Case 1 -

Strongyloides Stercoralis Colitis Joel Greenson, Univ/Michigan Hospitals, Ann Arbor, MI

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Clinical History The patient is a 78 year old man with a previous medical history of COPD, type 2 diabetes mellitus, pulmonary hypertension, degenerative joint disease, chronic kidney disease, gastroesophageal reflux, and chronic anemia with eosinophilia. His anemia was worked up in 2005 with a bone marrow that only showed eosinophilic hyperplasia. He was recently discharged from the hospital after developing pneumonia that was treated with antibiotics and steroids. He was readmitted for shortness of breath. Chest X-ray showed bilateral pulmonary infiltrates and blood cultures grew out vancomycin-resistant enterococcus. The patient began complaining of abdominal pain and constipation which led to a CT scan that showed a diffuse circumferential thickening of right colon that was interpreted as being "consistent with colitis". Colonoscopy revealed erythema and decreased vascular pattern consistent with "mild non-specific colitis." Random colon biopsies were taken. Case 1 - Figure 1 Low-power view of 4 mucosal biopsies showing architectural distortion and increased inflammation of the lamina propria. Case 1 - Figure 2 Two biopsies with increased chronic inflammation and crypt distortion resembling ulcerative colitis. Case 1 - Figure 3 Medium-power view highlighting lamina propria inflammation with basal plasma cells and clusters of eosinophils. Case 1 - Figure 4 Higher-power view of "eosinophilic microabscess" and basal plasma cells. Case 1 - Figure 5 High-power view showing Strongyloides organism on the lower right. Note the rows of nuclei that almost look like small yeast. Also note single multinucleated giant cell and eosinophils adjacent to the nematode. Case 1 - Figure 6 Similar view showing another organism with a rim of histiocytes and eosinophils around it. Pathology Four mucosal biopsies were taken and all four showed diffuse inflammation of the lamina propria with marked crypt distortion indicative of chronic colitis. A diffuse basal plasmacytosis was also present. The lamina propria had patchy intense eosinophilia with rare multinucleated giant cells. Ulcers and crypt abscesses were not present. On higher-power one could identify several parasitic organisms in the areas of intense eosinophilic infiltrates and giant cells. These organisms appeared to be the larval form of the helminthic infection Strongyloides stercoralis. Differential Diagnosis Low-power review of the mucosa shows typical features of chronic colitis. The crypts are distorted with crypt drop out, crypt shortfall and rare branched crypts. The lamina propria is hypercellular with basal plasma cells. These are classic features of chronic inflammatory bowel disease, particularly ulcerative colitis. When trying to differentiate acute infectious colitis from chronic inflammatory bowel disease, the presence of crypt distortion and basal plasma cells is key. If the submitting pathologist hadn't noticed the parasitic larvae I would have signed this case out as chronic colitis involving all biopsies, favor ulcerative colitis. The presence of the larvae makes one ask the question of whether the histologic changes are all due to the infection, or does the patient also have UC? The fact that the patient gives no history of diarrhea certainly makes me think twice about the diagnosis of ulcerative colitis. The literature is full of case reports of chronic colitis due to strongyloidiasis. While data is limited, many cases of strongyloidiasis involving the colon show skip lesions, rectal sparing/ right-sided predominance, and submucosal or even transmural inflammation (if one has a resection specimen). Intense lamina propria eosinophilia with eosinophilic microsbscesses and granulomatous inflammation are also commonly seen. The fact that the active inflammation is present in the lamina propria rather than the epithelium is a tip off to look for the organism. Based on this one would think Strongyloides would most often be misdiagnosed as Crohn's disease. Of interest, however, it is most often misdiagnosed as ulcerative colitis (38.5% in one series versus 7.7% for Crohn's). The large number of eosinophils in the lamina propria may also make one think of eosinophilic/allergic gastroenteritis. I have had one case that I was going to diagnose as eosinophilic/allergic gastroenteritis that turned up a Strongyloides organism in a recut section. Misdiagnosing strongyloidiasis as chronic inflammatory bowel disease or eosinophilic gastroenteritis can have catastrophic consequences as immunosuppressive therapy may trigger hyperinfection which has a 60 - 90% fatality rate. Other nematodes may be found in the gut. The larval forms of hookworm are quite similar to Strongyloides and the reader is referred to the CDC website for the finer points of this discussion (http://www.dpd.cdc.gov/dpdx/HTML/MorphologyTables.htm). Hookworms typically cause asymptomatic iron deficiency anemia rather than colitic symptoms since they stay in the small bowel Capillaria philippinensis is another worm that may inhabit the small bowel of humans. This parasite infects humans who eat infected fresh water fish and is endemic to the Philippines and Thailand. While the vast majority of infectious colitides are acute infections that do not lead to chronic changes in the colon, some agents can, in rare instances, cause a chronic colitis that mimics IBD. Cryptosporidia in AIDS patients who are not on antiviral therapy can mimic ulcerative colitis while amebic colitis may mimic Crohn's disease. Final Diagnosis Strongyloides Stercoralis Colitis Strongyloides stercoralis is an intestinal nematode that is found in the tropics and subtropical / temperate areas. In the US, it may be endemic in the southern Appalachian states, although one typically thinks of Africa, the West Indies, Southeast Asia and South America as more common places to be exposed to the infection. Prevalence rates of up to 4% have been reported in Tennessee, while in undeveloped tropical locations it runs as high as 85%. The organism has a complex life cycle that often results in autoinfection and chronic infection. Filariform larvae can easily penetrate human skin and typically infect people who go barefoot in fecally contaminated soil. These larvae enter the circulatory system and infiltrated the alveolar parenchyma of the lung. Ultimately they work their way up the bronchial tree and are swallowed. Once they reach the small intestine they mature into adult females. The adult female deposits eggs which hatch into Rhabditiform larvae. These may then be passed into the stool or they may initiate autoinfection by becoming infective filariform larvae. This can lead to low-level longstanding infection (in some cases many decades after initial exposure). The longest lasting case on record is 65 years. In patients that become immunosuppressed the infection can become widely disseminated. Surgical pathologists may recognize adult female worms, eggs and larvae in the small bowel and occasionally the stomach (most commonly seen in the duodenum). The larval forms may also be seen in the colon. The adult worm is typically seen within the small intestinal crypts. Cross-sections will often show multiple eggs within the worm. The worms' ovaries stain intensely with hematoxylin and make one think about large viral inclusions. The larval stages are smaller with a diameter of 14-16 microns. They have a thin cuticle and rows of small 1-2 micron nuclei that when seen by themselves can make one worry about a small yeast such as Histoplasma. Up to 30% of infected patients are asymptomatic. While most patients with symptomatic Strongyloidiasis are immunosuppressed, not all of them are. Aside from GI complaints, patients may also have skin lesions, pulmonary disease, renal disease and gram-negative sepsis. Immunosuppressive therapy, diabetes mellitus, HTLV-1 infection, organ transplantation, hematologic malignancy, hypogammaglobulinemia, uremia, malnutrition and chronic alcoholism are risk factors for hyperinfection. One must always be careful starting immunosuppression on a patient that has been in an endemic area (even many decades ago). A classic example is that of Viet Nam war veterans who were exposed back in the 1960's and 70's who are asymptomatic, but can develop hyperinfection if immunosuppressed. Stool testing for Strongyloides is not that sensitive with false negative rates reported between 25 and 46%. Multiple repeat stool exams can raise the sensitivity with one report stating 90% sensitivity if 7 or more stool samples are tested. Examining duodenal fluid aspirates may be the most sensitive technique. Serologic testing (ELISA) is also available. Treatment is relatively simple and effective (if started in time). The drugs ivermectin, albendazole and thiabendazole have all been used (either alone or in combination. References Minematsu H, Hokama A, Makishi T, Arakaki K, Kinjo F, Fujita J. Colonoscopic findings and pathologic characteristics of Strongyloides colitis: a case series. Digestion. 2011;83(3):210-4. Epub 2011 Jan 21. Berry AJ, Long EG, Smith JH, Gourley WK, Fine DP. Chronic relapsing colitis due to Strongyloides stercoralis. Am J Trop Med Hyg. 1983 Nov;32(6):1289-93. Al Samman M, Haque S, Long JD. Strongyloidiasis colitis: a case report and review of the literature. J Clin Gastroenterol. 1999 Jan;28(1):77-80. Genta RM, Weesner R, Douce RW, Huitger OC, Walzer PD. Strongyloidiasis in US veterans of the Vietnam and other wars. JAMA 1987;258:49-52. Genta RM. Global prevalence of strongyloidiasis: critical review with epidemiologic insights into the prevention of disseminated disease. Rev Infect Dis 1989;11:755-67. Qu Z, Kundu UR, Abadeer RA, Wanger A. Strongyloides colitis is a lethal mimic of ulcerative colitis: the key morphologic differential diagnosis. Hum Pathol. 2009 Apr;40(4):572-7. Epub 2009 Jan 13. Segarra-Newnham M. Manifestations, diagnosis, and treatment of Strongyloides stercoralis infection. Ann Pharmacother. 2007 Dec;41(12):1992-2001. Epub 2007 Oct 16. Sridhara S, Simon N, Raghuraman U, Crowson N, Aggarwal V. Strongyloides stercoralis pancolitis in an immunocompetent patient. Gastrointest Endosc. 2008 Jul;68(1):196-9. Epub 2008 Mar 7. Weight SC, Barrie WW. Colonic Strongyloides stercoralis infection masquerading as ulcerative colitis. J R Coll Surg Edinb. 1997 Jun;42(3):202-3. Thompson BF, Fry LC, Wells CD, Olmos M, Lee DH, Lazenby AJ, Monkemuller KE. The spectrum910. of GI strongyloidiasis: an endoscopic-pathologic study. Gastrointestinal Endoscopy 2004 59(7):906-910. Gutierrez Y, Bhatia P, Garbadawala ST, Dobson JR, Wallace TM, Carey TE. Strongyloides stercoralis eosinophilic granulomatous enterocolitis. Am J Surg Pathol. 1996 May;20(5):603-12. Ghoshal UC, Alexender G, Ghoshal U, Tripathi S, Krishnani N. Strongyloides stercoralis infestation in a patient with severe ulcerative colitis. Indian J Med Sci. 2006 Mar;60(3):106-10. Banerjee D, Deb R, Dar L, Mirdha BR, Pati SK, Thareja S, Falodia S, Ahuja V. High frequency of parasitic and viral stool pathogens in patients with active ulcerative colitis: report from a tropical country. Scand J Gastroenterol. 2009;44(3):325-31. http://www.dpd.cdc.gov/dpdx/HTML/Strongyloidiasis.htm