Rheumatology (conditions continued) Flashcards
Systemic lupus erythematosus (SLE)
- is a multisystem autoimmune disease of unknown aetiology that can present at any age.
- SLE is prone to relapses and remissions and can result in morbidity due to flares of disease activity and accumulating damage over time, along with an increased risk of premature death due to infection or cardiovascular disease.
Lupus erythematosus describes the typical rash seen in SLE. The “systemic” part indicates the potential for multi-organ involvement.
Antiphospholipid syndrome can happen secondary to SLE, which carries an increased risk of venous thromboembolism.
SLE pathophysiology
Pathophysiology
SLE is thought to be a type III hypersensitivity reaction where impaired clearance of dead cells and failure of processes giving immune tolerance to nuclear antigens may lead to the development of antibodies against double-stranded DNA and nuclear proteins.
RF for SLE
* female
* >30
* African-caribbean descent
* Drugs e.g. sulfasalazine, phenytoin
* family history
* smoking
SLE is associated with
- Antiphospholipid syndrome
- RA
- Other autoimmune e.g. thyroiditis
- Atherosclerosis/HTN/dyslipidaemia, diabetes, osteo
- Non-hodgkins lymphoma
presentation of SLE
General
- Fever
- Fatigue
- Lymphadenopathy
- Mouth ulcers
Skin and hair
- Butterfly rash
- Photosensitive rash
- DIscoid rashes
- Raynauds
- Alopecia
- Vasculitis rashes
MSK
- Myalgia
- Arthritis
Pulmonary
- Pleurisy
- alveolitis
- PE (antiphospholipid association)
Cardiovascular
- Pericarditis
- HTN
- Myocardiits
Renal
- Protien uria, haematuira, HTN
Neuropsychiarric symptoms
- Anxiety
- Depression
- Psychosis
- Seizures
- Strokes secondary to vascultiis
Antibodies for SLE
Common
- ANA (high sensitivity)- all patients with SLE will have this, but some without will also have it
- Anti-dsDNA (high specificity) - patients with SLE will defo have this
Others
Anti-Smith, anti-Ro (SS-A), and anti-La (SS-B)
Monitoring disease activity: SLE
- Erythrocyte sedimentation rate (ESR) is used
- C-reactive protein (CRP) may be normal during active disease
- If CRP is raised, this may indicate an underlying infection
- C3 and C4 may be low in active disease
investigations for SLE
Autoantibodies
- ANA
- anti-dsDNA
FBC
- anaemia, leukopeia, thrombocytopenia
APTT
- prolonged if antiphospholipid sydnrome - think VTE
UE
- renal manifeststions e.g. glomerulonephritis
- calcium can be high
Urinalysis
- haematuria
- casts
- proteinuria
CXR
- pleural effusion
- inflitrates
- cardiomegaly
ECG
- chest pain - rule out cardiopulmonary symptoms
Antiphospholipid antibodies
- venous thromboembolism
- recurrent miscarriages
- prolonged APTT
management of SLE
First line
- NSAIDS for MSK pain and headaches e.g. naproxen (PPI)
- Sunscreen
Second line
- Hydroxychloroquine
advice to patients with SLE
- Patients should avoid excessive sun exposure and use effective sun screen
- Patients should be aware that some drugs can exacerbate SLE
- Patients should have smoking cessation help and aim to stop
- Oestrogen-containing hormonal contraception can worsen SLE, but the lowest dose can cautiously be used if there are no contraindications and no anticardiolipin antibodies present
- Fertility is normal and pregnancy is safe in stable/mild SLE
- If SLE is severe, pregnancy should be delayed until the disease is better controlled:
drug-induced lupus vs SLE
- Drug-induced lupus (DIL) is an autoimmune condition where a patient develops signs and symptoms similar to systemic lupus erythematosus after exposure to certain drugs.
- DIL carries a more favourable prognosis compared to SLE and resolves within a few weeks after discontinuing the offending drug.
causes of drug induced lupus
Drug Causes
- Procainamide
- Hydralazine
- Minocycline
- Terbinafine
- Sulfasalazine
- Isoniazid
- Phenytoin
- Carbamazepine
investigations for drug induced lupus
Anti-nuclear antibodies (ANA):
* Nearly positive in all patients
Anti-double-stranded DNA (anti-dsDNA):
* Absent in most patients, used to screen for SLE
Anti-histone antibodies:
* Present in up to 90% of patients
antiphospholipid syndrome
an autoimmune disorder characterised by:
* arterial and venous thrombosis,
* adverse pregnancy outcomes
* raised levels of antiphospholipid (aPL) antibodies.
antiphospholipid syndrome can occur secondary to
SLE or other autoimmune conditions
antiphospholipids associations
- 30% of people who have systemic lupus erythematosus have aPL antibodies
- Higher prevalence in black people
- Most seen in young women of childbearing age with a male: female ratio of 1:3.5
- Accounts for 20% of recurrent thrombosis in young people
- Accounts for 15% of cases of recurrent foetal loss
presentation of antiphospholipid syndrome
- Recurrent foetal loss
- Features of thrombocytopenia:
- Petechial rashes
- Mucosal bleeding
- Arthralgia
- Due to possible underlying systemic lupus erythematosus
- Livedo reticularis
- Coagulation assays show a prolonged APTT
- Pulmonary hypertension
- Pregnancy morbidity:
- Pre-eclampsia
- Placental abruption
- Intrauterine growth restriction
Investigations for antiphospholipid syndrome
Autoantibodies
1) If associated with SLE: ANA and anti-dsDNA antibodies
2) Any of these positive/elevated on 2 occasions 12 weeks apart:
- Lupud anticoagulant
- Anticardiolipin antibodies
- Anti-beta2-glycoprotein I antibodies
Coagulation assays
- Prolonged APTT
Others
- Full blood count - thrombocytopenia
- Venous doppler US - if DVT suspected
- CTPAor V/Q scan - if PE suspected
-
diagnosing antiphospholipid syndrome
The diagnosis of APS requires at least 1 clinical criterionand 1 laboratory criterion.
Clinical criteria are:
- 1 or more episodes of vascular thrombosis
- 1 or more unexplained losses of morphologically normal foetuses at or beyond the 10th week of gestation
Laboratory criteria are (must be positive on 2 or more occasions at least 12 weeks apart):
- Lupus anticoagulant present
- Anticardiolipin antibody present
- Anti-beta2-glycoprotein I antibody
management of antiphospholipid syndrome: Non-pregnant patients
2 scenarios
1) No previous VTE: low dose aspirin
2) Single VTE episode: life long warfarin
- initially aim for an INR of 2-3
- if recurrent: increase INR to 3-4 and consider adding low-dose aspirin
management of antiphospholipid syndrome: pregnant patients
Different stages:
Stage 1
* Low-dose aspirin once the pregnancy is confirmed via urinary beta-hCG testing
Stage 2
* Low molecular weight heparin (LMWH) once the foetal heart is seen on ultrasound until 34 weeks gestation when it is then stopped
Stage 3
* Return to warfarin (teratogen) post-delivery
Systemic sclerosis
a multisystem autoimmune disease leading to increased fibroblast activity causing abnormal growth of connective tissue -> this leads to vascular damage and fibrosis:
- Skin
- GI tract
- Heart
- Lungs
-
There are three main patterns of SSc:
- Limited cutaneous SSc (lcSSc)
- Diffuse cutaneous SSc (dcSSc)
- Scleroderma
presentation of limited cutaneous systemic sclerosis (lcSSc) (limited systemic scleroderma)
most common type - commonly affecting face and distal limbs
CREST syndrome features
- Calcinosis
- Raynaud’s disease
- (O)Esophageal dysmotility and gastro-oesophageal reflux (GORD)
- Sclerodactyly
- Telangiectasia
Diffuse cutaneous systemic sclerosis (dcSSC) (diffuse scleroderma)
Less common- commonly affecting the trunk and proximal limbs
- Usually more rapid onset with skin thickening and Raynaud’s phenomenon happening together or with a short interval
- Internal organ involvement more common such as interstitial lung disease
Presentation of diffuse cutaneous systemic sclerosis
Diffuse cutaneous systemic sclerosis includes the CREST features and also affects internal organs, causing:
- Cardiovascular problems (e.g., hypertension and coronary artery disease)
- Lung problems (e.g., pulmonary hypertension and pulmonary fibrosis)
- Kidney problems (e.g., glomerulonephritis and scleroderma renal crisis)
general features of systemic sclerosis
- Raynauds
- Calcinosis
- Swelling of fingers and toes
- Sclerodactyly
- Prayer sign
- Digital ulcers
- tightening of skin around the face and mouth
- Telangiectasia
- Salt and pepper skin
features of systemic sclerosis: skin
- Raynaud’s phenomenon is common in around 90% of cases
- Calcinosis
- Symmetrical swelling of fingers and toes
- Sclerodactyly – hard and thickened skin
- Prayer sign – swelling and sclerosis cause patients to be unable to make a fist or place the palmar surfaces together
- Digital ulcers
- Tightening of skin around the face and mouth
- Telangiectasia
- “Salt and pepper” appearance of skin due to areas of hypopigmentation and hyperpigmentation
Scleroderma vs sclerodactyly
Scleroderma refers to the hardening of the skin, giving the appearance of shiny, tight skin without the normal skin folds. These changes are most notable on the hands and face.
Sclerodactyly describes the skin changes in the hands. Skin tightening around the joints restricts the range of motion and reduces function. The fat pads on the fingers are lost. The skin can break and ulcerate.
telangiectasia
refers to dilated blood vessels in the skin measuring less than 1mm in diameter.
Calcinosis
refers to calcium deposits under the skin, most commonly found on the fingertips.
Systemic sclerosis: Musculoskeletal symptoms
- Joint pain and swelling
- Myalgia
- Restriction of joint movement
systemic sclerosis : GI
- GORD
- Dysphagia
Oesophageal dysmotility is caused by atrophy and dysfunction of the smooth muscle, as well as fibrosis of the oesophagus. It causes swallowing difficulties, chest pain, acid reflux and oesophagitis.
Systemic sclerosis: respiratory
- Pulmonary fibrosis
- Pulmonary hypertension
* Leading cause of death in SSc
.
Systemic sclerosis: Cardiovascular features
- Microvascular coronary artery disease and subsequent MI
- Pericarditis
- Arrhythmias
- Left ventricular dysfunction
systemic sclerosis: Renal features
Scleroderma renal crisis
Presents with accelerated hypertension with:
* Oliguria
* Headache
* Fatigue
* Oedema
* Rapidly rising serum creatinine
* Proteinuria
* Microscopic haematuria
Systemic sclerosis: Genitourinary features
- Erectile dysfunction in 80-90% of men due to vascular changes
- Women may have dyspareunia
autoantibodies for systemic sclerosis
Antinuclear antibodies (ANA):
* In 90% of patients
Anti-centromere antibodies:
* Associated with limited cutaneous systemic sclerosis
Anti-scl-70 antibodies:
* Associated with diffuse cutaneous systemic sclerosis
management of systemic sclerosis
First line: smoking cessation, exercise, and physiotherapy
Second line
* Immunosuppression is considered in patients with lung involvement, myositis, or inflammatory arthritis:
* Inflammatory arthritis/myositis present: methotrexate
* nterstitial lung disease present: mycophenolate, cyclophosphamide, azathioprine, rituximab
management of renal crisis caused by systemic sclerosis
- 1st line: Angiotensin-converting enzyme (ACE) inhibitors + IV 0.9% saline
- This is to control hypertension in renal crises due to systemic sclerosis
Raynaud’s phenomenon
is where the fingertips change colour in response to even mildly cold triggers (e.g., opening the fridge). It is caused by vasoconstriction of the vessels supplying the fingers. The typical pattern is:
- First white, due to vasoconstriction
- Then blue, due to cyanosis
- Then red, due to reperfusion and hyperaemia
Raynaud’s disease
is where Raynaud’s phenomenon occurs without an associated systemic disease. It is idiopathic and makes up 80-90% of patients with Raynaud’s phenomenon
Treatment options for Raynaud’s include:
- Keeping the hands warm (e.g., gloves and hand warmers)
- Calcium channel blockers (e.g., nifedipine)
- Other specialist drugs include losartan, ACE inhibitors, sildenafil and fluoxetine
sjogrens syndrome
is an autoimmune condition of unknown aetiology affecting the exocrine glands leading to the main symptoms of:
- dry eyes (xerophthalmia)
- dry mouth (xerostomia)
- enlargement of the parotid glands.
It can happen in isolation or be secondary to another autoimmune condition such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or systemic sclerosis (SSc).
having sjogrens syndrome put you at an increased risk of which diseases
- lymphoid malignancy
- Patients may develop primary biliary cirrhosis or chronic hepatitis
risk factors for Sjogrens
- Female
- History of rheumatological disease: RA, SLE, or SSc
presentation of Sjogrens
- Dry eyes
- Dry mouth
- Vaginal dryness
- Recurrent parotitis
- Enlarged parotid glands (bilateral0
- Fatigue
- Raynauds phenomemnon
- Chronic pain
investigations for Sjogrens
- Schirmer’s test
- Anti- Ro and and anti-La (SS-B) antibodies (ORAL backwards)
- Salivary gland biopsy if patient has unilaterally enlarged salivary glands to rule out malignancy
Schirmers test
- Filter paper is placed in the lower eyelid
- The test is positive if <5mm of paper is wet after 5 minutes
management of Sjogrens
Management primarily involves treating the symptoms:
- Artificial saliva for dry mouth
- Artificial tears for dry eyes
- NSAIDs for musculoskeletal symptoms
Behçet’s disease
is a multi-system disorder of unknown aetiology characterised by recurrent oral ulcers and is presumed to be an autoimmune disease.
It involves the mucocutaneous, ocular, cardiovascular, renal, gastrointestinal, pulmonary, vascular, musculoskeletal, urological, and central nervous systems
risk factors for Behcets
- Family history
- Age 20-40 years
- HLA-B51
presentation of Behcets
classic triad of:
- oral ulcers
- genital ulcers
- anterior uveitis
other symptoms of Behcets
Skin manifestations:
* Acne in atypical areas e.g. the arms and legs
* Erythema nodosum
Musculoskeletal manifestations:
* Arthritis
Vascular manifestations:
* Superficial thrombophlebitis
* Deep vein thrombosis
Gastrointestinal manifestations:
* Abdominal pain
* Diarrhoea
* Gastrointestinal ulceration – may present with features similar to inflammatory bowel syndrome
Respiratory manifestations – may suggest pulmonary aneurysm:
* Shortness of breath
* Cough
* Chest pain
* Haemoptysis
Neurological manifestations:
* Meningeal inflammation and signs of meningitis
* Memory loss
* Dysphasia
* Ataxia
investigations for Behcets
Pathergy testing
- Subcutaneous skin prick with a sterile needle shows induration with or without a pustule within 48 hours
Autoantibdies
- ANA and ANCA
Other tests are used depending on the presentation:
Lumbar puncture:
* Indicated when neurological involvement suspected
MRI brain with contrast:
* When large phlebitis or CNS involvement suspected
Colonoscopy:
* When gastrointestinal symptoms are present
Upper GI endoscopy:
* When gastrointestinal symptoms are present
CT chest, CT angiography of the chest, and pulmonary angiography:
* If a pulmonary aneurysm suspected
diagnosis of Behcets
Recurrent ulcers + 2 of the following in the absence of other systemic disease
- Recurrent genital ulceration
- Skin lesions are seen by a physician in an adult not receiving corticosteroids
- Eye involvement (uveitis/retinitis) observed by an ophthalmologist
- Positive pathergy test interpreted by a physician at 48 hours
manageemnt of Behcets
Ulcers
* 1st line: topical or oral corticosteroids e.g. triamcinolone paste
* 2nd line: colchicine or oral corticosteroid or immunosuppression therapy
* 3rd line: TNF inhibitors
Eyes, GI, CNS, Vascular
- Prednisolone
- ANticoagulation in vasc involvement
Polymyositis and dermatomyositis
are autoimmune disorders causing muscle inflammation (myositis)
Dermatomyositis just means there is involvement of the skin too e.g. Gottrens papules and Heliotrope rash affecting the eyelids
Polymyositis or dermatomyositis can be caused by
- underlying cancer, making them paraneoplastic syndromes.
- A viral infection may be the trigger (e.g., Coxsackie virus or HIV).
- Certain HLA genes are risk factors.
presetation of polymyositis and dermatomyositis
key: symmetrical proximal muscle weakness leading to difficulties standing froma chair, climbing stairs or lifting overhead
- gradual onset
- distal muscles usually spared util late disease
Polymyositis occurs without skin features
Dermatomyositis occurs with skin changes
- Gottrons
- Heliotrope rash
- Periorbital oedema
- Photosensitive erythematous rash
investigations for Polymyositis or dermatomyositis
KEY: Creatine Kinase- raised
Serum aldolase
- Raised
Muscle biopsy
- Perivascular or inter-fasciular inflammation
- Endothelial hyperplasia in intramuscular blood vessels
Anti-Mi-2 antibodies
- posiitve
Other causes of a raised creatine kinase include:
- Rhabdomyolysis
- Acute kidney injury
- Myocardial infarction
- Statins
- Strenuous exercise
most common myositis-specific antibodies
anti-jo-1 antibodies
management of polymyositis
Patients should be screened for malignancy
In combined muscle and skin disease
- **1st line: **oral corticosteroid initial therapy + photoprotection + treatment of skin disease + treatment of underlying malignancy
- 2nd line: methotrexate or azathioprine + photoprotection + treatment of skin disease + treatment of underlying malignancy
- 3rd line: other immunosuppressants e.g. ciclosporin
In skin disease alone
- 1st line: topical corticosteroids e.g. hydrocortisone/betamethasone/clobetasol
- Combined with moisturisers and photoprotection
- 2nd line: hydroxychloroquine
- 3rd line: immunosuppressants e.g. methotrexate
