Woman with COVID develops bilateral periorbital pain, edema
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A 27-year-old woman was urgently transferred to Tufts Medical Center, from an outside hospital, for painful worsening facial cellulitis and pansinusitis. Her medical history was notable only for frontal bone fracture in 2001.
Eleven days before transfer to Tufts Medical Center, she awoke acutely ill with several symptoms including sore throat, fever, malaise, and loss of taste and smell. On day 7 of the illness, she developed left-sided midface swelling and pain and subsequently went to an outside hospital for emergency care. She was diagnosed with SARS-CoV-2 and facial cellulitis and was prescribed cephalexin 500 mg three times daily. Two days after beginning antibiotics, her symptoms worsened; the swelling spread to both periorbital areas, and she developed pain with extraocular movement, a severe headache, light sensitivity and inability to breathe out of the left naris.
She returned to the outside hospital, where she was admitted to the ICU. CT imaging of the face showed pansinusitis, and she underwent emergent sinonasal debridement. The preliminary report from the sinonasal debridement revealed gram-negative rods and mucopurulent exudate with areas concerning for necrotic debris. Given the rapid clinical deterioration, bacterial and fungal etiologies remained on the differential. The patient was treated empirically with ceftriaxone, clindamycin, posaconazole, oxymetazoline nasal spray and one dose of dexamethasone to reduce facial swelling. She was then transferred to the Tufts ICU for higher level of care.
Examination
When the patient arrived at Tufts Medical Center, an ophthalmology consult, along with infectious disease and ENT consults, were immediately requested. On examination, she was in moderate distress due to pain but was otherwise awake, alert and oriented. There was extensive periorbital and facial edema, erythema and petechial lesions (Figure 1) along the nose and midface with skin breakdown along the medial canthus and tear trough of the left eye. Visual acuities were 20/20 in the right eye and 20/20-2 in the left eye. Confrontation visual fields were full, and color vision was normal bilaterally. The pupillary response was brisk in both eyes without an afferent pupillary defect in either eye. Extraocular motility was painful in all directions, and there was limitation in supraduction in the right eye. IOPs were normal bilaterally.
Source: Allison V. Coombs, DO, MS, and Laurel N. Vuong, MD
The conjunctiva was white and quiet without chemosis, and the rest of the anterior segment exam was normal. On posterior segment exam, the optic nerves were pink with sharp margins bilaterally. The retinal vasculature was dilated and tortuous in both eyes, without retinal or choroidal pathology. Within hours of her initial ophthalmic examination, her symptoms and findings worsened. Her subsequent exam showed worsening elevation limitation with a new abduction limitation in the right eye. Visual acuities decreased to 20/25 in both eyes.
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Worsening condition
Given the rapidly worsening nature of the patient’s condition, there was continued concern for an infectious process, as she was previously treated with a dose of dexamethasone, and a noninfectious process would have likely improved with steroids. Initially, it was also unclear if her clinical presentation was worsening due to inappropriate antibiotic/antifungal coverage or if the previously administered steroids had worsened the process. It was also difficult to differentiate if she had a bacterial vs. a fungal infection. Given her worsening extraocular motility, the differential included orbital extension of the infection or cavernous sinus involvement, such as thrombosis in the setting of infection. Additional information was needed.
Workup and management
Given the concern for an invasive infectious sino-orbital sinusitis, empiric antimicrobial coverage was initiated immediately with vancomycin and piperacillin/tazobactam along with amphotericin for antifungal coverage.
The patient underwent an emergent functional endoscopic sinus surgery (FESS) for further evaluation and debridement. She was found to have necrotic and mucopurulent debris in the maxillary, ethmoidal and sphenoid sinus cavities. Brain and orbital MRI with and without contrast showed right intraorbital extension of the infectious process. MRV of the head showed bilateral superior ophthalmic vein thrombosis (SOVT) (Figure 2). Blood cultures were also obtained. The FESS was ultimately repeated four times over the course of the first 4 hospital days due to continued nasal and sinus tissue necrosis. Unfortunately, this resulted in significant loss of facial tissue and disfigurement. Tissue reconstruction was deferred due to active, uncontrolled infectious disease.
Tissue specimens obtained during FESS revealed a necrotic, invasive pseudomonas infection, and blood cultures from admission ultimately grew Pseudomonas aeruginosa.
Discussion
Recently, there have been many reports in the literature regarding the increased frequency of rhino-orbital invasive fungal sinusitis after COVID, or COVID-19-associated mucormycosis (CAM). Notably, Tooley and colleagues reported a significant increase in CAM seen at the Mayo Clinic over a 3-month period during the ongoing COVID pandemic. The article suggests that the typical risk factors of diabetes, immunosuppression or immunocompromise, and steroid treatment for COVID-19-related inflammatory or pulmonary disease are the leading risk factors for CAM. Additionally, none of the patients reported by Tooley and colleagues were fully vaccinated. Given that CAM is both vision- and life-threatening, and given the patient’s positive COVID status, invasive fungal rhino-orbital sinusitis was high on our differential diagnosis, and she was therefore treated empirically with amphotericin as we awaited tissue culture results.
P. aeruginosa isolated from tissue samples from the FESS was imperative in our patient’s diagnosis and management, highlighting the importance of obtaining tissue or culture in similar clinical situations, especially given some concern for an invasive fungal process. Positive tissue culture for Pseudomonas allowed for narrowing of antimicrobial therapy by eliminating amphotericin, a highly nephrotoxic and poorly tolerated medication. In addition, the surgical management of invasive fungal disease is typically much more involved and aggressive than in bacterial processes.
Invasive necrotic sino-orbital Pseudomonas is a rare entity that is typically seen in immunocompromised individuals. There are some case reports characterizing this disease, clinical course and effective management. Chen and colleagues reported invasive sino-orbital disease from Pseudomonas in two immunocompromised patients. Our patient had an extensive workup that did not show any typical underlying immunocompromising conditions. We hypothesized, however, that our patient may have had some immune dysfunction secondary to COVID.
Superior ophthalmic venous thrombosis is also rare and usually occurs in the setting of sepsis or a hypercoagulable state. The bilateral SOVT was likely the cause of our patient’s limitation in extraocular motility secondary to venous congestion and ischemia. The orbital extension of the infection may have also contributed to the limitation in extraocular motility as well. Our patient had a negative hypercoagulable workup during her hospital course. The thromboses were thought to be secondary to her COVID status. Prothrombotic events have been reported at an increased frequency with COVID. The pathophysiology of hypercoagulability in COVID is attributed to systemic endothelial dysfunction, causing thrombosis via upregulation of platelet activation and proinflammatory cytokines such as interleukin 6. To our knowledge, this is the first report of bilateral SOVT in a patient with no other pro-thrombotic risk factors except active COVID.
The bilateral SOVT required anticoagulation. Because of the frequent surgical interventions, a heparin drip was used early in the patient’s hospitalization.
Clinical case continued
The patient’s clinical presentation started to improve on hospital day 8 with the appropriate intervention. The ophthalmoplegia resolved, and her pain improved. Visual acuity returned to 20/20 in both eyes without any further disease progression. Once her condition improved and no additional procedures were needed, she was transitioned to oral anticoagulation, under the guidance of the hematology-oncology service. Because the thrombi were provoked, rather than due to a primary hypercoagulable dysfunction, she will be able to discontinue anticoagulation in the future.
The patient is pending reconstructive facial surgery at this time but has been medically stable, discharged to home and is back to her usual activities of daily living.
- References:
- Abdel-Aziz M, et al. J Craniofac Surg. 2021;doi:10.1097/SCS.0000000000008231.
- Chen X, et al. Ophthalmic Plast Reconstr Surg. 2016;doi:10.1097/IOP.0000000000000558.
- Desai EJ, et al. Indian J Otolaryngol Head Neck Surg. 2021;doi:10.1007/s12070-021-02807-2.
- El-Kholy NA, et al. Laryngoscope. 2021;doi:10.1002/lary.29632.
- Sotoudeh H, et al. Eur J Radiol Open. 2019;doi:10.1016/j.ejro.2019.07.002.
- Tooley AA, et al. JAMA Ophthalmol. 2021;doi:10.1001/jamaophthalmol.2021.5202.
- van der Poel NA, et al. Orbit. 2019;doi:10.1080/01676830.2018.1497068.
- For more information:
- Allison V. Coombs, DO, MS, and Laurel N. Vuong, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Allison V. Coombs, DO, MS, and Nisha S. Dhawlikar, MD, MPH. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.