RA, AS, SLE, Sjogren's, SS, Vasculitis (Week 3--Weinreb) Flashcards
Rheumatoid arthritis (RA)
Chronic systemic autoimmune disease defined by presence of symmetric inflammatory polyarthritis that primarily affects small joints of the hands (PIP, MCP) and can have variable extraarticular involvement
Can be associated with significant morbidity and disability due to irreversible joint damage and increased mortality, but early treatment can result in significantly improved outcomes (early recognition is key!)
Prevalence of RA
Prevalance from 0.1-1.1%
Higher prevalence in populations of European descent and lower prevalence in populations of Asian descent
Native American populations have prevalence of 5-7% (so maybe caused by “New World” infection)
Associated with smoking especially in HLA-BRD1 allele
>20 candidate genes for susceptibility
Women have 2-3 times increased risk
Key pathophysiologic features of RA
Articular and systemic inflammation:
1) Pannus formation: synovial swelling, inflammation; cartilage loss and bone erosions; joint damage and loss of function
2) Osteoclast activation: bone erosions; periarticular osteopenia and joint damage
3) Extraarticular manifestations
Overall: swelling, bone erosions, joint damage
Other pathology you can see with RA
Hypertrophic villous synovium
Proliferation, inflammatory cell infiltration and lymphocytic clusters
Pannus causing (?) eroded cartilage
RA clinical presentation: history
Insidious with increasing symptoms over weeks to months that progress to characteristic chronic symmetrical polyarthritis
Fatigue, low grade fever, weakness, weight loss
Pain, swelling, stiffness (morning or after prolonged inactivity, >30 min to hours) of hands and to varying degrees of other small, intermediate, and large joints; tenosynovitis
Loss of function acutely secondary to pain and stiffness from active inflammation and chronically secondary to joint deformities associated with joint damage from progression of marginal bony erosions and joint space narrowing
Spontaneous remissions rare
RA clinical presentation: articular findings on exam
Symmetric synovitis (inflammatory arthritis) of PIP and MCP joints, not DIPs
Deformities: finger joint tendon weakening resulting in subluxations (swan-neck, boutonniere, ulnar deviation); severe deformity due to progressive bony erosions (arthritis mutilans); muscle atrophy from disuse
Rheumatoid nodules: granulomatous nodules at sites of pressure or friction (subcutaneous, tendons, bursae, less commonly in soft tissues); usually benign but may interfere with joint function and associated with more disease
Finger extensor tendon rupture: loss of extension due to tendon rupture from mechanical forces related to joint deformities, nodules, and/or tenosynovitis
Spine: cervical spine only, transverse ligament weakening and subluxation of C1 on C2 and risk of spinal cord impingement/compression by odontoid (dens) leading to extremity weakness or sensation loss; C1/2 joint synovitis can result in spinal cord impingement
Radiologic changes seen in RA
Marginal bony erosions associated with increased risk of deformities and further cartilage and bony destruction leading to loss of joint function!
Symmetrical joint space narrowing
What tests are associated with increased risk of erosive disease in RA?
Elevated CRP
Seropositivity (positive RF or anti-CCP (cyclic citrullinated antibody) titers)
RA deformities
Swan neck (extension of PIP, flexion of DIP)
Boutonniere (flexion of PIP, extension of DIP)
Ulnar deviation of fingers
Arthritis mutilans (feel like bag of bone)
Tendon rupture/nodules in RA
Swelling of tendon sheaths due to synovitis of lining synovium
Rupture of extensor tendons results in inability to extend fingers
Rheumatoid nodules on extensor tendons (nodules are monocytes, vascular inflammation, mostly not problem other than cosmetic, mostly occur on extensor surfaces; associated with more erosive RA)
RA clinical presentation: extraarticular findings
Muscle weakness: disuse atrophy, drug related, neuropathy, inflammatory (rare)
Bone: osteopenia secondary to inflammation, decreased activity, steroids
Eye: dry eyes common; “red eye RA”; episcleritis due to superficial scleral inflammation; scleritis due to deeper scleral inflammation; scleral thinning and/or perforation; keratitis or corneal inflammation (“corneal melt”) that can result in corneal destruction and loss of vision–medical emergency; infections secondary to treatment
Pulmonary: mild inflammatory (interstitial) lung disease, small airway obstruction; nodules; Caplan’s syndrome (nodulosis secondary to exposure to coal dust, seen in West Virginia, not much in CA…)
Cardiac: rarely pericarditis, myocarditis; increased risk of CAD
Hematologic: Felty’s syndrome characterized by splenomegaly and neutropenia; severe neutropenia (<1,000/mm3) associated with increased risk of infection
Malignancy: increased risk of B-cell lymphoma; less commonly large granular lymphocyte syndrome (T-cell/NK cell lymphoproliferative syndrome)
Rheumatoid scleritis vs. rheumatoid episcleritis
Rheumatoid scleritis: painful inflammation of deeper scleral layers; often associated with rheumatoid vasculitis
Rheumatoid episcleritis: painless or minimally painful inflammation of superficial scleral layers
How useful is RF in diagnosing RA?
Helpful when history and exam suggestive of RA
Sensitivity is 80% and specificity is 85%
Due to decreased specificity, should not be used as screening test for RA
RF positivity associated with increased risk of nodules and erosive disease
Changes in RF titer not associated with changes in disease activity
Cyclic citrullinated peptide antibody (Anti-CCP)
Antibody that recognizes peptide of protein fillagrin containing citrullinated arginine residue; associated with heavy tobacco use
Sensitivity 48% (less than RF); specificity 96% (more than RF)
Associated with increased risk of developing bony erosions
May be positive 3-4 years prior to onset of RA (role in early diagnosis?)
Diagnosis of RA
History and physical find symmetrical polyarthritis
Positive RF and/or anti-CCP support diagnosis but don’t rule in or out RA on their own
Symmetrical joint space narrowing, marginal erosions help assess severity but may be absent in early stage or not develop
MRI or ultrasound help detect subclinical synovitis or erosive changes not seen on plain X-rays
Management of RA
Determine severity of involvement
Control pain from inflammation and improve function
Prevent development or progression of bony erosions/joint damage
Treat extraarticular manifestations
Medication: NSAIDs, steroids, DMARDs (disease modifying antirheumatic drugs), biologics (antibodies or receptor antagonists targeting specific RA pathways–inflammation, erosions (anti-IL1, anti-TNF, anti-I16, anti-CD20, costim inhibition)
Seronegative spondyloarthropathy (SpA)
Group of inflammatory arthritic diseases that variably share similar pattern of asymmetric oligoarticular (2-4 joints) peripheral arthritis
Variably present with sacroiliitis, spondylitis, enthesitis, extraskeletal involvement (eye, bowel, lungs, heart)
Negative for RF (seronegative!!)
Axial involvement (spine, SI joints) typically associated with presence of Class I HLA-B27 allele
Ankylosing Spondylitis (AS) pathophysiology
Axial spondylarthritis: bilateral symmetric sacroiliitis (SI joint inflammation that progresses to erosion and widening then fusion (ankylosis))
Spondylitis to a variable extent: enthesitis of spinal ligaments and capsular attachments resulting in erosions (vertebral squaring, shiny corners) then ligament calcification (syndesmophytes–thin whispy calcification from one corner/margin to the other); progressive ligamentous calcification results in vertebral fusion (“bamboo” spine) from lumbar to cervical spine regions
Prevalence of AS
90% of disease susceptibility due to genetics with 90% contributed by HLA-B27 (+8 additional susceptibility genetic loci/genes); environmental factors unknown
More common in men, peak age of onset between 20 and 30
Ethnic differences because of population differences in HLA-B27 allele
AS clinical presentation: axial
Sacroiliitis: inflammatory back pain, variable morning pain and back stiffness (>30 min) improves with exercise and worse with rest, buttocks pain, nighttime pain while sleeping
Spondylitis: progressive spine fusion leads to loss of lumbar lordosis, decreased cervical spine ROM and cervical kyphosis, decreased chest expansion due to enthesitis of costovertebral joints; spine fusion results in extremely limited range of spinal motion and disability and stiff chalk-like spine increases risk of pseudofracture through fused segments
Costosternal/manubriosternal joints can get enthesitis and chest pain
AS clinical presentation: peripheral joint arthritis
15% of AS patients
Shoulder and hip arthritis are most common
Progressive hip joint arthritis is bad bc can lead to hip joint fusion and fixed flexion contractures; with fused spine, hip joint contractures result in forward bending which exacerbates disability
Enthesitis at elbow condyles, pelvis, spinous processes, patella, tibial tubercle, Achilles tendon, plantar fascia
AS clinical presentation: extraarticular involvement
Opthalmologic: acute anterior uveitis; unilateral and characterized by redness, pain, diminished visual acuity, photophobia; associated with HLA-B27
Cardiac: aortic inflammation can lead to aortic dilatation and aortic valve incompetence
Pulmonary: rarely interstitial lung disease (upper lobes)
GI: “cryptic” or asymptomatic colitis of ilium and/or colon
Neurologic: secondary to nerve impingement from spinal disease; cord impingement secondary pseudofractures and formation of unstable pseudoarthrosis
Diagnosis of AS
History of inflammatory back pain, limited spinal ROM, enthesitis, radiologic findings
>95% of patients with AS are HLA-B27 positive but only 5% of carriers of HLA-B27 develop AS, so not a good screening test
Positive HLA-B27 with strong history, exam, X-ray supports AS diagnosis
Negative HLA-B27 with weak history, exam, X-ray rules out AS diagnosis
But negative result does NOT rule out AS if clinical findings are strong
Reactive Arthritis
Oligoarticular arthritis develops 1-4 weeks after infection (may be subclinical but usually is GI, GU (STDs like chlamydia), URI)
Peripheral arthritis: acute, asymmetric, oligoarticular; erosive in 10-15%, chronic in 15-50%
Axial skeletal involvement: asymmetric sacroiliitis in 20% and asymmetric spondylitis
Tenosynovitis and enthesitis: digital tendon sheath and enthesial inflammation can result in dactylitis which appears as sausage-like swelling of the digit
Extraacticular: conjunctivitis, urethritis, oral ulcers, genital ulcers, circinate balanitis (rash on glans of penis), hyperkeratotic vesicular psoriasis-like rash on palms and soles called keratoderma blennorrhagica
HLA-B27: (less impt than in AS); 60-80% positive, associated with more severe arthritis, sacroiliitis and spondylitis, extraarticular manifestations, more chronic disease course
Psoriatic Arthritis (PsA)
Inflammatory arthritis of variable joint involvement associated with psoriasis (prevalence: 7-40% with psoriasis) but rarely occurs without psoriasis
Variable presentation: arthralgias, true synovitis, enthesitis, dactylitis (sausage fingers)
Variable patterns of joint involvement: distal arthritis (DIPs), asymmetric oligoarthritis, symmetric polyarthritis (similar to RA but with DIP involvement), arthritis mutilans, spondylarthritis
Variable characteristic peripheral radiologic findings: normal, enthesitis, erosive arthritis, “pencil in cup”, joint fusion (ankylosis)
Variable axial radiologic findings: normal, asymmetric sacroiliitis, asymmetric spondylitis (axial involvement more likely in HLA-B27+ individuals)
Systemic lupus erythematosus (SLE)
Systemic autoimmune disease affecting multiple organ systems
Pathologic antibody production
Susceptibility genes and environmental factors (maybe UV light, poorly understood)
Key pathophysiologic mechanisms in SLE
1) Impaired apoptosis leading to secondary necrosis, intracellular antigen exposure, innate immune system inflammation
2) Loss of tolerance and immune system dysregulation –> increased production of pathogenic autoantibodies
3) Increased formation and impaired clearance of immune complexes
4) Inflammation and tissue damage from immune complex complement activation, other autoantibodies and the effects of altered cytokine production (ex: increased production of INF-alpha)
Different types of pathogenic antibodies in SLE
1) Depleting or neutralizing antibodies: directed against plasma protein or cells that results in loss of function; can form immune complexes
2) Cytotoxic (antibody dependent cellular cytotoxicity (ADCC)): against self-antigens on cells leading to cell death
3) Agonistic/Activating antibodies: specifically stimulate a cell receptor or plasma protein leading to activation of cell/protein
4) Inhibitory antibodies: bind cell receptor and inhibit a cellular function
Key inflammatory cytokine abnormality in SLE
Interferon-alpha is increased
SLE epidemiology
51/100,000 prevalence or 2-8/100,000 per year
Female 9x more likely to get it than male, and might be due to sex hormones
Disease onset between 16-55 for the most part
Prevalence and severity of disease higher in AA and hispanics (however, prob due to socioeconomic status, not pathophysiology…)
Clinical presentation of SLE
Systemic autoimmune inflammation involving multiple organ systems
Varying symptoms, and can be mild (“rodeo drive lupus”) or life-threatening
Chronic medical problems secondary to end-organ damage
“I’M DAMN SHARP”
Immunoglobulins
Malar rash
Discoid rash
ANA
Mucositis (oral ulcers)
Neurologic disorders
Serositis (pleuritis, pericarditis)
Hematologic disorders
Arthritis
Renal disorders
Photosensitivity
1997 ACR criteria for SLE
Sensitive and specific clinical lab findings to define patients as having SLE (for reserach) and to diagnose SLE
Malar rash (“butterfly” spares nasolabial folds), discoid rash (scaly erythematous rash w/follicular plugs, heals w/scaring), photosensitivity, oral ulcers, arthritis, seorsitis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder, antinuclear antibodies (ANA)
If 4/11 of these are present, 98% specificity and 97% sensitivity for SLE! (good for research purposes)
Subacute cutaneous lupus (SCLE)
Associated with anti-SSA (Rho) antibodies
Papulosquamous or annular skin disease
Lupus band test
Immunofluorescent staining for IgG and complement at the dermoepidermal junction
Can involve affected and unaffected skin
Not specific test
Clinical pearl for SLE!
Painless oral ulcer
May correlate with disease activity
Check for nasal mucosal ulcers!
Nephritis in SLE
Deposition/formation of immune complexes (IC) and complement binding in the kidney –> inflammation and lupus nephritis
Location of ICs associated with different types of nephritis: 1,2 (subepithelial), 3 (subendothelial), 4 (mesangial)
Find anti-dsDNA antibodies
Classification of SLE nephritis
Class I: minimal mesangial
Class II: mesangial proliferative
Class III: focal proliferative glomerulonephritis (GN)
Class IV: diffuse proliferative GN
Class V: membranous nephritis
Class VI: advanced sclerotic nephritis
Note: glomerulonephritis is inflammation involving glomerulus and resulting in damage and renal dysfunction
Clinical presentation of SLE nephritis
Varying degrees of renal failure, hematuria, pyuria, proteinuria; increased morbidity and mortality
Active renal involvement associated with increased anti-dsDNA antibodies and low complement C3/C4 (bc consumed by ICs! However, not always because you’re producing more C3/C4 also)
Neurospychiatric SLE
Many neuropsychiatric manifestations of SLE (NPSLE)
Many mechanisms: for example, agonistic antibody can activate NMDA receptor on neurons
ANA test for SLE
ANA test to detect antinuclear antibodies
Titer and pattern of staining is reported
Also, level of antibodies to specific nuclear antigens are determined to provide increased sensitivity and specificity for SLE and other conditions
99% sensitivity: less than 1% of people with lupus will have positive ANA
But low specificity
What rheumatic diseases is ANA useful for?
SLE (99% sensitivity)
Drug-induced lupus (95-100%)
ANA is not very specific, so what other non-rheumatic conditions is it elevated in?
Liver disease, pulmonary disease, chronic infections, hematologic conditions, malignancies, other
Patterns of ANA reactivity
Peripheral
Speckled
Homogeneous
Nucleolar
Antinuclear antibody associations
dsDNA: high sensitivity and specificity, helpful diagnostically for SLE, correlates with disease activity (esp nephritis)
Histones: drug-induced lupus
Ro(SS-A) and La(SS-B): neonatal lupus (subacute cutaneous lupus for Ro(SS-A)
Sm: high specificity for SLE (low sensitivity), helpful diagnostically but no SLE associations
(ANA: high sensitivity (good for screening), low specificity)
Activation of thrombosis by antiphospholipid (aPL) antibodies in SLE
Increased prevalence of aPL antibodies in SLE patients (20-50%)
aPL antibody binding results in release of tissue factor (TF) and other inflammatory mediators, promoting a prothrombotic state (activating antibody)
What can antiphospholipid (aPL) antibodies cause?
Central retinal artery occlusion
Cerebral infarct
Recurrent miscarriage
Deep vein thrombosis
Digital ischemia
Livedo reticularis
Clinical use of ANA and antinuclear antibody subsets in SLE
+ANA only helpful if SLE clinically suspected
Not a useful screening test
ANA titer doesn’t correlate with SLE disease activity
ANA sensitivity for SLE (99%) so negative test means SLE very unlikely
anti-dsDNA and anti-Sm very specific for SLE
Drug-induced lupus
Strong association with hydralazine, isoniazid, minocycline, anti-TNFalpha
More abrupt onset and less severe manifestations of SLE (fever, rash, arthralgias/arthritis, serositis)
Positive ANA and anti-histone antinuclear antibodies
Symptoms resolve after stopping medication
Treat just with NSAIDs, steroids for symptoms
Mechanism of disease unclear
Management of SLE
Treat early and aggressively to prevent end-organ damage
Prevent flares (hydroxychloroquine)
NSAIDs, steroids, antimalarials, immunosuppressives
Sjogren’s Syndrome
Autoimmune lymphocytic (primarily CD4+ and B-cell) infiltration of exocrine glands resulting in glandular damage and subsequent dysfunction/loss of funtion
Extraglandular involvement: arthritis, lymphocytic infiltration of various organs, lymphoma
Can antibodies be used to diagnose Sjogren’s syndrome?
Only if clinical findings suggestive, because antibodies are not sensitive or specific
ANA, anti-SSA, anti-SSB, RF
What is the gold standard for diagnosis of Sjogren’s syndrome?
Biopsy shows lymphocytic infiltration and salivary gland destruction
Do minor salivary gland biopsy from inner lip
Clinical features of Sjogren’s syndrome
Dry mouth (xerostomia –> leads to dental cavities (carries)
Dry eyes (xeroophthalmia)
Dry tracheobronchial mucosa (xerotrachea)
Dry skin (xerosis) and vaginal mucosa
Major salivary gland enlargement
Pancreatic exocrine dysfunction and hypochlorhydria
Extraglandular: constitutional (fatigue, low grade fever, myalgias), arthritis/arthralgias
Sicca (dry eyes and mouth together) related findings in Sjogren’s syndrome
Xerostomia
Dental decay
Parotid enlargement
Keratoconjunctiva sicca: rose bengal staining showing corneal abrasions (abrasions happen because of dryness)
(STEP 1 says: dry eyes, dry mouth, nasal and vaginal dryness, chronic bronchitis, reflux esophagitis, NO arthritis)
Neonatal lupus
Subacute cutaneous SLE (SCLE)
Anti-SSA (Rho) antibodies
These antibodies can react and lead to a range of cardiac electrical abnormalities (cytotoxic effect of anti-SSA)
Systemic sclerosis (Scleroderma)
Complex systemic disease characterized by excessive extracellular matrix deposition that is caused by underlying autoimmunity, vasculopathy and tissue fibrosis
Interaction between genes and environment
More prevalent in women, increased susceptibility of AAs
Can be limited or diffuse cutaneous sclerosis
Proposed environmental triggers for systemic sclerosis
Infection
Drugs
Chemical exposures (vinyl chloride, silica)
Maternal lymphocyte exposure in fetus or felat lymphocyte exposure in mother causing graft vs. host reaction that progresses to SS
However, not clear
Early and late phases of SS
Early: (1) immunologic and inflammatory (T and B cell activation, monocytes, autoantibodies, cytokines, growth factors); (2) vascular (endothelial cell damage and apoptosis, increased vascular reactivity, vascular smooth muscle cell and pericyte proliferation leading to increased vessel wall thickness, ROS, hypoxemia, vascular loss)
Late: fibrotic (fibroblast activation and differentiation to myofibroblasts (contractile cells), collagen overproduction, increased deposition, remodeling in blood vessel walls and other tissues)
Limited sclerosis vs. diffuse sclerosis
Clinical subgroups defined by extent of skin thickening and tightening; limited and diffuse have overlapping systemic features
Limited sclerosis: 60% of cases; only involves distal extremities (up to elbows and/or knees), face and neck but NOT the trunk; longstanding Raynaud’s that may preceed onset; no tendon friction rubs; isolated pulmonary HTN, anticentromere antibodies (60-90%); more gradual and less extensive skin involvement
Diffuse sclerosis: 30% of cases; involves entire extremities, face, neck and trunk; Raynaud’s associated with skin changes or later; tendon friction rubs; more widespread and extensive internal organ involvement (renal disease, ILD (fibrosis), severe and diffuse GI disease, cardiac); anti-Scl-70 antibodies (20-30%); more rapid and extensive skin involvement
Other types of sclerosis
Don’t need to know these
Scleroderma sine scleroderma: systemic disease without skin involvement, rare
Overlap syndromes: association of findings with other autoimmune diseases
Systemic sclerosis: cutaneous
On skin biopsy, see denser collagen, loss of skin appendages (hair follicles), focus of inflammation
Early finding is edema of hands (immune/inflammatory)
Skin thickening on hands and neck
Sclerodactyly: tightened skin (shiny, loss of creases) and tethered of tendons resulting in fixed flexion contractures; can be severe causing significant disability (fibrotic)
Tightening of skin over face and mouth resulting in diminished oral aperture (fibrotic)
Furrowing of skin around mouth secondary to skin tightening (fibrotic)
Cutaneous calcinosis and subcutaneous calcinosis (immune or vascular?)
Facial and inner lip telengictasia (vascular)
Capillary loop dilation and capillary dropout/loss
Raynaud’s phenomenon (vascular)
Digital tip ulcerations secondary to ischemia (vascular), cause digital pits/scars after they heal
Digital gangrene secondary to severe vasculopathy (vessel constriction and obliteration)
Digital phalangeal tuft resorption (bone resorption) (vascular)
Systemic sclerosis: vasculopathy
Vasoconstriction, impaired relaxation
Over time, get vascular wall remodeling (proliferation of smooth muscle cells, then fibrosis)
Vascular obliteration and tissue hypoxia (which contributes to fibrosis)
Raynaud’s Phenomenon
Characteristic sequence of white, blue, red in fingers (and other extremities)
First in response to cold, get constriction of arterioles and white blanching (constriction) –> then because of decreased blood flow to fingers and decreased outflow so get blue (congestion) –> then get increased inflow again and become red (hyperemia)
Note: Raynaud’s symptoms can occur in the absence of any underlying disease
Systemic sclerosis: fibrosis
Collagen production, deposition; matrix contracture, remodeling
Tissue fibrosis; organ dysfunction
Systemic sclerosis: pulmonary disease
Primary cause of morbidity and mortality in systemic sclerosis
Spectrum of pulmonary infolvement:
1) isolated pulmonary arterial hypertension (PAH)
2) Interstitial lung disease/pulmonary fibrosis
3) Combined presentation
Systemic scleorsis: pulmonary disease–PAH
Isolated pulmonary hypertension (PAH):
More often in limited sclerosis
Secondary to vasoconstriction/impaired vascular relaxation
Characteristic history of dyspnea on exertion; O2 desaturation with exertion
Can result in right sided heart failure (cor pulmonale)
Treatment with arterial vasodilators can improve symptoms and survival
Systemic sclerosis: pulmonary disease–ILD
Interstitial lung disease/pulmonary fibrosis:
More frequent and extensive in systemic sclerosis
Secondary to fibrosis
Presents with chronic dry cough and worsening dyspnea; hypoxemia
Both lung inflammation (alveolitis) and fibrosis result in destruction and irreversible loss of lung tissue
Usually progressive, resulting in increased mortality
No treatments to reverse process; cytotoxic therapy may slow/prevent progression
Honeycombing seen on CT (?), characteristic of fibrosis
Systemic sclerosis: cardiac
Symptomatic cardiac involvement also associated with increased mortality
Most common type of involvement is right heart failure secondary to PAH
Less commonly, primary involvement due to vasculopathy (ischemia and arrhythmias) and/or fibrosis (heart failure and arrhythmias) can occur
Systemic sclerosis: renal
Scleroderma renal crisis:
More commonly associated with diffuse sclerosis
Usually occurs within first five years of disease
Characterized by acute renal failure and severe hypertension
Used to be major cause of mortality until ACE inhibitors found to be effective
See pruning and loss of vasculature on angiogram
See onion skin appearance of glomerulus on renal biopsy from patient with scleroderma renal crisis
Systemic sclerosis: GI
Diminished oral aperture may contribute to poor oral intake
Early esophageal dysmotility (vascular): poor peristalsis and impaired lower sphincter function can result in sensation of food getting stuck in chest (dysphagia) and GERD; see dilated distal esophagus on imaging
Late esophageal dysmotility (fibrotic): poor peristalsis results in dilated esophagus with associated dyphagia; chronic GERD can result in distal esophageal stricture and obstruction
GI bleeding from colonic telengiectasia and gastric telengiectasia (severe GI bleeding, also watermelon stomach (vascular))
Intestinal dilatation (vascular and fibrotic): slow transit, constipation and ileus (functional obstruction)
Diagnosis of systemic sclerosis
Presence of characteristic cutaneous findings in conjunction with other findings of systemic involvement
Early in disease, systemic features subclinical and need special testing to identify
Skin findings of other fibrosing conditions may seem similar to systemic sclerosis; but systemic nature of scleroderma is distinguishing
Treatment of systemic sclerosis
Treatment for symptoms, directed at involved systems
In general, treatment of complications due to vasculopathy has been more susccessful than treatment of those due to fibrosis (no great therapy for fibrotic manifestations)
Vasculitis
Inflammation/autoimmunity targeted to the wall of a blood vessel that results in injury to the vessel wall with subsequent occlusion of the vessel due to thrombosis and/or loss of vessel integrity
Usually systemic and clinical manifestations primarily due to ischemia from vascular occlusion or loss of vascular wall integrity
Main mechanisms include immune complex deposition, ADCC, direct immune cell cytotoxicity
Clinical manifestations reflective of size and distribution of affected vasculature
Classification of vasculitis
Large vessel: aorta and branches
Medium vessel: small and medium sized arteries
Small vessel: vessels smaller than arteries such as capillaries and venules
Note: small vessel vasculitis can either be (1) immune complexes in vessels, or (2) paucity of vascular Ig (often with ANCA)
General clinical features of small vessel vasculitis
Non-blanching palpable purpuric lesions due to RBC extravasation from damaged vessels in small vessel vasculitis
Immune cell infiltration of small vessel supplying a nerve (vasa nervorum) results in neuropathy
RBC cast due to vasculitis involving glomeruli (glomerulonephritis)
General clinical features of medium vessel vasculitis
Immune cell infiltration with destruction of medium vessel wall and obliteration of lumen
Skin ulcer secondary to occlusion of medium sized arteriole
Celiac artery anneurysmal dilatations with areas of stenosis of medium sized mesenteric arteries resulting in abdominal pain after meals, GI bleeding and possible perforation with severe ischemia
General clinical features of large vessel vasculitis
Giant cell arteritis: disrupted internal elastic membrane, thickened temporal artery, stenoses of subclavian and axillary arteries that can cause ischemic pain with exertion in the arm (limb claudication)
Takayasu’s arteritis: large vessel stenoses (limb claudication), thickening and narrowing of the carotid arteries
Antineutrophil cytoplasmic antibodies (ANCA)
Antibodies directed against cytoplasmic antigens in neutrophils
Two types of reactivity: cytoplasmic (C) and perinuclear (P)
C-ANCA: antibodies against serine proteinase-3 (PR3)
P-ANCA: antibodies against myeloperoxidase (MPO), lactoferrin, and others
Antibodies may play a pathogenic role by activating neutrophils
Play a role in non-immune complex types of small vessel vasculitis
Are anti-dsDNA and anti-Sm antibodies specific for SLE?
YES!
(but ANA is NOT specific for SLE, it is sensitive)
