Case 1 -

Disseminated strongyloidiasis Laura W. Lamps University of Arkansas/Medical Sciences Little Rock, AR

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Clinical History A 60 year old woman from Arkansas presented with a one month history of worsening nausea, vomiting, and abdominal pain. She had a past medical history of Crohn's disease and had been taking 20mg of prednisone daily for more than ten years. Upon physical examination she had diffuse abdominal pain and distension, with tenderness to palpation in the right upper quadrant. The remainder of her physical exam was unremarkable except for diffuse expiratory wheezes that were heard on pulmonary examination. Initial laboratory results included a white blood cell count of 8500/µl (86 % neutrophils, 12 % lymphocytes, 1 % monocytes and 1 % eosinophils). Blood cultures were obtained and were negative. The patient was started on antibiotics including levofloxacin and metronidazole. A CT scan of her abdomen on hospital day 2 revealed edema of the right colonic wall as well as air in the wall of the cecum. CT scan of the chest revealed infiltrates in the right middle and right lower lobes. The patient then underwent exploratory laparotomy with right hemicolectomy on hospital day 3. The patient remained intubated postoperatively. A sputum specimen was obtained while intubated, and Strongyloides stercoralis was identified via cytological examination. Stool examination revealed ova of Strongyloides stercoralis. The patient improved and was extubated on hospital day 5. Antimicrobials were continued through hospital day 14. Serial stool examinations continued to reveal Strongyloides until hospital day 8, and ivermectin was continued for 2 weeks beyond this date. Her steroids were tapered by the time of discharge to home. Case 1 - Figure 1 A low power view of the colon resection shows chronic, active colitis. Case 1 - Figure 2 Higher power view shows architectural distortion and basal plasmacytosis. Case 1 - Figure 3 Epithelioid granulomas with associated eosinophils are found within the bowel wall. Case 1 - Figure 4 Some sections of the colectomy show larvae within the glandular epithelium. Case 1 - Figure 5 Numerous larvae with pointed tails are present within the crypts, consistent with strongyloides. Case 1 - Figure 6 Larvae were also present within numerous lymph nodes in the pericolonic fat. Introduction: The nematode Strongyloides stercoralis has a worldwide distribution. It is endemic in tropical climates; in the United States, it is endemic in the southeastern states, in urban areas with large immigrant populations, and in mental institutions. Risk factors include alcoholism, low socioeconomic status, occupations involving contact with soil contaminated with human waste, hospitalization, chronic illness, and immunocompromise. Corticosteroids and HTLV-1 viral infection are also associated with strongyloidiasis. Interestingly, AIDS patients do not appear to be unusually susceptible to strongyloidiasis. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Infection may occur in the stomach, small bowel, and/or colon. Macroscopically, findings are variable and include hypertrophic mucosal folds, edema, petechial hemorrhage and erythema, and ulcers. Raised polypoid lesions of the small and large bowel have been reported, sometimes with associated xanthoma-like changes. In mild infection, histologic features include mucosal congestion and an increased mononuclear infiltrate in the lamina propria. In more severe infections, there is edema, villous blunting, cryptitis, and a dense eosinophilic and neutrophilic infiltrate in the lamina propria. Ulceration may be seen in severe infections, and is most often seen in hyperinfections; it may be accompanied by fibrosis and stenosis. Perforation has been described rarely. Granulomas are occasionally present as well. Both adult worms and larvae may be found in the crypts, but they may be difficult to detect. Worms typically have sharply pointed tails that may be curved. In severe infections, larvae may be seen transmurally, and in lymphatics and small vessels. Rarely, larvae may be found within mesenteric lymph nodes, with an accompanying eosinophilic infiltrate. S. sterocoralis is also a rare cause of appendicitis. Patients may have symptoms that are clinically indistinguishable from acute nonspecific appendicitis, and the diagnosis of strongyloidiasis is almost always made post-surgically. Affected appendices typically show organisms within the appendiceal crypts, with a marked transmural eosinophilic infiltrate and variably present granulomas. Differential Diagnoses: The presence of larvae with sharply pointed, sometimes curved tails within the glands of the gastrointestinal mucosa is essentially diagnostic of strongyloidiasis. In the proper clinical and geographic setting, however, Capillaria infection is also in the differential diagnosis. Rarely, fulminant intestinal strongyloidiasis may mimic chronic idiopathic inflammatory bowel disease. Final Diagnosis: Disseminated strongyloidiasis Key Words: parasite, Strongyloides stercoralis, disseminated strongyloidiasis, diarrhea, eosinophilia, nematode, infection, Crohn's disease Discussion Background The nematode Strongyloides stercoralishas a worldwide distribution. It is endemic in tropical climates; in the United States, it is endemic in the southeastern states, in urban areas with large immigrant populations, and in mental institutions. Risk factors include alcoholism, low socioeconomic status, occupations involving contact with soil contaminated with human waste, hospitalization, chronic illness, and immunocompromise. Corticosteroids and HTLV-1 viral infection are also associated with strongyloidiasis. Interestingly, AIDS patients do not appear to be unusually susceptible to strongyloidiasis. Pathogenesis S. stercoralis is contracted from soil containing the organism. Filariform larvae initially penetrate the skin and enter the venous system. When they reach the pulmonary circulation, they exit the vascular sytem and enter the alveolar spaces. The larvae then migrate up the respiratory tree and down the esophagus to reach the small intestine. The female lives in the small intestine and lays eggs there that hatch into rhabditiform larvae, which are excreted in stool in the form of filariform larvae, maintaining the life cycle. Filariform larvae can also penetrate the intestinal mucosa or perianal skin, leading to persistent infection. An extremely important feature of the Strongyloides life cycle is that rhabditiform larvae can mature into infective filariform larvae within the host, via molting. This autoinfective (also known as hyperinfective) capability allows the organism to infect the host and cause illness for long periods of time, sometimes upwards of 30 years, and is associated with increased larval migration. In addition, widespread dissemination (defined as migration of the organism to organs beyond the lung and gastrointestinal tract) may occur in immunocompromised patients, causing severe and even fatal illness. Corticosteroids appear to be responsible for the conversion of chronic, low-grade strongyloidiasis into fulminant disseminated infection in many cases. Although the mechanism is incompletely understood, possible mechanisms include the ability of steroids to deplete eosinophils, as well as the possibility that steroids may trigger larval molting. Fulminant strongyloidiasis is also associated with disseminated bacterial infections, apparently because the worms carry enteric bacteria with them as they invade the intestinal wall and migrate to other sites. Clinical Features Strongyloidiasis occurs mainly in adults. The spectrum of strongyloidiasis ranges from chronic asymptomatic infection to severe disseminated disease with a mortality rate that can exceed 80%. When patients are symptomatic, the presentation is quite variable and includes diarrhea, abdominal pain and tenderness, nausea, vomiting, weight loss, and GI bleeding. Gastrointestinal manifestations may be accompanied by numerous extra-intestinal manifestations, including mesenteric adenopathy, skin rash, urticaria, pruritis, and concomitant pulmonary symptoms. Laboratory abnormalities include mild anemia, peripheral eosinophilia, and leukocytosis. Rarely, severe or chronic infection may lead to bowel obstruction and stenosis. Detection of increased numbers of larvae in stool and sputum is characteristic of hyperinfection. Disseminated strongyloidiasis is defined by increased migration of larvae and subsequent involvement of ectopic organs beyond the usual range of an autoinfective cycle, such as the central nervous system, lymph nodes, liver, and other organs. The increased mortality among patients with severe strongyloidiasis is in large part due to concurrent dissemination of bowel flora along with the migrating larvae. Pathologic Features Infection may occur in the stomach, small bowel, and/or colon. Macroscopically, findings are variable and include hypertrophic mucosal folds, edema, petechial hemorrhage and erythema, and ulcers. Raised polypoid lesions of the small and large bowel have been reported, sometimes with associated xanthoma-like changes. In mild infection, histologic features include mucosal congestion and an increased mononuclear infiltrate in the lamina propria. In more severe infections, there is edema, villous blunting, cryptitis, and a dense eosinophilic and neutrophilic infiltrate in the lamina propria. Ulceration may be seen in severe infections, and is most often seen in hyperinfections; it may be accompanied by fibrosis and stenosis. Perforation has been described rarely. Granulomas are occasionally present as well. Both adult worms and larvae may be found in the crypts, but they may be difficult to detect. Worms typically have sharply pointed tails that may be curved. In severe infections, larvae may be seen transmurally, and in lymphatics and small vessels. Rarely, larvae may be found within mesenteric lymph nodes, with an accompanying eosinophilic infiltrate. S. sterocoralis is also a rare cause of appendicitis. Patients may have symptoms that are clinically indistinguishable from acute nonspecific appendicitis, and the diagnosis of strongyloidiasis is almost always made post-surgically. Affected appendices typically show organisms within the appendiceal crypts, with a marked transmural eosinophilic infiltrate and variably present granulomas. Differential Diagnosis The presence of larvae with sharply pointed, sometimes curved tails within the glands of the gastrointestinal mucosa is essentially diagnostic of strongyloidiasis. In the proper clinical and geographic setting, however, Capillaria infection is also in the differential diagnosis. Ancillary diagnostic tests include stool examination for larvae, worms, or eggs, and serologic tests. Rarely, as seen in this case, fulminant intestinal strongyloidiasis may mimic chronic idiopathic inflammatory bowel disease. The entire scenario in this particular case was confounded by the fact that the patient reportedly had "Crohn's disease," and this diagnosis was perpetuated through numerous generations of medical records, although no pre-treatment diagnostic biopsies were ever located retrospectively. It is doubtful that the patient ever had Crohn's disease at this point, and it is believed that she most likely had chronic strongyloidiasis with transition into the autoinfective state when she was given a large bolus of steroids. Despite the widespread dissemination to the lungs and lymph nodes, the patient made a full recovery. In summary, infections should always be considered in the differential diagnosis of chronic idiopathic inflammatory bowel disease, but especially if: 1. The clinical presentation is atypical. 2. The patient gets acutely worse on steroids. 3. There is no initial pre-treatment biopsy that is indicative of chronic idiopathic inflammatory bowel disease. 4. The patient has risk factors such as chronic steroid use, exposure to environmental pathogens, etc. References Al-Hasan MN, McCormick M, Ribes JA. Invasive enteric infections in hospitalized patients with underlying strongyloidiasis. Am J Clin Pathol 128:622-7, 2007. Al Samman M, Haque S, Long JD. Strongyloidiasis colitis: a case report and review of the literature. J Clin Gastroenterol 28:77-80, 1999. Berry AJ, Long EG, Smith JH, et al. Chronic relapsing colitis due to Strongyloides stercoralis. Am J Trop Med Hyg 32:1289-93, 1983. Concha R, Harrington W Jr., Rogers AI. Intestinal strongyloidiasis: recognition, management, and determinants of outcome. J Clin Gastroenterol 39:203-11, 2005. Genta RM, Haque AK. Strongyloidiasis. In Connor DH, Chandler FW et al (eds): Pathology of Infectious Diseases, Stamford, CT, Appleton and Lange, 1997, pp. 1567-76. Gutierrez Y, Bhatia P, Garbadawala ST, et al. Strongyloides stercoralis eosinophilic granulomatous enterocolitis. Am J Surg Pathol 20:603-12, 1996. Heyworth MF. Parasitic diseases in immunocompromised hosts. Cryptosporidiosis, Isosporiasis, and Strongyloidiasis. Gastroenterol Clin N Amer 25 (3): 691-707, 1996. Keiser PB, Nutman TB. Strongyloides stercoralis in the immunocompromised population. Clin Microbiol Rev 17:208-17, 2004. Kishimoto K, Hokama A, Hirata T, et al. Endoscopic and histopathological study on the duodenum of Strongyloides stercoralis hyperinfection. World J Gastroenterol 14:1768-73, 2008. Lamps LW. Appendicitis and infections of the appendix. Sem Diag Pathol 21:86-97, 2004. Lessnau KD, Can S, Talavera W. Disseminated Strongyloides stercoralis in human immunodeficiency virus-infected patients. Treatment failure and a review of the literature. Chest 104:119-22, 1993. Meyers WM, Neafie RC, Marty AM. Strongyloidiasis. In Meyers WM, Neafie RC, Marty AM, Wear DJ. Pathology of Infectious Diseases: Vol. 1, Helminthiases. Washington, D.C.: AFIP Press, 2000, pp.341-352. Milder JE, Walzer PD, Kilgore GK, et al. Clinical features of Strongyloides stercoralis infection in an endemic area of the United States. Gastroenterology 80;1481-8, 1981. Nadler S, Cappell MS, Bhatt B, et al. Appendiceal infection by Entamoeba histolytica and Strongyloides stercoralis presenting like acute appendicitis. Dig Dis Sci 35:603-8, 1990. Noodleman JS. Eosinophilic appendicitis: demonstration of Strongyloides stercoralis as a causative agent. Arch Pathol Lab Med 105:148-9, 1981. Ramdial PK, Hlatshwayo NH, Singh B. Strongyloides stercoralis mesenteric lymphadenopathy: clue to the etiopathogenesis of intestinal pseudo-obstruction in HIV-infected patients. Annals Diag Pathol 10:209-14, 2006. Rivasi F, Pampiglione S, Boldorini R, Cardinale L. Histopathology of gastric and duodenal Strongyloides stercoralis locations in fifteen immunocompromised subjects. Arch Pathol Lab Med 130: 1792-8, 2006. Thompson BF, Fry LC, Wells CD, et al. The spectrum of GI strongyloidiasis: an endoscopic-pathologic study. Gastro Endosc 59:906-10, 2004. Weight SC, Barrie WW. Colonic strongyloides infection masquerading as ulcerative colitis. J R Coll Surg Edinb 42:202-203, 1997.