Primary immunodeficiency: signs, tests and treatment

PIDs are conditions in which parts of the immune system are missing or not working. Immunodeficiency UK explains that this leaves reduced or no natural defence against the bacteria, fungi and viruses that surround us every day. As a result, people get infections more often than normal, may take longer to get better with antibiotics, and can find the infections keep coming back.

The word primary refers to the intrinsic, built-in nature of the problem. The charity says PIDs are caused by errors in the genes of the cells that make up the immune system, and most people are born with the condition. In some types, such as common variable immune deficiency, the specific faulty genes are not yet clear. Secondary immunodeficiency, in contrast, is caused by something else, for example HIV, chemotherapy or malnutrition.

Immunodeficiency UK explains that an international committee reviews the classification every two years, and PIDs currently fall into eight main groups based on which part of the immune system is affected. Many conditions are extremely rare, and for some fewer than ten cases have been identified.

• Combined immunodeficiencies, including severe combined immune deficiency (SCID), where many people need a bone marrow transplant early in life.

• Well-defined syndromes with immunodeficiency, such as DiGeorge syndrome and Wiskott-Aldrich syndrome.

• Predominantly antibody deficiencies, including common variable immune deficiency (CVID) and X-linked agammaglobulinaemia.

• Diseases of immune dysregulation, where the immune system cannot control certain viruses or fails to switch off.

• Phagocyte disorders, such as chronic granulomatous disease.

• Defects in innate immunity, autoinflammatory disorders (inherited fever syndromes) and complement deficiencies.

The charity says the main symptoms are frequent, repeated and long-lasting infections, and unusual infections. It also notes that PIDs can present through non-infectious complications such as autoimmunity, inflammatory problems with fevers, swollen joints, rashes and bowel problems, angioedema, and sometimes cancers, particularly lymphomas.

A memory aid is SPURR: severe, persistent, unusual and recurrent infections, with a history of PID running in the family. The ten warning signs have long been used as a screening tool, although the charity says UK clinicians are re-evaluating them. The major indicators it lists are below, and two or more could point to an underlying PID.

• A baby or child who does not gain weight or grow normally.

• Needing intravenous antibiotics to treat infections.

• A family history of PID.

• Four or more new ear infections within one year, or two or more sinus infections within one year.

• Two or more months on antibiotics with little effect, or two or more pneumonias within three years.

• Deep skin or organ abscesses, persistent thrush or fungal infection beyond six months, or two or more deep-seated infections.

When PID is suspected, the doctor reviews medical and family history and orders simple blood tests, including a full blood count and measurement of immunoglobulin levels, according to Immunodeficiency UK. If suspicion remains, more specialised tests identify the particular type. Antibody deficiencies are typed by measuring immunoglobulin levels and the number and function of B-cells.

Test immunisations can sometimes be used, with antibody response checked three to four weeks later. The charity says the earlier a diagnosis is made, the less damage is done and the easier treatment often is. It advises asking, after a serious infection, whether an underlying immune problem could explain it, and raising family screening where one relative has a PID.

Infections need prompt treatment. The charity says antibiotics, anti-fungals and sometimes antivirals are the treatments most used, and some people take them preventively. People with severe antibody deficiency may be offered immunoglobulin replacement therapy, a blood-based treatment containing antibodies that can be given intravenously or under the skin and must be given regularly. It is available subject to strict NHS eligibility criteria, and infections can still occur.

More specialised treatments include haematopoietic stem cell (bone marrow) transplant, enzyme replacement therapy, thymus transplantation and gene therapy for certain PIDs. Immunodeficiency UK notes that multidisciplinary teams led by a consultant immunologist look after people with PIDs at specialist centres in the UK, because the disorders are rare and complex.

The charity gives two golden rules: seek advice from your immunology team before any immunisation, and do not have live vaccines unless your immunologist has explicitly said it is safe. Live vaccines can cause problems because the weakened germs grow unhindered in a person whose immune system is not working normally.

Examples it gives include the nasal spray flu vaccine Fluenz, BCG and MMR, which are avoided or only given with specific advice. Most immunology centres recommend that patients, carers and close family have an injectable flu jab. The charity also says some vaccines add little for people already on immunoglobulin, and that taking preventive measures against infection plays a key role in staying well.

The effects can be wide. The charity says prolonged ill health can disrupt a child's schooling and social contacts and can make working life or family life harder for adults, and the strain of feeling isolated or caring for a sick child can take a psychological toll. Many people also live a fairly normal life with milder forms.

Practical steps include knowing your own diagnosis, keeping a record of infections and treatments, looking after your lungs, and telling any treating clinician about your condition. Patient organisations such as Immunodeficiency UK provide information, and families can take part in the UK registry. Genetic counselling is available because many PIDs are inherited, and the charity points to a booklet on genetic aspects.

A GP is usually the first stop, often after repeated infections. The charity says the majority of PIDs in children are picked up by paediatricians, and that for adults the pattern of infections is sometimes missed. A GP can arrange initial blood tests and refer to a clinical immunologist, and the British Society for Immunology lists a find-a-clinical-immunologist tool.

Immunoglobulin therapy is commissioned through the NHS under national criteria. Private immunology opinions are available for diagnosis, but the charity stresses that lifelong care is best led by a specialist centre. Seek urgent medical advice for a serious infection in someone known to have an immune problem, using 999 or NHS 111 as the situation requires.