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.
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.