Letter to the Editor

We read with interest the article by Durucan et al. about a 24 years-old previously healthy male who developed myalgia in upper and lower extremity muscles 14 days after the second dose of the Biotech Pfizer Vaccine (BPV) [1]. Twenty-four days after the vaccination “dark urine” was noted and rhabdomyolysis diagnosed [1]. Work-up revealed myositis, which partially resolved upon glucocorticoids [1]. Thirty-three days after vaccination the patient developed exertional dyspnoea and palpitations being attributed to myocarditis with heart failure, which resolved upon application of standard heart failure therapy and continuation of prednisolone [1]. The study is appealing but raises concerns that should be discussed.

We disagree with the diagnosis myocarditis in the index patient [1]. Palpitations, sinus-tachycardia, exertional dyspnea, global hypokinesia, systolic dysfunction, elevated troponin and elevated Creatine-kinase (CK) do not allow a diagnosis of myocarditis. Myocarditis is diagnosed upon enhancing myocardium on cardiac Magnetic Resonance Imaging (MRI) or by endo-myocardial biopsy. 

Concerning cardiac compromise, we should know if Takotsubo cardiomyopathy (TTS) was ruled out as a differential of the cardiological complaints. TTS has been repeatedly reported as a complication of SARS-CoV-2 vaccinations [2]. Arguments for TTS are that the myocardium was hypokinetic, that the ECG showed ST-depression and that troponin and CK were elevated. TTS mimics myocardial infarction clinically, chemically, electro-physiologically and on echocardiography but coronary angiography is normal.  

Rhabdomyolysis has been repeatedly reported as a complication of SARS-CoV-2 vaccinations [3]. However, symptoms started with sensory disturbances [1]. Because the patient complained about sensory disturbances at onset and because nerve conduction studies (NCSs) of the lower extremities revealed reduced amplitude of the sensory nerve action potential (SNAP), sensory polyneuropathy or small fiber neuropathy (SFN) need to be ruled out appropriately. Both sensory polyneuropathy and SFN have been previously reported as complications of SARS-CoV-2 vaccinations [4]. 

Vaccination-triggered rhabdomyolysis can be also the   first   manifestation  of   malignant  hyperthermia susceptibility [5]. We should know if the patient ever underwent generalized anesthesia and if general anesthesia was ever complicated by hyperthermia or malignant hyperthermia-like manifestations. 

Focal or generalized myalgia following a SARS-CoV-2 vaccination is a common complaint, which usually occurs within four weeks after a SARS-CoV-2 vaccination. We should know if the patient was ever seen by a neurologist and if there is an explanation for the discrepancy between myalgia in the upper limb muscles but normal muscle strength and myalgia and muscle weakness in the lower limbs.

The patient had leg edema already 24 days after vaccination [1]. We should know if they were attributed to mild renal insufficiency or to heart failure which could have been present already prior to the occurrence of palpitations and exertional dyspnea. 

The patient had microhematuria without erythrocytes in the urine sediment. An explanation should be provided. Is it conceivable that this was a false positive result? Was porphyria excluded? Myoglobin should have been determined in the serum and the urine. 

Several essential data are missing in the case description. Missing is the information about the treatment of myocarditis. We should know if steroids were increased or if immuno-suppressants were added. Heart failure treatment is not sufficient to treat myocarditis. Missing are the drugs the patient received for muscle pain starting 2 weeks after vaccination. We should know which non-steroidal anti-inflammatory drugs and which muscle relaxants were applied. Knowing the specific compounds and their dosage is crucial, as some of them can trigger rhabdomyolysis. Missing is the EMG interference pattern analysis. Missing is also the blood sedimentation rate. Missing are the reference limits for the blood tests of which the results were reported. Missing is the information if the parents were consanguineous and if the parents were seen by a neurologist.

Because the needle electromyography revealed myotonic discharges, a myotonic disorder should be excluded. CK was still elevated at discharge after the third hospitalization [1]. Did it normalize at the last follow-up? 

Overall, the interesting study has some limitations that call the results and their interpretation into question. Clarifying these weaknesses would strengthen the conclusions and could improve the study.
 

Patients experiencing rhabdomyolysis time-linked to a SARS-CoV-2 vaccination should undergo extensive work-up for subclinical NMD that became symptomatic upon a SARS-CoV-2 vaccination.

Author Contribution

Josef Finsterer

Design, literature search, discussion, first draft, critical comments, final approval.

Disclosures

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

1. I. Durucan et al. "Post COVID-19 vaccination inflammatory syndrome: A case report." Modern Rheumatology Case Reports, 12 May 2022, rxac041. https://doi.org/10.1093/mrcr/rxac041.

2. H. Yamaura et al. "Reverse takotsubo cardiomyopathy as a cause of acute chest pain in a young woman following COVID-19 vaccination." Circulation: Cardiovascular Imaging, vol. 15, no. 1, Jan. 2022, e013661. https://doi.org/10.1161/CIRCIMAGING.121.013661.

3. E. Cirillo et al. "Case Report: Severe rhabdomyolysis and multiorgan failure after chadox1 nCOV-19 vaccination." Frontiers in Immunology, vol. 13, 17 Mar. 2022, 845496. https://doi.org/10.3389/fimmu.2022.845496.

4. J. Finsterer and F.A. Scorza. "Small Fiber Neuropathy." Acta Neurologica Scandinavica, vol. 145, no. 5, May 2022, pp. 493–503. https://doi.org/10.1111/ane.13591.

5. L.R. Van den Bersselaar et al. "The neuromuscular and multisystem features of ryr1-related malignant hyperthermia and rhabdomyolysis: a study protocol." Medicine (Baltimore), vol. 100, no. 33, 20 Aug. 2021, e26999. https://doi.org/10.1097/MD.00000000000 26999.