Malarial pancreatitis: Case report and systematic review of the literature.

Malaria can cause a wide spectrum of clinical manifestations ranging from uncomplicated febrile illness to multiorgan failure. Pancreatitis is a rare complication of malaria with only a few reported cases. Herein, we describe a case of acute pancreatitis with multiorgan failure due to Plasmodium falciparum managed successfully with antimalarials and conservative treatment. We also perform a systematic review of literature for reports of acute pancreatitis due to Plasmodium infection.

Introduction

Malaria is one of the most important protozoan parasitic infection of humans and remains endemic in India. It is responsible for 1.8% of cumulative deaths before the age of 70 years.[1] It is one of the common causes of acute febrile illness in endemic areas and can cause single or multiorgan dysfunction including acute renal failure, acute respiratory distress syndrome (ARDS), jaundice, myocarditis, hemolytic anemia, coma, and others.[23] Acute pancreatitis is a rare manifestation of malaria with only a few cases reported in literature. Herein, we report a case of acute pancreatitis and multiorgan dysfunction caused by Plasmodium falciparum. We also perform a systematic review of literature on acute pancreatitis caused by malaria.

Case Report

A 40-year-old man presented with acute onset high-grade fever, jaundice, and abdominal pain of 10 days duration. He did not have any vomiting, passage of clay-colored stools, or any alteration in his bowel habit. Three days before the presentation, the patient had also developed breathlessness, drowsiness, and decreased urine output. There was no cough, chest pain, or hemoptysis. There was no history of any seizures, sensory or motor complaints. The patient did not have any comorbidities or addictions. On examination, the pulse rate was 124 per min, respiratory rate 40 per min, blood pressure 100/60 mmHg, and temperature 101°F. Glasgow coma score was 10. Pallor and icterus were present. Auscultation of the chest revealed bilateral basal crackles. The abdomen was distended with epigastric tenderness and hepatosplenomegaly.

Investigations revealed anemia, thrombocytopenia, and neutrophilic leukocytosis with deranged renal and liver functions [Table 1]. Peripheral blood examination showed trophozoites of P. falciparum (parasite index 1.5%) and rapid diagnostic test (QDx Malaria Pv/Pf malaria card test, Piramal Healthcare Limited, India) for P. falciparum was positive. Hypoxemia (PaO2/FiO2 ratio = 69) was present with bilateral alveolar opacities on chest radiograph suggesting ARDS [Figure 1]. Bacterial cultures of blood and endotracheal aspirate were sterile throughout the hospital stay. Serum amylase was 391 U/L and lipase was 753 U/L [Table 1]. Contrast enhanced computed tomography (CT) scan of the abdomen revealed evidence of pancreatitis with a modified CT score of 10 [Figure 2] and bedside index of severity in acute pancreatitis (BISAP) score of 4. There were no gallstones on ultrasound or CT of the abdomen.

Table 1

Clinical characteristics at baseline and discharge

Figure 1

Chest radiograph showing bilateral infiltrates consistent with acute respiratory distress syndrome

Figure 2

Contrast enhanced computed tomography of the abdomen showing pancreatic necrosis

The patient was diagnosed as severe falciparum malaria with acute pancreatitis. He was electively intubated and mechanically ventilated. He was kept nil per oral and a nasogastric tube was placed. Intravenous artesunate (120 mg every 12 h for 3 days followed by 120 mg every 24 h) and oral doxycycline (200 mg/day in two divided doses) were administered. Despite treatment, there was progressive abdominal distension with the development of abdominal compartment syndrome (indicated by a high abdominal pressure of 28 cm of saline, hypotension, and worsening renal failure). Intravenous normal saline, vasopressors (noradrenaline and vasopressin), and intravenous meropenem were started. An abdominal drain was placed to decrease the intraabdominal pressure, and intermittent hemodialysis was performed.

Abdominal pressure decreased, fever abated, and hypotension resolved on the 5th day. Renal function improved and dialysis was stopped after six sessions. The patient was subsequently discharged after 4 weeks of hospitalization and continued to do well on follow-up.

Discussion

The case highlights that acute pancreatitis can occasionally complicate the course of falciparum malaria. We made a diagnosis of malaria-associated pancreatitis as the patient did not consume alcohol; there were no gallstones on abdominal imaging, no history of consumption of any drug known to cause pancreatitis and normal serum calcium with only mildly raised serum triglycerides. Although the exact mechanism of pancreatitis is unclear, the possible reason can be obstruction of capillaries due to parasite-laden erythrocytes causing ischemic damage to pancreatic parenchyma or massive hemolysis associated with malaria.[456]

Pancreatitis as a complication of malaria is a rare entity with the first case reported in 1907.[7] A systematic review of the PubMed and EmBase databases using the search string (“malaria” or “falciparum” or “vivax” or “malariae” or “ovale”) and “pancreatitis” yielded 18 reports (22 cases) on pancreatitis caused by malaria [Table 2].[489101112131415161718192021222324] The most common species responsible was P. falciparum (17/22), which was also the causative species in the index case. Abdominal pain was reported in all cases while icterus was seen in 12 cases. Abdominal pain in malaria can be due to various causes such as acalculous cholecystitis, splenic infarction, splenic rupture, hepatitis, acute renal failure, and others. The review suggests that in patients with malaria presenting with abdominal pain, pancreatitis may also be considered as a possible etiology.

Table 2

Studies reporting pancreatitis due to malaria

The diagnosis of malaria-associated pancreatitis is based upon clinical symptoms (abdominal pain, jaundice, abdominal tenderness, and guarding), laboratory investigations (elevated serum amylase and lipase are seen in 19/22 and 15/22 patients, respectively, in the systematic review), and radiology (ultrasound and contrast-enhanced CT abdomen) and is considered after the common causes of pancreatitis are excluded.

Pancreatitis in malaria might be associated with dysfunction of other vital organs such as renal failure (n = 9), ARDS (n = 3), hypotension (n = 2), which may be attributable to malaria per se or to the ensuing pancreatitis. The index case also had multiorgan dysfunction syndrome (hypotension, ARDS, renal failure, thrombocytopenia, and liver failure). Further, our patient also developed abdominal compartment syndrome (seen in 11% of cases of pancreatitis of any cause).[25]

The index case suffered from severe pancreatitis (BISAP score of 4) with a predicted mortality of >15%.[26] Yet, he responded well to management with intravenous artesunate and doxycycline consistent with the results of the systematic review in which most reported cases had moderate to severe pancreatitis and responded favorably to antimalarial therapy [Table 2]. Four out of 22 (18.2%) patients died. Of the four patients, one patient did not receive antimalarial therapy (identified postmortem) while in one case, antimalarial therapy was started in the 2nd week of illness. This highlights the importance of the early institution of antimalarial therapy which along with nonsurgical management is usually associated with a favorable outcome.

Conclusion

Malaria may rarely be complicated by pancreatitis. It is essential to suspect it clinically in patients with abdominal pain, to confirm it early, and to treat it appropriately to have a good outcome.

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Conflicts of interest

There are no conflicts of interest.