A rare cause of rhabdomyolysis.

To the Editor: Rhabdomyolysis is an acute condition involving skeletal muscle injury and release of potential toxic contents into plasma. Common etiologies include trauma, muscle ischemia, excessive exertion, bacterial and viral sepsis, electrical bums, other injuries related to heat or cold, prolonged muscle compression as often seen in the unconscious state after alcohol, seizures, hypokalemia and shock. Infectious mononucleosis, a common disease of teenagers and young adults caused by Epstein-Barr Virus (EBV), has rarely been associated with development of rhabdomyolysis.

An 18-year-old Caucasian male college student presented to the emergency room with bilateral lower extremity muscle aches and dark colored urine. He was diagnosed with infectious mononucleosis four weeks earlier. The patient, an avid volleyball player, had not played any contact sports for the previous 4 weeks due to infectious mononucleosis as per medical instructions. However, he had performed a light work out in the gym two days before presentation in the emergency room. Subsequently, he began to experience back pain and muscle aches in his lower extremities along with weakness in the thighs that soon increased in intensity to the point where he found it difficult to walk.

Family history was negative for any muscular or metabolic disorders. On physical examination, the patient had mild pain with active and passive movements of both thighs. The muscles of his thighs felt firm and were tender. Muscle strength in the lower extremities was decreased bilaterally. Laboratory investigations revealed normal complete blood count and serum electrolytes. Liver enzymes were elevated but serum BUN and creatinine were normal. Total serum creatine kinase was 179,200 IU/L and serum aldolase was 636 U/L. Urine was brown and cloudy with pH of 6.5, protein 500 mg/dL, urobilinogen 4.0EU/dL, positive for leukocyte esterase and blood, negative for nitrites, RBC of 2 to 4/HPF, WBC of 5 to 10/HPF and highly positive for myoglobin. A diagnosis of acute rhabdomyolysis was made. Further investigations of EBV antibody panel revealed elevated serum immunoglobulin titers of IgM -3.52 and IgG -1.99. Further investigations revealed negative results for Jo-1 antibody, hepatitis B Surface antigen, hepatitis B core IgM antibody, hepatitis C virus antibody and hepatitis A IgM antibody. A computed tomography (CT) scan of the abdomen and pelvis was unremarkable for any pathology.

On days 2, 3 and 4 after presentation to the emergency room, his creatine kinase continued to decrease progressively. The patient gradually recovered with a decrease in muscle aches, and there was also significant improvement in the muscle strength. He was discharged on day 5 with advice to avoid any physical exertion for 4 more weeks.

This case demonstrates rhabdomyolysis as a rare and possibly often unrecognized complication of acute and subacute infectious mononucleosis. (1-4) In the majority of cases of mononucleosis, the disease manifests with typical signs of sore throat, fever and myalgias. Acute myalgia may be seen in up to 20% of cases, and it improves slowly as other symptoms improve. Recurrence of muscle aches after initial recovery from acute phase may represent rhabdomyolysis. Two principle markers of rhabdomyolysis are high serum creatine kinase (CK) levels and myoglobinuria. (1) Myoglobinuria can often lead to acute renal failure as the most serious complication of rhabdomyolysis and warrants generous fluid therapy to flush the kidneys. (1) There have been three reports of rhabdomyolysis in isolated acute EBV infection leading to mononucleosis, and all cases occurred early in the disease course in contrast to our patient, who developed the complication approximately 4 weeks after the diagnosis of infectious mononucleosis. Patients are generally instructed to avoid contact sports for 4 weeks after the diagnosis of infectious mononucleosis to avoid the risk of splenic rupture. We recommend that patients also need to be instructed to avoid any physical exertion due to the risk of rhabdomyolysis. The duration of rhabdomyolysis risk after initial diagnosis of infectious mononucleosis is unknown at this time.

In conclusion, we recommend that physicians should consider instructing patients with infectious mononucleosis to temporarily refrain from not only contact sports but also any deliberate physical activity for up to 6 to 8 weeks after diagnosis of the disease. Because most infectious mononucleosis patients are in younger age groups, especially teenagers, the chances of indulging in physical exercise remains very high unless they are specifically instructed not to do so.

It is not known what could be the exact cause of rhabdomyolysis in these patients. It may be a direct virus-induced toxicity or, on the other hand, mediated by possible myotoxic effect of the antibodies elaborated as a consequence of the infection. We hope future research will throw some light on this issue.

Nirmalya Roychowdhury, MD, MPhil

Ashwin Shivakumar, MD, MS

Nadia Mustafa, MD

Raju Patil, MD

Department of Internal Medicine

University of Illinois College of Medicine at Urbana-Champaign, Urbana-Champaign, IL

Naveed Salahuddin, MD

Department of Rheumatology 

Carle Foundation Hospital, Urbana-Champaign

Urbana-Champaign, IL

References

1. McCabe JL, Duckett S, Kaplan P. Epstein-Barr virus infection complicated by acute rhabdomyolysis. Am J Emerg Med 1988;6:453-455.

2. Osamah H, Finkelstein R, Brook JG. Rhabdomyolysis complicating acute Epstein-Barr virus infection. Infection 1995;23:119-120.

3. Friedman BI, Libby R. Epstein-Barr virus infection associated with rhabdomyolysis and acute renal failure. Clin Pediatr (Phila) 1986;25:228-229.

4. Poels PJ, Ewals JA, Joosten EM, et al. Rhabdomyolysis associated with simultaneous Epstein-Barr virus infection and isolation of echovirus 6 from muscle: a dual infection. J Neurol Neurosurg Psychiatry 1989;52:412-414.