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31 January 2025: Articles  USA

Rhabdomyolysis of Infectious Etiology with Creatine Kinase Above One Million: A Case Report

Unusual clinical course, Challenging differential diagnosis

Marshall Weber12ABCDEF, William Goss1BCDE, Colton Hoffer23BCDEF, Joseph Ogunsulire4CDEG, Ferdinand Schafer1ADE*

DOI: 10.12659/AJCR.946364

Am J Case Rep 2025; 26:e946364

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Abstract

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BACKGROUND: Rhabdomyolysis occurs commonly in hospitalized patients due to many etiologies. It is characterized by elevated creatine kinase, weakness, and myalgias, with severe forms causing electrolyte imbalances. However, many of these patients have a mild disease course with no symptoms. Those with more severe disease often have associated acute kidney injury. When acute kidney injury occurs solely due to rhabdomyolysis, it is unlikely to cause the patient to require renal replacement therapy. Regardless of how common this disease is, little research has been done to determine prognosticating factors for renal recovery in the patients who do require renal replacement therapy.

CASE REPORT: We present the case a young patient who developed severe kidney damage from rhabdomyolysis, requiring renal replacement, and who had renal recovery in a relatively short time. Our patient’s maximum creatine kinase was 1 353 105 IU/L. Yet regardless of this severe elevation, his kidneys showed full recovery in under 3 weeks.

CONCLUSIONS: We present a case of a patient with rhabdomyolysis and CK above one million. In our literature review, we found that exertion and genetic defects were found to cause CK elevations above one hundred thousand, but infection is perhaps the most common cause of such extreme elevations. Regardless of how high CK is, there are no consistent factors reported in the literature correlating with degree of and rate of renal recovery in these patients.

Keywords: Coxsackievirus Infections, Kidney Diseases, rhabdomyolysis

Introduction

Rhabdomyolysis is a common condition caused by breakdown of skeletal muscle, resulting in systemic release of muscle breakdown products, including myoglobin. Presentation can vary from asymptomatic patients to those acute kidney injury (AKI) requiring renal replacement therapy (RRT). Commonly reported symptoms include diffuse weakness and myalgias. Physical exam might reveal weakness and dark, cola-tinged urine, and urinalysis (UA) consistent with myoglobinuria might stain for blood on urine dipstick, but have minimal-to-no red blood cells on urine microscopy. On a cautionary note, this same pattern on UA is seen in hemoglobinuria, which can also cause AKI. Diagnosis of rhabdomyolysis is confirmed when serum creatine kinase (CK) levels are >1000 IU/L or >5 times the upper limit of normal. Other common laboratory findings in rhabdomyolysis include hypocalcemia, hyperphosphatemia, hyperkalemia, hypermagnesemia, metabolic acidosis, hyperuricemia, and transaminitis. Levels of 1,25-dihydroxyvitamin D3 may also decrease due to 1α-hydroxylase inhibition by phosphate [1].

Perhaps the most important factor determining the mortality rate of rhabdomyolysis is the presence of AKI. Patients in the intensive care unit with rhabdomyolysis were found to have a mortality rate of 59% when AKI was present and 22% otherwise. AKI occurs in 13–50% of rhabdomyolysis cases, and rhabdomyolysis is thought to account for 7–10% of cases of AKI in the USA [1]. The McMahon score is a validated clinical score that can determine the likelihood of a patient with rhabdomyolysis requiring RRT. While there are reports of patients with exceptionally high CK and normal kidney function [2–5], a higher CK is associated with higher risk and severity of AKI, as is noted in the McMahon score criteria of CK >40 000 U/L.

Below, we present a case of a young man who presented with rhabdomyolysis and CK elevation in the millions. We have only found 10 other cases in the literature with CK elevations above one million, so we hope this case contributes to the literature on such extreme rhabdomyolysis to be able to better understand how this laboratory test correlates with disease severity and patient outcomes.

Case Report

A man in his 20s with no known past medical history presented to an emergency department with lightheadedness, possible syncope, and 2 days of diarrhea. He was a long-distance truck driver and reported that he experienced the diarrhea after eating at a fast-food restaurant. The diarrhea happened 3 times a day. He also had lightheadedness for 1 day only and it had resolved by the time of presentation. The patient thought he fainted because he woke up on the floor of his garage and was not sure what had happened or how he got there. He did not know how long he was unconscious. A review of systems was positive for feeling flushed and warm while at home. A physical exam showed obese habitus (BMI 51.3) and lungs clear to auscultation bilaterally. Vital signs showed heart rates of 130–140 bpm and temperature of 39°C. Initial laboratory test results were significant for leukocytosis of 21.5 (×103 cells/L), troponin I of 0.129 ng/mL (ref 0.010–0.059 ng/mL), blood urea nitrogen of 41 mg/dL (ref 9–23 mg/dL), creatinine of 5.40 mg/dL (ref 0.60–1.60 mg/dL), potassium of 3.1 mEq/L, bicarbonate of 11 mmol/L (ref 20–31 mmol/L), aspartate aminotransferase (AST) of 688 units/L (ref 11–35 units/L), alanine aminotransferase (ALT) of 179 units/L (ref 10–49 units/L), alkaline phosphatase (ALP) of 69 IU/L (ref 45–129 IU/L), C reactive protein of 24.841 mg/dL (ref 0–0.50 mg/dL), and total bilirubin of 0.4 mg/dL (ref 0.3–1.2 mg/dL). Urine dipstick stained for significant amounts of blood with 5–10 RBCs/hpf and urine protein-to-creatinine ratio was 7.8 g/day. Initial arterial blood gas (ABG) showed pH of 7.30, pCO2 of 26.6 mmHg, pO2 of 75 mmHg, and bicarbonate of 13.0 mmol/L. This was consistent with a high anion gap metabolic acidosis from severe kidney injury with appropriate respiratory compensation (expected pCO2 of ~25). The patient’s hypokalemia was attributed to his diarrhea, and his rapid development of severe hyperphosphatemia was attributed to the rhabdomyolysis. The troponin I changed from 0.129 ng/mL to 0.140 ng/mL to 0.059 ng/mL before the trend was stopped. A chest X-ray showed left upper-lobe opacity. Given the transaminitis with normal ALP and total bilirubin, CK was ordered and the result was 161 743 IU/L (ref 32–200 IU/L). Given the patient’s initial CK level and AKI, he was diagnosed with severe rhabdomyolysis. The initial differential diagnosis for the etiology of our patient’s rhabdomyolysis was broad, including infection (esp. Legionella and viral myositis), genetic disorders, drug abuse, and toxin exposure.

Given the patient’s physical exam revealing likely hypervolemia on admission, we did not believe he was dehydrated even though he had some diarrhea prior to admission. Given his fluid overload and the elevated troponin on presentation, a transthoracic echocardiogram (TTE) was obtained. The TTE showed borderline concentric left ventricular hypertrophy, ejection fraction of 55–60%, minimal pericardial effusion, and overall poor windows even after administration of contrast.

The patient was treated with a 5-day course of azithromycin and ceftriaxone for pneumonia. He was later treated with doxycycline for presumed tick-borne infections. We do not believe the patient had a meaningful clinical response to this antibiotic regimen given the timeline of his illness. His diarrhea and lightheadedness had already resolved by the time of presentation to the hospital, and his oxygen requirements did not change with antibiotics, but rather fluctuated throughout admission depending on his degree of pulmonary edema secondary to his anuric AKI and fluid administration for rhabdomyolysis. He was given lactated Ringer’s infusion at a rate of 150 mL/h to prevent further kidney damage. He initially required 5 L/min of oxygen via nasal cannula. The patient was oliguric on presentation and soon thereafter became anuric. Given his decreasing urine output, he was started on hemodialysis (HD) within 24 hours of admission. While receiving HD, the CK and phosphorus continued to climb to extreme levels, so he was transitioned to continuous renal replacement therapy (CRRT) to attempt to remove CK and limit further renal damage. However, the CRRT filter clotted within 24 hours. Nonetheless, his phosphorus and CK levels responded well to his limited time on CRRT (Table 1). CRRT was stopped and intermittent hemodialysis was started, as the patient’s severe CK elevation and hyperphosphatemia had already become more manageable at this time.

Testing for etiology was broad and we obtained negative results for the following etiologies: hypothyroidism, drug abuse, autoimmune diseases (Sjogren’s disease, systemic lupus erythematosus, idiopathic inflammatory myopathies, mixed connective tissue disease, anti-glomerular basement membrane disease), infections (blood cultures, stool cultures, HIV, viral hepatitis, CMV, coxsackie A, EBV, adenovirus, coronavirus, influenza A or B, metapneumovirus, parainfluenza viruses, RSV, rhinovirus, Chlamydia pneumoniae, Mycoplasma pneumoniae, Bordetella pertussis, Clostridium difficile, Shigella, Ehrlichia chaffeensis, Anaplasma phagocytophilum, Babesia microti, Lyme disease), and sickle-cell anemia. One limitation of our case was that while urine samples were collected twice for Legionella antigen testing, neither sample made it to the laboratory for testing. The only part of our work-up that was positive was antibody titers of 1: 160 for coxsackie B virus, serotype 3.

After the etiology was determined and CK levels decreased to below 1000 IU/L, he continued to require intermittent HD. During this time, his potassium levels remained low and were refractory to repletion. After many hundreds of milliequivalents of oral and intravenous potassium repletion, serum potassium stabilized. On day 20 after admission, his urine output increased to over 600 mL in 24 hours. His urine output and creatinine continued to improve, and he was discharged 27 days after admission. The patient followed up in clinic about 1 month after discharge and kidney function at that time had returned to his baseline normal levels. Further HD and nephrology follow-up was not necessary at the time of publication of this report.

Discussion

In our case, a young man presented with a severe AKI that was found to be due to massive rhabdomyolysis. A couple of aspects of this case are unique. Elevations of CK to this degree are rarely reported in the literature; we were only able to find 10 reported cases with CK elevation over one million. In patients with CK elevations of this magnitude, there is little evidence of prognosticating factors for renal recovery. Furthermore, the patient had no weakness or myalgia, which is unusual in patients with rhabdomyolysis. Why our patient lacked these common symptoms/signs is unclear at this time and it is unknown if it is related to the etiology.

The differential diagnosis of rhabdomyolysis is broad, and specific etiologies are summarized in Table 2. Given the broad range of possible CK values that can be seen in rhabdomyolysis, we reviewed the literature to determine if the degree of CK elevation could narrow the differential diagnosis for patients with rhabdomyolysis and exceptionally high CK.

Of the 10 previously mentioned cases with elevations of CK above one million, causes included infection (5), exertion (1), and multifactorial (4). Of the cases with multiple causes, infection was a cause in 2 cases and exertion was involved in the other 2. The maximum reported CK we found was 5 366 100, which was caused by coxsackie B4 infection. Other infectious etiologies were influenza A, Legionella spp., COVID-19, and varicella zoster virus (VZV). As is expected given their increased muscle mass on average compared to age-matched females, all these cases involved male patients [3–5,8,19–24]. Further details on these cases are provided in Table 3.

Of the other cases found with CK elevations in the hundreds of thousands, many were also infection- or vaccine-related. Two cases occurred after COVID-19 vaccination, and the other cases included an unknown etiology of pneumonia, Salmonella typhi, influenza A, Legionella spp., and COVID-19 [25–32]. In 1996, Singh and Scheld reported on infectious causes of rhabdomyolysis; those with elevations of CK in the hundreds of thousands or more also included HIV, EBV, enterovirus, adenovirus, HSV, Leptospira spp., Brucella spp., Listeria spp., Streptococcus pyogenes, Streptococcus pneumoniae, and Francisella tularensis [16].

Apart from infections and exertion, other etiologies that were identified to commonly elevate CK to the hundreds of thousands include drug abuse [32,33], trauma [31], and genetic abnormalities [26].

Given the patient’s normal ejection fraction and only mild elevation of troponin I, we do not believe he had clinically significant myocardial involvement from coxsackie B3. We believe, instead, that his elevated troponin I was likely due to hypervolemia on presentation and/or a mild form of demand ischemia. The patient also had no signs of pericarditis from coxsackie B3 (chest pain, pericardial friction rub, EKG changes) aside from minimal pericardial effusion.

Our patient required HD for 20 days. On our review of the literature, we were unable to find evidence to predict the duration of HD for patients who require it. As shown in Table 3, patients with CK above one million had diverse renal outcomes, from no change in creatinine to requiring HD for over a month [3–5,8,19–24]. While some factors may logically predict the need for and duration of HD, such as age, pre-existing CKD, simultaneous additional etiology of AKI, and presence of significant comorbidities, more research in this area is needed to predict survival and renal outcomes for patients with severe rhabdomyolysis.

Finally, there is no evidence that performing RRT for the sole purpose of removal of myoglobin improves recovery or mortality. Nonetheless, there is a theoretical benefit to lowering myoglobin, as it likely plays a key role in the pathogenesis of renal damage; therefore, we used RRT to remove myoglobin. We performed initial intermittent HD sessions with Theranova 500 and saw some short-lived decrease in CK. It was only after initiating CRRT that sustained decreases were seen.

Conclusions

This case report of a young man is unique for CK elevation above one million and a lack of muscular symptoms. Our report had a few limitations. First, we did not obtain some laboratory test results, such as legionella urine antigen. Second, there were no biopsies taken, as our team did not believe it would significantly impact patient care or outcomes. However, coxsackie B3 infection could explain our patient’s presentation. We measured total antibody titers and did not obtain an IgM level for coxsackie B3 virus. Therefore, it is possible that this virus was not the cause of his rhabdomyolysis. However, his presentation was consistent with an infectious etiology (eg, febrile, leukocytosis, infectious symptoms), and a viral infection or Legionella infection fits with the specific organ systems involved.

In our review of the literature, we determined that while exertion and genetic defects can cause and/or contribute to CK elevations of the magnitude seen in our patient, infection is a common and perhaps the most common cause of such exceptional elevations. Thus, infection should be at the top of every differential diagnosis for patients with rhabdomyolysis and CK elevations of hundreds of thousands or higher. Furthermore, more research needs to be done to determine factors associated with probability and degree of renal recovery in patients with severe rhabdomyolysis.

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923