Virus-associated rhabdomyolysis is very rare. We report 15 patients with rhabdomyolysis caused by various viruses.
Fifteen patients who were diagnosed with rhabdomyolysis and a viral infection were included in this study. Clinical, laboratory, and radiologic findings were evaluated through retrospective chart reviews.
Chief complaints were severe bilateral lower leg pain and leg weakness. The median age was 5.7 years. The male:female ratio was 2:5. The viral infections were caused by influenza virus B, parainfluenza virus, and rhinovirus. One patient with influenza virus B had coinfection with coronavirus. Median initial laboratory values and ranges were as follows: serum creatinine, 0.4 (0.1-0.5) mg/dL; serum aspartate transaminase, 124 (48-1,098) IU/L; serum alanine transaminase, 30 (16-1,455) IU/L; serum creatine kinase, 2,965 (672-16,594) IU; serum lactate dehydrogenase, 400 (269-7,394) IU/L; serum myoglobin, 644 (314-3,867) ng/mL; urine myoglobin, 3 (3-10,431) ng/mL. All patients recovered without complications.
This is the first report of the simultaneous occurrence of rhabdomyolysis caused by various viruses. This is also the first report of rhinovirus-associated rhabdomyolysis.
Rhabdomyolysis means the dissolution of striped (skeletal) muscle, which is characterized by the leakage of muscle cell contents, such as electrolytes, myoglobin, and other sarcoplasmic proteins (e.g., creatine kinase (CK), aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) into the circulation [
Virus-associated rhabdomyolysis is very rare in adults [
A retrospective chart review was conducted based on medical records filed between January 2010 and December 2016 at Asan medical center children’s hospital. Patients were included in the study if they were aged below 18 years, and had a diagnosis of rhabdomyolysis. Patients who had an underlying disease or previous history of exercise, trauma, drug intoxication or recurrent rhabdomyolysis were excluded. Diagnostic criteria of rhabdomyolysis were based on the increased level of serum myoglobin above the normal range. Patients who had serum creatine kinase (CK) level was above 1,500 IU/L, which is six times the upper limit of normal, were included in this study. Acute kidney injury was diagnosed when estimated creatinine clearance is under 35 mL/min/1.73m 214). All children had increased level of other muscle contents including serum lactate dehydrogenase (LD), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). A multiplex reverse transcriptase polymerase chain reaction for respiratory viruses from a nasopharyngeal aspiration sample was also performed in all patients with the history of viral illness such as fever, cough, rhinorrhea and myalgia, and only those with positive results were finally included in this study.
Whole-body planar bone scintigraphy was performed 4 hours after injection of 1,110×(Body weight in kilograms/70 kg) MBq 99mTc-dicarboxypropane diphosphonate (DPD) in 3 patients to evaluate the severity and to detect the sites of the rhabdomyolysis. Anterior and posterior whole body scans were obtained, respectively using a dual-head gamma camera (Bodyscan; Siemens, Hoffman Estates, IL, or BiadXLT; Trionix, Twinsburg, OH) equipped with high resolution or ultra-high-resolution collimators.
Electrospray tandem mass aminoacid and acylcarnitine analyses was performed in 4 patients for a differential diagnosis of very rare cases of metabolic myopathies [
All data were analyzed using the SPSS statistical software version 21 (SPSS Inc., Chicago, IL, USA). Wilcoxon signedrank test was performed to compare the results of laboratory test between onset and the final follow-up.
Fifteen patients were admitted due to rhabdomyolysis between 2010 and 2016. Chief complaints on admission were suddenly developed severe both calf pain causing progressive difficulty in walking (9 patients, 60.0%) and leg weakness (5 patient, 33.3%). The median age was 5.0 years (range 3-9 years). Male to female ratio was 11 to 4. All patients had a history of a recent viral infection from 3 to 10 days (median 5 days) prior to the presentation of rhabdomyolysis. The month of onsets of viral infections were shown in
All patients received all their routine immunizations. No patient showed red to brown-colored or dark urine. Their causal viruses were influenza virus B (10 patients, 66.7%), influenza virus A (2 patinets, 13.3%), boca virus+ rhinovirus, parainfluenza virus type 1+enterovirus or respiratory syncytial virus (1 patient each, 6.7%).
Their median values and range of laboratory findings were shown in
Only one patient (6.7%) had acute kidney injury due to rhabdomyolysis. As initial symptom of rhabdomyolysis, drowsy mentality was presented in this patient. Initial GFR was decreased as 20.8 ml/min/1.73m2. He was treated with dialysis and recovered to normal GFR (138.1 ml/min/1.73 m2) without complication. Influenza A was detected in this patients. Other patients were treated with saline hydration and alkalinization without dialysis. The median hospital days were 3 days (1-10 days) and all patients were discharged within 65 days except 1 patient who had prolonged admission due to acute kidney injury and prolonged increased CK level. All patients were recovered without any complications.
The most common cause of rhabdomyolysis was influenza type B in this study. Most reports of influenza associated rhabdomyolysis are about type A [
We had two patients with rhabdomyolysis due to parainfluenza type 1 infection. There are only 4 case reports of rhabdomyolysis associated with parainfluenza virus on a medical online library search in Pubmed (http://www.ncbi. nlm.nih.gov/) so far [
We had one patient with rhabdomyolysis associated with bocavirus and rhinovirus coinfection. There was only one report of rhabdomyolysis caused by rhinovirus [
No patient in this study showed red to brown-colored urine. All the patients had increased serum myoglobin level, but only 2 of them (13.3%) had clinically significant myoglobinuria. Only those with serum myoglobin level above 2,000 ng/mL had myoglobinuria and positive urine occult blood without microscopic hematuria. The classic triad of rhabdomyolysis includes myalgia, red-to-brown or dark urine and muscle weakness [
There was a male predominance in virus associated rhabdomyolysis in this study. All patients were between 3- 9 years old. Patients who had a previous history of exercise or trauma were excluded. In general, it was reported that male patient is usually more prevalent in rhabdomyolysis even in non-exertional, non-traumatic cases such as virus associated rhabdomyolysis [
99mTc-DPD bone scintigraphy revealed increased soft tissue radiotracer uptake in both legs in all five patients who had the test in this study. Phosphate derivative tracers such as 99mTc-DPD, used for bone imaging, are taken up by some soft tissue lesions [
We did not perform muscle biopsy nor cytokine analysis for the pathogenic evaluations because clinical courses in all patients in this study were benign and recovered without complication. The mechanism of rhabdomyolysis due to viral infection has not been established with certainty yet. The following possibilities have been proposed: First, direct viral invasion of muscle tissue is one possibility; however, the identification of virus or viral particles in affected muscles has been difficult to demonstrate consistently [
There are some limitations in this study. First, not all patients conducted Whole-body planar bone scintigraphy since this study is retrospective study. Second, as this study was conducted in the single center, the selection bias may exist. At last, since sample size is not enough to represent all Korean children, the larger study will be required.
In conclusion, we have experienced patients with rhabdomyolysis due to different kinds of respiratory viral infections, mostly influenza B, followed by parainfluenza and rhinovirus during their outbreaks in the spring of 2010. This is the first report of the simultaneous occurrence of rhabdomyolysis due to multiple viral etiologies. We are not sure if these findings are just coincidental findings by chance or if there are any reciprocal actions among different viruses which favor rhabdomyolysis. This is also the first report of rhinovirus associated rhabdomyolysis.
No potential conflict of interest relevant to this article was reported.
The months of occurrence of viral infections. The months of onsets of viral infections of patients of virus-associated rhab- domyolysis were shown.
The Median Values and Range of Laboratory Findings of Patients
Initial lab finding (median values and range) | Follow-up lab finding (median values and range) | Change | ||
---|---|---|---|---|
Serum calcium (mg/dL) | 9.0 (7.4-9.6) | 9.3 (8.9-9.8) | 0.4 (-0.1-1.9) [4.4 (-1.1-25.7) %] | 0.001 |
Serum albumin (g/dL) | 3.8 (3.2-4.2) | 4.3 (3.3-4.7) | 0.6 (-0.5-1.3) [16.7 (-13.2-40.6) %] | 0.007 |
Serum sodium (mmol/L) | 137 (134-143) | 140 (137-143) | 3 (-2-6) [2.2 (-1.4-4.4) %] | 0.036 |
Serum AST (IU/L) | 137 (69-5,029) | 33 (23-96) | 109 (-4997--13) [-77.9 (-99.4-18.8) %] | 0.001 |
Serum ALT (IU/L) | 38 (18-3,843) | 20 (12-126) | 11 (-3,825-27) [-40.0 (-99.5-77.1) %] | 0.083 |
Serum CK (IU/L) | 4,022 (1,840 ~30,255) | 152 (95-1,887) | -3,870 (-2,8368--1462) [-95.4 (-98.7-79.5) %] | 0.001 |
Serum LD (IU/L) | 388 (277-4651) | 293 (193-617) | 84 (-4,408-170) [-23.1 (-94.8-49.6) %] | 0.023 |
Serum BUN (mg/dL) | 6 (4-42) | 9 (4-13) | 2 (-5-7) [33.3 (-50.0-175.0) %] | 0.174 |
Serum Cr (mg/dL) | 0.37 (0.2-2.99) | 0.41 (0.28-0.55) | -0.02 (-2.54-0.22) [-5.4 (-84.9-100.0) %] | 0.608 |
Serum myoglobin (ng/mL) | 766.5 (140-5,589) | 30.5 (17-185) | -688.5 (-5,568--84) [-95.8 (99.6--60.0) %] | 0.001 |