Approach to Common GI Syndromes: Odynophagia, Abdominal Pain, and Diarrhea

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

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. 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. 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. 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. Case 1: Anh (4) Physical Exam • 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

7. What is the Differential Diagnosis?

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

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. What Should be Done Next?

12. Approach to Odynophagia Odynophagia 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. Treat presumptively for esophageal candidiasis Fluconazole 200-300 mg / day Improved after 7 days of treatment Consider presumptive treatment for herpes simplex Improved within 7 days of treatment Esophagoscopy No No Yes Yes • Continue the treatment for 14 days • Prophylaxis with CTX • Start ARV treatment

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

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

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

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. Abdominal Pain: General Principles (1) • Clinical signs and symptoms may be misleading • In general:

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. 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. 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. Diarrhea

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. 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 • Stool culture, O&P if possible • Azithromycin or cipro x 5 days • Loperamide, Smecta • Rehydration • Nutritional counseling • Review medications • Loperamide, Smecta • Rehydration • Nutritional counseling • Review medications • Observe Not improved Metronidazole x 7 days (especially if suspect entamoeba)

35. Management of Acute Diarrhea (2) 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 3rd gen. cephalosporin • Give Metronidazole

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

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. Thank you! Questions?