Atypical Presentation of Exertional Rhabdomyolysis in Older Adults: Two Case Reports and Literature Review

Introduction

Rhabdomyolysis (RM) involves a series of clinical syndromes induced by the release of cellular contents and their degradation products into the bloodstream after various factors have caused striated muscle injury. Depending on disease severity, patients with RM may be asymptomatic or may present with myalgia and dark urine. Auxiliary examinations typically reveal increased creatine kinase (CK) and myoglobin (Mb) levels [1–3]. RM may have multiple causative factors, including drugs, trauma, high-intensity exercise, infections, toxins, and autoimmune disorders [3,4]. Exertional rhabdomyolysis (ER) is a pathological skeletal muscle injury caused by high-intensity physical activity. ER is common among individuals who participate in strenuous, prolonged, and repetitive muscle overload activities. Patients with mild ER may have no obvious clinical symptoms, whereas those with severe ER may develop serious complications such as acute kidney injury (AKI), osteofascial compartment syndrome, disseminated intravascular coagulation, and arrhythmias, which may be life-threatening [5]. Here, we describe 2 patients with ER who exhibited atypical symptoms.

Case Reports

CASE 1:

A 72-year-old man was admitted to the hospital due to asthenia, palpitations, and non-pitting edema of the limbs. The patient was 169 cm tall and weighed 65 kg. He had previously been in good health and did not regularly engage in strenuous exercise. Three months before admission, he had developed mild asthenia, palpitations, and non-pitting edema of the limbs after high-intensity physical labor, which included 1 week of continuous house renovation work involving the lifting and moving of heavy objects; his symptoms had persisted since onset. He denied experiencing nausea, vomiting, tea-colored urine, myalgia, chest pain, or other symptoms.

The patient had sought treatment at a local hospital. Laboratory examination revealed a CK level of 750.56 U/L (reference range: 26–174 U/L), a creatine kinase isoenzyme MB (CK-MB) level of 39.99 U/L (reference range: 0–40 U/L), and a lactate dehydrogenase (LDH) level of 336.24 U/L (reference range: 120–250 U/L). Because we initially considered a diagnosis of idiopathic inflammatory myopathy, the patient received methylprednisolone 40 mg/day, but limb swelling was not alleviated. He was discharged despite persistent symptoms. Because the swelling remained mild and did not affect daily life, he did not seek further medical evaluation at that time. The patient was admitted to our center 3 months after discharge from the local hospital. At admission, his vital signs were within normal limits. Physical examination revealed only mild limb swelling, without other abnormalities. Laboratory testing showed substantial increases in CK and Mb and slight increases in CK-MB, LDH, alanine aminotransferase, and aspartate aminotransferase. Cardiac troponin, renal function, coagulation studies, electrocardiography, and echocardiography findings were unremarkable. Antinuclear antibody testing, myositis antibody testing, electromyography, muscle magnetic resonance imaging, and other related examinations also showed no abnormalities.

Based on the examination findings, cardiogenic disease and idiopathic inflammatory myopathies were excluded. Because the CK level was more than 10 times the upper limit of normal, mild myositis or subclinical muscle injury was not considered. Given the history of high-intensity physical labor, RM was suspected. After aggressive fluid replacement (volume: 1500 mL daily, approximately 200 mL/h; high water intake was also encouraged), the patient’s limb swelling gradually resolved. Repeat testing showed a slow but steady decline in CK levels (Figure 1). After other differential diagnoses had been ruled out, and considering the clinical improvement that occurred after treatment, the patient was diagnosed with ER. Telephone follow-up at 1 and 3 months after discharge confirmed substantial improvement in limb swelling.

CASE 2:

A 52-year-old man who worked in water and electricity engineering presented with bilateral lower limb edema and asthenia accompanied by palpitations that had persisted for 1 month after a period of short-term high-intensity physical labor, which involved continuous moving (for relocation purposes) over 1 week. The patient was 169 cm tall and weighed 74 kg. He had previously been in good health and rarely engaged in strenuous exercise at work or in daily life. He did not report nausea, vomiting, tea-colored urine, myalgia, chest pain, or other symptoms.

The patient had initially sought treatment at a local hospital. Biochemical testing revealed a CK level of 2266.0 U/L, CK-MB level of 73.0 U/L, and LDH level of 294.0 U/L. He was diagnosed with myocardial injury and received myocardial-nourishing therapy. The local hospital classified the patient’s condition as a “cardiac-related disease”; treatment solely consisted of cardiac support, during which his CK level continued to increase to 2950 U/L. He was subsequently transferred to another facility. Although the diagnosis remained unclear, adequate fluid replacement therapy was administered, and his CK level gradually decreased to 1500 U/L. However, his symptoms did not improve, and he was admitted to our hospital for further evaluation.

Based on the prior findings, idiopathic inflammatory myopathy or rhabdomyolysis was suspected. Laboratory examination at admission revealed a CK level of 1936.8 U/L, CK-MB level of 37.0 U/L, and LDH level of 288.0 U/L. Cardiac troponin, renal function, coagulation studies, electrocardiography, echocardiography, electromyography, and antinuclear antibody testing showed no abnormalities. The patient again denied nausea, vomiting, tea-colored urine, myalgia, and chest pain. Idiopathic inflammatory myopathy was therefore excluded. Given that his CK level was more than 10 times the upper limit of normal, mild myositis or subclinical muscle injury was also ruled out.

Following aggressive fluid replacement (volume: 1500 mL daily, approximately 200 mL/h; high water intake was also encouraged), CK levels declined gradually but at a slow rate (Figure 2). Limb swelling and palpitations also gradually resolved. As in the previous case, based on the patient’s symptoms, auxiliary examination findings, positive response to fluid replacement therapy, and exclusion of other possible diagnoses, he was diagnosed with ER. Telephone follow-up at 1 and 3 months after discharge confirmed full recovery.

Discussion

Multiple case reports and literature reviews on ER have been published. We searched PubMed using the keyword “exertional rhabdomyolysis” for case reports from the past decade (January 2015 to December 2024); our findings are summarized in Table 1 [6–26]. To our knowledge, this report is the first description of 2 atypical ER cases. Both cases were triggered by short-term high-intensity physical labor and were primarily characterized by limb swelling, asthenia, and palpitations, without the typical symptoms of myalgia and dark urine.

As a rare subtype of RM (approximately 2.1%) [27], ER mainly manifests as myalgia and dark urine. Luetmer et al [28] conducted a case series analysis of 21 patients with ER and found that all patients exhibited myalgia. Therefore, the assessment of myalgia has important diagnostic value in ER. Although both patients in the present report had a history of overexertion before disease onset, they lacked common clinical manifestations such as myalgia and dark urine; instead, they presented with limb swelling and asthenia. Moreover, CK elevation was modest in both patients, differing from the substantial increases typically observed in ER [27]. No similar reports have been published to date, which complicates early diagnostic efforts. ER is generally more prevalent in young individuals who engage in high-intensity physical labor; it is rarely reported in middle-aged and older adults. This rarity may reflect lower participation in strenuous activity in these age groups. However, both patients in the present report were middle-aged or older and developed limb swelling, asthenia, and palpitations after short-term high-intensity physical labor without prior conditioning. These findings highlight the risk of misdiagnosis in clinical practice. To improve diagnostic accuracy, clinicians should obtain detailed medical histories (particularly regarding recent high-intensity physical labor), conduct appropriate laboratory tests, and pursue timely multidisciplinary collaboration. Larger studies are needed to further characterize the clinical course of this patient population.

ER may be induced by various etiological factors, and patients typically develop this condition at a younger age. Boden et al [29] analyzed 40 654 ER cases and found that common triggers included no-equipment exercises (such as push-ups, sit-ups, and squats), ball games, and cycling. Most ER cases occurred in individuals between 16 and 35 years of age. The present report describes 2 middle-aged and older patients – neither had engaged in the above strenuous activities before disease onset, which hindered initial diagnosis.

Different populations and environmental conditions may exert substantial effects on ER occurrence [30,31]. The incidence of ER is relatively low among individuals who maintain long-term exercise habits, likely due to their adaptation to regular exercise intensity. In contrast, individuals who do not exercise regularly are more likely to develop ER when they suddenly perform prolonged strenuous activity. The intensity and duration of physical exertion are also important contributing factors, given that prolonged strenuous exercise may lead to heat exposure and electrolyte disturbances, which are closely associated with ER. Obesity further increases ER risk; each 1-unit increase in body mass index can increase ER risk by 14%, possibly due to reduced heat tolerance and impaired thermoregulation among individuals with higher body fat [31]. In the present report, neither patient participated in strenuous exercise in daily life, which increased their likelihood of developing ER after sudden prolonged exertion.

Patients with ER typically exhibit greatly elevated CK levels. In a study of 42 patients with ER, the average CK level was 16 884 U/L, and the maximum observed level was 240 000 U/L [27]. Therefore, clinicians may find it more difficult to suspect ER in patients with only modest CK elevation, which might contribute to missed diagnoses.

Currently, ER is primarily diagnosed based on medical history and blood biomarkers such as CK and LDH. However, these biomarkers considerably vary among individuals and may therefore affect diagnostic accuracy. It has been reported that certain urinary proteins, such as cathepsin H (CTSH), may help to confirm the diagnosis of ER [32]. CTSH demonstrates high sensitivity in detecting exercise-induced muscle injury, and it shows correlations with CK and LDH levels in affected patients. Thus, CTSH may serve as a potential biomarker for ER, although its clinical application requires further study.

The differential diagnosis of ER is essential, particularly in atypical cases. Common etiologies that require consideration include drugs, toxins, metabolic disorders, trauma, infections, and idiopathic inflammatory myopathies. For atypical presentations, a detailed medical history aids in excluding drug exposure, toxin exposure, and traumatic injury. Comprehensive laboratory testing is necessary to identify infections and metabolic abnormalities. The differential diagnosis of idiopathic inflammatory myopathies requires thorough electromyography assessment, autoantibody profiling, and muscle imaging. The 2 atypical cases described in this report were diagnosed only after detailed history-taking and comprehensive supplementary evaluations.

ER is mainly treated with timely and adequate fluid replacement to correct hypovolemia and prevent AKI. Fluid replacement is central to ER management. Sodium lactate solution or 0.9% saline is commonly used, with an initial infusion rate of approximately 400 mL/h or a range of 200 to 1000 mL/h, adjusted according to urine output. Renal replacement therapy (RRT) should be considered if anuria persists despite adequate fluid replacement [2]. Some researchers have proposed the use of sodium bicarbonate or mannitol to prevent AKI in patients with ER. However, evidence increasingly does not support this approach. Accordingly, sodium bicarbonate or mannitol is not recommended as routine treatment for ER [33]. Although diuretics may increase urine output during fluid resuscitation, thereby reducing myoglobin deposition in renal tubules, no evidence currently confirms the effectiveness of this method. In contrast, diuretics may promote the deposition of Tamm-Horsfall protein in renal tubules and further increase myoglobin deposition, resulting in tubular obstruction [34,35]. Thus, diuretics are not routinely recommended in ER cases unless fluid overload is present [34]. RRT plays an important role in the treatment of ER; however, its routine use is not recommended because it does not prevent AKI. The decision to initiate RRT should be based on the severity of renal impairment and the presence of life-threatening complications such as hyperkalemia, hypercalcemia, hyperazotemia, anuria, or hyperhydration unresponsive to diuretics [2,36]. Hyperkalemia, hyperphosphatemia, and hypocalcemia are common electrolyte disturbances in patients with ER. These complications require appropriate management, given that inadequate treatment may induce additional complications. In early-stage ER, treatment of hypocalcemia may aggravate calcium salt deposition in injured muscles; during the convalescent stage of ER, serum calcium levels may normalize or increase [37].

For individuals at risk of ER, certain preventive measures are recommended. Moderate water supplementation before exercise may reduce ER incidence because dehydration increases physiological load, decreases sweating, heightens perceived fatigue, and raises core body temperature [31,38]. Dehydration is also a risk factor for acute renal failure. Increased fruit consumption and appropriate potassium supplementation may further contribute to ER prevention [31].

Currently, no consensus exists regarding the resumption of exercise by patients with ER. Recommendations may follow the standards proposed by O’Connor et al [39]. Patients with ER can be categorized into low-risk and high-risk groups with respect to recurrence. For low-risk patients, a 3-stage guideline may be used to facilitate gradual resumption of exercise. For high-risk patients, the presence of myopathy or metabolic disease should be evaluated. Patients without myopathy or metabolic disease may gradually resume exercise under close medical supervision using the same 3-stage guideline applicable to low-risk individuals. Those with myopathy or metabolic disease require evaluation by healthcare professionals and should gradually resume exercise under their guidance.

Conclusions

Both patients in this report were middle-aged and older; they did not engage in long-term high-intensity physical labor. They experienced limb swelling and palpitations after short-term high-intensity physical labor without prior conditioning. Although these patients had no structural cardiac abnormalities and maintained normal renal function, they remained at risk for subsequent cardiac rhythm disturbances (such as arrhythmias), electrolyte disorders, and AKI. These patients also had prolonged disease courses, slow treatment responses, and a high likelihood of recurrence. Such patients require close monitoring and follow-up. Despite the rarity of ER in this population, timely and thorough differential diagnosis is essential to prevent adverse events.

Data Availability

Data that support the findings presented in this report are available from corresponding author Zai-Chun You upon request.