Malaria causes nearly one million deaths each year and with its recent re-emergence, several fatal complications are seen such as cerebral malaria, hypotension or shock, renal failure, pulmonary oedema/adult respiratory distress syndrome, and hypoglycaemia. Symmetric peripheral gangrene (SPG) is a severe but extremely rare complication of malaria. It has a rapid and sudden onset leading to necrosis which cannot be reversed. A 26 year old male was admitted and treated for complicated malaria and developed SPG. He was given intravenous artesunate, doxycyline, clopidogrel and acetyl salicyclic acid for the gangrene; however, he went into multiple organ dysfunction syndrome and septic shock and thus could not be resuscitated. We report this case to highlight that physicians treating malaria should always look for these signs for timely correction and to improve the patient outcome

Bhore, Amol R

Kamble, Sham P

Kumar, Sandeep

Rahatekar, Parag H

Ronghe, Ashwini M

Sequeira, Rohan S

Wadikhaye, Manju B

English

Atharva Scientific Publications (E-Jounals)

Sequeira et al                      Falciparum malaria with peripheral gangrene 
Vol 2 Issue 3 Jul – Sep 2016                                                         Indian J Case Reports / 58 
Case Report 
A complicated case of Plasmodium falciparum malaria with symmetrical 
peripheral gangrene with a review of literature 
Rohan S Sequeira, Manju B Wadikhaye, Sham P Kamble, Ashwini M Ronghe, Amol R Bhore, 
Parag H Rahatekar, Sandeep Kumar 
From, Department of Medicine, Grant Government Medical College, Mumbai, Maharashtra, India 
Correspondence to: Dr Ashwini Ronghe, Department of Medicine, Grant Government Medical College, Mumbai, 
Maharashtra, India, Email: ashuronghe@gmail.com. 
Received: 01 July 2016  Initial Review:  10 July 2016   Accepted: 01 August 2016  Published Online: 11 August 2016 
ABSTRACT 
Malaria causes nearly one million deaths each year and with its recent re-emergence, several fatal complications are seen such 
as cerebral malaria, hypotension or shock, renal failure, pulmonary oedema/adult respiratory distress syndrome, and 
hypoglycaemia. Symmetric peripheral gangrene (SPG) is a severe but extremely rare complication of malaria. It has a rapid 
and sudden onset leading to necrosis which cannot be reversed. A 26 year old male was admitted and treated for complicated 
malaria and developed SPG. He was given intravenous artesunate, doxycyline, clopidogrel and acetyl salicyclic acid for the 
gangrene; however, he went into multiple organ dysfunction syndrome and septic shock and thus could not be resuscitated. We 
report this case to highlight that physicians treating malaria should always look for these signs for timely correction and to 
improve the patient outcome. 
Keywords: Complicated malaria, Gangrene, Plasmodium falciparum, Peripheral gangrene 
 
alaria is a disease caused by protozoa 
transmitted by the bite of infected Anopheles 
mosquito. Malaria is one of the major causes of 
mortality worldwide and was responsible for 627,000 
globally in 2012. According to the World Malaria Report 
2013, about 97 countries had on-going malaria 
transmission. It was found that there were 1,067,824 
confirmed cases of malaria in India; out of which, 524,370 
were attributed to Plasmodium falciparum [1]. 
If treated appropriately and in time, it has a mortality 
rate of 0.1% only. However, if total proportion of 
erythrocytes infected increases to >2% or if there is vital 
organ dysfunction, mortality risk rises steeply [2]. 
Symmetric peripheral gangrene (SPG) is a rare 
complication, with a high mortality (up to 40%) which 
leads to ischemic gangrene of two or more sites in the 
absence of large vessel obstruction or vasculitis [1-3]. Its 
exact pathophysiology is not understood well and several 
factors such as parasitemia, adhesion molecules etc. have 
been considered over the period of years [1]. 
CASE REPORT 
A 26 year old male presented to our hospital with 
complaints of fever and chills for 5 days. There was no 
history of rashes, trauma to limb, exposure to cold, 
diabetes or hypertension, drug intake, burning micturition, 
cough or drowsiness. On admission, the pulse was 80/min, 
respiratory rate was 18/min, blood pressure was 120/80 
mm Hg and SpO2 was 98% on room air. Other systemic 
examinations were within normal limits. 
M 
Sequeira et al                      Falciparum malaria with peripheral gangrene 
Vol 2 Issue 3 Jul – Sep 2016                                                         Indian J Case Reports / 59 
 
Figure 1 – Onset of gangrene on bilateral extremities 
 
Figure 2 - Symmetrical gangrene on bilateral extremities 
 
Figure 3 - Symmetrical gangrene on bilateral extremities 
Blood investigations showed a decreased platelet count 
of 50,000/mm
3
 with normal leukocyte counts. Serum 
electrolytes were normal (K
+
=5.3 Meq/l and 
Na
+
=153Meq/l). SGOT was 720U/l and SGPT was 200U/l 
and total bilirubin was 6.8g/dl. Serum creatinine was 
1.4g/dl. Tests for HBV, HCV, HIV, Leptospirosis and 
syphilis were negative. Blood gas analysis showed pH of 
7.26 with pCo2 of 31.3 mmHg and pO2 of 163mmHg. 
The next day the patient developed a petechial rash all 
over his body. The patient complained of pain and 
numbness of lower extremities which on examination 
showed bluish darkening of the toes and fingers of his 
lower limbs (Fig.1). The skin was cold and dry. Dorsalis 
pedis pulses were absent. There was a clear line of 
demarcation between the live and the dead tissue (Fig. 2 
and 3). Tests for DIC panel showed D dimer 5.4 mcg/ml, 
PT at 15.8 seconds, INR of 1.8 and LDH of 1791U/l. A 
Doppler examination was done to see the arterial 
circulation and to rule out other causes of gangrene. 
Management in the form clopidogrel and acetylsalicylic 
acid was started. 
Over the period of next two days, the condition 
worsened and the patient required ventilatory support. 
Despite intensive care support, the patient developed 
MODS and went into cardiac arrest after one day and 
despite extensive efforts could not be resuscitated. 
DISCUSSION 
Plasmodium falciparum causes 95% of all the cases of 
complicated malaria, which is defined by World Health 
Organisation as those with an impaired level of 
consciousness (Glasgow Coma Scale score ≤7), severe 
anaemia, hypoglycaemia, acidosis, hyperlactatemia, 
hyperparasitemia (of more than 5%), and renal impairment 
[4]. SPG which leads to ischemic gangrene of two or more 
sites in the absence of large vessel obstruction or vasculitis 
was first described in 1891 by Hutchinson [5]. However, a 
common aetiology has not been established yet and 
following aetiologies have been proposed: 
Heavy parasitemia activates the complement system 
and triggers the coagulation pathway causing alteration in 
lipid distribution across the infected erythrocytes. These 
erythrocytes get sequestrated by interacting with 
endothelial receptors, chiefly intercellular adhesion 
molecule (ICAM-I), Vascular adhesion molecule (VCAM-
Sequeira et al                      Falciparum malaria with peripheral gangrene 
Vol 2 Issue 3 Jul – Sep 2016                                                         Indian J Case Reports / 60 
I), endothelial leukocyte adhesion molecule-1 (ELAM-1), 
thrombospondin, and histidine-rich protein. Rosetting of 
uninfected erythrocytes around the parasitized ones also 
adds to the vascular obstruction. This thus initiates a 
microcirculatory obstruction in malaria similar to the 
process in cerebral malaria [4]. 
Another theory states that an adhesion protein family in 
Plasmodium falciparum named erythrocyte membrane 
protein 1 (PfEMP1), encoded by var genes, is responsible 
for both antigenic variation and cell to cell adhesion of 
infected red blood cells at microcirculation sites 
throughout the body [6-7]. This PfEMp1 interacts with 
endothelial receptor protein C receptor (EPCR), which 
mediates protective effects of activated protein C [7-8]. 
During haemolysis, which occurs in infected cells, 
negatively charged phosphatidylserines are exposed 
promoting the formation of prothrombinase. Furthermore, 
inflammatory cytokines, especially TNF-α and interleukin-
6, increase tissue factor expression on mononuclear cells, 
leading to thrombus formation [4]. 
There is also a recent interest in deficiency of 
ADAMTS13, (a von Willebrand factor cleaving protease) 
activity in severe malaria causes accumulation of 
prothrombogenic, unusually large VWF multimers in 
plasma [9]. The presence of reduced ADAMTS13 activity 
may contribute to microvascular obstruction. However till 
now, there is no direct link between ADAMTS13 activity 
and the occurrence of SPG [9]. 
Finally, the life cycle of the Plasmodium has been 
shown to have an effect on the membrane of infected 
erythrocytes. As merozoites mature to trophozoites and 
schizonts, the erythrocyte membrane composition changes 
which leads to the appearance of knobs on their surfaces 
[2]. This alteration changes both their adherence to 
endothelial cells as well as non-infected and other infected 
red blood cells. This results in sequestered erythrocytes 
within the microcirculation, and ultimately vascular 
obstruction [4]. Thus, obstruction and endothelial 
activation play a major role in the pathogenesis of SPG. 
This condition did not respond to artisunate and 
literature of review also did not mention role of 
antimalarial drugs in preventing SPG. SPG usually occurs 
within the first 3 days of effective antimalarial therapy, at 
which time parasitemia is often very significantly reduced 
which may be misleading [9]. Treatment of SPG is largely 
empirical with treatment of the underlying cause. There is 
no evidence that blood exchange transfusions or fresh 
frozen plasma administration could be effective treatment 
options for patients with DIC and SPG. Heparin or 
streptokinase is not indicated unless SPG is associated 
with DIC. Surgery and use of vasopressors should be 
delayed when the delimitation of dry necrotic areas is 
evident [9-10]. 
Other treatments can be intravenous nitropruside, 
phentolamine and prostaglandin (epoprostenol) which are 
vasodilators or sympathetic ganglion blockade can be 
done. Papaverine, dextran and hyperbaric oxygen therapy 
have not been shown to be beneficial [10]. 
CONCLUSION 
The exact pathogenesis of SPG is still not known and the 
immediate onset of the ischemia followed by rapidly 
progressing complications like necrosis makes prevention 
and management of the gangrene difficult as 
anticoagulants are not routinely in the treatment regime of 
common malaria. The physician should thus be on the 
lookout for these signs while managing a malaria case. 
REFERENCES 
1. World Health Organisation Factsheet on the World 
Malaria Report 2013, viewed on 10
th
 January 2016, 
http://www.who.int/malaria/media/world_malaria_report_
2013/en/. [Last accessed on June 12, 2016]. 
2. Rana A, Singh DP, Kaur G, Verma SK, Mahur H. 
Symmetrical peripheral gangrene: A rare complication of 
plasmodium falciparum malaria. Trop Parasitol. 
2015;5:130-2. 
3. Gupta A, Dwivedi Y, Saxena AK, Joshi K. Symmetrical 
peripheral gangrene with Plasmodium falciparum malaria. 
J Nat Sc Biol Med. 2013;4:262-264. 
4. Alkizim FO, Matheka D, Mwanda OW. Malaria 
complicated by gangrene: a case presentation and review. 
Pan Afr Med J. 2011;10:46. 
5. Hutchinson J. Notes of uncommon cases. Br Med J. 
1891;2:8–9. 
6. Sriboonvorakul N, Leepipatpiboon N, Dondorp AM, 
Pouplin T, White NJ, Tarning J, et al. Liquid 
chromatographic–mass spectrometric method for 
simultaneous determination of small organic acids 
potentially contributing to acidosis in severe malaria. J 
Chromatogr B Analyt Technol Biomed Life Sci. 2013;941 
(100):116-122. 
Sequeira et al                      Falciparum malaria with peripheral gangrene 
Vol 2 Issue 3 Jul – Sep 2016                                                         Indian J Case Reports / 61 
7. Kraemer SM, Smith JD. A family affair: var genes, 
PfEMP1 binding, and malaria disease. Curr Opin 
Microbiol. 2006;9:374–380. 
8. Turner L, Lavstsen T, Berger SS, Wang SS, Petersen JE, 
Avril M, et al. Severe malaria is associated with parasite 
binding to endothelial protein C receptor. Nature. 
2013;498 (7455):502-505. 
9. Masse E, Hantson P. Plasmodium falciparum Malaria 
Complicated by Symmetrical Peripheral Gangrene, Bowel 
Ischemia, Repeated Candidemia, and Bacteraemia. Case 
Reports in Medicine. 2014;Article ID 696725:4 pages. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10. Abdali N, Malik AM, Kamal A, Ahmad M. Symmetrical 
peripheral gangrene due to Plasmodium falciparum 
malaria. BMJ Case Rep. 2014. pii:bcr2014204268. 
How to cite this article: Sequeira RS, Wadikhaye MB, 
Kamble SP, Ronghe AM, Bhore AR, Rahatekar PH, 
Kumar S. A complicated case of Plasmodium 
falciparum malaria with symmetrical peripheral 
gangrene with review of literature. Indian J Case 
Reports. 2016; 2(3): 58-61. 
Conflict of interest: None stated, Funding: Nil 


A complicated case of Plasmodium falciparum malaria with symmetrical peripheral gangrene with a review of literature

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A complicated case of Plasmodium falciparum malaria with symmetrical peripheral gangrene with a review of literature

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