Rhabdomyolysis is a clinical syndrome characterized by intense muscle breakdown and subsequent necrosis. ¹ Exertional or exercise-induced rhabdomyolysis (exRML) is most commonly reported in military professionals, athletes, and new or deconditioned individuals who engage in strenuous exercise. Although the sickle cell trait (SCT) is generally considered benign, multiple cases have linked it to exRML. ^{1, 3}

Generalized aches and pains, sometimes localized to the upper or lower limbs depending on the type of exercise, are common clinical manifestations of exRML. ⁷ Measuring creatine kinase (CK) levels is considered the most reliable method for diagnosing rhabdomyolysis in a laboratory setting. CK serves as an indicator of muscle tissue breakdown. While there is no universally agreed-upon threshold, a CK concentration exceeding five times the normal upper limit, or 1,000 IU/L, is commonly employed for diagnostic purposes. ⁸ Rhabdomyolysis can lead to a severe complication known as acute kidney injury (AKI), which occurs when myoglobin is depleted and accumulates in the tubules of the kidneys. We present the case of a young patient with sickle cell trait who developed exercise-induced rhabdomyolysis with an atypical presentation, which was successfully managed with aggressive intravenous hydration.

A 31-year-old male with a background medical history of sickle cell trait presented to the emergency department with a 1-week history of left-sided, non-pleuritic, dull aching chest pain that began following the resumption of gym activity after a long period. His exercise regimen consisted of heavy weightlifting, with a maximum weight of 60 kg. He denied fever, recent illness, cough, immobilization, leg swelling, dyspnea, palpitations, arthralgia, dark urine, anabolic steroid use, significant alcohol or drug abuse, or drug allergies.

There was no indication of inherited skeletal muscle or metabolic disorder in the patient's family medical history. He was not taking any regular medication. On examination, vital signs were stable, with normal chest expansion, equal bilateral air entry, and no anterior chest wall tenderness. Electrocardiography ECG showed normal sinus rhythm. Initial investigations, including complete blood count (CBC), troponin, D-dimer, and chest radiography, were unremarkable. Although rhabdomyolysis was considered less likely given his presentation, given the onset of pain with exercise resumption, CK levels were also measured and found to be markedly elevated at 20,792 U/L.

A diagnosis of exertional rhabdomyolysis was made, and aggressive IV hydration was initiated, which was continued in the Acute Medical Unit. The patient was also reviewed by a rheumatology team. Further investigations to rule out immunological and inflammatory causes of the elevated CK levels were negative. With treatment, his pain resolved and CK levels steadily declined over several days. The patient was discharged after several days with acceptable CK levels and appropriate safety netting advice.

The clinical symptoms and signs of rhabdomyolysis include tachycardia, fatigue, palpitations, nausea, vomiting, skin discoloration of the affected muscles, discomfort in the lower back and thighs, and muscle soreness. ⁸ The most typical presentation includes reddish-brown or tea-colored urine accompanied by muscle weakness, pain, cramps, and edema. There have been rare case reports of statin-induced rhabdomyolysis presenting solely as a compressive chest pain. ⁷ exRML can present with diffuse myalgia or localized upper or lower limb pain, depending on the type of exercise. However, a literature search did not reveal any cases of exRML that presented solely with chest pain. Therefore, the isolated, localized, left-sided chest pain with an unremarkable examination in our patient represents a unique presentation of exRML. We recommend considering rhabdomyolysis in the differential diagnosis of patients presenting with isolated chest pain after heavy weight lifting.

Several factors can predispose individuals to rhabdomyolysis, including physical exertion or exercise, trauma, drugs/toxins, dehydration, sickle cell trait (SCT), and high temperature. Studies have shown that exRML was more common among military professionals until the later years of the 20th century. ³ However, there has been a recent significant increase in the number of cases among athletic populations. This upward trend is likely attributable to the widespread adoption of new exercise forms, increased gym attendance, and the use of personal trainers. ⁴

The sickle cell trait (SCT) is another recognized risk factor for exRML. A study of 47,944 US soldiers found that those with SCT had a significantly increased adjusted risk of exRML (hazard ratio 1.54, 95% CI 1.12-2.12, P = .008). ⁵ SCT can predispose individuals to dehydration during intense exercise due to impaired renal concentrating ability. This can lead to erythrocyte sickling and lactic acid accumulation. ⁶ The cause of exRML in this patient was probably due to multiple factors, including the resumption of physical activity following an extended period of inactivity in the context of SCT, which may have heightened his vulnerability. However, it is important to acknowledge that most individuals with SCT do not develop exRML and its presence in our patient could be incidental. Further studies are required to confirm the association between exRML and SCT. If future studies establish a definitive link between exRML and SCT, screening for SCT before initiating intense exercise regimens may be warranted to allow tailored precautions and potentially prevent exRML.

Acute kidney injury (AKI) is a major complication of rhabdomyolysis. The risk of AKI increases with a CK levels of 15,000-20,000 U/L. Nevertheless, numerous studies have demonstrated a limited association between creatine kinase (CK) levels and acute kidney injury (AKI). In fact, AKI has been observed in cases where CK levels were as low as 5,000 U/L. CK levels become a particular concern for AKI when they reach 5,000 U/L in individuals with severe comorbidities such as volume depletion, sepsis, or acidosis. ⁷ Despite markedly elevated CK levels in our patient, there was no evidence of AKI. This may be attributable to the patient's young age and lack of significant comorbidities. Recent studies have also suggested that patients with exRML may be at a lower risk of developing AKI than those with other forms of rhabdomyolysis. ⁴

Given that isolated chest pain is an atypical presentation of exRML, it is easy to miss a diagnosis in such patients. They can be easily misdiagnosed as having muscle strain, particularly if they are otherwise fit and healthy, and have no symptoms other than chest pain. Therefore, maintaining a high index of suspicion for rhabdomyolysis in these patients is crucial. High-intensity exercise is a recognized risk factor for exRML. Therefore, high-risk individuals should consult their primary care physicians before starting or resuming high-intensity exercise. Adequate hydration may help prevent exRML in SCT patients, although further research is needed to establish a definitive link between SCT and exRML.

Written informed consent was obtained from the patient for participation in this case study and publication of anonymized clinical details. Owing to the non-identifiable nature of the case and the absence of any patient images or personal data, written consent was deemed unnecessary. This approach was reviewed and deemed appropriate by the Institutional Review Board. No identifiable patient information has been disclosed in this manuscript.