Connective Tissue Diseases Flashcards
+ ANA is loosely associated with underlying autoimmune diseases. ANA patterns are not specific for individual autoimmune disorders, and a positive test by indirect immunofluorescence often leads to additional testing to detect specific, disease-associated autoantibodies. What defines a normal vs. positive ANA titer?
Normal/negative = titer of <1:40
Positive/clinically significant = 1:160 [higher the ratio, more clinically significant]
Another name for c-ANCA
PR3-ANCA
Another name for p-ANCA
MPO-ANCA
A homogenous staining pattern on immunofluorescence means that the entire nucleus is diffusely stained. What antibodies typically stain this way?
Antibodies include those directed against chromatin, histone proteins, and DNA
Typically corresponds with:
*Drug-induced SLE
Sjogrens syndrome
SLE
A speckled staining pattern on immunofluorescence means that fine or coarse speckles are seen throughout the nucleus. What antibodies typically stain this way?
This is a nonspecific pattern — many different Abs stain this way, including those against UI RNP, Sm, and La
Typically corresponds with: Mixed CT disease Diffuse systemic sclerosis Sjogren’s syndrome SLE
________ pattern of immunofluorescence staining that refers to the presence of 30-60 uniform speckles distributed through the nucleus of resting cells.
In mitotic cells, the speckles localize to the chromosomes at the metaphase plate. This pattern is seen with ________
Centromere
Limited systemic sclerosis (CREST)
_______ pattern of immunofluorescence refers to homogenous or speckled staining of the nucleolus
Typically corresponds to Abs directed against fibrillarin, ___________, Th, PM-Scl, and RNA helicase.
Corresponds with conditions such as ______ and _______
Nucleolar
RNA polymerase I and III
Diffuse systemic sclerosis; SLE
SLE is a multisystem inflammatory autoimmune disease of unknown etiology, but is related to T and B cell hyperactivity with autoantibodies to nuclear antigens, making it a ____________ HSR
It is characterized by spontaneous remissions and relapses with varying severity and presentation. It is more common in females, and in terms of race it is more common in _____ and _____. Socioeconomic factors are correlated with increased incidence as well. Genetic and environmental factors are also suspected, including sex hormones, UV light, and viruses such as ______
Type III HSR
African Americans; Hispanics; EBV
Constitutional, cutaneous, and joint findings associated with SLE
Constitutional: fatigue, fever, malaise, weight loss
Cutaneous: rashes (malar), photosensitivity, vasculitis, alopecia, oral ulcers
Joints: inflammatory, symmetric, non-erosive arthritis
Hematologic, cardiopulmonary, and renal features of SLE
Hematologic: anemia (may be hemolytic), neutropenia, thrombocytopenia, LAD, splenomegaly, venous or arterial thrombosis
Cardiopulm: pleuritis, pericarditis, myocarditis, endocarditis; increased risk of MI d/t accelerated atherosclerosis
Renal: lupus nephritis
GI and neurologic features of SLE
GI: peritonitis, vasculitis (may present with intestinal angina)
Neurologic: organic brain syndromes, seizures, psychosis, cerebritis
Labs to order when SLE is suspected
CBC
ESR
ANA + ANA subtypes
Antibodies to: dsDNA, Sm, Ro/SS-A, La/SS-B, histone
Complement levels (C3, C4, CH50)
PT, PTT
Anti-cardiolipin antibody
Lupus anticoagulant
Urinalysis
SLE serology includes positive ANA, positive __________, which correlates with disease activity, and _________ - which does NOT correlate with disease activity
_______ or _____ may also be decreased indicating increased consumption during an inflammatory process, suggesting disease activity. These will return to normal when in a period of remission
Anti-dsDNA; Anti-Sm
C3; C4
1/3 of SLE pts have a secondary ______ ______ ______ which may be categorized as type 1, type 2, or type 3; Note that antibodies should be measured on 2 occasions, 12 weeks apart
Antiphospholipid antibody syndrome
Type of antiphospholipid antibody syndrome associated with SLE that is a risk factor for venous and arterial thrombosis and miscarriage and causes prolongation of the aPTT
Type 2: Lupus anticoagulant
How is presence of lupus anticoagulant confirmed in type 2 APA with SLE?
Abnormal dilute Russel viper venom time (DRVVT) — corrects with addition of phospholipid but not normal plasma
Type of antiphospholipid antibody syndrome associated with SLE that is directed at serum cofactor beta-2glycoprotein I (Beta2GPI)
Type 3: Anti-cardiolipin antibodies
Type of antiphospholipid antibody syndrome associated with SLE that causes biologic false-positive tests for syphilis (VDRL) due to measurement of IgG and IgM antibodies to a cardiolipin-lecithin-cholesterol antigen complex
Type 1
Describe treatment of SLE with secondary APS — note how this changes during pregnancy
Anticoagulation, continued indefinitely
Start LMWH first, then bridge to vitamin K antagonists (like warfarin, which remain the standard of care) to achieve INR of 2-3 (goal 2.5)
Pregnancy — LMWH (enoxaparin) + aspirin [warfarin contraindicated]
Cotton wool spots in the setting of suspected immune-mediated disease are indicative of _______ retinopathy
SLE/APS
Drug-induced lupus occurs when there is promotion of ________ of DNA. Contrary to SLE, there are no associated ______ or _______ symptoms.
These pts will be positive for ANA as well as _______ antibodies (95%)
Demethylation; renal; neurologic
Anti-histone
Drugs associated with drug-induced lupus
Hydralazine Isoniazid Minocycline TNF inhibitors Quinidine Chlorpromazine Methyldopa Procainamide
_____ antibiotics are associated with risk of SLE flare
Sulfa
Lupus in pregnancy is associated with what complications?
Gestational HTN (preeclampsia)
Fetal growth restriction
Fetal distress —> fetal loss or premature delivery
Neonatal lupus affects children born of mothers with what antibodies?
Anti-Ro (SSA) or Anti-La (SSB)
Clinical features associated with neonatal lupus
Transient symptoms include: rashes, thrombocytopenia, hemolytic anemia, arthritis
Complications: permanent complete heart block
Non-pharmacologic/preventative treatment measures in SLE pts
Avoid sun exposure and wear sunscreen
Avoid smoking and minimize other risk factors for atherosclerosis
Annual influenza vaccine and pneumococcal vaccine every 5 years
Preventative cancer screening recommendations should be followed closely since these pts have increased risk of malignancy
Be wary of degree of corticosteroid use — long-term increases risk of avascular necrosis of bone
Pharmacologic treatment options for SLE
NSAIDs
Corticosteroids (topical or systemic)
Hydroxychloroquine
Azathioprine Methotrexate Mycophenolate mofetil Cyclophosphamide IVIG Plasmapheresis Monoclonal Abs
Describe the bimodal pattern of mortality associated with SLE
In the early years after diagnosis:
Opportunistic infections; active SLE issues with kidney or CNS disease
In later years: Accelerated atherosclerosis (linked to chronic inflammation) — increased rate of MI and thromboembolic events
Libman sacks endocarditis is associated with _____
SLE
Type of lupus that resembles ringworm or psoriasis
Discoid lupus
Demographics of scleroderma (systemic sclerosis)
Age 30-60
W>M
Increased severity seen in African Americans
Hallmark clinical findings associated with scleroderma
Thickening and hardening of skin
Microangiopathy and fibrosis of skin and visceral organs; affects skin, lungs, GI, kidney, MSK, and heart
Virtually all scleroderma (systemic sclerosis) pts experience secondary ______ phenomenon
Raynaud
What causes the dry, itchy skin associated with scleroderma?
Obliteration of eccrine sweat glands and sebaceous glands
T/F: There is no approved disease-modifying therapy for scleroderma; treatment involves symptomatic control to improve quality of life and prolong survival
True
Name the 3 types of scleroderma and which one has the worst px
Diffuse (dcSSc) = worst px
Limited (lcSSc)
Localized
Clinical features of diffuse scleroderma
Systemic, diffuse involvement including proximal extremities and trunk
Early and progressive internal organ involvement — especially kidney, cardiac, and INTERSTITIAL LUNG DISEASE
Worst prognosis
Clinical features of limited scleroderma
Fingers, toes, face/neck, distal extremities
Raynaud’s commonly precedes other symptoms (susceptible to digital ischemia)
CREST syndrome
Indolent course
Good prognosis
Clinical features of localized scleroderma
Benign skin conditions; affects CHILDREN
Discrete areas of discolored skin induration (patches = morphea, coalesced patches = generalized morphea)
NO Raynaud’s
NOT systemic
Histologically indistinguishable from SSc
What are the components of CREST syndrome and what autoimmune condition is this associated with?
Calcinosis cutis
Raynauds
Esophageal dysmotility
Sclerodactyly
Telangiectasia
[associated with limited scleroderma]
Scleroderma serology includes positive ANA titers.
What other antibody titers are present in diffuse cutaneous scleroderma?
Anti-Scl 70 (aka anti-DNA topoisomerase I)
Anti-RNA polymerase III
Scleroderma serology includes positive ANA titers.
What other antibody titers are present in limited cutaneous scleroderma?
+ Anti-centromere
T/F: no therapy to date significantly alters disease course of scleroderma, and tx goal is to manage organ system involvement
True
However tx strategies do exist, including education, CCBs, ACEIs, PPIs, glucocorticoids, cyclophosphamide, PDE5-I, etc
What component of H and P is important to consider in work up of a scleroderma pt?
Blood pressure — heralding feature of renal disease
What labs, radiographs, and additional studies are important to consider in a scleroderma pt?
Labs: ESR, ANA
Radiographs: CXR, barium swallow if indicated, hand X-ray may show distal tuft resorption and calcinosis
Additional studies: ECG, echo, PFT, consider skin biopsy