Connective tissue diseases Flashcards
What is the prevalence of common CTD worldwide?
RA
- 16% in women
- 44% in men
Global2
0.24% (of 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency)
Total (direct, indirect, and intangible) annual societal costs
>39 billion USD
SLE
Malaysia
43/100,000 overall
uk
28 per 100,000
estimated patient group of 10500 in England and Wales
Racial/gender differences
Afro-Caribbean women 206 per 100,000
SLE is 8 to 10 times more common in women than in men
globally
40-100 per 100,000
global burden
Total 12-month direct costs for all patients withSLEamount to more than US$207 million ($13,305 per patient)
Primary Sjogrens 250 per 100,000(commonest)
Systemic sclerosis 20 per million
Polymyositis/Dermatomyositis 5 per 100,000
MCTDincidence 2 persons per 100,000 person-years
What are the impact and outcomes of RA?
Physical and work disability
Almost 40 percent of patients with RA will have work disability within 10 years of diagnosis
Reduced quality of life
Joint replacement surgery
Up to 25% of patients with RA will have a joint replacement in the 20 years after disease onset
Development of other chronic diseases
Cardiovascular disease, lung diseases, psychiatric disorders, osteoporosis and fractures, and some malignancies (eg lymphoma, lung and non-melanotic skin cancers)
Premature mortality compared with the general population
cardiovascular disease, respiratory disease, and cancer leading causes of death in RA
What are the issues with epidemiological data for CTD(especially RA)
Data (US centric)
Recognition
Impact in developing countries
Impact of new therapies
What is mixed connective tissue disease?
Mixture of RA, SLE, Myositis, Scleroderma
Raynauds, digital ulcers Puffy hands Fatigue Muscle Involvement Skin Arthritis ILD-interstital lung PAH
What Investigations are done for mixed connective tissue disease?
It does have its own antibody…………………. RNP Anti-U1 RNP Higher incidence If RNP antibody positive checg for EROSIVE ARTHRITIS PAH -CXR for ILD
How does Antiphospholipid syndrome manifest and what are the complications?
Antiphospholipid syndrome (APS)
Pathophysiology
Antibodies to cell membrane phospholipids.
Presentation
CLOT:
Arterial (cerebral, renal) and venous (PE)CLOTs. Recurrent PEs may lead to pulmonary hypertension.
Coagulation defects.
Livedo reticularis.
Obstetric problems: recurrent miscarriage.
Thrombocytopenia
In most cases it is a standalone condition, but it affects 25% of SLE patients.
Hypercoagulability and recurrent thrombosis can affect virtually any organ system, including the following:
Peripheral venous system (DVT)
CNS (stroke, sinus thrombosis, seizures, chorea, reversible cerebral vasoconstriction syndrome)
Obstetric (pregnancy loss, eclampsia)
Pulmonary (PE, PH)
Dermatologic (livedo reticularis, purpura, infarcts/ulceration)
Cardiac (Libman-Sacks valvulopathy, MI, diastolic dysfunction)
Ocular (amaurosis, retinal thrombosis)
Adrenal (infarction/hemorrhage)
MSK (AVN of bone)
Renal
(thrombotic microangiopathy)
What is the diagnostic criteria for antiphospholipid syndrome?
At least one clinical and one lab criteria
Clinical
Vascular thrombosis
Pregnancy morbidity
≥1 late-term spontaneous abortions
≥1 premature births of a morphologically healthy neonate at or before 34 weeks’ gestation because of severe preeclampsia or eclampsia or severe placental insufficiency
≥3 unexplained, consecutive, spontaneous abortions (<10 weeks’ gestation)
Lab criteria
Elevated levels of immunoglobulin G (IgG) or immunoglobulin M (IgM) anticardiolipin (aCL) Anti–beta-2 glycoprotein I
Lupus anticoagulant
On at least two occasions at least 12 weeks apart
What DMARDS are safe to use in pregnancy?
Hydroxychloroquine in all SLE pregnancies
Azathioprine is safe in pregnancy
In severe refractory maternal disease consider pulsed iv methylprednisolone, IVIG or 2nd or 3rd
trimester cyclophosphamide
Withdraw known teratogens
Mycophenolate, methotrexate and cyclophosphamide
What maternal antibodies need to checked in pregnancy and why?
Maternal Ro/La should be checked due to the 1-2% risk of foetal congenital heart block. If positive, a foetal cardiac scan should be performed at 16-20 and 28 weeks gestation.
How can Antiphospholipid syndrome be investigated & managed?
Investigations
Coagulation:
Paradoxical ↑aPTT: proteins are anticoagulant in vitro, but pro-thrombotic in vivo. Normal PT. Same pattern seen in heparin use and clotting factor deficiencies.
Follow with mixing study. In a factor deficiency, clotting will be normalised, but in APS it will remain abnormal.
Antibodies:
Anti-cardiolipin IgG/M.
Lupus anticoagulant test: looks for clotting pattern characteristic of presence of lupus anticoagulant IgG/M. ‘Anticoagulant’ refers to in vitro property, as in vivo it’s pro-thrombotic.
Anti β2-glycoprotein IgG/M.
Diagnosis
{Clotsormiscarriage >10 weeks} plus {Ab +ve (any antibody) on 2 occasions}.
Management
Manage vascular risk factors: smoking cessation, weight loss, exercise, blood pressure and lipid control.
Aspirin for primary prevention of arterial thrombosis and obstetric complications, though evidence of benefit is mixed.
If thrombosis occurs, give LMWH followed by long-term warfarin. Prednisolone, IVIG, or rituximab can be used if anticoagulation is insufficient.
During pregnancy: aspirin once pregnancy confirmed and LMWH once fetal heart visualised.
What Conditions give the following patterns on immunofluorescence
1) Homogenous
2) Speckled
3) Nucleolar
4) Centromere
1)Homogenous
DsDNA-SLE
Histones-DLE,Autoimmune hep
2)Speckled
RNA polymerase-Diffuse SS Scl-70-Diffuse SS Anti sm-SLE,drug induced SLE RO-Sjogens LA-Sjogrens 3)Nucleolar-SS and polymyositis 4)Centromere-Limited ss
What is Sjorgen’s Syndrome
Sjogren’s syndrome
Background
Pathophysiology
Autoimmune disease characterised by lymphocytic infiltration of exocrine glands, especially salivary and lacrimal.
Extraglandular manifestations also occur, due to vasculitis and lymphocytic infiltration of other organs.
Classification
Primary Sjögren’s syndrome: standalone condition.
Secondary Sjögren’s syndrome: SS in the presence of another (usually autoimmune) disease, most commonly RA (30% of RA patients), SLE (20%), systemic sclerosis (50%), or primary biliary cirrhosis (10%).
Epidemiology
Affect 0.1-4%
Like many autoimmune conditions, it is commoner in women (x10) and middle age
What are the clinicals manifestations of Sjorgens and what are they at risk of?
Presentation
Sicca symptoms (Latinsiccus= dry) are the commonest manifestation:
Dry eyes (‘keratoconjunctivitis sicca’ or ‘xerophthalmia’), often described as ‘gritty’.
Dry mouth (‘xerostomia’). Can lead to eating difficulty, salivary stones, dental caries, and candidiasis.
Other features:
Parotid enlargement.
Dryness of other mucous membranes: respiratory tract (→cough), GI tract (→dysphagia), vagina (→dyspareunia).
Extraglandular presentations: arthralgia, fatigue, lymphadenopathy, interstitial lung disease, polyneuropathy, renal tubular acidosis, thyroid disease, pancreatitis.
Fatigue
Skin features: dryness (‘xerosis’), purpuric rash, Raynaud’s, annular erythema.
Non-Hodgkin’s lymphoma: >18.9x commoner than general population
20 fold increase in lymphoma
What are the differentials for wlSicca syndrome?
DDx: Sicca symptoms
Age-related gland atrophy. Commonest cause.
Drugs: anticholinergics, antihistamines, sympathomimetics, benzodiazepines, antidepressants, opioids.
Sjogren’s syndrome.
Parotid infiltration: sarcoidosis, lymphoma/leukaemia.
Infection: hepatitis C, HIV.
What Investigations and management are done for Sjorgen’s
Diagnosis and investigation
Diagnosis requires all 3 of:
Subjective dry eyes and/or mouth.
Objective evidence of dry eyes and/or mouth. Tests of dry eyes include Schirmer’s test of tear function (filter strip under eyes), or ocular surface staining (Rose Bengal, lissamine green, or fluorescein). Tests of ↓salivary production include whole sialometry (spit into test tube), parotid sialography, or salivary scintigraphy.
Serological or histopathological evidence of SS. Diagnostic autoantibodies are anti-Ro/SS-A (50%) and anti-La/SS-B (35%). Biopsy of minor salivary glands may show focal lymphocytic sialoadenitis.
Other investigations:
Basic bloods: ↓Hb (20%), ↑ESR/CRP (30%).
Non-diagnostic autoantibodies: ANA (70%), RF (50%).
Others immunological features:screen development of lymphoma ↑gammaglobulins, ↑cryoglobulins, ↓complement.
Management
Lifestyle and preventative:
Regular fluid sips and chewing gum.
Good oral hygiene.
Avoid exacerbating drugs, including smoking and alcohol.
Medical:
ACR/EULAR criteria for diagnosis- BSR management guidelines
Sicca symptoms-
Dry eye- tears/stimulants
Dry mouth- sugar free pastilles, artificial saliva, oral hygiene
Dry skin- moisture
Dry vagina- vaginal creams
Lung involvement- Prednisolone/DMARDs/Cyclophosphomide/ Rituximab
Neurologic involvement- conservative management and systemic treatments
Cytopenias- Cyclosporine/ Systemic
What are the risk factors for Raynaud’s ?
6 -10%population
F > M
Raynaud phenomenon manifests as recurrent vasospasm of the fingers and toes and usually occurs in response to stress or cold exposure
In individuals with Raynaud phenomenon, one or more body parts experience intense vasospasm with associated color change and subsequent hyperemia. Patients often describe 3 phases of change with intial white (vasoconstriction), followed by blue (cyanosis), and then red (rapid blood reflow). The affected body parts are usually those most susceptible to cold injury. A clear line of demarcation exists between the ischemic and unaffected areas (see the image below).
Progressive systemic sclerosis including the diffuse and limited
SLE
Mixed connective tissue disease
DM and PM
RA
Sjögren syndrome
Vasculitis
Primary pulmonary hypertension
Episodic vasospasm of extremities triggered by:
COLD
Emotional Stress
Primary - common
Secondary - multiple causes
Caused by reversible constriction of small arteries, capillaries arterioles and venules.
Associated with many Connective Tissue Diseases
What are the 2 main types of systemic sclerosis and how they present?
Limited cutaneous systemic sclerosis (lcSSc): skin fibrosis restricted to hands, distal arms, face, and neck.
Diffuse cutaneous systemic sclerosis (dcSSc): skin fibrosis includes chest, abdomen, and upper arms. Internal organ disease more common.
Epidemiology
1/10,000 UK prevalence.
5x commoner in women.
Peak onset in 40s.
Diffuse
Scl-70, RNA polymerase III
Raynauds Digital ulceration Diffuse skin thickening ILD GI Renal(RNA polymerase III associated with scleroderma renal crisis) Cardiac
Limited
Anti centromere
Calcinosis Raynauds oEsophageal (GI general) Sclerodactly Telangiectasia Scleroderma of neck and face PH Fibrotic lung disease Mild GI disease
How does systemic sclerosis present?
Presentation
Thickened, firm, tight skin (scleroderma):
Commonly affects the fingers, ‘sclerodactyly’. May lead to finger flexion contractures. Other finger changes in SSc include abnormal nailfold capillaries, fingertip pitting scars or ulcers, and puffiness. Similar changes seen in toes.
In the face, it can lead to microstomia (small mouth).
May be pruritic.
Often has a shiny appearance, and skin may become hyper/hypopigmented.
In addition to the GI tract, almost any internal organ can be affected, including:
Lungs: interstitial lung disease (SOB, cough, crackles), pulmonary hypertension.
Kidneys: scleroderma renal crisis, presenting with AKI, hypertension, and microangiopathic haemolysis or thrombocytopaenia.
Heart: heart failure (esp. RHF due to pulmonary HTN), pericardial disease, myocardial fibrosis, arrhythmias.
Connective tissue disease:
Tendon or bursal friction rubs.
Arthritis
Sicca symptoms: dry mouth, dry eyes.
Carpal tunnel syndrome.
Muscular pain/cramps. May be due to inflammatory myositis.
Non-specific symptoms, including fatigue, weakness, and sleeping difficulties, are also common.
What investigations are done for Systemic sclerosis?
Investigations
Diagnosis
Diagnosis requires presence of bilateral finger skin thickening, or a combination of other clinical features and auto-antibodies. Skin thickening which spares the fingers is unlikely to be SSc.
90% are anti-nuclear Ab +ve, including the following sub-types:
Anti-centromere Ab (50%). Associated with lcSSc.
Anti-Scl-70, aka anti-topoisomerase I (30%). Associated with dcSSc.
Anti-RNA polymerase III (20%).
Capillaroscopy – magnified nailfold visualisation to look for abnormal capillaries – can aid diagnosis.
Assessing disease extent
Basics bloods:
FBC: Hb may be low due to GI bleeding.
↑ESR/CRP suggests ongoing inflammation.
Organ involvement:
Kidneys: U&E, urinalysis.
Heart: ECG, echo.
Lungs: PFTs, CXR, CT chest.
GI tract: barium swallow, endoscopy.
How is systemic sclerosis managed?
Management
Skin and connective tissue disease:
Skin thickening: cyclophosphamide, methotrexate, or mycophenolate mofetil. Emollients or antihistamines for itch.
Raynaud’s: 1st line calcium channel blockers (e.g. amlodipine), 2nd line add/switch to PDE-5 inhibitors (e.g. sildenafil, tadalafil).
Calcinosis: consider surgical resection if severe.
Internal organ disease:
Oesophageal dysmotility: PPIs, prokinetic agent (e.g. metoclopromide, erythromycin).
Scleroderma renal crisis: ACEi, renal replacement therapy if severe.
ILD: cyclophosphamide, transplantation if severe.
Pulmonary HTN: PDE-5 inhibitor,endothelin receptorantagonist (bosentan, ambrisentan, macitentan).
Ongoing inflammation (synovitis, myositis, arthritis): low dose steroids.
Prognosis
dcSSc: 30% 10 year mortality, usually due to internal organ involvement, especially the lungs.
lcSSc: better prognosis, but requires monitoring for progression to diffuse disease.
What are the causes of secondary vasculitis?
Rheumatological
SLE
Rheumatoid arthritis
Sjogren’s syndrome
Malignancy
Haematological
Para-neoplastic
Drugs hydralazine propylthiouracil allopurinol sulfasalazine penicillamine
Infection (Direct damage to vessel wall) Steptococcus Staphylococcus Syphilis Rickettsia
Infection (immune complex) HIV Hepatitis B Hepatitis C!
What are eye symptoms of vasculitis?
Episcleritis is present in the superficial layers of the nasal portion of the eye, causing tenderness and discomfort. The patient has rheumatoid arthritis, but this reaction is nonspecific and occurs in other disorders.
Anterior uveitis is present. Although blindness can arise from anterior uveitis, this complication is much more common in posterior uveitis, which affects the vitreous body and retina.
The dark area in the sclera is typical of the scleromalacia. This darkening results from thinning of the sclera, which allows the pigment of the underlying choroid to be seen. Inflammatory manifestations such as episcleritis, scleritis, conjunctivitis, and iritis may precede scleromalacia.
Other disease with uveitis= Ankylosing spondylitis: iridocyclitis with synechiae
Ciliary injection and irregularity of the pupil are present. Adhesions between the iris and lens (synechiae) appear at the 1-o’clock and 4-o’clock positions. Synechiae are caused by repeated episodes of iritis and may eventually lead to glaucoma and blindness. The pupil is dilated from medication. The medial aspect of the sclera has been blanched by topical medication.
What are specific features of a vasculitic rash
Vasculitic ulcers can have quite specific features–deep,punched out appearance,painful,purpura associated,edges are bluish or redish
What are the red flags of mimics of vasculitis
Presence of a heart murmur Necrosis of lower extremity digits Splinter haemorrhages Prominent liver dysfunction History of recreational drug use History of high-risk sexual activity Prior diagnosis of neoplastic disease Unusually high fevers
mimics
Multiple myeloma Antiphospholipid Infective endocarditis Paraneoplastic syndromes Athermoatous vascular disease Cocaine and amphetamine use atheroembolic disease Hypersensitivity reactions Genetic(Marfans)
What are the causes of Purpura
In the blood Abnormal clotting - leakage Reduced platelets - leakage In the vessel wall Corticosteroids (thinned supporting tissue) - leakage Vasculitis – vessel death Meningococcaemia (infection → vasculitis) – vessel death Thrombosis – vessel death
Palpable purpura: vasculitis likely
Blisters, necrosis and ulcers: suggest vessel death
Look carefully at any ulcer : blue/purple edge suggests vasculitis
How is vasculitis treated?
Induction of remission
Risk of relapse – therefore maintenance needed
If relapse despite maintenance then consider escalation of treatment
Withdraw maintenance if persistent remission
Corticosteroids* (Induction then taper)
High dose – often IV initially
Consider steroid sparing strategies for maintenance
Cyclophosphamide / Rituximab (induction)
Methotrexate / Azathioprine (maintenance)
Plasma exchange (rescue / severe disease)
Rituximab (for relapsing disease)
Anti-cytokine biologics (for relapsing disease)
How can GPA present?
Systemic / ‘Vasculitic’ (67% ) Immediately organ threatening Alveolar haemorrhage Glomerulonephritis Scleritis Mononeuritis multiplex Systemic symptoms Fever Weight loss
Localised / ‘Granulomatous’ (33%) Not immediately organ threatening Upper respiratory tract ENT (sinusitis) Episcleritis Skin More often female / younger Only 5% will remain localised
Pulmonary lesions
Pulmonary nodules - may cavitate(eclude other causes such aspergillus,TB-bronchoscopy may be done
Diffuse alveolar haemorrhage
Summary
Features
upper respiratory tract: epistaxis, sinusitis, nasal crusting
lower respiratory tract: dyspnoea, haemoptysis
rapidly progressive glomerulonephritis (‘pauci-immune’, 80% of patients)
saddle-shape nose deformity
also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions
Investigations
cANCA positive in > 90%, pANCA positive in 25%
chest x-ray: wide variety of presentations, including cavitating lesions
renal biopsy: epithelial crescents in Bowman’s capsule
Management steroids cyclophosphamide (90% response) plasma exchange median survival = 8-9 years
How does Eosinophilic
Eosinophilic granulomatosis with polyangiitis (EGPA) is now the preferred term for Churg-Strauss syndrome. It is an ANCA associated small-medium vessel vasculitis.
Features
asthma
blood eosinophilia (e.g. > 10%)
pANCA positive in 60%
ENT - sinusitis / polyposis
NEUROLOGY - mononeuritis multiplex
SKIN - (biopsy shows eosinophils / granulomas)
CARDIAC (25%) - (myocarditis) - CCF»_space; angina
GI - abdo pain / bleeding / (poor prognostic sign)
Leukotriene receptor antagonists may precipitate the disease.
How does Microscopic polyangitis present?
Microscopic polyangiitis is a small-vessel ANCA vasculitis.
Features
renal impairment: raised creatinine, haematuria, proteinuria
fever
other systemic symptoms: lethargy, myalgia, weight loss
rash: palpable purpura
cough, dyspnoea, haemoptysis
mononeuritis multiplex
GI tract - abdominal pain, bleeding, ischaemia, ulceration
Investigations
pANCA (against MPO) - positive in 50-75%
cANCA (against PR3) - positive in 40%
How does HSP present?
Classic tetrad:
Rash: initially macular then purpuric symmetrical rash on buttocks and back of legs.
Severe skin necrosis in adults
Abdominal pain: may be accompanied by bloody diarrhoea, nausea, and vomiting.
Arthralgia: commonly knees and ankles, which may be swollen and tender.
Glomerulonephritis in following weeks, due to IgA deposition. Occurs in 30%, usually causing haematuria or proteinuria. Rarely causes nephrotic system or renal failure.
Investigations
ANCA negative
HSP:
Kidneys: urinalysis, U&E.
CRP
If the diagnosis is unclear, a renal biopsy could confirm it by showing IgA deposition.
Leucocytoclastic vasculitis with extravasation of erythrocytes
Check for other causes of purpura:
FBC: ↓platelets in ITP and leukaemia. ↓Hb in leukaemia.
Blood film: abnormal in ITP, leukaemia.
Abnormal clotting: LFTs, coagulation studies.
LP and blood culture if meningococcal disease suspected.
Adverse prognostic features:
Severe abdominal pain / bloody diarrhoea
Renal impairment (can progress to renal failure) – IgA nephropathy
Persistent rash > 1/12
Management
Simple analgesia.
Corticosteroids may be kidney protective.
How does Kawasaki present?
Medium vessel vasculitis.
Commonest around age 2, and rare after 5.
Signs and symptoms
Persistent fever, >5 days.
Dry, bilateral conjunctivitis.
Non-vesicular, desquamating rash, which starts at the extremities (inc. palms and soles).
Strawberry tongue.
May cause coronary artery aneurysms
Management
Acute: aspirin and IVIG. The one time where aspirin is used in kids, despite the risks of Reye’s.
Long-term: lifelong aspirin as 25% develop coronary artery aneurysms and are at risk of early MI
What is poly arteries nodosa?What are the triggers and how does it present?
Polyarteritis nodosa (PAN)
Pathophysiology and epidemiology
Necrotizing vasculitis of medium and small arteries, causing aneurysms, bleeds, and thrombosis.
ANCA -ve and does not cause glomerulonephritis.
Very rare, but commonest in middle-aged and in men.
20% are triggered by hepatitis B or C.
Signs and symptoms
Constitutional: general malaise, fever, weight loss, arthralgia, myalgia.
Skin: palpable purpura, ulcerations, tender nodules, livedo reticularis.
Neuro: asymmetric peripheral neuropathy (including mononeuritis multiplex), TIA.
Renal impairment due to ischaemia, with haematuria and proteinuria.
Abdominal pain from visceral vasculitis.
Management
Corticosteroids (e.g. prednisolone) are 1st line. Add methotrexate or azathioprine if needed.
Cyclophosphamide if organ involvement
How does giant cell arteritis present and what are the risk factors?
50% of patients also have polymyalgia rheumatica.
Signs and symptoms
Pain:
Unilateral throbbing headache.
Scalp tenderness e.g. on combing hair.
Jaw claudication.
Neck pain
Other symptoms:
Systemic symptoms: malaise, fever.
Painless, sudden visual loss, usually monocular, but can be bilateral. Transient loss initially (amaurosis fugax), but permanent loss is a potential complication. Usually due to anterior ischaemic optic neuropathy.(pale disc,cotton wool spots,irreversible blindness,haemorrhage)
Morning stiffness and shoulder pain due to polymyalgia rheumatica.
Chest or abdominal pain from aortitis (15%).
Signs:
Tender temporal artery.
Weak or uneven temporal artery pulse.
Pale, swollen optic disc.(Central retinal artery occulsion-pale retina,cherry red spot)
Cranial nerve lesions permanent diploma opthalmoplegia
Risk factors
Polymyalgia rheumatica.
Age >50 years.
Northern climates.
How is GCA diagnosed and managed?
3 out of 5 criteria
1) Age >50
2) new headache
3) abnormal biopsy
4) high ESR
5) temporal artery tenderness,reduced pulsation
Investigations
Bloods:
Inflammatory markers: ↑ESR, ↑CRP. The sensitivity of both is around 85%.
FBC: ↑platelets, ↓Hb.
↑Alk phos.
Temporal artery biopsy:
Mononuclear/granulomatous infiltration.
Don’t delay treatment while awaiting biopsy.
Skip lesions-if biopsy normal but symptoms suggest GCA -treat
Management
Immediate high dose prednisolone. Continued for 1 month, then tapered down over 6-12 months.
Add tocilizumab(IL-6R blockade-also given for refractory GCA) or methotrexate if steroids ineffective or causing side effects.
Adding aspirin is thought to reduce the risk of visual loss and stroke. Optimal length of therapy unclear.
PPI for gastric protection while on steroids and aspirin.
Manage Cardiovascular risk factors-BP/lipids
And complications
Consider endovascular surgery/stent
How does Takayasu arteritis present?
Granulomatous panarteritis - aorta & branches
Clinically - three phase disease
Inflammatory (pre-pulseless)
Constitutional symptoms
Ischaemic pulseless phase
Limb claudication/dizziness/hypertension
‘Burnt out’ phase
Persistent symptoms of vascular insufficiency
Stenotic lesions (90%) : Aneurysms (25%)
Systemic symptoms early on: fatigue, fever, weight loss, headache, myalgia.
Uneven BP between arms. Radial and brachial pulse may be absent on one side.
Bruits: carotid, subclavian, brachial, abdominal aorta.
Aortic regurgitation.
Limb claudication.
Hypertension due to renal artery stenosis.
Subclavian steal syndrome: lesion proximal to vertebral artery origin causing neuro symptoms.
Investigations
CTA, MRA, Doppler USS, CT PET
Management
Corticosteroids (e.g. prednisolone) are 1st line. Add methotrexate or azathioprine if needed.
Angioplasty or valve replacement may be needed in some.
What is Behcet’s syndrome?
Behcet’s syndrome is a complex multisystem disorder associated with presumed autoimmune-mediated inflammation of the arteries and veins. The precise aetiology has yet to be elucidated however. The classic triad of symptoms are oral ulcers, genital ulcers and anterior uveitis
Epidemiology
more common in the eastern Mediterranean (e.g. Turkey)
more common in men (complicated gender distribution which varies according to country. Overall, Behcet’s is considered to be more common and more severe in men)
tends to affect young adults (e.g. 20 - 40 years old)
associated with HLA B51
around 30% of patients have a positive family history
Features
classically: 1) oral ulcers 2) genital ulcers 3) anterior uveitis
thrombophlebitis and deep vein thrombosis
arthritis
neurological involvement (e.g. aseptic meningitis)
GI: abdo pain, diarrhoea, colitis
erythema nodosum
Diagnosis
no definitive test
diagnosis based on clinical findings
positive pathergy test is suggestive (puncture site following needle prick becomes inflamed with small pustule forming)
What are the main patterns of rash?
Epidermal Eczematous Psoriasiform Lichenoid Vesiculobullous/blistering
Dermal
Vasculopathic
Granulomatous
Tissue deposition
- How does Pseudoxanthoma elasticum present?
Pseudoxanthoma elasticum-lipid deposit,disorder of connective tissues(elastic tissue)
Pseudoxanthoma elasticum Arterial aneurysms Elastomas Plucked chicken Angioid streaks
How does Neurofibromatosis type 1 present?
Type 1-alot of skin signs(renal tumours,brain tumoura)
Type 2-less skin signs ,bilateral acoustic neuroma
Multiple café au lait spots
Axillary freckling-pathogenemic
Lisch nodules (iris)
What are the Aquired causes of rash with systemic disease?
Endocrine Metabolic Nutritional Haematological Inflammatory Infective Paraneoplastic
How does Endocrine disorders manifest in the skin?
Cushing’s Striae, atrophy-blood vessels, acne Addison’s Hyperpigmentation Palmar creases Buccal Hyperpigmentation occurs due to increase production of ACTH in response to reduce adrenal function in Addison’s disease. When ACTH production is stimulated another factor called melanocyte stimulate hormone is produced (due to splitting a long molecule called fancy to ACTH and MCH).This causes hyperpigmentation. doesn’t happen in pituitary insufficiency because ACTH is not produced and results pale alabaster type skin
Thyroid disease Myxoedema Periorbital oedema(loss of outer 3rd of eyebrow) Dry skin loss outer eyebrows Graves disease Pretibial myxoedema-Due to mucin deposition Acropachy (clubbing) exophthalmos
How does Metabolic disorders manifest in the skin?
Porphyria’s
Hyperlipidaemia Xanthelasma Normal/several dyslipidaemias Tendon xanthomas Familial hypercholesterolaemia Eruptive xanthomas(genetic hyperlipidemias) Hypertriglyceridaemia
Diabetes Acanthosis nigricans Also occurs in obesity Necrobiosis lipoidica(common in type 1(poor control)-due to collagen degeneration-attract histiocytes forming granulomas) Infections eg candida Gout Tophi periarticular urate crystals
