Drs. Fatemi and Fang propose adding IgG4-related pharyngitis to the preferred nomenclature of individual organ manifestations of IgG4-related disease. We concur that this is now appropriate. At the International Symposium on IgG4-Related Disease, at which the consensus document on nomenclature was drafted, the attendees agreed that a minimum of 5 reports of involvement in any given organ should be published before that organ could be included as an individual organ manifestation of IgG4-related disease. Fatemi and Fang cite 2 other cases of IgG4-related disease involving the pharynx ([1, 2]) in addition to their own. Herein we describe 2 more cases evaluated at our center in the past few months.

The first patient, a 51-year-old woman, immigrated to the US at age 19 years. The patient reported a 6-year history of throat pain exacerbated by swallowing. A computed tomography scan revealed an irregular, circumferential soft-tissue thickening and enhancement along the left pharyngeal wall, with extension into the left tongue base and tonsillar pillar. A pharyngeal malignancy was suspected, but biopsy of the mass showed marked chronic inflammation and eosinophilia. Special stains and cultures were negative. In situ hybridization of κ and λ light chains showed a polyclonal plasma cell population, and immunohistochemistry analysis revealed >50 IgG4-positive plasma cells/high-power field, with an IgG4-to–total IgG ratio of >0.40. Findings of a serum assay for antibodies to antineutrophil cytoplasmic antibodies were negative. The serum IgG4 concentration was 154 mg/dl (normal <121). This case constitutes the second instance of IgG4-related disease isolated in the pharynx, without evidence of IgG4-related disease in any other organ (the one reported by Fatemi and Fang is the first). Treatment of the patient with rituximab (1 gm intravenously) and methylprednisolone (100 mg) in the context of a clinical trial led to the swift and complete resolution of the pharyngeal lesion, as demonstrated by results of fiberoptic bronchoscopy on the day of her second rituximab infusion. Remission of this disease has now been maintained for 6 months following treatment.

The second patient, a 59-year-old man, presented with intermittent throat irritation on the right side of several years' duration. Fiberoptic bronchoscopy revealed periarytenoid and postcricoid edema in the laryngeal introitus. There was an exophytic swelling on the left base of the tongue and granular deposits in the right pyriform sinus and the right vocalis process. Diffuse inflammation involving the Waldeyer throat ring at the base of tongue, the pharynx, and the hypopharynx was also seen. Results of positron emission tomography performed with computed tomography showed asymmetric, intense uptake in the right oropharynx and foci of uptake in the left side of the neck. There was also moderate uptake in the left oropharynx. Biopsy of the left vallecula revealed sclerosis and a dense lymphoplasmacytic infiltrate containing reactive lymphoid follicles and a high concentration of IgG4-positive plasma cells (50 cells/high-power field), with an IgG4-to–total IgG ratio of >0.50. The serum IgG4 concentration was 196 mg/dl. Findings of a repeat fiberoptic bronchoscopy examination 2 weeks after the completion of therapy (1,000 mg of rituximab plus 100 mg of intravenous methylprednisolone, 2 doses each) showed resolution of pharyngeal and hypopharyngeal lesions.

IgG4-related disease is a systemic, fibroinflammatory illness characterized by a tendency for formation of tumefactive lesions that often mimic cancer. The diagnosis is based first and foremost upon the histopathologic features, supplemented by immunostaining for IgG4-positive plasma cells and the calculation of an IgG4-to–total IgG ratio within the tissue ([3]). Serum IgG4 concentrations are elevated in a majority of patients, but this is not required for the diagnosis. The case reported by Fatemi and Fang, as well as the 2 cases they cited ([1, 2]) and the cases reported herein, confirm that IgG4-related pharyngitis should be regarded as part of the IgG4-related disease spectrum. In addition, it is important to recognize that IgG4-related pharyngitis can occur in isolation, without other organ manifestations.


Dr. Stone's work was supported by a grant from Genentech for the study of IgG4-related disease.