Q:

11/13/2013
There is a lot written in chat rooms about the association of (true) coeliac disease and chronic sinusitis. To appease a patient with severe chronic sinusitis, normal immunoglobulins and antibody production and modest inhalant allergies, but minimal GI symptoms (more GERD like) I ordered serology, which was dramatically positive. Endoscopy was also positive.

I have not found literature supporting this as a reported association. Am I missing something?

A:

Thank you for your inquiry.

Certainly there are references to the relationship between coeliac disease and chronic sinusitis on message boards, blogs, and other Internet sources. However, when one does an Internet search of the medical literature, at least according to searches which I have performed, no such relationship is mentioned. The only relationship that appears in the academic literature is that between malabsorptive disorders and hypogammaglobulinemia (common variable or selective IgA deficiency). This of course is an indirect relationship, but for your interest, I have copied examples of the literature related to this topic below. These articles, however, do not apply to your patient who has normal immunoglobulins. In this case, I could not find any medical literature corroborating a relationship between coeliac disease and chronic sinusitis in patients with normal immunoglobulin levels.

However, because this is the first such inquiry that we have had in this regard, and because my search was nonrevealing, I am asking Dr. Daniel Hamilos, who is an internationally recognized authority in the pathogenesis of chronic sinusitis, to respond to your inquiry as well. As soon as we have heard from Dr. Hamilos, we will forward his response to you.

Thank you again for your inquiry.

Ann Clin Biochem. 2012 Sep;49(Pt 5):503-4. doi: 10.1258/acb.2012.012011. Epub 2012 Aug 2.
Immunoglobulin A deficiency on serological coeliac screening: an opportunity for early diagnosis of hypogammaglobulinaemia.
Bright P, Lock RJ, Unsworth DJ.
Source
Department of Immunology, Southmead Hospital, Bristol BS10 5NB, UK.
Abstract
We present a serendipitous case of clinically significant pan-hypogammaglobulinaemia, diagnosed after routine serological testing for possible coeliac disease led first to identification of IgA deficiency (discovered as a low background in IgA-based routine serological screening), and subsequently to confirmed pan-hypogammaglobulinaemia (antibody immunodeficiency). Hypogammaglobulinaemia is a relatively rare diagnosis (estimated at 1 in 36,000), in which delayed diagnosis and treatment are associated with chronic organ damage including bronchiectasis. Routine serological testing for coeliac disease using the IgA anti-tissue transglutaminase (IgA TTG) test is in widespread use and provides an opportunity for early diagnosis of hypogammaglobulinaemia. Routine serological screening for coeliac disease may uncover IgA deficiency, and we suggest that all IgA-deficient cases identified should also be checked for antibody deficiency by quantifying the other immunoglobulins (IgG, IgM).

Dig Liver Dis. 2004 Nov;36(11):730-4.
Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency.
Lenhardt A, Plebani A, Marchetti F, Gerarduzzi T, Not T, Meini A, Villanacci V, Martelossi S, Ventura A.
Source
Department of Paediatrics, IRCCS Burlo Garofolo, University of Trieste, Via dell'Istria 65/1, 34100 Trieste, Italy.
Abstract
Background: Selective IgA deficiency is associated with coeliac disease, and studies have shown an increased prevalence of coeliac disease in these patients ranging from 0.71 to 30.7%, depending on the test used for screening.
Aims: To determine the sensitivity of IgG anti-gliadin-antibodies and of IgG human-tissue-transglutaminase for diagnosing coeliac disease and assessing its prevalence in subjects with IgA deficiency.
Subjects: We tested serum samples from 126 IgA-deficient children (66 female, median age: 10.8 years).
Methods: All samples were analysed to measure IgG anti-gliadin-antibodies and IgG anti-human-tissue-transglutaminase. Patients testing positive to either test underwent intestinal biopsy. Subjects testing positive for IgG anti-human-tissue-transglutaminase underwent genetic testing for the human leucocyte antigen heterodimer.
Results: Twenty-seven of 126 subjects tested positive for IgG anti-gliadin-antibodies (five of whom tested positive also for IgG anti-human-tissue-transglutaminase) and 18 (including the aforementioned five) for IgG anti-human-tissue-transglutaminase. Intestinal biopsy was performed in 37 of the 40 patients who tested positive (three subjects refused). Eleven had positive intestinal biopsies all of whom tested positive for IgG anti-human-tissue-transglutaminase, but only five of these tested positive also for IgG anti-gliadin-antibodies. All 22 patients testing positive for anti-gliadin-antibody alone had normal intestinal mucosa. All the patients who tested positive for IgG anti-human-tissue-transglutaminase and underwent genetic screening (15/18) had the coeliac-related human leucocyte antigen. Overall, coeliac disease was diagnosed in 11 of the 126 subjects with IgA deficiency (8.7%).
Conclusions: The prevalence of coeliac disease in subjects with total IgA deficiency was 8.7%. Assay of IgG anti-human-tissue-transglutaminase can be recommended for screening coeliac disease in IgA-deficient subjects.

Gut. 1981 Feb;22(2):153-7.
Coeliac disease with severe hypogammaglobulinaemia.
Webster AD, Slavin G, Shiner M, Platts-Mills TA, Asherson GL.
Abstract
A patient with severe late onset primary hypogammaglobulinaemia developed coeliac disease. The case illustrates that coeliac disease can occur in the virtual absence of local antibody production by plasma cells in the mucosa of the small bowel. Furthermore, our inability to demonstrate specific cellular immunity to a subfraction of gluten raises doubts about the relevance of immunological reactions in the pathogenesis of coeliac disease.

Sincerely,
Phil Lieberman, M.D.

We received a response from Dr. Daniel Hamilos. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Daniel Hamilos:
Aside from the literature you cited, there is no published medical literature relating chronic rhinosinusitis (CRS) and celiac disease (CD). It is noteworthy that published reviews of CD patients which provide a comprehensive list of commonly associated symptoms and diseases as well as rare manifestations associated with CD do not even list CRS as a possible association (E.g. Kneepkens CM, von Blomberg BM. Clinical practice : coeliac disease. Eur J Pediatr. 2012 Jul;171(7):1011-21. PMID:22422192; and Celiloğlu C, Karabiber H, Selimoğlu MA. Atypical presentations of celiac disease. Turk J Pediatr. 2011 May-Jun;53(3):241-9. Review. PMID:21980803 ). This is remarkable considering that CRS is highly prevalent, affecting 13 percent of the US population.  

When looked at from the perspective of CRS, the prevalence of CD is unknown. There are no published studies of this prevalence. Yet, as you pointed out, there are Internet chat rooms maintaining such an association based on personal testimonials. A common testimonial is that a patient with recurrent sinus infections reports a dramatic improvement in infections within weeks of starting a gluten-free diet. Furthermore, in some testimonials, sinus infections were noted to promptly recur after gluten was reintroduced in the diet. Interestingly, the patients in these accounts sometimes do not have confirmation of CD by blood testing which only makes the putative relationship between CRS and CD more tenuous.

As a clinician, I have many patients with recurrent sinus infections whose problems cannot be explained based on testing for allergies or immune deficiency. When usual measures of treatment, such as antibiotics, nasal saline irritations, topical intranasal steroids and, in some cases, sinus surgery fail, some of these patients have resorted to trying either a milk-free diet, a wheat-free diet or both. In some cases, they have experienced a significant improvement on the diet. This is not something I can explain on an immunologic basis. Nonetheless, if other types of treatment have already failed, I have no objection to a patient trying a milk-free or gluten-free diet for 4-6 weeks to see if their symptoms improve.

Sincerely,
Daniel Hamilos, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology