Primary immunodeficiency
Primary immunodeficiency
Also known as:PID; PIDD; inborn errors of immunity; China Second Rare Disease Catalog item 66
Primary immunodeficiency is a large group of inherited or inborn immune system disorders that can cause recurrent, severe, or unusual infections and may also involve autoimmunity, allergy, inflammation, or cancer risk.
Start Here
A quick guide to the next step: which department to start with, what to prepare, and what to ask.
Recurrent pneumonia, sinusitis, ear infections, deep skin infections, opportunistic infections, severe vaccine reactions, or a family history of early infection deaths should be assessed by clinical immunology, pediatric immunology, or infectious disease.
PID is not one disease. It includes disorders of immune cells, antibodies, complement, or phagocyte function. Mild forms may be found in adulthood, while severe forms can cause life-threatening infant infections.
Care depends on subtype and may include prompt infection treatment, preventive antibiotics, immunoglobulin replacement, avoiding some live vaccines, and for severe forms stem cell transplant or targeted or gene therapy assessment.
Many PIDs are linked to single-gene variants with X-linked, autosomal recessive, or autosomal dominant inheritance; some remain genetically unresolved. Genetic counseling is important after diagnosis.
People may be treated repeatedly for ordinary colds, sinus infections, pneumonia, allergy, or poor constitution without the pattern of infection severity, organisms, and family history being recognized.
This page helps patients and families organize care leads. It does not replace a clinician’s diagnosis or treatment plan. For testing, medication, referrals, emergency care, and support applications, follow qualified clinicians, medical institutions, support organizations, and official sources.
Diagnosis Path
Organized around the practical patient journey: identify clues, avoid common delays, then prepare for care.
When to Suspect It
- Recurrent, severe, prolonged, or hospitalized infections, especially pneumonia, sinusitis, otitis, skin abscesses, or sepsis.
- Unusual organisms, opportunistic infection, fungal infection, disseminated BCG, or unusually severe reaction to a live vaccine.
- Autoimmune cytopenias, enteritis, eczema-like rash, granulomas, enlarged lymph nodes, or enlarged spleen in addition to infection.
- Infant thrush, chronic diarrhea, poor growth, consanguinity, early male deaths, or several relatives with severe infections.
Common Wrong Turns
- Treating each infection separately without counting infections, admissions, cultures, and antibiotic response over time.
- Repeated antibiotics or steroids without immunoglobulin, lymphocyte subset, and vaccine-response evaluation.
- Giving or catching up live vaccines before significant immune deficiency has been considered.
Departments to Start With
- Clinical immunology or allergy/immunology
- Pediatric immunology
- Infectious disease
- Hematology or rheumatology when immune dysregulation is prominent
Before the Visit
- Bring a timeline of infection sites, organisms, culture results, imaging, medicines, and hospitalizations.
- Bring vaccination records, vaccine reactions, immunoglobulins, CBCs, lymphocyte subsets, and complement results.
- Record growth, chronic diarrhea, eczema, thrush, autoimmune disease, malignancy, and lymph node or spleen enlargement.
- List early infection deaths, severe male-child infections, consanguinity, miscarriages, or known genetic diagnoses in relatives.
Tests to Ask About
- CBC with differential, IgG/IgA/IgM/IgE, lymphocyte subsets, and complement screening.
- Vaccine-specific antibody responses, oxidative burst testing, T-cell function, or NK-cell function when indicated.
- Cultures, viral loads, chest CT, and bronchiectasis assessment when lung infections recur.
- PID gene panel, exome sequencing, family confirmation, and relative screening after diagnosis.
Questions for the Doctor
- Which immune-deficiency category best fits my pattern, and which severe subtypes must be ruled out first?
- Which vaccines are safe, which live vaccines should wait, and do household vaccines need special planning?
- Do I need immunoglobulin replacement or preventive antimicrobials, and how will response be measured?
- Does this subtype have transplant, targeted treatment, gene therapy, or clinical trial options, and what is the family risk?
Basic Information
Medical Notes
More complete medical explanations are kept here for discussion with clinicians.
Symptoms
PID features depend on the immune pathway involved. Key clues are recurrent, severe, prolonged, or unusual infections such as pneumonia, sinusitis, otitis, deep skin infection, sepsis, fungal infection, or opportunistic infection. Children may also have poor growth, chronic diarrhea, persistent thrush, or delayed umbilical cord separation.
Some PIDs present mainly with immune dysregulation rather than infection alone, including autoimmune cytopenias, enteritis, eczema-like rash, granulomas, enlarged lymph nodes or spleen, allergy-like disease, and increased malignancy risk.
Diagnosis
Diagnosis starts with a detailed infection and family history, including frequency, severity, organisms, antibiotic response, vaccine reactions, growth, and autoimmune or inflammatory features.
Screening often includes CBC with differential, immunoglobulins, lymphocyte subsets, complement, vaccine antibody responses, and microbiology. Follow-up testing may assess phagocyte, T-cell, or NK-cell function, chest imaging, and genetic testing. Secondary immune deficiency from malnutrition, HIV, medicines, cancer therapy, or protein loss must also be considered.
Treatment
Care aims to prevent infections, protect organs, and manage immune dysregulation. Infections need prompt targeted treatment; some patients need preventive antibacterial, antifungal, or antiviral medicines. Antibody-deficiency disorders may need intravenous or subcutaneous immunoglobulin with monitoring of infection frequency and IgG trough levels.
Severe combined immunodeficiency, some phagocyte defects, and other high-risk forms may be evaluated for hematopoietic stem cell transplant. Selected conditions have enzyme replacement, targeted medicines, or gene therapy. Vaccine plans must be individualized, and many severe cellular immune defects require avoidance of live vaccines.
Long-term Care
Long-term care often involves immunology, infectious disease, pulmonology, gastroenterology, hematology, rheumatology, and genetics. Follow-up tracks infections, lung injury or bronchiectasis, immunoglobulin dosing, medication adverse effects, autoimmunity, inflammation, and malignancy screening.
Families should keep an emergency note listing the diagnosis, vaccine cautions, usual medicines, allergies, and specialist contacts. School and childcare planning may include fever plans, exposure management, and vaccination timing.
Fertility and Family
Many PIDs have a defined inheritance pattern. Once the causal variant is known, parents, siblings, and future pregnancies can be discussed with genetics professionals, including carrier testing, prenatal diagnosis, or preimplantation genetic testing where appropriate and available.
When to Seek Urgent Care
Urgent care is needed for persistent high fever, poor responsiveness, breathing difficulty, cyanosis, severe dehydration, altered consciousness, seizures, rapidly spreading skin infection, severe abdominal pain, or suspected sepsis. Tell the emergency team about suspected or confirmed PID and recent medicines.
Prognosis
Outlook depends on subtype, time to diagnosis, infection and organ damage, and access to treatment. Early diagnosis and prevention can greatly reduce long-term harm.