Infections in 252 patients with common variable immunodeficiency.

BACKGROUND Common variable immunodeficiency is characterized by recurrent infections and defective immunoglobulin production. METHODS The DEFI French national study prospectively enrolled adult patients with primary hypogammaglobulinemia. Clinical events before inclusion were retrospectively analyzed at that time. RESULTS From April 2004 through April 2007, 341 patients were enrolled, 252 of whom had received a diagnosis of common variable immunodeficiency; of those, 110 were male, 142 were female, and 228 were white. The median age at first symptoms was 19 years. The median age at common variable immunodeficiency diagnosis was 33.9 years. The median delay for diagnosis was 15.6 years for the 138 patients with initial symptoms before 1990 and 2.9 years for the 114 patients with initial symptoms from 1990 to the time of the study. The most frequent initial symptoms were upper respiratory tract infections: bronchitis (in 38% of patients), sinusitis (36%), pneumonia (31%), and/or bronchiectasis (14%). Overall, 240 patients had respiratory symptoms. Pneumonia was reported in 147 patients; Streptococcus pneumoniae and Haemophilus influenzae were documented in 46 and 17 cases, respectively. Recurrent or chronic diarrhea was reported in 118 patients. Giardia (35 cases), Salmonella (19), and Campylobacter (19) infections were more frequent in patients with undetectable serum immunoglobulin A (P<.001). Sixteen patients developed opportunistic infections. Persistent infections and requirement for antibiotics despite immunoglobulin substitution correlated with severe defect of memory switched B cells (P=.003) but not with immunoglobulin G trough levels (P=.55). CONCLUSION Although reduced within the past decade, the delay of diagnosis of common variable immunodeficiency remains unacceptable. Recurrence of upper respiratory tract infection or pneumonia should lead to systematic evaluation of serum immunoglobulin.

[1]  A. Plebani,et al.  Long-Term Follow-Up and Outcome of a Large Cohort of Patients with Common Variable Immunodeficiency , 2007, Journal of Clinical Immunology.

[2]  A. Sauvanet,et al.  Infection after cyanoacrylate injection: a fatal complication in a patient with portal hypertension associated with common variable immunodeficiency. , 2007, Endoscopy.

[3]  A. Durandy,et al.  Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. , 2006, Clinical immunology.

[4]  A. Smail,et al.  Efficiency of rituximab in the treatment of autoimmune thrombocytopenic purpura associated with common variable immunodeficiency , 2006, American journal of hematology.

[5]  M. van der Burg,et al.  An antibody-deficiency syndrome due to mutations in the CD19 gene. , 2006, The New England journal of medicine.

[6]  N. Rezaei,et al.  Effect of regular intravenous immunoglobulin therapy on prevention of pneumonia in patients with common variable immunodeficiency. , 2006, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[7]  C. Cunningham-Rundles,et al.  Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). , 2005, Journal of autoimmunity.

[8]  R. Geha,et al.  TACI is mutant in common variable immunodeficiency and IgA deficiency , 2005, Nature Genetics.

[9]  A. Schäffer,et al.  Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans , 2005, Nature Genetics.

[10]  A. Kokuludağ,et al.  Common variable immunodeficiency (CVID) presenting with malabsorption due to giardiasis. , 2005, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology.

[11]  A. Plebani,et al.  ICOS deficiency in patients with common variable immunodeficiency. , 2004, Clinical immunology.

[12]  H. Lyall,et al.  Recurrent meningitis in association with common variable immune deficiency. , 2004, Indian pediatrics.

[13]  É. Oksenhendler,et al.  Autoimmune Thrombocytopenic Purpura and Common Variable Immunodeficiency: Analysis of 21 Cases and Review of the Literature , 2004, Medicine.

[14]  E. Pallisa,et al.  Immunoglobulin therapy to control lung damage in patients with common variable immunodeficiency. , 2004, International immunopharmacology.

[15]  A. Schäffer,et al.  Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency , 2003, Nature Immunology.

[16]  H. Chapel,et al.  European surveillance of immunoglobulin safety--results of initial survey of 1243 patients with primary immunodeficiencies in 16 countries. , 2002, Clinical immunology.

[17]  C. Cunningham-Rundles,et al.  Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. , 2002, The Journal of allergy and clinical immunology.

[18]  A. Denz,et al.  Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. , 2002, Blood.

[19]  C. Kallenberg,et al.  The Effect of Two Different Dosages of Intravenous Immunoglobulin on the Incidence of Recurrent Infections in Patients with Primary Hypogammaglobulinemia , 2001, Annals of Internal Medicine.

[20]  I. Vořechovský,et al.  Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID) , 2000, Clinical and experimental immunology.

[21]  L. Notarangelo,et al.  Diagnostic Criteria for Primary Immunodeficiencies , 1999 .

[22]  C. Cunningham-Rundles,et al.  Common variable immunodeficiency: clinical and immunological features of 248 patients. , 1999, Clinical immunology.

[23]  A. Fischer,et al.  Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. , 1999, The Journal of pediatrics.

[24]  J. Björkander,et al.  1040 Prophylactic infusions with an unmodified intravenous immunoglobulin product causing few side-effects in patients with antibody deficiency syndromes , 1985, Infection.

[25]  Eren,et al.  The EUROclass trial: defining subgroups in common variable immunodeficiency. , 2008, Blood.

[26]  B. Piqueras,et al.  Common Variable Immunodeficiency Patient Classification Based on Impaired B Cell Memory Differentiation Correlates with Clinical Aspects , 2003, Journal of Clinical Immunology.

[27]  C. Kallenberg,et al.  The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. , 2001, Annals of internal medicine.

[28]  L. Notarangelo,et al.  Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). , 1999, Clinical immunology.

[29]  R. Hermaszewski,et al.  Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. , 1993, The Quarterly journal of medicine.