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
