My patient is a 66 year-old woman with HTN and GERD who was sent in for an evaluation as she was dissatisfied with her diagnosis of Burning Mouth Syndrome. She was seen by GI, ID, her dentist, hep PCP, and an oral pathologist, and no cause was found for her symptoms of mouth pain and burning which was also unrelated to the ingestion of any foods.

She had 2 separate endoscopies (not sure why there were 2 from the same doctor) but it was noted on both of them that she had some candida at the base of her tongue only. I was asked to rule out food allergy, which I did by having her keep a food diary, thus illustrating that there was no temporal relationship of her symptoms to anything that she was eating. This was especially relevant because she had essentially stopped eating which made proving this to her very easy. Of note, there was no clinical evidence of a contact allergy to either food, dental products, or anything else as her exam was normal.

I was asked to rule out an immunodeficiency because of the thrush. ID had done an HIV test which was negative. Her IgG, A, M were remarkable for a mildly decreased IgM and her subclasses were normal. Her lymphocyte screen was normal except for an increased Helper/Suppressor ratio of 4.58 (nl=1.00-3.00). She hails from Italy and had not had may vaccinations so she had no tetanus, or diphtheria titers. Her Pneumococcal titers were essentially negative except for one serotype. She was vaccinated with Pneumovax and was also given a dTap. She has an excellent response to her Pneumovax with a 4-fold rise in titer to 14/14 serotypes. She also had and excellent response to the tetanus portion of the dTap but no response to diphtheria at all and her level remained at 0.

While I do not think that this patient is truly immunodeficient I have not had anyone's diphtheria titers remain at 0. I also think that the thrush should be treated but that it is not related to an immunodefiencey, especially because it is only limited to the area at the base of her tongue. Any thoughts?


Thank you for your inquiry.

Burning mouth syndrome is a very frustrating entity of unknown cause and without a specific therapy. Because of its frustrating nature, allergists are not infrequently asked to evaluate such patients, usually in the setting of a "last resort." However, there is no documented evidence that allergy plays a role in this disorder. In addition, I agree with you that a workup of immunodeficiency is not normally indicated in the evaluation of such a patient. And I agree with you that I don't think your patient is immunodeficient. I can't explain the apparent lack of response to diphtheria immunization, but don't think it has relevance to your patient since a deficient antibody response would not be expected to produce the clinical scenario you describe. Defects in cell mediated immunity would be far more likely.

Thus I might mention parenthetically that since you have embarked on an evaluation for immunodeficiency in relation to the presence of thrush, and since you have spent time and energy pursuing this workup, the evaluation is incomplete. Such a workup would be designed to evaluate cell-mediated immune function. I have copied for you below a table taken from our Practice Parameters on Immunodeficiency which lists the tests one orders for the assessment of cell-mediated immunity.

I mention this not that I feel such a workup is indicated, but since you may want to report back to the physician asking for the evaluation that you have completed an immune workup, in order to do so, you might consider the screening tests mentioned in the table from our practice parameter copied below.

Thank you again for your inquiry and we hope this response is helpful to you.

1. Sun A, Wu KM, Wang YP, Lin HP, Chen HM, Chiang CP. Burning mouth syndrome: a review and update. J Oral Pathol Med 2013 Oct; 42(9):649-55. doi: 10.1111/jop.12101. Epub 2013 Jun 16.

2. Spanemberg JC, Cherubini K, de Figueiredo MA, Yurgel LS, Salum FG. Aetiology and therapeutics of burning mouth syndrome: an update. Gerodontology 2012 Jun; 29(2):84-9.

Table. Cellular immune function
Screening tests
Flow cytometry to enumerate T cells and natural killer cells
Cutaneous delayed hypersensitivity

Advanced tests
Enzyme assays (ADA, PNP)
FISH for 22q11 and 10p11 deletion
In vitro proliferative response to mitogens and antigens
Natural killer cell cytotoxicity
Cytokine production in response to mitogen or antigen stimulation
Expression of surface markers after mitogen stimulation

Source: Bonilla et al Practice parameter for the diagnosis and management of primary immunodeficiency: Ann Allergy Asthma Immunol 94; May 2005.

Phil Lieberman, M.D.

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