Kinder CIS- Antiphospholipid Antibody Syndrome Flashcards
Antiphospholipid Antibody Syndrome
Acquired disorder associated with circulating autoantibodies to anionic phospholipids and their protein binding complexes
Antiphospholipid Antibody Syndrome Clinical manifestations
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
Antiphospholipid Antibody Syndrome Deep venous thrombosis
Lower extremities Pulmonary Embolism Renal vein thrombosis Retinal vein occlusion Budd-Chiari syndrome Adrenal hemorrhage secondary to thrombosis of the adrenal veins
Antiphospholipid Antibody Syndrome Arterial Disease
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
Antiphospholipid Antibody Syndrome Pregnancy morbidity
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)
Antiphospholipid Antibody Syndrome clinical and lab criteria
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
Antiphospholipid Antibody Syndrome Diagnosis
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
Antiphospholipid Antibody Syndrome- the antiphospholipid antibodies
Antiphospholipid Antibodies
5-10% of healthy population
50% of patients with SLE
Antiphospholipid Antibody Syndrome Strongest thrombosis risk
Lupus anticoagulant, followed by Anti β₂-glycoprotein, followed by anticardiolipin antibodies
Highest risk of thrombosis occurs when all three antibody types present
Antiphospholipid Antibody Syndrome Anticardiolipin Antibodies
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
Antiphospholipid Antibody Syndrome Anti-β₂-glycoprotein I Antibodies
More specific than anticardiolipin antibodies
Not seen in the context of viral infections
Antiphospholipid Antibody Syndrome Lupus Anticoagulant activity
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.
Antiphospholipid Antibody Syndrome coagulation tests
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
flow chart where LAC is positive
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
Antiphospholipid Antibody Syndrome treatment
Heparin
Warfarin
Pregnant Women
Heparin and ASA
Scleroderma Most frequent symptoms
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
Scleroderma Diagnosis
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
Limited Scleroderma
Three or more features of the CREST Syndrome
Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia
Early or mild expression of Scleroderma
Raynaud’s phenomenon
with abnormal capillary loops or autoantibodies associated with scleroderma
Scleroderma Skin- limited vs diffuse
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
Scleroderma Skin later stages
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
Scleroderma and Raynaud phenomenon
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
Scleroderma Lung Disease
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
testing for scleroderma lung disease
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
Physical Findings and EKG findings of Pulmonary Hypertension
Prominent P2 Right ventricular heaves Hepatomegaly Lower extremity edema EKG - Right axis deviation P-pulmonale - RBBB - R/S > 1 in lead V1
Scleroderma and GERD with dysphagia
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)
Scleroderma GI
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
Scleroderma Renal
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)
Scleroderma Cardiac
Morbidity primarily in late stages of scleroderma
Microvascular disease and ischemia
Arrhythmias, cardiomyopathy, or overt CHF
Pericardial effusion frequently detected – usually clinically silent
Scleroderma Musculoskeletal
Arthralgias Erosive arthritis Joint contractures Tendon friction rub - Ankles, wrists, and knees - Associated with increased disease activity and poor prognosis Weakness
Scleroderma Laboratory
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
Scleroderma Differential Diagnosis
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
Scleroderma Prognosis
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
Dermatomyositis and Polymyositis
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
Dermatomyositis and Polymyositis Extramuscular Manifestations
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
Dermatomyositis and Polymyositis Physical examination
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
Dermatomyositis and Polymyositis Lab findings
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
Dermatomyositis and Polymyositis MRI imaging
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
Dermatomyositis and Polymyositis Nerve Conduction Testing and EMG Testing
Detects whether weakness is due to a defect in the anterior horn cell, nerve, neuromuscular junction, or muscle
Dermatomyositis and Polymyositis Muscle Biopsy
Should be performed in all patients except for those with the pathognomonic skin findings of dermatomyositis
Dermatomyositis and Malignancy
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
Dermatomyositis and Polymyositis Treatment
Glucocorticoids
Glucocorticoid sparing agents
- Methotrexate
- Azathioprine
