The following studies are presented in no particular order. They are connected by hyperlink to their abstracts in MedLine.
Gastroesophageal reflux: pathogenesis, diagnosis, and treatment., Zeiter DK, Hyams JS, Allergy Asthma Proc 1999 Jan-Feb;20(1):45-9
Department of Pediatrics, Connecticut Children's Medical Center, University of Connecticut, Hartford, USA.
Eosinophilic gastroenteritis in food allergy, Pfaffenbach B, Adamek RJ, Bethke B, Stolte M, Wegener M, [Article in German] , Z Gastroenterol 1996 Aug;34(8):490-3
Medizinische Universitatsklinik, St. Josef-Hospital, Ruhr-Universitat Bochum.
Eosinophils in allergy: role in disease, degranulation, and cytokines., Martin LB, Kita H, Leiferman KM, Gleich GJ, Int Arch Allergy Immunol 1996 Mar;109(3):207-15
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Allergic gastroenteropathy in children. [REVIEW], Moon A, Kleinman RE, Ann Allergy Asthma Immunol 1995 Jan;74(1):5-12; quiz 12-6
Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Eosinophilic gastroenteritis caused by bee pollen sensitization, Puente S, Iniguez A, Subirats M, Alonso MJ, Polo F, Moneo I, Med Clin (Barc) 1997 May 10;108(18):698-700
Servicio de Enfermedades Infecciosas-Seccion de Medicina Tropical, Centro de Investigacion Clinica, Madrid.
Evidence for an abnormal profile of interleukin-4 (IL-4), IL-5, and gamma-interferon (gamma-IFN) in peripheral blood T cells from patients with allergic eosinophilic gastroenteritis. Jaffe JS, James SP, Mullins GE, Braun-Elwert L, Lubensky I, Metcalfe DD, J Clin Immunol 1994 Sep;14(5):299-309
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Oral administration of cromolyn in a patient with protein-losing enteropathy, food allergy, and eosinophilic gastroenteritis., Van Dellen RG, Lewis JC, Mayo Clin Proc 1994 May;69(5):441-4
Division of Allergic Diseases and Internal Medicine, Mayo Clinic Rochester, Minnesota 55905.
[cromolyn sodium therapy is often used to investigate whether disorders have an allergic basis ... in other words, if the patient improves, then allergy was involved]
Eosinophilic gastroenteritis, Stringel G, Mercer S, Sharpe D, Shipman R, Jimenez C, Can J Surg 1984 Mar;27(2):182-3
Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut., Bischoff SC. Baillieres Clin Gastroenterol 1996 Sep;10(3):443-59
Sodium cromoglycate in the treatment of eosinophilic gastroenteritis., Di Gioacchino M, Pizzicannella G, Fini N, Falasca F, Antinucci R, Masci S, Mezzetti A, Marzio L, Cuccurullo F, Allergy 1990 Apr;45(3):161-6
Department of Medical Pathology, University of Chieti, Italy.
Eosinophilic gastroenteritis associated with food allergy and bronchial asthma., Park HS, Kim HS, Jang HJ, J Korean Med Sci 1995 Jun;10(3):216-9
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Korea.
Human intestinal mast cells produce IL-5 in vitro upon IgE receptor cross-linking and in vivo in the course of intestinal inflammatory disease.Lorentz A, Schwengberg S, Mierke C, Manns MP, Bischoff SC, Eur J Immunol 1999 May;29(5):1496-503
Department of Gastroenterology and Hepatology, Medical School of Hannover, Germany.
Definitions and diagnosis of food intolerance and food allergy: consensus and controversy, Ferguson A, J Pediatr 1992 Nov;121(5 Pt 2):S7-11
Department of Medicine (Western General Hospital), University of Edinburgh, Scotland.
Deposition of eosinophil granule major basic protein in eosinophilic gastroenteritis and celiac disease., Talley NJ, Kephart GM, McGovern TW, Carpenter HA, Gleich GJ, Gastroenterology 1992 Jul;103(1):137-45
Division of Gastroenterology and Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota.
Eosinophilic gastroenteritis with esophageal involvement., Chou CH, Shin JS, Wu MH, Chow NH, Lin XZ, J Formos Med Assoc 1996 May;95(5):403-5
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan ROC.
Marked eosinophilia in esophageal mucosal biopsies., Lee RG, Am J Surg Pathol 1985 Jul;9(7):475-9
Esophageal involvement in eosinophilic gastroenteritis., Matzinger MA, Daneman A, Pediatr Radiol 1983;13(1):35-8 [NO ABSTRACT]
Endogenous interleukin 4 is required for development of protective CD4+ T helper type 1 cell responses to Candida albicans" Mencacci A, Del Sero G, Cenci E, d'Ostiani CF, Bacci A, Montagnoli C, Kopf M, Romani L, J Exp Med 1998 Feb 2;187(3):307-17
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
Dr. Mencacci has done a LOT of very recent work on the connection of fungal infection and the immune system. I have not listed it here, but you can do a MedLine search for "mencacci a" to find it. Free MedLine can be reached at http://www.ncbi.nlm.nih.gov/PubMed
Following this paragraph is a long quote from Defense Brief in Medical Board of California vs. Robert Sinaiko, MD, an immunologist who believes antifungals can help in treatment of allergy (and according to Dr. Gupta, whom he quotes and who is doing research on this at U of CA-Irvine, lowering the level of GI yeast helps the immune system and decreases allergic reaction -- whether the original level is "high" or not is not necessarily relevant)
D. WHY DO (SOME) ALLERGISTS USE ANTIFUNGAL MEDICATIONS?BACK to Research Page || HOME
Sudhir Gupta, MD, PhD, Chief of the Allergy and Immunology Department at the School of Medicine at the University of California, Irvine, has observed, and teaches, that allergic disease is made worse by the colonization of the GI tract by Candida.(73) The immunologic mechanisms to explain this phenomenon are complex, and many of its details are being worked out as new investigative tools become available to the experimental immunology community.
Practicing allergists fall into two groups, those who agree with Prof. Gupta's teachings about the effect of fungi on the immune system in general and on allergy in particular, and those who disagree with Gupta. The debate among allergists as to when, in clinical allergy practice, antifungal medications are helpful, is an ongoing and legitimate scientific controversy, one that cannot be resolved satisfactorily by the fiat of any public agency, and one that is likely to remain undecided for some time. It is certainly inappropriate to attempt to discipline a doctor because of his or her adherence to one side or the other in such a debate.
The fact that Candida (a fungus that most frequently produces yeast infections) does exert a number of profound immunological effects has been well-demonstrated in many peer-reviewed reports published in major journals, and is no longer a proper subject for debate. In fact, only those unfamiliar with this extensive literature continue to do so. This body of scientific information is partially summarized in the chapter of Kurstak's 1989 textbook Immunology of Fungal Diseases.(74) Research immunologists know today that Candida colonization produces an imbalance between the dominance of Th1 and Th2 subsets of CD4 lymphocytes, and that such imbalance is a critical factor in the immunopathogenesis of many diseases. (75) (76)
Antifungal medications are useful for eradicating or limiting fungal or yeast colonizations of the GI tract. This helps normalize immune function and treat allergic and other immunologically mediated diseases. But antifungal medications also have other uses, making them an important tool for those allergists who have learned to use them. An explanation of some of these uses follows:
1. Antifungals for Alimentary Allergy to Yeast and Fungi
It has long been known that Candida and other fungi are potent allergens. (77) Dermatologists have been aware,(78) since early research on this subject by Maibach, that in women with recurring yeast vaginitis, painting the vulvar region with a suspension of dead yeast cells produces a local allergic inflammatory condition indistinguishable from infection by viable yeast organisms.
Like any foodstuff, food yeasts can produce allergic reactions in susceptible individuals who ingest them. While this form of allergy is not especially common, one of the cases currently before this Panel, JH, provides an example of it(79). This man noted allergic symptoms (severe itching and rash) each time he would ingest a particular nutritional supplement made from yeast. When he discontinued this supplement, the symptoms improved but did not clear. Further improvement occurred when he excluded yeast-containing foods like breads from his diet, but he continued to experience symptoms. On a diagnostic trial of Nystatin, significant further clearing occurred.
In cases of yeast allergy, the body has no good way of knowing whether the yeast got into the GI tract by being swallowed or by replicating there.(80) In either case, in susceptible individuals, allergic reactions can be expected to result from alimentary contact with the antigen, and proper treatment depends on avoidance, whether by dietary exclusion or by treating to prevent fungal GI colonization, or both. Colonization can be prevented very safely, since the polyene antifungals, Nystatin and Amphotericin B, are not significantly absorbed across the intestinal mucosa. For this reason, as we have discussed in the section, "What is Amphotericin B?" they can be used safely both for a brief diagnostic trial and, if needed, for prolonged treatment of yeast allergy, without significant risk.