The association of pernicious anemia with immunologic deficiency has previously been described in 16 patients. Two additional cases are presented in this report. The suggestion that serum gamma globulin levels are commonly reduced in patients with pernicious anemia was not confirmed by immunoquantitation of serum immunoglobulins in 18 patients with pernicious anemia in relapse. Quantitation of immunoglobulins in 10 patients with malabsorptive disorders of diverse cause did not show any instances of true hypogammaglobulinemia. Four of these patients exhibited increased serum immunoglobulin A levels, a phenomenon previously reported only in gluten enteropathy.
Although the anemia in these hypogammaglobulinemic patients was characteristic of pernicious anemia by hematologic and gastric criteria, it was unusual in several ways. First, the average age of the patients at onset of the anemia was 30 years, unusually early for pernicious anemia. Second, none had parietal cell or intrinsic factor antibodies. Third, Giardia lamblia was reported in half the patients with this combination of diseases.
The concurrence of pernicious anemia and hypogammaglobulinemia is too frequent to be explained by coincidence. Although the explanation of this relationship is not clear, the associations of hypogammaglobulinemia with malabsorption and of malabsorption with gastric atrophy suggest that gastric atrophy may be a secondary consequence of hypogammaglobulinemia which usually precedes the pernicious anemia. Further investigations are needed to clarify the pathogenesis of this fascinating syndrome.