Connective Tissue Disease Flashcards
Signs of active disease in DLE
Perifollicular erythema and easily extractable anagen hairs
Childhood DLE
Lower rate of photosensitivity and a higher rate of systemic involvement
DLE DIF
Old lesional skin
Concomitant DLE in SCLE
20%
SCLE DIF
Granular fluorescence throughout the cytoplasm and nucleus, particulate
SCLE drugs
Hydrochlorothiazide MC per Andrews
ACE inh, CCB’s, IFNs, AEDs, griseofulvin, glyburide, piroxicam, penicillamine, spironolactone, terbinafine, statins
Acral dermal mucinosis or telangectasias
May predominate in some NLE cases
*tel may occur in non sunexposed areas and be persistent
HLA in NLE
DR-3
Japanese infants have anti-dsDNA and 8% progress to SLE
C’ deficiency associated with lupus
C2 and C4
Tend to have SCLE annular lesions
C4 may have hyperkerarosis of palms and soles
Skin involvement in SLE
80%
DIF in SLE
IgG, IgM, IgA or C3 in a granular pattern at BMZ
Nailfold changes in SLE vs DM
SLE - wandering capillary loops
DM/scleroderma - symmetrical dilation and drop out
HHT - ecstasia of half of the capillary loop
Lupus hairs
Short frontal hairs from chronic telogen effluvium and increased fragility
Palisaded neutrophilic and granulomatous dermatitis
May be seen in SLE, RA or other IC mediated disease
Systemic symptoms in SLE
IC mediated
MC earliest systemic sx in SLE
Arthralgias
MC COD in SLE
First 5 years - infection and inflammatory SLE lesions
Late - thromboses
MC cardiac finding in SLE
Pericarditis
Raynauds in SLE
15%
Less renal dz associated = less morality
Have been reported in DLE evolving to SLE
Insulin receptor antibodies
UV sensitivity in SLE
Both UVA and UVB
Gene susceptibility in lupus
Defective CRP response in flares
APRIL (TNF alpha family) polymorphism sin SLE
Increased expression of TNF alpha and IFN inducible protein myxovirus protein A noted in cutaneous lupus
Polymorphisms in C1qA are associated with systemic and cutaneous lupus
Immune alterations in lupus
Reduced T suppressor function
Overproduction of gamma globulins and B cells and reduced clearance of IC may contribute to C’ mediated damage
Externalizations of cellular ag like SSA in response to sun,ignited may lead to cell injury by antibody dependent cellular toxicity
HLA-DR4 people, who are slow acetylators, predisposed to hyralazine induced LE
Penacillamine and etanercept may unmask disease with anti dsDNA
Pegylated IFN and ribavirin have produced SLE
L-canavanine (alfalfa sprouts) - can induce or worsen SLE
Smoking associated with increased disease activity and interferes with antimalarial drugs
Globulin increased, especially gamma and alpha 2 fraction
MC urine findings in lupus
Albumin, RBC’s, and casts
ANA positive rate in SLE
95%
Lupus band
Continuous granular along the Dej in 75% of well established DLE lesional skin
Positive in sun exposed skin in SLE
A positive test in non sun exposed skin correlates with dsDNA and renal disease
SLE
Increased risk of osteoporosis independent of steroids
Lupus treatment
Sun avoidance
vit d and ca supplementation
Local - steroids, CCI, ILTAC
Systemic - antimalarials (consider another agent if no response in 3 mo) –> retinoids –> immunosuppressants –> rituximab
steroids for flares (limit to 3 weeks unless renal or CNS)
Antimalarial side effects
Ocular, erythroderma, EM, purpura, urticaria, nervousness, tinnitus, Abducens nerve paralysis, leukopenia, thrombocytopenia, psoriasis, N/V/D
*may exacerbate (except in small doses) or cause hepatic necrosis in PCT
Tocilizumab
IL-6 inhibitor
May cause neutropenia
Wong type DM
DM with clinical findings of PRP
In DM: anti jo 1, anti pl-7, anti pl-12, anti-DJ and anti EJ
Correlate with pulmonary disease which is frequent COD
Higher risk of malignancy in DM
Highest in first 2 years of dx, age, constitutional sx, rapid onset, lack of raynauds, super high esr or ck, LCV
Childhood DM
Brunsting type - slower course, progressive weakness, calcinosis, steroid responsive
Banker - vasculitis of muscle and GI tract, rapid onset of severe weakness, steroid unresponsiveness, high death rate
*malignancy not associated but insulin resistance might
Initial immune response in DM
IFN alpha and beta induced with secondary stimulation of IFN gamma
Juvenile DM
DQA1*0501 in 85%
TNF alpha 308A allele associated with increased TNF synthesis and thrombospondin-1 and small v. Occlusion
Strep m protein may have homology to myosin
Adult DM
IL-1 alpha, TGF beta, myoblast production of IL-15 may be pathogenic
Terbinafine DM cases related to apoptosis induced by the drug
Path of DM vs lupus
More likely to become atrophic, less eccrine, fewer vertical columns of lymphocytes and fibrous tract remnants
ANA pos rate in DM
60-80%
Crest eponym
Thibierge-Weissenbach syndrome
MC initial presentation of SS
Raynauds
Scleroderma nail fold changes
Dilated capillary loops, nailfold capillary hemorrhage in 2 or more fingers
*HHT has dilation of only 1/2 of of the loop with no avascular areas
Childhood scleroderma
Less raynauds, more cardiac (1/2 deaths)
Major COD in scleroderma
Pulmonary
MC organ involved in scleroderma
Esophageal in 90%
Telangectasias in scleroderma associated with
Pulmonary vascular disease
MC cancers in scleroderma
Malignancy associated in 10%
Lung and breast MC
Most specific ANA Pattern in scleroderma
Anti nucleolar
Linear scleroderma ab
Anti-SS DNA
Sclerodermoid conditions
Occupational exposure to silica, epoxy resins, polyvinyl chloride, vibratory stimuli
Bleomycin, INH, pentazocaine, valproate sodium, vit k injections, Spanish rapeseed oil, tryptophan, nitrofurantoin, hydantoin
Presenting scleroderma like sx may be 1st sign of multiple myeloma and amyloidosis
Pathogenesis of scleroderma
Anticardiolipin and anti beta2 glycoproteins play a role
Plasma d diner correlates with macrovascular complications
Unregulated proteins - monocyte chemoattractant protein 1, pulmonary and activation-regulated chemokine, macrophage inflammatory protein-1, IL-8, PDGFR-beta, and TGF beta –> these factors stimulate ECM production, TGF-beta production and activation and chemoattraction of T cells
PHET (protein highly expressed in testes) - ab noted in diffuse cutaneous scleroderma and lung involvement
CD40 increased on fibroblasts - binding with ligand increases IL-6, 8, and monocytes chemoattractant protein 1
Etanercept shown to decrease TGF-beta1, tissue hydroxyproline, dermal fibrosis, and alpha SMA positive cells - bc TH2 cells reduce net collagen 1 synthesis through TNF alpha, biological should be used with caution
Balicatib
Cathepsin K inhibitor that causes drug induced morphea
HFS with sclerodactyly
Capecitabine
Raynauds treatment
Stop smoking - 3 to 4 times more likely to have digital vascular complications
Nifedipine is first line - may use diltiazem if worsening esophageal function
Vasodilation drug (CCBs, angiotensin II R antagonists, topical nitrates and prostanoids), ginkgo, L-arginine may reverse digital necrosis
Eosinophilic fasciitis
May occur after strenuous exercise
Indurstion of forearms and legs, peau d orange, hands/face spared, dry riverbed sign
Steroid responsive , hydroxyzine and cimetidine may also help
Environmental triggers - L-tryptophan, borrelia, trichloroethylene
Polycythemia vera, metastatic colorectal CA, multiple myeloma have been associated
May see sys sx- carpal tunnel, neuropathy, sz, optic neuropathy, pleuropericard eff, pancytopenia, hemolysis, sjogrens, LAD, pernicious anemia and IgA nephropathy
Striking elevation in TGF-beta1
TH17 mediated pathway
Eosinophilia in 10-40%
MCTD DIF
Particulate epidermal nuclear IgG deposition
Anti-TS1 RNA antibodies
MCTD with lupus like clinical features
Ab noted in NSF
Anti phospholipid
Immunostains in NSF
Increased CD34 and procollagen 1 - cells may represent circulating fibroblasts recruited to the dermis
Skin findings in sjogrens
Vasculitis (accounts for most patients with waldenstroms hypergamma) pruritus, xerosis, annular erythema, decreased sweating
Pathogenesis of sjogrens
Aquaporin family of water channels is imp
CD4 cells
IL-12 and IFN gamma upregulated
Th1 cytokines mediate the functional interactions bw APC’s and cd4 cells
Increased malignancy in sjogrens
NHL
*patients with palpable purpura, low C4 and cryoglobulinemia at a higher risk of malignancy
Sjogrens Tx
Pilocarpine and cevimeline to stimulate salivation
Topical CSA and topical IFN for oral lesions
Acid maltose losenges
JIA
Evanecsent eruption, neutrophilic panniculitis
IL1 beta, IL6, IL18 and s100 proteins important in patho
Correlate with dz activity in relapsing polychondritis
Elevated ESR, CRP and urinary type II collagen levels
Th1 disease
