Kinder CIS- Antiphospholipid Antibody Syndrome

Question 1

Antiphospholipid Antibody Syndrome

Answer 1

Acquired disorder associated with circulating autoantibodies to anionic phospholipids and their protein binding complexes

Question 2

Antiphospholipid Antibody Syndrome Clinical manifestations

Answer 2

Thromboses – can affect arterial and venous circulation
Pregnancy loss

Can be Primary or Secondary Antiphospholipid Syndrome

Secondary:
Systemic Lupus Erythematosus
Malignancy
Infections (HIV)
Drugs: phenytoin, chlorpromazine

Question 3

Antiphospholipid Antibody Syndrome Deep venous thrombosis

Answer 3

Lower extremities
Pulmonary Embolism
Renal vein thrombosis
Retinal vein occlusion
Budd-Chiari syndrome
Adrenal hemorrhage secondary to thrombosis of the adrenal veins

Question 4

Antiphospholipid Antibody Syndrome Arterial Disease

Answer 4

in the skin- Ulceration, gangrene, livedo reticularis

cerebrovascular: Stroke, transient ischemic attack, seizure, encephalopathy, chorea, myelopathy, mononeuritis

Cardiac: Myocardial infarction, cardiomyopathy, valvular vegetations and abnormalities

Renal: Renal infarction, thrombotic microangiopathy

Pulmonary: Pulmonary emboli, microvascular thromboses, pulmonary hypertension, alveolar hemorrhage

Gastrointestinal: Mesenteric ischemia, splenic infarction

Ophthalmologic: Retinal artery thrombosis and ischemia

Question 5

Antiphospholipid Antibody Syndrome Pregnancy morbidity

Answer 5

Fetal demise can occur at all gestational ages
Spontaneous abortions that occur from second trimester on are more specific for APS
Linked to preeclampsia
Linked to intrauterine growth retardation
HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)

Question 6

Antiphospholipid Antibody Syndrome clinical and lab criteria

Answer 6

Clinical Criteria:
Vascular Thrombosis
One or more clinical episodes without evidence of inflammation in the vessel wall

Pregnancy morbidity

• One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation
• One or more premature births of a morphologically normal neonate before the 34th week of gestation because of:
• – Eclampsia or severe preeclampsia, or
• – Recognized features of placenta insufficiency
• Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation

Laboratory Criteria

• Lupus anticoagulant in plasma
• Anticardioplipin antibody (IgG or IgM) present in medium or high titer
• Anti-β₂-glycoprotein I antibody (IgG or IgM) present in titer above the 99th percentile

Question 7

Antiphospholipid Antibody Syndrome Diagnosis

Answer 7

Patients should satisfy one or more clinical criteria and one or more laboratory criteria
Laboratory Criteria should be present on two or more occasions at least 12 weeks apart

Question 8

Antiphospholipid Antibody Syndrome- the antiphospholipid antibodies

Answer 8

Antiphospholipid Antibodies
5-10% of healthy population
50% of patients with SLE

Question 9

Antiphospholipid Antibody Syndrome Strongest thrombosis risk

Answer 9

Lupus anticoagulant, followed by Anti β₂-glycoprotein, followed by anticardiolipin antibodies
Highest risk of thrombosis occurs when all three antibody types present

Question 10

Antiphospholipid Antibody Syndrome Anticardiolipin Antibodies

Answer 10

Cross reacts with Rapid Plasma Reagin (RPR)
- False positive for syphilis
Greater sensitivity, but less specific than antibodies to β₂-glycoprotein I or lupus anticoagulants
Acute or chronic infections, especially viral, can induce anticardiolipin antibodies that do not correlate with APS and do not confer a risk of thrombosis

Question 11

Antiphospholipid Antibody Syndrome Anti-β₂-glycoprotein I Antibodies

Answer 11

More specific than anticardiolipin antibodies

Not seen in the context of viral infections

Question 12

Antiphospholipid Antibody Syndrome Lupus Anticoagulant activity

Answer 12

Antibodies that prolong in vitro phospholipid-dependent clotting assays, such as the Russel viper venom time
Not specific for SLE
Associated with risk of thrombosis, not bleeding
Antibody presence is inferred from their ability to interfere with a functional clotting assay in vitro
Patients with APS may have lupus anticoagulant activity but lack detectable anticardiolipin and anti-β2-glycoprotein I antibodies.

Question 13

Antiphospholipid Antibody Syndrome coagulation tests

Answer 13

Prolongation of in vitro coagulation test in which phospholipids are added to enhance the clotting reaction – dilute Russell viper venom time (dRVVT) or PTT

Antiphospholipid antibodies interfere with the added phospholipid causing prolongation of the clotting time

1:1 mix of patient and control plasma must fail to completely correct the abnormal clotting time, indicating presence of an inhibitor, rather than a factor deficiency is responsible for the abnormality

Inhibitor must be shown to be phospholipid-dependent by demonstrating normalization of the clotting time by the addition of molar-excess concentrations of the phospholipid reagent

Question 14

flow chart where LAC is positive

Answer 14

Step 1: functional clotting assay.  Prolonged clotting time?  Yes -->
Mixing study (1:1 patient/ control) -->  if clotting time corrects, it's a factor deficiency.  if NOT-->

Addition of excess phospholipid. Corrects? POSITIVE for LAC

Question 15

Antiphospholipid Antibody Syndrome treatment

Answer 15

Heparin
Warfarin

Pregnant Women
Heparin and ASA

Question 16

Scleroderma Most frequent symptoms

Answer 16

Raynaud phenomenon
Gastroesophageal reflux with or without dysmotility
Skin changes
Swollen fingers
Arthralgias

4-5 times more common in women

Average age of diagnosis is 50 years

Question 17

Scleroderma Diagnosis

Answer 17

A) Thickened skin changes proximal to the metacarpophalangeal joints

OR

B) Two out of the three following

1) Sclerodactyly
2) Digital pitting (loss of tissue on the finger pads due to ischemia
3) Bibasilar pulmonary fibrosis

Question 18

Limited Scleroderma

Answer 18

Three or more features of the CREST Syndrome

Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia

Question 19

Early or mild expression of Scleroderma

Answer 19

Raynaud’s phenomenon

with abnormal capillary loops or autoantibodies associated with scleroderma

Question 20

Scleroderma Skin- limited vs diffuse

Answer 20

Limited :
Face, distal to knees and elbows
CREST – sclerodactyly
No internal organ fibrosis
Associated with pulmonary                                                                                    hypertension

Diffuse:
Proximal extremity
Trunk
Internal organ fibrosis
Interstitial lung Disease
Worse Prognosis

Early on skin can be edematous and inflamed. This early disease is often associated with pruritus. Dermal fibroblasts overproduce extracellular matrix that leads to increased tissue collagen deposition in the skin. Collagen cross-linking then causes progressive skin tightening

Question 21

Scleroderma Skin later stages

Answer 21

Later Stages are associated with atrophy, dry, and scaly skin. Pruritus continues with excoriations and thickening of the skin.
Skin ulcers over contractures
Digital ischemic ulcers in 30-50% of patients
Pitted areas of distal fingers with loss of digital pad
Telangiectasias of face and palmer surface of hands
Subcutaneous calcinosis in small percentage of patients

Question 22

Scleroderma and Raynaud phenomenon

Answer 22

First disease manifestation in most scleroderma patients
Develops concurrently with other symptoms in diffuse disease
Precedes other symptoms by years in limited skin disease
Stress and cold temperature lead to an exaggerated vasoconstriction of small arteries, arterioles, and arteriovenous shunts or thermoregulatory vessels of the skin of the digits.
Pallor, cyanosis, and rubor
Often painful in scleroderma and can lead to digital ulcerations, gangrene, or amputation
Patients over the age of 30 with Raynaud phenomenon should be screened with an ANA and nailfold capillary examination

Question 23

Scleroderma Lung Disease

Answer 23

Interstitial fibrosis secondary to an inflammatory alveolitis

• Early diffuse scleroderma in the first 4 years
• Predictors of progression
• – Diffuse skin disease
• – African American Race
• – Early decline in FVC
• – Fibrosis on CT
• – Antitopoisomerase I antibodies (Anti-Scl-70)

Pulmonary Hypertension
- Occurs in longstanding disease

Question 24

testing for scleroderma lung disease

Answer 24

High Resolution CT Scanning
- Detects early pulmonary fibrosis

Pulmonary Function Testing

• Detect changes in FVC over time
• 80% of patients with scleroderma have restrictive disease
• 10-20% suffer from progressive severe interstitial lung disease

Echocardiography

• 25% of scleroderma patients have pulmonary hypertension
• 10-15% have severe pulmonary hypertension

Question 25

Physical Findings and EKG findings of Pulmonary Hypertension

Answer 25

``` Prominent P2 Right ventricular heaves Hepatomegaly Lower extremity edema EKG - Right axis deviation P-pulmonale - RBBB - R/S > 1 in lead V1 ```

Question 26

Scleroderma and GERD with dysphagia

Answer 26

Food getting stuck in esophagus, atypical chest pain, or cough Have to drink liquids to swallow meat or bread Secondary to smooth muscle atrophy Untreated can lead to esophagitis, esophageal ulceration, esophageal stricture, or Barrett esophagus Mucosal A-V malformations or telangiectasia in the wall of the stomach can lead to bleeding. GAVE (gastric antral vascular ectasia)

Question 27

Scleroderma GI

Answer 27

``` Small and Large Intestines: Smooth muscle atrophy Constipation alternating with diarrhea Pseudo-obstruction Pneumatosis coli intestinalis Bowel distention with leakage of air into the bowel wall Bowel Rupture Dysmotility Bacterial overgrowth leading to diarrhea and malabsorption Fecal incontinence ```

Question 28

Scleroderma Renal

Answer 28

Scleroderma Renal Crisis 5% of patients Sudden onset of malignant hypertension Untreated can lead to rapid renal failure and death Risk factors: - Treatment with glucocorticoids - Anti RNA-polymerase III antibodies - Diffuse scleroderma Symptoms - Headache, visual changes, or seizure Renal biopsy with intimal hyperplasia and vasospasm of the cortical arteries - Leads to activation of renin-angiotensin system and accelerated hypertension, proteinuria, microscopic hematuria, and thrombotic microangiopathy (schistocytes on peripheral blood smear)

Question 29

Scleroderma Cardiac

Answer 29

Morbidity primarily in late stages of scleroderma Microvascular disease and ischemia Arrhythmias, cardiomyopathy, or overt CHF Pericardial effusion frequently detected – usually clinically silent

Question 30

Scleroderma Musculoskeletal

Answer 30

``` Arthralgias Erosive arthritis Joint contractures Tendon friction rub - Ankles, wrists, and knees - Associated with increased disease activity and poor prognosis Weakness ```

Question 31

Scleroderma Laboratory

Answer 31

ANA with 95% sensitivity, but not specific Anticentromere antibodies - 20-40% of patients with scleroderma - Associated with limited skin involvement, more severe digital ischemia, and pulmonary hypertension (CREST) - Not specific to scleroderma - Also associated with primary biliary cirrhosis and Sjögren syndrome Antitopoisomerase I (anti-Scl-70) antibodies - 20-40% of patients with scleroderma - Diffuse skin changes, interstitial lung disease, and worse prognosis Anti-RNA Polymerase I/III antibodies - Rapidly progressive diffuse skin changes, higher risk or renal involvement, lower risk of interstitial lung disease

Question 32

Scleroderma Differential Diagnosis

Answer 32

Scleredema - Poorly controlled diabetics, monoclonal gammopathies, or post-infectious (Streptococcal pharyngitis - Upper back, proximal extremities, and mid-portion of back (spared in scleroderma) - Autoantibodies absent Scleromyxedema - Mucin deposition in the skin with cobblestone texture - Monoclonal gammopathy - Involves mid-back (spared in scleroderma), glabella, and ears - Neuro involvement in 10% of patients with seizures, global encephalopathy, and coma Eosinophilic fasciitis - Involves deeper tissues and has a “woody texture” - Peau d’orange texture of skin - Eosinophilia

Question 33

Scleroderma Prognosis

Answer 33

Limited Scleroderma - 90% 5 year survival Diffuse Skin Disease - 70-80% 5 year survival Predictors of poor outcome - High skin scores - Progressive lung disease - Tendon friction rubs - Evidence of heart disease - Pulmonary artery hypertension - Anemia - Scleroderma Renal Crisis

Question 34

Dermatomyositis and Polymyositis

Answer 34

Peak ages 45-60 years Symmetric proximal muscle weakness evolving over weeks to months - Difficulty rising from a low chair - Difficulty walking up stairs - Trouble washing or combing hair Severe cases - Weakness of neck flexors - Pharyngeal weakness - Diaphragmatic weakness

Question 35

Dermatomyositis and Polymyositis Extramuscular Manifestations

Answer 35

Systemic symptoms: fever, malaise, weight loss, arthralgia, and Raynaud phenomenon Joint Contractures Dysphagia Cardiac disturbance: AV defects, tachyarrhythmias, dilated cardiomyopathy, low ejection fraction, and CHF Dyspnea secondary to diaphragm weakness or interstitial lung disease Subcutaneous calcifications Arthralgias, synovitis, or deforming arthropathy

Question 36

Dermatomyositis and Polymyositis Physical examination

Answer 36

Weakness of proximal arm muscles and Hip Flexors - Deltoids, but often biceps and triceps - Hip Flexors, but hamstrings and quadriceps can be weak - Distal muscle weakness only with very severe proximal weakness ``` Skin: Gottron papules Photosensitive rash – Shawl Sign or V-sign Mechanic hands Periungal telangiectasias ```

Question 37

Dermatomyositis and Polymyositis Lab findings

Answer 37

Creatinine kinase, aldolase, AST, and LDH elevations after release from damaged muscles Anti-Jo-1 (aminoacyl tRNA synthetase) elevated in 30 % of patients - 50-75% will have interstitial lung disease - One of many synthetase autoantibodies Antisynthetase antibody positive patients may have one or more of the following clinical features - Interstitial lung disease - Nonerosive arthritis - Fevers - Raynaud phenomenon - Mechanics hands Antisynthetase syndrome – Antisynthetase antibody + 2 or more clinical features

Question 38

Dermatomyositis and Polymyositis MRI imaging

Answer 38

Most useful for evaluation of muscle edema as an indicator of active inflammation. Can detect areas of patchy involvement to locate a good biopsy site Useful to differentiate between active myositis and glucocorticoid-induced myopathy - Edema is indicative of ongoing inflammation Useful to monitor disease progression or response to treatment

Question 39

Dermatomyositis and Polymyositis Nerve Conduction Testing and EMG Testing

Answer 39

Detects whether weakness is due to a defect in the anterior horn cell, nerve, neuromuscular junction, or muscle

Question 40

Dermatomyositis and Polymyositis Muscle Biopsy

Answer 40

Should be performed in all patients except for those with the pathognomonic skin findings of dermatomyositis

Question 41

Dermatomyositis and Malignancy

Answer 41

Malignancy incidence increased in Dermatomyositis - ovarian cancer - breast cancer - melanoma - colon cancer - non-Hodgkin’s lymphoma These patients should have complete annual physicals with pelvic, breast, and rectal examinations. Mammograms and Colonoscopies as indicated

Question 42

Dermatomyositis and Polymyositis Treatment

Answer 42

Glucocorticoids Glucocorticoid sparing agents - Methotrexate - Azathioprine