Autoimmune rheumatic diseases:SLE Flashcards
List the main systemic autoimmune diseases
- systemic Lupus erythematosus
- Antiphospholipid syndrome
- Systemic sclerosis
- Inflammatory myopathies
What is the CRP & ESR in Lupus
CRP=0
ESR=100
-There are very few conditions that give you this rare pattern 4
-When the CRP>100 this tells you that the Lupus patient has infection
What are the characteristics of SLE?
- about 10 times more common in females than men
- cytopenia
- Lymphopenia
- Neutropenia
- Thrombocytopenia & low complement c3 & c4
- Lupus patients are very sensitive for anti-nuclear antibody (but these aren’t specific to Lupus)
What may someone with mild SLE present with?
- Mucocutaneous
- Arthritis
- Serositis
- Mouth ulcers
What may someone with severe SLE present with?
- Nephritis
- Vasculitis
- CNS lupus
- Thrombosis
- Cardiopulmonary
What are the basic screening tests in an auto-antibody disease?
- Anti-nuclear antibody test
- RF test
Outline the ACR classification criteria
- Malar erythema
- Discoid lesions
- Photosensitivity
- Oral or nasopharyngeal ulceration
- Arthritis
- Serositis
- Nephritis
- CNS
- Cytopaenia
- ANA
- Specific autoantibodies: anti-DNA, Sm, aCL, LA
- Classification>/= 4 criteria needed
- Classification criteria are NOT diagnostic criteria
Describe the immunological criteria for SLE according to SLICC
- ANA
- Anti-dsDNA
- Anti-Sm
- Antiphospholipid Abs
- Low complement
- Direct Coombs’ test
What is the direct Coombs’ test
- Used to test for autoimmune hemolytic anemia( a condition where the immune system breaks down red blood cells, leading to anemia).
- Used to detect antibodies or complement proteins attached to the surface of red blood cells.
How useful are Anti-dsDNA to diagnosis of Lupus
specific: 50-70%
What is an extractable nuclear antigen panel?
- Detects the presence of auto-antibodies in the blood that react with proteins in the cell nucleus
- Certain autoimmune disorders are characteristically associated with the presence of one or more anti-ENA antibodies
Outline the potential abs that may appear in an extractable nuclear antigen panel for SLE& their clinical features
Ro/SSA= photosensitivity
LA/SSB= neonatal Lupus
RNP= Raynaud’s/overlap
Sm=SLE specific (African ancestry)
When diagnosing SLE it may be seen that a patients has abs to something eg a cell component. List some of these and their clinical expression
Antibodies to…
- DNA= Renal, systemic
- Nucleosomes= Renal,skin]
- C1q= Renal
- Alpha-actinin= renal
- Sm=renal
- NMDA receptor=CNS
What is a potential link between EBV and Lupus
- EPV can trigger Lupus
- can also be a mimic of paediatric/juvenile onset Lupus
Contrast the classic cytokine in RA & SLE
RA= TNF-alpha
Lupus=type 1 IFN
Outline the course of SLE
Environmental triggers (sunlight, drugs,chemicals,smoking and viruses) & a genetic component together with defective apoptosis(resulting in autoantigens being exposed and a failure to clear these) lead to the onset of SLE
- PRE CLINICAL= autoantibodies present
- CLINICAL DISEASE= organ involvement; flares; damage
- CO-MORBIDITIES= infections, atherosclerosis, malignancies
- end result= potential death overtime
Describe the pathogenesis of SLE
- Defective apoptosis leads to autoantigens
- The germinal centre consists of Follicular dendritic cells and autoreactive B cells.
- With the help of type 1 interferons these germinal centre cells produce autoantibody producing plasma B cells
- These cells produce immune complexes& complement
- Complement/immune complexesbind to tissues and vascular inflammation or Lupus nephritis results
The cause of SLE is unknown, but outline the implicated factors
- Female hormones ( ratio 10:1 for F:M): disease onset after menarche, decline in disease activity with menopause, women have 2X chromosomes so double the genetic load
- Genetics: increased risk of sibling developing SLE; monozygotic 10 fold risk vs dizygotic from twin studies; HLA-a1,b8,dr3 and complement deficiency gene are all in the HLA and that’s the strongest associated with an increased risk of Lupus
- Drugs
- Environmental factors
- Ethnic origin
What ancestry is SLE common in?
African & Asian ancestry
- they have a polymorphism in FCGR2B gene which leads to decreased inhibitory function leading to B cell activation
- This polymorphism gives them protection against severe malaria but an increased risk of SLE
- Lupus is uncommon in Africa but is more common & more severe in migrants from African & Asian ancestry
What are the different types of Cutaneous Lupus?
- Discoid Lupus: central area of depigmentation; chronic; rarely seen on legs
- Subacute cutaneous Lupus: most photosensitive type; often flare up in summer ;no rash in sun protected areas
Outline Chilblain Lupus
- Variant of discoid Lupus
- Most patients have Raynauds
- The lesions feel cold
- Looks like vasculitis but isn’t
Outline Jaccoud’s arthritis
-Arthritis=common in Lupus& you often get deformities
(RA destroys joint,cartilages and tendons so you get fixed deformities)
-These patients instead would have normal functioning of their hands cos Lupus primarily affects the tendons
What may a patient present with if they have Lupus vasculitis?
- ) Cutaneous vasculitis
- )Small vessel vasculitis:
- splinter haemorrhages
- Digital infarcts
- Palpable purpura
- Vasculitic ulcers
- Urticarial vasculitis
Outline the predictors of poor outcome/mortality in SLE
- Female
- Black ethnicity
- Infections
- Younger age
- Disease duration<1 year
- Renal disease
Outline peripheral vascular disease in SLE
- Critical limb/digital ischaemia
- Gangrene
- Amputations
What other system can Lupus affect
every system
- Pulmonary involvement= Lupus pneumonitis, Lupus serositis
- Cardiac: pericarditis, myocarditis, endocarditis
- Lupus nephritis
What are the presenting features of Lupus nephritis ?
-Asymptomatic proteinuria
-Nephrotic syndrome
-Renal failure
-Rapidly progressing glomerulonephritis
-Dysmorphic/fragmented red cells
-Granular casts
Consider renal biopsy unless contraindicated.
Diagnosis=activity
Prognosis=damage
What can be used in the assessment of Lupus
- ) Assessing disease activity:
- BILAG
- SLEDAI - ) Assessing QoL:
- Lupus QoL
- SF36, HAQ - )Damage:
- ACR/SLICC
- Damage index
What are the characteristics of neuropsychiatric lupus?
- Psychosis
- Seizures
- Strokes
- Psychological disorders
- Transverse myelitis
How can we treat SLE
1.) Less severe stage=
-sun avoidance, topical steroids, calcineurin inhibitors & retinoids, Hydroxychloroquine(stop smoking), Mepacrine; analgesics- NSAIDS contraindicated
2.) Increasingly worse=
-corticosteroids: mycophenolate mofetil ;thalidomide ;Azathioprine; Dapsone; Retinoids; UVA
3.)Much worse=
Biologics these are B cell targets eg Belimumab, Rituximab, Cyclophosphamide
What is key to remember in corticosteroid therapy in SLE?
-Use the lowest effective dose for the shortest period of time (cos it’s a major contributor to damage)
Outline the use of antimalarials in SLE
- Hydroxychloroquine= standard of care, everyone gets this
- Mepacrine/Quinacrine (gives you a yellow discolouration)
- Combination antimalarials
- Long term use well tolerated inc pregnancy
- 65% decreased risk of cardiac neonatal Lupus
- Decreases relapse rate & risk of renal flares
- Improves lipid& glucose profiles
- Thromboprophylaxis
- Reduces risk of damage&mortality
- 1st line Rx for all SLE patients
- Smoking reduces anti-malarial efficacy
What threat does mycophenolate pose to women attempting to conceive
- Can cause fertility issues
- Can lead to teratogenicity in human pregnancies
- Treatment with such agents should be avoided in women for at least 6 weeks prior to attempted conception.
Outline the use of Belimumab in SLE
- Biologics
- Only one licensed for use
- Blocks BLyS (B lymphocyte stimulator)
- Apoptosis of autoreactive B cells
Outline the charactersitics of the antiphospholipid syndrome
-A disorder of the immune system that causes an increased risk of blood clots
-Thrombosis & pregnancy morbidity
-10-15% of Lupus patients have it
-Positive antiphospholipid abs= anticardiolpin abs( aCL); Lupus anticoagulant(LA); Anti-beta2 glycoprotein 1 abs
could result in:
1.)Uteroplacental insufficiency; IUGR= Fetal death, still birth
2.)Pre-eclampsia, abruption, premature delivery, thrombosis
Outline treatment of CNS lupus
- Focal disease aPL +ve= strokes/TIAs - anticoagulation needed
- Diffuse disease= organic brain syndrome- Immunosuppression needed
How do we handle pregnant women who are aPL +ve
- ) No thrombosis or pregnancy loss: careful monitoring & aspirin
- ) Previous maternal thrombosis: Hep& aspirin
- ) Recurrent embryonic loss (<10weeks): Hep& aspirin; low dose aspirin
- ) Late fetal death/IUGR/severe pre-eclampsia: Hep& aspirin
- ) Post partum: 6/52 aspirin
What inflammatory myopathies may result from Lupus
- Dermatomyositis
- Polymyositis
- Cancer associated myositis
- Inclusion body myositis
- Muscle weakness
- Raynaud’s
- Joint pains
- Fevers
- Rashes
How can we treat systemic sclerosis ?
- Early= low dose steroids immunosuppressives
- Late= symptomatic Rx BP control
Outline the characteristics of systemic sclerosis
High risk of mortality due to:
- early diffuse disease( <2yrs)
- Rapid cutaneous progression
- Renal crisis
- GI involvement
- Early ILD
- Pulmonary hypertension
- Pulmonary fibrosis
- Intestinal disease
What is CREST syndrome and what does it stand for?
aka Limited cutaneous systemic sclerosis
- A multisystem connective tissue disorder
- Refers to the five main features: Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia.
