Pure B-Cell Disorders Differential Diagnoses

Updated: Jan 27, 2015
  • Author: Issam Makhoul, MD; Chief Editor: Emmanuel C Besa, MD  more...
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DDx

Diagnostic Considerations

Although common variable immune deficiency (CVID) is the most frequent symptomatic primary immune deficiency in adults, there is no universally accepted definition of CVID. Definitions have been proposed by the European Society of Immune Deficiencies (ESID) and the Pan American Group for Immune Deficiency (PAGID). Ameratunga et al have proposed new criteria for the diagnosis of CVID based on recent scientific discoveries. [10]

In this approach, CVID is diagnosed using sequential application of four sets of criteria (none are specific individually). Category A comprises the following major criteria, all of which must be met:

  • Hypogammaglobulinemia (IgG < 5 g/L)
  • No other cause identified for immune defect
  • Age > 4 years

Category B comprises sequelae directly attributable to immune system failure. One or more of the following must have occurred:

  • Recurrent, severe, or unusual infections
  • Poor response to antibiotics
  • Breakthrough infections in spite of prophylactic antibiotics
  • Infections in spite of appropriate vaccination (eg, human papillomavirus disease)
  • Bronchiectasis and/or chronic sinus disease
  • Inflammatory disorders or autoimmunity

Category C comprises supportive laboratory evidence, three or more of which must be present:

  • Concomitant reduction or deficiency of IgA (< 0.8 g/L) and/or IgM (< 0.4 g/L)
  • Presence of B cells but reduced memory B cell subsets and/or increased CD21 low subsets by flow cytometry
  • IgG3 deficiency (< 0.2 g/L)
  • Impaired vaccine responses compared with age-matched controls
  • Transient vaccine responses compared with age-matched controls
  • Absent isohemagglutinins (if not blood group AB)
  • Serologic evidence of significant autoimmunity (eg, positive Coombs test)
  • Sequence variations of genes predisposing to CVID (eg, TACI, BAFFR, MSH5)

Category D comprises relatively specific histologic markers of CVID. These are not required for diagnosis, but their presence increases diagnostic certainty, in the context of category A and B criteria. The markers are as follows:

  • Lymphoid interstitial pneumonitis
  • Granulomatous disorder
  • Nodular regenerative hyperplasia of the liver
  • Nodular lymphoid hyperplasia of the gut
  • Absence of plasma cells on gut biopsy

Ameratunga et al propose that patients who meet criteria in categories ABC or ABD have probable CVID and should receive immunoglobulin therapy. Patients who meet only criteria A, AB, AC, or AD have possible CVID, and some of them may need immunoglobulin therapy.

Differential Diagnoses