Clinical-Pathological Conference Series from the Medical University of Graz

When the patient, a Syrian refugee, presented at the emergency department of the Medical University of Graz, he had already been in Austria for 2.5 years. A language barrier made it difficult to obtain a complete history. The patient had sought medical attention 3 days earlier at another hospital for epigastric pain of 2 weeks duration that increased after meals. Pantoprazole and sucralfate did not alleviate the epigastric pain. The patient presented at the emergency department of the Medical University of Graz with persistent abdominal pain 1 day prior to admission. Physical examination revealed blood pressure of 125/81 mm Hg, a regular pulse of 60 per min, temperature 35.0 ℃, soft abdominal wall and epigastric tenderness on deep palpation. Except for eosinophils 7% (normal: up to 5%), eosinophils absolute 0.7 × 10⁹/l (normal: up to 0.7 × 10⁹/l) and lactate dehydrogenase (LDH) 287 U/l (normal: 120–240 U/l), laboratory results were unremarkable. The C‑reactive protein (CRP) level was 1.2 mg/l (normal: up to 5.0 mg/l) and liver function tests were normal. Ultrasonography of the liver, the biliary tree, the spleen and the kidneys was unremarkable; the pancreas was not seen. Gastroscopy showed patchy erythema in the antrum, with minimal chronic inactive gastritis on histology. Biopsies from the antrum and corpus were negative for Helicobacter pylori. There were coarse folds in the duodenum and on endoscopic magnification the villous structures appeared to be diminished (Fig. 1). Since the patient was uncooperative and increasingly agitated, the procedure had to be terminated before duodenal biopsies could be obtained. Antibodies for serum anti-tissue transglutaminase were negative. The patient was sent home and advised to continue the proton pump inhibitor at double the standard dose and to take scopalamine butylbromide as needed. The next day, however, the patient returned when a banana he had eaten exacerbated the abdominal pain. Bowel sounds were hyperactive, otherwise physical examination was unchanged. Laboratory tests: leukocytes 13.4 × 10⁹/l (normal: 4.4–11.3 × 10⁹/l), eosinophils 9%, eosinophils absolute 1.2 × 10⁹/l, CRP 6.0 mg/l. Since treatment with i.v. esomeprazole, metamizole, scopalamine butylbromide, and fluids did not improve the discomfort, the patient was admitted to hospital. Subsequently, the abdominal pain shifted from the epigastrium to the lower abdomen. On physical examination the consulting gastroenterologist found a positive McBurney sign, a contralateral rebound and significant gas bloating. Computed tomography (CT) of the abdomen showed unremarkable parenchymatous organs, a few air-fluid levels in the colon and enlarged mesenteric lymph nodes (up to 1 cm) in the left upper quadrant thought to be inflammatory in nature. The appendix was unremarkable and there were no signs of diverticulitis. A surgical consultant saw no need for exploratory laparotomy to clarify an acute abdomen.

The patient is a young refugee from Syria who suffered from abdominal pain that increased in severity over several days. Since the condition did not improve with the medication received, the patient was admitted to hospital, where leukocytes, eosinophils and CRP continued to rise. Stool analysis was negative for common enteric pathogens.

In this case further microscopic stool analysis detected larvae but no eggs of Strongyloides stercoralis. Ivermectin therapy was initiated orally at 200 µg/kg/day for 2 days; this usually results in high degree of parasite eradication [47]. Ivermectin is the drug of choice in strongyloidiasis because it has fewer unfavorable side effects and a better rate of larval clearance from stool than thiabendazole and albendazole [48, 49]. The drug is available in oral or parenteral form but the Food and Drug Administration has approved only the oral formulation for human use [50]. According to the US Center for Disease Control and Prevention, veterinary subcutaneous ivermectin may be a therapeutic option when oral and/or rectal administration of the drug is not possible. Although the current literature on humans is limited there are some reports of successful subcutaneous ivermectin treatment for strongyloidiasis in immunocompromized patients with disseminated disease [51] and hyperinfection [52].

Strongyloides stercoralis is an intestinal parasite of vertebrates and exhibits a complex and unique developmental phase with a free-living and a parasitic part of its life cycle completed in the same host [39]. In the free-living phase male and female adults develop in the soil. In the parasitic phase noninfective larvae enter the host by penetrating the skin or by the fecal-oral route to moult to infective filariform larvae. At their portal of entry, larvae often cause a petechial hemorrhagic rash, pruritus, and local edema. After entry the larvae migrate to the pulmonary circulation through lymphatics and venules. There they move to the alveolar spaces and cause inflammation associated with eosinophilia; they then crawl up the respiratory tract and are swallowed, thereby reaching the intestine. Other options for larvae to enter the gastrointestinal tract are the fecal-oral route or autoinfection. Once the small bowel is reached larvae mature into adult females and produce eggs via parthenogenesis. The eggs hatch in the intestine into noninfective rhabditiform larvae that are excreted and continue the free-living life cycle. Premature transformation of noninfective to infective larvae allows penetration of the mucosa of the small bowel or colon, or the larvae penetrate the perianal skin, thus starting a new developmental phase within the host, i.e. causing autoinfection. This specific ability of Strongyloides stercoralis for repeated migratory cycles within the primary host is responsible for the increase in the worm burden without exogenous reinfection and the decade-long persistence of the infection in untreated individuals.

In Europe where hygiene standards are generally high, parasite infection is usually found in patients who migrated from or travelled to endemic countries; however, some cases of autochthonous infections have also been reported [53]. In Austria, strongyloidiasis is rare and in over 30 years of patient care in this department I can remember just one case of autochthonous strongyloidiasis. During my time at Southwestern Medical School in Dallas, Texas, I diagnosed several cases of strongyloidiasis. Characteristic findings with upper gastrointestinal endoscopy (Fig. 1) include gastric mucosal erythema and areas of atrophy. The duodenal mucosa presents with a coarse surface, enlarged and rigid villous structures, diffuse erythema, edema and friability. Duodenal biopsy may reveal larval infection. Fig. 2 (personal observation) shows brush cytology from the duodenal mucosa. In the discussed patient the endoscopic finding of an altered mucosal surface and altered villous appearance in the duodenum could have suggested strongyloidiasis, but since the patient’s noncompliance precluded a biopsy, the infection could not be confirmed histologically. Years ago I was the attending physician of a 32-year-old man working as a heavy machine operator for an oil company. He had been in Nigeria to lay pipelines in a swampy jungle area and back in the United States presented with fever, truncal rash, nausea, vomiting, and diarrhea with up to 12 bowel movements per day. In fact, epigastric pain and watery diarrhea are the most common gastrointestinal manifestations of strongyloidiasis, which was first described in 1876 in French soldiers returning from the old Indochina region and therefore was called Cochin-China diarrhea [54]. Treatment with opiates did not improve my patient’s condition. The patient became dizzy and complained of chest pain 6 weeks after the onset of diarrhea, which was due to an electrolyte imbalance/hypokalemia (serum potassium: 2.8 mEq/l) and consequently led to cardiac arrest. Finally, the patient was diagnosed and treated for strongyloidiasis (18% eosinophils). Perfusion studies revealed increased secretion instead of absorption of water and electrolytes in the jejunum, which had been responsible for the persisting diarrhea and subsequently hypokalemia and cardiac arrest [55].

Among 168 clinical-pathological cases in the last 31 years in this institution, 6 cases with infection by helminths have been discussed. These include one case of strongyloidiasis, one of fascioliasis, two cases of echinococcosis, one case of infection with Ancylostoma duodenalis, and one case with Clonorchis sinensis.