Acute Plasmodium vivax malaria presenting with pancytopenia secondary to hemophagocytic syndrome: case report and literature review.

Pancytopenia as an initial manifestation of acute plasmodium vivax malaria is extremely rare and mainly reported with plasmodium falciparum. We report a 37- year old Nepali patient who recently came to Saudi Arabia and presented with a three-week history of intermittent fever, chills and rigor. She was found to have spleenomegaly, pancytopenia, hyperferrtinemia, and hypofibronogenemia with positive peripheral blood smear for plasmodium vivax. The patient had a full recovery from pancytopenia with oral chloroquine.

INTRODUCTION

Unlike plasmodium falciparum, Plasmodium vivax malaria is rarely associated with severe complications. One of the complications is pancytopenia, which can occur in vivax infection secondary to microangiopathic hemolytic anemia. Another mechanism of pancytopenia in vivax infection is hemophagocytic syndrome, but this is extremely rare and few cases are reported in the world literature. We report a rare case of plasmodium vivax malaria with pancytopenia, secondary to hemophagocytic syndrome. The suggested management strategy of this unique presentation is highlighted. We think that physicians in Saudi Arabia should be aware of such a presentation since there are a lot of people from endemic regions who are working and residing in the Kingdom.

CASE REPORT

A 37-year old female patient from Nepal, who recently came to Saudi Arabia as a housemaid, presented at the Emergency Department in August 2008 with fatigue, headache, intermittent fever, chills and rigor of three weeks’ duration. She gave a history of several febrile illnesses in the past few years that were presumed to be malaria and treated as such, although no documentation was available. Upon presentation, she was febrile with a temperature of 39.5 ° C. She was very pale, had a palpable spleen, 5 cm below left costal margin. The rest of the physical examination was unremarkable. Her initial blood tests were remarkable for pancytopenia with WBC of 2.9 × 109/l, Neutrophils of 0.8 × 109/l, platelet of 52 × 109/l and hemoglobin of 5.6 g/dl. She had a normal reticulocytes count of 2% and an indirect bilurubin of 0.2 mg/dl. Her ferritin level was elevated more than 554 lg/l with Fibrinogen level of 0.8 g/L. Her initial peripheral blood smear showed ring forms, developing trophozites and mature schizonts of plasmodium vivax without any evidence of shiztocytes. She had negative serological evidence of CMV, Parvovirus B19 and hepatitis. All her septic blood and urine work up were unremarkable. Her abdominal ultrasound confirmed an enlargement of the spleen. She was treated with oral chloroquine 300 mg/d for 5 days and her condition improved rapidly with complete resolution of her pancytopenia and plasmodium vivax (Table 1). Bone marrow aspiration was not considered since she demonstrated quick recovery of pancytopenia following oral chloroquine on the third day of treatment. She was discharged on primiquine for 15 days to assure complete eradication of the vivax infection.

Table 1

Laboratory results before and after treatment

DISCUSSION

Plasmodium Vivax malaria is one of the parasitic infections transmitted by mosquitoes. It usually results in minimal complications with intermittent fever, chills and rigors following mosquito bites. Its life cycle is characterized by a hepatic phase which keeps the vivax infection in a dormant stage resulting in recurrence and relapse after treatment.1. We report a rare case of acute plasmodium vivax with pancytopenia secondary to hemophagocytic syndrome. Our patient had a fever, spleenomegaly, pancytopenia, hyperferritinemia and hypofibrinogenemia which are consistent with hemophagocytic syndrome based on the recent revised criteria 2007 (Table 2).1 This criteria did not mandate bone marrow aspiration for diagnosis.

Table 2

Diagnostic criteria for hemophagocytic syndrome1

Hemophagocytic syndrome (HPS) is probably due to inappropriate or excessive immunologic responses of T cells. In HPS, high levels of IFN-gamma, soluble IL-2 receptor, TNF-a, IL-1, and IL-6 have been demonstrated, suggesting that elaboration of activating cytokines by T-helper cells promotes activation of macrophages in this disease .These cytokines depress the proliferation of progenitor cells, which aggravate the pancytopenia as a result of phagocytosis of the blood cells .This has been attributed secondary to different infections including Viral (e.g. EBV, CMV, Varicella) Bacterial (e.g. Gram-negative rods, Pneumococcus, Mycoplasma pneumonia) Fungal (e.g. Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum) and Parasitic (e.g. Babesia microti, Plasmodium falciparum, Strongyloides stercoralis).2–4 A recent report from India revealed that pancytopenia is a completely atypical manifestation of plasmodium vivax which occurs in only 0.9 %.5

HPS secondary to plasmodium vivax is rarely reported in the literature. To our knowledge, there are four reported cases of plasmodium vivax with pancytopenia.4–8 Three cases had isolated vivax infection and one had combined vivax and falciparum infection.

Fortunately, we were able to detect the plasmodium vivax on the peripheral blood smear upon presentation. Chloroquine was started immediately resulting in quick recovery from the pancytopenia, thus eliminating the need for diagnostic bone marrow aspiration.

It is our belief that plasmodium vivax should be listed as one of the causes of hemophagocytic syndrome. Diagnostic bone marrow aspiration should not be recommended in patients with known plasmodium vivax and pancytopenia, since these patients respond quickly to oral chloroquine. Repeated peripheral blood smears are very essential to reduce false negative results and subsequent misdiagnosis in this type of presentation. Malaria should be considered in the differential diagnosis of fever and pancytopenia in all travelers from endemic areas.