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Health condition

APDS (PI3K delta)

Activated PI3K-delta syndrome (APDS) is a genetic overactivation of a key lymphocyte growth signal, causing recurrent chest infections, persistent EBV and CMV, enlarged lymphoid tissue and bronchiectasis - and it now has a licensed targeted therapy, leniolisib.

Why trust this guide

  • 01

    Editorial team

    Written by our editorial team from the UK sources listed on each page.

  • 02

    Sourced from guidance

    Checked against current NHS and UK specialist society guidance at the time of review.

  • 03

    Current for 2026

    Reviewed on 2026-09-27 with the next review scheduled for 2027-09-27.

Key facts

The essentials at a glance.

The symptoms to recognise, when to seek help, which specialist to see, and what treatment usually involves.

  • Gain-of-function variants in PIK3CD (APDS1) or regulatory-subunit loss in PIK3R1 (APDS2) leave the PI3K-delta pathway stuck 'on'

  • The pattern: recurrent bacterial respiratory infections from childhood, early bronchiectasis, big tonsils/adenoids/nodes/spleen, and trouble controlling herpes-family viruses (EBV, CMV)

  • Antibody profiles are deceptive: IgM often raised while IgG and IgA fall - easily misfiled as hyper-IgM or CVID

  • Lymphoma risk is increased, so persistent asymmetric node growth warrants biopsy

  • Leniolisib, a selective PI3K-delta inhibitor, is licensed for APDS and corrects the overactive signal; sirolimus, immunoglobulin replacement and transplant remain options

Understanding the condition

What it is and what happens next.

What causes it, how it is diagnosed, and the treatment routes available in the UK.

What it is and how it feels

PI3K-delta tells lymphocytes when to grow and multiply; in APDS the accelerator jams. Paradoxically, cells driven constantly toward activation exhaust themselves - senescent T cells lose their grip on EBV and CMV, B cells skew away from mature antibody production - so the child or adult suffers both ordinary bacterial infections and smouldering viral ones, while lymphoid tissue everywhere hypertrophies. Airway damage arrives early; many patients have bronchiectasis by their twenties, and repeated ENT surgery for regrowing adenoids and glue ear is a recurring theme in the histories.

Diagnosis and treatment routes

Recognising APDS among 'CVID' and 'hyper-IgM' populations became genuinely consequential when targeted therapy arrived: leniolisib normalises the pathway, shrinking lymphadenopathy and improving immune profiles in trials, layered onto established care - immunoglobulin replacement, antibiotic prophylaxis, airway clearance, EBV monitoring and lymphoma vigilance, with transplant for selected severe cases. Gene panel testing makes the diagnosis. If lifelong chest infections travel with big lymphoid tissue and stubborn viruses in your history, ask about genetic testing; private immunology review is typically available within about two weeks.

Seeing a specialist

Who to see, and how quickly you can be seen.

The specialist for this condition is usually a consultant clinical immunologist. Your GP can refer you on the NHS, or you can arrange a private consultation directly.

A quiet reminder

This guide is for information, not medical advice.

Your GP knows your history and can tell you which parts apply to you. If in doubt, see them - and seek urgent care for any of the emergency symptoms described above.

Frequently asked

Common questions about APDS (PI3K delta).

Quick, plain-English answers to what people ask us most.

  • What is APDS (activated PI3K delta syndrome)?

    APDS is a rare inherited immune disorder caused by overactivity of a specific enzyme pathway (PI3K delta), leading to recurrent infections, immune dysregulation, and an increased risk of certain lymphomas.

  • What causes APDS?

    It is caused by specific genetic mutations that lead to overactivation of the PI3K delta enzyme pathway, disrupting normal immune cell development and function.

  • What are the symptoms of APDS?

    Symptoms include recurrent respiratory and other infections, enlarged lymph nodes and spleen, autoimmune complications, and an increased risk of developing certain lymphomas over time.

  • Is APDS dangerous?

    Yes, it can cause significant, recurrent infections and complications including an increased lymphoma risk, requiring ongoing specialist immunology monitoring and management.

  • Is APDS genetic?

    Yes, it is an inherited condition, typically following an autosomal dominant pattern, meaning an affected parent has a 50% chance of passing it to each child, though new mutations can also occur.

  • Can APDS be treated?

    Yes, treatments including specific targeted medications that inhibit the overactive PI3K delta pathway, along with immunoglobulin replacement and management of infections, can significantly help control the condition.

  • How is APDS treated?

    Treatment may include regular immunoglobulin replacement therapy to reduce infection risk, targeted PI3K delta inhibitor medications where available and appropriate, and prompt treatment of infections as they arise.

  • How is APDS diagnosed?

    Diagnosis typically involves genetic testing to confirm the specific mutation, alongside clinical assessment of infection history, lymph node and spleen findings, and relevant immune function blood tests.

  • APDS vs common variable immunodeficiency — what's the difference?

    Both cause recurrent infections and immune dysfunction, but APDS is specifically caused by an identified genetic mutation affecting the PI3K delta pathway, confirmed by genetic testing, and has some distinct additional features like lymphoproliferation and specific lymphoma risk not typical of common variable immunodeficiency.

  • When should I see a doctor about possible APDS, and how quickly can I be seen privately?

    See a doctor for recurrent infections with enlarged lymph nodes or spleen, particularly with a relevant family history. NHS immunology referral can take several weeks, while private specialist assessment is often available within about two weeks.