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
How does Porphyrias manifest in the skin?
Porphyria(genetic ,complex)
Sun exposed (due to deposition of heme precursors containing Iron(undergoes reduction)
Blistering(tense blisters ,blood filled)
Myelia-(tomb stones of blisters-white cysts filled with keratin)
Scarring
Fragility
Urine can remit the photons in different colours when placed under immunofluorescent light
Facial hirsutism(especially in liver disease)
Most present porphyria’s present with skin signs
Except acute intermittent porphyria
Commonest enzyme defects cause build up of uroporphyrinogen-Porphyria cutaneous tada,another cause affecting this enzyme is liver disease
How does nutritional deficiencies manifest in the skin?
Scurvy(abnormal formation of collagen)
Corkscrew hairs
Perifollicular haemorrhages
Bleeding gums
Pellagra
Vitamin B3 Niacin
Dermatitis(weepy eczema), diarrhoea, dementia
Photosensitive
What are genodermatoses?
Congenital conditions that cause rash with systemic disease
Pseudoxanthoma elasticum
Neurofibromatosis type 1
How does Haemotological malignancy manifest in the skin
Neutrophilic dermatoses(infiltration of neutrophils without infection) Pyoderma Gangrenosum(painful expanding ulcer with purple black edge,looks like a vascultic rash)-myeloma,leukemia Tx-Steriods(Important to differentiate between pg and infection as treatment is opposite)
Sweet’s syndrome(plum like) = acute febrile neutrophilic dermatosis Myeloma Leukaemia Other malignancies Tx-Steriods
Cutaneous T cell lymphoma Skin t cells retains hooks-well defined plaques Misdiagnosed as psoriasis Patch and plaque stage 5-30 years PUVA phototherapy Tumour stage Undergo malignant transformation-terminal(t cells lose the hook and spread)
- What are important rashes seen in viral and bacterial infections?
Viral exanthems Morbilliform rashes Measles/Rubeola 10 day incub. lasts 7-10 days Prodrome 3-4 day high fever, Koplik’s spots, Coryza, Cough, Conjunctivitis (3 C’s) Vesicular exanthems Chickenpox Shingles
Spirochaetes Syphilis Primary - Chancre Secondary palms, soles, generalised Snail-track ulcers Gumma
Lyme disease-erythema migrans
Meningococcal sepsis
Purpuric/vasculitic
Purpura fulminans(DIC)
How does Inflammatory disorders present in the skin?
IBD-Pyoderma gangrenous
Reiter’s syndrome Urethritis, arthritis, uveitis Psoriasiform rashes Circinate balanitis Keratoderma blenorrhagica
Behcet’s
Orogenital ulcers, uveitis (triad)
Pyoderma
Pathergy
Sarcoid Lupus pernio(dermal-nose,earlones and cheeks)
Connective Tissue Disease Photosensitivity Vascular changes Nailfold changes Livedo and vasculitis Rheumatoid arthritis-Nodules,Nailfold infarcts,Vasculitic leg ulcers
Systemic lupus-Photosensitivity
DLE, Butterfly rash, Sub-acute rash,Livedo & vasculitis
systemic sclerosis Diffuse Sclerodactyly(Distally then progress proximally Los of tissue due to ischemia-tapering fingers Fingers are flexed as the dermis is fibrotic) Raynauds Nailfold changes Widespread sclerosis Localised (CREST)hands and mouth Sclerodactyly Raynauds Calcification Telangiectasia microstomia
What is erythema nodosum and what conditions can cause it?
Erythema nodosum-Sheets of neutrophils within septa between fat lobules-Painful nodules,fever-UC,Strep throat,sarcoidosis,TB
What can cause Pyoderma gangerinosum
RA,IBD-UC,Haemotogical malignancy
How does paraneoplastic syndromes present in the skin?
Acanthosis nigricans
Dermatomyositis-Extensive,purplish,involves skin and muscle, eye lid become swollen, ILD
What are the skin signs of vasculitis?
RBC leakage?
Vessel death?
Vasculitis or thrombosis?
Palpable purpura
Large or small vessel?
Number of lesions(small area-large vessel)
Livedo(large)
Look carefully at any ulcer
Blue/purple edge → vasculitis
How does vasculitis develop?
Intial-purpura
Palpable purpura due to inflmammed blood vessels causing blood to leak out
2nd stage -This then develops into a white area with blisters due to the underlying epidermal necrosis
Dermis also dies-necrotic ulcers
What are extra-articular manifestation of RA?
Synovial joints / tendons / ligaments
Skin (Rheumatoid nodules)
Eyes (episcleritis / keratoconjunctivitis sicca)
Cardio-Pulmonary (pericarditis / rheumatoid nodules in lungs)
Splenomegaly-neutropenia
Blood (anaemia of chronic disease)
Renal (amyloidosis)
Central / Peripheral nervous system (cervical spine / carpal tunnel)
What are the investigation done for RA?What are x-ray findings?
Blood Tests
- FBC, ESR, CRP, Rheumatoid Factor, Anti-CCP, ANA
Plain X-ray
Rheumatoid Arthritis – X-ray
Polyarthropathy often affects: Cervical Spine ; Hands ; Feet
Narrowing joint space Marginal erosions Periarticular osteopenia Irregular joint surface Deformity / subluxation / dislocation Soft tissue swelling Secondary Osteoarthritis
What is the role of surgery in RA?
Pain-steroid injections
Instability
Nerve compression-NCS,EMG
tendon rupture-Tendon transfer
Procedures done=Arthroscopic synovectomy,Arthrodesis,Excision Arthroplasty,total joint replacement
What are the Indications for total joint replacement?
Indications (elbow joint):
Painful synovitis / swelling
Reduction in range of movement (lack of full extension)
Ulnar nerve neuropathy (compression by inflamed synovium)
Laxity of soft tissues > instability
Destruction of articular surfaces (joint erosion / cyst formation / bone loss)
How can lupus disease activity be measured?
Treatment depends on severity
- Mild – stable disease without life threatening organ involvement SLEDAI 2K- <6/ BILAG B 1
- Moderate- moderate disease activity if left untreated will cause scarring SLEDAI -2K 2-6/ BILAG B 2 or more
- Severe- serious systemic disease causing life/ organ threatening condition requiring potent immunosuppression SLEDAI >12/BILAG A 1 or more
What are examples of sDMARDS used?the use, side effect and important information
Hydroxychloroquine
Methotrexate
Azathioprine
Mycophenolate-severe lupus ,scleroderma(Stop at least 6 weeks before a planned pregnancy)
Leflunomide
(Mild- moderate non renal lupus. RA. PSA
Caution in pre-existing subacute cutaneous lupus, as this may worsen as observed in other non-lupus studies.
SE- transiently abnormal alanine aminotransferase (ALT), leucopenia and hypertension
Consider stopping 2 years before conception/ if not cholestyramine washout
Standard monitoring - BP and weight at each monitoring visit
Cyclosporine
Tacrolimus(Moderate non renal lupus
Can be used (at the lowest possible dose) in women planning pregnancy, and in those who are pregnant or breast-feeding )
Apremilast
What baseline assessment needs to be done when using Hydroxychloroquine and what the side effects
Anti- malarial
RA, Mild lupus, Sjogrens, Mixed CTD
Lowers overall RA/CTD activity and reduced rates of flare
In skin and joint involvement, myalgia, fever, fatigue, pleurisy
Dose 200 mg bd 3 months- reduce dose to 200mg od
SE- Nausea, retinal toxicity with cumulative dosing- risk increased with renal impairment, concomitant tamoxifen use etc
Used in conjunction with MMF to reduce the development of renal disease and chronic damage in lupus/ with other DMARDS in RA
Patients should have baseline formal retinal assessment using optical coherence tomography, within 1 year of commencing and 5 yearly
No specific blood monitorng required
What are the Indications for Methotrexate and what is it often co prescribed with?
RA/PSA, mild- moderate Lupus, Limited scleroderma, Mixed CTD
Acts on Folinic acid pathway
Need baseline bloods , CXR, PFT
Dose 10- 25 mg weekly PO/ subcut injections
Should be co-prescribed folic acid 5 mg once weekly ( avoid on MTX day)
What are the side effects of Methotrexate and what drugs should be avoided
SE- GI side effects, pneumonitis, blood dyscrasias
Teratogenic - should not be used in women within 3 months of planning to conceive, or who are pregnant or breast-feeding
Use with caution in renal impairment- increases the risk of adverse events
Standard blood monitoring
Should not be co-prescribed with Trimethoprim/ Nitrofurantoin
What are the side effects of Methotrexate and what drugs should be avoided
SE- GI side effects, pneumonitis, blood dyscrasias
Teratogenic - should not be used in women within 3 months of planning to conceive, or who are pregnant or breast-feeding
Use with caution in renal impairment- increases the risk of adverse events
Standard blood monitoring-every to weeks for 6 weeks then every month
Should not be co-prescribed with Trimethoprim/ Nitrofurantoin
Alcohol should be reduced to 1 unit per day
What are the indications and side effects of cyclosporin
Moderate –severe CTD, PSA, RA
Dose ⩽2.5 mg/kg/day
Non-renal lupus- particularly helpful in the treatment of cytopenias
Can be used in renal/ neuropsychiatric manifestations
SE: hypertrichosis, gum hypertrophy, hypertension, paraesthesia, tremor, gastrointestinal symptoms and impaired renal function, especially at higher doses (>3 mg/kg/day)
Does not cause myelosuppression
Standard monitoring
BP and glucose at each monitoring visit
Can be used (at the lowest possible dose) in women planning pregnancy, and in those who are pregnant or breast-feeding
What Cautions need to be taken with the use of Apremilast?
PSA
Phosphodiesterase 4 (PDE4) inhibitors
Could be used pre /post biologics
Dose: increase gradually
Caution: Risk of suicidal thoughts and behaviour
SE:depression;diarrhoea;fatigue;gastrointestinal discomfort, headache
Reduce dose if eGFR less than 30 mL/minute/1.73 m2
Teratogenic- avoided in pregnancy and breast feeding
No specific blood monitoring required
What is the Monitoring Criteria when using sDMARDS?
Check FBC, creatinine/calculated GFR, ALT and/or AST and albumin every 2 weeks until on stable dose for 6 weeks; then once on stable dose, monthly for 3 months; thereafter at least every 12 weeks.
More frequent monitoring is appropriate in patients at higher risk of toxicity
Dose increases should be monitored every 2 weeks until on stable dose for 6 weeks then revert to previous schedule
Exceptions/additions to the monitoring schedule for specific DMARDs – refer to BSR guidelines
What is the Peri operative guidelines for the use of DMARDS?
Steroid exposure should be minimized prior to surgical procedures, and increases in steroid dose to prevent adrenal insufficiency are not routinely required
DMARD therapy should not routinely be stopped in the perioperative period, although individualized decisions should be made for high-risk procedures
What are reccomendations and advice for the use of sDMARDS in Pregnancy?What drugs are safe to use?
Pre-pregnancy counselling should be provided so that pregnancy is planned and occurs when Inflammatory arthritis/ CTD has been well controlled for at least 6 months
HXQ, AZA, Cyclosporine safe to use.
Appropriate use of effective contraception while on teratogenic DMARDs.
Regular folic acid daily
Coexisting Ro/La antibodies- increased risk of Neonatal heart blocks/ Neonatal lupus
Coexisting Antiphospholipid antibodies will need anticoagulation for optimising pregnancy outcome
Patient to remain under consultant obstetrician’s care with regular foetal growth monitoring and appropriate delivery planning.
What are the baseline Investigation done before starting bDMARDS?
Routine bloods- FBC, U&E, LFT, Albumin
CXR
Latent TB screening- Quantiferon Gold
Hepatitis B and C, HIV
Varicella screen
Special investigation: Immunoglobulins for Rituximab
Lipid profile for Tocilizumab
What bDMARDS can be used in Infection?
Not initiated in active infection
Vigilance for infection while on biologics
Use Etanercept and Abatacept where possible in high risk patient
Should bDMARDS be started if there is an infection?
All patients screened before commencement of biologics
If evidence of active TB/latent TB, require referral to Respiratory Physician
Active TB- treated before commencement of biologics
Prophylactic Anti TB treatment for latent TB – biologics commencement after 1 month into treatment with 3 monthly monitoring
Risk of TB reactivation is higher with certain Anti TNF therapies like Adalimumab and Infliximab- hence Etanercept is preferable in this circumstance
Screening
If HBV positive- Anti viral treatment, hepatology input and risk- benefit discussed before initiation of biologics
No detrimental effect on HBC infection- uses with caution and hepatologist input
HIV- close monitoring / treatment when using anti TNF therapies
Monitor LFTs and active viral load.
Treat occult infections concomitantly if deranged LFT /active viral load
What drugs are recommended in pre existing ILD?
Pre-existing ILD is not a contra-indiaction- caution in patients with poor respiratory reserve
Patients with ILD- regular review in specialist Respiratory clinic/ 4-6 monthly PFTs/ stop if worsening symptoms
Rituximab/Abatacept may be used 1st line
What drugs are reccomended and should be avoided Uveitis?
Adalimumab (ADA)/ Infliximab (IFX) may be considered
Etanercept associated with development of uveitis/ less treatment success.
Consider switching current treatment to ADA or IFX in patients who develop uveitis
What drugs should be avoided in demyelinating disease?
Anti TNF therapy not initiated if personal H/O multiple sclerosis/ other demyelinating diseases
Withdraw anti TNFs if patients develop demyelination and should not be re-challenged
Consider Non- anti TNFs in this case
What drugs can worsen Diverticular disease?
Use Tocilizumab (TCZ) and Baricitinib (JAK inhibitor) with caution if H/O diverticular disease(Increase risk of bowel peforation) Increased risk with concomitant use of NSAIDs and steriods Stop TCZ/ Baricitinib if bowel perforation and re-introduction not recommended
What are some other side effects of bDMARDS?
Baseline ANA checked
If CTD- lupus like illness with anti TNF- discontinue. Re- initiation with caution
Biologics therapies continued with VTE/Tofacitinib used with caution in VTE
If Psoriasis flares on initiation consider stopping/ Dermatologist/ conventional treatment initiated
What should be done if opportunistic infection is suspected with DMARDS ?Should vaccine be given?
Increased vigilance and suspicion for atypical/Opp infections
Prompt stopping of biologics/ treatment initiated with specialist guidance
Post exposure prophylaxis with varicella zoster- immunoglobulins considered in primary varicella exposure (in patients with no antibodies/ no H/O previous infection)
Vigilance for progressive multifocal leucoencephalopathy esp with Rituximab/ lesser extent with anti TNFs which should be stopped and rechallenging not recommended
Public Health England recommendations on immunizations in patients on immunosuppressive therapy should be adhered to
Live attenuated vaccines should be avoided, eg. herpes zoster vaccine, oral polio or rabies vaccine, Yellow fever vaccine
Influenza and pneumococcal immunizations recommended
Human papillomavirus vaccine for cervical cancer risk in young women is recommended
What are peri operative reccomendations for use bDMARDS?
Potential benefit of preventing post-operative infections by stopping biologics /balanced against the risk of a peri-operative flare in disease activity
Different surgical procedures pose different risks of infection and wound healing
Plan surgery when at least one dosing interval elapsed/ higher risk procedures consider stopping 3–5 half-lives before surgery
Restart when achieved good wound healing (typically around 14 days) and no evidence of infection
Refer to the American guidelines for specific drugs and duration of stopping treatment and reinitiation - eg RITUX stop 3-6 months before/ TCZ infusion 6 weeks/TCZ injections 2 weeks
How can severe CTD be managed?
IV Methyl prednisolone or high-dose oral prednisolone (up to 1 mg/kg/day) to induce remission, either on their own or more often as part of a treatment protocol with another immunosuppressive drug
MMF or CYC are used for most cases of Lupus nephritis and for refractory, severe non-renal disease , interstitial lung diseases.
Biologic therapies belimumab or rituximab may be considered, on a case-by-case basis, where patients have failed to respond to other immunosuppressive drugs, due to inefficacy or intolerance
IV IG and plasmapheresis may be considered in patients with refractory cytopaenias, thrombotic thrombocytopaenic purpura, rapidly deteriorating acute confusional state and the catastrophic variant of APS
What are the side effects of Cyclophosamide?
Lupus Nephritis and organ or life-threatening non-renal disease, severe Scleroderma/ Sjogrens
Oral CYC is associated with an increased risk of bladder cancer and has been replaced by i.v. CYC pulses
Teratogenic and is contra-indicated in women trying to conceive, or who are pregnant or breast-feeding.
It is gonadotoxic and can cause infertility, and men should not father children while on CYC
SE- gastrointestinal side effects, alopecia, infection, amenorrhoea and infertility due to ovarian failure
What bDMARD is safe in pregnancy?
Certolizumab
What bDMARD should be avoided in neutropenia?
analinra
What bDMARD can cause severe psychiatric disease?
Belimumab
What bDMARD requires immunoglobulin monitering?
Rituximab
What is Raynaud’s and what are the risk factors for it?
Intense vasopasms with associated colour change and hyperemia.Generally affecting the digits.Goes through 3 phases with initial white(vasoconstriction) followed by blue(cyanosis) and then red (rapid reflow).Can be primary or secondary
Female gender, smoking,beta blockers, cold exposure
What conditions can cause Raynaud’s?
Systemic sclerosis
Polycythemia-Any cause of hyper viscosity-lymphoma,leukemia
SLE
What are the causes of raised ESR?
The most common cause of high ESR Malignancy
May feature deranged FBC Haematological
A connective tissue cause SLE
A vasculitic cause Polymyalgia rheumatica
A rheumatological cause Rheumatoid arthritis
A vasculitic cause Giant cell arteritis
A connective tissue cause Systemic sclerosis
An infective cause Tuberculosis
An infective cause Hepatitis
A variant of normal! Pregnancy
What are the possible causes of elevated CK and muscle weakness?
Inflammatory muscle disease -polymyositis dermatomyositis rhabdomyolysis motor neurone disease Musular dystrophy Iatrogenic-statin induced myositis
What Investigations are done for dermatomyositis?
myositis specific antibodies
MRI -Used to show muscle inflammation and edema,guide biopsy
Muscle biopsy-can differentiate from polymyositis.Shows perivascular and interfasicular inflammatory infiltrates with adjoining groups of muscle fibre degeneration
EMG-detecting muscle inflammation and damage
Skin biopsy
What might reduced TLCO indicate?
restrictive picture of ILD-Pulmonary fibrosis
What follow up Investigations are important with dermatomyositis?
25% has an increased risk of malignancy and risk remain for 3-5 years.Need to have CT chest abdomen pelvis, bronchoscopy may be considered.OGD and colonoscopy maybe considered in the presence of anemia
What role does joint arthroscopy surgery have in the treatment of rheumatoid arthritis?
Rheumatoid arthritis is an autoimmune mediated inflammatory arthropathy. It affects synovial joints and results in an effusion along with enlarged and inflamed synovial tissue which lines the joints. Inflamed microvilli within the synovium can invade the joint and is called pannus which can then lead onto erosions of bone and cartilage, attenuation of ligaments and joint instability.
The role of joint arthroscopy (key hole surgery) is to debrided the red and inflamed synovium which is a major source of joint pain. This helps to reduce pain and stiffness in early disease. However, the diseased synovium can recur and grow back in aggressive disease patterns that is refractory to medical therapy which may require further arthroscopic debrided and repeat synovectomy.
In some cases of diagnostic doubt following clinical, radiological and blood chemistry evaluation, an arthroscopy and synovial tissue biopsy (which is then sent for histopathologic assessment) can help with the diagnosis of the disease and thus arthroscopy can be of both diagnostic as well as therapeutic benefit.
What is the pathophysiology of Polymyositis and Dermatomyositis?
Autoimmune diseases involving myositis (polymyositis) or myositis plus characteristic skin signs (dermatomyositis).
Polymyositis features T-cell-mediated muscle damage, while dermatomyositis features immune complex deposition in vessels.
Associated with underlying cancer in around 50% of patients, especially if adult-onset. Also associated with other inflammatory diseases (‘overlap syndromes’) e.g. RA, SLE, systemic sclerosis, sarcoidosis
What are the signs and symptoms of Polymyositis and dermatomyositis?
Signs and symptoms
Muscles and joints:
Weakness, especially proximal myopathy.
Polyarthritis
Myalgia
Skin and hand signs in dermatomyositis:
Pink-purple (‘heliotrope’) rash around eyes ± periorbital oedema.
Gottron’s papules: scaly red patched on knuckles.
Other rashes: ‘V-sign’ on neck and chest, ‘shawl sign’ on back of neck and shoulders.
Nail-fold capillary dilation.
Dermatomyositis can present with skin signs alone, while muscle symptoms may be sub-clinical.
Organ involvement:
GI: dysphagia, reflux.
Lungs: ILD, aspiration pneumonia.
Cardiac and renal involvement is possible but rare.
What are the clinical features of Löfgrens Syndrome
Acute & Benign form of Sarcoid.
Triad of:
Erythema Nodosum
Arthralgia/ arthritis (Bilateral ankle)
Bilateral Hilar Adenopathy
May have associated systemic features.
Mainly self limiting (NSAIDs & steroids).
1% evolve a chronic arthritis.
Serum ACE level may be elevated.
Sarcoidosis : a Multi-systemic Inflammatory Disorder Characterised by epitheliod non-caseating granuloma in involved organs Erythema nodosum (EN) is an acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs. Chronic or recurrent erythema nodosum is rare but may occur. Erythema nodosum is presumed to be a hypersensitivity reaction and may occur in association with several systemic diseases or drug therapies, or it may be idiopathic. The inflammatory reaction occurs in the panniculus.
What antibodies are specific for myositis(dermato and poly)
Investigations
Bloods:
↑WBC/ESR/CRP.
Muscle enzymes: ↑CK, ↑aldolase.
Auto antibodies: ANA (80% sensitive) and myositis-specific Abs such as anti-Jo-1 and anti-SRP.
Other tests:
Electromyography (EMG) shows abnormal muscle activity.
Muscle and skin biopsy for definitive diagnosis
Muscle biopsy
Dermatomyositis-Perivascular and perimysial
Endomyosial-Polymyositis
How can polymyositis and dermatomyositis be treated?
Management
Myositis:
High dose PO steroids are first line.
Other immunomodulators such as methotrexate, tacrolimus, MMF, or azathioprine can be considered.
IVIg if refractory.
Skin disease:
Topical steroids.
Encourage to use sunscreen all year.
What can Alopecia be a sign of?
CTD
What medications can cause CTDs such as drug induced lupus?
Chlorpromazine-Antipsychotic
Anti-TB
Anti epileptics
What lifestyle factor can worsen psoriasis?
Alcohol
What is an important complication of systemic sclerosis?
Renal stenosis causing dangerous hypertension
What advice should be given to patients with SLE in regards to pregnancy and what contraceptives should be used?
Pre pregnancy counselling
Need disease control by meds for at least 6 months other worse outcomes
Avoid Oestrogen containing contraceptives-increases thrombosis risk
What can cause SLE and what are the risk factors?
Background
Pathophysiology
Multi-system, autoimmune condition.
Cause unknown, but may involve formation of autoantibodies due to defective apoptosis.
Epidemiology
10x commoner in women.
Onset usually in child-bearing years.
Prevalence by ethnicity: black 1/500, Asian 1/1000, white 1/2000.
Risk factors
Genetic: HLA-DR2 and DR3, complement deficiencies (C1q, C2, C4).
Drugs: minocycline, sulfasalazine, procainamide, isoniazid, phenytoin, carbamazepine.
Environment: UV light, EBV, smoking.
What are the multi system signs and symptoms of SLE
Signs and symptoms
Overview:
Relapsing-remitting course.
Wide range of severity.
Symptoms by system:
Systemic: malaise/fatigue (90%), fever (50%), weight loss, lymphadenopathy.
Musculoskeletal (90%): arthritis, usually symmetrical, non-erosive polyarthritis with morning stiffness but without swelling. Also: myalgia, tenosynovitis, and tendon rupture.
Skin: malar rash (60%), photosensitivity (40%), discoid rash (20%), Raynaud’s (50%).
Lupus nephritis (50%): 6 classes from minimal mesangial to advanced sclerosis.
Serositis (50%): pleurisy, pericarditis. Causes SOB and chest pain.
Respiratory: pleurisy, interstitial lung disease, pulmonary haemorrhage (causes haemoptysis and anaemia).
Cardiovascular: IHD (5-fold risk), HTN, vasculitis, pericarditis, myocarditis, endocarditis, antiphospholipid syndrome (causes arterial and venous thrombosis).
Mouth and face: painless oral and nasal ulcers (30%), alopecia (non-scarring), Sicca.
Eyes-Anterior uveitis,Sjorgen’s, retinal exudates
GI: diarrhoea, vomiting, abdo pain, splenomegaly (10%), dysphagia (rare).
Neurological: seizures or psychosis (20%), peripheral neuropathy, transverse myelitis, optic neuritis.
Jakoubs arthropathy
Fertility-Oligomenorrhea, amenorrhea, hemorrhagic,recurrent miscarriage
What are the laboratory findings of SLE?
Investigations and diagnosis
Bloods
FBC: ↓Hb (of chronic disease or Coomb’s +ve hemolytic anaemia), ↓WBC (↓lymphocytes), ↓platelets.
↑ESR but CRP may be normal (or raised); do both as this can help distinguish from infection.
U&E: ↑urea, ↑creatinine.
Coag: ↑aPTT in APS.
CK. Check if there is myalgia or weakness.
Immune markers
Anti-nuclear antibodies
Overview:
Anti-nuclear antibodies (ANA, aka anti-nuclear factor) are autoantibodies which bind to elements of the cell nucleus.
95% sensitive – so screen with this first – and 50% specific.
Mildly +ve in 10% of healthy population.
Also +ve in systemic sclerosis (plus anti-centromere Ab and Scl70 Ab), polymyositis (plus Jo-1 Ab), dermatomyositis, Sjogren’s, and 30% of RA.
Subtypes:
Double-stranded DNA (dsDNA) Ab is highly specific for SLE, but only 60% sensitive. Especially associated with lupus nephritis. Good for monitoring disease activity.
Anti-Smith (Sm) Ab. Highly specific for SLE.
Anti-Ro and anti-La Ab. Can be seen in SLE, but commoner in Sjogren’s.
Others
APS: anti-cardiolipin Ab, lupus anticoagulant, false +ve syphilis serology (rarely done).
Complement: ↓C3 and ↓C4. Varies with disease activity.
Other tests
Urinalysis: protein, blood, casts (red cell, tubular, granular).
Imaging as per symptoms e.g. CXR if CV or resp symptoms.
BILAG questionnairefor monitoring disease activity.
How can SLE be treated,
Management
Immunomodulation
As with most autoimmune diseases, goal is to rapidly induce remission in flares, then maintain control with less aggressive therapy. Mild disease may require no treatment, though most need at least HCQ.
Skin, MSK, and systemic symptoms:
Hydroxychloroquine (HCQ) PO 1st line. May be sufficient as monotherapy in mild flares and for patients in stable remission, while part of combination therapy in moderate-severe flares.
Steroids often required alongside HCQ, but always aim to minimize dose and duration. For mild flares, may be topical or intra-articular only (or none at all), but moderate-severe disease typically requires systemic therapy (PO, IM, or IV).
Adjuncts if HCQ insufficient and/or for minimizing steroids: methotrexate, azathioprine.
Organ-threatening or resistant disease:
Renal or resistant non-renal disease: {steroids} plus {cyclophosphamide [CYC] IV pulse or mycophenolate mofetil [MMF] PO}.
Neuropsychiatric: {steroids} plus {CYC IV pulse}.
Further options if CYC/MMF ineffective: belimumab IV (B-cell activating factor inhibitor), rituximab IV.
Supportive treatment
Symptomatic and adjunctive treatments:
Lifestyle changes: avoid sun exposure (and use SPF >15), smoking cessation.
Short-term NSAIDs for arthritis.
Ulcer treatment: chlorhexidine mouthwash, lidocaine ointment.
Manage CV risk factors as needed: HTN, cholesterol.
Use low dose estrogen if contraceptive required, as hormones can exacerbate disease.
Monitoring:
Bloods: FBC (↓Hb), U&E and urinalysis (renal function), LFT (drug side effects).
Disease activity, BCDE:BILAG questionnaire,C3/4, dsDNA Ab,ESR.
Monitor side effects: annual visual acuity (HCQ), BP (cyclophosphamide).
Complications and prognosis
Cardiovascular:
Atherosclerosis: manage cholesterol and BP (aim <130/80). ACEi if proteinuria.
Antiphospholipid syndrome (25%).
Pregnancy:
Fetal: miscarriage (especially if APS), IUGR.
Maternal: pre-eclampsia, VTE, worsening of SLE including nephritis.
Prognosis:
Poor signs: extensive disease, multiple autoantibodies, neurological or renal disease.
90% 10 year survival.
Causes of death: IHD, renal disease, infection from immunosuppression
What are the diagnostic criteria for SLE?
Refer EUCR guidelines-score greater than 10 or more if entry criterion fulfilled
