Chapter 6- SLE and autoimmune dieases Flashcards
What condition regarding the esophagus is common in scleroderma
Dysphagia due to esophageal fibrosis, in almost 50% of patients
What are the characteristics of type 3 renal lesions aka focal lupus nephritis
Involvement of less that 50% of all glomeruli
-Red cell casts in the urine
What are the diagnostic antibodies in SLE
Antibodies to dsDNA and Smith (sm) antigens
What is polyarteritis nodosa characterized by
Necrotizing inflammation of the walls of blood vessels
Patients with high titers of SS-A are more likely to what
Early Sjogren syndrome onset, longer disease duration, and extraglandular manifestations, such as cutaneous vasculitis and nephritis
What is the percent of cardiac involvement in SLE
50% of pts
What are the characteristics of class 2 renal lesion aka mesangial proliferative lupus nephritis
- masangial proliferation and accumulation of matrix
- Deposits of Igs and complement without involvement of glomerular capillaries
What are the most common causes of death in SLE patients
Renal failure and inter current infections
Specifically, what are the antibodies in SLE against
Antinuclear antibodies (ANA)
Which antibodies are commonly found in patients with Sjogren syndrome
Antibodies against two ribonucleoprotiens, SS-A (Ro) and SS-B (La)
What is the epidemiology of scleroderma
3:1 female to male ratio, with peak in 50-60
Which disease is sicca disorder associated with
Aka Sjogren syndrome, and is assocaited with RA
What percent of lung presentation is seen in SLE
50% of pts have pleuritis or pleural effusion
What is keratoconjunctivitis sicca
Dry eye
What is assocaited with scleroderma (systemic sclerosis) early in the course presentation
Vascular damage, especially microvascular
What is the changes seen in skin during scleroderma (systemic sclerosis)
Diffuse atrophy of skin, beginning in the fingers and distal regions
How does lupus antibodies affect clotting time
In Vitro, it will increase the PTT timing
What are the complications of mixed connective tissue disease
Pulmonary hypertension, interstitial lung disease, renal disease
What is the most prominent renal abnormality in scleroderma
Vascular lesion and interlobular arteries show thickening due to fibrosis
What is the percentage of scleroderma patients that have renal involvement
2/3
What is xerostoma
Dry mouth
What is the characteristic of joints in SLE
Nonerosive synovitis with little deformity (as opposed to RA)
Which HLA is more common to form a reaction following administration of hydralazine
HLA-DR4
Which HLA is more common to form a reaction following administration of Procainamide
HLA-DR6
What is the skin presentation in SLE
Butterfly rash (50% of pts) -Urticaria, bullae, maculopapular lesions, ulceration
What are possible effects of the changes to esophagus in scleroderma
GERD and subsequent Barrett’s metaplasia
What is libman sacks endocarditis
Aka valvular endocarditis
What is limited scleroderma
Skin involvement and confined to fingers, forearms, and face
What are the four categories of antinuclear antibodies (ANAs)
1) antiDNA
2) Antihistone
3) anti nonhistone proteins attached to RNA
4) Antinucleolar antigens
Patients with scleroderma and anti topoisomerase antibodies (anti-Scl-70) are more likely to develop which condition
Pulmonary fibrosis and peripheral vascular disease
What percentage of patients with scleroderma have ailment tract involvement
90%
How is scleroderma associated with malnutrition
Loss of microvilli in the small bowel
What is the etiology of Sjogren syndrome
Decrease in tears and salivary glands as a result of lymphocyte infiltration and fibrosis
What does the infiltrate in Sjogren Syndrome Primarily contain
CD4+ T cells
What are the characteristics of class 4 renal lesions aka diffuse lupus nephritis
- most common and most severe
- similar to 3, except more that 50% of glomeruli involved
- May form the wire loop look aka vascular thickening
- Proteinuria and hematoureia
What is the condition of chronic discoid lupus erythematosus
Skin manifestations mimic SLE, but no systemic presentations
What is noninfectious vasculitis
Conditions where vasculitis occurs due to something other than a direct infection of the vascular wall, such as an abcess
What percentage of Sjogren patients are likely to develop lymphoma
5%, which is 40 times higher than normal (due to development of a dominant B cell clone)
What gender and age range is Sjogren syndrome common
Women between the ages of 50 to 60
What is the likely antigen in Sjogren syndrome
Alpha-fodrin, a cytoskeletal protein
In patients with scleroderma, what percentage of patients have lung involvement and what are the two common complications
50%, Most commonly with pulmonary hypertension and interstitial fibrosis
Damage during SLE is generally due to what
Deposition of immune complexes and antibodies binding to various cells and tissues
Mixed connective tissue disease is characterized by high titer levels of what
Ribonucleoprotein particle containing U1 ribonucleoprotein
Deficiency in which complement proteins may lead to SLE
C1q, C2, C4
What is the genetic and antibody association with subacute cutaneous lupus erythematosus
Antibodies against SS-A antigen
HLA-DR3 genotype
What portions of the heart are usually affected by SLE
Mitral and aortic valves, usually by leaflet thickening
How does SLE result in hypocomplementemia
Flare ups cause the increase formation of immune complexes, which exhaust the amount of complement proteins
What are the clinical presentations of chronic discoid lupus erythematosus
Skin plaques, edema, scaliness, skin atrophy surrounded by erythematosus border
What is the primary cause of death in patients with scleroderma
Pulmonary disease
Pulmonary fibrosis in scleroderma commonly causes which condition
Right side cardiac dysfunction, leading to arrhythmias and cardiac failure
What presentation in bone marrow is indicative of SLE
LE bodies in the bone marrow
What percentage if patients with scleroderma die of renal failure
50%
What does speckled pattern staining indicate
Aka uniform or variable sized speckles. Indicates non-DNA nuclear components, such as Sm antigen, and SS-A and SS-B antigens
What percentage of Lupus patients contain antiphospholipid antibodies
30-40%
How common is SLE in women of child bearing age
1 in 700
What are LE or hematoxylin bodies
Damaged cell nuclei are bound by ANA, lose their chromatin pattern and become homogeneous. Usually results in LE cells, which are neutrophils or macros with an engulfed nucleus of injured cell
What is the level of dsDNA antibodies in chronic discoid lupus erythematosus
Rarely present
What are the state of the fingers in late stages of scleroderma
They become claw like, tapered,with very limited motion in the joints, andthe face becomes a drawn mask
What are patients with antiphospholipid syndrome more likely to develop
-Venous and Arterial thrombosis
-Miscarriages
Focal cerebral or ocular ischemia
What race is scleroderma more common in
Black, especially black women
What association does the parotid gland have with Sjogren syndrome
Enlarged in 50% of pts
What are three drugs that can induce a SLE like attack
1) Hydralazine
2) Procainamide
3) D-penicillamine
What class of renal lesion is most uncommon
1
What are the race ratios of SLE
2 to 3 times higher for blacks and Hispanics compared to whites
What is the ration of women no child bearing age to males
2 to 1 females to males
What are the state of LN in Sjogren patients
Enlarged lymph nodes due to hyperplasia
What percentage of scleroderma patients have Raynaud phenomenon
Virtually all cases
What are the drugs that can induce a lupus like affect
1) hydralazine
2) Procainamide
3) Isoniazid
4) D-penicillamine
5) Anti-TNF
What does a centromeric pattern indicate
Antibodies against centromeres, common in systemic sclerosis
What is Mikulicz syndrome
Enlargement of the lacrimal or salivary glands due to any reason
Which viruses are associated with Sjogren syndrome
Human T lymphoproliferative virus (HTLV), HIV, Hep C
What are the two types of ANAs that are strongly associated with scleroderma
1) DNA topoisomerase (antiScl-70)
2) anticentromere
What are the common SLE presentations in the spleen
-Splenomegaly, capsular thickening, follicular hyperplasia
How are SLE flare ups usually treated
Corticosteroids or other immunosuppressive drugs
Where in the ailment tract are patients with scleroderma most affected
Any portion will undergo fibrosis, but the esophagus is the primary location (forms a rubber hose like inflexibility.
Which HLA alleles are common in patients with antibodies to SS-B or SS-A
HLA-DQA1 and DQB2
In patients with Sjogren and high titers of SS-A are more likely to have which conditions
-synovitis, diffuse pulmonary fibrosis, and peripheral neuropathy
What is the involvement of TLR in activation of autoreactive B cells
Self reactive B cells also are activated by TLR to pathogenic DNA/RNA. This serves as the second signal to activate and produce autoantibodies
What have the HLA-DQ allele been linked to
Antibodies against dsDNA, anti-Sm, antiphospholipid
What does rim or peripheral staining patterns indicate
Antibodies to dsDNA and some envelope proteins
What is essential for the diagnosis of Sjogren syndrome
Biopsy of the upper lip to examine minor salivary glands
What is Sjogren syndrome characterized by
Dry eyes and dry mouth via destructions of lacrimal and salivary glands
What is CREST syndrome
Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia
Patients with scleroderma and anticentromere antibodies are more likely to develop which condition
CREST syndrome
Mixed connective tissue disease presents with which clinical findings
Synovitis of the fingers, Raynaud, mild myositis
What is the most widely used method for detecting ANAs
Indirect immunoflourescence
What does nucleolar pattern staining indicate
Antibodies against RNA, most common in MS
What are the general mechanisms of tissue injury
1) Deposition of immune complexes
2) Autoantibodies against RBCs, WBCs, and platelets
3) Antiphospholipid antibody syndrome
What is diffuse scleroderma
Widespread skin involvement, rapid progression, and early visceral involvement
What are the characteristics of class 6 renal lesions aka advanced sclerosing lupus nephritis
More than 90% of glomeruli, and represents end stage renal diease
-occasionally tubulointerstitial lesions
What percent of Sjogren syndrome patients have Rh factor
75%
What is the ratio of women in child bearing age to men for SLE
9 to 1 female to male ratio
What are the components recognized by antiphospholipid antibodies
1) Prothrombin
2) Annexin V
3) B2 Gp1
4) Protein S and C
What class of renal lesions is most common
Type 4
What is the significance of CD4+ cells involvement in SLE
It means that there is T cell dependant antigen, so it must be protein
How is subacute cutaneous lupus erythematosus differentiated from chronic discoid
Rash is more widespread, superficial, and no scarring
What is the earliest form of histological finding of Sjogren syndrome
Periductal and perivascular lymphocytic infiltrate
What is the significance of Type 1 interferons in the blood of SLE patients
It means that antigenic nucleic acids are almost acting as molecular mimicry of their viral counterparts, leading to activation of B cells
In drug enduced erythematosus, what antibody is common, and which is more rare
Rare to find dsDNA antibodies, but very common to find histone antibodies
What are the characteristics of class 1 renal lesions aka minimal mesangial lupus nephritis
Immune complex deposition in the mesangium by electron microscopy, but no light microscopy damage
What is systemic sclerosis characterized by
1) Chronic inflammation
2) Widespread damage to blood vessels
3) progressive interstitial and perivascular fibrosis in skin
Overall, systemic fibrosis
What is the fundamental defect in patients with SLE
Failure of the mechanism that maintains self tolerance
What doe homogenous or diffuse nuclear staining usually reflect
Antibodies to chromatin, histones, dsDNA
Scleroderma is common with which condition
CREST syndrome
What is Raynaud phenomenon
Vasoconstriction of Arteries and arterioles in extremities
