Download uni-5-Dermatomyositis, Scleroderma, SCLE and DLE

Unit 5.
Dermatomyositis，Scleroderma
– Etiology, Clinical features, Diagnosis and Treatment. 1.5 hr
Subacute cutaneous lupus erythematosus
Discoid lupus erythematosus
- Etiology, Clinical features, Diagnosis and Treatment. 0.5 hr
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Connective Tissue Diseases(CTD)
-concept
• Autoimmune diseases–
diseases associated with specific autoantibodies
• Connective-tissue disorders—
collagen-vascular disorders,
are characterized by autoantibody-mediated
connective-tissue abnormalities.
• Histopathology:
--Perivascular collagen deposition
=Collagen Vascular Diseases
• Symptoms nonspecific & overlapping
Sir Run Run Shaw Hospital Prof. Cheng
Connective Tissue Diseases(CTD)
•Dermatomyositis
•Scleroderma-Systemic Sclerosis-Diffuse Sclerosis*
Localized Fibrosing Disorders
- Linear Scleroderma
Morphea, & Regional Fibrosis
•Lupus Erythematosus (LE):
Acute-, Subacute Cutaneous-LE, Discoid-LE,
Drug-Induced -, Bullous -, Systemic -, Neonatal •Mixed Connective Tissue Disease, MCTD
•Sjogren Syndrome
•Eosinophilia-Myalgia Syndrome
•Eosinophilic Fasciitis
•CREST Syndrome
Sir Run Run Shaw Hospital Prof. Cheng
Dermatomyositis，DM
皮肌炎
Sir Run Run Shaw Hospital Prof. Cheng
Definition of DM
• an idiopathic inflammatory myopathy (IIM) with
characteristic cutaneous changes
• a systemic disorder that frequently affects the
joints, esophagus, lungs, heart (rarely)
• Related to Malignancy (>60y)
• Calcinosis (in children, 40%)
• Prognosis
– Level of myopathy
– y/n malignancy
– Cardiopulmonary Involvment
Sir Run Run Shaw Hospital Prof. Cheng
Dermatomyositis
-concept
• Proximal muscle weakness
nonsuppurative inflammation of skeletal muscle
• 5 cases per million per year
• 2:1 female:male
• No racial disposition
• Can occur at any age, 2 peaks
– Adults – 50y(40-60)
– Children – 5-15y
Sir Run Run Shaw Hospital Prof. Cheng
Cause & Pathophysiology of DM
• Genetic –
HLA DR3,DR5,DR7, TNF-a polymorphism
• Immunologic abnormalities –
antibody-mediated cell cytotoxicity
vascular inflammation
• Infectious –
viral agents, Toxoplasma, Borrelia
• Drug-induced –
Hydrea, penicillamine, statin, quinidine, phenylbutazone
• Silicone breast implants –
anecdotal
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features of DM
• eruptions on exposed surfaces-as one of the initial manifestations
• Muscle involvement –
manifests as proximal muscle weakness.
• Systemic manifestations may occur
--arthralgia, arthritis, dyspnea, dysphagia,
arrhythmia, dysphonia
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features of DM
Hallmark Skin lesion
• the characteristic
– a heliotrope discoloration on the upper eyelids
– Gottron papules:
violaceous, scaly papule-macule
– nailfold telangiectasia
– poikiloderma in a photodistribution.
– Pruritic
– Scaly scalp or hair loss
Classic Cutaneous
Manifestations
Sir Run Run Shaw
Hospital Prof. Cheng
The heliotrope flower
The heliotrope rash is a characteristic and pathognomonic
cutaneous feature of DM.
Sir Run Run Shaw Hospital Prof. Cheng
Systemic Manifestations/Associations
of Dermatomyositis/Polymyositis
•Musculoskeletal
• Myositis with proximal weakness
• Muscle atrophy and contracturea
• Muscular calcificationa
•Cardiac
• Cardiomyopathy
• Conduction defects
•Respiratory
• Dysphonia
• Diffuse interstitial pneumonitis/fibrosis
• Aspiration pneumonia
• Respiratory failure from muscle weakness
•Gastrointestinal
• Proximal dysphasia
• Large bowel infarction/perforation secondary to
vasculopathya
•Ophthalmologic
• Retinopathya
• Internal malignancyb
Sir Run Run Shaw Hospital Prof. Cheng
Lung disease —
•Interstitial lung disease (ILD)
is an important complication
may be associated with rapidly progressive
pulmonary failure and death
•respiratory insufficiency
may result from diaphragmatic
and chest wall muscle weakness
Sir Run Run Shaw Hospital Prof. Cheng
Malignancy of DM
•paraneoplastic processes
---linked to oncogenesis & autoimmunity
•Including:
Nasopharyngeal cancer
breast cancer
pancreatic cancer
ovarian cancer
cholangial cancer
laryngeal cancer
tongue cancer
Lymphoma
lung cancer
colorectal cancer
stomach cancer
esophageal cancer
liver cancer
renal cancer
Sir Run Run Shaw Hospital Prof. Cheng
Complications
•Cutaneous Ulceration
•Systemic Vasculopathy
•Calcinosis
•Internal Malignancy
•Opportunistic Infections and Lymphoma
Sir Run Run Shaw Hospital Prof. Cheng
Amyopathic DM (ADM)
•
•
•
•
Typical cutaneous manifestations
No muscle symptoms
Normal muscle enzymes
Subclinical muscle disease
– Px – mild proximal weakness
– EMG – mildly abnormal
– Abnormal US, MRI, Biopsy
• new autoantibodies (140 kDa, 155 kDa, and Se) might
serve as serologic markers
• may reflect an underlying malignancy
!
Sir Run Run Shaw Hospital Prof. Cheng
Laboratory Studies of DM
• elevation of Muscle enzyme
creatine kinase（CK）level，aldolase level test
Aspartate aminotransferase（AST）
lactate dehydrogenase （LDH）tests
• serologic abnormalities:
*ANA，
* three major categories of myositis-specific Abs (MSAs):
1,Abs to aminoacyl-tRNA synthetases (antisynthetase Abs )
including anti-Jo-1;
2, Abs to signal recognition particle (anti-SRP Abs);
3,Abs to Mi-2, a nuclear helicase.
* other myositis-specific autoantibodies
Sir Run Run Shaw Hospital Prof. Cheng
Autoantibodies in Idiopathic Inflammatory Dermatomyositis
Autoantibody Median
Molecular
Prevalence Specificity
Clinical Association
High Specificity for DM/PM
155 kDa
and/or Se
140 kDa
Fer
20%–80% transcriptional
Classic DM, clinically amyopathic DM with
intermediary factor-1
increased risk of internal malignancy
53%
helicase C domain protein Clinically amyopathic DM with increased
1 (IFIH1)/melanoma
risk for interstitial lung disease
differentiation-associated
gene 5 (MDA-5)
20%
Histidyl-tRNA synthetase PM, antisynthetase syndrome
15%
Helicase nuclear proteins Shawl sign, cuticular overgrowth
5%
Signal-recognition particle Fulminant DM/PM, cardiac involvement
3%
Threonyl-tRNA
Antisynthetase syndrome
synthetase
3%
Alanyl-tRNA synthetase Antisynthetase syndrome
Rare
Isoleucyl-tRNA
Antisynthetase syndrome
synthetase
Rare
Glycyl-tRNA synthetase Antisynthetase syndrome, possibly
increased frequency of skin changes
Rare
Elongation factor 1
—
Mas
Rare
Small RNA
KJ
Rare
Translation factor
—
Sir Run Run Shaw Hospital Prof. Cheng
Jo-1
Mi-2
SRP
PL-7
PL-12
OJ
EJ
—
Autoantibodies in Idiopathic Inflammatory Dermatomyositis
Autoantibody Median
Molecular
Prevalence Specificity
Low Specificity for DM/PM
ANA
40%
SsDNA
40%
PM-Scl (PM-1) 40%
Ro (52-kDa Ro) 15%
U1RNP
Ku
10%
3%
U2RNP
1%
Clinical Association
Clinically amyopathic DM (80%)
SLE, SSc
Overlap with scleroderma
Ribosomal RNA
processing enzyme
RNP
Overlap with SSJ, SCLE, neonatal LE/CHB,
SLE
U1RNP
Overlap connective tissue disease
DNA end-binding Overlap with scleroderma
repair protein
complex
U2RNP
Overlap with scleroderma
Sir Run Run Shaw Hospital Prof. Cheng
Imaging Studies
•
•
•
•
•
MRI
Chest radiography
A barium swallow
Ultrasonography
Electromyography
(EMG)
• CT scanning
Other tests
•Pulmonary function
studies
•Electrocardiography
(ECG)
•skin biopsy
•Muscle biopsy
Sir Run Run Shaw Hospital Prof. Cheng
Histologic Findings
Skin biopsy
an interface dermatitis
Muscle biopsy
perivascular and
interfascicular lymphocytic
inflammation
Sir Run Run Shaw Hospital Prof. Cheng
perivascular and perimysial
inflammation,
& Hospital
perifascicular
necrosis.
Sir Run
Run Shaw
Prof.
Cheng
Diagnosis of DM
•
•
•
•
Proximal muscle weakness
Elevated serum creatinine kinase
Myopathic changes on electromyography
Muscle biopsy with evidence of
lymphocytic inflammation
• Rashs（Gottron’s sign, heliotrope rash）
• Positive auto-antibody：ANA，Jo-1
Sir Run Run Shaw Hospital Prof. Cheng
Differential Diagnoses
CREST Syndrome
Parapsoriasis
Graft Versus Host Disease
Pityriasis Rubra Pilaris
Lichen Myxedematosus
Polymorphous Light Eruption
Lichen Planus
Psoriasis, Plaque
Lupus Erythematosus, Acute
Rosacea
Lupus Erythematosus, Discoid
Sarcoidosis
Lupus Erythematosus, Subacute Cutaneous
Tinea Corporis
Morphea
Urticaria, Chronic
Multicentric Reticulohistiocytosis
Sir Run Run Shaw Hospital Prof. Cheng
Treatment of DM
– general
• difficult
• Bed rest - in severe myopathy
• Physical therapy prevents curvatures in children, lasting joint
damage (rare)
• Elevate head after eating –
prevent aspirations,
may need NGT(nasogastric tube)
• High protein diet
Sir Run Run Shaw Hospital Prof. Cheng
Treatment
• photosensitive
- sun avoidance and sun protective measures,
sunscreens； Hydroxychloroquine, chloroquine
• symptomatic patients：Steroids
• non-responders： immunosuppressive agents
methotrexate
cyclosporine
azathioprine
tacrolimus
fludarabine
cyclophosphamide
leflunomide
chlorambucil
mycophenolate mofetil
• Anti-TNF agents (Infliximab)
• Rituximab，anti-CD20 antibody
specific in targeting the antibody-producing B cells
• IVIG
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Scleroderma
(Systemic Sclerosis)
Sir Run Run Shaw Hospital Prof. Cheng
Scleroderma-Background
• Scleroderma is derived from the Greek words
skleros (hard or indurated) and derma (skin)
• Hippocrates first described this condition as thickened skin
• 1752, Carlo Curzio offered the first detailed description of scleroderma in
a patient with hard skin-- described as woodlike or containing a dry hide
• 1836, Giovambattista Fantonetti applied the term scleroderma to a
patient's condition--described as dark leather-like skin who exhibited a
loss of range of joint motion due to skin tightening.
• 1945, Robert H. Goetz first described the concept of scleroderma as a
systemic disease-he introduced the term progressive systemic sclerosis(PSS) to
emphasize the systemic & often progressive nature of the disease
Sir Run Run Shaw Hospital Prof. Cheng
Scleroderma
definition
• a chronic multisystem disorder characterized by :
--the overproduction & accumulation of collagen:
**excessive fibrosis of the skin
--with skin thickening & induration
**fibrosis & chronic inflammatory infiltration in organs
--structural and functional abnormalities
of blood vessels & organs
--GI tract, lung, heart and kidneys
**immune system activation (autoimmunity)
** vasculopathy.
Sir Run Run Shaw Hospital Prof. Cheng
Etiology
• Environmental factors
1) silica dust
2) organic solvents
3) biogenic amines
4) urea formaldehyde
• Genetic predisposition
• Defective immunoregulation
1) cell mediated immunity:
CD4/CD8 , cytokines
2) humoral immunity
5) polyvinyl chloride
– hypergammaglobulinemia
6) rapeseed oil
– autoantibody production
7) bleomycin
– antinuclear antibody (+) > 95%
8) L-tryptophan
9) silicone implant (?)
Sir Run Run Shaw Hospital Prof. Cheng
Pathogenesis
Susceptible host
Exogenous events
Immune system
activation
Fibroblast activation
Endothelial cell
activation/damage
End stage pathology
Obliterative vasculopathy
Fibrosis
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Pathogenesis
• 1. Vasculopathy of small artery and capillary
•
•
•
•
•
•
•
•
•
•
- endothelial cell injury
- adhesion and activation of platelet
- PG F, thromboxane A2 release
- vasoconstriction & growth of endothelial cell and fibroblast
- narrowing or obliteration, increased permeability
2. Fibrosis
- aberrant regulation of fibroblast cell growth
- increased production of extracellular matrix
(collagen, fibronectin, and glycosaminoglycan)
- thickening of the skin & fibrosis of internal organs
Sir Run Run Shaw Hospital Prof. Cheng
Classification
1. Systemic sclerosis (Scleroderma)
– Diffuse cutaneous systemic sclerosis
– Limited cutaneous systemic sclerosis
–
Overlap syndromes
2. Localized scleroderma
-Morphoea
-Linear scleroderma
3. Overlap syndromes
–
Features of systemic sclerosis together with those of at least
one other autoimmune disease, e.g. SLE, RA, or polymyositis
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features of Scleroderma
Diffuse
Limited
Skin Involvement
Distal and proximal
Distal to elbows, face
extremities, face, trunk
Raynaud’s
Phenomenon
Onset within one year
or at time of skin
changes
Organ Involvement
Pulmonary (interstitial GI, pulmonary
fibrosis); renal (renal
hypertension
crisis); gastrointestinal;
cardiac
Nail Fold Capillaries
Dilation and dropout
Dilation without
significant dropout
Antinuclear Antibodies
Anti-topoisomerase
Anti-centromere
* CREST
May precede skin
disease by years
syndrome
- calcinosis, Raynaud's phenomenon, esophageal
sclerodactyly,
Sir Rundysmotility,
Run Shaw
Hospitaltelangiectasia
Prof. Cheng
Clinical features of Scleroderma
1. Vascular abnormalities Vasculopathy
1) Raynaud's phenomenon
- cold hands and feet
• reversible skin color change (white to blue to red)
• - induced by cold temperature or emotional stress
• - initial complaint in 3/4 of patients
• - 90% in patients with skin change
•
(prevalence in the general population: 4-15%)
2) digital ischemic injury
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features
Scleroderma
2. Skin involvement (1)
1) stage-- - edematous phase
- indurative phase
- atrophic phase
2) firm, thickened bound to underlying soft tissue
3) decrease in range of motion loss of facial
expression inability to open mouth fully
contractures
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features
2. Skin involvement (2)
ulceration
loss of soft tissue of finger tip
pigmentation
calcific deposit
3. Musculoskeletal system
Polyarthritis and flexion contracture
Muscle weakness and atrophy
(primary /secondary)
Sir Run Run Shaw Hospital Prof. Cheng
Terminal digit resorption
Acrolysis
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Acrosclerosis
Prof. Cheng
Calcinosis
Calcinosis & acrolysis
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features
4. gastrointestinal involvement
1) esophagus: hypomotility and retrosternal pain,
reflux esophagitis, stricture
2) stomach: delayed emptying
3) small intestine: pseudo-obstruction,
paralytic ileus
malabsorption, weight loss,
cachexia
4)large intestine: chronic constipation
fecal impaction diverticula
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features
5. lungs
1) 2/3 of patients affected
- leading cause of mortality and morbidity in later stage
2) pathology
- interstitial fibrosis
- intimal thickening of pulmonary arterioles
(pulmonary hypertension)
3) Complains - dry cough
breathlessness (Progressive dyspnea )
Sir Run Run Shaw Hospital Prof. Cheng
Pulmonary fibrosis
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features
6. kidney
1) pathology
- intimal hyperplasia of the interlobular artery
- fibrinoid necrosis of afferent arterioles
- glomerulosclerosis
2) proteinuria, abnormal sediment, azotemia,
microangiopathic hemolytic anemia, renal failure
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features
7. Cardiovascular system
• Pericarditis,pericardial effusion,myocardial
fibrosis
--Congestive heart failure
--Dyspnea
• conduction abnormalities
--arrhythmia (irregular heart beats)
--Palpitations
--syncope
8.Exocrine glands
– Xerostomia
– xerophthalmia
Sir Run Run Shaw Hospital Prof. Cheng
Laboratory findings
1. ANA, RF
2. anti-Scl-70 (DNA topoisomerase I) antibody
– 20-40% in diffuse scleroderma
– 10-15% in limited scleroderma
3. anticentromere antibody
– 50-90% in limited scleroderma
– 5% in diffuse scleroderma
Sir Run Run Shaw Hospital Prof. Cheng
Scleroderma Autoantibodies
7 known scleroderma specific autoantibodies
•Anticentromere Antibodies (ACA)
•Anti-Scl-70 or anti-topoisomerase (TOPO)
•Anti-U1-RNP (U1-RNP) or (antifibrillarin)
•Anti-RNA Polymerase III (Pol 3)
•Anti-U3-RNP (U3-RNP)
•Anti-Th/To (Th/To)
•Anti-Pm/Scl (Pm/Scl)
Sir Run Run Shaw Hospital Prof. Cheng
Clinical Association of Hallmark Autoantibodies in
Systemic Sclerosis (SSc)
Reactivity
Target Antigen
Frequency in HLA Association
SSc (%)
Centromere CENP proteins
20–30
HLA-DRB1 HLAspeckled pattern
DQB1
Scl-70
Topoisomerase-1 15–20
speckled pattern
RNAP III
RNA polymerase 20
III speckled
pattern
nRNP
U1-RNP speckled
pattern
Polymyositis/Scl
nuclear staining
pattern
U3-RNP nuclear
staining pattern
7–2RNP nuclear
staining pattern
PM-Scl
Fibrillarin
Th/To
15
3
4
2–5
Clinical Association
Limited skin sclerosis, severe
gut disease, isolated PAH,
calcinosis
HLA-DRB1 HLADiffuse skin sclerosis,
DQB1 HLA-DPB1
pulmonary fibrosis and
secondary PAH, increased
SSc-related mortality rate
HLA-DQB1
Diffuse skin sclerosis,
hypertensive renal crisis,
correlated with a higher
mortality rate
HLA-DR2, -DR4
Overlap features of SLE,
HLA-DQw5, -DQw8 arthritis
HLA-DQA1 HLALimited skin sclerosis,
DRB1
myositis–sclerosis overlap,
calcinosis
HLA-DQB1
Diffuse skin sclerosis, myositis,
PAH, renal disease
HLA-DRB1
Limited skin sclerosis,
Sir Run Run Shaw
Hospital
Prof. Cheng
pulmonary
fibrosis
Imaging Studies
•
•
•
•
•
Chest radiography
Echocardiography
Ultrasonography
CT scanning
Esophagraphy
Other tests
•Pulmonary function
test
•Serum NT-proBNP
•ECG
Sir Run Run Shaw Hospital Prof. Cheng
Scleroderma Diagnostic Criteria
• One major criterion:
scleromatous skin changes proximal to the
metacarpal-phalangeal joints（近端掌骨，指骨关节）
• Two of three minor criteria:
sclerodactyly,
digital pitting scars,
or loss of substance from the finger pads
bi-basilar pulmonary fibrosis on CXR
* one major or 2 or more minor criteria
Sir Run Run Shaw Hospital Prof. Cheng
Recommended Diagnostic Procedures in SSc
Organ
Clinical Feature
Involvement
Vascular
Raynaud
system
phenomenon
Skin
Scleroderma
Calcinosis cutis
Musculoskel Arthralgia/Synovitis
etal system Muscle weakness
Diagnostic Procedures
•Coldness provocation
•Nail fold capillaroscopy
•Antinuclear antibody levels
•Clinical assessment regarding puffy fingers,
telangiectasias, mechanic hands, hypo/hyperpigmentations, digital ulcerations,
dermatogenous contractures
•Modified Rodnan skin score
•20-MHz ultrasound
•Radiography (X-ray, MRI, CT)
•Clinical assessment regarding fist closuredeficiency, joint contractures, tendon friction rub,
muscle weakness
•Laboratory parameters: erythrocyte
sedimentation rate, rheumatoid factor,
antinuclear autoantibodies
•Creatine kinase (>threefold?)
•MRI, electromyography
•Muscle
Sir Runbiopsy
Run Shaw Hospital Prof. Cheng
Recommended Diagnostic Procedures in
SSc
Organ
Involvement
Clinical Feature
Diagnostic Procedures
Gastrointestinal Reflux Dysphagia
•Gastro-/Esophageal-endoscopy
tract
Diarrhoea, obstipation •Oesophageal-szintigraphy
•Oesophagus-manometry
•Coloscopy
Respiratory
Dyspnoea
•Lung function test (TLCOc SB, TLC, FVC)
system
•Radiography (X-ray or HR-CT)
•Bronchioalveolar Lavage (BAL) (optional)
Cardiac system Dyspnoea, arrhythmia •Electrocardiography (conduction blocks?)
•Echocardiography (mPAP, diastolic
dysfunction?, ventricular ejection fraction)
•(Spiro-)Ergometry
•24-hour blood pressure controls
•Right-heart catheterization
Kidney
Renal function failure •Regular blood pressure controls (>140/90
mm Hg)
•Ultrasound
•Serum levels of creatinine, urine-analyses
Sir Run Run Shaw Hospital Prof. Cheng
(protein-, albuminuria, microelectrophoresis)
Treatment
• thickening & indurative Skin
•
•
•
- D-penicillamine
- methotrexate
- immunosuppressive agent:
cyclosporin, IFN-,mycophenolate mofetil,
cyclophosphamide, photopheresis,
allogeneic bone marrow transplantation
• Symptomatic (organ-specific) treatment
Sir Run Run Shaw Hospital Prof. Cheng
Treatment
• Raynaud’s phenomenon and ischemia
1) avoid cold exposure
layers of warm, loose-fitting clothing
2) quit smoking
3) vasodilator therapy
- calcium channel blocker (nifedipine), prazosin, ACE-I
-dipyridamole, aspirin
4) thrombosis and vascular flow compromise,
tissue plasminogen activator--heparin, and urokinase
5) finger / toe necrosis
- intravenous prostaglandin (PGE1, PGI2)
- Bosentan
- amputation
Sir Run Run Shaw Hospital Prof. Cheng
Treatment
• Gastrointestinal
• 1) reflux esophagitis and dysphagia
•
- elevation of head of bed
•
- small frequent meal
•
- avoid lying down within 3-4 hours of eating
•
- abstaining from caffeine-containing beverages,
•
cigarette smoking
•
- H2 blocker, proton-pump inhibitor
• 2) gastroparesis: promotility agent (metoclopramide)
• 3) malabsorption syndrome: broad spectrum antibiotics
Sir Run Run Shaw Hospital Prof. Cheng
Treatment
•
Pulmonary
1) Interstitial fibrosis
- corticosteroid
- cyclophosphamide, azathioprine
2) pulmonary artery hypertension
- calcium channel blocker
- prostacyclin
- transplantation
•
Renal
renal crisis episodes are best prevented and treated with
the aggressive use of ACE inhibitors (eg:captopril) at
the earliest signs of hypertension
- later: dialysis
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Prognosis of scleroderma
• quite variable and difficult to predict
• cumulative survival
diffuse
limited
5 yr
70%
90%
10 yr
50%
70%
• major cause of death
1) renal involvement
2) cardiac involvement
3) pulmonary involvement
(Pulmonary hypertension, pulmonary fibrosis )
Sir Run Run Shaw Hospital Prof. Cheng
Cutaneous Lupus
concept
• Affects only the skin
• 1 of 10 patients will go on to develop SLE
• Symptoms –
rashes, hair loss,
cutaneous vasculitis, skin ulcers,
photosensitivity
• Treatmentssunscreen, steroid creams and gels,
antimalarials, immunosuppressives
Sir Run Run Shaw Hospital Prof. Cheng
Cutaneous Lupus
Etiology
• Genetic predisposition
– Most cases are sporadic but may cluster in families
(5-12% of family members have SLE)
– Lupus is polygenic (more that one gene responsible)
• Hormones (estrogen)
• Environmental factors
– Infections, stress, sunlight
• Medications
Sir Run Run Shaw Hospital Prof. Cheng
Subacute cutaneous lupus erythematosus
(SCLE)
synonyms
Subacute Cutaneous Lupus Erythematosus SCLE,
Lupus Erythematosus Chronicus Disseminatus Superficialis
definition
•Subset of LE
•intermediate between DLE and SLE
•characterized by papulosquamous discoid plaques or
annular polycyclic lesions
•Photosensitivity
•arthritis being the most frequent feature
•Renal involvement is rare and mild
Sir Run Run Shaw Hospital Prof. Cheng
Etiology of SCLE
*occurs in genetically predisposed individualshuman leukocyte antigen B8 (HLA-B8), HLA-DR3,
HLA-DRw52, and HLA-DQ1
*A strong association exists with anti-Ro (SS-A) Abs
*be related to -ultraviolet (UV) light modulation of autoantigens
epidermal cytokines, and adhesion molecules
with resultant keratinocyte apoptosis
*Several drugs may induce SCLE:
hydrochlorothiazide calcium channel blockers
angiotensin-converting enzyme inhibitors, terbinafine,
and TNF antagonists.
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features of ScLE
**papular eruptions-annular erythema or psoriasiformmay show a photosensitive distribution
worsening each spring and summer
pruritus,or asymptomatic
SCLE may wax and wane
**50% joint involvement
small joints (hands and wrists).
Arthritis may occur but is unusual (<2%).
**Systemic complain
fatigue
May have Sjögren syndrome
may manifest symptoms of SLE
An necessary assessment for symptoms of pleuritis,
pericarditis, neurologic involvement, and renal impairment
Sir Run Run Shaw Hospital Prof. Cheng
Physical of SCLE
• clinical types:
Annular or polycyclic (ring-shaped) erythematous
--may mimic erythema annulare centrifugum
Papulosquamous (scaly bumps)
--may mimic psoriasis or lichen planus
Vasculitis (purple spots)
Nodular (lumps)
• photodistributed-occurring mainly around the neck,
on the back and front of the trunk
• heal without scarring
Sir Run Run Shaw Hospital Prof. Cheng
Laboratory tests of SCLE
Serologic testing
positive ANA
Anti-Ro (SS-A) in a high proportion:
Annular SCLE - 90%
Papulosquamous SCLE - 80-85%
SCLE with vasculitis, SS, or C2d deficiency - ≥ 95%
Mothers of neonates with LE - ≥90%
Drug-induced SCLE - 70-80 %
Anti-La (SS-B) Abs may occur
Anti-native DNA (ds-DNA or nDNA) Abs may occur
Other laboratory tests
Anemia, leukopenia, and/or thrombocytopenia may be present
Elevated ESR, RF. Complement levels,UA
Sir Run Run Shaw Hospital Prof. Cheng
Other Tests- biopsy
LBT--60% positive on lesional skin.
lupus band test
Histologic Findings
(1)vacuolar alteration of the basal cell layer
(2)an inflammatory perivascular,periappendiceal cell infiltrate
(usually lymphocytic), or in a subepidermal location
(3)Epidermal atrophy, common,
(4)follicular plugging is less frequent than inDLE.
(5) An abundance of mucin often is seen within the dermis.
Sir Run Run Shaw Hospital Prof. Cheng
DDx of SCLE
Dermatomyositis
Lupus Erythematosus, Acute
Erythema Annulare Centrifugum
Lupus Erythematosus, Discoid
Erythema Gyratum Repens
Polymorphous Light Eruption
Erythema Multiforme
Psoriasis, Plaque
Granuloma Annulare
Sarcoidosis
Henoch-Schönlein Purpura (Anaphylactoid Purpura)
Tinea Corporis
Hypersensitivity Vasculitis (Leukocytoclastic Vasculitis)
Lichen Planus
Sir Run Run Shaw Hospital Prof. Cheng
Treatment of SCLE
sun-protective measures:
sunscreens, protective clothing, behavior alteration.
Standard therapy:
includes corticosteroids (topical, intralesional) and
antimalarials（Hydroxychloroquine Chloroquine）
Additional therapies:
may be considered in selected patients include
auranofin, dapsone, thalidomide, retinoids, interferon,
and immunosuppressive agents.
Sir Run Run Shaw Hospital Prof. Cheng
Discoid lupus erythematosus (DLE)
synonyms
Discoid Lupus Erythematosus (DLE),
Lupus Erythematosus Chronicus Discoides
definition & Background
•Benign subtype of LE
•characterized by
various-sized, well-defined, erythematous, scaly patches,
with atrophy, scarring and pigmentation
•Serologic abnormalities are uncommon
Sir Run Run Shaw Hospital Prof. Cheng
Causes & Pathophysiology of DLE
•genetic predispositionUV light exposure
Toll-like receptors
are possibly involved in
•heat shock protein -is induced in the keratinocyte following UV exposure or stress
may act as a target for gamma (delta) T-cell–mediated
epidermal cell cytotoxicity
Sir Run Run Shaw Hospital Prof. Cheng
Clinical features of DLE
•a chronic, scarring, atrophic, photosensitive dermatosis
• most are asymptomatic—
mild pruritus or occasional pain
Arthralgia or arthritis may occur
•may manifest any symptom of SLE
•5% or less patients accompanying systemic involvement-an assessment for symptoms of pleuritis, pericarditis,
neurologic involvement, and renal involvement.
Sir Run Run Shaw Hospital Prof. Cheng
Physical of DLE
•primary lesion –
erythematous papule
or plaque with slight-to-moderate scaling
unsightly red scaly patchesleave postinflammatory pigmentation and white scars
may be localised or widespread
predominantly affects the cheeks, nose and ears,
upper back, V of neck, backs of hands
•Hypertrophic LE –
thickened and warty skin resembling warts or skin cancers
•Rarely, palmoplantar LE
•hair follicles involvement-- scarring alopecia
•may affect lips & mouth--causing ulcers & scaling.
Sir Run Run Shaw Hospital Prof. Cheng
DDx
Actinic Keratosis
Psoriasis, Plaque
Dermatomyositis
Rosacea
Granuloma Annulare
Sarcoidosis
Granuloma Faciale
Squamous Cell Carcinoma
Keratoacanthoma
Syphilis
Lichen Planus
Warts, Nongenital
Lupus Erythematosus, Subacute Cutaneous
Sir Run Run Shaw Hospital Prof. Cheng
Comparison of the Major Types of LE-Specific
Skin Disease
Disease Features
ACLE
SCLE Classic DLE
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Clinical features of skin lesions
Induration
Dermal atrophy
Pigment changes
Follicular plugging
Hyperkeratosis
Histopathology
Thickened basement membrane
Lichenoid infiltrate
Periappendageal inflammation
Lupus band
Lesional
Nonlesional
Antinuclear antibodies
Ro/SS-A antibodies
By immunodiffusion
By ELISA
Antidouble-stranded DNA antibodies
Hypocomplementemia
Risk for developing SLE
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Laboratory tests of DLE
Serologic testing:
20% manifest positive ANA.
Anti-Ro (SS-A): approximately 1-3%
Antinative DNA (ds- or n-DNA) or anti-Sm Ab <5%
Elevated ESR in some patients.
RF may be positive.
Complement levels may be depressed
Sir Run Run Shaw Hospital Prof. Cheng
Other Tests
•Immunopathology findings (LBT):
ca 90% lesional skin manifest a positive DIF-Deposition of Ig &/or complement at dermalepidermal junction
--is a characteristic feature of LE
• Mucin deposition
•Urinalysis
•Cytopenias may be present
Sir Run Run Shaw Hospital Prof. Cheng
Sir Run Run Shaw Hospital Prof. Cheng
Treatment of DLE
sun-protective measures
Cosmetic measures
Standard medical therapy:
corticosteroids (topical or intralesional)
antimalarials—
Hydroxychloroquine chloroquine phosphate)
Alternative therapies:
auranofin dapsone, thalidomide,oral，topical retinoids,
immunosuppressive agents—
methotrexate (MTX), azathioprine, mycophenolate mofetil,
lenalidomide phenytoin, interferon, acitretin,
& chimeric monoclonal antibody.
systemic corticosteroids are rarely effective
Sir Run Run Shaw Hospital Prof. Cheng
Thanks & questions?
Sir Run Run Shaw Hospital Prof. Cheng