Correspondence (reply): In Reply

We thank Dr. Tsamaloukas for enriching our comprehensive list of differential diagnoses of chronic recurrent aphthous ulcers (1).

The “ulcerations and oral gangrene” affecting some patients with acatalasemia (Takahara’s disease)—a rare enzymopathy (estimated prevalence 1:31 250) (2) that is usually asymptomatic and has an autosomal recessive pattern of inheritance—are pronounced hemorrhagic mucosal necroses and ulcerations caused by H₂O₂ (3). For this reason, acatalasemia should be added to the group of “Other oral disorders” in our list.

We also thank Dr. Glaenz for his comment. We consider the reduction of neutrophil granulocytes in the epidermis and corium (4) and of the total lymphocyte number in the peripheral blood (5), that is caused by fumaric acid, as a possible mechanism of action of fumaric acid esters in chronic recurrent aphthous ulcers. These events may be interpreted in the sense of an immunosuppressant effect (5).

Because of the large number of reported therapeutic approaches in chronic recurrent aphthous ulcers, however, we felt obliged to only include those therapeutic schemes in our article that have a higher evidence level (1). This didactic approach did not aim to cast aspersions on the value of such therapies, which in spite of long years of positive clinical experiences have not been considered in the planning of evidence based studies.