This document discusses the case of a 63-year-old woman with rheumatoid arthritis and diabetes who presented with chest pain and was diagnosed with a myocardial infarction. She subsequently developed fever and pancytopenia. Further tests found very high ferritin levels and a bone marrow biopsy confirmed macrophage activation syndrome, a severe complication caused by overly active immune cells. She was started on treatment including steroids and IVIG but unfortunately died shortly after being transferred to the ICU. The key lessons are that macrophage activation syndrome can occur in adults with autoimmune conditions and be fatal if not recognized and treated promptly.

1. Myocardial Infarction is not always a
simple diagnosis.
Case discussion
1

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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