1. CPC 01.12.10 John O. Clarke, M.D. Assistant Professor of Medicine Director of Esophageal Motility Johns Hopkins University

2. Questions to Address (1)What were the patient’s risk factors for bleeding? (2)How does HIV affect the differential? (3)What is the most likely diagnosis?

3. Differential Diagnosis of Upper GI Bleed Ulcerative or erosive –Idiopathic –Drug-induced –H. pylori –Other Infectious –Stress-induced –Zollinger-Ellison Syndrome Esophagitis –Peptic –Infectious –Pill-induced Portal hypertension –Varices –Portal hypertensive gastropathy Vascular –Idiopathic angiomas –Osler-Weber-Rendu syndrome –Dieulafoy’s lesion –Gastric antral vascular ectasia –Radiation-induced telangectasia –Blue rubber bleb nevus syndrome Traumatic or post-surgical –Mallory-Weiss tear –Surgical anastomosis –Aortoenteric fistula –Post-polypectomy Tumors

4. DDx of Massive Upper GI Bleed Ulcer –Idiopathic –Drug-induced –H. pylori –Other infections Esophagitis –Infectious Portal hypertension –Varices Vascular –Dieulafoy’s lesion Traumatic –Mallory-Weiss tear –Aortoenteric fistula Tumors

5. What affect does HIV have? All items on the prior slide are still possible Infection and tumors become more likely

6. Relationship of CD4 Count to Infection & Tumor Wilcox C M. Gut 2008;57:861-870

7. What Were This Patient’s Risk Factors? (1) Esophageal ulcer (5-6cm but clean-based) (2) Esophageal varices (though small) (3) Gastric polyp (possible neoplasm) (4) Bluish lesion at GEJ (vascular, infection or tumor)

8. Esophageal Ulcer “An ulcer was found in the mid esophagus 5-6cm in length... not bleeding” What is the differential diagnosis? (1) Pill-induced (2) Infectious - HSV (IgG +) - CMV (PCR +) - Primary HIV - Other (no indication from history) (3) Neoplasm - Adenocarcinoma - Squamous cell - Lymphoma - Kaposi’s sarcoma Unlikely to be the primary source unless it eroded into a varix/artery or rapidly grew in size

9. Esophageal Varices “There were 2-3 small associated esophageal varices... 2 bands were placed” Esophageal varices are indicative of portal hypertension, either from cirrhosis and/or portal vein thrombosis The patient clearly had cirrhosis based on history, exam, blood labwork (prothrombin time, albumin, bilirubin, platelets, ammonia), and ascitic fluid analysis Mortality from variceal hemorrhage remains approximately 35% On a side note, he should have had antibacterial therapy given an active GI bleed in the context of cirrhosis and known ascites... Could be the source of bleeding but slightly atypical for small varices to result in catastrophic hemorrhage

10. Gastric polyp “A 2-cm polyp was seen near the angularis. This lesion was not biopsied” DDx –Benign (hyperplastic, fundic gland polyp, adenoma) –Primary cancer Gastric adenocarcinoma –Metastatic or diffuse Lymphoma Kaposi’s sarcoma Unlikely to be the source of bleeding

11. Bluish Lesion at GEJ “A 1.5 cm bluish ‘bean-like’ lesion was seen at the GEJ. This appeared to be a vermiform lesion rather than a visible vessel” What is this? –Tumor Kaposi’s sarcoma Lymphoma Metastatic –Vascular Dieulafoy’s lesion (atypical to be at GEJ) Gastric varix (atypical description) –Infection (atypical) Unlikely to be primary source of bleeding (unless eroded into a varix)

12. Other Factors to Consider (1)The stomach was not cleared during endoscopy (2)Ascitic fluid represents portal hypertension; however, infection/neoplasm could be superimposed (SAAG less accurate) (3) Travel to Asia & Mexico may have led to atypical exposure not listed above (4) Left pleural effusion less common with ascites than right (and may be masking another process)

13. Specific Topics To Cover

14. Gastrointestinal CMV Occurs in up to 5% of untreated patients with AIDS Most cases occur when CD4 < 50 Prior to HAART, universally fatal on diagnosis –Colitis: 4 months –Esophagitis: 8 months Often complicated by hemorrhage or perforation Can occur anywhere throughout the GI tract Multiple large ulcers Multiple biopsies required to make diagnosis

15. Gastrointestinal HSV Less common than CMV in patients with HIV/AIDS Occurs in 3-5% of HIV patients with esophagitis Rarely causes ulcers larger than 2cm Usually causes multiple ulcers

16. Primary HIV Ulcers Mechanism poorly understood May occur in 4-12% of patient with HIV/AIDS with esophageal symptoms Typically very large in size; often solitary Can be associated with bleeding or perforation Biopsies are routinely non-diagnostic Responds to prednisone or thalidomide

17. Kaposi’s Sarcoma Low-grade vascular tumor a/w HHV-8 20,000 times more frequent in AIDS patients than general population GI involvement in 40% of patients Appear as hemorrhagic nodules on endoscopy Usually associated with skin findings (not reported in this case) HH8 also associated with primary effusion lymphoma (theoretically possible in this case but less likely)

18. Non-Hodgkin Lymphoma 25-40% of HIV patients eventually develop malignancy; 10% are NHL Risk of NHL 60-165 fold greater if HIV CD4 count usually < 100 Can present as esophageal ulcers, polyps or nodules in the GI tract Can be associated with hemorrhage (although not classic)

19. What Remains On The Differential? Esophageal varices related to HBV/Cirrhosis Gastrointestinal CMV Possible malignancy (Kaposi’s Sarcoma > NHL) Possible primary HIV ulcer

20. Clinical Diagnosis Kaposi’s Sarcoma Gastrointestinal CMV Cirrhosis re: HBV with esophageal varices HIV/AIDS