Immune related multisystem disorders Flashcards
What is Ankylosing Spondylititis?
Chronic spinal inflammation that can result in spinal fusion and deformity Site of inflammation includes the enthesis No autoantibodies (‘seronegative’)
What are the main features of SLE?
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
What are some examples of connective tissue diseases?
Systemic lupus erythematosus Sjogren’s syndrome Autoimmune Inflammatory muscle disease Systemic sclerosis (scleroderma) Overlap syndromes
What are the key autoantibodies in SLE?
Antinuclear antibodies
Anti-double stranded DNA antibodies
Anti-phospholipid antibodies
What is Arthralgia?
Pain in joints
Tenderness but not obvious inflammation
Common in connective tissue disorders
What are the main features of autoantibodies?
Characteristic
May aid diagnosis
Correlate with disease activity
May be directly pathogenic
What is 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
What are the main manifestations of Lupus?
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’)
Cerebral disease – ‘cerebral lupus’ e.g. psychosis, depression
Haematological - pancytopenia
Who typically gets Lupus?
female aged between 15 – 45 years
Which rheumatoid conditions are seronegative?
OA
Reactive arthritis
Gout
Ankylosing Spondylitis
What are the key investigations for Lupus?
ESR
CRP is usually normal
Autoantibodies (ANA - immunofluroscent)
Antiphospholipid antibodies
What haematological investigations are done in Lupus?
Haemolytic anaemia, Lymphopenia, Thrombocytopenia
What renal i
investigations are done in Lupus?
very important to measure urine protein (most commonly urine protein:creatinine ratio [uPCR])
look at albumin
How can we measure disease activity in SLE?
Immune complexes
Unwell lupus patient has LOW complement C3 and C4 levels and HIGH levels of anti-ds-DNA antibodies
What is the aim of SLE treatment?
Treatment in SLE aims at remission or low disease activity and prevention of flares
What should patients with SLE be assessed for?
antiphospholipid antibody status
infectious and cardiovascular diseases risk profile
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 needs to be considered re management in Lupus patients?
Pregnancy planning
What is Sjorgren’s syndrom?
Autoimmune exocrinopathy
lymphocytic infiltration of especially exocrine glands and sometimes of other organs (extra-glandular involvement)
What does exocrine gland pathology result in?
Dry eyes (xerophthalmia) Dry mouth (xerostomia) Parotid gland enlarg
What is inflammatory muscle disease?
Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash
What is systemic scelrosis?
Thickened skin with Raynaud’s phenomenon
Dermal fibrosis, cutaneous calcinosis and telangiectasia
Skin changes may be limited or diffuse
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
Describe the pathology of Malar rash?
Lymphocytic invasion of the upper dermis
Immune complex deposition at the dermis/epidermis junction
How does SLE affect kidneys?
Thickening of Y-loop capillaries in glomeruli due to immune-complex deposition in the basement membranes
How does SLE affect the heart?
Libman sacks - non-infective endocarditis
Present with emboli/stroke
Depositions on the valves
What causes scleroderma aka systemic sclerosis?
Fibrous and excess collagen in the skin
What are the two forms of Scelroderma? What antibodies are involved?
Diffuse form: Antibodies to DNA topoisomerase
(Trunk involvement)
Limited form: Anticentromere antibody
(No Trunk involvement)
What are the limited form manifestations of scleroderma?
CREST
Calcinosis
Raynauds
Esophageal dysmotility
Sclerodactyly
Telangiectasia
What immunoflurosecnce pattern is seen in scleroderma?
Nucleolar immunofluorescence
What is indicated by a speckled ANA pattern?
Mixed connective tissue disease
What are some features of Dermatomyositis?
Tender inflamed muscles
Gottron’s papules (erythematous rash on dorsal aspect of hand on knuckles)
High CK
Where in the body is affected by Sarcoidosis?
Joints
Skin
Lungs
Lymphadenopathy
Heart
Eyes
Neuro
Liver
What are some cutaneous manifestations of sarcoidosis?
Lupus pernio (nasal lesion)
Erythem Nodosum (lower limb lesions)
What CNS affects seen in sarcoidosis?
Meningitis
CN lesions
What affects of sarcoid on the eyes?
Uveitis
Keratoconjuctivitis
What are the affects of sarcoid on the lungs?
Bi-hilar lymphadenopathy
Lymphocytosis
Fibrosis
How can sarcoid affect the liver?
Hepatitis
Cholestasis
Cirrhosis
What happens to Ca in Sarcoidosis?
Hypercalcaemia
Vit D hydroxylation by activated macrophages
How can we classify Vasculitis?
By the size of vessels:
Large vessel vasculitis
Medium vessel vasculitis
Immune complex small vessel vasculitis
ANCA-associated small vessel vasculitis
What are some large cell vasculitides?
Giant cell arteritis - elderly w headache (jaw claudication, scalp tenderness)
Takayasu Arteritis
What are some medium cell vasculitides?
Polyarteritis nodosa - commonly renal/mesenteric vessles (beading of vessels), Associated with Hep B
Kawasaki disease
What are some ANCA-associated small cell vasculitides?
Granulamatosis with polyangitis (prev Wegners’)
Eosinophilc granulamatosis with polyangitis (prev Churg-Strauss)
What rash is characteristic of vasculitis?
Palpable purpuric rash
What are the presenting features of Kawasaki’s disease?
Fever
Erythema of palms & soles
Conjunctivitis
Lymphadenopathy
Can affect coronary arteries (MI)
Diagnosis and management of temporal arteritis
Biopsy - granulomas, narrowing of lumen, lymphocytic infilitration of tunic media, multinuclear giant cells
ESR will be high
High dose steroids
What are the features of polyarteritis nodosa?
Necrotising arteritis
Often renal/mesenteric arteries
Nodular appearance on angiography (small aneurysms)
What are the features of granulmatosis with polyangitis?
ENT - nosebleeds
Lung - breathlessness
Kidneys - proteinuria/haematuria
c-ANCA directed against proteinase
What are the features of eosinophilic granulomatosis with polyangitis?
Asthma
Eosiniphilia
Vasculitis
P-ANCA directed against myeloperoxidase
