ALTHOUGH Primary Immunodeficiencies (PID or just PI) affect the same number of individuals as haemophilia, it is likely that many will be less familiar PID, while the majority will have some recollection of haemophilia due to it affecting several members of the European Royal families at the turn of the 20th Century.

Admittedly, with 4,300 patients registered on the UK Primary Immunodeficiency database, numbers are small. It is estimated that PIs affects about 5,000 in England and Wales in total.

However, the number of distinct Primary Immunodeficiencies is somewhere in the region of four hundred, such that individual conditions can be so rare as to only affect one or two persons worldwide.

The immune system is responsible for fighting infection, as well as destroying faulty cells, which if left unchecked may develop into cancer. Any disorder of this highly complex system is termed an immunodeficiency.

Immunodeficiencies are divided into primary, the focus of this article, and secondary. PIs are typically due to one or more faulty genes. These can occur spontaneously, called “de novo”, or as a result of the faulty gene being inherited from a parent. Often if one faulty gene is inherited, it is overridden by the normal gene from the other parent. The chances of inheriting two faulty genes are greatly increased if parents are closely related, for example cousins.

Secondary or acquired immunodeficiencies can be due to illness, or treatment such as chemotherapy. Acquired Immunodeficiency Syndrome (AIDS), is the result of untreated or uncontrolled HIV. There is no overlap between Primary and Secondary Immunodeficiencies; primary cannot lead to secondary. Our immune system also weakens with age as well as certain lifestyle choices, notably excess alcohol.

The spectrum and severity of PIs range from those diagnosed very soon after birth, to conditions which may take several years to pick up, and where the sufferer is only vulnerable to certain bugs.

According to Immunodeficiency UK (www.immunodeficiencyuk.org), features that should raise suspicion are frequent bouts of severe infection that take longer to clear, often require more aggressive treatment in the form of intravenous antibiotics, and involve unusual bugs, referred to medically as “causative organisms”.

The SPURR tool is useful sieve for doctors when considering PI as a potential diagnosis. Infections are typically Severe, Persistent, Unusual, Recurrent, and there is a history of PI in the person’s family.

Many PIs in children are discovered by paediatricians. In addition to recurrent infections, failure to thrive is an important sign to consider, although the majority of cases of failure to thrive are not due to PI.

It is estimated that delay in the diagnosis of PI may be anywhere between four to ten years in “milder” cases, due to PI being thought of. In addition, patients are often seen by multiple healthcare providers rather than a dedicated clinician. There is also ambiguity over what is a normal number of infections to have in any given time period. Unfortunately, during the delay in diagnosis, permanent damage can be done.

If you feel you may have PI, it is certainly worth raising this concern with your routine GP. A set of blood tests is the first step, with referral to an immunologist if appropriate.

The treatment of PIs is wide-ranging and an ever-advancing field. Single gene faults may be treated with gene therapy, where a healthy gene is inserted to replace the defective one. PIs due to a reduced number of antibodies, or reduced antibody function can be treated with intravenous drugs. In some areas these can be offered in the person’s own home.

If left undiscovered PI has the potential to cause significant harm. However, if picked up and treated, patients can hope to have a good quality of life, which will be further enhanced by sensible lifestyle choices.

The British Society for Immunology (BSI) advocates that individuals with an immunodeficiency should have any of the three Covid vaccines currently available in the UK. None of these vaccines contain the active virus, or any part thereof. Although there may be concern about potential harm as a result of the vaccine, BSI advise this should not be a worry, but that those with a reduced immune system may not mount the same response as those with a health immune system. As a result, levels of protection would be less. However, this would still be better than forgoing immunisation. Currently they recommend having both doses at the appropriately spaced interval.

“The number of distinct Primary Immunodeficiencies is somewhere in the region of four hundred, such that individual conditions can be so rare as to only affect one or two persons worldwide”

“If you feel you may have PI, it is certainly worth raising this concern with your routine GP. A set of blood tests is the first step, with referral to an immunologist if appropriate”.

“The British Society for Immunology (BSI) advocates that individuals with an immunodeficiency should have any of the three Covid vaccines currently available in the UK”.

USEFUL WEBSITES:

www.immunology.org

www.immunodeficiencyuk.org

www.ukpin.org.uk