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Symmetrical Peripheral Gangrene: A Rare Complication of Malaria

Symmetrical Peripheral Gangrene (SPG) is one of the very rare and devastating complication of malaria. We report a 45-year-old gentleman who presented with fever and blackish discoloration of digits. Examination revealed mild splenomegaly, cold peripheries with dry gangrene involving bilateral fingers and toes. Investigations revealed thrombocytopenia and transaminitis. Rapid malaria test was positive for both Plasmodium falciparum and Plasmodium vivax . Patient was treated with antimalarials. Clinicians managing malaria should be more vigilant for this rare devastating complication.


Introduction
Malaria is one of the commonest infections seen in Indian population, which often presents with various complications but Symmetrical Peripheral Gangrene (SPG) as a complication of malaria is very rare. SPG is one of the devastating complications of malaria which is characterized by distal ischemic gangrene of two or more sites in the absence of large vessel obstruction or vasculitis. 1 This is rarely anticipated during management of malaria patients. We report a 45-year old gentleman who presented with symmetrical peripheral gangrene, a rare complication of malaria.

Case Report
A 45-year-old man presented with seven days history of high-grade fever with chills and rigors. Patient developed blackening of his toes and fingers on the fifth day of fever which was associated with pain ( Figure 1). There was no history of diabetes mellitus, hypertension, drug intake, recent trauma to limbs, exposure to cold, bleeding from any site, alcohol use, and smoking. Examination revealed pulse rate of 110 beats/ min, regular, bounding, with all peripheral pulses were palpable, blood pressure of 120/ 70 mmHg (comparable in all four limbs), temperature of 101.2°F and respiratory rate of 20 breaths/ min. His peripheries were cold with dry gangrene involving bilateral fingers and toes. Respiratory, cardiovascular and abdominal system examination were unremarkable. Neurological examination revealed decreased sensations over gangrenous area. Clinical diagnosis of septicemia with symmetrical peripheral gangrene was kept.

Discussion
Malaria is a mosquito-borne infectious disease which often presents with multiple complications especially in a case of Plasmodium falciparum (pf) malaria. Common complications  of malaria include thrombocytopenia, acute kidney injury, acute respiratory distress syndrome, hepatitis, cerebral malaria (hypoglycemia, seizures), metabolic acidosis and hemolysis. 2 SPG as a complication of malaria is very rare and it is described mostly in pf malaria cases. In our case there was dual infection with Plasmodium vivax and Plasmodium falciparum malaria. Few theories have been proposed to explain SPG in a case of malaria. In Plasmodium falciparum infections, heavy parasitemia stimulate complement system which in turns activate coagulation pathway leading to thrombosis of microcirculation resulting in peripheral gangrene. 3,4 In another explanation, infected erythrocytes via intercellular adhesion molecule 1 (ICAM-1) get attached to receptors on capillary endothelium (cytoadherence). Infected erythrocytes stick inside and eventually block microcirculation leading to thrombosis and eventually gangrene. 5 Various treatment modalities have been tried in SPG associated with malaria including anticoagulants, vasodilators, hyperbaric oxygen therapy etc. but none of them have been shown to be beneficial. 6 In our case, we did not use any anticoagulants or vasodilators for SPG. According to the literature, mortality rate may be as high as 35% with rate of amputation ranging from 70% to 90%. 7 Fortunately, outcome was positive in our case with almost full functional recovery of all four limbs.
Other causes of SPG include sepsis, low cardiac output states like dilated cardiomyopathy, vasopressor use, ergot poisoning but its association with malaria is rare. In our case, all the other possible causes of symmetrical peripheral gangrene were ruled out. Our patient remained hemodynamically stable throughout the course of the disease. The patient improved after receiving antimalarial therapy only which clearly indicates that malaria was the underlying cause of SPG in this case. SPG has been reported with Plasmodium falciparum as well as Plasmodium vivax malaria. 8,9 However, our case had mixed infection with both.
To conclude, SPG is a rare complication of malaria and clinicians must be aware of this complication while dealing with cases of malaria.