1. 1 Approach to Common GI Syndromes: Odynophagia, Abdominal Pain, and Diarrhea HAIVN Harvard Medical School AIDS Initiative in Vietnam

2. 2 Learning Objectives By the end of this session, participants should be able to: List the differential diagnoses for odynophagia, abdominal pain, and diarrhea Explain how to examine, diagnose, and treat these conditions

3. 3 Case 1: Anh (1) Anh, a 23 year old HIV positive female, presents with severe pain on swallowing which has lasted for 2 weeks She reports 2 kg loss of body weight and poor food intake Pain occurs with both eating and drinking No fever, no diarrhea

4. 4 Case 1: Anh (2) Past medical history HIV positive for 3 years Briefly took stavudine (d4T) and didanosine (ddI) but could only afford 6 months of therapy Pulmonary TB, treated with 3 drugs for 8 months 3 years earlier She takes no medications now

5. 5 Case 1: Anh (3) Social History She lives in Hanoi Her husband passed away from TB 2 years ago She has 2 children who are both HIV negative She does not smoke or drink She denies IDU

6. 6 Case 1: Anh (4) General: mildly ill, in obvious pain Vital signs: temperature 38.6° C heart rate 90 bpm BP 134/80 Head/neck: moderate oral thrush (+) cervical adenopathy 1-2 cm Thyroid is normal Severe pain and difficulty when swallowing Lungs: clear Heart: regular rhythm Abdomen: soft, thin, non-tender Skin: normal Physical Exam

7. 7 What is the Differential Diagnosis?

8. 8 Odynophagia (Pain with Swallowing) Causes: Candida most frequent pathogen: 50 – 70% of cases Virus: 30% of cases Herpes simplex virus (HSV) esophagitis Cytomegalovirus (CMV) esophagitis Other causes: Mycobacterium avium complex esophagitis Ulcers (aphthous, acid) Kaposi’s sarcoma Histoplasmosis

9. 9 What Other Information Do You Want to Know About this Patient?

10. 10 Laboratories Complete blood count: WBC 4,200 (N 78%, L 18%) Hematocrit 34% Platelets 346,000 Total lymphocyte count: 756 Glucose 5.1 mmol/L (92 mg/dL) BUN 2.1 mmol/L (5.6 mg/dL) CD4: 128

11. 11 What Should be Done Next?

12. 12 Approach to Odynophagia Treat presumptively for esophageal candidiasis Fluconazole 200-300 mg / day Improved within 7 days of treatment Continue the treatment for 14 days Prophylaxis with CTX Start ARV treatment Consider presumptive treatment for herpes simplex Esophagoscopy Odynophagia Improved after 7 days of treatment Yes No Common Causes: Candida, HSV, CMV, HIV History: Pain or difficulty with swallowing, decreased oral intake. History: Note any new medications, any signs of AIDS Clinical exam: Note any oral thrush or ulcers, dehydration, nutritional status. No Yes

13. 13 Case 1: Anh (5) Treatment Anh is started on fluconazole 200 mg/day When she returns in 7 days, the oral thrush has resolved However, she still has severe pain with swallowing and is unable to eat What should be done next?

14. 14 Case 1: Anh (6) Further Work up Consider treatment for HSV with acyclovir (if odynophagia is not improved after 7 days on fluconazole) Acyclovir dose: 400 mg x 3/day x 7 days 200 mg x 5/day x 7 days If endoscopy available, patient can be referred for this along with biopsy of any lesions

15. 15 Case 1: Anh (7) Follow-up Anh was given acyclovir 200 mg 5x/day She returned 7 days later and her swallowing had improved She was eating better and gained 1.5 kg in the last week She is continued on acyclovir for 1 more week and referred for ARV counseling

16. 16 Odynophagia: Summary Odynophagia and dysphagia are extremely common Most common causes are esophageal candidiasis, HSV and CMV Most patients with esophageal candidiasis will also have oral thrush However, esophageal candidiasis can be present even without visible oral thrush Esophageal candidiasis and HSV are usually seen when CD4 count is < 200

17. 17 Case 2: Thai (1) Thai, a 42 year old man, presents with: 3 weeks of fever 8 kg weight loss progressive abdominal pain mild nausea, but no diarrhea or vomiting Review of systems: Mild cough without dyspnea No headaches, visual problems, sore throat, chest pain, dysuria, hematuria, joint pains or neurologic symptoms

18. 18 Case 2: Thai (2) Past medical and social history Diagnosed with HIV 2 months ago He denies: any previous illness and has continued to work as a motorcycle repairman until 3 weeks ago ever using IV drugs any alcohol or cigarette use States that he has visited commercial sex workers

19. 19 Case 2: Thai (3) Medications He bought 2 ARVs in a pharmacy and has been taking them daily

20. 20 Case 2: Thai (4) Physical exam Thin man in obvious pain; lies on bed curled in a ball Heart rate: 110bpm, BP: 122/84, T: 37.6C, RR: 16 Oropharynx is clear, no scleral icterus, no lymphadenopathy. Lungs are clear Heart is tachycardic, but without murmurs or gallops Abdominal exam is notable for diffuse mild tenderness without peritoneal signs No masses, no hepatosplenomegaly. Genital exam, extremities, skin are normal

21. 21 What Other Information do you Want to Know About this Patient?

22. 22 Abdominal Pain: Important Points One important cause of abdominal pain in HIV is due to side effects from ARVs NRTI can cause hepatitis with lactic acidosis (especially D4T, DDI) Pancreatitis is also a side effect seen with the use of D4T and DDI

23. 23 Case 2: Thai (5) Work up Complete blood count: WBC 3,200 (N 78%, L 18%) Hematocrit 33 Platelets 213,000 Total lymphocyte count: 634 Amylase: normal AST/ALT and bilirubin are normal CD4 count 42 cells/mm3 What would you do next?

24. 24 Case 2: Thai (6) Work up Continued Abdominal X-ray shows no signs of obstruction Chest X Ray negative Abdominal Ultrasound reveals multiple lymph nodes up to 3 cm and ascites Paracentesis is done: WBC is 200 cells/ml, mostly lymphocytes Protein is 6 g/dL Fluid AFB and gram stain are negative, sent for culture Sputum is sent for AFB Stool is sent for culture, ova and parasites

25. 25 What is the Cause of the Abdominal Lymph Nodes?

26. 26 Case 2: Thai (6) Treatment On hospital day 2, sputum returns positive for AFB Peritoneal fluid remained AFB negative He is started on 4 drugs for TB ARVs are discontinued and patient is counseled that mono and dual therapy are not effective Cotrimoxazole 960 mg/day is started

27. 27 Abdominal Pain: General Principles (1) Clinical signs and symptoms may be misleading In general: CD4 CountLikely OIs CD4 > 500 Common bacteria Neoplasia CD4 100-500 TB Bacteria CD4 < 100 TB Mycobacterium avium complex (MAC) Fungi Cytomegalovirus (CMV) Unusual protozoa can occur

28. 28 Abdominal Pain: General Principles (2) In advanced HIV, abdominal pain is usually a sign of systemic infection E.g. TB, MAC, CMV or disseminated fungal infection Diagnosis is often difficult even with available resources Work up should be guided by quality and location of symptoms Focus on treatable causes

29. 29 Abdominal Pain: General Principles (3) Look for TB! CXR, sputum AFB, or aspiration of peripheral lymph node may make diagnosis of TB and allow treatment If patient has abdominal lymph nodes and no definite diagnosis is possible, consider empiric treatment for TB

30. 30 Infectious Causes of Abdominal Pain in Vietnam Likely to be seen TB Fungal disease Penicilium marneffei Cryptococcus Salmonella Unknown due to lack of diagnostics CMV Lymphoma MAC Kaposi’s sarcoma Histoplasmosis Toxoplamosis Cryptosporidium

31. 31 Diarrhea

32. 32 Overview One of the most common manifestations of HIV Associated with wasting syndrome, poor prognosis Chronic infectious diarrhea usually occurs in advanced HIV disease (CD4 < 50-100) Diarrhea may be due to: Infectious or non-infectious agents HIV itself Therapy is mostly empiric in Vietnam

33. 33 Causes of Acute vs. Chronic Diarrhea Acute Bacterial Food poisoning Malabsorption dairy products fatty foods Increased motility Medication side effects (esp. PIs) Chronic Organisms typical of HIV infection Parasitic infections Malabsorption Mucosal immune defects and inflammation (HIV enteropathy)

34. Management of Acute Diarrhea (1) Acute diarrhea. No dehydration or hypotension < 3 days> 3 days Loperamide, Smecta Rehydration Nutritional counseling Review medications Observe Stool culture, O&P if possible Azithromycin or cipro x 5 days Loperamide, Smecta Rehydration Nutritional counseling Review medications Not improved Metronidazole x 7 days (especially if suspect entamoeba)

35. Acute diarrhea with dehydration or hypotension, fevers, abdominal pain Suspect bacterial diarrhea Suspect bacteremia Admit to hospital Conduct blood culture, stool culture, O&P, special stains if available Rehydrate with IVF Give Cipro or 3 rd gen. cephalosporin Give Metronidazole Management of Acute Diarrhea (2)

36. Take history Do clinical examination Complete the treatment in 14 days Improved? Treatment trial with fluoroquinolone and metronidazole for 7 days Treat for detected causes Stool examination not available Albendazole + CTX Treat with loperamide Complete the treatment for 21 days Consider other causes, such as TB, MAC; give appropriate treatment Consider ARV treatment Give CTX prophylaxis Evaluate severity of dehydration Give rehydration Correct electrolyte disturbance Counsel on proper diet Yes No Causes not found Yes No Improved? MOH Flowchart for Management of Chronic Diarrhea Stool microscopy and culture for causes, other lab tests and investigations

37. 37 Key Points Candida esophagitis is the most common cause of odynophagia Treat with fluconazole 200mg /day In advanced HIV, abdominal pain is usually a sign of systemic infection e.g. TB, MAC, CMV or disseminated fungal infection Diarrhea is common in PLHIV Most acute diarrhea is self-limited; can be treated with supportive measures Most chronic diarrhea will resolve with ART and recovery of the immune system

38. 38 Thank you! Questions?