2. History
Mrs. P a 30 year old house wife and a
mother of two from Mamangam
Presented with a fever for 2 weeks duration
It was a low grade intermittent fever which
was associated with chills but not rigors and
responded well to antipyretics
She complained of loss of appetite and loss
of weight of about 2 -3kg over the
preceding weeks.
She also complained of lethargy and
tiredness.
3. No sore throat, ear ache or discharge
No cough, sputum or shortness of breath
No dysuria frequency or haematruia.
No history of any contact with mud or stagnant
water.
She denied headache, constipation, diarrhea
and abdominal pain.
Fever was not associated with joint pain or
early morning stiffness, no alopecia,
photosensitivity or pleuritic type chest pain
No haemoptysis, night sweats, past or contact
history of TB.
No past history of valvular heart disease or
childhood rheumatic fever.
4. No history of consumption of raw milk/ meat
or contact with animals or birds.
No sexual promiscuity, blood transfusions,
tattoos or any other high risk behaviour.
No history of foreign travels.
No history of recurrent infections or
bleeding.
She has not been on any long term drugs.
She has regular menstrual periods no
history of miscarriages or abortions
No significant surgical history
Not known allergies for drugs, foods or
plasters
No significant family history
She was a house wife and her husband
6. Examination
Febrile
Pale
Not icteric
There was palpable cervical
lymphadenopathy
No peripheral stigmata of infective
endocarditis
ENT examination was normal
No rashes, alopecia or skin changes
7. PR-88 beats /min, good volume ,regular
BP- 100/70 mmHg both supine and
standing
JVP –not elevated
Apex-not deviated
S1 S2 normal
No audible murmurs
RR-14 beats/min
Lungs-vesicular breathing
No added sounds
8. Abdomen not distended
Soft,Non tender
No hepatosplenomegaly
No ballotable masses
No free fluid
DRE-Normal
9. Upper limbs –Normal
Lower limbs – Normal
Cranial nerves –Normal
No cerebellar signs
Fundus- normal
10. Summary
30 year old female with fever and
constitutional symptoms for 2 weeks
duration.
On examination she was febrile and
pale with cervical adenopathy, rest of
the examination was normal.
23. Blood picture
Normocytic normochromic anaemia
with leucopenia and thrombocytopenia
No abnormal cells
24. Bone Marrow aspiration and
trephine biopsy (at NHSL) with
Bone Marrow TB PCR
(Routinely done at that ward)
No abnormal cells in bone marrow
histology
Bone Marrow TB PCR positive
25. 2D Echo cardiogram
EF – 60%
Mitral, aortic, tricuspid and pulmonary
valves normal
No vegetations or cardiac masses
27. Ultrasound Scan of Abdomen
Liver-normal in size & texture
GB-Normal
Spleen-not enlarged
Kindney-B/L normal size ,shape &
texture
Bladder-Normal contour with normal
wall thickness
No free fluid
No enlarged Para - aortic LN
28. Contrast Enhanced CT Chest
and Abdomen
Lung parenchyma normal with no
focal lesions
No pleural effusions
Liver normal
Hepatic duct and Gall bladder normal
Spleen and kidney normal
No enlarged para – aortic nodes
No free fluid
34. Liver Function Tests
AST(u/l) 42 61 127 129 203 42
ALT (u/l) 42 63 163 124 110 36
T. Prot
(mg/dl)
68 73
Alb
(mg/dl)
47 26
Glo
(mg/dl)
41
T. Bil
(µmol/l)
5.5 2.6
D. Bil
(µmol/l)
1.5 1.9
GGT 25
35. Lymphnode biopsy
The lymph node architecture is effaced.
There are areas of necrosis surrounded by
histiocytes.
Multinucleated giant cells and well – formed
granulomas are not present.
The back ground contains a polymorphous
lymphoid infiltrate.
There is no evidence of apoptotic debris
suppuration or lymph node malignancy
Conclusion – Necrotizing lymphadenitis
with histiocytes. Possibilities include
SLE
37. Chronology of events
Patient was first admitted in early December with
fever and investigated for pancytopenia
Transferred to NHSL for haematology opinion
Lymph node biopsy, BM biopsy done at NHSL
Retransferred back to THB
Respiratory Referral done
ATT started for extrapulmonary tuberculosis
Patient developed acute hepatitis following the
start of ATT
ATT were withdrawn and LFT returned back to
normal
41. Problems with ACR criteria
Patients classified in to
◦ Classic SLE – Has many of ACR criteria
◦ Definite SLE – 4 of ACR criteria
◦ Possible SLE – Less than four of ACR criteria
◦ Undifferentiated Connective tissue disorder
Patient may have SLE but may not meet all the
criteria. Eg. – Patient with lupus nephritis on
renal biopsy while being investigated for
proteinuria but may not have other criteria
Hence, new criteria is suggested by Systemic
Lupus International Collaborating Clinics -
SLICC criteria
42. ACR Criteria SLICC criteria
Serositis Acute cutaneous lupus
Oral ulcers Chronic cutaneous lupus
Arthritis Non scarring alopecia
Photosensitivity Oral or nasal ulcers
Blood disorders Joint disease
Renal involvement Serositis
Neurologic disorder Renal involvement
Malar rash Neurologic involvement
Discoid rash Haemolytic anaemia
ANA Leucopenia/lymphopenia
Anti DS DNA thrombocytopenia
ANA
Anti DS DNA
Antiphopholipid Ab
Low compliments
DAT
43. Autoantibodies
ANA
◦ Best diagnostic test for SLE
◦ 93% Sensitivity
◦ Other conditions with positive ANA
Scleroderma – 85%
Mixed connective tissue disorders – 93%
PM/DM – 61%
Rheumatoid arthritis – 41%
Drug induced Lupus – almost 100%
Discoid lupus – 15%
44. Anti dsDNA
◦ Highly specific for SLE and associated with
disease activity
◦ Titers of anti dsDNA antibodies fluctuate with
disease activity, therefore useful in the
management
◦ Other conditions with anti – dsDNA antibodies
Rheumatoid arthritis
Scleroderma
Raynaud’s phenomenon
Mixed connective tissue disease
TB and other infections
Malignancies
45. Extrapulmonary and Miliary
Tuberculosis
Miliary TB refers to clinical disease resulting from the
haematogenous dissemination of Mycobacterium
tuberculosis – a term used since 1700s
Clinical manifestations
◦ Disseminated pulmonary disease
◦ Lymphatic disease
◦ Bone and joint involvement
◦ Gastrointestinal disease
◦ Genito urinary disease
◦ CNS involvement
◦ Other Organs – Adrenal, Heart, Eye, thyroid, laryngitis, otitis
media
46. Haematological manifestations
of Tuberculosis*
Normocytic normochromic anaemia is the most
commonly observed abnormality (84% in MTB/DTB
and 86% in PTB)
Leucopenia (25% in DTB/MTB but very rare in
PTB)
Pancytopenia occurs only in MTB
Thrombocytosis more common in PTB, where as
thrombocytopenia was more in DTB/MTB
Haemophagocytic syndromes also are described
MTB – Milliary Tuberculosis
DTB – Disseminated Tuberculosis
PTB – Pulmonary Tuberculosis
* Singh KJ, et al 2001 J. of associated Physicians India2001
Aug;49:788
47. TB PCR in Bone marrow in patients
presenting with PUO*
PCR appears to be valuable in establishing
the diagnosis of tuberculosis in patients
presenting with PUO
*Singh UB at el American J of Tropical Medicine 75(5), 2006, pp960-963
48. Problems with Bone Marrow TB
PCR
High rate of false positives, due to
macrophages in bone marrow which
contain dead TB bacilli will give a positive
PCR result.
In this patient with
◦ Negative Mantoux
◦ Normal CRP
◦ Normal CXR
◦ Normal CECT chest and abdomen
◦ LN biopsy not suggestive of TB
Diagnosis of TB is less likely
49. Side effects of ATT
Drug Common Side Effects Rare Side Effects
1. Isoniazid • Nausea and vomiting
• Peripheral neuropathy
• Hepatitis
• Histamine reaction
• Skin rashes
• Convulsions
• Psychosis
• Optic neuritis
• Hematological
• SLE like syndrome
2. Rifampicin • Hepatitis
• Potent hepatic enzyme
induction
• Rashes
• ARF
• Hemolytic anemia
3. Pyrazinamide • Skin rashes
• Joint pain
• Hepatitis
• Sideroblastic
anemia
4. Streptomycin • Renal damage
• Auditary / vestibular
damage
• Imparied
neuromuscular
transmission
5. Ethambutol • Optic neuritis
50. ATT induced acute Hepatitis
Most commonly by Isoniazid, Pyrazinamide
and rifampicin.
A transaminase rise of 2 -3 folds is normal,
elevated AST ALT is not an indication to
stop ATT provided that bilirubin is normal
LFTs should be performed if the patient is
having symptoms of acute hepatitis.
If drug induced hepatitis is suspected all
ATTs should be stopped
ATT should be re – introduced once LFTs
are normal in sequential order Rifampicin,
Isoniazid and Pyrazinamide
51. Bridge Therapy in ATT induced
Hepatitis
In some patients we may not be able to
completely withdraw ATT in acute hepatitis.
Streptomycin, Ethambutol and a quinolone
(Levofloxacin) when both serum bilirubin
and transaminases are high used in such
patients.
Once LFTs return to normal the original
drugs reintroduced in sequential order
Isoniazid, Rifampicin and Pyrazinamide.
Do not do it by your self – Get the help of a
Respiratory Physician.
52. Coming back to our patient Mrs.
P
Plan of management
◦ Do a Quantiferon gold test to rule out TB
– awaiting the report
To start managing SLE with Isoniazid
cover
53. Management of Mrs. P
Prednisolone 30mg/d
HCQ 200mg/d
Enalapril 2.5mg/d
Vitamin D and Calcium
supplementation
Alandronate 75mg/ week
Isoniazid 300mg/d (until Quantiferon
report available)
Eye screening
DEXA scan planned via clinic follow
up
