Severe hyperalgesia and pain during botulinum toxin injection avoiding application in a patient 1 week after COVID‐19 infection

Available evidence suggests that coronavirus disease 2019 (COVID19) infection is associated with myalgia, pain, and widespread hyperalgesia.1 SARS-CoV-2 virus may lead a strong inflammatory response via elevation of cytokine levels including IL-6, IL-10, and TNF-α. 2 Particularly IL-6 is a significant inflammatory cytokine involved in muscle pain, and intraplantar administration of IL-6 to mice leads mechanical hyperalgesia.3,4 Furthermore, IL-6 not only produces acute muscle hyperalgesia but also induces chronic latent hyperalgesia, pointing a crucial role of IL-6 not only in acute but also in chronic muscle pain.3 A 55-year-old-woman presented with a demand for botulinum toxin type A (BTX) injection for correction of facial wrinkles. Past medical history revealed that BTX injection has been performed regularly to the patient's upper face by the same dermatologist for every 4-6 months for 7 years without any anesthetic administration. She responded very well to the BTX injections without any side effects or complications. Detailed history revealed that she has been recovered from COVID-19 infection 1 week before. She has been exposed to COVID-19 infection with a proven positive PCR test 3 weeks before BTX procedure with the onset of symptoms including myalgia, nasal discharge, headache, and malaise. Three days after the onset of symptoms, severe facial pain, low back pain, and inguinal pain started, and her pain gradually continued to increase. The patient received favipiravir, enoxaparin sodium, and paracetamol tablet in this period. Despite negative swab testing on the 11th day, the pain regressively affected the knees and ankles accompanied with weakness. As usual, BTX is diluted with 2.5 ml saline and drawn up into the 1 ml 30G insulin syringes. Glabellar frown lines, crow's feet at the side of the eyes, and horizontal forehead creases are marked as appropriate sites for BTX injection. However, the patient experienced severe pain during the BTX administration into her left glabellar crease. After the first application, the patient's pain improved slightly although cold packs were applied to the treatment site prior to and immediately after BTX injection. Despite ongoing but reduced pain, the second BTX injection was performed to the right glabellar crease. But this time, the patient stated that she did not experience such pain in her life and that she could not continue the injection. Therefore, the BTX injection was obliged to have been stopped. The patient was questioned to rate her pain severity on a 10-point scale. The pain score was 10 for the current BTX application, while it was 3 for the last BTX administration performed 4 months before. Her medical history showed that she was undergoing levothyroxine sodium for hypothyroidism for 20 years. The COVID-19 outbreak brought along the problem of chronic pain and hyperalgesia. In addition to direct viral damage, excessive inflammation and increased pro-inflammatory cytokine levels including IL-6, IL-8, TNF-α, and IL-1β are associated with disease severity and outcome in COVID-19.5 Especially administration of IL-6 could lead mechanical allodynia or thermal hyperalgesia, and intrathecal injection of anti-IL-6 neutralizing antibody may improve these pain-related behaviors.6 We think that the pain in the muscles of the patient may have led her to be unable to undergo BTX injection, which is already a painful procedure. Since there may be long-term chronic pain and hyperalgesia after COVID-19 infection even if swab tests come back negative, it may be necessary to wait for a while for cosmetic procedures such as BTX injection following COVID-19 infection. Although the waiting period is not certain, we think that waiting for a period of at least 1 month in such patients or applying topical anesthetics prior to the procedure may be reasonable for the patient and the practicing physician.