بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم "وفي أنفسكم أفلا تبصرون" صدق الله العظيم (الذاريات 21)

2. Commentary case By: Prof.Dr.: FawzyMegahed Ass.Lec.: MahmoudNegm

3. Personal history A 57 year old retired nurse, hypertensive, not diabetic, married with 4 offsprings with no special habits of medical importance.

4. Chief complaint this admission Severe headache and jaw pain for the last few days.

5. Telling the story The condition started 6 months ago with dry cough, decreased appetite, and moderate but poorly localized abdominal pain.

6. This was associated with unintentional weight loss from 122.5 kg to 108.9 kg over a short time.

7. Tests revealed mild anemia, mild eosinophilia , high ESR, normal CRP, a negative tuberculin skin test and normal stool analysis.

8. Abdominal MRI revealed enlarged periportal lymph nodes and mild splenomegaly with normal liver, pancreas and kidneys.

9. EGD was done and pathological examination of gastric antrum biopsy specimens revealed mild chronic and focally active gastritis.

10. Immunohistochemical staining for H. pylori was negative, and the small-bowel villi were normal.

11. She received treatment in the form of PPI, empiric antibiotics, and anti-tussives with poor response.

12. During the following month, fatigue and myalgias occurred, followed by the appearance of painless “red dots” around her ankles.

13. At that time, Rh. Factor, ANA, ANCA, anti-Ro, anti-La, anti-dsDNA, anti-RNP, anti-sm and anti-CCP antibodis all were negative .

14. Evaluation of a skin-biopsy specimen revealed findings consistent with early pigmented purpuric dermatosis.

15. CT of the chest, abdomen, and pelvis, performed with IV contrast, revealed mild bronchial-wall thickening,

16. lymphadenopathy in the axillae , right epicardial , portacaval, peripancreatic, and mesenteric regions .

17. D.D.?

18. Pathological examination of a right axillary lymph node, revealed preserved architecture.

19. with follicular and paracortical hyperplasia, along with a polytypic plasmacytosis with negative immunostaining for HHV-8 DNA.

20. Examination of a bone marrow (BM) –biopsy specimen revealed hypercellular BM with maturing trilineage hematopoiesis,

21. increased eosinophils, megakaryocytes and polyclonal plasma cells. These findings were consistent with reactive process.

22. Treatment with oral cetirizine, metoclopramide, omeprazole, and budesonide and inhaled fluticasone–salmeterol was given.

23. There was no improvement. The patient continued to lose weight.

24. FDG-PET examination with CT for attenuation correction was done . The liver and spleen were enlarged with diffuse FDG uptake.

25. There were enlarged FDG-avid LNs in the axillary, paracardiac, internal thoracic artery, retroperitoneal, iliac and inguinal regions.

26. There was diffuse, mild, smooth bronchial-wall thickening with no pulmonary nodules, opacities or hilar lymphadenopathy.

27. Liver biopsy revealed moderate portal, periportal and lobular inflammation predominantly composed of plasma cells

28. (with polytypic expression of kappa and lambda light chains), with occasional eosinophils and sinusoidal fibrosis

29. Bile duct proliferation, focal damage, scattered apoptotic hepatocytes and intraepithelial lymphocytes.

30. The findings were consistent with an overlap syndrome of autoimmune hepatitis and focal sclerosing cholangitis.

31. Treatment with prednisone was begun but was discontinued by the patient for unspecified reasons.

32. Azathioprine therapy was also begun at this time. A decrease in abdominal pain and fatigue was reported.

33. D.D?

34. The patient continued to lose weight. The dry cough also persisted. Advanced investigations were ordered.

36. Pathological examination inguinal LN revealed the same as the old axillary one. Immunohistochemical studies were done this time.

37. On immunohistochemical studies for IgG and IgG4, only a small fraction of the plasma cells were immunoreactive for IgG4.

38. 3 months ago, the patient was re-evaluated for a dry cough, severe fatigue, weight loss (to 88.5 kg), anorexia, abdominal pain,

39. nausea, vomiting, joint pain, diffuse aches, swelling of the right knee and night sweats.

40. Laboratory tests revealed anemia, leucopenia, absolute eosinophilia, high ESR, normal CRP and markedly reduced C3 and C4.

41. Again, ANA, anti-CCP and ANCA were negative. TSH was normal and serum uric acid was 9.5 mg/dl.

42. On presentstion this time She had severe and increasing bitemporal headache over the last few days.

43. The patient reported daily headaches and pain in her jaw on chewing food. She did not report dry eyes or dry mouth.

44. Medications included budesonide, azathioprine, omeprazole, metoclopramide and losartan.

45. She had undergone a hysterectomy. She had no known allergies or history of atopy. She has irrelevant family history.

46. To summarize the history…..

47. A 57-year-old hypertensive woman with weight loss, persistent dry cough, anorexia, abdominal pain, fatigue, myalgias, purpura, nausea, vomiting, joint pain, night sweats,

48. severe bitemporal headache, jaw pain, anemia, high ESR, normal CRP, bronchial-wall thickening, hypocomplementemia,

49. hypercellular BM with polyclonal plasma cells, lymphadenopathy with follicular hyperplasia and a polytypic plasmacytosis,

50. hypergammaglobulinemia and overlap syndrome of AIH and focal sclerosing cholangitis.