A Patient with Recurring Infections

Julia Wright, M.D.

Clinical Associate Professor of Medicine

Section of General Internal Medicine

Case Illustration

• 62-year-old woman with PMH rheumatoid arthritis, seizures and malabsorption

• Healthy before gastrectomy; recurrent hospitalizations for multiple acute issues, predominantly infectious.

• Infections are recurrent, relapsing, do not respond to outpatient management—very challenging

Evaluating the Patient with Recurrent Infections

• Criteria for “recurrent”• Causes

– Therapeutic failure: resistant organism, atypical infection

– Patient-specific: underlying structural or immunologic impairment

Case Patient’s Evaluation• Immunodeficiency suspected—recurrent sinopulmonary

infections, poorly responsive, severe, multisystem illnesses, ? Family history. Frequently neutropenic, rarely febrile

• Results of immunoglobin panel =

– IgA 138 (85-450 mg/dL)– IgG 302 (700-1600 mg/dL)– IgM 44.3 (40-230 mg/dL)

• T cell profile =

– CD4% 318 (>490)– CD8 62 (>180)– CD3 53 (>840)

Common Variable Immunodeficiency (syndrome)

• Paradoxically named—1:40 patients with recurrent infections have CVID

• Variable immunodysregulation; T cell and B cell defects; monocyte as well

• A syndrome—common endpoint of multiple conditions/defects

Clinical Features: Multisystem Disease

• Infections:– B cell predominant; encapsulated organisms, sinopulmonary

• All types, recurrent, refractory or poorly responsive• Unusual/nonpathologic (septic arthritis, meningitis)

• Autoimmune:– CVD, IBD, ITP, hepatitis, thyroid, cytopenias

• Inflammatory:– Malabsorption (GI atrophy), granulomatous disease

• Malignancy:– T and B cell lymphoma, MALT

CVID Specifics

• Phenotype varies—course, infection types

• Serologies negative; cultures may be negative

• Subtypes—several classification schemata

Diagnostic Criteria for CVID

• Immunodeficiency:– Ig levels: IgG less than 500, 2 SD below mean

• B cell function: – Illness/immunization status and serology– Post-vaccination Ig levels

• Exclusion of other diagnoses:– Primary immunodeficiencies– Drugs– Protein losing states– Lymphoproliferative d/o– Post-infection; asplenia

Practical Approach

• Clinical Features, Family History, Medications

• Ig levels; T cell Profile• Flow cytometry; Ig subclass• Post-vaccination Ab response• Exclusion—Clinical Grounds (flow

cytometry, HIV, complement, UA, SPEP, CBC, sprue, genetic testing?)

Management

• Vaccination• Infections

– Prevention– Treatment

• Biopsy enlarged lymph nodes• Pulmonary

– PFTs and CT, chest physiotherapy, surgery

Treatment: Immune Globulin

• Data on Efficacy– Decreased infections, end organ

damage/autoimmune– Dosing and frequency– Risks:

• Infection• Dementia?!!• Infusion Reactions

Other Treatments

• Immunomodulating Therapies

• Gene Therapy?

• Indications for glucocorticoids

• Indications for prophylactic antibiotics

Case Patient’s Results

• Abnormal T cells, nonresponsive to pneumovax/Td

• Our patient’s course:– Phenytoin induced? Not reversible; progressive

• Two other patients

Conclusions

• A rare disease that is not rare in the primary care setting

• Multisystem disease

• Easy to diagnose—at first

• Treatment is challenging

• Refer, refer, refer.

References1. Weiler CR, Bankers-Fulbright JL. Common Variable

Immunodeficiency: Test Indications and Interpretations. Mayo Clin Proc. 2005;80(9):1187-1200.

2. Carrock Sewell WA, Buckland MS, Jolles SRA. Therapeutic Strategies in Common Variable Immunodeficiency. Drugs. 2003;63(13):1359-1371.

3. Spickett GP. Current perspectives on common variable immunodeficiency (CVID). Clinical and Experimental Allergy. 2001;31:536-542.

4. Travin, et al. Reversible Common Variable Immunodeficiency Syndrome Induced by Phenytoin. Arch Intern Med. 1989;149:1421-1422.