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Diagnosing primary immunodeficiency

No matter your specialty, you may have patients with undiagnosed primary immunodeficiency (PI).

Are you missing patients with PI?

Primary immunodeficiencies (PIs), also known as inborn errors of immunity (IEI), are a group of 450+ rare and chronic disorders caused by genetic variants. Patients average 9-15 years from symptom onset to diagnosis and experts estimate that >70% of individuals with a PI remain undiagnosed. 

Because those with PI can have a variety of symptoms that are not specific to one organ, they tend to see multiple specialists while seeking a diagnosis. You can be the provider that puts the picture together and makes a difference.

Does your patient have...

  • Infections that are frequent, persistent, unusual, and/or difficult to treat? 
  • Unusual complications of common infections? 
  • Unusual autoimmunity? 
  • Enlarged lymph nodes that persist and/or hepatosplenomegaly? 
  • Failure to thrive (including adults)? 
  • Non-healing skin ulcers?  
  • Recurrent fevers with no source?

Download flyer for primary care.

Get a medical kit

Be prepared to treat a zebra with our free medical kit:

  • A poster, pens, and stickers for your waiting room.
  • Patient & Family Handbook.
  • Diagnostic & Clinical Care Guidelines.
  • Guide to Ig Therapy.
  • An IDF brochure, along with other resources for children, parents, and adult patients to learn about their immune system and PI and find support. 
Order your kit

Additional signs and symptoms by specialty

Dermatology

  • Extensive warts or molluscum contagiosum. 
  • Recurrent boils.  
  • Herpes simplex, extensive or chronic. 
  • Mucocutaneous candidiasis.  
  • Severe atopic dermatitis in setting of recurrent infections.

Download dermatology flyer.

Ear, nose, & throat

  • Recurrent sinus infections without anatomic abnormality. 
  • New onset recurrent otitis media in teens and adults.  
  • Thrush (culture-positive) outside of infancy.

Download ENT flyer.

Gastroenterology

  • Candida esophagitis without predisposing factors.  
  • ‘Celiac disease’ that is not gluten sensitive. 
  • Villous atrophy without etiologic explanation.  
  • Inflammatory bowel disease with onset <6 years of age. 
  • Nodular lymphoid hyperplasia that is extensive.  
  • Liver abscess.  
  • Nodular regenerative hyperplasia of the liver. 
  • Absence of plasma cells on biopsy.

Download gastroenterology flyer.

Hematology/Oncology

  • Recurrent or refractory autoimmune cytopenias. 
  • Very early thrombocytopenia that does not resolve. 
  • Cytopenias in combination with infections or with positive family history. 
  • Monocytopenia. 
  • Hemophagocytic lymphohistiocytosis. 
  • Lymphomas in unusual primary sites.

Download hem/onc flyer.

Hepatology

  • Nodular regenerative hyperplasia.  
  • Recurrent liver failure or family history of liver failure. 
  • Veno-occlusive disease without bone marrow transplant. 
  • Infantile acute liver failure. 
  • Liver abscess.

Download hepatology flyer.

Infectious disease

  • Opportunistic infection. 
  • Infection of unusual severity. 
  • Recurrent infections. 
  • Deep-seated infections of lung, liver, or bone in infancy or early childhood.

Download infectious disease flyer.

Pulmonology

  • Recurrent pulmonary infections particularly with unusual organisms. 
  • Bronchiectasis.  
  • Pneumatocele. 
  • Nodular lymphoid hyperplasia of the bronchi. 
  • Unexplained ground glass opacities, interstitial lung disease, and/or pulmonary granulomas.

Download pulmonology flyer.

Rheumatology

  • Systemic lupus erythematosus with onset <6 years of age (early onset lupus). 
  • Multiple autoimmune conditions at the same time. 
  • Infections out of proportion to the degree of immunosuppressive treatment.

Download rheumatology flyer.

Misconceptions about PI

Primary immunodeficiencies are not just pediatric disorders; ~75% of patients are diagnosed as adults.

Not all primary immunodeficiencies are life-threatening, many are mild or moderate and patients don't 'look' sick.

Start a diagnostic workup

  1. Collect a detailed patient history, including family history. 

    Patient history: infections (site, organism, frequency, and severity), any malignancy or lymphoproliferation, frequency and severity of any autoimmune or autoinflammatory symptoms, failure to thrive, or unintentional weight loss. 

    Family history: diagnosed PI, early childhood deaths, family members with PI-like symptoms.

  2. Order complete blood count with differential and compare absolute counts of lymphocytes, neutrophils, eosinophils, and monocytes to age-adjusted reference ranges.

  3. Order serum immunoglobulin (Ig) test to assess the patient’s overall IgG, IgA, and IgM levels, and antibody titers to vaccine antigens.

    Some patients with PI lack functional antibodies, which can be masked by normal overall serum Ig levels. Titers to tetanus toxoid and/or pneumococcal conjugate vaccine measure specific antibody response.

  4. Consider referral to an immunologist/allergist even if initial diagnostic labs appear normal.

Consulting Immunologist Program

Healthcare providers can connect for free with an immunologist specializing in PI to go over the diagnosis, treatment, or management of patients with PI.

Submit your request

Tell your patients about us

If your patient has been diagnosed with PI, encourage them to check out IDF through our website and social media accounts. By joining the IDF community, patients and families can access resources, educational opportunities, a community of support, and so much more.

Doctor talking to a patient.

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This page contains general medical and/or legal information that cannot be applied safely to any individual case. Medical and/or legal knowledge and practice can change rapidly. Therefore, this page should not be used as a substitute for professional medical and/or legal advice. Additionally, links to other resources and websites are shared for informational purposes only and should not be considered an endorsement by the Immune Deficiency Foundation.

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