teams will incorporate the expertise needed to treat disease in the specific tissue or organ affected. These teams might include doctors who look after your:

  • Lungs  respiratory physicians
  • Gut  gastroenterologists
  • Joints  rheumatologists
  • Skin  dermatologists
  • Blood  haematologists
  • Kidneys  nephrologists
  • Ear, nose and throat – ENT specialists
  • Cancer – an oncologist or a haematologist depending on the type of cancer involved.

Your doctor will talk through what treatment options might work for you and what benefits could be achieved. The aim is to try and achieve a good outcome by keeping you healthy and maintaining your quality of life.

All treatments have pros and cons. Your doctor will be happy to discuss these with you. Remember that it’s OK to ask questions about the treatment options your doctor proposes.

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