Connective tissue disease Dan Flashcards
T/F
In dermatomyositis children get more contractures and calcinosis but better prognosis
True
also get more vasculitis
T/F
Raynauds disease may ulcerate
False
Raynauds doesn’t ulcerate
scleroderma with Raynauds often ulcerated in fingertips though
Sjogren’s is the most common CTD
False
second most common after RA
Sjogren’s has more than 10x increased risk of lymphoma
True
16 - 40x increased risk lymphoma
esp non-Hodgkin B cell
T/F
nipples and areolae are spared in generalized morphoea
True
T/F
There is an association between Silicone Breast Implants and autoimmune disease
False
What are the ARA diagnostic criteria for SLE?
Need 4 out of 11 features
MD SOAP BRAIN
Malar rash
Discoid rash
Serositis such as pleuritis or pericarditis
Oral ulcers
Arthritis (usually oligo or polyarticular)
Photosensitivity
Blood dyscrazias: hemolytic anaemia, leukopenia, lymphopenia, and thrombocytopenia
enal involvement with nephrotic picture – persistent proteinuria (>0.5g/day) or cellular casts
ANA (95% of patients)
mmunological abnormalities such as Anti-Sm, Anti-dsDNA, Anti-phospholipid, false positive syphilis serology
Neurological/Psych: mainly seizures and psychosis
What drugs can flare/unmask SLE
griseofulvin itraconazole beta blockers sulphonamides testosterone oestrogens TNFalpha blockers Penicillamine
T/F
Scleroderma means the same as sclerodermoid
True
However usually scleroderma is used to mean an form of systemic sclerosis and sclerodermoid is used for skin tightening changes
T/F
Skin changes occur in only a small proportion of scleroderma cases
False
Skin changes are usually prominent in all forms of SSc
Pts who present w/ Raynauds, internal disease and serology but no skin disease is called ‘systemic sclerosis sine scleroderma’
T/F The pathoaetiology of SSc involves the following 3 features; Tissue fibrosis Vascular dysfunction Immune dysregulation (Th2 profile)
True
T/F
SSc is twice as common in women
False
4x more in women
NB SLE 8x more in women
T/F
Black people rarely develop SSc
False
earlier onset and more likely to be diffuse Dx in blacks
T/F
SSc can affect children
True
rare
T/F
An affected family member confers a 10x increased risk of developing SSc
True
T/F
Internal organ disease doesnt occur in limited SSc
False
can occur but usually after decades of disease
Joints and oesophagus most common
then small bowel disease
then lung fibrosis, Proximal myopathy, Sicca syndrome and pulmonary HTN
T/F
Raynauds and sclerodactyly mean pt most likely has SSc
False
sclerodactyly commonly occurs in Raynauds
Only 1 in 25 pts with Raynauds and sclerodactyly will develop SSc
In SSc the scleroerma extends proximally beyond the MCPJs - this is critical
Check nailfold capillaries for changes and test for serology to help identify SSc
What are the stages of hand changes in SSc?
Oedematous
Indurated - taught and shiny
Atrophic - thin skin
- most often start with pitting oedema of hands
What are the facial changes in scleroderma?
Skin tightening - loss of wrinkles; look youthful
microstomia with perioral fissures
beaked nose
What are the ARA diagnostic criteria for scleroderma?
Need to have either 1 or 2; 1) Symmetrical cutnaoeus sclerodermid change proximal to the knuckles or MTPJs of feet 2) Any 2 of; Sclerodactyly Digital pitted scarring Bibasal pulmonary fibrosis
T/F
In diffuse SSc there is usually widespread skin involvement
True
and nearly always early internal organ involvement
- within 1 yr of Raynauds and skin changes in 90%
T/F
sclerodermoid changes on the proximal limbs or trunk are indicative of diffuse SSc
True
Limited SSc is confined to distal limbs and sometimes face
T/F
finger swelling is common in diffuse SSc but not in limited SSc
False
Occurs in >90% in both diseasess
What are the possble clinical features of Sjogren’s syndrome?
Signs + symptoms of dry eyes and mouth (see diagnostic criteria) Arthritis Skin - VX LUNES; Vulvovaginal dryness common Generalised skin Xerosis and pruritus Leukocytoclastic vasculitis Urticarial vasculitis Nodular amyloidosis Erythema nodosum Sweet’s syndrome Respiratory, renal, bone marrow, CNS all can be involved
Remember; 16x increased risk of lymphoma (usually B-cell and extranodal such as salivary or lacrimal glands) esp if vasculitis, cryoglobulins or low complement
What are the derm manifestations of Rheumatoid arthritis?
Palmar erythema atrophic skin esp dorsa of hands brittle nails Yellow nail syndrome Bywater's lesions (small periungual necrotic lesions) rheumatoid nodules (also seen in SLE) Sclerodermoid change (pseudoscleroderma) Rheumatoid vasculitis Rheumatoid neutrophilic dermatosis (resembles Sweets) Pyoderma gangrenosum Interstitial granulomatous dermatitis Leg ulcers and Felty's syndrome Cutaneous AEs of drugs used Systemic onset JIA (Still's) - 90% get transient mac-pap eruption, can get subcut nodules like rheumatic fever nodules (not Rheum nods)
NB DD of leg ulcers in RA; PG Rheumatoid neutrophilic dermatosis ulcerated vasculitis Feltys - ulcers may be multifactorial; mix of other listed causes Any of the other usual causes of ulcers
What are the diagnostic criteria for Sjogren’s syndrome?
Primary SS - Need 4 out of 6 features Positive which must include 1 or both of; positive salivary gland biopsy or positive autoantibodies
Secondary SS – Need oral or eye symptoms + any 3 of oral or eye signs or positive histo (serology not diagnostic in secondary dx)
- Positive salivary gland biopsy (inflammatory infiltrate of lymphocytes)
- Presence of autoantibodies (anti-Ro/SS-A or anti-La/SS-B)
- Symptoms of xerophthalmia – related to Keratoconjunctivitis sicca (destruction of lacrimal gland leads to: ocular dryness, foreign body sensation, pain, photophobia)
- Signs of xerophthalmia (Schirmer test, Rose Bengal test)
- Symptoms of xerostomia (destruction of salivary glands may present as dry, sore, burning mouth and lips, difficulty swallowing, require frequent ingestion of fluids, candidal overgrowth can lead to thrush) NB: salivary glands may become transiently enlarged (20% of patients) however persistent swelling or lymphadenopathy should prompt evaluation for B-cell lymphoma of salivary glands
- Signs of impaired salivary gland function (sialogram, scintigraphy – dye injected under X-ray exam)
What is ‘systemic sclerosis sine scleroderma’
SSc with internal organ disease + Raynauds + positive serology and no skin involvement
T/F
Calcinosis and telangiectasia are more common in limited than diffuse SSc
T
What triggers accellerated rheumatoid nodulosis?
eruptive rheumatoid nodules
Initiation of MTX or dose of TNF-alpha antagonists
also some patients with tapering of prednisone
What are the types of Interstitial granulomatous dermatitis?
Palisaded neutrophilic and granulomatous dermatitis (PNGD)
Interstitial granulomatous dermatitis (IGD)
Interstitial granulomatous drug reaction (IGDR)
Which drugs can cause Interstitial granulomatous drug reaction (IGDR)?
When do they occur?
common ABCD STAT ACEI – enalapril, lisinopril Beta blockers – atenolol, propanolol, labetolol, metoprolol Calcium channel blockers – verapamil, diltiazem, nifedepine Diuretics - Frusemide (+HCTZ) Statins – Simva, Prava, Lova TNFα blockers Antihistamines (H1 or H2), Anakinra Thalidomide, lenalidomide
Uncommon HCTZ Carbamazepine Diazepam Bupropion Ganciclovir Darifenacin Sennosides (senna) onset after months-years of taking the drug Can mimic Interstitial granulomatous dermatitis or Palisaded neutrophilic and granulomatous dermatitis clinically and histologically
What are the subtypes of chronic cutaneous LE?
DLE
Lupus tumidus
Lupus panniculitis
Chillblain lupus
What is Rowell’s syndrome?
Erythema Multiforme - like lesions and cutaneous lupus
SCLE>ACLE>DLE
Is not true EM
Papules on hands, chest, face and neck and in mouth turn into annular lesions with vesicular edge and atrophic/ necrotic centre. Often have perniosis
Speckled ANA, RF and anti-La Abs (also homogenous ANA if has SLE)
Lupus type skin lesions positive IMF but EM-like lesions negative
What is the topical and systemic treatment ladder for cutaneous lupus?
Gen measures - sun avoidance most important, cosmetic camouflage, assess for associations and complications Topical - potent TCS (even on face) - tacrolimus - topical retinoid Systemic - HCQ (stop smoking) - Pred esp to gain control or if recalitrant - Acitretin/Isotretinoin - AZA - MMF Also; - ILCS for tumid lupus, panniculitis or resistant DLE - for chillblain LE nifedipine or IV prostacyclin in winter - IVIg (SCLE) - Etanercept (SCLE) - Rituximab or other immune modifiers - MTX (CCLE, SCLE) - Gold For resistant lupus panniculitis; - Thalidomide also for chilblain type - Cyclophosphamide - IVIg Also; - Dapsone - mainly for bullous SLE Other physical; small lesions can be excised CO2 laser for scarring PDL for telys
What are the risks for SLE in pts with various types of cutaneous LE?
ACLE - 50% SCLE - 15% DLE - 5% (20% if disseminated) Lupus panniculitis - 3% alone, 20% if also DLE Tumid lupus - very low Chillblain lupus - 15%
T/F
the lichenoid tissue reaction is most vigorous in acute lupus compared to other cutaneous LE types
F
most vigorous in SCLE
T/F
DLE on hair-bearing skin always causes a scarring alopecia
F
alopecia only in one third of cases on hair-bearing skin
What are the associations of DLE?
Rowell’s syndrome PMLE Porphyrias Alopecia areata Hereditary angioedema/C1q esterase inhibitor deficiency CLL MGUS Multiple myeloma MG Thymoma Pemphigus Macroglobulinaemia Thyroiditis Polychondritis Sheehan’s syndrome Carpal tunnel
What is the ‘tin-tack’ sign?
removing adherent scale reveals horny plugs in dilated follicular orifi
e.g. DLE, localized pemphigus foliaceus
T/F
facial lesions of DLE can resemble rosacea but has papules, no pustules
T
7.5% like this
need to biopsy to distinguish
What is ‘lupus erythematosus telangiectoides’?
Dissmeinated telangictatic variant of DLE
Reticulate telys on arms, dorsa of hands, legs/calves, feet, face, neck, ears, breasts.
What are the variants of DLE?
Rosacea-like
Hypertrophic
Bullous
lupus erythematosus telangiectoides
T/F
DLE may have significant systemic symptoms without being SLE
T
arthralgias (>20%)
chilblains (20%)
poor peripheral circulation (25%) or Raynauds (15%) are also not uncommon
Rarely sclerodactyly + hyperextension of DIPJs
subungual hyperkeratosis, dilated nailfold capillaries
thick rough red lips +/- erosions, erythematous lesions of mouth or vulva or oral leukoplakia
nasal mucosa ulcerations
red oedematous conjunctivae
T/F
50% of SCLE pts meet ARA criteria for SLE
T
but often not ‘true SLE’; mainly photosensitivty and mucocutaneous criteria
settles with SCLE treatment
However in SCLE 50% gte arthralgia esp small joints +
can get Fever, malaise and CNS involvement and up to 15% get Renal disease - usually mild
What is the main DD for tumid lupus?
classically is Jessner’s - some belive these are the same things as hard to differentiate
both have dense lymphocytic infiltrate
Others are PMLE and REM
T/F
+ve DIF at DEJ helps identify lupus panniculitis on histo
T
linear IgM and C3 at BMZ
Also;
Prominent lymphocytic infiltrate in subcutis often involving deep dermis
Deep dermal and subcut necrobiosis and sometimes vasculitis
Lobular or periseptal panniculitis
What are the features of Lupus panniculitis (profundus)?
Rubbery well-defined deep nodules, 1-several cms
Face, upper arms, upper trunk, breasts, buttocks, thighs
Can be perforating esp on legs
T/F
chillblain lupus pts may have cryoglobulinaemia
F
Some pts have cryofibrinogenaemia or cold agglutinins
What is Senear-Usher syndrome?
Pemphigus erythematosus
cutaneous lupus + pemphigus folliaceus overlap
T/F
Smoking associated with cutaneous lupus and worse response to antimalarials
T
T/F
‘Bullous SLE’ resembles pemphigus vulgaris
F
resembles DH/BP/EBA
What are the common features of SLE?
Fevers (90%)
(usually non-erosive) arthritis/arthralgia (90%)
rash - ACLE>DLE>SCLE or non-specific (80%)
weight loss (50%)
fatigue
myalgia
lymphadenopathy (50%)
Serositis - Pleuritis (40%), pericarditis (25%)
Libman-Sacks endocarditis
haemolytic anaemia w/ reticulocytes, low WCC, low lymphocytes, low platelets
Lupus nephritis - proteinuria, casts (66%)
Hepatomegally (25%)
CNS features – seizures etc (25%)
Menstrual irregularities are common; >80% and rash flares prementsrually in 20% of women
Hyper or hypothyroidism
Diffuse alopecia in 50% and ‘lupus hair’ – dry, brittle with broken off hairs
Rarer - splenomegally, abdo pain and GI upset, psychosis
What are the non-specific skin changes of SLE?
maculopapular erythematous scaly photosensitive eruption Calcinosis Rheumatoid nodules Raynaud's (30-60%) Sclerodactyly Nailfold telys and erythema Urticaria, Urticarial vasculitis Purpura Palmar erythema Palmar keratoderma Livedoid vasculopathy Gyrate erythema Erythromelalgia diffuse alopecia Inflamed ear or nose cartilages Erythromelalgia Papulonodular mucinosis Anetoderma EAC Large areas of hypopigmentation Cheilitis, cracked lips or tongue nasal, oral or genital ulcers CSVV vasculitis skin ulcers digital gangrene Cutaneous signs of possible antiphospholipid syndrome (suggestive, not diagnostic. Can be seen in any SLE patient) - Livedo reticularis - Ulcerations - Acrocyanosis - Atrophie-blanche-like lesions (cutaneous infarction) - Degos’-like lesions (cutaneous infarction)
T/F
Up to 23% of pts with Cutaneous LE will develop SLE
T
over average 8 years
Mostly mucocutaneous criteria - Systemic SLE features are uncommon in these patients and only a minority develop mod/severe systemic disease
What are the associations of SLE?
RA
Systemic sclerosis
Sjogrens
PMR – esp in cases presenting in the elderly
Morphoea – linear, plaque, en coup de sabre
PBC
Angio-oedema of C1q esterase inhibitor deficiency
MG and/or thymoma
Pernicious anaemia
Pemphigus
Kikuchis disease
What investigations should be done in pts presenting wit
low risk cutaneous LE and no other features (DLE, tumidus, panniculitis)?
Basic lupus screen; Full Hx and exam Punch Bx; H+E +/- lesional IMF FBC, ELFT, ANA, ENA(Ro, Sm), Anti-dsDNA, ESR, C3/C4 Urinalysis –P/RBC/C
Which pts need a more full lupus work up?
Pts presenting w/ ACLE, SCLE or chilblain LE or clinically suspected of having SLE before or after basic screen performed
What is involved in an extended lupus work up?
Punch Bx; H+E +/- lesional IMF, +/- sun-protected non-lesional skin for lupus band IMF
FBC, ELFT, ANA, ENA(Ro, Sm), Anti-dsDNA, ESR, C3/C4 (+/- Coombs test, syphilis serology, LE cell test, anticardiolipin or anti-phospholipid Abs)
B12, folate, TFTs and thyroid auto-Abs, RF, AMA (for PBC), EPP/Immunofixation (associations)
Urinalysis –P/RBC/C
ECG, echo
Xray affected joints
Work up by Rheum/renal/neuro/psych as required
T/F
Anti cytoplasmic Ab may be +ve in true ANA negative SLE
T
T/F
Anti-Sm and anti-dsDNA are specific for SLE
T
T/F
complement C1-4 all tend to be high in SLE
F
all low
T/F
the speckled ANA pattern is most common in SLE
F
Homogenous 75%
Speckled 25%
Nucleolar about 5%
Homogenous pattern most common in all forms of lupus, seckled 2nd most common
What is the lupus band test?
Granular IgG and/or IgM mainly, can also be IgA + usually complement proteins; C4 most common, C1q also common esp in SLE (90%) at DEJ
should take non-lesional skin - more likely significant result if from non-exposed site
Whats the main DD for lupus panniculitis?
Subcutaneous panniculitis-like T cell lymphoma
Others include any lobular/mixed panniculitis
If perforating - pancreatic panniculitis
T/F
Many pts with DLE relapse after clearance
T
Often relapse within 6/12 when treatment stopped
Only 50% complete remission in long term
If clearance achieved should stop treatment. May need multiple courses over years to achieve relapse-free cure
T/F
The presence of C1q on IMF in cutaneous lupus carries increased risk of SLE
T
What are the complications of cutaneous LE?
Scarring - >50% of DLE Atrophy of skin Tissue destruction (esp DLE) Dyspigmentation – 35% of DLE SCC – can develop in longstanding DLE lesion Alopecia - Scarring from DLE SLE drug AEs
T/F
HCQ effective in 75% of DLE cases
T
Takes 1.5-3 months to start to work – most will respond in 6 weeks
When controlled reduce to lowest effective dose
What are Rx of SLE?
NSAIDs 1st line for mild disease (no dangerous organ involvement) with joint pain
Mod-severe disease; corticosteroids, leflunomide, AZA, pulsed cyclophosphamide
immune response modifiers if refractory
Antimalarials less useful than in DLE but may help if photosensitivity
3rd line; MMF, MTX, CsA, Rituximab, plasmapheresis, IVIg
T/F
lupus anticoagulant antibodies cause blood thinning
F lupus anticoagulant is not anticoagulant causes thrombosis Does cause prolongation of APTT and PT Only associated w/ Lupus in less than half of cases Is type of antiphospholipid Ab
T/F
anticardiolipin Abs are types of antiphospholipid Ab
T
The main anticardiolipin Ab is anti-β2-glycoprotein-1 Ab
T/F
Antiphospholipid syndrome usually occurs in the setting of autoimmune CTD
F
primary (no AICTD) or secondary (associated with AICTD)
53% are primary
What are the associations of secondary Antiphospholipid syndrome?
SLE (36% of cases) drug-induced SLE PMR Giant cell arteritis lymphoma
What are the skin findings of Antiphospholipid syndrome?
Livedo reticularis most common (24%) can be proximal livedo reticularis with or w/out distal retiform purpura) leg ulcers occur in 5% Purpura ecchymosis livedoid vasculopathy Sneddon’s syndrome thrombophlebitis (migrans) vasculitis-like lesions, cutaneous necrosis, gangrene, splinter haemorrhages, nailfold ulcers Degos-like lesions, Behcet’s-like lesions anetoderma-like lesions with thrombosis atrophie blanche pseudo-kaposi’s sarcoma Raynaud's
What are the systemic findings of Antiphospholipid syndrome?
VTE arterial thrombosis miscarriage premature delivery MI, valvular heart disease or libman-Sacks endocarditis, epilepsy, chorea, myelitis, retinopathy, AVN, Addisons disease, haemolytic anaemia
What are Diagnostic criteria for Antiphospholipid syndrome?
Need at least 1 clinical and 1 lab feature
Clinical;
- One or more episodes of arterial, venous or small vessel thrombosis
- Pregnancy complications
One or more unexplained foetal loss at 10 wks or later (normal foetus)
One or more prem delivery of normal neonate before 34 wks
3 or more unexplained consecutive miscarriages before 10 wks
Laboratory;
- IgM or IgG anticardiolipin Abs at mod-high levels on ≥2 occasions ≥12 wks apart
- Positive lupus anticoagulant Ab test on ≥2 occasions ≥12 wks apart
- Positive β2-glycoprotein 1 Abs test on ≥2 occasions ≥12 wks apart
NB thrombocytopenia is no longer in the diagnostic criteria
What features are seen in the hands in scleroderma?
Raynaud’s
Sclerodactyly
Scleroderma proximal to knuckles if diffuse
fingertip ulcers
sequntial skin changes; oedema, induration; atrophy
flexion contractures
Erythema of thenar and hypothenar emini
Telangiectasia esp of palms
digital calcinosis (10x more common in F)
Dilated nailfold capillaries + drop out in diffuse SSc
Dry skin, hypohidrosis
May be hyperpigmentation
Can get gangrene, osteomyelitis or autoamputation
Feet may also show Scleroderma and ulceration
What skin features are seen away from the hands and feet?
scleroderma of limbs, face and trunk beaked nose, microstomia sicca syndrome Salt and pepper leukoderma hyperpigmentation - face, mainly also thighs, legs and lower abdo or diffuse Telys esp face, lips calcinosis esp around limb joints hyper or hypo trichosis Dry skin, hypohidrosis
What are the systemic complications of SSc?
Pulmonary fibrosis Pulmonary HTN Myocardial fibrosis/cardiomyopathy Renal disease/renal crisis GI fibrosis Oesophageal dysmotility Tendon friction rubs Arthralgia Proximal weakness Sicca syndrome
Which features occur more commonly among pts with limited tham diffuse SSc?
Raynaud's - 99% vs 90% Calcinosis - 40% vs 20% Matt telys - 90% vs 60% Oesophageal dysmotility 90% vs 80% small bowel involvement - 60% vs 40% Sicca syndrome - 35% vs 15% Pulmonary HTN - 25% vs 20%
T/F these systemic features may occur in limited SSc; Pulmonary HTN Pulmonary fibrosis Cardiomyopathy Arthralgia Tendon friction rubs Proximal weakness Oesophageal dysmotility small bowel involvement Renal crisis
T Arthralgia 90% Oesophageal dysmotility 90% Small bowel involvement 60% Proximal weakness 60% Pulmonary fibrosis 35% Sicca syndrome 35% Pulmonary HTN 25% Tendon friction rubs 5% Renal crisis 1%
What is CREST syndrome?
Calcinosis Raynauds (E)Oesophageal dysmotility Sclerodactyly Telangiectasia
Which autoAbs are found in SSc?
ANA high in 97% nucleolar and speckled patterns most common
Anticentromere Abs 70% limited, 20% diffuse
Scl-70 (Anti-topoisomerase 1) Abs 10% limited, 45% diffuse (specific for SSc)
RF +ve in 30%
Anticardiolipin Abs in 25%
Anti-RNA polymerase Abs - if positive indicates increased risk of diffuse disease
T/F
skin biopsy can differentiate morphoea and scleroderma
F
morphea usually has more infiltrate in early stages but in late stages cannot distinguish scleroderma and morphoea
T/F
Scl-70 (Anti-topoisomerase 1) Abs in SSc indicate likely limited disease
F
Anti-Scl-70 (Anti-topoisomerase 1) Abs and Anti-RNA polymerase Abs both indicate likely diffuse disease
Anticentromere Abs indicate likely limited disease
think ‘S’ for ‘Systemic’ and ‘C’ for CREST
T/F
Sjogrens occurs in about 45% of SSc pts
False
20% (often Ro and La +ve)
arthralgia and sicca syndrome can be part of SSc so hard to diagnose unless Abs present
What tests should be considered when working up SSc?
BP Schirmers test FBC, ELFT Serum calcium (exclude metastatic calcinosis) ESR (raised in 50%) C3, C4 (may also have lupus) CK – myopathy marker Serology; ANA, Anti-Scl-70 (topoisomerase 1), Anti-centromere Abs, RF, Anticardiolipin Abs, antiphospholipid Abs, Anti-RNA polymerase Abs, Ro and La, Myositis Abs, Anti-dsDNA, Anti-Sm Urinalysis for P/C/RBCs RFTs including DLCO CXR and high res CT chest EMG, MRI (if myopathy) ECG, Echo (for cardiac Dx and Pulm HTN) Cardiologist or resp physician may request Rt heart catheterization to assess myopathy and pulmonary HTN OGD/barium swallow/oesophageal manometry
Which pts have a worse prognosis in systemic sclerosis?
Male Black Older age of onset Truncal skin fibrosis Internal organ involvement at diagnosis Extensive lung involvement Raised ESR
In SSc there is no proven effective treatment to stop or reverse the disease
T
Each system/complication treated separately
Dont forget physio, OT and psych/ support groups
General measures for skin;
Regular emollient
Keep warm esp hands/ treat Raynauds
Stop smoking
Tretinoin cream may reduce facial tightening
Can treat telys with PDL
Which systemics may be tried in SSc?
MTX 15-25mg/wk Cyclophosphamide (used for lung dx) Prednisolone/ pulsed dexamethasone Acitretin/Isotretinoin (1mg/kg) CsA Colchicine (little evidence) MMF Penicilamine PUVA UVA1 ECP Plasmapheresis/ plasma exchange Factor XIIIa
How are ulcers managed in SSc?
Treat Raynauds, keep warm, stop smoking
Occlusive hydrocolloid dressings
Bosentan (enothelin receptor antagonist)
Iloprost IV (prostacyclin analogue)
How is calcinosis managed in SSc or dermatomyositis?
No good treatment Antacids if hyperphosphataemic Diltiazem may help some pts (antagonise calcium-sodium ion pump) Warfarin – low dose Bisphosphonates ILCS IV sodium thiosulfate 25% Surgical excision Extracorporeal shockwave lithotripsy
What are the causes of Raynaud’s disease?
I have COLD HANDS
Idiopathic
Cold injury, carpal tunnel
Obstruction of large vessels; thoracic outlet syndrome, Takayasu’s, Buerger’s, crutches
Lupus (SLE) and AI CTDs; SSc, MCTD, Antiphospholipid syndrome, Dermatomyositis
Diabetes and metabolic; myxoedema, Fabry’s disease
Haematological; cryoglobulinaemia, cryofinrinogenaemia, cold agglutinins, myeloproliferative Dx (thrombocythaemia, polycythaemia, leukaemia)
Arterial (small vessel); vibration injury, vinyl chloride, chemo, arsenic
Neurological; reflex sympathetic dystrophy, migraine, Pintzmetals var angina
Drugs; (ergot) alkaloids, bromocriptine, interferon, oestrogen, cyclosporine, sympathomimetic agents, clonidine, cocaine, nicotine
Secreting tumours; Phaeochromocytoma, Carcinoid, lung adneocarcinoma
What are the treatments of Raynaud’s disease?
General measures (avoid cold, vibration etc, stop smoking)
0.2% GTN oint (rectogesic cream)-headaches
Nifedipine 10-20mg QDS
Diltiazem
Reserpine
Losartan
Sildenafil
Aspirin and/or pentoxyfyline
Prazosin 1mg TDS reduced episodes of vasospasm
What are the types of Morphoea?
Generalized
Localized
- Plaque morphoea
- Linear morphoea
- Frontoparietal morphoea (en coup de sabre)
- Subcutaneous (deep) morphoea
- Bullous
- Others – guttate, nodular/keloidal etc
Some consider atrophoderma of Pasini and Pierini to be a form of superficial morphoea
Some consider Hemifacial atrophy (Parry-Romberg) in this group
T/F
all types of morphoea are more common in women
F
linear morphoea is M=F (and more common in children)
other types 3x more in women
T/F
SSc is associated with other AI CTD
T Sjogrens SLE Dermatomyositis but not associated with other AI diseases
T/F
20% of new cases of morphoea are children
T
mean age of onset 7 years
T/F
Morphoea has associations in adults but none in children
F Other way around children may have – arthralgia neurological, vascular, occular, GI, resp or cardiac anomalies (get work up by paediatrician if any concerns clinically)
T/F
plaques of morphoea are oedematous and elevated initially then become sclerotic later
T
become sclerotic as they expand centrifugally
alos turn from red-violet to white or brown
A persisting lilac border is the hallmark of an active lesion
T/F
linear lesions of morphoea have no complications
F
occur in kids and can affect growth of the area/limb and use of nearby joints
soemtimes circumfrential rather than longitudinal - can constrict limb
Can cause permanent limb asymmetry
T/F
Linear moprhoea may be triggered by allogenic BMT
T
T/F
Linear frontoparietal moprhoea can extend from parietal scalp down face as far as neck
T
T/F
Parry Romberg syndrome is hemifacial atrophy without cutaneous sclerosis
T
But Linear frontoparietal moprhoea (en coup de sabre) can also cause hemifacial atrophy and can go as deep as brain
What is the natural Hx of morphoea?
progresses over 3-5 years then arrests and slowly resolves spontaneously leaving burnt out scars
What is treatment ladder for morphoea?
Photos for monitoring important Potent TCS Topical tacrolimus Daivonex (calcipotriene) ILCS Retinoids – low dose with PUVA or UVA1 Oral steroids MTX (15-20mg/wk) +/- pulsed high dose IV methyl pred (1g 3 days per month) Acitretin (10-50mg/day appears effective in some pts) Penicillin or penicillamine PUVA (mainly as bath PUVA) UVA1 Physio to prevent joint contractures OT and physio for lymphoedema surgery to excise scarred areas or reconstruct
What are the causes of sclerodermoid change?
SCLERODERMA K
S- Scleroderma, scleredema, scleromyxoedema, Stiff skin syndrome
C – CTD (mixed), carcinoma en cuirasse, chronic GVHD, Carcinoid
L – Lichen sclerosus (extragenital), lipodermatosclerosis
E – Eosinophilic fasciitis, EBA
R – Renal (nephrogenic systemic fibrosis)
O – Oedema (gravitational)
D – Drugs + Toxins (bleomycin, Gadolinium contrast, penicillamine, tryptophan, Phenytoin, Atorvastatin, PVC, solvents, silica, dry cleaning solvents, epoxy resins)
E – Endocrine (hyperthyroidism – pretibial myxoedema) diabetic cheiroarthropathy
R – Radiation, Rapeseed toxic oil
M – Metabolic (PKU, PCT)
A – Amyloidosis
Vitamin K injection (Texier disease)
What are clinical features of Eosinophilic fasciitis?
Adults or children, M>F
Acute pain, swelling and tenderness of distal limbs - become sclerodermoid
‘pseudo-cellulite’ rippled appearance
‘groove sign’ – linear depression at site of veins
no systemic features/ can be Raynaud’s
What are triggers of Eosinophilic fasciitis?
Strenuous physical activity (up to 30% of cases)
Neoplasia – malignancy screen
Drugs – atorvastatin, phenytoin, tryptophan
Autoimmune thyroiditis
Hypercalcaemia
Eosinophilic colitis
What are histo findings of Eosinophilic fasciitis?
dermal sclerosis
lymphocytic inflam of fat and fascia + eos
fibrosis of fat and fascia
Fascia is thick and infiltrated by lymphocytes, plasma cells, histiocytes and eos, can be mast cells
What is treatment of Eosinophilic fasciitis?
Rx with steroids – see response in weeks and taper over 6-24 months
If needed add MTX, CsA, HCQ, dapsone, infliximab or PUVA
Can use UVA1 alone or with retinoid
Can be spontaneous remission
What is Nephrogenic systemic fibrosis (NSF)?
How is it treated?
AKA nephrogenic fibrosing dermopathy
Triggered by the use of gadolinium based contrast medium in pts with renal disease
Redish papules that coalesce into red/brawny plaques with peu d’orange (or cobblestone) appearance
Symmetrical on legs and arms and trunk and progress rapidly
become thick and woody causing joint contractures
Also get yellow scleral plaques
Poor response to Rx
Topical – steroids, calcipotriol
Systemic – steroids, IVIg, d-penicillamine, CsA, cyclophosphamide, thalidomide, IFNα, imatinib, rapamycin
Procedural – UVA1, PDT, ECP
Also discontinuation of Erythrompoeitin
T/F
Mixed Connective tissue disease often has high titre homogenous ANA
F high titre speckled ANA Anti-U1RNP antibodies on ENA often RF +ve Usually negative for specific Abs for SLE or SSc
T/F
Mixed Connective tissue disease has overlapping clinical and serologic features of various combinations of RA, systemic sclerosis, SLE, and polymyositis
T
MCTD is least common of the autoimmune CTDs
Death due to pulmonary HTN
T/F
Dermatomyositis F:M = 2-3:1
T
T/F
25% of adults and children with dermatomyositis get malignancy
F
25% of adults
not children
T/F In dermatomyositis autoreactive CD8 T cells invade myocytes expressing MHC class I antigens and cause necrosis via perforin pathway
F
That is polymositis
In dermatomyositis complement is deposited in capillaries causing capillary necrosis and ischemia
This is directed by auto antibodies
T/F
Dermatomyositis is assoc w/ HLA DR3, DR5, DR7
T
What are triggers for dermatomyositis?
Malignancy
- lung, breast, female genital tract, stomach, rectum, kidney or testis
Infection
- Staph, strep, Toxoplasmosis, parvovirus B19, coxsackie B, HTLV-1, HIV
Drugs + Vaccination
- PHD TO BOOST (the) CV
Penicillamine, Hydroxyurea, Diclofenac
Tamoxifen, TNFalpha blockers, Benzalkonium Chloride
Carbamazepine, cyclophosphamide, Vaccination (BCG)
What are the types of dermatomyositis?
Adult-onset; Classic DM Classic DM with malignancy Classic DM as part of an overlapping CTD Clinically amyopathic DM; - Amyopathic DM - Hypomyopathic DM
Juvenile-onset; Classic DM Clinically amyopathic DM - Amyopathic DM - Hypomyopathic DM
Antisynthetase syndrome
What is Antisynthetase syndrome?
variant of dermatomyositis; Anti-aminoacyl tRNA synthetase Abs – includes; anti-Jo-1, anti-PL-7, anti-PL-12 Fever Raynauds Myopathy Interstitial lung disease Non-erosive arthritis Mechanics hands +/- Gottrons papules
What are the associations of Dermatomyositis?
Malignancy - ?association/trigger AI CTD; SLE, SSc, Sjogren’s, RA, MCTD other AID; autoimmune Thyroid disease Myasthenia gravis T1 Diabetes Primary biliary cirrhosis Coeliac/Dermatitis herpetiformis Vitiligo
T/F
Anti-Jo1 Abs in DM are associated with / antisynthetase syndrome
T
Also anti-PL-7, anti-PL-12 Abs
T/F
Anti-p140 Abs have been linked to juvenile DM and calcinosis
T
T/F
Anti-SAE Abs assoc w/ acute onset necrotizing myopathy, may be refractory to treatment
F That is Anti-SRP Abs Anti-SAE Abs – skin and muscle DM with few/absent systemic features/may be amyopathic SRP = Some refractory people SAE = Some are easy (mild/amyopathic)
T/F
Anti-MDA5 (Anti-CADM 140) Abs - associated with clinically amyopathic DM and possibly interstitial lung disease and may have other features of antisynthetase syndrome
T
MDA5 = Muscles Do A 5 as in 5/5 power (amyopathic)
T/F
Anti-p155/140 Abs - malignancy associated myopathic DM + severe skin disease
T
55 = SS = Severe Skin, tumour within
Which autoantbodies are associated w/ amyopathic dermatomyositis?
Anti-MDA5 (Anti-CADM 140)
anti-synthetase Abs; anti-Jo-1, anti-PL-7, anti-PL-12
SAE - sometimes amyopathic
Anti-Mi2 - mild muscle disease
T/F
Anti-Mi2 Abs associated with skin and muscle DM with few/absent systemic features/may be amyopathic
F
This is anti-SAE
Anti-Mi2 Abs associated with severe but responsive skin disease, Hypomyopathic muscle disease; responds well to Rx
T/F
Most often the malignancy is already present when dermatomyositis starts
F
Most often DM precedes the neoplasm 40%
neoplasm occurs first in 35%
Concurrent in 25%
T/F
Patients with amyopathic DM dont get malignancy
F
risk is the same
T/F
In dermatomyositis, myositis may occur concurrently, precede, or follow skin disease by weeks to years
T
If no sign of myositis at presentation of dermatomyositis what is course of action?
If no sign of myositis at presentation is clinically amyopathic
Do full Ix to see if actually hypomyopathic;
Serum CK, Aldolase, LDH
EMG
Triceps muscle biopsy if no obvious involved muscle
MRI (T2 weighted) or USS of proximal muscles if EMG or muscle Bx negative or declined
If still amyopathic then need to monitor for myopathy (at least clinical muscle weakness and measurement of CK and aldolase) every 2-3 months for 2 years – if remains amyopathic can change diagnosis from clinically amyopathic to amypathic DM
If no sign of malignancy at presentation of dermatomyositis what is course of action?
Full age and sex-appropriate maligancy screen
If still negative repeat every 4-6 months or at least annually for at least 3 years
Some evidence that if no maligancy after 2-5 years risk goes back to baseline
What is age and sex-appropriate maligancy screen e.g. in Dermatomyositis
FSE
EPP/Immunofixation, BJP
Urine cytology
Stool FOBx3
Men – PSA, LDH, AFP (testicular)
Women - Mammography, smear, Transvaginal pelvic USS (CA125 only if mass found on USS)
CT chest/abdo/pelvis
Colonoscopy if age appropriate, Fe deficiency anemia, occult blood in stool, or symptoms
Upper endoscopy – if colonoscopy negative in setting of the above (see colonoscopy)
For Asians get ENT rw
NB LDH can be raised in cancer or muscle disease as wellas cardiac or liver Dx or haemolysis
T/F
Bone marrow biopsy is important in work up of dermatomyositis
F
mostly solid organ malignancies
What are the systemic features of Dermatomyositis?
Fever, arthralgias, malaise, weight loss
Raynauds phenomenon
Dysphagia, reflux
Cardiac disease - arrhythmias or conduction defects
Respiratory disease - diffuse interstitial fibrosis; also weakness of thoracic muscles; may also develop ARDS
Skin biopsy findings in dermatomyositis
often subtle
Lichenoid similar to LE
sparse lymphocyte infiltrate
dermal interstitial mucin deposition
What investiagtions should be done in Dermatomyositis?
Skin biopsy
FBC, ELFT, CK
Myositis antibody screen
Associations screen - fasting glucose, HbA1c, ANA, ENA, dsDNA, thyroid autoantibodies, TFTs, AMA, coeliac serology
Full myositis screen if clinically amyopathic
Malignancy screen
Systemic complications screen - RFTs with DLCO, HRCT chest, ECG, Echo +/- Holter, If symptoms; barium swallow/ manometry
Pre treatment tests;
DEXA bone density scan pre steroids
Qgold and infection screen prior to immunosuppression
Eye exam and G6PD prior to HCQ
T/F
Skin, lung and muscle disease of dermatomyositis often respond well to steroids
F
muscle often does but not always
often disocrdance between responses in the 3 areas
What is treatment of Dermatomyositis?
General; make appropriate referrals; Physio, Speech path, Rheum, Gastro, Cardiol, Resp bed rest for severe myositis, physiotherapy, raising head of bed to prevent reflux/aspiration if dysphagia or GORD sometimes NGT feeds Sun avoidance and protection Skin; Topical steroid TCNI HCQ - books say can add quinacrie but not available in Aus; below Rxs can be added to HCQ rather than replace MTX - 2nd choice MMF - 3rd choice Others that have reported benefit; dapsone, thalidomide, anti-TNFα (etanercept), IVIg Muscle; High dose prednisolone - responds in 4 weeks, taper dose to half in 1st 6 months then taper off over 1-2 years pulse methyl-prednisone steroid-sparing agent MTX or AZA high dose IVIG pulsed cyclophosphamide Cyclosporine MMF Biologics (infliximab)
What are the clinical subtypes of SCLE?
Annular - 40% Papulosquamous (psoriasiform) - 40% Bullous Hypertrophic (keratotic) TEN-like
Which autoantibodies are most important in morphoea work up?
None very specific for morphoea
ANA, ssDNA and antihistone Abs most important
In what proportion of morphoea pts are anti ssDNA Abs +ve?
Anti-single stranded DNA Abs +ve in;
25% plaque
50% linear
75% generalised
Which morphoea pts are more likely to have a raised ANA?
children or in linear, generalized or deep morphoea
T/F
In plaque morphoea antihistone Ab titres correlate to extend and activity
F
this is true in linear morphoea
Antihistone Abs also may be +ve in other types esp in generalised or widespread plaque morphoea
T/F
Muscle involvement occurs before skin involvement in demratomyositis with anti-SUMO-1 antibodies
F
Skin first - Su
Muscle later - Mo
T/F
25% of kids presenting with DLE will have SLE when investigated fully
F
15% have SLE at presentation
T/F
Of kids with skin limited DLE at diagnosis;
25% go on to develop SLE
45% develop lab abnormalities but not SLE
30% maintain skin limited disease
T
T/F
90% of children who had DLE and SLE get systemic disease
F
Only 10% get true systemic disease
90% of children who had DLE and SLE (by criteria) meet criteria by mucocutaneous features only without getting systemic disease
