Recurring Bilateral Parotid Gland Swelling: Two Cases of Sialodochitis ﬁbrinosa

The Journal of Laryngology & Otology (2006), 120, 330–333. Clinical Record # 2006 JLO (1984) Limited doi:10.1017/S0022215106000296 Printed in the United Kingdom First published online 18 February 2006

Recurring bilateral parotid gland swelling: two cases of sialodochitis ﬁbrinosa

KAZUAKI CHIKAMATSU, MD, MASATO SHINO, MD, YOICHIRO FUKUDA, MD, KOICHI SAKAKURA, MD, NOBUHIKO FURUYA,MD

Abstract Salivary gland swelling is a commonly encountered clinical symptom, but the establishment of a diagnosis is occasionally difficult. Here, we present two sialodochitis fibrinosa patients with recurring bilateral parotid swelling. In both patients, secretion of mucous plugs containing numerous eosinophils was observed from Stensen’s ducts. As expected, the level of interleukin-5 in the saliva was much higher than that in the serum. One patient had no medical history of allergic disease; the other had allergic rhinitis which had never been associated with parotid gland swelling. Microbiological examination was unable to isolate significant bacterial specimens from the mucous plugs. Thus, although allergy and/or bacterial infection are reportedly implicated as causes of sialodochitis fibrinosa, there may exist other possibilities for its pathogenesis. Interleukin-5 seems to play a crucial role in the pathogenesis of sialodochitis fibrinosa. Key words: Salivary Gland Diseases; Parotid Gland; Interleukin-5

Introduction symptoms had recently progressed and she was referred Salivary gland swelling is a commonly encountered clinical to our hospital. On physical examination, she had diffuse symptom and can be caused by various inflammatory or bilateral swelling of the parotid glands. She had neither noninflammatory disorders. Inflammatory salivary dis- facial nerve palsy nor palpable cervical nodes. orders can be grouped according to the aetiology of the An intraoral examination showed unremarkable find- infection and its time course. In the case of acute inflamma- ings, except that mucous plugs extruded from the bilateral tory disorders such as bacterial or viral infections, the gland Stensen’s ducts when the parotid glands were compressed becomes swollen and tender after a rather short onset. In (Figure 1a). Eosin staining showed that these plugs were contrast, the gland is not as tender on palpation or as indu- composed of numerous eosinophils (Figure 1b), and rated in chronic inflammatory disorders such as chronic microbiological examination of the plugs revealed sclerosing sialadenitis, Sjo¨ gren’s syndrome or granuloma- normal bacterial flora. A computed tomography (CT) tous diseases. Alternatively, certain systemic disorders scan revealed diffuse swelling of both parotid glands. can be associated with salivary gland swelling; therefore, There was no evidence of tumour or stones (data not secondary salivary gland disorders must be considered in shown). Sialography was performed and the sialogram the differential diagnosis. Thus, it is occasionally difficult showed ectasia and duct leakages but no displacement to diagnose salivary gland swelling due to this variety of (Figure 2). A blood examination, including a haemogram, possible causes. Sialodochitis fibrinosa, first reported by C-reactive protein and autoantibodies to nuclear antigens, Kussmaul,1 is a rare salivary disorder and allergy seems was within normal limits. The serum amylase concen- to be implicated as a cause;2–4 however, the aetiology tration was slightly increased (193 IU/l; normal range and pathophysiology of this condition remain poorly 49–136 IU/l). understood. Our literature review revealed few reports of To evaluate the patient’s allergy status, cytology of nasal sialodochitis fibrinosa. secretions and measurement of the serum immunoglobulin Here, we present two sialodochitis fibrinosa patients E (IgE) level were performed. A radioallergosorbent test with recurring bilateral parotid swelling. (RAST) against major allergens, including Japanese cedar, Japanese cypress, hogweed, mugwort, mites, house dust and candida, was performed. As shown in Table I, Case reports the overall results of these examinations were negative. We next investigated the serum and salivary interleukin Case one (IL)-5 levels, because of the accumulation of eosinophils A 60-year-old woman complained of recurring bilateral into the mucous plugs. Interestingly, the salivary IL-5 parotid gland swelling and pain persisting for several level was 22.6 pg/ml whereas the serum IL-5 level was less decades, which had not diminished. However, her than 5.0 pg/ml (normal ,10 pg/ml) (Table II).

From the Department of Otolaryngology–Head and Neck Surgery, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Japan. Accepted for publication: 23 August 2005.

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FIG.1 (a) The mucous plug extruded from the Stensen’s duct. (b) Eosin staining of the mucous plug, showing numerous eosinophils (Original magniﬁcation, 100 in b).

Case two A 58-year-old woman presented complaining of recurring bilateral parotid gland swelling and pain persisting for the past 20 years. Her medical history was unremarkable except for allergic rhinitis caused by Japanese cedar FIG.2 pollen. Her symptoms were not associated with food. On The sialogram demonstrates ectasia and leakage from the physical examination, the patient had a slight enlargement Stensen’s duct. (a) Front view; (b) side view. of the parotid glands, which were not tender on palpation. An intraoral examination showed neither dryness nor atrophy of the oral mucous membranes. The Stensen’s Tests for autoantibodies, such as the antinuclear antibody, ducts were seen to be discharging mucous plugs, which SS-A autoantibody and SS-B autoantibody, were all on examination showed numerous eosinophils. Microbio- negative. logical examination of the mucous plugs showed normal Allergy examinations were performed (Table I). bacterial ﬂora. Imaging studies, including CT and magnetic Although eosinophils were not detected on cytological resonance imaging (MRI), revealed no tumours or stones examination of nasal secretions, the serum IgE level was in the parotid glands. Blood examinations, including 554.1 IU/ml (normal range 0–295 IU/ml) and the RAST serum amylase (86 IU/l), were all within normal limits. scores for Japanese cedar and Japanese cypress were

TABLE I in some cases.4,7 These results suggest that allergic reac- PATIENTS’ ALLERGY STATUS tions are closely related to the pathogenesis of this disease. Unexpectedly, in our first patient, there was no medical Clinical parameter Case 1 Case 2 history of allergic disease. Furthermore, the allergic examinations, including the cytology of nasal secretions, the WBC (% eos) 5600 (5.2%) 5200 (3.6%) Nasal secretion cytology Eos (2) Eos (2) serum IgE level and RAST score, were all negative. Serum IgE (IU/ml) 292.7 554.1 Although the second patient had allergic rhinitis caused RAST positive allergen None Japanese cedar by Japanese cedar pollen, parotid gland swelling had Japanese cypress never been associated with hypersensitive nasal symptoms History of allergic disease None Allergic rhinitis such as increased secretion, blockage and sneezing. However, in both patients, the IL-5 level in the saliva was WBC ¼ white blood cells; eos ¼ eosinophils; IgE ¼ immuno- much higher that that in the serum. Interleukin-5 plays a globulin E; RAST ¼ radioallergosorbent test crucial role in the proliferation, differentiation, survival and activation of eosinophils.9 Moreover, it is one of the most important eosinophil chemoattractant cytokines.10 TABLE II Interestingly, Burgel et al. have shown that activated eosi- PATIENTS’ INTERLEUKIN-5 LEVELS nophils induce mucin synthesis in human airway epithelial cells via epidermal growth factor receptor (EGFR) acti- IL-5 Case 1 Case 2 vation.11 In the epithelium of the Stensen’s duct, it is Serum (pg/ml) ,5.0 ,5.0 likely that activated eosinophils stimulate mucin synthesis, Saliva (pg/ml) 22.6 51.6 resulting in the production of mucous plugs. Parotid gland swelling is probably due to oedema and mucous plugs IL-5 ¼ interleukin-5 obstructing the Stensen’s duct rather than inflammatory The normal serum IL-5 level is less than 10 pg/ml and/or allergic reactions of the glandular tissue itself. Thus, the potency of IL-5 in the process of eosinophil infiltration and mucous hypersecretion suggests a key role for this molecule in the pathogenesis of sialodochitis fibrinosa. classes four and one, respectively. Meanwhile, those for Interleukin-5 is mainly produced by Th2 cells and mast hogweed, mugwort, mites, house dust and candida were cells as well as eosinophils; therefore, it seems likely that all class zero. These results were compatible with the certain inflammatory reactions induced in the epithelium patient’s medical history of allergic rhinitis. As shown in of the Stensen’s duct could trigger primary immune Table II, the salivary IL-5 level was found to be as high responses. as 51.6 pg/ml, whereas the serum IL-5 level was less than Various inflammatory reactions, especially eosinophilic 5 pg/ml. inflammation, are of great importance in allergic reactions; however, an increased number of eosinophils or concen- tration of IL-5 in a tissue does not necessarily indicate an Discussion allergic reaction. The report published as the official Sialodochitis fibrinosa is a rare salivary gland disease with European Academy of Allergology and Clinical Immu- paroxysmal and recurring swelling of the salivary glands, nology (EAACI) position statement (‘A revised nomencla- which was first reported by Kussmaul in 1879.1 Criteria ture for allergy’) has proposed that hypersensitivity be for the diagnosis of this condition have yet to be clearly subdivided into two groups.12 The first category is ‘allergic established. However, there are several distinctive findings, hypersensitivity’, which includes conditions, such as aller- including: (1) paroxysmal, recurring swelling of the salivary gic asthma and allergic rhinitis, mediated by confirmed gland(s); (2) a medical history of allergic diseases such as immunologic mechanisms. The EAACI has also proposed asthma, allergic rhinitis, urticaria and food allergy; (3) the term ‘nonallergic hypersensitivity’ to categorize increased blood eosinophils and/or an increased serum conditions, such as nonallergic asthma and nonallergic IgE level; (4) secretion from the Stensen’s duct(s) of rhinitis, in which immunological mechanisms cannot be mucous plugs containing numerous eosinophils; (5) sialo- confirmed. Accordingly, sialodochitis fibrinosa may also gram findings of ectasia, interruption and/or leakages of be subdivided into such two groups, namely, allergic sialo- the ducts; and (6) histopathological findings of duct dochitis fibrinosa and nonallergic sialodochitis fibrinosa thickening and/or infiltration of lymphocytes and eosino- with eosinophilia. phils into the stroma surrounding the duct. In our cases, Bacterial infection may also be another possible cause of recurring swelling of both parotid glands and the secretion sialodochitis fibrinosa. Several reports have isolated of mucous plugs containing eosinophils were observed. a-streptococcus from mucous plugs.4,8,13 However, in our Moreover, sialograms showed ectasia and leakages from two cases, microbiological examination isolated no signifi- the Stensen’s duct. These findings were compatible with cant bacterial specimens, only normal flora. Thus, other sialodochitis fibrinosa. Although several diseases, includ- possibilities, besides allergy and bacterial infection, ing sialolithiasis, Sjo¨ gren’s syndrome and salivary gland should be considered in the pathogenesis of sialodochitis tumours, should be considered in the differential diagnosis, fibrinosa. imaging studies and laboratory tests are considered highly The initial management of sialodochitis fibrinosa useful. depends on the severity of the symptoms. In general, The aetiology of sialodochitis fibrinosa is not yet fully massage to compress the salivary glands, the administration understood; however, numerous studies have implicated of antihistamines and/or steroids, or irrigation of the allergies.2–6 Waldbott and Shea2 and Swinny3 have Stensen’s ducts using a steroid solution should be reported cases of allergic parotitis caused by food allergy. considered. Occasionally, patients will develop massive In these cases, allergen avoidance and immunotherapy enlargement of the parotid glands. In these instances, were curative. Alternatively, several cases have displayed parotidectomy may be considered. In both our patients, similar salivary gland inflammatory responses on oral pro- massage to compress the salivary glands was effective in vocation tests using suspected allergens such as candida controlling their symptoms; they were thereafter followed and mites;7,8 moreover, antihistamines have been effective up without treatment.

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