Recurrent Facial Swelling, Itching in a Young Woman

What caused persistent facial swelling and itchiness to develop around a woman's right ear and left lower jaw? That's the question posed in a recent case report.

When the 32-year-old Black woman presented with facial edema and itching, she had already been living with these symptoms for a year, noted Rebecca G. Brady, MD, of the Naval Medical Center San Diego, and colleagues in JAMA Otolaryngology–Head & Neck Surgery.

The patient said the symptoms had developed around the time she moved to California about 1 year ago. She could not pinpoint any other changes in her surroundings or her diet that might have triggered the symptoms, although she noted that they tended to occur more often when she was at home.

Although her swelling and itching were usually of moderate intensity, occasionally they were severe enough to prompt a trip to the emergency department, she said. On one of these occasions, she had been assessed by clinicians who suggested she had acute parotitis, a diagnosis based on the presence of diffuse gland edema, with no evidence of salivary stones or masses as observed on clinical examination and confirmed by an x-ray.

Initial treatment with oral prednisone bursts and diphenhydramine (Benadryl) relieved her symptoms, while second-generation antihistamines or montelukast (Singulair) were of no help.

Lab tests showed that immune serology and total immunoglobulin (Ig) E levels were within normal limits. A differential blood cell count revealed 10% eosinophils (normal <6%) and an absolute eosinophil count of 500/μL. Titers for antinuclear antibodies, rheumatoid factor, anti-Ro (SS-A), and anti-La (SS-B) were negative.

The team used sialendoscopy to examine her right parotid and left submandibular glands, and did not observe any obstructing stones or strictures. During that procedure, they also irrigated the salivary gland with steroids, with no significant benefit.

They then performed an open biopsy of the right parotid tail, which revealed generalized inflammatory changes and otherwise normal parenchyma. Because the patient had been experiencing severe symptoms so regularly, and had no response to a variety of treatments, she decided to undergo a right superficial parotidectomy. Clinicians performed the procedure without complications. Histologic analysis of the surgical specimen identified substantial periductal inflammatory infiltrate with eosinophils. The patient was diagnosed with eosinophilic sialodochitis (ES).

Discussion

Brady and colleagues noted that "recurrent salivary swelling is a common complaint among otolaryngology patients, and ES -- although rare -- should be part of the differential diagnosis."

In many patients, recurrent salivary gland swelling is due to chronic obstructive sialadenitis (COS), they added, often with salivary calculi that have caused salivary stasis and obstruction. Less frequently, the symptoms may be due to "autoimmune disorders and nonspecific lymphocytic infiltration," they wrote.

While ES is rare, it was first observed over 100 years ago, with reports as far back as 1879 using the terms "sialoadenitis fibrosa," "allergic parotitis," or "eosinophilic sialodochitis."

ES tends to cause "relapsing and remitting major salivary gland swelling with parotid and submandibular glands equally and often bilaterally affected," Brady and team noted. Presenting symptoms generally include pain and swelling of the affected gland, with itching of the overlying skin, and "string-like mucous discharge from the salivary duct orifices."

"These symptoms overlap greatly with those of other types of COS," the authors wrote, citing data suggesting that as many as nine in 10 people with ES have increased levels of serum IgE and peripheral blood eosinophils. This suggests it may be due to an allergic reaction, as reflected by its recent description as "allergy-related sialodochitis."

The group emphasized that while blood test findings seem to indicate "a robust allergic response," only 62% to 66% of patients diagnosed with ES have a co-existing atopic condition, with one study showing allergic rhinitis or asthma in about 88% of patients, atopic dermatitis or urticaria in 41%, and drug or food allergies in 29%.

As in their patient, Brady and colleagues said, imaging tends to show "diffusely enlarged glands without identifiable calculi." Thus, confirmation of an ES diagnosis generally involves "histopathologic findings of dense eosinophil infiltration (50±39/high-power field) around dilated main and interlobular ducts, mucous metaplasia, intraductal mucus plugs rich in eosinophils, and perifollicular hyperplasia."

On sialograms, ES presents "as 'snowflake' or flocculent changes of branch ducts accompanied by irregular stenosis and ectasia of the main duct," which is thought to be caused by mucous plugging, they added.

While there is no consensus on diagnostic criteria for ES, a previous review proposed diagnostic criteria, which helped define the following cardinal features of ES:

• Recurrent paroxysmal swelling of the major salivary glands
• Salivary duct mucus plugs containing numerous eosinophils
• Peripheral blood eosinophilia and elevated IgE level
• Associated atopic disease
• Ductal dilatation and occasional focal narrowing of the major salivary gland ducts
• Periductal eosinophil- and lymphocyte-rich inflammation and fibrosis with associated reactive ductal epithelial cells
• Failure to satisfy the diagnostic criteria of IgG4-related disease

The original case report was presented as a diagnostic challenge that asked readers to determine whether the symptoms were caused by ES, Sjogren syndrome, sialolithiasis, or Mikulicz syndrome. The latter three diagnoses were "less likely in this scenario," Brady and team noted. They explained that the lack of evidence of salivary calculi eliminates sialolithiasis, and as for Sjogren syndrome, there were no clinical or serologic findings aside from salivary gland edema. Furthermore, the absence of lacrimal gland swelling precludes a diagnosis of Mikulicz syndrome, since diagnostic criteria requires swelling of submandibular, parotid, and lacrimal glands.

"Differentiating ES from other forms of COS is particularly relevant to its treatment, although no standard options exist," the authors wrote. In general, persistent symptoms of COS respond to sialendoscopy in 80% to 90% of patients, and possible treatments for ES include "antihistamines, antileukotrienes, and systemic glucocorticoids, with gland excision as a final option."

Immunohistochemical analyses of glandular tissue samples of patients with ES have identified "infiltration of interleukin (IL)-4, IL-13, IL-5, and exotoxin-positive cells, which are key cytokines in atopic disease; as such, biologic therapies may have a potential role in treatment," the group noted.

The patient had some clinical response to treatment with the anti-IL-5 receptor antibody benralizumab (Fasenra) after she was found to have ES on gland excision, they said.

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