Multi-System Disease Flashcards
Describe the aetiology of SLE
Not fully understood
Loss of tolerance to self
production of immune complexes - autoantibodies and antigens
These are the deposited in affected organs
How might SLE present?
CONSTITUTIONAL SYMTPOMS
fever, fatigue, weight loss
MUCOUS MEMBRANES
ulceration of hard palate
SKIN
acute lupus malar rash with sparing of nasolabial folds
ALOPECIA
REYANUDS PHENOMENON
VASCULITIS
RENAL
~50% of patients, lupus nephritis
LUNG
pleuritis, pneumonitis, ILD, pulmonary HTN, alveolar haemorrhage
CARDIAC
pericarditis, non-infective endocarditis (Libman Sacks Syndrome), myocarditis, CAD
NEURO
cognitive dysfunction, delirium, psychosis, seizures, headache, peripheral neuropathies
OPTHALMOLOGIC
keratoconjunctivitis sicca (secondary sjogrens)
HAEMATOLOGIC
anaemia, leukopenia, thrombocytopenia, lymphadenopathy, splenomegaly
GI TRACT
oesophagitis, lupus hepatitis, acute pancreatitis
Describe Jaccoud’s Arthropathy
Seen in 90-95% of patients with Lupus at some point in the disease
Deforming NON-EROSIVE Arthropathy
Characterised by ulnar deviation of the 2nd - 5th fingers with MCP subluxation
Thought to be caused by ligamentous laxity
when hand relaxed - looks normal
when patient tries to move hands and use ligaments - hand looks deformed
What are the 6 screening questions you should ask in a patient who you suspect CTD?
Hair Loss Dry Eyes Rashes (esp photosensitive) Mouth Ulcers Raynauds Joint Pains
What could you argue is one of the most important tests in a patient with SLE to look at disease activity
Urine Dipstick
= MUST TEST - FIRST SIGN OF RENAL INVOLVEMENT
look for proteinuria and haematuria for nephritis
What specific blood test results would you expect to see in a patient with SLE?
Anti-nuclear antibody ANAs (increased - useful in distinguishing SLE from other CTDs)
Anti ds DNA antibody (increased in active disease)
Complement levels (decrease in active disease)
Lymphocytes (classically reduced in active lupus)
How do you diagnose anti-phospholipid syndrome?
AT LEAST ON CLINICAL FEATURE
Vascular event e.g. DVT, VTE, stroke, TIA
Pregnancy morbidity including fetal death after 10 weeks gestation, pre-eclampsia or placental insufficiency, multiple (3 or more) embryonic losses (
List the aetiology of antiphosphlipid syndrome
Can be PRIMARY
Or SECONDARY - most commonly to SLE
should always ask SLE patients if they have a history of VTE or pregnancy morbidity
To diagnose SLE you need 4 out of 11 of the diagnostic criteria (at least one clinical and one immunologic), what are the 11 diagnostic criteria?
1- Malar Rash
2 - Discoid Rash
3- Photosensitivity
4- Oral Ulcers
5 - Non-erosive arthritis
6 - Serositis e.g. pleuritis, pericarditis
7 - Renal Disorder - persistent proteinuria or cellular clasts
8 - CNS Disorder - seizures or psychosis
9 - Haematological Disorder - haemolytic anaemia, lymphopenia, thrombocytopenia
10 - Immunological Disorder anti dsDNA antibody
11 - ANA positive
If the APTT is prolonged in a patient with ?antiphopholipid antibody syndrome, what further test should be done?
A lupus anticoagulant effect that effects APTT will not correct in a mixing study with normal plasma, then do dRRVT (will also be prolonged)
What patient population does SLE usually affect?
Women of child bearing age
Describe Reynauds Phenomenon
Episodic vasospasm of extremities triggered by cold and emotional stress, fingers go white (decreased circulation due to vasospasm), then blue (as recirculated blood is deoxygenised very quickly to hypoxic tissue) and then painful and red (as tissues go back to normal)
Primary Reynauds is common 6-10% of general population
Secondary Reynauds has many causes
List some of the causes of Secondary Reynauds and when are you more likely to think of a secondary cause?
CHEMICAL OR DRUG EXPOSURE
e.g. beta blockers, COCP, chemotherapy
OCCLUSIVE ARTERIAL DISORDERS
e.g. external compression, carpal tunnel syndrome, buergers disease, thrombosis and embolization
OCCUPATION
e.g. vibrating machinery, cold
INTRAVASCULAR
e.g. ploycythemia vera, leukaemia, thrombocytosis,
MISCELLANEOUS
e.g. malignancy, anorexia nervosa
INCREASING AGE OF ONSET - more likely to be pathological process than primary.
Describe the spectrum of scleroderma
Localized Scleroderma -Thickening of skin and dermis
Systemic Sclerosis
Limited Systemic Sclerosis (CREST)
Diffuse Systemic Sclerosis
Describe the clinical features of LIMITED SYSTEMIC SCLEROSIS
Formerly known as CREST syndrome - anti centromere
Calcinosis (deposits of calcium phosphate in fingertips)
Raynauds
E(oesophageal dysmotility)
Sclerodactyly (distal) + scleroderma face and neck
Telangectasia
(now can also get pulmonary hypertension, fibrotic lung disease and mid gut disease)
Describe the clinical features of DIFFUSE SYSTEMIC SCLEROSIS
Raynauds Digital Ulceration Scleroderma proximal to elbows Interstitial Lung Disease GI Renal Cardiac Scl-70 and RNA polymerase III antibodies
If you had a patient with Reynauds, what test could you do to look for progression to systemic sclerosis?
Nail Fold Capillaroscopy - changes very strongly associated with progression to systemic sclerosis.
Why do you have to be careful when prescribing steroids in a patient with systemic sclerosis?
Can precipitate a RENAL CRISIS
Hypertension, rapidly deteriorating renal function, flash pulmonary oedema, seizures
Can protect patients from this by giving them ACE inhibitors
Describe what is meant by Sicca Symptoms
Lymphocytic infiltration of exocrine glands
Mucosal Dryness - eyes, mouth, larynx, pharynx and vagina
What are the causes of Sicca Symptoms?
Primary Sjogrens Syndrome
most strongly associated - systemic autoimmune
Secondary Sjogrens Syndrome
e.g. to RA, SLE, systemic sclerosis, MCTD
What disease are people with Primary Sjogrens Syndrome at a 20% increased risk from?
Lymphoma (often MALT - mucosal associated lymphoma)
What symptoms do you get in Primary Sjogrens Syndrome?
Fatigue Dry Eyes Dry Mouth Vaginal Dryness Parotid and Submandibular Gland Swelling
What is the typical autoantibody profile of Primary Sjogrens Syndrome?
RF+ ANA+ anti Ro + anti La+ IgG++++ ESR ++++ (>100)
What investigations can be done to investigate Primary Sjogrens Syndrome?
Autoantibodies Schirmer Test Parotid and submandicular gland USS Minor labial gland biopsy Salivary Flow
Myalgia is commonly associated with many autoimmune diseases, what symptoms would make you more concerned and make you think of an inflammatory myopathy?
Muscle Weakness (usually proximal and symmetrical) Raised Muscle Enzymes
Describe the salient points of polymyositis
Inflammation of striated muscle Proximal Muscle Weakness Distal muscles spared until late disease Occular muscles usually spared NO RASH Creatine Kinase raised, also AST and ALT (produced by muscle) 20% have Jo-1 mutation - should be investigated for interstitial lung disease Definitive Test = muscle biopsy
Describe the salient points of dermatomyositis.
Proximal muscle weakness with distal sparing until late disease and occular sparing
Usually systemic upset - fever, arthralgia, weight loss
RASH - blue purple discolouration of upper eyelids, periorbital oedema, flat red rash on face and upper trunk, raised purple/red scaly patches on extensor surfaces (Gottrons Papules)
Investigations - again raised CK, AST and ALT, muscle biopsy is definitive test, also thorough malignancy screen - STRONG ASSOCIATION WITH MALIGNANCY.
What antibody is associated with mixed connective tissue disease?
RNP
What clinical features have a higher incidence in MCTD?
Erosive Arthritis
Pulmonary Artery Hypertension
In one sentence describe Sarcoidosis
A multisystem disorder with unknown aetiology, characterised by non-caeseating granulomas in involved organs
What is the organ most commonly affected in Sarcoidosis?
Lung
Describe the staging of pulmonary involvement in sarcoidosis
STAGE 0 Normal CXR STAGE 1 Bilateral Hilar Lymphadenopathy (BHL) STAGE 2 BHL + Infiltrates STAGE 3 Dense pulmonary infiltrates with functional limitation +/- cor pulmonale + no BHL STAGE 4 Fibrosis
How does acute sarcoidosis usually present?
With erythema nodosum and polyarthralgia
If you see BHL on CXR what next investigation should be ordered?
HRCT
What are the 4 differential diagnoses when you see BHL on a CXR
Sarcoidosis
Lymphoma
Pulmonary TB
Malignant Infiltration of Mediastinal LN e.g. from carcinoma of bronchus
Describe the investigations you would do in Sarcoidosis.
BLOODS
Raised ESR, serum ACE, LFTs, lymphopenia, hypercalcaemia, and raised immunoglobulin’s
CXR + HRCT
ECG and lung function tests
Tissue Biopsy - will show non-caeseating granulomas
Describe the management of sarcoid
BHL only
No Tx - most recover spontaneously
Acute Sarcoidosis
Bed rest and NSAIDs
Indications for corticosteroids include
parenchymal lung disease, uveitis, hypercalcaemia, neurological or cardiac involvement. High Dose 4-6 weeks and then taper down based on clinical picture
In refractory disease - immunosuppressant’s, or lung transplantation.
What are the names of the large vessel vasculitises and Ix to diagnose them?
Temporal Arteritis - ESR, biopsy
Takayasu’s Arteritis - ESR, MRI
What are the names of the medium vessel vasculitises and Ix to diagnose them?
Polyarteritis Nodosa - ESR, renal angiography
Kawasaki’s Disease -
What are the names of the small vessel vasculitises?
ANCA positive
Wegeners -renal biopsy, red cell clasts, c-ANCA
Microscopic Polyangitis - renal biopsy, red cell clasts, p-ANCA
Churg Strauss Syndrome
ANCA negative
Henonch-Schonlein Purpura
Describe the salient points of Henoch-Schonlein Purpura
IgA mediated autoimmune hypersensitivity vasculitis if childhood (peak 4-6 years)
Often preceding URTI
Main Sx - purpura, arthritis, adbo pain and Gi bleed, orchitis and nephritis
What are the red flag symptoms that make you think of vasculitis?
Rash - palpable purpura (commonest)
PUO and other constitutional Sx
Inflammatory arthritis/general arthralgia
Myositis/Myalgia
Neuropathy - mononeuritis, polyneuritis
Glomerulonephritis
End organ ischamiea - abdo pain, acute visual loss
Anaemia, raised inflammatory markers with no ?cause
Multi-system disease
Describe the pathophysiology of vasculitis?
Inflammatory condition of blood vessel walls
Leads to either destruction (aneurysm or rupture) or stenosis - which leads to end organ damage in various organs.
What are the cutaneous manifestations associated with cushings syndrome?
Purple Abdominal Straie
Facial Acne
Plethora
What are the cutaneous manifestations associated with Addisons Disease?
Hyperpigementation - Buccal Muscoa, Palmar Creases,
What are the cutaneous manifestations associated with Hypothryoidism?
Peaches and Cream Complexion
Loss of Lateral 1/3 eyebrow
Dry Skin
Periorbital oedema
What are the cutaneous manifestations associated with Hyperthryoidism?
Pretibial Myxoedema (mucin deposits in skin)
Acropachy (mucin deposits in nail bed)
Eye signs - exopathlamos - Graves
What are the cutaneous manifestations associated with Porphyria?
Sun exposed- Blistering, Scarring, Fragility
Facial hirsutism
What are the cutaneous manifestations associated with Hyperlipidaemia?
Xanthalasma
Tendon Xanthomas (familial hypercholesterolaemia)
Eruptive Xanthomas (hypertriglyceridaemia)
Corneal Arcus
What are the cutaneous manifestations associated with Diabetes?
Acanthosis nigricans - Also occurs in obesity
Necrobiosis lipoidica - thin skin, full of granulomas
Infections e.g. candida
What are the cutaneous manifestations associated with Gout?
Tophi
and periarticular urate
Describe what can cause neutrophilic dermatoses (have a bluey edge to lesion)
Pyoderma Gangrenosum
e.g. IBD, haematological malignancy, RA
Sweet’s syndrome = acute febrile neutrophilic dermatosis
e.g. Myeloma, Leukaemia, Other malignancies
What are the 2 stages of cutaneous T cell Lymphoma (mycosis fungoides)
Patch and plaque stage - 5-30 years, PUVA phototherapy, looks like psoriatic plaques that are refractory to treatment.
Tumour stage - get abnormal T cells stuck in the skin
Describe the cutaneous manifestations of the three stages of syphilis
SPIROCHETES Primary Painless chancre Secondary rash - classically affects palms and soles, or can be systemic, can also see snail track ulcers Tertiary Gumma - form of granuloma, growth
What is the name of the rash seen in Lyme Disease
Erythema Migrans
Describe the triad of Reiters Syndrome and the classic cutaneous manifestations
Urethritis, arthritis, uveitis
Psoriasiform rashes
e.g. Circinate balanitis, Keratoderma blenorrhagica
What are the cutaneous manifestations seen in IBD?
erythema nodosum
pyoderma ganrenosum
Describe the salient points of Bechets Disease?
Orogenital ulcers, uveitis (triad)
Pyoderma Gangrenosum
Pathergy (skin condition in which a minor trauma such as a bump or bruise leads to the development of skin lesions or ulcers that may be resistant to healing)
What are the cutaneous manifestations of sarcoid?
Erythema Nodosum
Lupus Pernio
Subcutaneous Nodules
Describe the cutaneous manifestation associated with CTD
Photosensitivity Rashes
e.g. acute malar rash in lupus
Nailfold changes
Livedo
What are the cutaneous manifestations of scurvy?
Corkscrew hairs
Perifollicular haemorrhages
Bleeding gums
Describe the cutaneous manifestations of neurofibromatosis Type 1
Multiple café au lait spots
Axillary freckling
Lisch nodules (iris)
What is the commonest cause of erythema nodosum?
Strep Throat
What are the 5 types of acanthosis nigracans based on cause
1 - Familial 2 - Endocrine 3 - Obesity 4- Drug related 5 - Malignancy
What malignancies are commonly implicated in dermatomyositis?
Breast, Lung, Ovarian, GI
What is Lofgrens Syndrome?
BHL + polyarthralgia + erythema nodosum = acute presentation of sarcoid
