APS in Lebanon.

Imad Uthman, MD, MPHImad Uthman, MD, MPHProfessor of Clinical MedicineProfessor of Clinical MedicineHead, Division of RheumatologyHead, Division of RheumatologyAmerican University of Beirut Medical CenterAmerican University of Beirut Medical CenterBeirut, LebanonBeirut, Lebanon

Study Of The Clinical And Serological Characteristics And Long-term Evolution of APS Patients

At The American University of Beirut Medical Center (AUBMC).

The Lebanese APS Study Group.

Purpose: – To evaluate prospectively the clinical

manifestations and the long-term evolution of the APS patients seen at AUBMC and, in the future, expand this to other centers in the country.

The Lebanese APS Study Group.

Methods: – All patients included have fulfilled at least

one clinical criterion and one laboratory criterion.

– A standardized questionnaire was used to collect demographic data, risk factors for thrombosis, coexisting autoimmune disorders, and specific morbidities due to APS, and data was stored into a registry.

The Lebanese APS Study Group.

Results: – 200 patients logged into the registry so

far.– Cases were identified from the lab records

(positive ACA and/or LAC tests)

Demographic

Lebanon Europe*

Female: 144 (72%) 820 (82%)

Male 46 (28%) 180 (18%)

Cervera R, et al on behalf of the "Euro-Phospholipid Project Group”: Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46: 1019-1027

Underlying Conditions

Lebanon Europe*

SLE 78 (39%) 362 (36.2%)

Primary APS 70 (35%) 531 (53.1%)

RA 4 (2%) 18 (1.8%)

Systemic Sclerosis 4 (2%) 7 (0.7%)

Sjogren’s Syndrome

2 (1%) 22 (2.2%)

Lupus Like Syndrome

2 (1%) 50 (5.0%)

*Cervera R, et al : Arthritis Rheum 2002; 46: 1019-1027

Neurological Manifestations

Lebanon Europe

Stroke 34 (17%) 198 (19.8%)

Transient Ischemic Attack

16 (8%) 111 (11.1%)

Epilepsy 16 (8%) 70 (7.0%)

Migraine 14 (7%) 202 (20.2%)

Cerebellar ataxia: 6 (3%) 7 (0.7%)

Cerebral venous thrombosis:

4 (2%) 7 (0.7%)

Vertigo 4 (2% )

Cardiac Manifestations

Lebanon Europe

Angina 6 (3%) 27 (2.7%)

Valve dysfunction 3 (1.5%) 116 (11.6%)

Coronary artery bypass graft

2 (1%) 11 (1.1%)

Chronic cardiomyopathy

2 (1%) 29 (2.9%)

Myocardial infarction 55 (5.5%)

Intestinal Manifestations

Lebanon Europe

Splenic infarcts: 10 (5%) 11 (1.1%)

Pancreatic infarction:

6 (3%) 5 (0.5%)

GI ischemia: 6 (3%) 15 (1.5%)

Liver infarctions: 4 (2%)

Budd Chiari syndrome

1 (0.5%) 7 (0.7%)

Addison’s Disease: 1 (0.5%) 4 (0.4%)

Pulmonary Manifestations

Lebanon Europe

Pulmonary embolism & infarction

15 (7.5%)

141 (14.1%)

ARDS 3 (1.5%)

7 (0.7%)

Osteoarticular Manifestations

Lebanon Europe

Arthralgias: 28 (14%) 387 (38.7%)

Arthritis: 10 (5%) 271 (27.1%)

Avascular necrosis:

8 (4%) 24 (2.4%)

Obstetric Manifestations

Lebanon Europe

Preeclampsia/ eclampsia:

4 (2%) 56 (9.5%)/

26 (4.4%)

Abruptio Placenta:

4 (2%) 12 (2.0%)

Fetal Manifestations

Lebanon Europe

pregnancies 296 1580

Early Fetal Loss (<10 weeks)

56 (19%) 560 (35.4%)

Late Fetal Loss (>10 weeks):

20 (6.75%) 267 (16.9%)

Live birth 200 (67%) 753 (47.7%)

Premature birth, no. premature/no. live births

12/200 (6%) 80/753 (10.6%)

Thrombotic Manifestations

Lebanon Europe

LE DVT 56 (28%) 389 (38.9%)

LE superficial phlebitis

6 (3%) 117(11.7%)

Renal Manifestations

Lebanon Europe

Renal vein thrombosis

3 (1.5%)

Renal infarction 2 (1%)

Renal Manifestations

27 (2.7%)

THE LEBANESE APS STUDY GROUP

Results: – In decreasing frequency, the most common

complications were: • DVT

• Obstetric problems

• Stroke

• TIA

• Seizures

• Migraines

• Splenic infarcts

THE LEBANESE APS STUDY GROUP

Conclusion: – DVT and strokes are the most common

non-obstetric complications of APS in Lebanon.

– Many patients suffer from more than one complication, such as DVT or ischemic stroke.

Nightmare On Bliss StreetCatastrophic Cerebral APS

Case Presentation

Mrs. HM 61 year old female presented to ER on March 8, 09 with acute onset of dysarthria and left cheek numbness.

One month before she had recurrent episodes of vertigo and unsteadiness, was told she had ear problems.

Background

Hypothyroid and dyslipidemic.Smoker Married 3 childrenNo Hx of abortion, fetal loss, or PreclampsiaHx of premature delivery twice (at 32,30wks)No Hx of DVT.

Physical Exam

BP: 200/100.Dysarthria.Right ptosis. Cerebellar signs: Normal Gait: Normal Sensory Exam: Normal

MRI Brain: 9 March 09

Impression: – Multiple acute lacunar infarcts in

watershed distribution in both centrum semi-ovale as well as in the left precentral gyrus.

– Subacute infarct in the left occipital area.

MRI Brain: 9 March 09

MRI Brain: 9 March 09

MRI Brain: 9 March 09

MRI Brain: 9 March 09

Assessment

Neurology: R/O Vasculitis

Rheumatology: R/O APS

Laboratory Evaluation

Lupus anticoagulant: Positive

ACA IgG: 96.4 GPLu/mL ACA IgM: <7 MPLu/mL

Anti ß2-Glycoprotein I IgG: >200 U/ml Anti ß2-Glycoprotein I IgM: <2 U/ml

Laboratory Evaluation

ANA: NegativeAnti ds-DNA: NegativeC-ANCA: Negative

Course in Hospital

Started on Heparin, Plavix.Next day ( March 10) marked

improvement in speech

Course in Hospital

March 11:– Worsening dysarthria.– PTT was in the therapeutic range.– Started on Prednisone 1mg/kg by the

neurology team (for suspicion of CNS vasculitis).

March 14 PM:– Worsening of numbness and weakness in the

right upper extremity + had tongue numbness – INR 2.6– BP: 175/110 – Solu-Medrol 250 mg IV given – Restarted on IV Heparin

Course in Hospital

15 March Evening:– Acute right sided weakness 0/5 motor power

Rt side + Aphasia.

Course in Hospital

MRI Brain: 15 March 09

Impression: – Acute infarcts in the left parietal and frontal

lobes and in the watershed territories bilaterally more so on the left.

– Small focus of hemorrhage in the left parietal lobe.

MRI Brain: 15 March 09

MRI Brain: 15 March 09

MRI Brain: 15 March 09

MRI Brain: 15 March 09

16 March:– 12 PM: Unconscious, seizure like activity.

– Acute respiratory distress: mechanical ventilation.

– Physical Exam: Pupils mid sized dilated Absent corneal reflexAbsent Oculocephalic reflex Decerebrate posturing Bilateral positive Babinski

Course in Hospital

CT Brain: 16 March 09

Impression: – Hemorrhagic transformation in the left frontal

lobe infarct with significant surrounding edema, mass effect, trans-tentorial and uncal herniations with brain stem infarct.

CT Brain: 16 March 09

CT Brain: 16 March 09

CT Brain: 16 March 09

CT Brain: 16 March 09

17 March (one week after her initial presentation):– Declared brain dead, family decided to stop

mechanical ventilation.

Course in Hospital

Nightmare on Bliss Street

The Autopsy

Brain Gross Pathology

Soft, edematous Lt Sub-falcial

herniationUncal herniation and

necrosis.

Terminal Massive ICH

Recent large intracerebral hemorrhage, left frontal and parietal lobes.

Fibrin thrombi within a vessel

Free-floating small fibrin thrombi within rare arterioles and venules in cortex, leptomeninges, and white matter hemorrhage.

LF WM, recent hemorrhage, fibrin

Small recent infarcts, Left Occipital Cortex

Focal Perivascular lymphocytic infiltration.

Microangiitis, vasa vasorum

Perivascular lymphocytic infiltrates, multifocal, involving small vessels of vasa vasorum, right and left carotid arteries, consistent with small vessel angiitis.

Summary

This is the first large series of APS patients from Lebanon.

Although testing for APS is available in major hospitals in the country, the condition is still largely unrecognized by the medical community.

Further testing including genetic studies are planned in our cohort.

Thank You