What is the recommended approach to determine if a patient is immunocompromised?

Determining Immunocompromised Status

Identify immunocompromised patients through a systematic evaluation of medical history focusing on specific conditions and medications, combined with targeted laboratory testing when the diagnosis is uncertain. 1

Definition and Classification

An immunocompromised host is a patient with an impaired or weakened immune system that prevents normal response to infections. 1

Primary Categories to Identify

Congenital Conditions:

• T-cell or B-cell defects 1
• Macrophage dysfunctions 1
• Present in newborns, children, and adults 1

Acquired Conditions:

1. HIV/AIDS patients - particularly those who have developed AIDS 1

   • HIV patients with CD4 count >200 cells/mm³ have mortality similar to general population 1
   • Lower CD4 counts and higher viral loads predict worse outcomes 1

2. Hematologic malignancies 1

3. Combined immunodeficiency states - patients with intrinsic immune conditions PLUS one of the following:

   • Solid malignancy 1
   • Solid organ transplant recipients 1
   • Inflammatory/rheumatologic disease 1
   • Concurrent use of immunomodulatory drugs or chemotherapy 1

4. Any physiologic or pathologic condition accompanied by immunodeficiency 1

Practical Approach to Identification

Step 1: Medication History Review

Identify patients on immunosuppressive medications:

• Current steroid therapy or steroid use within the past year 1
• Azathioprine (associated with severe leukopenia, thrombocytopenia, pancytopenia, and bone marrow suppression) 2
• TNF-α blockers 2
• Other immunomodulatory drugs or chemotherapy 1

Step 2: Disease History Assessment

Screen for conditions causing immunodeficiency:

• HIV infection status and CD4 count if known 1
• History of organ transplantation 1
• Active cancer, particularly hematologic malignancies 1
• Autoimmune or inflammatory diseases requiring immunosuppression 1

Step 3: Laboratory Evaluation When Diagnosis Uncertain

Initial screening tests:

• Complete blood count with differential (identify leukopenia, neutropenia, lymphopenia) 1
• Absolute neutrophil count (ANC <500 cells/μL indicates severe neutropenia) 3
• Serum immunoglobulin levels (IgG, IgA, IgM) 4
• Lymphocyte subset enumeration (CD4, CD8 counts) 4

Advanced testing for suspected primary immunodeficiency:

• Specific antibody titers in response to vaccines 4
• Functional lymphocyte testing 4
• TPMT (thiopurine S-methyl transferase) and NUDT15 (nucleotide diphosphatase) deficiency testing in patients with severe myelosuppression on azathioprine 2
• Genetic testing via Sanger sequencing or next-generation sequencing for monogenic disorders 4

Step 4: Severity Stratification

Classify immunodeficiency severity (mild to severe) based on:

• Degree of neutropenia 1
• CD4 count in HIV patients 1
• Extent of bone marrow suppression 2
• Number and type of immunosuppressive medications 1

Critical Clinical Pitfalls

Do not rely on normal clinical presentation to exclude immunocompromised status:

• Clinical signs become less reliable as immunocompromise worsens 1
• Fever, leukocytosis, and peritonitis may be mild or absent even with severe infection 1
• Laboratory tests may not accurately reflect disease severity 1

Recognize hidden immunocompromised states:

• Many ICU patients with no apparent immunosuppression harbor underlying conditions altering immune response 5
• ICU-acquired immune deficiencies develop from sepsis, trauma, or major surgery 5
• Secondary immunodeficiency is rising due to increased use of immunosuppressive drugs 4

Special Considerations

For HIV patients specifically:

• Always measure CD4 count and viral load when evaluating for surgery 1
• Consider HIV-specific surgical diseases (abdominal tuberculosis, Mycobacterium avium complex) 1

For patients on azathioprine:

• Monitor complete blood counts weekly during first month, twice monthly for months 2-3, then monthly 2
• Consider TPMT/NUDT15 deficiency testing if severe myelosuppression develops 2

For transplant recipients:

• Hematologic toxicities may be more severe during homograft rejection 2