Acute renal failure due to Dengue myositis: a rare cause of pigment cast nephropathy

Introduction

Dengue is a common viral infection of the tropics caused by four serotypes of Dengue virus belonging to the family of flavivirus. Clinical presentation of symptomatic Dengue virus infections can be wide, from a mild febrile illness to a life-threatening shock syndrome. We present a case of a young male with unusual presentation of Dengue as acute renal failure secondary to rhabdomyolysis.

Case report

A 35-year-old male patient was referred to our institute with a history of fever with myalgia and weakness for 15 days and decreased urine output for 7 days in the month of November. The fever was high grade, intermittent, and not associated with chills or rigours. There was a history of one episode of passing dark coloured urine. On examination, the patient was febrile (102°F), conscious and oriented. His vitals were stable (pulse rate 80/min, blood pressure 130/80 mmHg and respiratory rate 20/min). He was anuric. Neurological examination revealed the power to be three-fifth in the proximal part of all four limbs while the distal was 4+/5. There were no bleeding manifestations. Investigations revealed progressive anaemia (135–90 g/L). Platelet counts were consistently >100 × 10⁹/L. Peripheral blood was negative for malarial parasite and fragmented RBCs. Urine and plasma were negative for haemoglobin. Blood urea (900–2020 g/L) and serum creatinine (56.2–70 g/L) were elevated throughout. There was transient hyperkalemia. Liver enzymes were elevated. Creatine kinase N-acetylcysteine and creatine kinase MB were elevated (20 900 and 420 U/L). Creatine phosphokinase done once was >200 000 U/L. Serum lactate dehydrogenase was elevated. Arterial blood gas analysis revealed metabolic acidosis. Antigen capture ELIZA (IgM) for Dengue was positive while leptospira was negative. Electromyography done showed myopathic changes.

The patient was managed with intravenous fluids, maintenance haemodialysis (eight cycles), antibiotics and other supportive care. However, the patient developed acute respiratory distress syndrome, refractory septic shock and cardiac arrhythmia and died after 15 days.

A partial autopsy was conducted in this patient with removal of the abdomino-thoracic organs.

The kidneys were grossly congested. Microscopic examination showed normal glomeruli. The tubules showed extensive changes of tubular epithelial injury including tubulorrhexis and focal regeneration. Mild focal interstitial inflammation was noted. There were numerous bright red granular casts that were positive with peroxidase staining using diaminobenzidine (Figure 1) indirectly indicating the pigments to be haemoglobin/myoglobin casts. Specific immunostain for myoglobin were not available.

Fig. 1.

Photomicrograph shows a section from the kidney with diaminobenzidine positive casts in the tubules (Histochemistry, ×40 original, diaminobenzidine).

The heart done did not show any evidence of myocarditis. However, sections from the skeletal muscles showed diffuse and marked variation in the muscle fibre size and shape with many necrotic rounded muscle fibres with the loss of striations. There were focal areas of lymphomononuclear cell infiltrate and myophagocytosis by CD68 positive histiocytes suggesting myositis (Figure 2). Areas of regeneration with myotubule formation were also seen. Reverse transcriptase polymerase chain reaction for Dengue viral genome was attempted from the formalin fixed skeletal muscle tissue, but was non-contributory.

Fig. 2.

Photomicrograph of skeletal muscle shows histiocytes destroying skeletal muscle fibres (immunohistochemistry, ×40 original, CD68).

The lung showed oedema, hyaline membrane formation and alveolar haemorrhages. Overall features were of Dengue virus associated rhabdomyolysis resulting in myoglobinuria presenting as acute renal failure due to myoglobin cast nephropathy and respiratory symptoms due to diffuse alveolar damage.

Discussion

Dengue is a common viral infection occurring months of September to November in India [1]. The association of Dengue virus infection and rhabdomyolysis/myositis is being increasingly recognized. There are only a few case reports in literature regarding Dengue myositis/rhabdomyolysis in the literature [2]. A study from India suggested that there are two polar forms of neurological syndrome of Dengue virus infection—encephalopathy and myositis with variable degree of overlap [3]. The index patient had extensive myocytolysis and myositis with little encephalopathy or haemolysis and succumbed to the illness, the major role being played by the acute renal failure secondary to rhabdomyolysis.

Pigment cast nephropathy can occur in setting of haemolysis/rhabdomyolysis. Clinical manifestations can range from asymptomatic to that of acute renal failure depending on the severity of the injury. In a clinical scenario as in the present case where the patient presented with an unresolving acute renal failure, a kidney biopsy would have picked up the pigment cast nephropathy. In the absence of substantial haemolysis or myocarditis, a skeletal muscle biopsy could have established the source of the pigment.

The pathogenesis of Dengue myositis and myocarditis could be due to direct muscle invasion or due to production of cytokines, especially tumour necrosis factor-alpha, which is known to increase in human Dengue infection [4]. A study by Salgado et al. [5] demonstrated direct invasion of skeletal muscle fibres by the Dengue virus in vitro. It was also suggested that deranged calcium ion homeostasis could be responsible for the pathological effects.

The scarcity in the medical literature regarding rhabdomyolysis/myositis as an association with Dengue illness may be due to under-reporting and under-recognition of such a complication or may be due to the rarity of the entity. However, there are currently no way to predict which patients are likely to suffer this complication or its severity which has proven fatal in the index case. In the present case, rhabdomyolysis is almost the primary presentation with the absence of other classical features of the infection, suggesting a possible peculiar immunological response to the Dengue infection. Hence, more studies are required regarding the pathogenesis of rhabdomyolysis/myositis, which might provide a therapeutic advantage in managing these patients.

Conflict of interest statement. None declared.