Connective tissue diseases Flashcards
Give examples for seronegative arthritis
Ankylosing spondylitis
Reactive Arthritis (Reiters syndrome)
Arthritis associated with psoriasis (psoriatic arthritis)
Arthritis associated with gastrointestinal inflammation (enteropathic synovitis)
What is SLE? What tissues does it affect and what autoantibodies is it associated with?
Chronic tissue inflammation in the presence of antibodies directed against self antigens
Multi-site inflammation but particularly the joints, skin and kidney
Associated with autoantibodies:
Antinuclear antibodies
Anti-double stranded DNA antibodies
Anti-phospholipid antibodies
What type of arthritis/ arthralgia can be seen in connective tissue disorders?
Non- erosive
Significance of serum auto-antibodies in connective tissue disorders?
May aid diagnosis
Correlate with disease activity
May be directly pathogenic
Name a common phenomenon seen in connective tissue disorders. What happens in this?
Does this phenomenon always indicate a connective tissue disorder
Raynaud’s phenomenon- Intermittent vasospasm of digits on exposure to cold
Typical colour changes – white to blue to red
Vasospasm leads to blanching of digit
Cyanosis as static venous blood deoxygenates
Reactive hyperaemia
Does NOT always indicated connective tissue disorder- most commonly an isolated and benign condition (‘Primary Raynaud’s phenomenon’)
Give examples for connective tissue disorders
Systemic Lupus Erythematosus (SLE)
Sjögren’s syndrome
Autoimmune inflammatory muscle disease: Polymyositis, dermatomyositis
Systemic sclerosis (scleroderma): Diffuse cutaneous, limited cutaneous
Overlap syndromes
What demographic is SLE commonly diagnosed in?
Females aged between 15-45
Clinical manifestations of SLE
Malar rash – erythema that spares the nasolabial fold
Photosensitive rash
Mouth ulcers
Hair loss
Raynaud’s phenomenon
Arthralgia and sometimes arthritis
Serositis (pericarditis, pleuritis, less commonly peritonitis)
Renal disease – glomerulonephritis (‘lupus nephritis’)- see IgG, immune complexes, inflammatory cells (monoctyes, macrophages), complement components
Cerebral disease – ‘cerebral lupus’ e.g. psychosis
SLE pathgenesis
Incompletely understood, current paradigm is as follows
Key auto-antibodies in osteoarthritis
None
Key auto-antibodies in reactive arthritis
None
Key auto-antibodies in gout
None
Key auto-antibodies in ankylosing spondylitis
None
Key auto-antibodies in systemic vasculitis
Anti nuclear cytoplasmic antibodies (ANCA)
Key auto-antibodies in rheumatoid arthritis
Rheumatoid Factor
Anti-cyclic citrullinated peptide antibody
also termed antibodies to citrullinated peptide antigens (ACPA)
Key auto-antibodies in SLE
Antinuclear antibodies (ANA)
Anti-double stranded DNA antibodies (anti-dsDNA)
Anti-phospholipid antibodies a.k.a anti-cardolipin antibodies
Give examples for different types of anti-nuclear autoantibodies (ANA)
Anti-Ro
Anti-La
Anti-centromere
Anti-Sm
Anti-RNP
Anti-ds-DNA antibodies
Anti-Scl-70
Cytoplasmic antibodies include:
Anti-tRNA synthetase antibodies
Anti-ribosomal P antibodies
Significance of ANA
Seen in all SLE cases
Not specific for SLE
Significance of anti-dsDNA
Specific for SLE
Serum level of antibody correlates with disease activity
Significance of anti-Sm antobodies
What is the antigen to these antobodies
Specific for SLE
Serum level of antibody does NOT correlates with disease activity
antigen is ribonucleoprotein
Significance of anti-phospholipid antibodies (a.k.a. anti-cardolipin antibodies)
associated with risk of arterial and venous thrombosis in SLE
may also occur in absence of SLE in what is termed the ‘primary anti-phospholipid antibody syndrome
Significance of Anti-Ro antibodies and anti-La antibodies (antigen is ribonucleoprotein for both btw)
Secondary Sjögren’s syndrome
Neonatal lupus syndrome (transient rash in neonate, permanent heart block)
Significance of Anti-ribosomal P antibodies
Cerebral lupus
SLE investigations
Inflammation:
high ESR but C-reactive protein is typically normal unless infection or serositis/arthritis
Haematology:
Haemolytic anaemia, Lymphopenia, Thrombocytopenia
Renal:
very important to measure urine protein (most commonly urine protein:creatinine ratio [uPCR])
look at albumin
Immunological:
Antinuclear antibodies
Anti-double-stranded DNA antibodies - highly specific, correlate with disease activity
Complement consumption – e.g. low C4 and C3
Clotting – antiphospholipid antibodies
Lupus anticoagulant and anti-cardiolipin antibodies
In treated patients SOME changes may reflect ADVERSE REACTIONS TO MEDICATION
e.g. abnormal liver function (‘transaminitis’) or fall in neutrophil count (neutropenia)
What would happen to anti-dsDNA levels and complement levels in unwell lupus patients
Unwell lupus patient has LOW complement C3 and C4 levels and HIGH levels of anti-ds-DNA antibodies
What happens to eGFR, serum creatinine and urea, blood albumin level and urine protein level/ urine protein creatine ratio in SLE?
Fall in eGFR, leading to elevated serum urea and creatinine
Hypoalbuminuria and proteinuria/ elevated urine protein: creatine ratio in urine
What would happen to blood hemoglobin, platelet count, lymphocyte count and reticulocyte count in SLE
Fall, fall, fall, increase
What are the aims of treatment of SLE?
Induce remission and prevent relapse
How is SLE treated?
Hydroxychloroquine is recommended in all patients with lupus
Maintenance treatment glucocorticoids should be minimised and, when possible, withdrawn.
Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of glucocorticoids
In persistently active or severe disease we use cyclophosphamide and B cell targeted therapies (rituximab and belimumab)
What is Sjogren’s syndrome
Autoimmune exocrinopathy
lymphocytic infiltration of especially exocrine glands and sometimes of other organs (extra-glandular involvement)
What symptoms does exocrine gland pathology cause in Sjogren’s syndrome
Dry eyes (xerophthalmia)
Dry mouth (xerostomia)
Parotid gland enlargement
Extra-glandular manifestations of Sjogren’s sydrome
Commonest extra-glandular manifestations are non-erosive arthritis and Raynaud’s phenomenon
What is secondary Sjogren’s syndrome
Termed ‘secondary’ Sjögren’s syndrome if occurs in context of another connective tissue disorder e.g. SLE
What do we see on salivary gland biopsy in Sjogren’s syndrome
Lymphocytic infiltration predominantly CD4 helper T cells and to lesser extent B lymphocytes
What test can be used to assess tear production?
Schirmer’s test – a test to assess tear production. Filter paper is placed under lower eyelid and extent of wetness measured after 5 minutes. Abnormal is <5mm after 5 minutes
What is inflammatory muscle disease
Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash
Skin changes in dermatomyositis
Lilac-coloured (heliotrope) rash on eyelids, malar region and naso-labial folds
Red or purple flat or raised lesions on knuckles (Gottron’s papules)
Subcutaneous calcinosis
Mechanic’s hands (fissuring and cracking of skin over finger pads)
Abnormal investigations in INFLAMMATORY MUSCLE DISEASE
Elevated CPK, abnormal electromyography, abnormal muscle biopsy (polymyositis = CD8 T cells; dermatomyositis = CD4 T cells in addition to B cells)
What conditions are associated with inflammatory muscle disease?
Malignancy, pulmonary fibrosis
What is scleroderma
Thickened skin with Raynaud’s phenomenon
Dermal fibrosis, cutaneous calcinosis and telangiectasia
What are the two broad categories of scelroderma
Diffuse systemic sclerosis
Limited systemic sclerosis
Symptoms of diffuse systemic sclerosis
What autoantibody is associated with it?
Fibrotic skin proximal to elbows or knees (excluding face and neck)
Pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
Short history of Raynaud’s phenomenon
Anti-topoisomerase-1 (anti-Scl-70) antibodies
Symptoms of limited systemic sclerosis?
What autoantibody is involved?
Fibrotic skin hands, forearms, feet, neck and face
Pulmonary hypertension
Long history of Raynaud’s phenomenon
Anti-centromere antibodies
What is a subtype of limited systemic sclerosis
CREST
It stands for Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
Digital ischemia in scleroderma
What is overlap syndrome
When features of more than 1 connective tissue disorder are present e.g. SLE and inflammatory muscle disease we can use the term overlap syndrome
What term describes presence of incomplete features of a connective tissue disease
undifferentiated connective tissue disease
What is mixed connective tissue disease and what autoantibody is associated with it?
a group of patients with features of seen in SLE, scleroderma, rheumatoid arthritis, and polymyositis were identified by the presence of an autoantibody:
Anti-U1-RNP antibody
….this condition was termed Mixed Connective Tissue Disease (‘MCTD’)
((U1-RNP are uridine-rich small nuclear ribonucleoproteins))
Autoantibodies associated with Dermato-/Polymyositis
Anti-tRNA transferase antibodies
E.g. histidyl transferase (also termed anti-Jo-1 antibodies)
Autoantibodies associated with Sjögren’s syndrome
No unique antibodies but typically see
Antinuclear antibodies - Anti-Ro and anti-La antibodies
Rheumatoid factor
