New Diagnostic Criteria for Common Variable Immune Deficiency (CVID)

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immune deficiency condition in adults. The genetic basis for the condition is not known and no single clinical feature or laboratory test can establish the diagnosis; it has been a diagnosis of exclusion. In areas of uncertainty, diagnostic criteria can provide valuable clinical information.

New Diagnostic Criteria for Common Variable Immune Deficiency (CVID)

Revised ESID (2014) diagnostic criteria for CVID.

At least one of the following:

  • Increased susceptibility to infection
  • Autoimmune manifestations
  • Granulomatous disease
  • Unexplained polyclonal lymphoproliferation
  • Affected family member with antibody deficiency

AND marked decrease of IgG and marked decrease of IgA with or without low IgM levels (measured at least twice; <2 SD of the normal levels for their age);
AND at least one of the following:

  • Poor antibody response to vaccines (and/or absent isohemagglutinins); i.e., absence of protective levels despite vaccination where defined
  • Low switched memory B cells (<70% of age-related normal value)

AND secondary causes of hypogammaglobulinemia have been excluded
AND diagnosis is established after the fourth year of life (but symptoms may be present before)
AND no evidence of profound T-cell deficiency, defined as two out of the following (y = year of life):

  • CD4 numbers/microliter: 2–6 y < 300, 6–12 y < 250, >12 y < 200
  • % Naive CD4: 2–6 y < 25%, 6–16 y < 20%, >16 y < 10%
  • T-cell proliferation absent




New diagnostic criteria (Ameratunga) for CVID.

A- Must meet all major criteria

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

B- Sequelae directly attributable to immune system failure (ISF) (one or more)

  • Recurrent, severe, or unusual infections
  • Poor response to antibiotics
  • Breakthrough infections in spite of prophylactic antibiotics
  • Infections in spite of appropriate vaccination, e.g., HPV disease
  • Bronchiectasis and/or chronic sinus disease
  • Inflammatory disorders or autoimmunity

C- Supportive laboratory evidence (three or more criteria)

  • 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 to age-matched controls
  • Transient vaccine responses compared with age-matched controls
  • Absent isohemagglutinins (if not blood group AB)
  • Serological evidence of significant autoimmunity, e.g., Coombs test
  • Sequence variations of genes predisposing to CVID, e.g., TACI, BAFFR, MSH5, etc.

D- Presence of relatively specific histological markers of CVID (not required for diagnosis but presence increases diagnostic certainty, in the context of category A and B criteria)

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

Meeting criteria in categories ABC or ABD indicates probable CVID. Patients meeting criteria ABC and ABD should be treated with IVIG/SCIG. Patients meeting criteria A alone, AB or AC or AD but not B, are termed possible CVID. Some of these patients may need to be treated with IVIG/SCIG. Patients with levels of IgG > 5 g/l, not meeting any other criteria are termed hypogammaglobulinemia of uncertain significance (HGUS). These diagnostic criteria must be applied sequentially as none are specific individually.




References:

  1. Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, Espinosa-Rosales FJ, Hammarström L, Nonoyama S, Quinti I, Routes JM, Tang ML, Warnatz K. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):38-59. [Medline]
  2. Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol. 2013 Nov;174(2):203-11. [Medline]
  3. Abbott JK, Gelfand EW. Common Variable Immunodeficiency: Diagnosis, Management, and Treatment. Immunol Allergy Clin North Am. 2015 Nov;35(4):637-58. [Medline]
  4. Ameratunga R, Brewerton M, Slade C, Jordan A, Gillis D, Steele R, Koopmans W, Woon ST. Comparison of diagnostic criteria for common variable immunodeficiency disorder. Front Immunol. 2014 Sep 15;5:415. [Medline]

 

 

Created: Dec 19, 2018.