Purpura fulminans: a rare presentation of a common disease

Case history

A 22-year-old man, suffering a moderate to high grade fever associated with chills and rigors for 7 days, a history of an episode of malena 3 days prior to admission and swelling followed by the discolouration of both lower limbs for 3 days, was admitted. On examination he was pale, conscious, oriented, all peripheral pulses were palpable and the vitals were stable. A local examination showed swelling and bluish black discolouration of both feet and the legs up to 5 cm above the medial malleolus (Figure 1). The rest of the examination was within the normal limits. Investigations revealed haemoglobin of 9.3 g%, total leucocyte count 12800/mm³, differential leucocyte count (polymorphs 77%, lymphocytes 20%, eosinophils 1%, monocytes 2%), platelet count 19000/mm³, total serum bilirubin 1.57 mg/dL, serum alanine aminotransferase 110.1 U/L, serum aspartate aminotransferase 175.6 U/L, serum alkaline phosphatase 165 U/L, total serum protein 5.6 g/dL (albumin 3.0 g/dL), prothrombin time 25.9 s (control – 12.3), blood urea 99.9 mg%, serum creatinine 1.51 mg% and a peripheral smear for malarial parasite and malaria antigen was positive for Plasmodium falciparum (parasitic density +++). Chest radiograph and ultrasound abdomen were normal. Blood, stool and urine cultures were sterile. Viral markers for hepatitis B, C and antinuclear antibody were negative. An enzyme-linked immunosorbent assay for human immunodeficiency virus and a venereal disease research laboratories test were non-reactive. Arterial colour Dopplers of both lower limbs were normal. A diagnosis of complicated malaria with multisystem dysfunction with purpura fulminans (PF) was made.

The patient was started on intravenous (IV) artesunate, low molecular weight heparin followed by warfarin in addition to IV fluids, to which he showed gradual response as he became afebrile on day 3 and his laboratory parameters returned to normal within a week. Pedal oedema and discolouration also subsided, except for the gangrene in the terminal phalanx of the fourth and fifth toes of both feet. He was discharged on day 10 on warfarin and advised to attend regular follow-up. OPEN IN VIEWER

PF is a rare syndrome of intravascular thrombosis and haemorrhagic infarction of the skin that is rapidly progressive and accompanied by vascular collapse and disseminated intravascular coagulation. This syndrome usually occurs in children but it has also been noted in adults. There are three forms of this disease that are classified by triggering mechanisms. First, neonatal PF is associated with a hereditary deficiency of the natural anticoagulants protein C and protein S, as well as antithrombin III. Idiopathic PF usually follows an initiating febrile illness that manifests with rapidly progressive purpura. A deficiency of protein S is considered to be central to the pathogenesis of this form of the disease. The third, and most common type of PF, is acute infectious PF in which bacterial infections are the main culprits. ¹ Only a few cases of PF associated with falciparum malaria have been reported in literature. ^2,3 The exact mechanism responsible for disseminated intravascular coagulation in malaria is not well understood. It is believed that a large infestation of parasites in the blood cause the activation of a compliment system and an alteration in the lipid distribution across the parasitized erythrocytes activates the intrinsic coagulation pathway. Parasitized erythrocytes become sequestrated in the microcirculation by molecular interaction with endothelial receptors, chiefly intracellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), thrombospondin, endothelial leukocytes adhesion molecule (ELAM-1) and histidine rich protein. Cytoadherence and rosetting may lead to obstruction in the microcirculatory bed. ⁴

PF is sometimes used synonymously with symmetrical peripheral gangrene and is defined as symmetrical distal ischaemic damage at two or more sites in the absence of large vessel obstruction. The distal ischaemic damage occurs in the fingers and toes and, rarely, the nose, upper lip, ear lobules or the genitalia. ⁵ Disseminated intravascular coagulation (DIC) and haemorrhagic infarction of the skin with uninvolved proximal arteries are the hallmarks of this condition. Studies indicate that up to 85% of patients have associated DIC. The diagnosis of PF should not be entertained in the absence of DIC and there should be a presence of at least one positive test of the generation of thrombin in order to make a diagnosis of DIC. ² In our patient, a prolonged prothrombin time, thrombocytopenia, along with a positive D-dimer test established the diagnosis of DIC which, along with the skin lesions and typical peripheral smear, pointed to the diagnosis of PF due to falciparum malaria.

PF is a serious medical emergency, often requiring major amputations, and the main modality of treatment is the early recognition of aggravating factors together with the treatment of the underlying disease. We have presented this case in order to stress the necessity of physicians to be aware of falciparum malaria in the differential diagnosis of PF, as falciparum malaria is an easily treatable cause of such dreadful complications.