SLE; DLE; Sjorgren's; APS Flashcards
Define SLE [1]
SLE is a chronic multisystem disorder that most commonly affects women during their reproductive years.
It is characterised by the presence of antinuclear antibodies. In addition to constitutional symptoms, it most frequently involves the skin and joints
SLE typically takes a relapsing-remitting course, with flares of worse symptoms and periods where symptoms settle.
Describe the basic pathophysiology of SLE [1]
SLE is characterised by anti-nuclear antibodies (ANA). These are autoantibodies against proteins within the cell nucleus. These antibodies generate a chronic inflammatory response, leading to the condition’s features.
Describe the pathophysiology of SLE [+]
Body produces B cells. Normally when they react to self they get destroyed.
In SLE they escape from peripheral circulation - they differentiate into plasma cells and produce antibodies to nuclear parts of cells (thus ANA)
Complexes of antibody-antigen deposit in the body and cause damage e.g. skin, joints and renal are most common
When deposited the immune system causes complexes. But in SLE, have complement dysfunction. This adds to the inflam cascade and actives inflam cytokines
Over the course of lifetime, get waxes and wanes of SLE
Name a virus that can trigger SLE [1]
EBV
Describe the clinical presentation of SLE
Joint pain & swelling (without joint destruction)
Malar rash - spares nasolabial folds. Feels inflammed
Mouth ulcers
Reynauds
Livedo reticularis - broken lattice work in inflam. disease
Photosensitivity
Lupus nephritis
Alopecia
Discoid erythematosus
Lymphadenopathy
Name this manifestation of SLE [1]
Livedo reticularis
SLE symptoms
Other symptoms can be organ-specific caused by active inflammation these tend to develop within 5 years of diagnosis, such as:
Renal - lupus nephritis
Pleuritis; pneumonitis; PE
Pericarditis; Reynauds; Atherosclerosis
Headache or migraine; seizure; pyschosis
Which other autoimmune conditons is SLE associated with? [3]
anti-phospholipid syndrome (20-30%), Sjogren’s disease (17.5%) and autoimmune thyroid disease (7.5%).
> 4 criteria (at least 1 clinical and 1 lab. criteria) OR bx proven nephritis with positive ANA-or anti-DNA
NB need ANA or Anti-DNA for a dx really
Which antibodies need to know that are associated with SLE? [6]
ANA -
DS-DNA - highly specific to SLE, meaning a positive result suggests SLE rather than other causes. But only half have ds-ANA
Anti-SM - highly specific but not very sensitive
Anti-RNP
Anti-Ro
Anti-La
Describe the relationship between diagnosis of ANA and SLE
Just because have + ANA doesn’t mean have lupus.
- Low titre ANA are common in normal population
- ANA can increase in lots of inflam. diseases
- Need the clinical features and other antibodies for dx
- E.g. thyroid disease / malaria / other disease can have a positive ANA
Describe the diagnostic criteria for SLE
The European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) criteria (2019) can be used for diagnosis. This takes into account the clinical features and autoantibodies suggestive of SLE. uses 11 criteria of which 4 or more are required for diagnosis
Describe the general principles for treating SLE
go over MORE
Skin:
- hydroxychloroquine or azathriopine.
Joints
- hydroxychloroquine or methotrexate
Vital organs:
- Azathriopine
- MMF
- Cyclophosphamide - esp. if renal involvement
PassMed:
All patients - hydroxychloroquine
Mild Disease:
- hydroxychloroquine & low dose pred.
- Methotrexate and NSAIDs can also be used
Moderate disease:
- hydroxychloroquine with short term pred.
- Additional agents may include methotrexate, azathioprine, mycophenolate and ciclosporin.
Severe disease:
- induction therapy of intense immunosuppressants and then maintenence
- DMARDs (methotrexate; MMF; cyclophoshamide) & Biologics (Rituximab; Belimumab) may also be used
Describe the complications of SLE
Nephritis:
- Lupus nephritis: can lead to proteinuira; haematuria; end stage kidney disease
CV disease:
- CAD; myocarditis; pericarditis; heart failure
Pulmonary:
- ILD; pulmonary HTN; acute lupus pneumonitis
Neuropsyc:
- Head and mood to stroke or seizures
Hematologic abnormalities:
- leukopenia, lymphopenia, thrombocytopenia and autoimmune hemolytic anaemia.
anti-Smith: highly specific (> 99%), sensitivity (30%)
Young female, facial rash, neuropsychiatric features, Raynaud’s - systemic lupus erythematosus
What is the most common cardiac manifestation of SLE? [1]
Pericarditis
Type 3
Define discoid lupus erythematosus [1]
Discoid lupus erythematosus is a benign autoimmune disorder generally seen in younger females. It very rarely progresses to systemic lupus erythematosus (in less than 5% of cases).
Describe the presentation of discoid LE [3]
Photosensitive lesions of the face
Scarring alopecia
Hyper & hypopigmentation
What is the management for DLE? [3]
- topical steroid cream
- oral antimalarials may be used second-line e.g. hydroxychloroquine
- avoid sun exposure
Define Sjogrens syndrome [1]
Sjögren’s syndrome is an autoimmune condition where you get lymphocytic infiltration of exocrine glands notably the lacrimal and salivary glands, causing symptoms of dry mouth, eyes and vagina. Dry eyes and dry mouth can be called sicca symptoms.
Describe the pathophysiology of Sjogren’s syndrome
Aberrant immune response - autoreactive T cells become activated and infiltrate exocrine glands.
Within the affected glands, there is a marked increase in pro-inflammatory cytokines including interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ).
The local inflammatory milieu results in glandular dysfunction through both direct cytotoxic effects on acinar epithelial cells and disruption of normal glandular architecture.
B cell hyperactivity is another hallmark of Sjögren’s syndrome. There is increased production of autoantibodies such as anti-Ro/SSA and anti-La/SSB, which are directed complexes within the nucleus of glandular epithelial cells.
These autoantibodies may contribute to tissue damage either directly or via immune complex formation and deposition within glandular tissues.
Chronic inflammation leads to fibrosis and atrophy of the exocrine glands over time. The resultant loss of functional acinar cells impairs saliva and tear production, manifesting clinically as dry mouth and dry eyes.
Describe the clinical presentation of Sjogrens
Sicca (dryness)
- eyes (keratoconjunctivitis sicca)
- mouth
- vagina
Arthralgia
Raynaud’s, myalgia
Sensory polyneuropathy
Gland swelling (parotitis)
Which antibodies are most associted with Sjogrens? [2]
Anti Ro (70%)
Anti La (30%)
Describe how you diagnose Sjogrens
Assess clinical features:
- dry eyes > 3 months; use of tear substitutes more than three times daily or presence of keratoconjunctivitis sicca with ocular staining score ≥3.
- dry mouth consistently
Serology:
- anti-Ro; anti-La
- Elevated IgG levels
Further tests:
- Schirmer’s test - < 5 mm/5mins wetting and / or Rose Bengal scores of > 4
- Sialometry < 1.5ml/15mins
Histopathology
- Lip biopsy exhibiting focal lymphocytic sialadenitis with a focus score ≥1 per 4 mm² glandular tissue area.
What is Schirmer’s test? [1]
Describe how you perform it [4]
Schirmer’s test is used to look at tear production.
Test procedure:
* Step 1: Folded sterile filter paper is placed over the margin of the lower eyelid
* Step 2: The patient is asked to gently close their eyes
* Step 3: The filter paper is left for 5 minutes
* Step 4: The extent of paper wetting is assessed after 5 minutes
Wetting of filter paper ≤5mm within 5 minutes is suggestive of aqueous tear deficiency
Describe what is meant by Whole sialometry
How do you perform this test? [1]
Sialometry refers to the measure of saliva production.
Test procedure
* Step 1: Patient asked to expectorate at the start of the test
* Step 2: The patient then asked to collect all saliva in a pre-weighed container
* Step 3: Saliva should be collected over 5-15 minutes
* Step 4: The collection container is reweighed at the end of the time period
NB: Collection ≤ 0.1 mL/minute is indicative of abnormal salivary function.
Describe the primary [5] and secondary [4] treatment options for Sjogrens
Primary treatment options:
* Artificial tears (e.g., polyvinyl alcohol eye drops during the day and carbomer gel at night)
* Artificial saliva
* Vaginal lubricants
* Pilocarpine (oral) can be used to stimulate tear and saliva production
* Hydroxychloroquine may be considered, mainly in patients with associated joint pain
Secondary treatment options are usually prescribed by an ophthalmologist and include:
* Topical NSAIDs or Corticosteroids: usually short-term use. Associated with corneal complications long-term.
* Topical cyclosporin: reserved for patients needing recurrent courses of topical steroid.
* Serum tear drops: application of autologous or allogenic serum. Variable efficacy.
NB: Pilocarpine stimulates muscarinic receptors, stimulating the parasympathetic nerves and promoting salivary and lacrimal gland secretion.
The major complication of SS is [].
The major complication of SS is lymphoma.
A 35-year-old woman complains of a constant dry mouth and sore, dry eyes. She also describes painful hands and feet - Sjogren’s syndrome
RF
ANA
Anti-La
Define antiphospholopid syndrome [1]
Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia
APS is most associated with which other condition?
SLE
What are the antibodies seen in APS? [3]
- anticardiolipin antibodies
- anti-beta2 glycoprotein I (anti-beta2GPI) antibodies
- lupus anticoagulant
Describe the common complications of APS [3]
Venous thromboembolism (e.g., deep vein thrombosis and pulmonary embolism)
Arterial thrombosis (e.g., stroke, myocardial infarction and renal thrombosis)
Pregnancy-related complications (e.g., recurrent miscarriage, stillbirth and pre-eclampsia)
TOM TIP: In your exams, look out for the patient with thrombosis (e.g., deep vein thrombosis or stroke) and a history of recurrent miscarriage. The diagnosis is likely antiphospholipid syndrome.
Which skin condition is associated with APS? [1]
livedo racemosa permanent Livedo reticularis
Which cardiac complication is associated with APS? [1]
Libmann-Sacks endocarditis is a non-bacterial endocarditis with growths (vegetations) on the heart valves (most often the mitral and aortic valves). It is associated with SLE and antiphospholipid syndrome.
Describe the primary [1] and secondary thromboprophylaxis (initial VTE; recurrent VTE; arterial thrombosis [3]
primary thromboprophylaxis
- low-dose aspirin
secondary thromboprophylaxis
* initial venous thromboembolic events: lifelong warfarin with a target INR of 2-3
* recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then consider adding low-dose aspirin, increase target INR to 3-4
* arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
How do you treat APS in pregnancy? [2]
low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing
low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation
Dx:
- vascular event
- pregnancy morbidity: foetal death > 10 weeks or..)
