Acute pancreatitis associated with hemorrhagic fever with renal syndrome: clinical analysis of 12 cases

Abstract

Background: Acute pancreatitis is one of the rare complications of hemorrhagic fever with renal syndrome (HFRS), which easy to be misdiagnosed as acute abdomen, usually critically ill, poor treatment effect, highly mortality. In this study, we retrospectively analyzed to explore the clinical characteristics, 12 cases of hemorrhagic fever with renal syndrome complicated with acute pancreatitis treatment methods and prognosis. Methods: We conducted a retrospective study of HFRS in patients complicated with acute pancreatitis. 12 cases were collected from Ningbo first hospital between January 2001 and December 2012. Clinical information and laboratory parameters were obtained by reviewing literature and records. Results: Twelve from 156 cases (7.69%) HFRS complicated with acute pancreatitis. Men comprised more than half (75%) of the sample population, the mean age was (38 ± 19) years. Abdominal pain was the main clinical manifestations in all the patients, all of their serum amylase and serum lipase were increased, 10 patients were given the total abdomen CT examination, eight cases showed enlargement of the pancreas and surrounding leakage, two cases showed pancreatic necrosis and hemorrhage. Three cases complicated with pulmonary edema. In 12 cases, four of them received hemodialysis treatment, one gives surgical intervention. Eight cases were complete remission, three cases were partial remission and one case was death. Conclusions: Acute pancreatitis is one of rare of the serious complications of HFRS, whereas the correct diagnosis and clear the cause of disease is critical for improve the quality of life of patients and reduce the mortality, timely hemodialysis treatment is effective, early intervention can improve the prognosis.

• Abdominal pain
• acute pancreatitis
• hemodialysis
• hemorrhagic fever with renal syndrome

Introduction

Hemorrhagic fever with renal syndrome (HFRS) is a natural immunity to infectious diseases by rats, lice, ticks with Hantavirus transmission. HFRS can cause multiple organ function damage, which is a systemic disease, mainly to kidney damage, the second is the heart, liver, lung, brain, gastrointestinal and endocrine organs, always accompany with viremia and systemic capillary injury of systemic infection.1

Acute pancreatitis is a serious disease of itself, which is acute onset, rapid progression, can quickly develop into severe acute pancreatitis, many complications and highly mortality.2 Acute pancreatitis is a rare but life-threatening complication of HFRS. HFRS complicated with acute pancreatitis is not significant, with abdominal pain as the main clinical manifestation, misdiagnosis rate is very high, when the skin and mucosal appear bleeding signs, the disease has been developed into severity, may complicated with respiratory dysfunction.

HFRS is a global public health problem, until now no effective drugs can kill the HFRS virus.3 The majority of scholars believe that the acute pancreatitis is caused by Hantavirus invasion pancreas, belong to a part of HFRS. So, under the control of acute pancreatitis, the treatment of primary disease is the priority among priorities at the same time. Hemodialysis treatment for patients can effectively scavenge the metabolic wastes and inflammatory factors, help to alleviate the acute renal injury.4 In this study, we retrospectively analyzed the clinical data of our hospital, 12 cases of HFRS complicated with acute pancreatitis, and review of the literature, so as to improve the understanding of its diagnosis and treatment.

Materials and methods

We retrospectively reviewed the case records of 12 patients with HFRS complicated with acute pancreatitis, diagnosed during the major HFRS epidemic periods, from September through December, in 2001 and 2012, at the Ningbo first hospital in Zhejiang Province. The clinical diagnosis of HFRS infection was laboratory confirmed by indirect immunofluorescent antibody test for detection of serum IgG antibodies and by enzyme-linked immunosorbent assay (ELISA) for detection of serum IgM antibodies. The tests were performed by the Ningbo Reference Laboratory.

Clinical and laboratory data were obtained daily throughout hospitalization and were collected on standardized data collection forms. Including HFRS courses, clinical manifestations, laboratory examinations, imaging data, treatment and prognosis. Complete remission definition: the symptoms of acute pancreatitis and HFRS disease activity completely disappeared; partial remission definition: symptoms of acute pancreatitis and HFRS disease activity can be part of the control, but not completely better. No remission definition: symptoms of acute pancreatitis and HFRS disease activity had no obvious improvement. Continuous variables are presented as mean ± SD. Categorical and discrete variables are presented as frequencies and percentages.

Results

The 156 eligible patients who have been diagnosed as HFRS from January 2001 to December 2012, 12 (7.69%) patients developed acute pancreatitis. Nine patients of 12 cases were male (75%) and three female (25%). Patients ranged in age from 19 to 57 years; the mean age was (38 ± 19) years. All cases were induced acute pancreatitis by HFRS at activity stage. Abdominal pain is the main clinical manifestations in all the patients. Ten patients had fever, including six cases of temperature 38.1 ∼ 39.0 °C, two cases of 39.0 ∼ 40.0 °C, >40.0 °C in two cases. Only one case manifested as skin mucous membrane bleeding. In 12 cases, four patients in oliguric stage, 24 h urine volume of 250–400 mL one case in diuresis stage, 24 h urine volume 3600–5000 mL, Table 1 describes the general information of study participants.

Table 1. General information of 12 cases of HFRS complicated with acute pancreatitis.

No	Sex	Age (years)	Other clinical features	Kidney disease features	Abdominal signs
1	Male	34	Nausea and vomiting, abdominal distension	Oliguria, the eyelid and facial edema	Upper abdomen tenderness
2	Male	39	Nausea and vomiting, feeble, palpitation, maransis, dyspnea	Normal	Right upper quadrant tenderness, Murphy sign (+)
3	Male	27	Nausea and vomiting, abdominal distension, feeble, melena	Normal	Middle abdomen tenderness, muscular spasm
4	Female	40	Nausea and vomiting, diarrhea, feeble	Normal	Middle abdomen tenderness, muscular spasm
5	Male	48	Nausea and vomiting, maransis	Oliguria, the eyelid and facial edema	Middle abdomen tenderness, jaundice
6	Male	31	Nausea and vomiting, abdominal distension	Normal	Middle abdomen tenderness
7	Male	33	Dyspnea, abdominal distension, cough and expectoration	Oliguria, the eyelid and facial edema	Right middle abdomen tenderness
8	Female	35	Feeble, skin ecchymosis, melena	Gross hematuria, facial edema	Middle abdomen tenderness, jaundice
9	Male	19	Double lower limbs skin redness	Diuresis	Right middle abdomen tenderness
10	Female	38	Nausea and vomiting, cough and expectoration, dyspnea,	Oliguria, the eyelid and facial edema	Middle abdomen tenderness, jaundice
11	Male	57	Nausea and vomiting, diarrhea, feeble	Normal	Right upper quadrant tenderness, Murphy sign (+)
12	Male	43	Nausea, abdominal distension, feeble	Normal	Middle abdomen tenderness

Both serum amylase and serum lipase were increased significantly in all patients. The platelet was decrease in 10 patients, seven cases of platelet lower than 60 × 10⁹/L. White cells maintained at normal or slightly high level (83.33%). IgM antibody of HFRS was positive in all patients. Seven cases IgG antibody of HFRS was positive. Ten patients were given the total abdomen CT examination, eight cases showed enlargement of the pancreas and surrounding leakage, two cases showed pancreatic necrosis and hemorrhage. Three cases complicated with pulmonary edema.

On admission, acute pancreatitis was mainly diagnosis in most of cases. All of these patients were given antibiotics to prevent infection, somatostatin inhibition of enzyme, parenteral nutrition, fluid replacement and maintenance of water and electrolyte balance treatment. Four patients were given hemodialysis; one patient was given surgical operation intervention. After HFRS as primary disease was diagnosed, all patients were given antiviral treatment. Eight cases were complete remission, three cases were partial remission, one case was death (Table 2).

Table 2. Twelve cases of HFRS complicated with acute pancreatitis: auxiliary examinations, treatment and prognosis.

No	Laboratory examination	Total abdomen CT	Hemodialysis	Prognosis
1	AMY:713, LIP:2369, PLT: 64.2, Cr:593.1, BUN:27.1	Pancreatic enlargement and surrounding leakage	Yes	Complete remission
2	AMY:491, LIP:1731, PLT: 21.9, Cr:105.9, BUN:14.8	Pancreatic enlargement and expansion of pancreatic duct	No	Complete remission
3	AMY:1013, LIP:1929, PLT: 53.1, Cr:196.4, BUN:12.5	Pancreatic enlargement and surrounding leakage	No	Partial remission
4	AMY:2130, LIP:2498, PLT: 94.5, Cr:96.4, BUN:9.6	Necrosis in pancreatic central part, Massive ascites	No	Death
5	AMY:139, LIP:2176, PLT: 70.6, Cr:601.8, BUN:20.1	Pancreatic enlargement and surrounding leakage	Yes	Complete remission
6	AMY:279, LIP:135, PLT: 79.3, Cr:105.6, BUN:11.2	No	No	Complete remission
7	AMY:2100, LIP:1729, PLT: 29.6, Cr:401.7, BUN:28.1	Pancreatic enlargement and surrounding leakage	Yes	Complete remission
8	AMY:1935, LIP:367, PLT: 47.4, Cr:127.9, BUN:15.0	Pancreatic enlargement and surrounding leakage	No	Partial remission
9	AMY:697, LIP:121, PLT: 53.1, Cr:96.1, BUN:9.4	Pancreatic enlargement and expansion of pancreatic duct	No	Complete remission
10	AMY:3907, LIP:1923, PLT: 51.0, Cr:717.9, BUN:27.3	Necrosis in pancreatic tail and surrounding leakage	Yes	Partial remission
11	AMY:243, LIP:1874, PLT: 49.3, Cr:163.4, BUN:13.2	No	No	Complete remission
12	AMY:301, LIP:1316, PLT: 84.9, Cr:129.5, BUN:14.3	Pancreatic enlargement and surrounding leakage	No	Complete remission

Notes: AMY, Serum Amylase (U/L); LIP, Serum Lipase (U/L); PLT, Platelet Count (×10⁹/L); Cr, Creatinine (µmol/L); BUN, Blood Urea Nitrogen (mmol/L).

Discussion

HFRS is still popular in Asia, although the reported cases decreased year by year since 2005 in the world.5 South Korea reports about 300–500 cases per year since 2001, the average annual incidence about the 512/10 million people in Russia.6,7 In recent years, HFRS is increasingly serious in parts of Europe, such as Germany in 2007 alone the number of reported incidence was 1678 cases.8 The major clinical manifestations of HFRS are fever, hypotension, shock, hemorrhage and renal failure, its basic pathogenesis is leakage of small blood vessels and capillaries, can affect multiple organs. Acute pancreatitis is a rare complication of HFRS. In our study, HFRS complicated with pancreatic disease incidence rate was 7.69%, female incidence rate was lower, but more severity, the mortality rate was high, should be paid more attention. All patients were abdominal pain as the main symptom, the majority of patients with fever, nausea and vomiting. The patient who manifested as skin mucous membrane bleeding syndrome was rare.

As a kind of acute infectious disease, early and correct diagnosis is very important to improve the success rate of HFRS treatment. The method of ELISA to detection of IgM and IgG is used widely in China, the advantage of this method is relatively simple, but high specificity and easy operation.9 Reduction of peripheral platelet count contributes to assist in the diagnosis of the disease.10 The level of serum creatinine, Uric acid nitrogen, HDL-C, LDL-C and CT examination can be used to assessment patients conditions, to observe the curative effect and prognosis.11

HFRS complicate with acute pancreatitis is easy to be diagnosed, if only patients have the typical clinical manifestations. In the early of this disease, abdominal pain was always the most outstanding, easily misdiagnosed as acute cholecystitis, acute gastrointestinal perforation, acute intestinal obstruction, etc. Only for these secondary disease appropriate treatment measures, ignoring HFRS is the primary cause of the disease. In the data of these cases, two cases were misdiagnosed as acute cholecystitis, one case was misdiagnosed as acute gastrointestinal perforation. Eight cases were diagnosed as acute pancreatitis firstly, only one case was diagnosis as HFRS complicate with acute pancreatitis, misdiagnosis rate is as high as 90%. The main reasons of misdiagnosis: Physicians are not familiar with HFRS, over dependence on the auxiliary examinations, lack the whole thinking and comprehensive analysis of data.

Hemodialysis is an important measure for treatment of HFRS in oliguria period of acute renal dysfunction. According to the severity of disease, Hemodialysis can control volume load precisely, stable blood flow, solute clearance rate and filtration removal the middle molecular cytokines and inflammatory mediators. Multiple organ function widely used hemodialysis can block the kidney, damage process, significantly reduced mortality.12–14 In this clinical retrospective study, four patients received hemodialysis, three patients recovered completely; one patient complicated with acute respiratory distress syndrome, the symptoms improved after mechanical ventilation. Experience tells us that hemodialysis treatment shall begin in the stage of oliguria within 3 days or anuria, which can reduce the incidence of hypervolemia syndrome and pulmonary edema obviously, the hemodialysis treatment will achieve the best.

Surgical intervention should unequivocal the opportunity, Otherwise, not only has no effect, but also increase the mortality rate. In 12 cases, HFRS complicated with acute pancreatitis, one case’s clinical manifestation abdominal sign was severity, which was diagnosed as sever acute pancreatitis. Surgical intervention removed necrotic pancreatic tissue and drainage peritoneal effusion, the patient died of sepsis finally. So, we suggest that conservative treatment is relatively safe and effective, this view consistent with Bui-Mansfield et al.15 Nevertheless, CT-guided percutaneous catheter drainage is also a safe and effective technique to treat acute necrotizing pancreatitis.16

Conclusions

Acute pancreatitis is still one of the rare serious complications of HFRS. The cause of poor treatment effect is not be diagnosed timely, so the correct diagnosis and clear the cause of disease is critical for improve the quality of life of patients and reduce the mortality. In clinical work, suspected of HFRS should identify the cause as soon as possible. Timely hemodialysis treatment is effective, early intervention can improve the prognosis.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.