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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

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

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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.

References 1.

2. 3. 4.

Weiler CR, Bankers-Fulbright JL. Common Variable Immunodeficiency: Test Indications and Interpretations. Mayo Clin Proc. 2005;80(9):11871200. Carrock Sewell WA, Buckland MS, Jolles SRA. Therapeutic Strategies in Common Variable Immunodeficiency. Drugs. 2003;63(13):1359-1371. Spickett GP. Current perspectives on common variable immunodeficiency (CVID). Clinical and Experimental Allergy. 2001;31:536-542. Travin, et al. Reversible Common Variable Immunodeficiency Syndrome Induced by Phenytoin. Arch Intern Med. 1989;149:1421-1422.