Acute vision loss associated with IgG4-related, bacterial rhinosinusitis after COVID-19 infection

Corticosteroids and antibiotics may be indicated in patients with severe rhinosinusitis until either IgG4-related or bacterial rhinosinusitis can be ruled out.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic autoimmune fibroinflammatory disease that was recognized recently as manifesting in otolaryngologic diseases such as Mikulicz disease and Küttner tumor.1,2

The case of IgG4-related rhinosinusitis2 resolved with corticosteroid treatment.

Amro A. Harb, BA, from Columbia University Vagelos College of Physicians and Surgeons, New York, and colleagues reported possibly the first case of IgG4-related and Streptococcus constellatus rhinosinusitis and described the uncertainty of the diagnosis and treatment.3

The patient was a man in his 8th decade of life who presented with complaints of a 2-week headache and 2-day acute right-eye visual loss.

Three weeks before presentation, he had had rhinorrhea and was diagnosed with COVID-19. The history was negative for chronic/allergic rhinosinusitis.

Both complaints reported at presentation developed after he recovered from COVID-19. Computed tomography showed opacified sinuses on the right and diffuse inflammation.

A bony erosion of the medial orbital apex bone also was visualized, with inflammation that extended into the apex.

The patient underwent an emergency endoscopic right total ethmoidectomy, frontal sinusotomy, maxillary antrostomy, and sphenoidotomy; all sinuses had diffuse purulence.

Treatment was started with ampicillin-sulbactam with vancomycin for what the investigators presumed to be an acute rhinosinusitis infection with orbital apex cellulitis.

The patient’s condition improved postoperatively, but the headache and decreasing vision progressed, despite antibiotic therapy and confirmed S. constellatus.

The investigators also identified a dense infiltrate of IgG-containing plasma cells, with most IgG4-positive; the serum IgG4 level was elevated markedly at 277 mg/dL. The diagnosis was IgG4-related rhinosinusitis.

Further treatment with oral prednisone was added and the headache and vision improved markedly.

After discharge, the patient was instructed to take prednisone and amoxicillin-clavulanate.

At the 3-week follow-up visit, the headache was gone and the vision returned to the baseline level.

The investigators thought that the previous SARS-CoV-2 infection suggested 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. Increased representation of cytotoxic CD4-positive T-cells was recently discovered in SARS-CoV-2 reactive T-cells, with higher levels associated with hospitalization,4” they wrote.

They explained further that COVID-19 may have exacerbated the underlying IgG4-RD or an IgG4 response, with concomitant induction of the 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,” the investigators concluded. “Hence, corticosteroids and antibiotics may be indicated in patients with severe rhinosinusitis until either IgG4-related or bacterial rhinosinusitis can be ruled out.”


1. Perugino CA, Stone JH. IgG4-related disease: an update on pathophysiology and implications for clinical care. Nat Rev Rheumatol 2020;16:702-14. doi:10.1038/s41584-020-0500-7

2. Ikeda R, Awataguchi T, Shoji F, Oshima T. A case of paranasal sinus lesions in IgG4-related sclerosing disease. Otolaryngol Head Neck Surg 2010;142:458-9. doi:10.1016/j.otohns.2009.09.019

3. Harb AA, Chen Y, Ben-Ami JR, et al. Acute vision loss from IgG4-Related and Bacterial rhinosinusitis after COVID-19. JAMA Otolaryngol Head Neck Surg, Published online August 26, 2021. doi:10.1001/jamaoto.2021.2121

4. Meckiff BJ, Ramírez-Suástegui C, Fajardo V, et al. Imbalance of regulatory and cytotoxic SARS-CoV-2-Reactive CD4+ T cells in COVID-19. Cell 2020;183:1340-53.e16. doi:10.1016/j.cell.2020.10.001