Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID)

doi:10.1016/j.jaut.2005.04.006

Journal of Autoimmunity

Volume 25, Issue 1, August 2005, Pages 57-62

https://doi.org/10.1016/j.jaut.2005.04.006 Get rights and content

Abstract

Common variable immunodeficiency (CVID) is associated with autoimmunity, most commonly immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). In a retrospective chart review of 326 CVID patients, 35 (11%) patients had a history of autoimmune hematologic disease. Fifteen patients had ITP, 9 had AIHA, and 11 had Evans syndrome (both ITP and AIHA). The age at diagnosis for CVID ranged from 5 to 66 years and for autoimmunity, from 2 to 66 years. There were 16 males and 19 females. Nineteen patients (54%) had the first episode of thrombocytopenia or hemolytic anemia prior to the diagnosis of immunodeficiency, 11 (32%) were diagnosed concurrently, and 5 (14%) developed one or both of these autoimmune diseases following the diagnosis of CVID. Eight patients were known to have granulomatous changes in one or more organs. Treatments for autoimmunity included corticosteroids, anti-Rh immunoglobulin, and intravenous immunoglobulin; 11 patients underwent splenectomy. While 5 patients had recurrences of autoimmune hemolytic disease while receiving maintenance intravenous immunoglobulin, most episodes occurred for subjects not yet on this therapy (P < 0.0001). Most patients with frequent infections and hematologic autoimmunity should be evaluated for CVID.

Introduction

Common variable immunodeficiency (CVID) is one of the most frequently diagnosed of the primary immunodeficiency diseases, with an incidence of approximately 1:50,000 [1], [2], [3]. This diagnosis is established by a reduced serum IgG as well as reduced serum IgA and/or IgM, two standard deviations or more below the mean, coupled with documented antibody deficiency [1], [2]. CVID is a diagnosis of exclusion and is often made in the second and third decades of life; males and females are affected approximately equally. In most cases, the immune deficiency is suspected based on the occurrence of frequent pyogenic infections, most commonly involving the sino-pulmonary tract, or otherwise unexplained chronic lung disease. Other frequent clinical conditions include gastrointestinal diseases involving bacterial or protozoal agents, or gastrointestinal inflammatory conditions leading to diarrhea and malabsorption. Due to the lack of antibody, and poorly understood dysregulated immunity, some patients with CVID may experience other complications, including autoimmunity, malignancy, or the development of granulomatous infiltrations of lungs, lymph nodes or other sites. Autoimmune disease was previously found in 22% in a series of 248 CVID patients [2]. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) were the most frequent conditions. The mechanism linking CVID and autoimmunity is not understood, although recent work has shown that patients with granulomatous disease and in most cases, a more profound lack of isotype switched memory B cells, are more likely to develop autoimmunity [4], [5]. This report describes the treatment and outcome of ITP and AIHA in a large group of CVID patients.

Section snippets

Methods

A retrospective chart review of CVID patients in the Immunodeficiency Clinic at Mount Sinai Medical Center, a referral center for both pediatric and adult patients, was performed. Three hundred and twenty-six patients with CVID were included from 1973 to March 2004. Each patient had decreased serum IgG in combination with decreased IgA and/or IgM by more than two standard deviations below the mean [1], [2]. In all patients with serum IgG of 350 mg/dL or greater, antibody deficiency was verified

Patients

Of the 326 patients who had been referred for either consultation or ongoing medical care over this period of time, 35 (11%) had a history of ITP and/or AIHA. Fifteen of these patients had one or more episodes of ITP; 9 had AIHA, and 11 others had Evans syndrome. An overall summary of these subjects is given in Table 1. In this group are 16 males and 19 females; the mean age at the time of diagnosis of CVID was younger for the subjects who had had ITP and/or Evans syndrome than patients who

Discussion

Autoimmunity is a common complication in primary immune deficiency diseases in which B cell immunity is present, but impaired. In CVID, the most prevalent of the clinically significant B cell defects, the two most common autoimmune conditions are ITP and AIHA [2]. In this series of 326 patients, 11% had either or both of these illnesses. In the general population, ITP occurs in 1.0–12.5 per 100,000 per year, affecting children or adults [6]. Autoimmune hemolytic anemia is also rare in the

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Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID)

Abstract

Introduction

Section snippets

Methods

Patients

Discussion

Clin Immunol

Clin Immunol

Blood

Blood

J Allergy Clin Immunol

J Pediatr

Blood Rev