500 Asian Pacific Journal of Tropical Medicine (2013)500-501

Contents lists available at ScienceDirect

Asian Pacific Journal of Tropical Medicine

journal homepage:www.elsevier.com/locate/apjtm

Document heading doi:

A rare but potentially lethal complication of dengue

Yingjuan Mok1*, Jessica Quah2, Chuin Siau3
1
Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore
2
Department of General Medicine, Changi General Hospital, Singapore
3
Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore

ARTICLE INFO ABSTRACT

Article history: Severe rhabdomyolysis is an uncommon but potentially fatal complication of dengue fever that
Received 10 March 2013 is not well characterised and may be underreported. With the resurgence and continued rise of
Received in revised form 15 April 2013 dengue cases worldwide, physicians must be aware of the less common but serious complications
Accepted 15 May 2013 of dengue. Here, we report a patient who presented with severe rhabdomyolysis secondary to
Available online 20 June 2013 dengue fever with a serum creatine kinase of 742 900 U/L.

Keywords:
Dengue
Rhabdomyolysis
Acute renal failure
Shock

with a mountain hike in Malaysia. He reached the summit of

1. Introduction 2 000 feet above sea level with little difficulty. Upon return,
his symptoms worsened and he developed abdominal pain
Severe rhabdomyolysis is an uncommon but potentially and vomiting 2 d prior to admission. No medications were
fatal complication of dengue fever that is not well recently initiated and the patient denied illicit drug use.
characterised and may be underreported. Dengue fever, a There was no history of fall or injury. There was also no
mosquito-borne flavivirus endemic in Southeast Asia and family history of muscle diseases.
Western Pacific regions, has been increasingly reported On admission, the patient was alert and ambulant. He was
worldwide[1]. With the resurgence and continued rise of noted to be tachypnoeic with a respiratory rate of 35 breaths/
dengue cases in endemic regions, physicians must maintain min, a blood pressure of 174/85 mmHg and a pulse rate of
not only a high index of suspicion for the diagnosis but also 85 beats/ min. His laboratory tests are as follow: serum CK:
an awareness of the less common but serious complications 742 900 U/L, creatinine: 1 036 mmol, arterial bicarbonat:
of dengue. Here, we would like to report a patient who 7.4 mmol/L. The diagnosis of dengue fever was confirmed
presented with severe rhabdomyolysis secondary to dengue with both a positive dengue IgM and a positive dengue virus
fever with a serum creatine kinase (CK) of 742 900 U/L on PCR. His blood and urine cultures demonstrated no growth of
admission. organisms and the leptospiral and rickettsia serologies were
negative. His platelet count on admission was 33×103/毺L.
Soon after admission, he was transferred to the intensive
2. Case report care unit (ICU) for continuous renal replacement therapy.
However, within 24 h, his condition deteriorated in the
An active 50 year old Chinese male with a medical history ICU. He required both inotropic and ventilatory support.
of hypertension and hyperlipidemia on daily long term His stay was complicated by the development of acute
amlodipine 5 mg and simvastatin 10 mg, presented with compartment syndrome of bilateral lower extremities
fever of 5 d duration associated with myalgia. In the initial from severe rhabdomyolysis and likely intramuscular
2 d of illness, his symptoms were mild and he proceeded bleed, acute liver failure and disseminated intravascular
coagulation. He also had seizures from generalised cerebral
*Corresponding author: Dr Mok Yingjuan, Changi General Hospital, 2 Simei Street 3, edema and gastrointestinal bleeding requiring massive
Singapore 529889.
Tel: (65) 67888833
blood tranfusions. On day 19 of his illness, he suffered a
Fax: (65) 67880933 cardiorespiratory collapse and eventually demised.
E-mail: mokyingjuan@gmail.com
 Yingjuan Mok et al./Asian Pacific Journal of Tropical Medicine (2013)500-501
501

3. Discussion be aware of this complication, and possibly the ‘high-risk’

patient profile as described in our report. We hope that
Severe rhabdomyolysis is an uncommon complication of future studies may continue to further our understanding of
dengue[2-5]. Its pathogenesis has remained elusive although this enigmatic disease, thereby leading to improvements in
the release of cytokines, particularly tumour necrosis factor, patient care and clinical outcomes.
has been implicated[6-9]. The causal relationship between
dengue and rhabdomyolysis is often confounded by the
presence of established shock and multiorgan complications Conflict of interest statement
of the critically ill patient. However, in our patient, it
was clear that the rhabdomyolysis occurred before the The authors declare that they have no conflicts of interest.
development of shock, suggesting that this may be a true
complication of dengue.
It is also interesting to note that in our patient, there was References
a history of significant physical activity early in his illness.
Acharya et al[2] reported a patient with rhabdomyolysis from [1] W HO. Impact of Dengue. Global Alert and Response (GAR) 2012.
dengue who was involved in labour work during the period Geneva: WHO: 2012.
of illness while Lim et al[3] reported a case of readmission [2] Acharya S, Shukla S, Mahajan SN, Diwan SK. Acute dengue
for myalgia with rhabdomyolysis following resumption of myositis with rhabdomyolysis and acute renal failure. Ann Indian
exercise 2 d after a prior hospital discharge for dengue fever. Acad Neurol 2010; 13(3): 221-222.
It seems plausible that strenuous physical activity may be a [3] L im M, Goh HK, Rhabdomyolysis following dengue virus
potential risk factor for severe rhabdomyolysis peri-illness. infection. Singapore Med J 2005; 46(11): 645-646.
Hence, it may be prudent to advise dengue patients to avoid [4] D avis JS, Bourke P. Rhabdomyolysis associated with dengue virus
aggressive physical activity during the period of acute infection. Clin Infect Dis 2004; 38(10): e109-e111.
illness or convalescent phase. This is especially so for those [5] Karakus A, Banga N, Voorn GP, Meinders AJ. Dengue shock
who are engaged in laboriously demanding occupations or syndrome and rhabdomyolysis. Neth J Med 2007; 65(2): 78-81.
patients who enjoy strenuous recreational activities. [6] Gagnon SJ, Mori M, Kurane I, Green S, Vaughn DW, Kalayanarooj
W e concede that our patient was on long term low S, et al. Cytokine gene expression and protein production in
dose statin medication. However, fatal rhabdomyolysis peripheral blood mononuclear cells of children with acute dengue
associated with statins is rare[10] and appears to be dose virus infections. J Med Virol 2002; 67(1): 41-46.
dependent[11,12]. Studies have also attempted to look at [7] Remalayam B, Viswanathan S, Karanth S, Iqbal N, Muthu V.
exertion-induced muscle injury in patients on statins. In a Double trouble in dengue. Asian Pac J Trop Dis 2012; 2(1): 80-
study by Thompson et al, CK levels were 62% to 77% higher 81.
after treadmill exercise in patients on lovastatin versus [8] Juanarita J, Azmi M, Azhany Y, Liza-Sharmini AT. Dengue
placebo[13]. Nevertheless, exertion-triggered rhabdomyolysis related maculopathy and foveolitis. Asian Pac J Trop Biomed
in patients on statin therapy resulting in acute renal failure 2012; 2(9): 755-756.
requiring dialysis is extremely rare and the levels of CK [9] Wiwanitkit V. Concurrent malaria and dengue infection: a brief
reported were generally far below that of our patient[14]. summary and comment. Asian Pac J Trop Biomed 2011; 1(4):
Exercise and rhabdomyolysis has also been well described. 326-327.
However, exercise –induced rhabdomyolysis leading to [10]Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal
dialysis-requiring acute renal failure is rare too. In a series rhabdomyolysis. N Engl J Med 2002; 346(7): 539-540.
by Sinert et al, none of the 35 patients with pure exercise- [11]Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical
induced rhabdomyolysis developed acute renal failure in pharmacokinetics and drug interactions. Circulation 2004; 109(23
the absence of nephrotoxic cofactors[15] In addition, other Suppl 1): III50-57.
reports of severe exercise-induced rhabdomyolysis have [12]Brewer HB Jr. Benefit-risk assessment of Rosuvastatin 10 to 40
implicated predisposing factors such as the concomitant use milligrams. Am J Cardiol 2003; 92(4B): 23K-29K.
of performance enhancing compounds[16], sickle cell trait[17] [13]Thompson PD, Zmuda JM, Domalik LJ, Zimet RJ, Staggers J,
and genetic factors[18]. Guyton JR. Lovastatin increases exercise-induced skeletal muscle
Hence, given the clinical picture, simvastatin or exercise injury. Metabolism 1997; 46(10): 1206-1210.
alone was unlikely to have accounted for our patient’s [14]Unnikrishnan D, Satish B. Exertion-induced rhabdomyolysis in
extreme level of CK. To our knowledge, it is the highest level a patient on statin therapy. Nephrol Dial Transplant 2005; 20(1):
of CK reported in a dengue patient with rhabdomyolysis. 244.
O n the other hand, it is possible that the unfortunate [15]S inert R, Kohl L, Rainone T, Scalea T. Exercise-induced
combination of all 3 factors - dengue virus infection, rhabdomyolysis. Ann Emerg Med 1994; 23(6): 1301-1306.
coupled with statin use and exercise led to his fatal [16]Sandhu RS, Como JJ, Scalea TS, Betts JM. Renal failure and
rhabdomyolysis. exercise-induced rhabdomyolysis in patients taking performance-
I n conclusion, severe rhabdomyolysis is a rare but enhancing compounds. J Trauma 2002; 53(4): 761-763.
potentially lethal complication of dengue. The mechanism [17]M a k a ry u s J N , C a t a n z a ro J N , K a t on a K C. E x e rti o n al
as well as risk factors for this complication including rhabdomyolysis and renal failure in patients with sickle cell trait:
exercise peri-illness or concomitant statin use, remains to is it time to change our approach? Hematology 2007; 12(4): 349-
be determined. In Southeast Asia, dengue is endemic, statin 352.
use is common, and there is an increasing number of people [18]Landau ME, Kenney K, Deuster P, Campbell W. Exertional
engaging in endurance sports, with many more involved in rhabdomyolysis: a clinical review with a focus on genetic
physically demanding occupations, Thus, physicians must influences. J Clin Neuromuscul Dis 2012; 13(3): 122-136.