Symmetrical peripheral gangrene: A rare complication of plasmodium falciparum malaria.

Malaria, the most important of the parasitic diseases of humans, is transmitted in 108 countries containing 3 billion people and causes nearly 1 million deaths each year. With the re-emergence of malaria various life-threatening complications of malaria have been observed. Unarousable coma/cerebral malaria, severe normochromic, normocytic anemia, renal failure, pulmonary edema/adult respiratory distress syndrome, hypoglycemia, hypotension/shock, bleeding/disseminated intravascular coagulation (DIC), hemoglobinuria and jaundice are few of the common complications of severe malaria. Symmetrical peripheral gangrene (SPG) has been reported as a rare complication of malaria. We report a rare and unique case of Plasmodium falciparum malaria complicated by DIC, severe normocytic normochromic anemia, and SPG.

INTRODUCTION

Malaria is a protozoan disease transmitted by the bite of infected Anopheles mosquito. Despite enormous control efforts, increase in the drug resistance of the parasite, the insecticide resistance of its vectors, and human travel and migration have contributed to its resurgence. Appropriately and promptly treated, uncomplicated Plasmodium falciparum malaria carries a mortality rate of 0.1%. However, once vital-organ dysfunction occurs or the total proportion of erythrocytes infected increases to >2%, mortality risk rises steeply. The major manifestations of severe P. falciparum malaria are cerebral malaria, severe normochromic, normocytic anemia, renal failure, adult respiratory distress syndrome. Symmetrical peripheral gangrene (SPG) is a rare but devastating complication of septicemia, with a high mortality (up to 40%). It is characterized by distal ischemic gangrene of two or more sites in the absence of large vessel obstruction or vasculitis. The common organisms involved are Gram-positive organisms, but Gram-negative organisms have also been implicated. Malaria has been implicated rarely as a cause of SPG. Literature survey has documented 25 cases of SPG caused by malaria.[12] We report this rare entity in a 17-year-old boy presented with complicated malaria.

CASE REPORT

We present the case of a 17-year-old boy who was admitted to the medical ward of MBGH, RNT Medical College, Udaipur with complaints of fever with chills and rigor for 6 days. Patient noticed blackening of his toes and lower limbs on the third day of fever which was associated with pain and numbness. There was no history of trauma, any drug ingestion, alcohol use, and smoking. Examination revealed pulse 110 beats/min, regular, bounding, with all peripheral pulses felt normally, blood pressure - 100/40 mmHg in right brachial artery, temperature of 101.4°F, respiratory rate - 22 breaths/min. On examination, patient was found to have severe pallor, mild icterus, and blackening of third, fourth, and fifth toe of right foot and fifth toe of left foot with circumferentially patchy area of blackening of bilateral lower legs up to mid-shin [Figures 1 and 2]. Overlying skin was dry and wrinkled. Per abdominal examination revealed firm splenomegaly 2 cm below costal margin. Neurological examination revealed decreased sensations over hyper-pigmented area. Cardiovascular system examination revealed a soft functional ejection systolic murmur present at pulmonary area heard all over the precordium. Respiratory system examination was unremarkable. Provisional diagnosis of septicemia with SPG was kept and patient was investigated.

Figure 1

Image of right foot showing gangrenous third and fifth toes

Figure 2

Image of both feet showing symmetrical peripheral gangrene

Blood investigation revealed hemoglobin (Hb) 1.1 g%, total leucocytes count (TLC) 1000 cells/mm3, with 55% polymorphs and 40% lymphocytes, platelets 10,000/mm3 with normocytic normochromic picture on peripheral blood film (PBF) with no immature cells and no parasite was seen. Renal and liver functions tests were normal. Malarial parasite quantitative buffy coat was negative but rapid diagnostic kit for P. falciparum was positive. Anti-nuclear antibody, rheumatoid factor, C-reactive protein, human immunodeficiency virus, hepatitis B surface antigen, anti-hepatitis C virus were negative. Prothrombin time-international normalized ratio (PT-INR) was 18 and 1.41 (control 13). Bleeding time, clotting time were normal. Chest X-ray was normal. Ultrasonography of abdomen revealed gall bladder sludge and mild splenomegaly. Blood culture did not show growth of any pathogenic organism. Color Doppler of both lower limbs showed normal caliber, flow and Doppler indices of bilateral femoral, popliteal, anterior and posterior tibial arteries [Figure 3].

Figure 3

Color Doppler of both lower limbs reveals normal study

Diagnosis of complicated P. falciparum malaria with disseminated intravascular coagulation (DIC) with SPG was kept and patient was treated with injection quinine 600 mg intravenous (IV) 12 hourly slow infusion in 10% Glucose Distilled Water, tablet doxycycline 100 mg twice daily, injection ceftriaxone 1 g IV 12 hourly and with supportive three units of packed cell volume and six units of platelets. After a consultation from cardiothoracic vascular surgeon patient was started on low dose heparin infusion for SPG but patient developed epistaxis soon after starting the infusion, so infusion was stopped and managed conservatively. Patient had an uneventful recovery and discharged from hospital after 10 days. On discharge patient's vitals were normal, Hb - 6 g%, PBF showed normocytic normochromic anemia with occasional macrocytes, TLC - 11,000 cells/mm3, platelets - 1.8 lac/mm3, PT-INR - 15 and 1.19.

DISCUSSION

SPG is defined as symmetrical distal ischemic damage at two or more sites in the absence of large vessel obstruction. Also used synonymously with purpura fulminans, it was first described by Hutchinson (1891).[3] About half of the patients who survive require amputation of the affected limb. The common organisms involved are Pneumococcus, Staphylococcus and Streptococcus, but Gram-negative organisms have also been implicated[4] though it can present as a complication of malignant disease (paraneoplastic syndrome), ergotism or protein C deficiency. Most of the patients, i.e. up to 85%, of SPG have associated DIC.[5] The factors aggravating SPG include asplenia, immunosuppression, previous cold injury to extremities, diabetes mellitus, renal failure, increased sympathetic tone, and use of vasopressors.

Malaria is a mosquito-borne infectious disease of humans parasitic protozoans (a type of unicellular microorganism) of the genus Plasmodium transmitted by bite of female Anopheles mosquito. Among the complications of malaria most common are acute respiratory distress syndrome occurs in 5-25% of adults and up to 29% of pregnant women. Infection with P. falciparum may result in cerebral malaria, a form of severe malaria that involves encephalopathy, hypoglycemia, and hemoglobinuria with renal failure.[6]

SPG has been rarely reported as a complication of malaria. Till date 25 cases of SPG complicating malaria have been documented in literature and latest being reported by Gupta et al. (2013).[2] In P. falciparum infections, membrane protuberances appear on the erythrocyte's surface 12-15 h after the cell's invasion. These “knobs” extrude a erythrocyte membrane adhesive protein that mediates attachment to receptors on venular and capillary endothelium predominantly via intercellular adhesion molecule 1, an event termed cytoadherence. The infected erythrocytes, thus, stick inside and eventually block capillaries and venules.[7] This might be the pathogenesis of SPG seen in our patient. Furthermore, changes in membrane that occur in P. falciparum infected erythrocytes causes activation of the blood coagulation cascade to cause thrombosis. Of patients with severe malaria, <5% have significant bleeding with evidence of DIC which might also be responsible for the pathogenesis of SPG observed in our patient by activating coagulation cascade.

The unique feature of our case was that patient presented with severe normocytic normochromic anemia (Hb - 1.1 gm%) and pancytopenia and was managed conservatively and had an uneventful recovery.