Sir Run Run Shaw Hospital Prof. Cheng Unit 5. Dermatomyositis ， Scleroderma – Etiology, Clinical features, Diagnosis and Treatment. 1.5 hr Subacute cutaneous

Sir Run Run Shaw Hospital Prof. ChengSir Run Run Shaw Hospital Prof. Cheng

Unit 5.Unit 5.

DermatomyositisDermatomyositis ，， SclerodermaScleroderma– – Etiology, Clinical features, Diagnosis and Treatment. Etiology, Clinical features, Diagnosis and Treatment. 1.5 hr1.5 hr

Subacute cutaneous lupus erythematosusSubacute cutaneous lupus erythematosusDiscoid lupus erythematosus Discoid lupus erythematosus - Etiology, Clinical features, Diagnosis and Treatment. - Etiology, Clinical features, Diagnosis and Treatment. 0.5 hr0.5 hr



Connective Tissue Connective Tissue Diseases(CTD)Diseases(CTD)

--conceptconcept• Autoimmune diseasesAutoimmune diseases–– diseases associated with specific autoantibodiesdiseases associated with specific autoantibodies

• Connective-tissue disorders—Connective-tissue disorders— collagencollagen--vascular disordersvascular disorders, , are characterized by autoantibody-mediated are characterized by autoantibody-mediated

connective-tissue abnormalities. connective-tissue abnormalities. • Histopathology: Histopathology: ----Perivascular collagen depositionPerivascular collagen deposition =Collagen Vascular Diseases=Collagen Vascular Diseases• Symptoms nonspecificSymptoms nonspecific & overlapping & overlapping


Connective Tissue Diseases(CTD)Connective Tissue Diseases(CTD)

•DermatomyositisDermatomyositis•Scleroderma-Systemic Sclerosis-Diffuse Sclerosis*Scleroderma-Systemic Sclerosis-Diffuse Sclerosis* Localized Fibrosing Disorders Localized Fibrosing Disorders - Linear Scleroderma - Linear Scleroderma Morphea, & Regional FibrosisMorphea, & Regional Fibrosis•Lupus Erythematosus (LE):Lupus Erythematosus (LE):

Acute-, Acute-, Subacute Cutaneous-LESubacute Cutaneous-LE, , Discoid-LEDiscoid-LE, , Drug-Induced -, Bullous -, Systemic -,Drug-Induced -, Bullous -, Systemic -, Neonatal -Neonatal -•Mixed Connective Tissue Disease, MCTDMixed Connective Tissue Disease, MCTD•Sjogren Syndrome Sjogren Syndrome •Eosinophilia-Myalgia Syndrome Eosinophilia-Myalgia Syndrome •Eosinophilic FasciitisEosinophilic Fasciitis•CREST SyndromeCREST Syndrome


DermatomyositisDermatomyositis ，， DDMM

皮肌炎皮肌炎


Definition of Definition of DMDM• an idiopathic inflammatory an idiopathic inflammatory myopathymyopathy (IIM) with (IIM) with

characteristic characteristic cutaneous changescutaneous changes• a systemic disorder that frequently affects the a systemic disorder that frequently affects the

joints, joints, esophagus, lungsesophagus, lungs, heart (rarely), heart (rarely)• Related to Related to MalignancyMalignancy (>60y) (>60y)• Calcinosis (in children, 40%)Calcinosis (in children, 40%)• PrognosisPrognosis

– Level of myopathyLevel of myopathy– y/n malignancyy/n malignancy– Cardiopulmonary InvolvmentCardiopulmonary Involvment


DermatomyositisDermatomyositis-concept-concept

• Proximal muscle weakness Proximal muscle weakness

nonsuppurative inflammation of skeletal musclenonsuppurative inflammation of skeletal muscle• 5 cases per million per year5 cases per million per year• 2:1 female:male2:1 female:male• No racial dispositionNo racial disposition• Can occur at any age, 2 peaksCan occur at any age, 2 peaks

– Adults – 50y(40-60)Adults – 50y(40-60)– Children – 5-15yChildren – 5-15y


Cause & Pathophysiology of DMPathophysiology of DM• GeneticGenetic – – HLA DR3,DR5,DR7, TNF-a polymorphismHLA DR3,DR5,DR7, TNF-a polymorphism

• Immunologic abnormalitiesImmunologic abnormalities – – antibody-mediated cell cytotoxicityantibody-mediated cell cytotoxicity vascular inflammationvascular inflammation

• InfectiousInfectious – – viral agents, Toxoplasma, Borreliaviral agents, Toxoplasma, Borrelia

• Drug-inducedDrug-induced – – Hydrea, penicillamine, statin, quinidine, phenylbutazoneHydrea, penicillamine, statin, quinidine, phenylbutazone

• Silicone breast implantsSilicone breast implants – – anecdotalanecdotal



Clinical features of DMClinical features of DM

• eruptionseruptions on exposed surfaces-- on exposed surfaces-- as one of the initial manifestationsas one of the initial manifestations

• Muscle involvementMuscle involvement – manifests as proximal muscle weaknessmanifests as proximal muscle weakness.

• Systemic manifestationsSystemic manifestations may occur may occur ----arthralgia, arthritis, dyspnea, dysphagia, arthralgia, arthritis, dyspnea, dysphagia, arrhythmia, dysphoniaarrhythmia, dysphonia


Clinical features of DMClinical features of DMHallmark Hallmark Skin lesionSkin lesion

• the characteristic the characteristic – a a heliotrope heliotrope discoloration on the upper eyelidsdiscoloration on the upper eyelids – Gottron papulesGottron papules::

violaceous, scaly papule-maculeviolaceous, scaly papule-macule– nailfold telangiectasianailfold telangiectasia – poikilodermapoikiloderma in a photodistribution in a photodistribution.. – PruriticPruritic– Scaly scalp or hair lossScaly scalp or hair loss

• the characteristic the characteristic – a a heliotrope heliotrope discoloration on the upper eyelidsdiscoloration on the upper eyelids – Gottron papulesGottron papules::

violaceous, scaly papule-maculeviolaceous, scaly papule-macule– nailfold telangiectasianailfold telangiectasia – poikilodermapoikiloderma in a photodistribution in a photodistribution.. – PruriticPruritic– Scaly scalp or hair lossScaly scalp or hair loss

Classic Cutaneous Manifestations Classic Cutaneous Manifestations


The heliotrope rash is a characteristic and pathognomonic The heliotrope rash is a characteristic and pathognomonic cutaneous feature of DM. cutaneous feature of DM.

The heliotrope flowerThe heliotrope flower


•Musculoskeletal Musculoskeletal • Myositis with proximal weaknessMyositis with proximal weakness• Muscle atrophy and contractureMuscle atrophy and contractureaa

• Muscular calcificationMuscular calcificationaa

•Cardiac Cardiac • CardiomyopathyCardiomyopathy• Conduction defectsConduction defects

•Respiratory Respiratory • DysphoniaDysphonia• Diffuse interstitial pneumonitis/fibrosisDiffuse interstitial pneumonitis/fibrosis• Aspiration pneumoniaAspiration pneumonia• Respiratory failure from muscle weaknessRespiratory failure from muscle weakness

•Gastrointestinal Gastrointestinal • Proximal dysphasiaProximal dysphasia• Large bowel infarction/perforation secondary to Large bowel infarction/perforation secondary to

vasculopathyvasculopathyaa

•Ophthalmologic Ophthalmologic • RetinopathyRetinopathyaa

• Internal malignancyInternal malignancybb

Systemic Manifestations/Associations Systemic Manifestations/Associations of Dermatomyositis/Polymyositisof Dermatomyositis/Polymyositis


Lung disease — Lung disease — •Interstitial lung disease (ILD)Interstitial lung disease (ILD) is an important complication is an important complication may be associated with rapidly progressive may be associated with rapidly progressive pulmonary failure and deathpulmonary failure and death

•respiratory insufficiencyrespiratory insufficiency may result from diaphragmatic may result from diaphragmatic and chest wall muscle weaknessand chest wall muscle weakness


Malignancy ofMalignancy of DM DM•paraneoplastic processesparaneoplastic processes

---linked to oncogenesis & autoimmunity---linked to oncogenesis & autoimmunity•Including:Including: Nasopharyngeal cancerNasopharyngeal cancer

breast cancer lung cancer breast cancer lung cancer

pancreatic cancer colorectal cancer pancreatic cancer colorectal cancer

ovarian cancer stomach cancerovarian cancer stomach cancer

cholangial cancer esophageal cancercholangial cancer esophageal cancer

laryngeal cancer liver cancer laryngeal cancer liver cancer

tongue cancer renal cancertongue cancer renal cancer

LymphomaLymphoma


ComplicationsComplications

•Cutaneous UlcerationCutaneous Ulceration•Systemic VasculopathySystemic Vasculopathy•CalcinosisCalcinosis•Internal MalignancyInternal Malignancy•Opportunistic Infections and LymphomaOpportunistic Infections and Lymphoma


Amyopathic DM (ADM)Amyopathic DM (ADM)• Typical cutaneous manifestations Typical cutaneous manifestations • No muscle symptomsNo muscle symptoms• Normal muscle enzymesNormal muscle enzymes• Subclinical muscle disease Subclinical muscle disease

– Px – mild proximal weakness Px – mild proximal weakness – EMG – mildly abnormalEMG – mildly abnormal– Abnormal US, MRI, BiopsyAbnormal US, MRI, Biopsy

• new autoantibodies (140 kDa, 155 kDa, and Se) might new autoantibodies (140 kDa, 155 kDa, and Se) might serve as serologic markersserve as serologic markers

• may reflect an underlying malignancy !


Laboratory Studies of DMLaboratory Studies of DM• elevation of Muscle enzymeelevation of Muscle enzyme creatine kinasecreatine kinase （（ CKCK ）） levellevel ，， aldolase level test aldolase level test Aspartate aminotransferaseAspartate aminotransferase （（ AST ） lactate dehydrogenase lactate dehydrogenase （（ LDHLDH ）） teststests

• serologic abnormalities:serologic abnormalities: **ANAANA ，， * * three major categories of myositis-specific Abs (MSAs):three major categories of myositis-specific Abs (MSAs): 1,Abs to aminoacyl-tRNA synthetases (antisynthetase Abs ) 1,Abs to aminoacyl-tRNA synthetases (antisynthetase Abs ) including anti-Jo-1; including anti-Jo-1; 2, Abs to signal recognition particle (anti-SRP Abs); 2, Abs to signal recognition particle (anti-SRP Abs); 3,Abs to Mi-2, a nuclear helicase. 3,Abs to Mi-2, a nuclear helicase. ** other myositis-specific autoantibodiesother myositis-specific autoantibodies

Laboratory Studies of DMLaboratory Studies of DM• elevation of Muscle enzymeelevation of Muscle enzyme creatine kinasecreatine kinase （（ CKCK ）） levellevel ，， aldolase level test aldolase level test Aspartate aminotransferaseAspartate aminotransferase （（ AST ） lactate dehydrogenase lactate dehydrogenase （（ LDHLDH ）） teststests

• serologic abnormalities:serologic abnormalities: **ANAANA ，， * * three major categories of myositis-specific Abs (MSAs):three major categories of myositis-specific Abs (MSAs): 1,Abs to aminoacyl-tRNA synthetases (antisynthetase Abs ) 1,Abs to aminoacyl-tRNA synthetases (antisynthetase Abs ) including anti-Jo-1; including anti-Jo-1; 2, Abs to signal recognition particle (anti-SRP Abs); 2, Abs to signal recognition particle (anti-SRP Abs); 3,Abs to Mi-2, a nuclear helicase. 3,Abs to Mi-2, a nuclear helicase. ** other myositis-specific autoantibodiesother myositis-specific autoantibodies


Autoantibodies in Idiopathic Inflammatory Dermatomyositis Autoantibodies in Idiopathic Inflammatory Dermatomyositis

AutoantibodyMedian Prevalence

Molecular Specificity

Clinical Association

High Specificity for DM/PM155 kDa and/or Se

20%–80% transcriptional intermediary factor-1

Classic DM, clinically amyopathic DM with increased risk of internal malignancy

140 kDa 53% helicase C domain protein 1 (IFIH1)/melanoma differentiation-associated gene 5 (MDA-5)

Clinically amyopathic DM with increased risk for interstitial lung disease

Jo-1 20% Histidyl-tRNA synthetase PM, antisynthetase syndromeMi-2 15% Helicase nuclear proteins Shawl sign, cuticular overgrowthSRP 5% Signal-recognition particleFulminant DM/PM, cardiac involvementPL-7 3% Threonyl-tRNA

synthetaseAntisynthetase syndrome

PL-12 3% Alanyl-tRNA synthetase Antisynthetase syndromeOJ Rare Isoleucyl-tRNA

synthetaseAntisynthetase syndrome

EJ Rare Glycyl-tRNA synthetase Antisynthetase syndrome, possibly increased frequency of skin changes

Fer Rare Elongation factor 1 —

Mas Rare Small RNA —

KJ Rare Translation factor —


Low Specificity for DM/PMANA 40% Clinically amyopathic DM (80%)

SsDNA 40% SLE, SScPM-Scl (PM-1) 40% Ribosomal RNA

processing enzymeOverlap with scleroderma

Ro (52-kDa Ro) 15% RNP Overlap with SSJ, SCLE, neonatal LE/CHB, SLE

U1RNP 10% U1RNP Overlap connective tissue diseaseKu 3% DNA end-binding

repair protein complex

Overlap with scleroderma

U2RNP 1% U2RNP Overlap with scleroderma

AutoantibodyMedian Prevalence

Molecular Specificity

Clinical Association

Autoantibodies in Idiopathic Inflammatory Dermatomyositis Autoantibodies in Idiopathic Inflammatory Dermatomyositis


Imaging StudiesImaging StudiesImaging StudiesImaging Studies

• MRI • Chest radiography • A barium swallow• Ultrasonography• Electromyography

(EMG) • CT scanning

•Pulmonary function studies

•Electrocardiography

(ECG)

•skin biopsy

•Muscle biopsy

Other testsOther testsOther testsOther tests


Histologic FindingsHistologic Findings

Muscle biopsyMuscle biopsy perivascular and perivascular and interfascicular lymphocytic interfascicular lymphocytic inflammationinflammation

Skin biopsySkin biopsyan interface dermatitis

Sir Run Run Shaw Hospital Prof. ChengSir Run Run Shaw Hospital Prof. Cheng perivascular and perimysial inflammation, & perifascicular necrosis.


Diagnosis of DMDiagnosis of DM• Proximal muscle weaknessProximal muscle weakness

• Elevated serum creatinine kinaseElevated serum creatinine kinase

• Myopathic changes on electromyographyMyopathic changes on electromyography

• Muscle biopsy with evidence of Muscle biopsy with evidence of lymphocytic inflammationlymphocytic inflammation

• RashsRashs （（ Gottron’s sign, heliotrope rashGottron’s sign, heliotrope rash ））• Positive auto-antibody ： ANA ， Jo-1


Differential Diagnoses Differential Diagnoses CREST SyndromeCREST SyndromeParapsoriasisParapsoriasisGraft Versus Host DiseaseGraft Versus Host DiseasePityriasis Rubra PilarisPityriasis Rubra PilarisLichen MyxedematosusLichen MyxedematosusPolymorphous Light EruptionPolymorphous Light EruptionLichen PlanusLichen PlanusPsoriasis, PlaquePsoriasis, PlaqueLupus Erythematosus, AcuteLupus Erythematosus, AcuteRosaceaRosaceaLupus Erythematosus, DiscoidLupus Erythematosus, DiscoidSarcoidosisSarcoidosisLupus Erythematosus, Subacute CutaneousLupus Erythematosus, Subacute CutaneousTinea CorporisTinea CorporisMorpheaMorpheaUrticaria, ChronicUrticaria, ChronicMulticentric ReticulohistiocytosisMulticentric Reticulohistiocytosis


Treatment of DMTreatment of DM– general– general

• difficultdifficult• Bed rest - in severe myopathyBed rest - in severe myopathy• Physical therapy -Physical therapy - prevents curvatures in children, lasting joint prevents curvatures in children, lasting joint

damage (rare)damage (rare)• Elevate head after eating –Elevate head after eating – prevent aspirations, prevent aspirations, may need NGT(nasogastric tube)may need NGT(nasogastric tube) • High protein dietHigh protein diet


TreatmentTreatment• photosensitive photosensitive - sun avoidance and sun protective measures, - sun avoidance and sun protective measures,

sunscreenssunscreens ；； Hydroxychloroquine, chloroquineHydroxychloroquine, chloroquine• symptomatic patientssymptomatic patients ：： SteroidsSteroids• non-respondersnon-responders ：： immunosuppressive agentsimmunosuppressive agents methotrexate cyclosporinemethotrexate cyclosporine

azathioprine tacrolimusazathioprine tacrolimus fludarabine cyclophosphamide fludarabine cyclophosphamide leflunomide chlorambucilleflunomide chlorambucil mycophenolate mofetilmycophenolate mofetil

• Anti-TNF agentsAnti-TNF agents (Infliximab) (Infliximab)• RituximabRituximab ，， anti-CD20 antibodyanti-CD20 antibody specific in targeting the antibody-producing B cellsspecific in targeting the antibody-producing B cells• IVIGIVIG

• photosensitive photosensitive - sun avoidance and sun protective measures, - sun avoidance and sun protective measures,

sunscreenssunscreens ；； Hydroxychloroquine, chloroquineHydroxychloroquine, chloroquine• symptomatic patientssymptomatic patients ：： SteroidsSteroids• non-respondersnon-responders ：： immunosuppressive agentsimmunosuppressive agents methotrexate cyclosporinemethotrexate cyclosporine

azathioprine tacrolimusazathioprine tacrolimus fludarabine cyclophosphamide fludarabine cyclophosphamide leflunomide chlorambucilleflunomide chlorambucil mycophenolate mofetilmycophenolate mofetil

• Anti-TNF agentsAnti-TNF agents (Infliximab) (Infliximab)• RituximabRituximab ，， anti-CD20 antibodyanti-CD20 antibody specific in targeting the antibody-producing B cellsspecific in targeting the antibody-producing B cells• IVIGIVIG





Scleroderma Scleroderma ((Systemic SclerosisSystemic Sclerosis))


Scleroderma-Scleroderma-BackgroundBackground• Scleroderma is derived from the Greek words Scleroderma is derived from the Greek words sklerosskleros (hard or indurated) and (hard or indurated) and dermaderma (skin) (skin)• Hippocrates first described this condition as thickened skinHippocrates first described this condition as thickened skin• 1752, Carlo Curzio offered the first detailed description of scleroderma in 1752, Carlo Curzio offered the first detailed description of scleroderma in

a patient with hard skin-- described as woodlike or containing a dry hidea patient with hard skin-- described as woodlike or containing a dry hide• 1836, Giovambattista Fantonetti applied the term scleroderma to a 1836, Giovambattista Fantonetti applied the term scleroderma to a

patient's condition--described as dark leather-like skin who exhibited a patient's condition--described as dark leather-like skin who exhibited a loss of range of joint motion due to skin tightening.loss of range of joint motion due to skin tightening.

• 1945, Robert H. Goetz first described the concept of scleroderma as a 1945, Robert H. Goetz first described the concept of scleroderma as a systemic disease-- systemic disease--

he introduced the term progressive systemic sclerosis(PSS) to he introduced the term progressive systemic sclerosis(PSS) to

emphasize the systemic & often progressive nature of the diseaseemphasize the systemic & often progressive nature of the disease


SclerodermaSclerodermadefinitiondefinition

• a chronic multisystem disorder a chronic multisystem disorder characterized bycharacterized by ::

--the overproduction & accumulation of collagen:--the overproduction & accumulation of collagen:

****excessive excessive fibrosisfibrosis of the skin of the skin

--with skin thickening &--with skin thickening & indurationinduration

****fibrosis & fibrosis & chronic inflammatory infiltrationchronic inflammatory infiltration in organs in organs

--structural and functional abnormalities --structural and functional abnormalities

of of blood vesselsblood vessels & & organsorgans

--GI tract, lung, heart and kidneys --GI tract, lung, heart and kidneys

**immune system activation (autoimmunity)**immune system activation (autoimmunity)

** vasculopathyvasculopathy.


EtiologyEtiology

• Environmental factorsEnvironmental factors1) silica dust1) silica dust

2) organic solvents2) organic solvents

3) biogenic amines3) biogenic amines

4) urea formaldehyde4) urea formaldehyde

5) polyvinyl chloride5) polyvinyl chloride

6) rapeseed oil6) rapeseed oil

7) bleomycin7) bleomycin

8) L-tryptophan 8) L-tryptophan

9) silicone implant (?)9) silicone implant (?)

• Genetic predispositionGenetic predisposition

• Defective immunoregulationDefective immunoregulation 1) cell mediated immunity: 1) cell mediated immunity:

CD4/CD8 , cytokinesCD4/CD8 , cytokines

2) humoral immunity2) humoral immunity

– hypergammaglobulinemiahypergammaglobulinemia

– autoantibodyautoantibody productionproduction

– antinuclear antibody (+) > 95%antinuclear antibody (+) > 95%


PathogenesisPathogenesisPathogenesisPathogenesisSusceptible host

Exogenous events

Immune system activation

Endothelial cellactivation/damage

Fibroblast activation

End stage pathologyObliterative vasculopathy

Fibrosis



PathogenesisPathogenesis• 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


ClassificationClassification1. Systemic sclerosis (Scleroderma)Scleroderma)

– DiffuseDiffuse cutaneous systemic sclerosis– LLimitedimited 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


Clinical features of Clinical features of SclerodermaSclerodermaDiffuseDiffuse LimitedLimited

Skin InvolvementSkin Involvement Distal and proximal Distal and proximal extremities, face, trunkextremities, face, trunk

Distal to elbows, faceDistal to elbows, face

RaynaudRaynaud’’s s PhenomenonPhenomenon

Onset within one year Onset within one year or at time of skin or at time of skin changeschanges

May precede skin May precede skin disease by yearsdisease by years

Organ InvolvementOrgan Involvement Pulmonary (interstitial Pulmonary (interstitial fibrosis); renal (renal fibrosis); renal (renal crisis); gastrointestinal; crisis); gastrointestinal; cardiaccardiac

GI, pulmonary GI, pulmonary hypertensionhypertension

Nail Fold CapillariesNail Fold Capillaries Dilation and dropoutDilation and dropout Dilation without Dilation without significant dropoutsignificant dropout

Antinuclear AntibodiesAntinuclear Antibodies Anti-topoisomerase Anti-topoisomerase Anti-centromereAnti-centromere

* * CREST syndromeCREST syndrome - calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia- calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia


Clinical features ofClinical features of SclerodermaScleroderma

1. 1. Vascular abnormalities Vascular abnormalities VasculopathyVasculopathy 1) Raynaud's phenomenon1) Raynaud's phenomenon

- cold hands and feet - cold hands and feet • reversible skin color change (white to blue to red)reversible skin color change (white to blue to red)• - induced by cold temperature or emotional stress- induced by cold temperature or emotional stress• - initial complaint in 3/4 of patients- initial complaint in 3/4 of patients• - 90% in patients with skin change- 90% in patients with skin change• (prevalence in the general population: 4-15%)(prevalence in the general population: 4-15%)

2) digital ischemic injury2) digital ischemic injury


Clinical featuresClinical features SclerodermaScleroderma

Clinical featuresClinical features SclerodermaScleroderma

2. 2. Skin involvement (1)Skin involvement (1)

1) 1) stage-- - edematous phasestage-- - edematous phase

- indurative phase- indurative phase

- atrophic phase- atrophic phase

2) firm, thickened bound to underlying soft tissue2) firm, thickened bound to underlying soft tissue

3) decrease in range of motion loss of facial 3) decrease in range of motion loss of facial

expression inability to open mouth fullyexpression inability to open mouth fully

contracturescontractures

2. 2. Skin involvement (1)Skin involvement (1)

1) 1) stage-- - edematous phasestage-- - edematous phase

- indurative phase- indurative phase

- atrophic phase- atrophic phase

2) firm, thickened bound to underlying soft tissue2) firm, thickened bound to underlying soft tissue

3) decrease in range of motion loss of facial 3) decrease in range of motion loss of facial

expression inability to open mouth fullyexpression inability to open mouth fully

contracturescontractures


Clinical featuresClinical featuresClinical featuresClinical features2. 2. Skin involvement (2)Skin involvement (2) ulcerationulceration loss of soft tissue of finger tiploss of soft tissue of finger tip pigmentationpigmentation calcific depositcalcific deposit

3. 3. Musculoskeletal systemMusculoskeletal system Polyarthritis and flexion contracturePolyarthritis and flexion contracture Muscle weakness and atrophy Muscle weakness and atrophy (primary /secondary)(primary /secondary)

2. 2. Skin involvement (2)Skin involvement (2) ulcerationulceration loss of soft tissue of finger tiploss of soft tissue of finger tip pigmentationpigmentation calcific depositcalcific deposit

3. 3. Musculoskeletal systemMusculoskeletal system Polyarthritis and flexion contracturePolyarthritis and flexion contracture Muscle weakness and atrophy Muscle weakness and atrophy (primary /secondary)(primary /secondary)


Terminal digit resorptionTerminal digit resorption

AcrolysisAcrolysis

AcrosclerosisAcrosclerosis


Calcinosis Calcinosis

Calcinosis & acrolysisCalcinosis & acrolysis


Clinical featuresClinical featuresClinical featuresClinical 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

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


Clinical featuresClinical featuresClinical featuresClinical features

5. lungs1) 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 dyspneaProgressive dyspnea )

5. lungs1) 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 dyspneaProgressive dyspnea )


Pulmonary fibrosisPulmonary fibrosis


Clinical featuresClinical featuresClinical featuresClinical 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

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


Clinical featuresClinical features7. Cardiovascular system7. Cardiovascular system • PericarditisPericarditis,pericardial effusion,myocardial ,pericardial effusion,myocardial

fibrosis fibrosis --Congestive heart failure --Congestive heart failure --Dyspnea --Dyspnea • conduction abnormalities conduction abnormalities --arrhythmia--arrhythmia (irregular heart beats) (irregular heart beats) --Palpitations--Palpitations --syncope --syncope 8.Exocrine glands 8.Exocrine glands

– XerostomiaXerostomia – xerophthalmiaxerophthalmia


Laboratory findingsLaboratory findings

1. . ANA, RFANA, RF

2. 2. anti-Scl-70anti-Scl-70 (DNA topoisomerase I) antibody (DNA topoisomerase I) antibody

– 20-40% in 20-40% in diffusediffuse scleroderma scleroderma

– 10-15% in limited scleroderma10-15% in limited scleroderma

3. anticentromere antibody3. anticentromere antibody

– 50-90% in 50-90% in limitedlimited scleroderma scleroderma

– 5% in diffuse scleroderma5% in diffuse scleroderma


7 known scleroderma specific autoantibodies7 known scleroderma specific autoantibodies•Anticentromere Antibodies (ACA)Anticentromere Antibodies (ACA)•Anti-Scl-70 or anti-topoisomerase (TOPO)Anti-Scl-70 or anti-topoisomerase (TOPO)•Anti-U1-RNP (U1-RNP) or (antifibrillarin)Anti-U1-RNP (U1-RNP) or (antifibrillarin)•Anti-RNA Polymerase III (Pol 3)Anti-RNA Polymerase III (Pol 3)•Anti-U3-RNP (U3-RNP)Anti-U3-RNP (U3-RNP)•Anti-Th/To (Th/To)Anti-Th/To (Th/To)•Anti-Pm/Scl (Pm/Scl)Anti-Pm/Scl (Pm/Scl)

Scleroderma AutoantibodiesScleroderma Autoantibodies


Reactivity Target Antigen Frequency in SSc (%)

HLA Association Clinical Association

Centromere CENP proteins speckled pattern

20–30 HLA-DRB1 HLA-DQB1

Limited skin sclerosis, severe gut disease, isolated PAH, calcinosis

Scl-70 Topoisomerase-1 speckled pattern

15–20 HLA-DRB1 HLA-DQB1 HLA-DPB1

Diffuse skin sclerosis, pulmonary fibrosis and secondary PAH, increased SSc-related mortality rate

RNAP III RNA polymerase III speckled pattern

20 HLA-DQB1 Diffuse skin sclerosis, hypertensive renal crisis, correlated with a higher mortality rate

nRNP U1-RNP speckled pattern

15 HLA-DR2, -DR4 HLA-DQw5, -DQw8

Overlap features of SLE, arthritis

PM-Scl Polymyositis/Scl nuclear staining pattern

3 HLA-DQA1 HLA-DRB1

Limited skin sclerosis, myositis–sclerosis overlap, calcinosis

Fibrillarin U3-RNP nuclear staining pattern

4 HLA-DQB1 Diffuse skin sclerosis, myositis, PAH, renal disease

Th/To 7–2RNP nuclear staining pattern

2–5 HLA-DRB1 Limited skin sclerosis, pulmonary fibrosis

Clinical Association of Hallmark Autoantibodies in Clinical Association of Hallmark Autoantibodies in Systemic Sclerosis (SSc)Systemic Sclerosis (SSc)


Imaging StudiesImaging Studies

• Chest radiography Chest radiography

• EchocardiographyEchocardiography

• UltrasonographyUltrasonography

• CT scanningCT scanning

• Esophagraphy

•Pulmonary function Pulmonary function testtest•Serum NT-proBNPSerum NT-proBNP

•ECGECG

Other testsOther tests


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 criteriaone major or 2 or more minor criteria


Organ Involvement

Clinical Feature Diagnostic Procedures

Vascular system

Raynaud phenomenon

•Coldness provocation•Nail fold capillaroscopy•Antinuclear antibody levels

Skin Scleroderma Calcinosis cutis

•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)

Musculoskeletal system

Arthralgia/Synovitis Muscle weakness

•Clinical assessment regarding fist closure-deficiency, joint contractures, tendon friction rub, muscle weakness•Laboratory parameters: erythrocyte sedimentation rate, rheumatoid factor, antinuclear autoantibodies•Creatine kinase (>threefold?)•MRI, electromyography•Muscle biopsy

Recommended Diagnostic Procedures in SScRecommended Diagnostic Procedures in SSc


Organ Involvement

Clinical Feature Diagnostic Procedures

Gastrointestinal tract

Reflux Dysphagia Diarrhoea, obstipation

•Gastro-/Esophageal-endoscopy•Oesophageal-szintigraphy•Oesophagus-manometry•Coloscopy

Respiratory system

Dyspnoea •Lung function test (TLCOc SB, TLC, FVC)•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 (protein-, albuminuria, microelectrophoresis)

Recommended Diagnostic Procedures in Recommended Diagnostic Procedures in SScSSc


TreatmentTreatmentTreatmentTreatment• thickening & indurative Skin• - D-penicillamine• - methotrexate• - immunosuppressive agent:

cyclosporin, IFN-,mycophenolate mofetil,

cyclophosphamide, photopheresis,

allogeneic bone marrow transplantation • Symptomatic (organ-specific) treatment

• thickening & indurative Skin• - D-penicillamine• - methotrexate• - immunosuppressive agent:

cyclosporin, IFN-,mycophenolate mofetil,

cyclophosphamide, photopheresis,

allogeneic bone marrow transplantation • Symptomatic (organ-specific) treatment


TreatmentTreatment• Raynaud’sRaynaud’s phenomenon and ischemiaphenomenon and ischemia

1) avoid cold exposure1) avoid cold exposure

layers of warm, loose-fitting clothinglayers of warm, loose-fitting clothing

2) quit smoking2) quit smoking

3) vasodilator therapy3) vasodilator therapy

- calcium channel blocker (nifedipine), prazosin, ACE-I- calcium channel blocker (nifedipine), prazosin, ACE-I

--dipyridamole, aspirindipyridamole, aspirin

4) 4) thrombosis and vascular flow compromise, thrombosis and vascular flow compromise,

tissue plasminogen activator--heparin, and urokinasetissue plasminogen activator--heparin, and urokinase

5) finger / toe necrosis5) finger / toe necrosis

- intravenous prostaglandin (PGE- intravenous prostaglandin (PGE11, PGI, PGI22))

- - BosentanBosentan

- amputation- amputation


TreatmentTreatment• Gastrointestinal Gastrointestinal • 1) reflux esophagitis and dysphagia1) reflux esophagitis and dysphagia• - elevation of head of bed- elevation of head of bed• - small frequent meal- small frequent meal• - avoid lying down within 3-4 hours of eating- avoid lying down within 3-4 hours of eating• - abstaining from caffeine-containing beverages,- abstaining from caffeine-containing beverages,• cigarette smokingcigarette smoking• - H2 blocker, proton-pump inhibitor- H2 blocker, proton-pump inhibitor• 2) gastroparesis: promotility agent (metoclopramide)2) gastroparesis: promotility agent (metoclopramide)• 3) malabsorption syndrome: broad spectrum antibiotics3) malabsorption syndrome: broad spectrum antibiotics


TreatmentTreatmentTreatmentTreatment• PulmonaryPulmonary1) Interstitial fibrosis

- corticosteroid - cyclophosphamide, azathioprine

2) pulmonary artery hypertension - calcium channel blocker - prostacyclin - transplantation

• RenalRenal renal crisis renal crisis episodes are best prevented and treated with episodes are best prevented and treated with

the aggressive use of ACE inhibitors (eg:the aggressive use of ACE inhibitors (eg:captopril) captopril) at at the earliest signs of hypertensionthe earliest signs of hypertension

- later: dialysis- later: dialysis

• PulmonaryPulmonary1) Interstitial fibrosis

- corticosteroid - cyclophosphamide, azathioprine

2) pulmonary artery hypertension - calcium channel blocker - prostacyclin - transplantation

• RenalRenal renal crisis renal crisis episodes are best prevented and treated with episodes are best prevented and treated with

the aggressive use of ACE inhibitors (eg:the aggressive use of ACE inhibitors (eg:captopril) captopril) at at the earliest signs of hypertensionthe earliest signs of hypertension

- later: dialysis- later: dialysis



Prognosis of sclerodermaPrognosis of scleroderma

• quite variable and difficult to predictquite variable and difficult to predict• cumulative survivalcumulative survival

diffuse limiteddiffuse limited 5 yr5 yr 70% 70% 90% 90% 10 yr10 yr 50% 50% 70% 70%• major cause of deathmajor cause of death 1) renal involvement1) renal involvement 2) cardiac involvement2) cardiac involvement 3) pulmonary involvement 3) pulmonary involvement ((Pulmonary hypertension, pulmonary fibrosis )Pulmonary hypertension, pulmonary fibrosis )


Cutaneous LupusCutaneous Lupusconceptconcept• • Affects only the skinAffects only the skin• • 1 of 10 patients will go on to develop SLE1 of 10 patients will go on to develop SLE• • Symptoms –Symptoms – rashes, hair loss, rashes, hair loss, cutaneous vasculitis, skin ulcers, cutaneous vasculitis, skin ulcers, photosensitivityphotosensitivity

• • Treatments-Treatments- sunscreen, steroid creams and gels, sunscreen, steroid creams and gels, antimalarials, immunosuppressivesantimalarials, immunosuppressives


EtiologyEtiology• Genetic predispositionGenetic predisposition – – Most cases are sporadic but may cluster in familiesMost cases are sporadic but may cluster in families (5-12% of family members have SLE)(5-12% of family members have SLE) – – Lupus is polygenic (more that one gene responsible)Lupus is polygenic (more that one gene responsible)

• • Hormones (estrogen)Hormones (estrogen)• • Environmental factorsEnvironmental factors – – Infections, stress, sunlightInfections, stress, sunlight• • MedicationsMedications

Cutaneous LupusCutaneous Lupus


Subacute cutaneous lupus erythematosusSubacute cutaneous lupus erythematosus (SCLE) (SCLE)

synonymssynonymsSubacute Cutaneous Lupus Erythematosus SCLE,Subacute Cutaneous Lupus Erythematosus SCLE,Lupus Erythematosus Chronicus Disseminatus SuperficialisLupus Erythematosus Chronicus Disseminatus Superficialis

definitiondefinition•Subset of LESubset of LE•intermediate between DLE and SLEintermediate between DLE and SLE•characterized by papulosquamous discoid plaques or characterized by papulosquamous discoid plaques or annular polycyclic lesions annular polycyclic lesions •Photosensitivity Photosensitivity •arthritis being the most frequent featurearthritis being the most frequent feature•Renal involvement is rare and mildRenal involvement is rare and mild


**occurs in genetically predisposed individualsoccurs in genetically predisposed individuals-- human leukocyte antigen B8 (HLA-B8), HLA-DR3, human leukocyte antigen B8 (HLA-B8), HLA-DR3,

HLA-DRw52, and HLA-DQ1HLA-DRw52, and HLA-DQ1

**A strong association exists with anti-Ro (SS-A) AbsA strong association exists with anti-Ro (SS-A) Abs

**be related to --be related to -- ultraviolet ultraviolet (UV) light(UV) light modulation of autoantigens modulation of autoantigens

epidermal cytokines, and adhesion moleculesepidermal cytokines, and adhesion molecules

with resultant keratinocyte apoptosiswith resultant keratinocyte apoptosis

**Several drugs may induce SCLE:Several drugs may induce SCLE: hydrochlorothiazide calcium channel blockershydrochlorothiazide calcium channel blockers angiotensin-converting enzyme inhibitors, terbinafine, angiotensin-converting enzyme inhibitors, terbinafine, and TNF antagonists.and TNF antagonists.

Etiology ofEtiology of SCLESCLE


Clinical features of ScLEClinical features of ScLE****papular eruptions--papular eruptions-- annular erythema or psoriasiform-annular erythema or psoriasiform- may show a photosensitive distributionmay show a photosensitive distribution worsening each spring and summerworsening each spring and summer pruritus,or asymptomaticpruritus,or asymptomatic SCLE may wax and waneSCLE may wax and wane

****50% joint involvement50% joint involvement small joints (hands and wrists).small joints (hands and wrists). Arthritis may occur but is unusual (<2%).Arthritis may occur but is unusual (<2%).

****Systemic complainSystemic complain fatiguefatigue May have Sjögren syndromeMay have Sjögren syndrome may manifest symptoms of SLEmay manifest symptoms of SLE An necessary assessment for symptoms of pleuritis, An necessary assessment for symptoms of pleuritis, pericarditis, neurologic involvement, and renal impairmentpericarditis, neurologic involvement, and renal impairment


Physical of SCLEPhysical of SCLE• clinical types:clinical types: Annular or polycyclic (ring-shaped) erythematousAnnular or polycyclic (ring-shaped) erythematous --may--may mimic mimic erythema annulare centrifugum erythema annulare centrifugum Papulosquamous (scaly bumps) Papulosquamous (scaly bumps) --may--may mimic mimic psoriasis or lichen planus psoriasis or lichen planus Vasculitis (purple spots) Vasculitis (purple spots) Nodular (lumps) Nodular (lumps)

• photodistributed--photodistributed-- occurring mainly around the neck, occurring mainly around the neck, on the back and front of the trunkon the back and front of the trunk• heal without scarringheal without scarring


Laboratory tests of SCLELaboratory tests of SCLESerologic testingSerologic testing positive ANA positive ANA Anti-Ro (SS-A) in a high proportion:Anti-Ro (SS-A) in a high proportion: Annular SCLE - 90% Annular SCLE - 90% Papulosquamous SCLE - 80-85% Papulosquamous SCLE - 80-85% SCLE with vasculitis, SS, or C2d deficiency - SCLE with vasculitis, SS, or C2d deficiency - ≥≥ 95% 95% Mothers of neonates with LE - Mothers of neonates with LE - ≥≥90% 90% Drug-induced SCLE - 70-80 Drug-induced SCLE - 70-80 %%

Anti-La (SS-B) Abs Anti-La (SS-B) Abs may occurmay occur

Anti-native DNA (ds-DNA or nDNA) Abs may occur Anti-native DNA (ds-DNA or nDNA) Abs may occur

Other laboratory testsOther laboratory tests Anemia, leukopenia, and/or thrombocytopenia may be presentAnemia, leukopenia, and/or thrombocytopenia may be present Elevated ESR, RF. Complement levels,UAElevated ESR, RF. Complement levels,UA


Other Tests-Other Tests- biopsybiopsy LBT-LBT--60% positive on lesional skin.-60% positive on lesional skin. lupus band testlupus band test

Histologic FindingsHistologic Findings(1)(1)vacuolar alteration of the basal cell layer vacuolar alteration of the basal cell layer (2)(2)an inflammatory perivascular,periappendiceal cell infiltrate an inflammatory perivascular,periappendiceal cell infiltrate

(usually lymphocytic), or in a subepidermal location(usually lymphocytic), or in a subepidermal location(3)(3)Epidermal atrophy, common, Epidermal atrophy, common, (4)(4)follicular plugging is less frequent than inDLE.follicular plugging is less frequent than inDLE.(5)(5) An abundance of mucin often is seen within the dermis. An abundance of mucin often is seen within the dermis.


DDx of SCLEDDx of SCLEDermatomyositisDermatomyositisLupus Erythematosus, AcuteLupus Erythematosus, AcuteErythema Annulare CentrifugumErythema Annulare CentrifugumLupus Erythematosus, DiscoidLupus Erythematosus, DiscoidErythema Gyratum RepensErythema Gyratum RepensPolymorphous Light EruptionPolymorphous Light EruptionErythema MultiformeErythema MultiformePsoriasis, PlaquePsoriasis, PlaqueGranuloma AnnulareGranuloma AnnulareSarcoidosisSarcoidosisHenoch-Schönlein Purpura (Anaphylactoid Purpura)Henoch-Schönlein Purpura (Anaphylactoid Purpura)Tinea CorporisTinea CorporisHypersensitivity Vasculitis (Leukocytoclastic Vasculitis)Hypersensitivity Vasculitis (Leukocytoclastic Vasculitis)Lichen PlanusLichen Planus


Treatment of SCLETreatment of SCLEsun-protective measures:sun-protective measures:sunscreens, protective clothing, behavior alteration. sunscreens, protective clothing, behavior alteration. Standard therapy: Standard therapy: includes corticosteroids (topical, intralesional) and includes corticosteroids (topical, intralesional) and antimalarialsantimalarials （（ Hydroxychloroquine Chloroquine ）

Additional therapies:Additional therapies: may be considered in selected patients include may be considered in selected patients include auranofin, dapsone, thalidomide, retinoids, interferon, auranofin, dapsone, thalidomide, retinoids, interferon, and immunosuppressive agents.and immunosuppressive agents.


Discoid lupus erythematosus (DLE)Discoid lupus erythematosus (DLE)

synonymssynonymsDiscoid Lupus Erythematosus (DLE), Discoid Lupus Erythematosus (DLE), Lupus Erythematosus Chronicus DiscoidesLupus Erythematosus Chronicus Discoides

definitiondefinition & Background & Background•Benign subtype of LE Benign subtype of LE •characterized by characterized by various-sized, well-defined, erythematous, scaly patches, various-sized, well-defined, erythematous, scaly patches, with atrophy, scarring and pigmentationwith atrophy, scarring and pigmentation•Serologic abnormalities are uncommonSerologic abnormalities are uncommon


Causes & Pathophysiology of DLECauses & Pathophysiology of DLE

•genetic predisposition-genetic predisposition- UV light exposureUV light exposure Toll-like receptors Toll-like receptors are possibly involved inare possibly involved in

•heat shock protein --heat shock protein --is induced in the keratinocyte following UV exposure or stressis induced in the keratinocyte following UV exposure or stress may act as a target for gamma (delta) T-cell–mediated may act as a target for gamma (delta) T-cell–mediated epidermal cell cytotoxicityepidermal cell cytotoxicity


Clinical features of DLEClinical features of DLE•a chronic, scarring, atrophic, photosensitive dermatosisa chronic, scarring, atrophic, photosensitive dermatosis• most are asymptomatic—most are asymptomatic— mild pruritus or occasional painmild pruritus or occasional pain Arthralgia or arthritis may occurArthralgia or arthritis may occur•may manifest any symptom of SLEmay manifest any symptom of SLE•5% or less patients accompanying systemic involvement--5% or less patients accompanying systemic involvement--

an assessment for symptoms of pleuritis, pericarditis, an assessment for symptoms of pleuritis, pericarditis, neurologic involvement, and renal involvement.neurologic involvement, and renal involvement.


Physical of DLEPhysical of DLE•primary lesion – primary lesion – erythematous papule erythematous papule or plaque with slight-to-moderate scalingor plaque with slight-to-moderate scaling unsightly red scaly patches- unsightly red scaly patches- leave postinflammatory pigmentation and white scarsleave postinflammatory pigmentation and white scars may be localised or widespreadmay be localised or widespread predominantly affects the cheeks, nose and ears, predominantly affects the cheeks, nose and ears, upper back, V of neck, backs of handsupper back, V of neck, backs of hands

•Hypertrophic LE – Hypertrophic LE – thickened and warty skin resembling warts or skin cancersthickened and warty skin resembling warts or skin cancers•Rarely, palmoplantar LE Rarely, palmoplantar LE •hair follicles involvement-hair follicles involvement-- scarring alopecia - scarring alopecia •may affect lips & mouth-may affect lips & mouth--causing ulcers & scaling.-causing ulcers & scaling.


DDxDDxActinic KeratosisActinic KeratosisPsoriasis, PlaquePsoriasis, PlaqueDermatomyositisDermatomyositisRosaceaRosaceaGranuloma AnnulareGranuloma AnnulareSarcoidosisSarcoidosisGranuloma FacialeGranuloma FacialeSquamous Cell CarcinomaSquamous Cell CarcinomaKeratoacanthomaKeratoacanthomaSyphilisSyphilisLichen PlanusLichen PlanusWarts, NongenitalWarts, NongenitalLupus Erythematosus, Subacute CutaneousLupus Erythematosus, Subacute Cutaneous


Disease Features ACLE SCLE Classic DLEClinical features of skin lesions Induration Dermal atrophy Pigment changes Follicular plugging Hyperkeratosis

00+0+

00++0++

+++++++++++++++

Histopathology Thickened basement membrane Lichenoid infiltrate Periappendageal inflammation

0+0

++++

+++++++++

Lupus band Lesional Nonlesional

++++

+++

+++0

Antinuclear antibodies +++ ++ +

Ro/SS-A antibodies By immunodiffusion By ELISA

+++

++++++

0+

Antidouble-stranded DNA antibodies +++ + 0 Hypocomplementemia +++ + + Risk for developing SLE +++ ++ +

Comparison of the Major Types of LE-Specific Comparison of the Major Types of LE-Specific Skin DiseaseSkin Disease


Laboratory tests of DLELaboratory tests of DLESerologic testing:Serologic testing: 20% manifest positive 20% manifest positive ANA.ANA. Anti-Ro (SS-A): approximately 1-3% Anti-Ro (SS-A): approximately 1-3% Antinative DNA (ds- or n-DNA) or anti-Sm Ab <5%Antinative DNA (ds- or n-DNA) or anti-Sm Ab <5% Elevated ESR in some patients. Elevated ESR in some patients. RF may be positive. RF may be positive. Complement levels may be depressedComplement levels may be depressed


Other TestsOther Tests•Immunopathology findings (LBT):Immunopathology findings (LBT): ca 90% lesional skin manifest a positive ca 90% lesional skin manifest a positive DIF-- DIF-- Deposition of Ig &/or complement at Deposition of Ig &/or complement at dermal-dermal- epidermal junctionepidermal junction --is a characteristic feature of LE--is a characteristic feature of LE• Mucin depositionMucin deposition•Urinalysis Urinalysis •Cytopenias may be present Cytopenias may be present



Treatment of DLETreatment of DLEsun-protective measuressun-protective measuresCosmetic measuresCosmetic measuresStandard medical therapy:Standard medical therapy: corticosteroids (topical or intralesional)corticosteroids (topical or intralesional) antimalarials—antimalarials— Hydroxychloroquine chloroquine phosphate)Hydroxychloroquine chloroquine phosphate)

Alternative therapies:Alternative therapies:auranofin dapsone, thalidomide,oralauranofin dapsone, thalidomide,oral ，， topical retinoids, topical retinoids, immunosuppressive agents—immunosuppressive agents— methotrexate (MTX), azathioprine, mycophenolate mofetil, methotrexate (MTX), azathioprine, mycophenolate mofetil, lenalidomide phenytoin, interferon, acitretin, lenalidomide phenytoin, interferon, acitretin, & chimeric monoclonal antibody.& chimeric monoclonal antibody.

systemic corticosteroids are rarely effectivesystemic corticosteroids are rarely effective

Treatment of DLETreatment of DLEsun-protective measuressun-protective measuresCosmetic measuresCosmetic measuresStandard medical therapy:Standard medical therapy: corticosteroids (topical or intralesional)corticosteroids (topical or intralesional) antimalarials—antimalarials— Hydroxychloroquine chloroquine phosphate)Hydroxychloroquine chloroquine phosphate)

Alternative therapies:Alternative therapies:auranofin dapsone, thalidomide,oralauranofin dapsone, thalidomide,oral ，， topical retinoids, topical retinoids, immunosuppressive agents—immunosuppressive agents— methotrexate (MTX), azathioprine, mycophenolate mofetil, methotrexate (MTX), azathioprine, mycophenolate mofetil, lenalidomide phenytoin, interferon, acitretin, lenalidomide phenytoin, interferon, acitretin, & chimeric monoclonal antibody.& chimeric monoclonal antibody.

systemic corticosteroids are rarely effectivesystemic corticosteroids are rarely effective


Thanks & questions?Thanks & questions?Thanks & questions?Thanks & questions?

Documents

Sir Run Run Shaw Hospital Prof. Cheng Unit 5. Dermatomyositis ， Scleroderma – Etiology, Clinical features, Diagnosis and Treatment. 1.5 hr Subacute cutaneous