Oesophageal Fistula due to Tuberculosis in HIV Patients: Report of two Cases

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1 Oesophgel Fistul due to Tuerculosis in HIV Ptients: Report of two Cses Fístul esofágic por tuerculosis en pcientes con VIH: Presentción de dos csos Alejndro Zulug Sntmrí 1 Vlentin Grnd Vllejo 2 Pul Cristin Muñoz Gómez 2 Crolin Gutiérrez Márquez 2 Nicolás Zulug M. 3 Key words (MeSH) Tuerculosis Esophgel fistul HIV Plrs clve (DeCS) Tuerculosis Fístul esofágic VIH Summry Extrpulmonry tuerculosis (TB) is frequent in HIV ptients; nevertheless, the incidence of esophgel involvement is low nd high clinicl suspicion is required for proper dignostic pproch in order to identify Mycocterium TB s custive gent of infection. Imging studies such s conventionl chest rdiogrphy, esophgogrm, multislice computed tomogrphy (MCT), nd upper endoscopy provide informtion sed on specific findings tht cn led to the dignosis of TB. They serve s guide for tissue smpling nd confirmtory moleculr tests nd cultures. This rticle presents two cses of young mle ptients dignosed with HIV/AIDS C3 nd co-infected with TB, who developed esophgel nd medistinl lymph node involvement, with secondry perfortion nd medistinl fistul. Resumen En los pcientes con VIH es frecuente l tuerculosis (TB) extrpulmonr; sin emrgo, l incidenci de fectción esofágic es j. Se requiere de un lt sospech clínic pr relizr un decudo enfoque dignóstico y pr identificr l Mycocterium TB como gente cusl de infección. Los estudios por imgen, como l rdiogrfí convencionl de tórx, el esófgogrm, l tomogrfí computrizd multicorte (TCM) y l endoscopi digestiv superior portn informción sd en hllzgos específicos que pueden orientr hci el dignóstico de TB gnglionr y esofágic. Sirven como guí pr l tom de muestrs de tejidos y l relizción de estudios confirmtorios de presenci del cilo, como ls prues moleculres y cultivos. Se reseñn 2 csos de pcientes jóvenes, de sexo msculino, con dignóstico de VIH/sid C3 con coinfección por TB, quienes desrrollron compromiso gnglionr medistinl y esofágico, con perforción secundri y fístul medistínic. 1 Rdiologist doctor, CediMed, Ls Vegs Clinic. Rdiology professor CES university nd Universidd Pontifici Bolivrin. Medellín, Colomi. 2 Rdiologist resident, UPB, CediMed. Medellín, Colomi. 3 Medicl student, CES university. Medellín, Colomi. Introduction Tuerculosis (TB) represents glol pulic helth prolem nd hs hd secondry resurgence in the AIDS epidemic. In this popultion group TB is the most frequent opportunistic infection (1,2). The risk of developing it is 50 times greter for n HIV-infected person compred with helthy one (3). TB is considered the second cuse of deth in the world due to communicle diseses, fter the humn immunodeficiency virus (HIV / AIDS), with n nnul mortlity of pproximtely 2 million people. Thirteen percent of ptients with TB hve coexisting HIV infection (4). Although lung disese is the most common form of TB, ll orgns my e ffected, especilly in the group of ptients with compromised immunity (1,2). In HIV-positive ptients, extrpulmonry TB occurs most frequently nd its most common clinicl mnifesttion is lymphdenitis, with prevlence close to 35 % (2). The gstrointestinl trct is the sixth orgn in locliztion frequency of extrpulmonry TB with n incidence of 3-5 % (5). In the ltter, the most common loction is the ileocecl vlve, while the esophgus is one of the lest frequent occurrences, with 0.15 to 0.2 % of cses (1,2,6). 4630

2 Cse 1 28-yer-old mle ptient. He consulted for fever, dominl pin, dysphgi nd dirrhe of severl weeks of evolution nd hemtemesis from the dy efore dmission. During hospitliztion he ws dignosed s HIV/AIDS C3 (Elis nd Western Blot Positive, CD4 lymphocyte count of 188). In multi-slice CT scn (MCT) of thorx with contrst medium, denomeglis in vrious gnglionr stges of the medistinum were found. Through thorcoscopy lymph node iopsy ws performed, which resulted in positive Ziehl Neelsen (ZN), suggesting the dignosis of lymph node TB. Endoscopy of the upper digestive trct ws performed in which lesions were found in the esophgel mucos, suggestive of cndid infection. In ddition, two ulcers were found in the middle third of the esophgus (Figure 1). Biopsy nd culture of esophgel tissue were negtive for TB. During hospitliztion, nti-tb mngement ws strted. A month fter the strt of tretment he mnifested cough nd fever. Dysphgi persisted s well. A MCT ws performed with thorcodominl contrst medium in which conglomerte of necrotic medistinl denomeglies, with centrl ir content suspect of esophgel fistul nd multiple grnuloms in oth lungs (Figure 2). Imges of the domen showed heptomegly, splenomegly with multiple hypodense nodules suggestive of splenic microscesses; retroperitonel denomegly nd collection in the til of the pncres. Susequently, contrsted MRI of the domen confirmed these findings. An oesophgogrm nd fistulogrm guided y endoscopy were performed, to evlute the evolution of esophgel ulcers nd to rule out perfortion tht explins the tomogrphic findings of the thorx. In the endoscopy, perforted ulcer ws found in the third middle of the esophgus. In ddition, nrrowing of esophgel light due to extrinsic compression secondry to medistinl denomeglies ws oserved (Figure 3). Contrst medium ws injected with ctheter through the ulcer with which 7 cm fistul ws found etween the esophgus nd the medistinum in the right sucrinl region (Figure 4). A new chest MCT scn ws performed fter the oesophgogrm, which showed fistulous pth from the esophgus to the conglomerte of right sucrinl denomeglis nd into the inferior posteromedil pleurl spce of the right hemithorx (Figure 5). Three sputum smer microscopies were positive for cid-lcohol resistnt cilli (BAAR). The culture of sputum otined y roncholveolr wshing nd moleculr tests were lso positive for isonizid (H) nd rifmpicin sensitive TB (R). The definitive dignosis ws C3 AIDS with disseminted TB disseminted with lymph node, pulmonry nd splenic compromise, with perforted scroful to the esophgus nd n oesophgomedistinl nd pleurl fistul. Tretment with HAART therpy (highly ctivity nti retrovirl therpy) nd gstrostomy ws performed, which ws closed few months lter. Rev. Colom. Rdiol. 2016; 28(1): Figure 1. Upper digestive endoscopy. Smple of two esophgel ulcers (rrows). Multiple whitish punctiform lesions djcent to ulcers, which suggested cndid infection. Figure 2. Contrsted thorx MCT scn. ) Air trct y communiction of fistul to the pleurl spce in the sucrinl loction nd pleurocigoesophgel recess (white rrow). Necrotic denomegly (green rrow). ) Grnuloms in oth lungs. 4631

3 Figure 3. Upper digestive endoscopy. ) Ulcer nd perfortion in the middle third of the esophgus through which contrst medium is pssed through ctheter (rrow). ) Medistinl denomeglis tht produce compression of the light of the middle third of the esophgus (rrows). Cse 2 27-yer-old mle ptient. 6-month history of dysphgi, herturn, wet cough, dynmi, nocturnl diphoresis, loss of 15 kg of weight nd multiple cervicl nd xillry denomeglis. Upper digestive endoscopy showed ntrl gstropthy, ctive ulr duodenitis nd iliry gstric duodenum reflux. The gstric iopsy ws positive for Helicocter Pylori. He received ntiiotic tretment. Five Months lter he consulted with fever, hedche, dysphgi nd persistence of cervicl denomeglis. A dignosis of HIV-AIDS C3 ws mde with positive Elis nd Western Blot reports. CD4 lymphocyte count of 142 cells/mm 3 nd virl loding of 22,335 copies. A lumr puncture ws performed nd nlysis of the cererospinl fluid (CSF) reported glucose of 54 mg/dl, proteins of 42 mg/dl, leukocytes 0, no cteri; Adenosine dimine (ADA) tests nd polymerse chin rection (PCR) for TB, negtive; ltex nd chinese ink for Cryptococcus, negtives. A cervicl gnglion iopsy ws performed. The pthology reported the presence of cseous center, positive PCR for TB, sensitive to R, with negtive ZN nd KOH. The chest X-ry showed prtrchel medistinl enlrgement, incresed volume of right pulmonry hilum nd of the pleurocid esophgus recess, with lower prillry reticulonodulr opcities (Figure 6). Contrst CT scn of the chest showed multiple right inferior medistinl denomeglies with necrotic center suggestive of TB compromise nd fistulous pthwy ws defined with ir content etween the esophgus nd the right sucrinl denomegly. As well s pttern of udding tree with multiple centriloulillry nodules in the inferior right loe (Figure 7). MCT scn with contrst medium of the domen showed multiple mesenteric denomeglies with necrotic center suggestive of compromise y TB (Figure 8). MCT scn with neck contrst medium showed denomegly in severl cervicl gnglionic chins, lso with necrotic center (Figure 9). A new endoscopy of the upper digestive trct ws performed where n extensive ulcer with perfortion in the middle third of the esophgus ws found. It ws not possile to determine its depth. A gret mount of pus ws vcuumed tht left crter comptile with oesophgomedistinl fistul. Histopthology reported positive PCR for TB. The definitive dignosis ws C3 AIDS with disseminted TB, with pulmonry, cervicl-medistinl nd mesenteric gnglion compromise, perforted scroful to the esophgus nd esophgel-medistinl fistul. Figure 4. Imge of oesophgogrm-fistulogrm. Fistul of 7 cm of length etween the middle third of the esophgus nd the medistinum in the right sucrinl region (rrow) Figure 5. Chest MCT. ) Fistulous pth from the esophgus to the right sucrinl denomeglis conglomerte nd into the lower posteromedil pleurl spce of the right hemithorx, with contrst medium injected into the fistulogrm (rrows). ) Medium of contrst y the fistulous pth (long rrow) nd pleurl effusion right (short rrow) 4632 Oesophgel Fistul due to Tuerculosis in HIV Ptients: Report of two Cses. Zulug A., Grnd V., Muñoz P., Gutiérrez C., Zulug N.

4 Figure 6. PA chest X-ry. Right prtrchel medistinl enlrgement (dotted rrow). Incresed volume of right pulmonry hilum (long rrow) nd pleurocisoesophgel recess (rrow hed). Mixed lower right prillry opcities (short rrow). c d e Figure 7. Contrsted MCT chest scn. ) MCT xil section. Sucrinl denomeglies with necrotic center nd peripherl enhncement, suggestive findings of compromise for TB (rrow). ) MCT coronl slice. Necrotic denomeglies of right prtrchel predominnce, sucrinl nd in the pleurocigoesophgel recess (rrow). c) Fistulous pthwy with ir content etween the esophgus nd right sucrinl denomeglies (rrow hed). d) Conglomerte of denomeglies in pleurocigoesophgel recess. With centrl ir presence of fistul (rrow). e) MCT of xil thorx. Centriloulillry nodules in the lower loe of the right lung (hed of rrow). Budding tree pttern (rrow). Figure 8. MCT with contrst medium of domen. Mesenteric denomeglis with necrotic center (rrows). Rev. Colom. Rdiol. 2016; 28(1): Figure 9. Cervicl MCT with contrst medium. Necrotic denomegly with center suggestive of TB compromise (rrows). 4633

5 Discussion Esophgel TB is usully due to locl extension of medistinl denomeglies tht produce extrinsic compression of its wll. This phenomenon occurs minly in the third middle of the esophgus, t the level of crin (2,6-8). In MCT, the gnglionic involvement due to TB is chrcterized y low centrl ttenution indicting necrosis nd peripherl enhncement in ring (1,7,8). Primry esophgel TB due to coloniztion of the cillus in the mucos when swllowing sputum is rre. There re protective mechnisms, such s sliv, squmous epithelium, peristlsis, nd n oesophgic sphincter tht prevent reflux (8,9). The hemtogenous nd lymphtic retrogrde spred hs lso een descried, ut the ltter re very rre (5,10). Concomitnt pulmonry disese occurs in 25 % of ptient s cses of gstrointestinl TB. The min clinicl mnifesttion of esophgel TB is dysphgi (5,8,10-12). It occurs in 90 % of the cses (10) due to the presence of intrinsic ulcers, trcheoesophgel fistul or extrinsic compression y medistinl or cervicl nodules (5). Other ssocited symptoms re odynophgi, retrosternl pin, cough during swllowing in fistulizing presenttions, hemtemesis, fever nd weight loss (5,10,12). The clinicl picture is similr to tht of other esophgel pthologies, which delys the timely dignosis nd tretment. In some cses it cn lso e confused with esophgel crcinom nd this must considered s prt of the differentil dignosis (5,10). The dignosis of esophgel TB requires high index of suspicion in ptients with history of lymph node or pulmonry TB which present esophgel ulcers. The most frequent endoscopic finding of esophgel TB is the solitry ulcer with n excvted se nd rised edges (5). In these cses it is recommended to perform n oesophgoscopy or endoscopy with dditionl smpling routine for confirmtion of Mycocterium Tuerculosis or of cseifiyng grnuloms. Resistnt cid-lcohol stining is positive in less thn 25 % of the cses (5,9); for this reson, culture for mycocteri, which hs sensitivity > 80 % nd specificity of 98 % must e performed. Severl clinicl trils hve shown tht PCR for Mycocterium TB is currently test of gret vlue nd llows quick dignosis. It hs sensitivity nd specificity similr to conventionl culture techniques (13). A thorx MCT should lwys e performed with contrst medium to differentite primry esophgel TB from secondry. The ltter is defined y denomeglies tht suggest tuerculous lymphdenitis. The MCT lso ruled out lung TB (5) nd complictions such s perfortion, pneumomedistinum nd Pott s disese (13). Oesophgomedistinum fistuls re rre compliction of esophgel TB (9,11); they re produced y erosion of the wll of the esophgus y contiguity of medistinl denomegly during ctive tuerculous denitis or secondry to pneumoni due to TB. Also, they cn present y clcifiction of n denomegly tht erodes nd produces secondry roncolite (9). Esophgitis in retrovirl disese cn lso cuse ulcertion, perfortion nd formtion of fistuls (14). The finding y MCT of oesophgomedistinum fistuls is of liner imge with ir density, locted in the periphery of medistinl lymph node, minly on the right side (80 %) nd towrd the intermedite ronchus (11). The sign of Ono is pthognomonic of oesophgomedistinl fistul, includes proxysml coughing y ingesting liquids nd crepittion over the sixth right posterior intercostl spce (9). After the scrring process of the fistul occurs, trction diverticuli my pper in sites where fistuls were previously identified (9,15). With respect to tretment, cse series nd other studies hve demonstrted tht medicl tretment with nti-tb drugs hs een fvorle in the resolution of esophgomedistinl fistuls (9,10). In the cse of immunocompetent ptients, stndrd tuerculosttic therpy for period of 6 to 9 months is pplied (5). Conservtive tretment with prostheses nd nti-tb therpy, in generl, re successful (9,10). In the two cses presented, the ptients were dignosed with TB confirmed y PCR or culture, ssocited with HIV/AIDS. Cliniclly, oth ptients presented dysphgi s symptom ssocited which led to hospitliztion. In the imging studies we documented the finding of medistinl denomeglis with compromised contiguity of the esophgus nd perfortion with secondry medistinl fistul. Endoscopy mde it possile to dignose esophgel ulcers nd the fistulous trjectory ws documented y contrsted MCT scn of the thorx. Both received nti-tb medicl tretment with resolution of the infection nd cure of the oesophgomedistinl fistul. References 1. Prpruttm D, Hedgire SS, Mni SE, et l. Tuerculosis. The gret mimicker. Semin Ultrsound CT MRI. 2014;35: Rut AA, Nphde PS, Rmkntn R.Imging spectrum of extrthorcic tuerculosis. Rdiol Clin N Am. 2016;(54): Chou SH, Prhu SJ, Crothers K, et l. Thorcic diseses ssocited with HIV infection in the er of ntiretrovirl therpy: Clinicl nd imging findings. RdioGrphics. 2014;34: Restrepo CS, Ktre R, Mumower. Imging mnifesttions of thorcic tuerculosis. Rdiol Clin N Am. 2016; Sl Lozno A, Leiovich N, et l. Tuerculosis esofágic: presentción de un cso y revisión de l litertur. Act Gstroenterol Ltinom. 2011;41: Lee KH, Kim HJ, Kim KH, Kim HG. Esophgel tuerculosis mnifesting s sumucosl scess. AJR. 2003;180: Burrill J, Willims C, Bin G, et l. Tuerculosis: A rdiologic review. Rdio- Grphics. 2007;27: Glindo Sinz J, Tejd R. Fístul esofágic por tuerculosis en un pciente VIH positivo. Reporte de un cso y revisión iliográfic. Med Int Mex. 2009;25: Jáquez-Quintn J, Rodríguez-Pendás F. Endoscopic mngement of esophgo-medistinl fistul secondry to medistinl tuerculosis infection. Gst Endoscopy. 2015; Gomes J, Antunes A, Crvlho A, Durte R. Dysphgi s mnifesttion of esophgel tuerculosis: report of two cses. J Med Cse Rep. 2011;5: Teijo Núñez C, Mostz Fernández JL. Fístul esófgo-medistínic por M. tuerculosis en pciente con infección por VIH. Enfermedd Infecc Microiol Clin. 2007;25: Kim D, Kim J, Lee D, Chng H, et l. Multidrug-resistnt tuerculous medistinl lymphdenitis, with esophgomedistinl fistul, mimicking n esophgel sumucosl tumor. Clin Endosc Peixoto P, Ministro P, Sdi A, Cncel E, et l. Esophgel tuerculosis: An 4634 Oesophgel Fistul due to Tuerculosis in HIV Ptients: Report of two Cses. Zulug A., Grnd V., Muñoz P., Gutiérrez C., Zulug N.

6 unusul cuse of dysphgi. Gstrointestinl Endoscopy. 2009;69(6). 14. Low S, Ngiu S, Yee Hing E, Au Bkr N. Multiple esophgo-respirtory fistule: sequele of pulmonry tuerculosis in retrovirl infection. Singpore Med J. 2014;55(7). 15. Mzzie J, Wilson S. Imging of gstrointestinl trct infection. Semin Roentgenol. 2007;42: Correspondence Alejndro Zulug Sntmrí CediMed Clle 7 # Medellín, Colomi zsestin@gmil.com Received for evlution: My 31, 2016 Accepted for puliction: Novemer 28, 2016 Rev. Colom. Rdiol. 2016; 28(1):