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 use to treat autoimmune and malignant diseases.

The “punchline” of this Letter is that alternative treatments; so other than IgG replacement therapy (IGRT) and chronic antibiotics; which need to be develop to treat recalcitrant chronic sinusitis; so that causes poor quality of life patients after successful treatment; so of their autoimmune disease or cancer with medications that cause delayed or complete failure to reconstitute competent mucosal immunity.

Immuno deficiency conditions

There is an increasing incidence of drug induced, secondary immunodeficiency conditions; so in a sizable number of patients being treated for autoimmune disease or cancer; hence using various chemotherapeutic drugs and in particular, rituximab. These patients fail to recover adaptive immunity, mostly B cell function; so long after successful chemotherapeutic or immune modulator therapy has discontinue.

Two of these patients after immunologic evaluation had underlying primary immunodeficiency diseases (PIDD), previously unrecognized by the referring physicians; who treat them with rituximab and other chemotherapeutic drugs for autoimmune disease or cancer. Thus, the referring physicians had not an not suspect PIDD as a possible underlying cause of the autoimmune disease/cancer their patients had develop prior to giving them these drugs.

The second patient had a diagnosis of autoimmune sinusitis, lung disease, and GI disease and was maintaine on moderate doses of steroids, chemotherapy, rituximab, IGRT, and chronic antibiotics. She had abnormal serial immune phenotypes, including low B and T cell numbers; also poor function that were attribute to steroid, rituximab, and chemotherapy treatment.

Stem cell transplant

On SCID genetic screening, she was show to have Rag1 deficiency 5 years after presentation of her symptoms. This patient receive an allogeneic stem cell transplant; also is now stable on IGRT and antibiotics for chronic sinus and respiratory disease; but her sinus disease is poorly control on this regimen.

Thus, clinicians should anticipate the possible development of long-term secondary immunodeficiency disease in their patients successfully treat with modern aggressive chemotherapy / biologics, including, but not limit to rituximab, and as part of their follow up strategy be vigilant in instituting appropriate medical management when this condition develops.

While the authors of the Letter infer that secretory IgA in the supernatant of breast milk; hence is the reason why their patient improve her chronic sinusitis disease, breast milk also contains many anti-inflammatory molecules that can block inflammation and support bacterial clearance. Thus, it is unclear why the therapy report in this Letter was effective in controlling this patient’s chronic sinusitis.

An alternative approach might be the use of some of the immunosuppressive molecules present in the non-cellular fraction of human breast milk in clinical trials to determine if these molecules improve the quality of life of patients with persistent sinorespiratory infections refractory to chronic antibiotics and IGRT.