Report: Subset of Patients with Diabetes and COVID-19 Experience Craniofacial Pain

February 26, 2021
Jared Kaltwasser

The authors of a research letter say a small minority of patients with diabetes have facial pain that cannot otherwise be easily explained.

A new report suggests that COVID-19 may lead to severe craniofacial pain in a subset of patients with diabetes.

The paper comes from a team of investigators from Egypt, the Czech Republic, and Italy. They report that, between April and August 2020, 21 patients of the 5,730 diabetic patients with COVID-19 who sought outpatient care at their clinics sought specialist care for pain in their facial regions.

Most of the 21 consecutive patients were in relatively good health prior to their infections and 76% had their diabetes under control. The mean hemoglobin A1c (HbA1c) level of the group was 6.7. The patients had an average age of 51.71 years, were mostly male (66.67%), and had a mean body mass index of 21.76.

Six of the patients had no systemic comorbidities, but 3 had cardiac conditions, 4 had renal impairment, and 8 had asthma. The patients were taking a variety of antidiabetic drugs, including thiazolidinediones, sodium-glucose cotransporter 2 inhibitors, metformin, and insulin.

The patients’ reported COVID-19 cases were not severe. Most (18 patients) had mild cases and the remaining patients (3) had moderate cases. Only 3 patients had a fever, and it was considered mild in all cases. Four patients had a dry cough, and 2 patients had a sore throat. Two patients reported myalgia.

However, if their COVID-19 symptoms were generally unremarkable, one key feature of their clinical representation was unique: they reported severe pain in the masseter (12 patients) and temporalis (4 patients) regions, or in both regions (5 patients). For 10 patients, the pain was bilateral. For the remaining 11 patients, it was focused on one side or the other.

When asked to rank the pain from 0 (no pain) to 10 (pain as bad as you can imagine), the patients chose an average severity of 7.4. For most patients (85.7%), the pain was made worse when they touched the affected region, and when they chewed (52.4%).

When asked what provided relief, more than half of the patients (62%) said hot fomentation helped. Paracetamol gave relief to 24% of patients, and ibuprofen and diclofenac potassium aided 5% each.

Corresponding author Abanoub Riad, DDS, of Masaryk University, in the Czech Republic, and colleagues, wrote that many potential explanations for the craniofacial distress experienced by these patients could be excluded.

For instance, diabetic neuropathies were unlikely to be the cause since those are mainly caused by long-standing hyperglycemia, and these 21 patients had their blood glucose levels under control. Another possible cause could be paid due to increases in psycho-emotional stress associated with the pandemic, which could increase bruxism and temporomandibular disorders. However, none of the patients in the series had a history of bruxism or orofacial pain.

That left Riad and colleagues to conclude that the coronavirus infection must play a key role in the pain. They pointed to a number of potential factors at play.

“In addition to the well-known pathophysiologic mechanisms by which the diabetic patients are imposed to a greater risk of viral infections such as impaired neutrophil chemotaxis and phagocytosis; the increased expression of angiotensin-converting enzyme 2 in pancreatic islets and the persistent hyperglycemia in [severe acute respiratory syndrome] patients indicated transient damage to beta cells,” Riad and colleagues wrote.

They also noted that viral infections can amplify the cytokine response in adipose tissues, which could lead to craniofacial inflammation.

“Given that our cases’ median age was 49 years old, the relationship between diabetes and pain in the orofacial muscles can be related to glutamate’s role whose neurotoxicity is mediated by the NMDA receptors found on neuronal tissues and peripheral non-nueruonal tissues and cells as β-cells,” they said.

The authors concluded that their cases are the first reported evidence suggesting a link between COVID-19 and pain in the craniofacial tissues. They said the link warrants further investigation.

The study, "Craniofacial pain in COVID‐19 patients with diabetes mellitus: Clinical and laboratory description of 21 cases," was published online in Journal of Medical Virology.


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