LAUSR

The Letter to the Editor by Dr. Palmeira et al. in this issue of the Journal of Clinical Immunology brings up several challenges for clinical immunologists who care for patients with secondary immunodeficiency disease caused by modern aggressive chemotherapy or biologics that are used to treat autoimmune andmalignant diseases. The authors describe a case of recalcitrant sinusitis in a 76-year-old woman who was treated for lymphoma with several cycles of rituximab. The Bpunchline^ of this Letter is that alternative treatments, other than IgG replacement therapy (IGRT) and chronic antibiotics, need to be developed to treat recalcitrant chronic sinusitis that causes poor quality of life patients after successful treatment of their autoimmune disease or cancer with medications that cause delayed or complete failure to reconstitute competent mucosal immunity. There are three challenges inherent in this Letter. First, secondary immunodeficiency occurs in some patients treated for autoimmune disease or cancer by modern aggressive chemotherapy/biologics, especially rituximab. These drugs can cause a failure to restore adaptive immunity once the underlying disease has successfully been treated. They develop chronic sinorespiratory disease that is not responsive to chronic antibiotics and/or IGRT. Second, although not addressed in this case report, some of the patients who fail to recover immunologically from these treatments have an underlying primary immune deficiency disease (PIDD). Third, and addressed in this Letter, the development of alternative strategies is needed to treat such patients who develop poorly controlled sinorespiratory disease. Such protocols may greatly improve the quality of life of these patients. There is an increasing incidence of drug induced, secondary immunodeficiency conditions [1, 2], in a sizable number of patients being treated for autoimmune disease or cancer, using various chemotherapeutic drugs [3] and in particular, rituximab [1–3]. These patients fail to recover adaptive immunity, mostly B cell function, long after successful chemotherapeutic or immune modulator therapy has been discontinued [1, 2]. Rituximab has been successfully used in treating many diseases that were previously refractory to chemotherapeutic protocols alone. On occasion, rituximab can cause persistent B cell failure that persists many years after completion of this therapy when patients are in remission. In some patients, there is a significant or complete failure of B cell reconstitution, with poor expression of protective serum immunoglobulin levels to multiple pathogens greater than 8 years following the discontinuation among of rituximab [1]. While we were among the first to report this phenomenon [1], others have confirmed these findings [3]. At the time of our report, we had not yet completed an in-depth immunologic evaluation of the original 14 patients we reported who failed to reconstitute B cell numbers and/or function. Two of these patients after immunologic evaluation had underlying primary immunodeficiency diseases (PIDD), previously unrecognized by the referring physicians who treated them with rituximab and other chemotherapeutic drugs for autoimmune disease or cancer. Thus, the referring physicians had not an not suspected PIDD as a possible underlying cause of the autoimmune disease/cancer their patients had developed prior to giving them these drugs. The first patient presented with autoimmune thrombocytopenia (Evan syndrome) and we identified a gain of function, PI3Kinase defect in this patient by whole exon sequencing. Unfortunately, no immunophenotype was performed prior to * Vincent R. Bonagura [email protected]