RRP ISA Survey Results

    Sense, Sensibility, Science (& MMR)

    The following message was posted on RRP ISA's discussion board on January 30, 2006. It comes from a very respected immunologist who is currently doing on HPV/RRP off of a substantial NIH grant:

    Sense, Sensibility, and Science, before Undergoing Experimental Treatments:

    No doubt, the relentless recurrence of respiratory papillomas drives patients with Recurrent Respiratory Papillomatosis (RRP) to desperate measures, and at times to disregard sound medical advice from highly qualified clinicians and scientists who study and treat this disease. One such desperate venue to treat RRP is the introduction of multiple doses of vaccine antigens (such as the MMR vaccine) into respiratory tissues that contain papillomas. The presumed hypothesis, which has not been tested scientifically, is that repeated immunizations into human papillomavirus (HPV)-infected respiratory tissues will induce an inflammatory immune response to these vaccines that will generate, as a side effect, a potent immune response to HPV proteins in papillomas, thus eliminating HPV-infected cells in the upper airway and preventing papilloma recurrence.

    While this scenario sounds appealing, several serious concerns must be pointed out. First, introducing multiple vaccine doses at one time into upper airway tissues, and often repeating this procedure multiple times, could cause immediate swelling of the larynx causing a mechanical obstruction of the airway due to the sheer volume of the vaccine doses placed into the upper airway. Second, an additional consequence of this approach in treating RRP is the induction of an overwhelming inflammatory response in the airway generated by preformed antibodies to these vaccines that all individuals have previously generated when they were first immunized as children, or when re-immunized as adults. Such a response, called an Arthus reaction, usually occurs within 24 hours and is antibody and complement (a blood protein) dependent. If severe enough, the larynx could be swollen to a critical level that would require intubation.. Furthermore, circulating immune complexes, containing vaccine antigen mixed with antibodies to these antigens could activate complement in the blood inducing a “serum like sickness” condition that manifests as joint inflammation and body aches, as well as kidney and arterial inflammation.

    In addition to the short-term effects of this kind of therapy is the concern that there may be long-term complications of this treatment. In those individuals prone to develop autoimmune disease, it is unclear whether repeated, multi-dose immunizations with vaccines may precipitate or exacerbate the development of autoimmunity. It is controversial whether individuals who have allergies and autoimmune disease should undergo allergen desensitization (shot therapy). Although these patients might well benefit from allergen desensitization, using increasing doses of allergen extracts over an extended period of time, it is possible that this treatment given to patients prone to autoimmune may exacerbate autoimmunity. It is possible that perturbing the immune system, already geared at making an abnormal response to normal body tissues that is characteristic of autoimmunity, might be further provoked by repeated immunizations with allergen extracts. This concept should also be a recognized and of concern to patients and physicians who use multi-dose immunization as an alternate treatment for recurrent respiratory papillomatosis.

    Also of great concern is the lack of systematic evaluation of the patient undergoing this treatment, including the absence of pre- and post treatment blood tests to identify vaccine-specific immune responses made by patients who will undergo this treatment. Blood tests should identify the presence of pre-existing antibodies to the vaccines used that will be used in this procedure and be used to assess whether revaccination might cause an Arthus reaction. Furthermore, the absence of a supervisory board monitoring physicians and patients that would ensure that patients are fully informed, and a written consent obtained before the procedure, is of great concern. All individuals undergoing experimental procedures should be provided with detailed information about the potential benefits by the investigator and all side effects of the treatment should be fully explained in common language. Written informed consent should be obtained and the language contained in the consent explained by the physician. In addition, the patient’s signature should be obtained at that time. This is “standard procedure” for any experimental treatment. In addition, a copy of the informed consent should be given to the patient and the original kept on file by the investigator.

    While it is clear that desperate situations sometimes encourage patients to pursue desperate treatments, investigational treatments must have convincing preliminary data to justify putting a patient at potential risk of developing a serious side effect. Furthermore, the absence of close supervision by the scientific community should raise concern by the patient. The better part of valor is always to be cautious when pursuing unproven treatment, ask questions, and insist on full disclosure and being informed about all possible side effects.

    Vincent Bonagura, MD
    Chief, Division of Allergy/Immunology
    Professor of Pediatrics, Microbiology and Immunology
    Albert Einstein College of Medicine