Clinical Report
Complex regional pain syndrome type II following severe acute respiratory syndrome coronavirus 2 vaccination: a case report
2023 Volume 30 Issue 8 Pages 207-211
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2023 Volume 30 Issue 8 Pages 207-211
Most of the population has been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we describe the case of a 17-years-old girl who developed breakthrough pain in the left forearm following SARS-CoV-2 vaccination and was diagnosed with complex regional pain syndrome (CRPS) type II. The patient received several treatments including brachial plexus block, stellate ganglion block, xenon light irradiation, and Japanese Kampo medicine. At 22 weeks after the vaccination, the patient achieved a visual analog scale score of 0 for both pain at rest and breakthrough pain, illustrating the efficacy of the combined treatment for CRPS type II.
Most of the population has been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a worldwide pandemic. In this report, we describe the case of a patient with complex regional pain syndrome (CRPS) type II due to radial nerve injury following the administration of SARS-CoV-2 vaccination through intramuscular injection. This case indicates the possibility of nerve damage after intramuscularly administration of the SARS-CoV-2 vaccine.
This report was approved by the institutional review board of the study institution. Verbal consent was obtained from the patient and her mother for the publication of this case report and accompanying images, and requirement for written informed consent was waived by the institutional review board. This manuscript adheres to the applicable EQUATOR guideline.
The patient was a 17-years-old girl. The patient had a height of 151 cm and a weight of 48 kg. She had no medical history. In 20XX, she received the first vaccine against SARS-CoV-2 in the left deltoid muscle. The injection site is shown in Figure 1a. The next day, the patient developed difficulty in raising the left upper limb and hand edema on the inoculated side. There was no radiating pain at the time of injection. Two days after the vaccination, the patient experienced breakthrough pain in the left radial nerve area and edema of the left hand and sought medical attention from a primary care physician. Blood test results showed no evidence of infection, inflammation, or thrombotic disease. X-rays, bone scintigraphy, thermography, and quantitative sensory testing, nerve conduction tests were not performed. The patient was prescribed 1,200 mg/day acetaminophen and 180 mg/day loxoprofen for pain and an extract from the inflamed rabbit skin induced by the inoculation of vaccinia virus (12 units/day). For edema, she was prescribed 9.0 g/day saireito (Tsumura, Tokyo, Japan), which is a Japanese Kampo medicine. The symptoms were not resolved, and the patient was referred to our department 12 days after the vaccination.
Injection site, radial nerve palsy and color change in the left hand
a: Injection site. The arrow is the injection site. b: Radial nerve palsy. c: Color change in the left hand.
The patient presented to the hospital with pain at rest and breakthrough pain that had visual analog scale (VAS) scores of 5.5/100 and 92/100 mm, respectively. No factors that could induce breakthrough pain were identified. Although the patient did not present with a dropping hand, she could not move her left thumb in upward direction due to motor paralysis. Based on these symptoms, we suspected that she might have radial nerve palsy. The patient underwent ultrasound-guided brachial plexus block (BPB) with 10 ml of 1％ mepivacaine and 1.65 mg dexmedetomidine using the interscalene approach.
Figure 2 shows the treatment and progress of the patient, who was evaluated once a week. There was no change in symptoms at the second visit; therefore, she was diagnosed with CRPS type II. Diagnosis of CRPS was made using Budapest diagnostic criteria1), which included the following conditions:
Changes in visual analog scale score over time
1．the presence of an initiating noxious event or a cause of immobilization;
2．continuous pain, allodynia, or hyperalgesia in which the pain is disproportionate to any known inciting event;
3．evidence of at least one incidence of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain (can be sign or symptom); and
4．absence of other conditions that would otherwise account for the degree of pain and dysfunction.
Our patient met all these criteria.
Anti-epileptic or anti-depressant medications were not administered because the patient was a student preparing for a test and expressed her desire not to suffer the side effects of drowsiness and dizziness. A total of three BPBs were performed. The frequency of the protrusion pain declined, and the pain at rest weakened; therefore, the treatment was switched from BPB to low-level laser therapy of the stellate ganglion area using the Super Lizer PXTM (Tokyo Iken, Tokyo, Japan) and xenon light irradiation of the vaccine injection site using a xenon phototherapy device (AUVE, Nihon Iko, Tokyo, Japan). Thirty-five days after the vaccination, the patient developed cold allodynia of the left hand. Forty days after the vaccination, the patient was initiated on 7.5 g/day of keishikajutsubuto (Tsumura, Tokyo, Japan), a Japanese Kampo medicine, to keep the patient hand warm. Evaluation 50 days after the vaccination revealed the disappearance of pain at rest, breakthrough pain, and motor paralysis. Edema gradually disappeared; therefore, saireito was discontinued. The patient indicated that cold allodynia was not present unless she touched something cold. With winter and the drop in temperature, the cold allodynia worsened. One hundred eleven days after vaccination, the complaint of cold allodynia became more potent, and stellate ganglion block (SGB) was performed with 10 ml of 1％ mepivacaine hydrochloride (Sandoz Pharma, Tokyo, Japan), which relieved cold allodynia for four days. SGB was revised with a switch from mepivacaine to ropivacaine (0.75％ anapain; Aspen, Tokyo, Japan) and the addition of dexamethasone injection (DEXART, Fuji Seiyaku Co., Tokyo, Japan). The effect of the SGB lasted for one week after the change in medication, and SGB was performed once a week. Despite winter, the patient had a VAS score of 0/100 for pain at rest and a VAS score of 11/100 for protrusion pain with SGB using ropivacaine and dexamethasone. SGB was performed four times. The VAS score was 0 for both the pain at rest and projection pain at 22 weeks after the vaccination. The patient was not followed thereafter.
The current case of a patient, who was diagnosed with CRPS type II caused by vaccination against SARS-CoV-2, was notable in two aspects. First, the vaccination site was higher than the recommended site2), causing neurological damage. Second, while antidepressants and anticonvulsants were unavailable, the patient recovered after treatment with BPB, SGB, Japanese Kampo medicine, and xenon phototherapy.
SARS-CoV-2 vaccine using muscular injection is administered worldwide. Iatrogenic nerve damage following injection is a long-standing issue3,4). Nakajima et al. proposed a safer injection site2), which is located at the intersection between the anteroposterior axillary line and the perpendicular line drawn from the mid-acromion process. At this site, the appropriate depth of needle insertion for intramuscular injections are 5 mm greater than that for the subcutaneous injection at a needle angle of 90°. Administering the injection at the correct site is crucial to avoid nerve damage caused by intramuscular injection. In this case, the injection site was higher and anterior to the injection site recommended by Nakajima et al., and administering injection at this site injured the radial nerve. The injection site of the patient was in the area innervated by the axillary nerve5), and literature indicates that the radial nerve runs in this area6). We suspect that the patient sustained a radial nerve injury. Conversely, the lack of radiating pain while administering the injection suggested that the radial nerve injury may not have been severe. Whether CRPS type II developed due to direct needle-induced nerve damage or an immunological response to a vaccine was not determined. Reports on possible exacerbation of CRPS due to vaccination7), development of radial nerve palsy after vaccination against COVID-198), and onset of CRPS after severe COVID-19 illness9) are available in the literature. If neuropathy is severe enough to cause motor paralysis and CRPS, the patient may experience a radiating pain at the puncture site. However, our patient did not experience radiating pain at the time of the vaccine puncture. This CRPS type II may be a double crush syndrome10) that could have been caused by a slight nerve damage from the needle and the generated immunological response. Lee et al. reported a case of ipsilateral radial neuropathy following COVID-19 mRNA vaccination8). According to the report, nerve conduction studies (NCSs) and compound muscle action potentials (CMAPs); therefore, axillary radiculopathy and axonal injury with demyelination were suspected. The results of magnetic resonance imaging (MRI) revealed multiple enlarged lymph nodes in the axilla, and ultrasonography results indicated the compression of the radial nerve by lymph nodes, indicating compressive neuropathy. Intravenous steroids and physiotherapy were administered to the patient. The neurological examination showed normalization, and the patient completely recovered after 1.5 months. However, we did not perform NCSs in the present case, nor did we perform, MRI, and ultrasound examinations in this case. Therefore, we cannot demonstrate any objective evidence of radial nerve palsy.
Figure 1b, c shows the patient having difficulty in moving the thumb in upward direction. Difficulty in elevating the fingers alone was the first sign of posterior interosseous nerve palsy, and pain could not be ruled out as a cause of difficulty in elevation. However, the patient experienced pain in the area innervated by the radial nerve.
First introduced by Atanasoff et al. in 201011), shoulder injury related to vaccine administration (SIRVA) will be observed more often in the future. Therefore, safe practices and caution should be exercised while administering intramuscular injections to avoid SIRVA or CRPS type II.
The current patient received specialized treatments including various nerve blocks, including BPB and SGB, pain medications including acetaminophen and nonsteroidal anti-inflammatory drugs, Kampo medicine, and laser therapy. First, three sessions of BPB were effective in resolving the forearm pain. BPB was performed using the interscalene approach, which was more central than the vaccine injection site. BPB was performed under ultrasound guidance to prevent complications. Studies suggest that dexamethasone in addition to mepivacaine during BPB may prolong the duration of action of the local anesthetic and reduce the inflammatory response to tissue injury12). Furthermore, Kampo medicine was suitable for the current patient and had no side effects such as drowsiness or lightheadedness. The Kampo medicine used in the present case were saireito and keishikajutsubuto. Saireito is a Kampo medicine that has been shown to be effective for postoperative edema and inflammation13). After 8 weeks of administering the vaccine, the patient began complaining of cold allodynia. The current patient was also administered keishikajutsubuto, a strong warming Kampo medicine that is effective against cold allodynia14). Additionally, SGB improved blood flow to the arm and was effective for cold allodynia. Finally, the patient received laser therapy. Xenon light, generated by high-intensity electrical stimulation of xenon gas, is used to sterilize wounds, aid in tissue repair, and relieve pain as a low-level light therapy15). No physiotherapy intervention was performed in this case. Our patient is a pianist, and she was able to resume piano practice after her pain abated.
In summary, as illustrated in the treatment course of a patient who developed CRPS type II after vaccination against SARS-CoV-2, correct muscle injection is important and a combination of approaches including BPB, SGB, xenon phototherapy, and Kampo medicine were useful in the resolution of CRPS type II. Here we presented a case of CRPS type II concomitant with adial nerve palsy. The possibility of double crush syndrome was considered; however, we could not draw a firm conclusion about the uncertainty of diagnosis.
Acknowledgements: We would like to thank Enago (www.enago.jp) for English language editing.
