Lupus Flashcards
What is lupus?
- chronic multi-system disorder
- inflammation - joints, skin, organs
serositis, nephritis, hematological cytpoenia, neurological - no cure
- flare ups & remissions in some cases
Lupus - risk factors
Women
- reproductive years (15-45 years old) 12:1; >45 2:1
- suggests sex hormone roles - increased risk with OCP, but HRT does not increase risk of flare ups in stable disease
Age 15-45
- >50 years less common and milder
African/Asian descent in Europe and US
Drugs
Lupus - pathogenesis
Genetic factors:
- Higher rates in twins, familial aggregation
- Higher in those with complement deficiency (C2-deficient homozygotes and C4 heterozygotes)
Environmental:
- May increase oxidative stress and cause cell damage
- Drugs – procainamide, minocycline, terbinafine, sulfasalazine, isoniazid, phenytoin, carbamezapine
- Infectious - EBV? Endogenous retroviruses?
- UV light
Antigen-driven immune-mediated
- High affinity IgG antibodies to dsDNA & nuclear proteins
- T cell dysregulation of B cells
- Hypothesis – persistently high levels of exposure to endogenous nuclear material may arise from apoptotic cells (mechanism for clearing apoptotic cells impaired) -> modified to antigens -> provoking immune response
Lupus - History
MOST: fatigue, typical rash, and/or musculoskeletal symptoms
Fatigue, weight loss
Headache,
Lymphadenopathy
Fever (50% - active disease)
Oral ulcers (12-45% / painless, but prolonged)
Alopeacia (hair thinning and patchy alopecia)
- Usually non-scarring. Areas of scarring → chronic discoid lupus
Arthralgia/arthritis – similar to RA but non-erosive.
- Monoarthritis rare.
- Early morning stiffness
Fibromyalgia (poorly localised symmetrical musculoskeletal pain with no diurnal variation)
Raynauds (colour changes of digits induced by cold/emotion. Bilateral)
Pleuritis (chest pain/shortness of breath)
- 17% at onset. May have other cardio manifestations.
Hypertension
Signs of nephrosis (oedema)
Venous/arterial thrombosis
Abdo pain, vomiting, diarrhoea
Lupus - 3 types of rashes
Malar (butterfly) rash
- 30-40%
- erythema over cheeks and bridge of nose, sparing nasolabial folds
- lasts a few days
- painful, pruritic
- heals without scarring, may recur after sun exposure
Photosensitive rash
- occurs after sun exposure
- Can be painful and pruritic
- usually lasts a few days
- heals without scarring
Discoid rash
- erythematous raised patches with adherent keratotic scaling and follicular pludding
- atrophic scarring may occur in older lesions
Lupus - history (head to toe)
General: fatigue, fever, weight loss
Head - CNS (4 F’s) - fitting, fainting, feeling low, feeling headaches
Hair - more hair loss (in shower or on pillow)
Face/skin - variable
(1) photosensitivity
(2) rashes - butterfly rash, purpura
(3) Vasculitis
Mouth
(1) Ulcers
(2) Are your mouth or eyes dry or sticky?
Throat
(1) Do your glands swell up?
Arms
(1) Are your muscles weak?
(2) Myalgia common - severe muscle weakness
Hands
(1) Raynauds - Do your hands go white, blue, cyanosed in response to cold?
(2) Do you have joint pain that lasts for a few days and then moves onto another joint?
(3) Do you have sore swollen stiff joints?
Lungs
(1) Do you get shortness of breath?
(2) dry cough
(3) chest pain
CVS
(1) pericarditis - sharp and stabbing pain - may increase with coughing, swallowing, deep breathing or lying flat
(2) history of MIs, angina
GI
(1) esophagitis, intestinal psuedo-obstruction
Renal
(1) previous renal problems? Protein noted in pregnancy
Fibromyalgia
Other
(1) DVTs, arterial clots
(2) second trimester of pregnancy loss (may be due to having anti-Ro antibodies)
Lupus - Investigations
FBC & clotting screen
- Prolongation of partial thromboplastin time → lupus anticoagulant -> Check antiphospholipid antibodies (also if have history of recurrent spontaneous abortions and thrombosis)
- Elevated ESR & CRP → suggest active disease -> Need to exclude infection
Infection screen – blood and urine cultures in febrile patients
Exclude: septic arthritis if present with monoarthritis
Urea & electrolytes – exclude/confirm renal involvement
Urinalysis
- Regularly in patients with SLE
- Lupus nephritis → proteinuria
Autoantibodies for anti-nuclear factor, dsDNA, ENA (extractable nuclear antigen) and Smith antigen
- ANA – detects group of antibodies directed against components of nucleus of cell (DNA/RNP) – including anti-DNA & anti-ENA
+ve in 95-98% lupus /10% healthy people
+ve ANA – not diagnostic as may be +ve in other connective tissue diseases (RA, systemic sclerosis, Sjogren’s syndrome, thyroid disease, chronic infectious diseases, IBD or if on certain drugs – procainamide, hydralazine, isoniazid, chlorpromazine). Low titre – may occur in healthy.
–ve ANA may also occur in SLE (rare) –anti-RO-antibody-positive lupus
Anti-dsDNA and anti-Smith antibodies – highly specific for SLE
- Often confirm diagnosis
- Anti-dsDNA = markers of disease activity + high levels predict worse outcome in lupus nephritis
ENA panel – tests for range of other autoantibodies – Sm, Ro, RNP, La
- May be found in lupus variants – Sjogren’s syndrome and mixed connective tissue disorder (MCTD)
Lupus - diagnosis criteria
Need to have 4 of the 11 criteria to be diagnosed o Malar rash o Discoid rash o Photosensitivity o Oral ulcers (oral/nasopharyngeal) o Arthritis o Serositis o Renal disorder o Neurological disorder o Haematological disorder o Immunological o Antinuclear antibody (ANA)
Lupus - treatment
Diet – keep in mind late complications of premature cardiovascular disease
Healthy weight, reduce salt intake if hypertension due to renal disease
Stop smoking
Sun protection – minimum SPF>15
Mild:
- NSAID, analgesic, sunblock
- Hydroxychloroquine
- Low dose steroids
Moderate:
- Steroids plus azathioprine or methotrexate
Resistant or life-threatening disease
- Pulse steroids and cyclophosphamide
- Pulse steroids and mycophenolate
- Rituximab / Belimumab (inhibits B-cells)
Ongoing – joint symptoms and serositis
- Hydroxychloroquine
- Adjunct: NSAID - naproxen / Corticosteroids (If hydroxychloroquine and NSAID inadequate) / Methotrexate + folinic acid
What is anti-phospholipid syndrome?
Also known as Hughes syndrome
Autoimmune condition -> antibodies target phospholipids -> blood more likely to clot
Can affect people of all ages: Most 20-50
3-5: 1 F>M
Risk of: DVT, arterial thrombosis (-> stroke/MI), blood clots in brain, pulmonary embolism
Pregnant - increased risk of early miscarriage
- recurrent (3 or more) early miscarriages - usually during first 10 weeks
- 1 or more later miscarriages - after 10 weeks
- Premature brith - usually at/before week 34 of pregnancy -> may be caused by pre-eclampsia
Symptoms
- high BP
- balance + mobility problems
- Vision problems – double vision
- Speech and memory problems
- Tingling sensation / pins and needles in arms/legs
- Fatigue
- Repeated headaches/migraines
- Livedo reticularis – skin condition – small blood clots inside blood vessels of skin; Blotchy red/blue appearance; May also develop ulcers and nodules;Often more severe in cold weather
- Superficial thrombophlembitis - Inflammation of vein under skin – usually in leg; Symptoms similar to DVT but not as severe;Swelling, redness and tenderness along affected vein, high temp. of 38C or above; Usually resolve within 2-6 weeks
- Similar to MS
Diagnosis: blood test for antibodies responsible for APS
Treatment: No cure
- Anticoagulant – warfarin
- Antiplatelet – low dose aspirin
Treatment during pregnancy – 80% chance of successful pregnancy
Lupus - pregnancy
Important to plan properly
Ideally lupus should have been inactive for at least 6 months on stable therapy
Conceiving during active lupus – increases risk of disease flares during pregnancy and increases chance of complications for mother and baby
Meet doctor 3-6 months before planning to try to become pregnant
Screen for RF: kidney involvement, high BP, heart or lung problems
Changes to meds:
- Hydroxycholoroquine and/or azathioprine may need to be changed
- Methotrexate / Cyclophosphamide / Mycophenolate mofetil (stop 3 months prior to conception)
- Rituximab /Belimumab (stop 1 year prior to conception)
- Leflunomide /Bisphosphonates (stop 2 years before prior to conception)
- ACE inhibitors & warfarin
