Salivary Gland Disease in IgG4-Related Disease is Associated with Allergic Conditions

Background/Purpose: The etiology of IgG4-related disease (IgG4-RD) remains unknown. The role of T-helper type 2 (Th2) cells in the pathogenesis of IgG4-RD is controversial. Given Th2 cells’ involvement in allergic responses and prior IgG4-RD studies suggesting their importance in the pathogenesis, it has been hypothesized that allergic mechanisms contribute to the development of IgG4-RD. We investigated the association between allergies and IgG4-RD. Methods: The Center for IgG4-RD at Massachusetts General Hospital maintains a database of all IgG4-RD patients, including details of demographics and disease history. Allergy histories were obtained from patients via a 34-question allergist-developed survey administered at their baseline visit. Patients were considered to have a history of allergies if they reported prior symptoms or diagnosis. We included all patients who completed the allergy survey; for certain analyses, some patients were excluded because of missing data. Statistical significance was determined by Fisher’s exact test or unpaired t-test, as appropriate. P values < 0.05 were considered significant. Results: Our study included 185 IgG4-RD patients from a database of 289 patients. Of the 185 patients, 140 (76%) reported any allergic symptom or diagnosis (Table 1). There was no significant difference with regard to age (P=0.1) or sex distribution (P=0.7) between patients with and without allergy symptoms. Respiratory allergies appear more prevalent in this cohort than the general US population: 61% of cohort patients reported a history of respiratory allergies, compared to 30% of Americans who completed a similar survey (Allergy Asthma Proc 2008; 29:600). Skin allergies (41%), food allergies (20%), and anaphylaxis (8%) were less common than respiratory allergies in IgG4-RD. Patients with allergies tended to have any ear, nose, and throat (ENT) manifestations of IgG4-RD more often than those who did not have allergies (55% vs 36%, P=0.058). This trend was largely driven by a significant difference in the proportion of patients with salivary gland IgG4-RD (e.g., sialoadenitis) among those with allergies compared with those without a history of allergies (41% vs 22%, P=0.03). We found a similar difference when comparing salivary gland involvement between those with and without respiratory allergies (72% vs 28%, P=0.039). Conclusion: In a large IgG4-RD cohort, we found a significant association between IgG4-related salivary gland disease and allergic histories. More generally, we found a trend towards an association between ENT involvement and allergic histories. Of the reported allergies, respiratory allergies were most common. While it is possible that shared pathogenesis is responsible for these observations, a shared upper respiratory exposure may also explain our observations given the associations between head and neck disease with allergic histories.