How do we de knot THE Gordian_knot?.pptx

A challenging case of 46year old monk presented with left arm painful swelling for 6 months which was initially treated as abscess. Not responding to injection antibiotics. Histopathology report of left axillary lymph node revealed as chronic reactive lymphadenitis. After muscle biopsy, diagnosis was confirmed as tuberculous Myositis and patient’s condition and swelling significantly improved after steroid and fixed dose combination of anti TB.

1. Gordian knot Professor Dr Moe Moe San Dr Nang Khin Hnaung Tint Tropical & Infectious Disease Department YGH 03-Mar-19 1

2. 46 year old monk, from Kan- Gyi - daunk tsp, referred from Yangon Orthopedic Hospital on the last week of 29.1.2018 c/o Left arm swelling x 6 months 03-Mar-19 2

3. 03-Mar-19 3 Small lump of tamarind seed size just below the axilla (not red nor itchy) Egg size Constitional symptoms (low grade fever, LOW, LOA) 4 mths later Surgical treatment at station hospital But swelling recurs with induration At district hospital I & D with biopsy done acute on chronic non specific inflammation, from left arm swelling spread from surgical site to the whole arm, left shoulder and scapula, up to left axilla Seeked for help from traditional healer ( temaygufq&m ) Puncture of the surgical site – Swelling worsen, became painful, skin color – increasing redness which later changes to brownish and darkened compared to right arm

4. Associated features Fever (+) LOW (+) LOA(+) Enlarged glands in left axilla (+) Preceding h/o trauma (-) insect bite (-) Not associated with redness or itchyness , joint pain, skin rash, limitation of movement 03-Mar-19 4

5. ~ 6month of swelling Consulted with orthosurgeon at YOH Done biopsy and after results, he was referred to Tropical and Infectious Diseases Department for further management 03-Mar-19 5

6. Sytem review Rheumatological system No history of oral ulcers, photosensitivity and skin rashes apart from that swelling No joint swelling nor pain nor deformity No limitation of movement Haematological No bleeding manifestation and other lymph nodes enlargement apart from left axillary gland 03-Mar-19 6

7. CNS CVS not relevant Resp GI Genitourinary – no ulcer nor discharge 03-Mar-19 7

8. PMH- Hypertension (-), DM(-), TB(-), malignancy (-), TB contact(-), no h/o hospitalization Drug H/o – H/o taking herbal medicine and applying traditional medicine to the lesion (+) Personal H/o – non smoker, teetotaler, not a betel chewer 03-Mar-19 8

9. Social H/o – he’s entered monk-hood since 25 years of age, living alone in a small monastry , supported by the villagers and his brothers and sisters Family H/o – no known family history of malignancy or medical illness 03-Mar-19 9

10. On exmination Middle age monk , Body wt – 66kgBMI – 20kg/m 2 Mild pallor , Jaundice (-) no clubbing, no leuconychia , no palmar erythema , no features of IE No pedal oedema , No unilateral leg swelling Marked swelling of left arm (+) 03-Mar-19 10

11. No cervical lymph nodes enlargement 3 enlarged lymph nodes in left axilla , largest 3 x 3 cm, smallest 2 x 1 cm 03-Mar-19 11

12. Local examination of left arm 03-Mar-19 12 extending from shoulder down to mid forearm (12 cm ) occupying the whole circumference of arm Smooth surface with incisional mark for biopsy (+) No pus discharge from wound Signs of inflammation on overlying skin with redness, tenderness, swollen and increased in temperature Regional lymph node enlargement – Left anterior and lateral axillary lymph nodes Largest 3x3cm, smallest 2x1cm

13. Picture of left arm 03-Mar-19 13 ARM CIRCUMFERENCE – 46cm

14. Other systems Rheumatological – no joint swelling nor tenderness, no limitation of movement, oral uclers , mouth ulcer, skin rash (-) CNS CVS NAD Respiratory system Abd – soft, no mass, no organomegaly , no free fluid, BS (+) 03-Mar-19 14

15. Provisional Diagnosis 03-Mar-19 15 Myositis Pyogenic Sarcoma Fungal Tuberculous Autoimmune

16. Initial investigations CP (auto) Hb Hct MCV WBC Neu Lym Mono PLT 29.1.18 10.9 35.3 74.6 9.6 5.6 3.1 0.9 380 Urea Creatinine K ESR CRP RBS 4.1 mmol 88 umol 4.7 130 46 146mg/dl LFT Bilirubin AST ALT ALP CK Ca PO4 0.17mg/dl 48 11 85 200 2.3 1.1 03-Mar-19 16

17. ANA – 1/100 ENA – Negative Blood C & S – Sterile Sputum C & S – Sterile Sputum AFB & Gene X pert – MTB not detected Tuberculin skin test - negative 03-Mar-19 17 HBs Ag Anti-HCV Ab Anti-HIV Ab Non reactive Non reactive Non reactive

18. Recheck B,C,R at NHL – Non reactive CD4 count – 436 cells/ uL Iron study – Normal Hb electrophoresis – Normal Fungal Culture – Negative Wound Swab C & S – Sterile Cysticercal antigen - negative 03-Mar-19 18

19. Imaging CXR USG ( Abd & pelvis) – fatty liver Shoulder X Ray ( Left) MRI left arm 03-Mar-19 19

20. CXR (PA) Perihilar and right middle zone pneumonitis 03-Mar-19 20

21. Left shoulder jt X Ray Sub- luxation of shoulder jt with reduced bone density Soft tissue swelling 03-Mar-19 21

22. MRI left arm ( Jan, 2018) 03-Mar-19 22

23. 03-Mar-19 23

24. Incisional Biopsy results (1.2.18) 03-Mar-19 24

25. 03-Mar-19 25

26. 03-Mar-19 26

27. Provisional Diagnosis 03-Mar-19 27 Myositis Pyogenic Sarcoma Fungal Tuberculous Autoimmune

28. 03-Mar-19 28 Chronic persistent myositis Constitutional symptoms – Low grade fever, LOW, LOA Raised ESR, CRP Heterogenous intensity of muscles on MRI findings Multiple granulomas with Langhan’s giant cells Caseation necrosis Tuberculous Myositis

29. Started anti-TB initial regimen with 4FDC 4 OD on 9.2.2018 Supportive treatment Multivitamin 1 OD Symptomatic treatment for pain 03-Mar-19 29

30. 3 months after anti TB Clinical wellbeing – status quo Body weight – 64kg (↓) Arm circumference – 39 cm (↓ ) 03-Mar-19 30 CP (auto) Hb MCV WBC Neu Lym Mono PLT 12.5.18 8 74 9 5.6 2.4 0.9 380 Urea Creatinine Na K Cl HCO3 ESR CRP 5.8 67 umol 137 4.5 88 20 120 105 LFT Bilirubin AST ALT ALP CK 12 33 11 112 100

31. Picture of the arm 03-Mar-19 31 ARM CIRCUMFERENCE – 39CM

32. Recheck MRI after 3 mths Anti TB 27.1.2018 12.5.2018 03-Mar-19 32

33. 6 months after anti TB Clinical wellbeing – productive cough Body weight – 64kg (↓) Arm circumference – 39 cm (↓ ) 03-Mar-19 33 CP (auto) Hb MCV WBC Neu Lym Mono PLT 27.7.18 6 74.6 14 10 3.1 0.9 450 Urea Creatinine Na K Cl HCO3 ESR CRP 2.4 54 umol 133 4.8 87 26 120 140 LFT Bilirubin AST ALT ALP CK 8 20 11 100 70

34. Picture of the arm 03-Mar-19 34 ARM CIRCUMFERENCE – 35CM

35. Sputum AFB Gene X pert – negative Sputum AFB C&S -negative Imagings CXR 03-Mar-19 35

36. Sputum C & S – ESBL Klebsiella pneumoniae Urine C & S – Sterile Blood C & S – Sterile Sputum AFB & Gene X pert - negative 03-Mar-19 36

37. Recheck muscle biopsy ( 6 th mth ) 03-Mar-19 37

38. 03-Mar-19 38

39. Muscle AFB + C&S - Negative 03-Mar-19 39

40. 9 mth after antiTB Clinical wellbeing – improved Body weight – 60kg (↓) Arm circumference – 31cm (↓ ) 03-Mar-19 40 CP (auto) Hb MCV WBC Neu Lym PLT ESR CRP 11 76 7 5.4 2 359 110 20 LFT Bilirubin AST ALT ALP 9.5 22 20 98

41. 03-Mar-19 41 ARM CIRCUMFERENCE – 31CM

42. 11 mth after anti TB 03-Mar-19 42 ARM CIRCUMFERENCE – 26CM

43. 03-Mar-19 43 Dec, 2018 Recheck MRI

44. 03-Mar-19 44 c Before anti TB After 3 months After 6 months After 9 months After 11 month

45. 03-Mar-19 45 Cough with whitish sputum Anorexia Resp Exam – VBS only CXR – NAD Sputum AFB & Gene X pert - Negative

46. CT chest 7.1.2019 03-Mar-19 46

47. Consulted with chest physician Bronchoscopy Abnormal mucosa and inflammation present at left upper lobe bronchus 03-Mar-19 47

48. 03-Mar-19 48

49. Left axillary lymph node biopsy Chronic non specific lymphadenitis A ntibiotics according to C & S was given and waited for response 03-Mar-19 49

50. CT Chest Recheck (1.3.19) 03-Mar-19 50 Comparison was done with previous CT film Radiological assessment is more severe than the previous film Chest infection at apical and posterior basal segment of right lower lobe Left sided pleural effusion Pericardial effusion

51. Final diagnosis Improving TB myositis Right apical and basal pneumonia with pleural and pericardial effusion 03-Mar-19 51

52. Brief Literature review TB – an ancient killer & 2 nd most common infectious disease following malaria and a leading cause of death from infectious disease worldwide Incidence 2000 - 8.3 million 2006 - 9.2 million 2010 - 8.8 million Ali N et al. Musculoskeletal Tuberculosis: Two Year Experience at a Tertiary Care Teaching Hospital of Northern India and Review of Literature. J Commun Dis 2017; 49(4): 44-51. 03-Mar-19 52

53. Primary tuberculous pyomyositis – less than 1% of skeletal tuberculosis Ali N et al. Musculoskeletal Tuberculosis: Two Year Experience at a Tertiary Care Teaching Hospital of Northern India and Review of Literature. J Commun Dis 2017; 49(4): 44-51. 03-Mar-19 53 Most common site of EPTB is the lymph node followed by Spine (60% of all EPTB) central nervous system Abdomen extra spinal skeletal system pleura, pericardium genitourinary system skin and others Pulmonary tuberculosis is the most common form of tuberculosis Extra pulmonary tuberculosis (EPTB) accounts for 10–15% of all the forms of tuberculosis

54. PATHOPHYSIOLOGY/NATURAL HISTORY cold abscess is composed of serum, leukocytes, caseation , bone debris, and bacilli David A. Spiegel et al,Techniques in Orthopaedics ®, Vol. 20, No. 2, 2005 8% of the cases cause is direct inoculation 03-Mar-19 54

55. Diagnosis of TB myositis Modi et al, Case Reports in Infectious Diseases Volume 2013, Article ID 723879, 4 pages 03-Mar-19 55 Non specific (diagnostic dilemma) Constitutional symptoms - low-grade fevers, night sweats, weight loss, anorexia, and malaise Musculoskeletal complaints - swelling, stiffness, and pain usually a delay in diagnosis because of its atypical presentation, lack of knowledge of the disease absence of early specific signs large number of differentials High index of clinical suspicion is the key in diagnosis especially in endemic areas D/ Dx soft tissue sarcoma Parasitic infection like cysticercosis or hydatid cyst, and Inflammatory myositis or hematoma with secondary infection

56. Investigations No single test can lead to a correct diagnosis A variety of direct and indirect methods have to be employed 03-Mar-19 56 DIRECT METHODS Ziehl Neelsen staining fluorescent microscopy Lowenstein Jensen culture BACTEC culture system PCR Antigen based serology Molecular methods IHC and ICC INDIRECT METHODS histopathology which offers an advantage of differential diagnosis Cytology antibody based serology skin tests interferon release assay adenosine deaminase assay

57. Blood investigation are usually normal except ESR which is consistently high 03-Mar-19 57 histopathology of tissue along with ZN staining and culture for Mycobacterium Tuberculosis is considered the method of choice for the diagnosis of EPTB MRI is investigation of choice for localization of the lesion and to help diagnosis

58. MRI findings and benefits 03-Mar-19 58 Modi et al, Case Reports in Infectious Diseases Volume 2013, Article ID 723879, 4 pages low signal intensity on T1WI high signal intensity on T2WI in a single muscle with peripheral rims showing subtle hyperintensity on T1WI and hypointensity on T2WI After gadolinium infusion, peripheral rim enhancement is observed in all cases anatomical extent of muscle lesions and guiding the surgeons in debridement superior to CT or USG in differentiating the lesion from malignancy Can differentiate between tuberculous and other bacterial pyomyositis such as staph myositis in which there is neither cellulitis nor thrombosis

59. Modi et al, Case Reports in Infectious Diseases Volume 2013, Article ID 723879, 4 pages 03-Mar-19 59

60. Modi et al, Case Reports in Infectious Diseases Volume 2013, Article ID 723879, 4 pages 03-Mar-19 60

61. Treatment & outcome Modi et al, Case Reports in Infectious Diseases Volume 2013, Article ID 723879, 4 pages 03-Mar-19 61 Outcome depends on characteristics and sensitivity of the organism status of the host immune system stage of disease at presentation & treatment

62. Outcomes range from resolution with minimal or no morbidity, healed disease with residual deformity walled off lesions with calcification of caseous tissue a low-grade chronic granular lesion local or miliary spread of the disease that may result in death 03-Mar-19 62 David A. Spiegel et al,Techniques in Orthopaedics ®, Vol. 20, No. 2, 2005

63. Case reports 03-Mar-19 63

64. Case Reports in Infectious Diseases Volume 2013, Article ID 723879, 03-Mar-19 64

65. [ Indian J Tuberc 2013; 60: 241-244] 03-Mar-19 65

66. Rheumatology 2003;42:836–840 doi:10.1093/rheumatology/keg228 03-Mar-19 66

67. Clin . Pract . (2017) 14(4), 244-247, Tunisia 03-Mar-19 67

68. Take home message TB myositis is a rare type of EPTB Need high index of suspicion for TB in case of chronic myositis in TB endemic area MRI & histopathology are investigations of choice 03-Mar-19 68

69. Multidisciplinary team approach along with anti-tuberculosis treatment can achieve good response and best outcome Just like how Alexandar the Great solved the Gordian Knot 03-Mar-19 69

70. References 03-Mar-19 70 Primary Tuberculous Pyomyositis of Quadriceps Femoris in an Immunocompetent IndividualCase Reports in Infectious Diseases Volume 2013, Article ID 723879, 4 pages Rheumatology 2003;42:836–840 doi:10.1093/rheumatology/keg228 Primary muscular tuberculosis in immunocompetent patient Clin . Pract . (2017) 14(4), 244-247, Tunisia [Indian J Tuberc 2013; 60: 241-244] David A. Spiegel et al,Techniques in Orthopaedics ®, Vol. 20, No. 2, 2005 Ali N et al. Musculoskeletal Tuberculosis: Two Year Experience at a Tertiary Care Teaching Hospital of Northern India and Review of Literature. J Commun Dis 2017; 49(4): 44-51.

71. 03-Mar-19 71 THANK YOU SO MUCH FOR YOUR KIND ATTENTION