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  • 1. Case Presentation Miliary TB Causing Pancytopaenia
  • 2. Dr Mathonsi Registrar: Department of Internal Medicine Dr George Mukhari Hospital University of Limpopo
  • 3. Objective  Present a clinical case of miliary TB with haematological disturbance  Review the significance of pancytopenia in miliary TB
  • 4. Mr M C  A 41 year old male from Zimbabwe  Married with two children  Non smoker and non drinker  Employed as an accountant in a firm in Zimbabwe  Came to South Africa to seek medical attention after months of seeking medical attention in Zimbabwe without improvement in his condition
  • 5. Presenting Complaint  Abdominal pains >4 mo duration, located on the epigastrium and right hypochondrium,  The pain is constant, none radiating, graded a 7/10 by Mr MC, relieved by analgesia and is worsened after meals  Abdominal swelling > 1mo, associated with swelling of the feet  He has loss of appetite and loss of weight  Experiences pain when swallowing
  • 6. Systemic enquiry  Complains also of epistaxis, fatigue and general tiredness  Night sweats, loss of weight and loss of appetite  He has no history of upper nor lower GIT bleeding  No history of diarrhoea
  • 7. PMH  Tested HIV positive Nov 09  Treated for PTB In 1983 in Zimbabwe (AntiTB therapy treatment completed).  No history of CD4 count and viral load  Currently antiretroviral naive
  • 8. Drug History  Takes myogel as and when needed  Not on any chronic medication  No previous blood transfusion
  • 9. Clinical Examination General physical examination  Weight 63 kg (Reports to have lost more than 10% of his body weight)  BP 118/60 mmHg, T 37.5  Pulse 105  Pale ++, no jaundice, no lymphadenopathy , grade 1 oedema
  • 10. Clinical Examination  Abdomen distended with fullness of the flanks,  Umbilicus everted (ascites)  No abdominal veins noted  Hepatomegaly : span 14 cm, tender, smooth, with rounded edges, no bruit  Splenomegaly : massive (palpable just below the umbilicus)
  • 11. Clinical Examination  Oral thrush  Skin unremarkable for previous zoster, or eczema and ulcers  No stigmata of chronic liver disease
  • 12. Clinical Examination  CVS : JVP not raised  :N S1S2  OTHER systems unremarkable
  • 13. Summary of Clinical Findings  Hepatosplenomegaly with ascites  Grade 1 oedema  No lymphadenopathy nor jaundice  Oral thrush ? Oesophageal involvement  Weight loss, night sweats without cough  Previous history of PTB  Current staging: WHO stage 4, Karnofsky performance index of 80
  • 14. DDX 1 HAEMATOLOGICAL DYSCRASIA - Bleeding tendencies - Pallor - B symptoms - Splenomegaly - Hepatomegaly - RVD Background: lymphoma - Massive splenomegaly: CML & CLL
  • 15. DDX  2. Malaria , (Tropical Splenomegaly SYNDROME)  3. However presence of ascites leads to consideration of: - -TB - Chronic liver disease but very enlarged liver , not cirrhotic and no stigmata for CLD - Portal Hypertension: no hx of GIT bleed, no caput medusae, but in light of ascites and travel hx
  • 16. DDX  4. Primary splenic lymphoma: spleen massively enlarged with another reason for the ascites
  • 17. Haematological Parameters FBC 26.06.10 14.07.10 16.07.10 22.07.10 Hb 7.3 4.9 4.6 MCV 70 74 72 MCH 22.8 23.6 23.3 RDW 16.6 15.4 15.8 Platelets 71 48 37 Blood smear Marked anaemia, anisocytosis, round macrocytes,poi kolocytos, mod pencil cells, mod tear drops Marked anaemia, anisocytosis, round macrocytes,poi kolocytos, mod pencil cells, mod tear drops
  • 18. Chemistry Parameters 26.06.10 22.07.10 Na 130 133 K 3.5 3.9 Urea 13.7 8.3 Creatinine 248 170 Anion gap 15 13
  • 19. Chemistry Parameters 29.06.10 15.07.10 16.07.10 22.07.10 ALT 17 25 12 15 AST 43 63 46 64 ALP 205 440 398 741 GGT 169 239 216 372 Albumin 17 18 18 19 Tot protein 80 72 68 76
  • 20. Additional Tests 26.06.10 16.07.10 22.07.10 ESR >150 > 150 HAV, HCV Neg HBV HBcAb+, HBsAg - RPR Non reactive TPHA Reactive Bilharzia serology 512 Pos >16 Cercarial IgG IFA & IgM IFA Positive
  • 21. Additional Tests 29.06.10 22.07.10 CMV IgM Equivocal Anticardioli pin Neg Antiphosph otyidal IgG/IgM 13.21 34.79 Coagulation profile INR 1.11, PTT 15.7 INR 2, Ddimers 17.02, fibrinogen 4.8 Blood cultures No anaerobic org isolated
  • 22. Summary of Laboratory Investigations  HIV positive, CD4 11 (4.36%)  Hyponatremia  Obstructive cholestatic pattern  Pancytopaenia  Derranged clotting profile
  • 23. CXR
  • 24. Endoscopy  G –SCOPE : showed no varices, oesophageal candidacies and gastritis
  • 25. Ultrasound of Abdomen  Abdominal sonar to look for: 1. Paraaortic nodes  2. Spleen for abscess  3.Liver for :SOL and Cholangitis
  • 26. Ultrasound of Abdomen  Outcome of sonar in keeping with clinical suspicion of HS,  Periportal fibroses and Para-aortic nodes
  • 27. Ultrasound of Abdomen  Periportal fibroses suggested to us : possible Schistosomiasis,  However haematological dyscrasia still not discount as a higher DDX because of LN and RVD  Stool for OOP came positive for S. Mansoni
  • 28. Ultrasound Abdomen Outcome of sonar was in keeping with our clinical suspicion of HS, but more importantly there was periportal fibroses and para-aortic nodes Gallbladder enlarged with a gallstone
  • 29. Bone Marrow Aspirate  Aspirate myelogram : iron stain : - Iron stores : 4 - Sideroblasts : not seen Mildly increased iron stores with no incorporation( iron transfer block)
  • 30. Bone Marrow Trephine  BMAT -Macroscopy: Specimen consists of single greyish white fragment of tissue measuring 0.6 cm in length -Microscopy: Histological examination of the specimen shows small trephine biopsy( 4,5 bone marrow spaces)
  • 31. Bone Marrow Trephine  All systems are present. Megakaryocytes adequate, increased in groups up to 3 on different stage of maturation.  Granulocytes show typical maturation.  Erythroblast scanty, scattered. There is diffuse presence of plasma cells and increase of macrophages with areas suggestive of granuloma and focal accumulation of lymphocytes.
  • 32. Bone Marrow Trephine  Reticulin network is diffusely increased and confirms the presence of granuloma  Iron deposit are scanty, but present  ZN stains are positive for AFB.  Diagnosis : -Bone marrow Miliary tuberculosis
  • 33. Treatment  Initiated on bactrim prophylaxis  Fluconazole orally 200 mg bd  Augmentin  Fluid resuscitation
  • 34. Treatment  Praziquantel  Anti-TB + pyridoxine  Plan for ARV’s after 2 weeks (d4T, 3TC and EFV)
  • 35. Miliary TB : Introduction  There are many haematological states associated with tuberculosis especially miliary tuberculosis.  The majority of patients have little disturbance in their haematology other than the normochromic of hypochromic, normocytic anaemia of chronic disease.
  • 36. Miliary TB : Introduction  The degree of anaemia tends to reflect duration of illness rather than the severity
  • 37. Miliary TB: Introduction  A raised erythrocyte sedimentation  rate (ESR) and blood viscosity are also common;  The ESR may be over 100 especially in cryptic miliary tuberculosis.'  White cell counts are usually slightly reduced or within normal limits with a 'left shift' (increase in premature forms)
  • 38. Miliary TB : Introduction  FBC count Leukopenia/leukocytosis may be present. Leukemoid reactions may occur. Patients may have anemia. Thrombocytopenia or, rarely, thrombocytosis may be present.
  • 39. Miliary TB : Introduction  The diagnosis of tuberculosis must be entertained in all patients with unexplained fever who have haematological disease and/or immunodeficiency and  In these situations bone marrow and liver biopsy are most useful for  histology and culture
  • 40. Miliary TB : Introduction  A, variety of abnormal haematological pictures is described as part of, or dominating the presenting clinical picture in tuberculosis, especially with disseminated disease.'  These include leukaemoid reactions,  myelofibrotic changes, the haemophagocytic syndrome,'3 polycythaemia and pancytopenia.
  • 41. Miliary TB : Introduction  Rarely tuberculosis presents with pancytopenia.  Cooper describes a patient where pancytopenia resolved with the removal of an enlarged tuberculous spleen.  Otherwise pancytopenia attributable to tuberculous hypersplenism has rarely been seen.
  • 42. Summary of Findings in Miliary TB  Splenomegaly is uncommon in tuberculosis; 13% of Munt's series had mild splenomegaly but only 1 in 68 patients and 3 of 24 post-mortem in Biehl's series' of cases of miliary tuberculosis.
  • 43. Summary of Findings in Miliary TB: CXR Findings are typical in 50% of cases. A bright spotlight helps to reveal miliary nodules. Bilateral pleural effusions indicate dissemination versus localized and unilateral pleural TB. This may be a useful clinical clue. Nodules characteristic of miliary TB may be better visualized on lateral chest radiography (especially in the retrocardiac space).
  • 44. Summary of Findings in Miliary TB: US Abdomen  Ultrasonography may reveal diffuse liver disease, hepatomegaly, splenomegaly, or para-aortic lymph nodes
  • 45. Summary of Findings in Miliary TB: History  Patients with miliary tuberculosis (TB) may experience progressive symptoms over days to weeks or occasionally over several months. Symptoms include the following: Weakness, fatigue (90%) Weight loss (80%) Headache (10%)
  • 46. Signs of miliary TB include the following: Subtle signs, such as low-grade fever (20%) Fever (80%) Cough (60%) Generalized lymphadenopathy (40%) Hepatomegaly (40%) Splenomegaly (15%) Pancreatitis (<5%) Multiorgan dysfunction, adrenal insufficiency
  • 47. Miliary TB with pancytopenia: Pathogenesis  Experimental support from Sabin et al who demonstrated that animals with disseminated TB involving the marrow developed pancytopenia  Hypothesis further supported by cases where recovery of peripheral blood counts with anti-TB drugs is taken to indicate that there is no underlying haematological disease
  • 48. Conclusion  Patient MC is still alive  However, patients with miliary TB accompanied by pancytopenia rarely survive their disease  If the peripheral blood picture does recover, it has been taken that there is no underlying haematological disease
  • 49. References  Cooper, W., Pancytopenia associated with disseminatedtuberculosis. Ann Intern Med 1959, 50: 1497-1501.  Meredith, H.C., Early, J.Q. & Becker, W. Tuberculous splenomegaly with the hypersplenism syndrome. Blood 1949, 4: 13671.  Munt, R.W. Miliary tuberculosis in the chemotherapy era: with a clinical review in 69 American adults.  Medicine 1972, 51: 139
  • 50.  THANK YOU

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