Traditional herbal medicine therapy of gallbladder ascariasis: a case report

Background Ascariasis is one of the common intestinal infections in developing countries, including China. Migration of Ascaris lumbricoides into the gallbladder is rare, unlike ascariasis of the bile duct and when it does occur, treatment is generally by endoscopic or surgical extraction. Case presentation A 4-year-old Uyghur boy with a history of ascariasis developed intermittent upper abdominal pain for 7 days, was being treated by a local practitioner, and when the pain worsened with yellow sclera for 3 days, he was admitted to our hospital. On physical examination, found out the patient with yellowish skin tone, pale yellow fur on tongue, mild yellow staining of the sclera and tenderness in epigastrium. Laboratory data plus liver function test showed damage of liver function. Abdominal Ultrasonography (USG) and Magnetic resonance cholangiopancreatography (MRCP) showed a long, linear, echogenic structure in the gallbladder neck near to the common bile duct. Once the ascariasis diagnosis was established, he was given conservative treatment of magnesium sulfate with herbal medicine. In 4 days, the patient discharged Ascaris through the stool. Conclusions Conservative treatment of magnesium sulfate with Uyghur medicine treatment according to syndrome differentiation is proven to have curative effect.


Background
Ascaris lumbricoides, Helminths or roundworm, is considered as the most common parasitic infection worldwide. The adult form of Helminths usually resides in the human intestinal lumen (most frequently in the jejunum and middle ileum) and does not cause symptoms [1,2]. Migration of the worm into the biliary tree is not uncommon and is considered to be a frequent complication of intestinal ascariasis [3,4]. Gallbladder involvement is very rare, it leads to 2.1% of all biliary tract ascariasis cases [1,4]. Ultrasonography (USG) is the most commonly used diagnostic modality for this pathology [5,6]. Computed tomography (CT) magnetic, resonance imaging (MRI) and endoscopic retrograde cholangiopancreatography (ERCP) are also useful [7]. Most of the patients were treated through endoscopy or surgery [8][9][10]. There are a few reports of conservative medical treatment [11][12][13][14][15]. In this article, we present the radiologic findings, clinical manifestations and successful herbal medicine treatment of a patient with gallbladder ascariasis (GA). A 4-year-old Uyghur boy suffered from intermittent pain in upper abdomen for 7 days, treated by a local practitioner with anthelmintic drugs; however, the pain worsened with yellow sclera for 3 days, then he was admitted to our hospital on October 3, 2016. The boy had a history of roundworm disease nearly a year ago and recovered after a combination treatment with pumpkin seeds and anti-ascaris drugs. On physical examination, we found him moderate nutrition, moderate subcutaneous lipid barrier, medium body size, yellowish skin tone, slightly lower skin temperature, slightly dry skin, red tongue with pale yellow fur, mild yellow staining of the sclera, no yellow staining of the skin and mucous membranes. Furthermore, tenderness was found in epigastrium, the rest of abdomen was soft and non-tender. Bowel sound was normal, no lump palpable. Laboratory data showed (Oct 3, 16.): eosinophils 0.02 × 10 9 ; stoll ova and parasite (O&P) test was negative; total bilirubin (TBIL): 128.57 umol/l, direct bilirubin (DBIL): 116.38 umol/l, Alanine aminotransferase (ALT): 2122 u/l, Aspartate aminotrans-ferase (AST): 389 u/l, Gamma glutamyltransferase (GGT): 209 u/l, Serum total bile acid (TBA): 214 u/l, Cholinesterase (CHE): 5057 u/l, Adenosine deaminase (ADA): 26.30 u/l, respectively. Abdominal USG showed a long, linear, moving echogenic structure in the gallbladder, but no abnormal dilation of the bile duct (Fig. 1a). Abdominal magnetic resonance cholangiopancreatography (MRCP) showed liver volume was normal, no obvious abnormal signals was seen in the liver parenchyma, the intrahepatic bile duct and common bile duct were unclear, the gallbladder volume was enlarged, the wall was rough, with curved (linear) long signals more obvious than USG image (Fig. 1c, d). After the diagnosis was established, our patient was given conservative treatment of magnesium sulfate 30 ml/qd with TUM Sirkenjibin buzuri(SB) 10 ml/tid (Sirikanjiben buzure heji, Sirkenjibin buzuri mixture, Xinjiang Drug Approval No. M20041575), Dinar sherbiti(DS) 50ml/tid (Xiaoyan dinaer tangjiang, Dinar syrup, Xinjiang Uygur Pharmaceutical Co., Ltd. Z65020183), Kasin Jewhiri(KJ) 6 g/ tid (Qingre kasen keli, Kasen granules, Xinjiang Uyghur Pharmaceutical Co., Ltd. Z65020172). In 4 days, the patient discharged roundworms through the stool. After 5 days, repeated USG showed disappearance of Ascaris from the gall bladder and common bile duct (Fig. 1b).

Follow-up
The follow up monitoring of the patient was carried out. On 04 October, 2016, test repeated report see Table 1.
Other test results were urine specific gravity 1020, pH 6.5, protein nil, blood nil, pus cells nil, cast nil, crystals nil, bacteria nil, patient was evaluated clinically and BP was 90/60 mm Hg, no lumber pain, no edema, urine output was normal all other complains were also normal. Whereas on 7 October and 16 October 2016, 20 April 2017, test repeated report also see Table 1. Other test results were urine specific gravity 1.015, pH 6.0, albumin negative, blood nil, red blood cell (RBC), casts, crystals were nil, bacteria (−) reported. Laboratory test values are summarized in Table 1.

Discussion
Unlike bile duct ascariasis, Ascaris rarely enters the gallbladder, once ascariasis occurs; it is usually treated by endoscopy or surgical removal. We describe a case of successful conservative treatment of GA in a 4-year-old boy. The treatment method of Uyghur herbal preparations based on syndrome differentiation has practicality and curative effect, which suggests that it may treated GA with liver protection, choleretic, anti-inflammatory and open obstructive effects. Early combination therapy can help optimize management and avoid preventable complications of GA.
Ascaris lumbricoides, an intestinal roundworm, is one of the most common helminthic human infections worldwide; it infects more than 1 billion people worldwide. Infections are mostly asymptomatic, adult Ascaris worms can survive in the human intestines for over 1-2 years [16][17][18]. The most common presentation is small bowel obstruction due to the mass of worms which obstructs the lumen of the intestine [16][17][18]. The most common settlement of the worm is in the jejunum middle of small intestine [16]. Due to the narrow and tortuous structure of the biliary tract, it is rare for the Helminth to invade into the gallbladder, constituting 2.1% of hepatobiliary ascariasis [4]. GA may result in severe complications such as ascending cholangitis, acute acalculous cholecystitis, obstructive jaundice, empyema, pericholecystic abscess, pancreatitis, liver abscesses and septicemia [19][20][21]. The worm can enter the biliary tree from the duodenum and causes variable symptoms such as biliary colic and obstructive jaundice [1,2].
USG is an important non-invasive diagnostic procedure in the evaluation of the patients who usually present with a clinical picture suggesting gallstone disease [5,6,22]. USG appearance of biliary ascariasis is well documented. The worm is usually seen as a long, linear or curved, no shadowing echogenic strip, containing a central, longitudinal anechoic tube, probably representing the digestive tract [5][6][7][8]. Movement of worms in the biliary tree is characteristic and is confirmatory evidence in USG diagnosis [5,6,22]. Javid et al. reported [2] that 47 of 56 patients with GA were diagnosed by USG and 9 were unable to be diagnosed by USG. After surgery, GA was confirmed, all of which were dead roundworms. USG readily show the movement of the worm in the biliary tree and this is an advantage of USG over CT and MRI [5][6][7], which is supported by Cha et al. [11].
Therefore, patients are usually treated by endoscopy or surgery. In this patient, epigastric and right upper quadrant pain with yellow sclera was the main symptom, which is considered to be due to the acute cholecystitis. Contrary to our expectations, there was moderate biliary tree dilatation in this case. The patient had a history of Ascaris in the past year, and his parents reported that he had been cured by pumpkin seeds combined with anti-Ascaris drugs. This time, there were intermittent right upper abdominal pain, jaundice, liver function decline and other clinical manifestations. USG indicates that  The powdered material (1000 g) add water and boiled for three times, 1.5 hours each time, combined the decoction, filtered, the filtrate was concentrated to a thick paste with a relative density of 1.35 to 1.38 (50 to 60 °C), add an appropriate amount of sucrose and β-cyclodextrin, and mixed well. It was made into granules, dried and made into 1000 g [28,29] there was linear substance without curling movement in gallbladder. MRCP reported that there was linear substance in the gallbladder. Combined with the history, it was diagnosed as GA. Eosinophils slightly increased, O&P experiment was negative, and Ascaris had no movement during the USG examination. GA responds poorly to medical treatment because less than 1% of the antihelminthic drugs are excreted in bile. After the worms migrate out of the biliary tree into the duodenum, the antihelminthic drugs can act upon them [2,4]. Considering the dead Ascaris, we chose conservative treatment. In this case, we administered combined therapy magnesium sulfate with SB, DS, and KJ [23][24][25][26][27][28][29]. Ingredients, treatment effects, uses, preparations of these herbals are summarized in Table 2. The purpose of the combined treatment is to protect the liver, promote the contraction of the gallbladder, change the suitable environment for Ascaris survival, and eliminate it [23][24][25][26]. Inoue et al., found that after oral administration, magnesium sulfate can reflexively cause the relaxation of the sphincter muscles of the common bile duct and the contraction of the gallbladder, promote the emptying of the gallbladder and produce a cholagogic effect, which is conducive to the expulsion of Ascaris from the bile duct [30]. After 4 days combined treatment, and we found dead Ascaris bodies excreted from stool. We reviewed by USG the roundworm was found to disappear from the gallbladder (Fig. 1b).

Conclusions
Magnesium sulfate combined Uyghur herbal preparations have resolved GA within 4 days, as analyzed by USG, serum and urine tests. Further follow up for another 10 days showed sustained improvement. The early combined treatment can help to optimize management and avoid the preventable complications of GA. Based on syndrome differentiation, the herbal medicine treatment has applicability and curative effect; which indicate liver-protecting, choleretic, anti-inflammatory and open obstruction effect.
In sum up, the results of the study show that there may an effect of above medicine in the treatment of GA. Magnesium sulfate combined Uyghur herbal preparations can improve clinical curative effect of GA, which provides a new way of thinking to clarify herbal preparation's molecular mechanism and potential curative target not only for the treatment of GA, but also for biliary ascariasis.