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August 26, 2021

Acute Vision Loss From IgG4-Related and Bacterial Rhinosinusitis After COVID-19

Author Affiliations
  • 1Columbia University Vagelos College of Physicians and Surgeons, New York, New York
  • 2Division of General Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York
  • 3Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York
  • 4Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York
  • 5Department of Otolaryngology-Head and Neck Surgery, Columbia University Irving Medical Center, New York, New York
JAMA Otolaryngol Head Neck Surg. 2021;147(10):914-915. doi:10.1001/jamaoto.2021.2121

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune fibroinflammatory disease that can affect nearly every organ, with otolaryngological diseases such as Mikulicz disease and Küttner tumor recently recognized as manifestations of IgG4-RD.1,2 The first case of IgG4-related rhinosinusitis was described in 2009, with complete resolution after treatment with corticosteroids.2 To our knowledge, no case of IgG4-RD with coinciding bacterial rhinosinusitis has been found, highlighting an uncertainty in diagnosis and treatment of such cases. Herein, we present a patient with acute vision loss following SARS-CoV-2 infection who was diagnosed with IgG4-related and Streptococcus constellatus rhinosinusitis, with complete resolution after treatment with surgery, antibiotics, and corticosteroids.

Report of a Case

The patient was a man in his 70s with no history of chronic or allergic rhinosinusitis who presented to the emergency department with a headache for 2 weeks and vision loss in the right eye for 2 days. Three weeks prior, he had rhinorrhea and was diagnosed with COVID-19. He recovered from COVID-19 but developed a worsening right-sided headache 1 week later and right vision loss 2 days prior to presentation. On physical examination, right eye visual acuity was limited to hand-motion detection, with severe pain on ocular motion. Maxillofacial computed tomographic scan revealed opacification of all sinuses on the right with diffuse inflammation. Notably, there was bony erosion of the medial orbital apex bone, with extension of inflammation into the apex (Figure 1). Emergency endoscopic right total ethmoidectomy, frontal sinusotomy, maxillary antrostomy, and sphenoidotomy were performed, with diffuse purulence noted in all sinuses. Sinus specimens were collected, and ampicillin-sulbactam with vancomycin was initiated for presumed acute bacterial rhinosinusitis with orbital apex cellulitis.

Figure 1.  Contrast-Enhanced Computed Tomographic Scans
Contrast-Enhanced Computed Tomographic Scans

Complete opacification of the (A) right frontal sinus, (B) right ethmoid sinus with erosion of the medial orbital apex bone, extension of inflammation into the apex, and an air-fluid level in the sphenoid sinus, and (C) right maxillary sinus.

Although there was initial improvement after surgery, the patient’s headache and vision progressively worsened on treatment with antibiotics, despite sinus cultures confirming the presence of S constellatus. Histopathologic analysis later revealed a dense infiltrate of IgG-containing plasma cells, with most being IgG4 positive (Figure 2). Likewise, serum IgG4 was elevated at 277 mg/dL (normal, <123 mg/dL). Consequently, IgG4-related rhinosinusitis was diagnosed based on comprehensive diagnostic criteria.3 Oral prednisone was added to the patient’s regimen, which was followed by remarkable improvement in his headache and vision, and he was thus discharged with prednisone and amoxicillin-clavulanate. Follow-up 3 weeks later revealed that his vision returned to baseline, and his headache completely resolved.

Figure 2.  Histopathologic Images
Histopathologic Images

A, A dense band-like infiltrate of lymphocytes and plasma cells was present beneath the epithelium (original magnification ×40). B, IgG stain demonstrates 50 to 100 plasma cells in many high-power fields (original magnification ×40). C, Most of the IgG-containing plasma cells were IgG4 positive (original magnification ×40).


To our knowledge, this is the first case describing simultaneous IgG4-related and acute bacterial rhinosinusitis after an earlier SARS-CoV-2 infection. Although rare, rheumatological workup for IgG4-RD in patients with severe rhinosinusitis and acute vision loss is critical because treatment of IgG4-RD differs from that of bacterial rhinosinusitis. In this patient, more than 40% IgG4-positive plasma cells on histopathologic analysis and elevated IgG4 serum levels fulfilled comprehensive diagnostic criteria for IgG4-RD.3 Moreover, cultures grew S constellatus, a commensal bacterium associated with orbital invasion,4 although acute vision loss in rhinosinusitis can occur from other bacteria.

Importantly, this patient’s prior SARS-CoV-2 infection suggests a possible relationship between COVID-19 and IgG4-RD. Immunoglobulin G4-RD is mediated by cytotoxic CD4-positive T-cells, an atypical subset of helper T-cells with cytotoxic ability.1 Increased representation of cytotoxic CD4-positive T-cells was recently discovered in SARS-CoV-2 reactive T-cells, with higher levels associated with hospitalization.5 This finding signals a possible link between COVID-19 and IgG4-RD, which was suspected earlier in another patient who developed IgG4-related subglottic stenosis after COVID-19.6

Overall, COVID-19 may have led to either exacerbation of underlying IgG4-RD or an IgG4 response, with simultaneous precipitation of an acute bacterial rhinosinusitis. Although corticosteroids are standard for IgG4-RD and antibiotics for bacterial rhinosinusitis, simultaneous use of both was effective in this patient who had both diseases. Hence, corticosteroids and antibiotics may be indicated in patients with severe rhinosinusitis until either IgG4-related or bacterial rhinosinusitis can be ruled out.

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Article Information

Corresponding Author: Amro A. Harb, BA, Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032 (aah2181@cumc.columbia.edu).

Published Online: August 26, 2021. doi:10.1001/jamaoto.2021.2121

Conflict of Interest Disclosures: Dr Turk does consulting work for Ventana/Roche. No other disclosures were reported.

Additional Contributions: We are grateful to the patient for providing consent to publish this case report, and we thank Stephen M. Lagana, MD, for obtaining and analyzing the histopathologic slides in this case report.

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