APDS Diagnosis for Hematologists & Oncologists

Hematologists/oncologists may encounter patients with primary immunodeficiencies like APDS with the following manifestations:

Lymphoproliferation¹

Includes lymphadenopathy, splenomegaly, hepatomegaly, and/or nodular lymphoid hyperplasia

Autoimmune Cytopenias²

A substantial portion (>15%) of patients with autoimmune cytopenias have underlying primary immunodeficiencies such as APDS³
Patients with primary immunodeficiencies are at a much higher risk for autoimmunity³
- Autoimmune cytopenia: 120x higher
- Pediatric autoimmune hemolytic anemia (AIHA): 830x higher
- Immune thrombocytopenic purpura (ITP): 60x higher³

Malignancy (primarily Lymphoma)⁴

Lymphoma was the initial diagnosis for 21% of patients with APDS⁵
Risk of lymphoma is 8–10x higher among patients with primary immunodeficiencies⁶
Lymphoma treatment failure could indicate a primary immunodeficiency⁷

Clinical Suspicion

Recurrent or refractory ITP or AIHA
Adenopathy or splenomegaly
Multiple autoimmune cytopenias
Unusual lymphoma presentation (e.g. in children)

Genetic Testing

Primary immunodeficiency genetic panel

APDS can resemble autoimmune lymphoproliferative syndrome (ALPS) and should be considered a differential diagnosis.⁸

Lymphadenopathy, splenomegaly, cytopenias, and lymphoma are common manifestations of both APDS and ALPS. Physicians of patients with probable but not definitive ALPS may consider referring to an immunologist for genetic testing, or ordering a primary immunodeficiency genetic testing panel.⁸

Genetic testing may reveal underlying primary immunodeficiencies.

In a study of 80 patients with pediatric Evans syndrome, 40% were discovered to have variants in genes involved with primary immunodeficiency.⁹

Learn about a sponsored
genetic test and counseling for APDS.

Eligibility requirements apply.

Not actual patients

APDS is inherited in an autosomal dominant pattern, meaning that a person needs a pathological variant from only one parent to have it themselves.

However, APDS may be difficult to trace based on clinical history as symptoms can vary even within the same family.

As there is a 50% of chance of APDS being passed from parent to child, family members of patients with APDS should also be genetically tested.

Family members of diagnosed APDS patients should also be genetically tested for APDS.

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1. Coulter TI, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597–606.e4. 2. Redenbaugh V, Coulter T. Disorders related to PI3Kδ hyperactivation: Characterizing the clinical and immunological features of activated PI3-kinase delta syndromes. Front Pediatr. 2021;9:702872. 3. Fischer A, et al. Members of the CEREDIH French PID study group. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140(5):1388–1393.e8. 4. Elkaim E, et al. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study. J Allergy Clin Immunol. 2016;138(1):210–218.e9. 5. Jamee M, et al. Clinical, immunological, and genetic features in patients with activated PI3Kδ syndrome (APDS): A systematic review. Clin Rev Allergy Immunol. 2020;59(3):323–333. 6. Mayor PC, et al. Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry. J Allergy Clin Immunol. 2018;141(3):1028–1035. 7. Shapiro RS. Malignancies in the setting of primary immunodeficiency: Implications for hematologists/oncologists. Am J Hematol. 2011;86(1):48–55. 8. Bride K, Teachey D. Autoimmune lymphoproliferative syndrome: More than a FAScinating disease. F1000Res. 2017;6:1928. 9. Hadjadj J, et al. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood. 2019;134(1):9–21.