macrophageactivation

1. Myocardial Infarction is not always a
simple diagnosis.
Case discussion
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2. Background
 Mrs. S, 63 year old lady
 Adult onset sero-negative rheumatoid
Arthritis since 2009
 On Methotrexate 7.5mg weekly since 2010
 Diabetes Mellitus since 2012,on diet control
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3. At ETU
 Central tightening chest pain
 Persistent
 severe
 No radiation
 Autonomic disturbances
 Worsening shortness of breath for three days.
 No palpitation
 No history of fever or cough
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4. On examination
 In pain
 Mildly dyspnoeic at rest
 Afebrile
 Pallor
 JVP- not elevated
 PR – 90 bpm, BP – 110/80 mmHg, SpO2 – 94%
 B/L basal crepitation
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5. ECG
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6. At ETU
 Dual antiplatelets with Atorvastatin
 Thrombolysis with Streptokinase
 IV Frusemide boluses.
 Taken over to CCU for further care.
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7. What they have done at CCU
 2D Echo revealed extensive anterior wall
motion abnormalities
 Started LMWH
 Rheumatology review.
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8. At CCU
 Cardiac Enzyme profile
cpk MB – 109u/l, cpk-609, SGOT -87u/l , LDH – 1080 u/l
 FBC Hb – 7.1 g/dl, WBC – 12300 cumm3, N-89%, Plt – 303000
 Blood picture
NCNC anaemia, mild Neutrophil leucocytosis, adequate Plt
 ESR - 146 mm 1st hour
 Scr - 136 mmol/l
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9. Liver function test
Total Protein 62 g/l
Albumin 31 g/l
Globulin 31 g/l
AST 61 u/l
ALT 31 u/l
ALP 396 u/l
T. Billi 7.8 mmol/l
INR 1.0
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10. On admission to ward - 15
 She does not complain of chest pain. Mild short of
breath.
 LOA
 Malaise, body weakness
 Multiple small joint pain and swelling with no
significant morning stiffness.
 Bleeding from mouth, no other bleeding
manifestations.
 UOP was adequate.
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11. On admission to ward - 15
 Conscious and rational.
 Not in pain.
 Mildly dyspoenic.
 Mild temperature.
 Gum bleeding.
 Pallor, Anicteric
 Painful oral ulcers, no genital ulcers
 No skin rashes, few ecchymotic patches.
 No lymph node enlargement.
 Haemodynamically stable.
 B/L crepitation.
 Abdomen – soft, no organomegaly.
 Multiple small joint tenderness and swelling, no evidence of extra articular
manifestations.
 No neurological weakness.
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12.  FBC
 WBC – 600 cumm3
 HB – 7.6 g/dl
 PLT – 23000 cumm3
 Blood Picture
 RBC – normocytic normochromic
 WBC – marked leukopaenia with neutropaenia
 PLT – low with some large platelets.
Conclusion :
Pancytopaenia; most probably drug related.
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13.  ESR – 133 mm 1st h
 CRP – 129 mg/dl
 UFR – RBC field full
 S.cr – 3.24 mg/dl
 Clotting profile
 APTT – 35 sec.
 INR - 1
 Serum Ferritin – 1196 ng/ml [20 – 400 ng/l]
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14. Liver enzyme profile
Total protein 58 g/dl
Albumin 32 g/dl
Globulin 25 g/dl
T. Billi 1.87 mg/dl
AST 80 u/l
ALT 100 u/l
ALP 1072 mg/dl
GGT 130 mg/dl
INR 1.2
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Problem list

15.  Problem list.
 In a patient with sero negative RA, on Methotrexate
 Recent, STEMI
 Mild Fever with Pancytopaenia
 Gum bleeding with normal clotting profile [low platelet].
 Multiple small joint pain, swelling, with minimal morning stiffness with
high inflammatory markers.
 Deranged liver function, marginally low albumin, predominantly
cholestatic
 Renal impairment (Acute kidney injury)
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16.  Could single disease entity explain all her
problems??
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17.  Questions to be answered?
 Methotrexate toxicity?
 Acute flare of RA ?
 Rheumatoid vasculitis?
or
 Is it something else?
 Does MI part of systemic illness?
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18.  How should we investigate her,now?
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19. Is it a acute flare?
Common indicators of disease activity in RA include the
following measurements
 Swollen and tender joint counts
 Pain
 Patient and evaluator global assessments of disease activity
 Erythrocyte sedimentation rate and C-reactive protein (ESR, CRP)
 Duration of morning stiffness
 Fatigue
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20. Is it Methotrexate toxicity?
 Oral ulcers
 Pancytopaenia
 Deranged liver function
 Acute kidney injury
 General ill health
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23. Is it Rheumatoid vascuilitis?
 Typically occurs in patients with long-standing, joint-
destructive RA when the inflammatory arthritis is "burned
out,"
 Presentations of RV within five years of the RA diagnosis
are very unusual
 Significant constitutional symptoms.
 Nearly always have rheumatoid nodules.
 strongly positive for rheumatoid factor.
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24.  Is it something else?
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25.  Causes for Pancytopaenia in a patient with
rheumatoid arthritis?
 Mostly related to drugs,(Methotrexate, Leflunomide,
Azathioprine, Infliximab)
 Lymphoma
 Felty’s syndrome
 Macrophage activation syndrome
 Visceral leishmaniasis
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26.  Causes for Ferritin > 1000 ng/l
 Still’s disease
 Milliary Tuberculosis
 Catastrophic APLS
 Haemophagocytic syndrome / Macrophage
activation syndrome(MAS)
 SIRS
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27. Bone marrow biopsy
 Conclusion:
Peripheral cytopaenia with increased bone marrow
macrophages and haemophagocytosis suggestive of
macrophage activation syndrome.
suggest; urgent treatment with IV Ig
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33. What we have done here.
“Multi disciplinary approach”
 IV Methylprednisolone 1 g daily for five days.
 Broad spectrum IV antibiotic on Microbiologist
guidance
 IV PPI
 Withheld Methotrexate
 IV Folinic acid “rescue therapy”
 Started IvIg 0.4 mg/kg daily.
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34. What happened to the our patient?
 Respiratory arrest on D1 IvIg
 Transferred to ITU for ventilatory support
 Succumbs on D 4, admission to ICU
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35.  What's new about ferritin?
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36. Ferritin
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40. Take home message
 MAS is a potentially fatal condition and it is
often missed in adults.
 Goals for the future include increasing
awareness of the condition, which requires
both early diagnosis and early effective
therapy to further reduce mortality.
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