Macrophage activation

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Myocardial Infarction is not always a simple diagnosis.

Case discussion

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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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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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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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ECG

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At ETU

Dual antiplatelets with Atorvastatin Thrombolysis with Streptokinase IV Frusemide boluses.

Taken over to CCU for further care.

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What they have done at CCU

2D Echo revealed extensive anterior wall motion abnormalities

Started LMWH Rheumatology review.

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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 pictureNCNC anaemia, mild Neutrophil leucocytosis, adequate Plt

ESR - 146 mm 1st hour

Scr - 136 mmol/l

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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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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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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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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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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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Liver enzyme profile

Total protein 58 g/dlAlbumin 32 g/dlGlobulin 25 g/dlT. Billi 1.87 mg/dlAST 80 u/lALT 100 u/lALP 1072 mg/dlGGT 130 mg/dlINR 1.2

Problem list

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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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Could single disease entity explain all her problems??

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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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How should we investigate her,now?

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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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Is it Methotrexate toxicity?

Oral ulcers Pancytopaenia Deranged liver function Acute kidney injury General ill health

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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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Is it something else?

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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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Causes for Ferritin > 1000 ng/l Still’s disease Milliary Tuberculosis Catastrophic APLS Haemophagocytic syndrome / Macrophage

activation syndrome(MAS) SIRS

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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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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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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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What's new about ferritin?

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Ferritin

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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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