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Salivary gland involvement in granulomatosis with polyangiitis: Case report and review of literature

 Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Submission27-May-2021
Date of Acceptance18-Jul-2021
Date of Web Publication03-May-2022

Correspondence Address:
Kunal Chandwar,
Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_105_21


We present a case of granulomatosis with polyangiitis (GPA) presenting with salivary gland enlargement and right parotid abscess, left-sided facial palsy, Lacrimal Gland, extraocular muscle involvement and rapidly progressive necrotizing keratitis. Followed by review of available literature on salivary gland involvement in GPA and how salivary gland involvement may be a good prognostic factor with less renal and central nervous system involvement and argue for greater vigilance in diagnosing salivary gland involvement in GPA. An approach to a patient with salivary gland involvement and suspected autoimmune disease wtih Sjögren's Syndrome, IgG4 disease,Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis and Sarcoidosis is discussed.

Keywords: Antineutrophil cytoplasmic antibody-associated vasculitis, granulomatosis with polyangitis, lacrimal gland, parotids, salivary glands, Wegener's granulomatosis

How to cite this URL:
Chandwar K, Kishor K, Mukherjee S, Dhakad U. Salivary gland involvement in granulomatosis with polyangiitis: Case report and review of literature. Indian J Rheumatol [Epub ahead of print] [cited 2023 Feb 7]. Available from:

  Introduction Top

Granulomatosis with polyangiitis (GPA) or Wegener's Granulomatosis is an anti-neutrophil cytoplasmic antibody-associated (ANCA) vasculitis characterized by granulomatous necrotizing inflammatory lesions involving the upper and/or lower respiratory systems and a tendency to cause pauci-immune glomerulonephritis which may progress rapidly in a lot of cases. Salivary gland involvement is commonly seen in patients with Sjogren's syndrome, IGG4 disorders, and Sarcoidosis and is considered to be uncommon in patients with GPA. We describe a case of GPA involving both parotids and presenting with rapidly progressive necrotizing keratitis leading to phthisis bulbi.

  Case Report Top

A 47-year-old female presented with swelling over the right parotid area which progressed over a month to cause painful mastication and mouth opening and tenderness over the right parotid area. She went to an ear, nose, and throat (ENT) surgeon for the same and fine-needle aspiration cytology (FNAC) was performed after which she developed a discharging sinus and a parotid abscess. Within a few days, after the onset of the parotid swelling, she developed redness and discharge from the right eye associated with periorbital swelling, followed by similar symptoms of redness, discharge, and periorbital swelling in the left eye. About a fortnight later, despite treatment with topical steroids and antibiotics, the symptoms progressed to gradually progressive painful diminution of vision in bilateral eyes further progressing to gradual loss of pressure in her right eye with a complete visual loss with neither projection of rays nor perception of light in the right eye over the next 2–3 months. Later, she also complained of decreased hearing with a discharging left ear along with left-sided facial palsy.

On examination, she was found to be pale, with diffuse tender swelling of right parotid having a discharging sinus at the FNAC site, left infra-nuclear facial palsy, bilateral mixed hearing loss with a left-sided chronic suppurative otitis media. The right eye showed a perforated corneal ulcer with phthisis bulbi with the left eye showing evidence of both scleritis and conjunctivitis with multiple healed corneal ulcers [Figure 1]. Parotid FNAC suggested granulomatous parotitis with normal ACE and IgG4 levels. Erythrocyte sedimentation rate (71 mm/h), C-reactive protein (23 mg/l) levels were elevated, an automated count revealed anaemia (Hb-9.9 g/dl), leukocytosis (16,000/ml) and thrombocytosis (4.48 lakh/ml), renal and liver functions were normal. MPO and PR3 by ELISA were performed where MPO was >100 AU/ml. Cultures from the parotid sinus were sterile. Ultrasonography and elastography of parotids suggested a right parotid abscess and enlarged left parotid with altered elastography. A noncontrast computed tomography (CT) of paranasal sinuses suggested sinusitis of maxillary sinuses and a high-resolution CT thorax showed a single cavitary lung lesion extending from right upper to middle lobe and nodules were seen in the right middle and left lower lobe [Figure 2]. Magnetic resonance imaging brain showed involvement of extraocular muscles, lacrimal, parotid, and submandibular glands bilaterally [Figure 3] without any bony destruction and the pure-tone audiometry was suggestive of moderate-to-severe sensorineural and conductive hearing loss. The renal function and urine examination were within normal limits with no evidence of other systemic involvement. Considering a rapidly progressive organ-threatening ANCA vasculitis a provisional diagnosis of GPA was kept and the patient was given pulse methylprednisolone (1 g) for 3 days followed by oral prednisolone 1 mg/kg/day along with cotrimoxazole prophylaxis. Intravenous cyclophosphamide induction according to the European vasculitis group (CYCLOPS) protocol was initiated. The ophthalmology and otorhinolaryngology departments' consults were sought and duly followed. A 3-week course of broad-spectrum antibiotics was given considering the parotid and ear infection. On 4 months of follow-up, the patient's parotitis stands resolved, with no further deterioration of vision, no new corneal ulcers, and hearing loss having resolved significantly (by about 80%).
Figure 1: Phthisis bulbi of right eye with collapse of anterior chamber and loss of globe volume compared to left eye in magnetic resonance imaging, right eye showing large corneal ulcer with hyperaemia from necrotising keratitis and left eye showing healed corneal ulcers with conjunctival hyperaemia

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Figure 2: High resolution computed tomography thorax (axial cuts) showing pulmonary nodules (*) in right lower and left upper lobe (a and b) and cavitary lesion in right middle lobe (c)

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Figure 3: Magnetic resonance imaging findings: Parotid glands (blue *) appear swollen and oedematous with fluid collection inside right parotid s/o parotitis/parotid abscess (a and b: coronal cuts and d: axial cuts); submandibular gland (b: yellow *) and lacrimal gland (c: green *) also appear enlarged

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  Discussion Top

Search strategy

A MEDLINE and PubMed search was done for “Wegener's granulomatosis” or “granulomatosis with polyangiitis” or “ANCA associated vasculitis” and “salivary glands,” “parotid,” “sub-mandibular” or “sublingual.” The search was last done on June 19, 2021. A total of 49 case reports/case series were studied, of which 7 case reports were excluded due to lack of adequate data and three case reports had eosinophilic granulomatosis with polyangiitis (EGPA) associated with parotid gland involvement. Details of 49 cases from these 39 case reports totaling 50 including the present case were analyzed for the type of salivary gland involvement (parotid, submandibular or sublingual and unilateral and bilateral) and other associated clinical and epidemiological features. The charecteristics then compared to the population cohort studies available.

In our review [Table 1], the average age of GPA patients with parotid involvement was 50 years with a male: female ratio of 1.27:1. 36 (72%) patients were C-ANCA/PR3 positive, 2 (4%) MPO positive, 1 was ANCA negative and the ANCA status was not known for 11 patients. Parotids were the most frequently involved salivary gland, 44 (88%) patients had parotid involvement, of these 38 (76%) had isolated parotid involvement and 24 (48%) had unilateral involvement. One patient had only parotid involvement as the sole manifestation of GPA. Isolated submandibular involvement was seen in 11 patients (22%) amongst whom 8 had unilateral involvement and 2 patients had sublingual involvement. 18 of the 44 patients with parotid involvement (41%) had a sterile parotid abscess. Constitutional symptoms were present in 40 (80%) patients. 39 (78%) patients had ENT involvement and 33 (66%) had lower respiratory tract involvement. Renal involvement was seen in 18 (36%) patients. Ocular involvement was in 13 (26%) patients and mucocutaneous in 10 (20%) patients. Nervous system seen in 17 (34%) patients with cranial or peripheral nerves being predominantly involved (16/17) and facial nerve being the most common nerve to be involved (11/16). Musculoskeletal involvement in form of arthralgias and arthritis was seen in 10 (20%) ([Table S1] Refer to Table S1 for more details ).
Table 1: Charecteristics patients with salivary gland involvement

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In previously published population cohort studies [Table 2], salivary gland involvement was rare in GPA with prevalence varying from <1%[41] to 3%.[44] We saw a mild predilection of GPA with salivary gland involvement in males as compared to females (60:40 in male: female) similar to most studies on GPA [Table 2] though a few studies showed slight female preponderance.[47],[48] GPA is known to present most commonly in the fifth and sixth decades and the mean age of presentation in our review was 50. Constitutional symptoms were present in almost 80% of patients as seen with recent prevalence studies.[48],[49] Upper respiratory tract (ENT) involvement was most commonly present in patients where the salivary gland was involved followed by lower respiratory tract involvement. Both lung and ENT involvement had similar prevalence irrespective of salivary gland involvement but patients who had parotid involvement were much less likely to have renal dysfunction (36% vs. 55–95% in quoted studies). Patients who had salivary gland involvement had lesser mucocutaneous and ocular involvement than usual and the and central nervous system was rarely involved. The facial nerve was quite frequently involved and the affection coincided with the involvement of parotids of the same side.
Table 2: Comapring previously published studies in GPA with our study granulomatosis with polyangiitis patients with parotid involvement with previously published studies

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What would have been interesting to see is if any of the patients with salivary gland involvement in GPA had co-existent IGG4 disease as seen in case reports of EGPA with salivary gland involvement,[50] given the recent interest in the co-existence of ANCA associated vasculitis with IGG4 disease and association of ANCA positive IGG4 more commonly with the Mikulicz/systemic phenotype similar to the case presented by us. Though we did perform an IGG4 serology and the levels weren't elevated, further studies are needed.

Furthermore, the commonality of parotid abscess in patients with salivary gland involvement may throw up an etiological association as the most common organism to cause a parotid abscess – Staphylococcus also has an association with recurrence of GPA and a causal relationship suggested. Our patient had a parotid abscess that was attributed to post-FNAC complications but in hindsight might just be a manifestation of the disease itself. Greater awareness regarding the same in rheumatologists, otolaryngologists, and physicians may help them in suspecting GPA in patients presenting with parotid abscess apart from the usual suspects of tuberculosis, lymphoma, and bacterial infections including staph.

It can be proposed that salivary gland involvement in GPA is a good prognostic factor though larger prospective studies are required to confirm the same, given the fact that salivary gland involvement was more frequently associated with ENT involvement (which is a good prognostic factor) and less frequently with renal and CNS involvement [Table 2] which are known to be associated with a poorer prognosis. When renal involvement is seen in case reports/case series [Table 1], it can be noticed that renal involvement associated with parotid involvement was more common in studies published before 1990 (6/6) than those published after (13/44, 30%), this could be explained by the fact that the GPA would have been diagnosed earlier given better access to healthcare and more sensitive and specific diagnostic modalities and improvement in treatment modalities available to patients, preventing progression to full-blown disease.

More constitutional symptoms and lesser ocular and mucocutaneous involvement may point to the fact that salivary gland involvement offers distinct phenotypic charecteristics to patients with GPA. If one is more observant to look for salivary gland involvement in patients with GPA more cases might be diagnosed and a greater understanding of how salivary gland involvement alters the phenotype may be gained. Salivary gland ultrasound is an accessible, nonexpensive, simple point of care investigation when combined with elastography may detect subtle changes in echotexture and indicate gland involvement when clinical examination may not.

Parotid involvement can be commonly seen in patients with Sjogren's, IgG4 related disorders (IGG4RD), and Sarcoidosis apart for GPA when suspecting an autoimmune cause for parotid involvement [Figure 4]. Our patient had a negative antinuclear antibody, normal serum IgG4 levels (no lymphoplasmacytic infiltrates or storiform fibrosis and a granuloma goes against a diagnosis of IgG4) though there are recent reports of ANCA overlap with IgG4,[51] no hilar adenopathy and a positive MPO with ENT and orbital involvement that favoured GPA.
Figure 4: Differential diagnosis of parotid enlargement in rheumatic diseases

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Our patient was an MPO positive GPA, though MPO positivity has been associated with lesser renal involvement in one study[52] while others were unable to demonstrate important clinical differences between MPO-ANCA–positive and PR3-ANCA–positive patients with GPA.[53] Our patient did not have any renal, cardiac, or CNS involvement and had only asymptomatic lung involvement but the rapidly progressive necrotizing keratitis was a challenging manifestation that leads to the patient losing sight in one of her eyes and significantly damaging the other.

  Conclusion Top

Salivary gland involvement in rheumatology can be seen with Sjogren's, IgG4RD, sarcoidosis, and GPA [Figure 4]. Salivary gland involvement GPA though uncommon may be associated with a better prognosis with less renal and rare CNS involvement, whereas constitutional symptoms and ENT involvement are common. Parotid abscess formation and facial nerve involvement are common in patients with parotid involvement in GPA and parotid abscess can be a manifestation of GPA, though infections and malignancy should be ruled out. Sensitizing physicians, otorhinolaryngologists, ophthalmologists, and rheumatologists to keep a high suspicion of GPA in patients presenting with salivary gland swelling or parotid abscess may help in early diagnosis and prompt management of a disease known to have devastating consequences if left untreated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

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