Commentary case

1. Commentary case By Prof. Dr. FawzyMegahed Khalil Ass. Lec. RaafatSaied 15-3-2017

2. A 53-year-old man presented with fevers, left eye redness, and abdominal pain.

3. The condition started one month previously when the patient developed fever while undergoing workup for aortic valve replacement .

4. He has a history of remotely treated Hodgkin’s lymphoma, severe aortic stenosis and moderate mitral stenosis attributed to chemoradiation .

5. Medical history also included hypertension and hypothyroidism for which he was prescribed aspirin, furosemide, levothyroxine, and metoprolol succinate.

6. He also had a 6-year history of polyarthritis, 100-pound unintentional weight loss, and declining short-term memory

7. Long-term treatment with prednisone and methotrexate for presumed seronegative rheumatoid arthritis was stopped 2 months prior.

8. He was a nonsmoker with minimal alcohol consumption denied recent travel or insect bites

9. As a retired wood worker, he described frequent exposure to untreated wood imported from South America and Sub-Saharan Africa.

10. What is your differential diagnosis?

11. Infective endocarditis. • Systemic lupus erythematosis • Sero-negative arthropathy. • Recurrence of Hodgkin’s lymphoma. • Behcet’s disease. • AIDS. • Polyarteritisnodosa. • Other diagnosis.

12. What are the next steps to reach a diagnosis ?

13. Blood cultures obtained before antibiotics were negative.

14. Serologiesfor Coxiella, Brucella, and Bartonella species were negative.

15. Tests for human immunodeficiency virus antibody, Treponemalimmunoglobulin-G, and Whipple’s DNA whole blood polymerase chain reaction were all negative.

16. Transthoracicechocardiogram showed aortic valve vegetation 1.2 ˣ0.8 cm .

17. A diagnosis of culture-negative endocarditis was made .

18. That hospitalization was complicated by recurrent fevers and bilateral uveitis despite broad-spectrum antibiotics.

19. He was discharged with ceftriaxone and vancomycin for culture-negative endocarditis and had completed 4 weeks of a planned 6-week course.

20. Now he is presenting with fever, left eye redness and abdominal pain.

21. Band-like abdominal pain began 5 days previously, wrapped around his back, and radiated into the groin with associated dysuria.

22. He denied vision changes or headache, but he acknowledged photophobia.

23. On physical examination, he was febrile to 100.7F with a heart rate of 109 beats/min and a blood pressure of 106/ 54 mm Hg. Left-sided conjunctival injection and decreased visual acuity were noted.

24. Auscultation revealed a harsh III/VI systolic murmur radiating to the carotid arteries, a II/VI diastolic murmur, and fine bibasilar crackles.

25. Physical examination was notable for lower abdominal tenderness without peritoneal signs, scrotal erythema with associated warmth and tenderness, and bilateral inguinal lymphadenopathy

26. Laboratory results were significant for an elevated erythrocyte sedimentation rate of 111 mm/h, C-reactive protein of 143.7 mg/L, and leukocyte count of 16.12 K/mL.

27. Blood cultures again showed negative results.

28. What is your differential diagnosis?

29. Infective endocarditis. • Maranticendocarditis. • Crhon’s disease. • Recurrence of Hodgkin’s lymphoma. • Behcet’s disease. • AIDS. • Polyarteritisnodosa. • Whipple’s disease. • Other diagnosis.

30. Lumbar spine magnetic resonance imaging was negative for osteomyelitis or epidural abscess, but showed paraspinal and psoas muscle inflammation.

31. Computed tomography scan of the abdomen and pelvis was negative apart from longstanding mesenteric lymphadenopathy

32. Scrotal ultrasound demonstrated bilateral epididymitis and mild orchitis • Transthoracic echocardiogram showed progression of the aortic valve vegetation from 1.2 ˣ0.8 cm to 1.8 ˣ0.8 cm.

33. What is your differential diagnosis?

34. Infective endocarditis. • Systemic lupus erythematosis • Crhon’s disease. • Behcet’s disease. • AIDS with Mycobacterium avium-intracellulareinfection. • Polyarteritisnodosa. • Whipple’s disease. • Other diagnosis.

35. Fundoscopic examination revealed vitritis (Figure 1) and bilateral chorioretinal infiltrates, suspicious for Endophthalmitis. Vitreous fluid cultures were negative.

36. Figure 1 : Color photomicrograph with hazy view of the left retina due to significant vitritis.

37. Despite intravitreal injection of ceftazidime, vancomycin, and amphotericin B, the patient’s vision deteriorated, prompting bilateral vitrectomy.

38. He then underwent aortic and mitral valve replacement with tricuspid valve and aortic root repair for progressive valvular disease with culture-negative endocarditis thought not to be responding to empiric vancomycin and ceftriaxone.

39. Histology of the aortic valve was consistent with healing endocarditis (Figure 2).

41. What is your differential diagnosis?

42. Infective endocarditis. • Systemic lupus erythematosis • Crhon’s disease. • Amyloidosis. • Behcet’s disease. • AIDS. • Polyarteritisnodosa. • Whipple’s disease. • Other diagnosis.

43. Vitreal and aortic valve samples sent to the University of Washington for 16S ribosomal RNA sequencing returned positive for Tropherymawhipplei.

44. This provided a diagnosis of Whipple’s disease with cardiac, ocular, genitourinary, musculoskeletal, and neurologic manifestations.

45. How could you explain the deterioration of the patient condition despite 4 weeks therapy with ceftriaxone, a first-line treatment for Whipple’s disease,??????? .

46. The multisystem inflammatory symptoms were attributed to immune reconstitution inflammatory syndrome.

47. The migratory polyarthritis, myositis, epididymitis, and orchitis improve with a 14-day course of ceftriaxone postoperatively followed by trimethoprim-sulfamethoxazole maintenance therapy.

48. Eight months into trimethoprim-sulfamethoxazole therapy, he developed progressive fatigue, malaise, and limited exercise capacity. Workup was notable for profound iron deficiency anemia and hemolysis attributed to mechanical valve shear forces

49. Positron emission tomography computed tomography was negative for evidence of Whipple’s recurrence, but increased inflammatory markers raised concern for relapsed infection.

50. So ceftriaxone was reinitiated for 3 additional months with plans to resume oral maintenance therapy thereafter.