connective tissue disease 國泰醫院皮膚科. connective tissue diseases lupus erythematosus...

Connective tissue diseaseConnective tissue disease

國泰醫院皮膚科國泰醫院皮膚科

Connective tissue diseasesConnective tissue diseases

Lupus erythematosusLupus erythematosus Dermatomyositis/PolymyositisDermatomyositis/Polymyositis SclerodermaScleroderma Others:Others: Sjögren's syndromeSjögren's syndrome Relapsing polychondritisRelapsing polychondritis Raynaud’s phenomenonRaynaud’s phenomenon … …....

Lupus ErythematosusLupus ErythematosusI. Cutaneous LE :I. Cutaneous LE : A. Acute cutaneous LE (ACLE):A. Acute cutaneous LE (ACLE): 1. Localized ACLE (malar rash; butterfly rash)1. Localized ACLE (malar rash; butterfly rash) 2. Generalized ACLE 2. Generalized ACLE B. Subacute cutaneous LE (SCLE):B. Subacute cutaneous LE (SCLE): 1. Papulosquamous (psoriasiform) SCLE1. Papulosquamous (psoriasiform) SCLE 2. Annular (polycyclic) SCLE2. Annular (polycyclic) SCLE C. Chronic cutaneous LE (CCLE):C. Chronic cutaneous LE (CCLE): 1. Classic Discoid LE (DLE)1. Classic Discoid LE (DLE) a. localized DLEa. localized DLE b. generalized DLEb. generalized DLE 2. Hypertrophic DLE2. Hypertrophic DLE 3. Lupus profundus/ Lupus panniculitis3. Lupus profundus/ Lupus panniculitisII. Systemic lupus erythematosus (SLE)II. Systemic lupus erythematosus (SLE)

American College of Rheumatology (ACR) Criteria for the ClassifiAmerican College of Rheumatology (ACR) Criteria for the Classification of SLEcation of SLE

This classification is based on 11 criteria: This classification is based on 11 criteria: ＞＝＞＝ 4/11 diagnosis4/11 diagnosis 1.1. Malar rashMalar rash2.2. Discoid rashDiscoid rash3.3. PhotosensitivityPhotosensitivity4.4. Oral ulcers, usually painlessOral ulcers, usually painless5.5. Arthritis, nonerosive, involving two or more peripheral joints, with tendeArthritis, nonerosive, involving two or more peripheral joints, with tende

rness, swelling, or effusionrness, swelling, or effusion6.6. Serositis (pleurisy or pericarditis)Serositis (pleurisy or pericarditis)7.7. Renal disorder (persistent proteinuria exceeding 0.5 g/day or cellular casRenal disorder (persistent proteinuria exceeding 0.5 g/day or cellular cas

ts)ts)8.8. Neurologic disorders (seizures or psychosis)Neurologic disorders (seizures or psychosis)9.9. Hematologic disorders (hemolytic anemia; leukopenia of less than 4000/Hematologic disorders (hemolytic anemia; leukopenia of less than 4000/

mmmm33; lymphopenia of less than 1500/mm; lymphopenia of less than 1500/mm33; or thrombocytopenia of less t; or thrombocytopenia of less than 100,000/mmhan 100,000/mm33))

10.10. Immunologic disorder (positive LE-cell preparation; anti-DNA in abnormImmunologic disorder (positive LE-cell preparation; anti-DNA in abnormal titer; antibody to Sm nuclear antigen; or false-positive serologic test fal titer; antibody to Sm nuclear antigen; or false-positive serologic test for syphilis)or syphilis)

11.11. Antinuclear antibody (ANA) Antinuclear antibody (ANA)

Systemic Lupus ErythematosuSystemic Lupus Erythematosuss

Cause:Cause: An autoimmune disorder involving multisystem inflaAn autoimmune disorder involving multisystem infla

mmation and the generation of autoantibodies. mmation and the generation of autoantibodies. The specific cause of SLE is unknown, immune system The specific cause of SLE is unknown, immune system

dysregulation leading to immune complex formation idysregulation leading to immune complex formation is postulated to induce tissue damage. s postulated to induce tissue damage.

Multiple influences, including genetic, racial, hormonaMultiple influences, including genetic, racial, hormonal, and environmental factors, are associated with the l, and environmental factors, are associated with the development of SLE. development of SLE.

Hormonal factors are suspected to influence the coursHormonal factors are suspected to influence the course of SLE, with a high frequency in females, peak disease of SLE, with a high frequency in females, peak disease onset in the childbearing years.e onset in the childbearing years.

Overview of the ExtracutaneousOverview of the ExtracutaneousManifestations of SLEManifestations of SLE

General: Fever, fatigue, malaise, weight lossGeneral: Fever, fatigue, malaise, weight loss Musculoskeletal: Symmetric small joint arthralgia, arthritis (nondMusculoskeletal: Symmetric small joint arthralgia, arthritis (nond

eforming and deforming)eforming and deforming) Hematologic: Hematologic: Anemia: Normocytic normochromic, HemolyticAnemia: Normocytic normochromic, Hemolytic Leukopenia: Lymphopenia, GranulocytopeniaLeukopenia: Lymphopenia, Granulocytopenia ThrombocytopeniaThrombocytopenia CardiopulmonaryCardiopulmonary RenalRenal NeuropsychiatricNeuropsychiatric GastrointestinalGastrointestinal OcularOcular Lymphatic system: Lymphadenopathy, SplenomegalyLymphatic system: Lymphadenopathy, Splenomegaly


Autoantibody testing: Autoantibody testing: ANA: screeningANA: screening Anti-dsDNA: levels may correlate with disease activity, pAnti-dsDNA: levels may correlate with disease activity, p

articularly with SLE nephritis.articularly with SLE nephritis. Anti-DNA histones: drug- induced lupus.Anti-DNA histones: drug- induced lupus. Anti-Sm: highly specific for SLEAnti-Sm: highly specific for SLE Anti-SSA/Ro and Anti-SSB/La: SCLE, neonatal LE, other Anti-SSA/Ro and Anti-SSB/La: SCLE, neonatal LE, other

connective tissue disease, including Sjogren syndrome.connective tissue disease, including Sjogren syndrome. Antiphospholipid Ab: Anticardiolipin Ab and lupus antiAntiphospholipid Ab: Anticardiolipin Ab and lupus anti

coagulantcoagulant Other autoantibodies: rheumatoid factor, Coomb’s aOther autoantibodies: rheumatoid factor, Coomb’s a

ntibodyntibody VDRL/RPRVDRL/RPR


Treatment:Treatment: Guided by the individual patient's Guided by the individual patient's manifestations. manifestations.

The goals of therapy are reversal of the immunThe goals of therapy are reversal of the immune dysregulation and inflammation, prevention e dysregulation and inflammation, prevention of permanent organ dysfunction, and improveof permanent organ dysfunction, and improvement of symptoms. ment of symptoms.

Prevention: Prevention: Avoid ultraviolet light and sun exAvoid ultraviolet light and sun exposure to minimize worsening symptoms due posure to minimize worsening symptoms due to photosensitivity. to photosensitivity.

Dermatomyositis/PolymyositisDermatomyositis/Polymyositis Dermatomyositis: autoimmune inflammatory iDermatomyositis: autoimmune inflammatory i

njury occur in striated muscle and skin. njury occur in striated muscle and skin. Clinical subgroups:Clinical subgroups: 1. Polymyositis1. Polymyositis

2. Dermatomyositis2. Dermatomyositis3. Polymyositis or dermatomyositis associated 3. Polymyositis or dermatomyositis associated with malignancywith malignancy4. Childhood dermatomyositis4. Childhood dermatomyositis5. Polymyositis or dermatomyositis with an as5. Polymyositis or dermatomyositis with an associated connective tissue disorder sociated connective tissue disorder

Associated with malignancy: ≧60 Y/O, NPC in Associated with malignancy: ≧60 Y/O, NPC in Taiwan.Taiwan.

DermatomyositisDermatomyositis Diagnostic criteriaDiagnostic criteria

1. Typical skin rash1. Typical skin rash2. Symmetric proximal muscle weakness with or witho2. Symmetric proximal muscle weakness with or without dysphagia or respiratory muscle involvementut dysphagia or respiratory muscle involvement3. Abnormal muscle biopsy specimen3. Abnormal muscle biopsy specimen4. Elevation of skeletal muscle–derived enzymes4. Elevation of skeletal muscle–derived enzymes5. Abnormal electromyogram5. Abnormal electromyogram

Confidence limits for diagnosis of dermatomyositisConfidence limits for diagnosis of dermatomyositis1. Definite dermatomyositis—rash and three of the fo1. Definite dermatomyositis—rash and three of the four other diagnostic criteriaur other diagnostic criteria2. Probable dermatomyositis—rash and two of the fou2. Probable dermatomyositis—rash and two of the four other diagnostic criteriar other diagnostic criteria3. Possible dermatomyositis—rash and one of the four 3. Possible dermatomyositis—rash and one of the four other diagnostic criteria other diagnostic criteria

DermatomyositisDermatomyositis 1. Adult-onset classic dermatomyositis1. Adult-onset classic dermatomyositis

2. Classic dermatomyositis with malignan2. Classic dermatomyositis with malignancycy3. Juvenile-onset classic dermatomyositis3. Juvenile-onset classic dermatomyositis4. Classic dermatomyositis as part of an o4. Classic dermatomyositis as part of an overlap connective tissue disorderverlap connective tissue disorder5. Amyopathic dermatomyositis (adult an5. Amyopathic dermatomyositis (adult and juvenile onset)d juvenile onset)

DermatomyositisDermatomyositis PathognomonicPathognomonic

1. 1. Gottron's papulesGottron's papules: Papules having a violaceous hu: Papules having a violaceous hue overlying the dorsal-lateral aspect of interphalangeae overlying the dorsal-lateral aspect of interphalangeal and/or metacarpophalangeal joints. When fully forml and/or metacarpophalangeal joints. When fully formed, these papules become slightly depressed at the ceed, these papules become slightly depressed at the center, which can assume a white, atrophic appearance. nter, which can assume a white, atrophic appearance. Associated telangiectasia can be present.Associated telangiectasia can be present.2. 2. Gottron's signGottron's sign: Symmetric confluent macular viola: Symmetric confluent macular violaceous erythema with or without edema overlying the ceous erythema with or without edema overlying the dorsal aspect of the interphalangeal/metacarpophaladorsal aspect of the interphalangeal/metacarpophalangeal joints, olecranon processes, patellae, and medingeal joints, olecranon processes, patellae, and medial malleoli. al malleoli.

Gottron's papulesGottron's papules

Heliotrope signHeliotrope sign

DermatomyositisDermatomyositis Treatment:Treatment: involves general measures and m involves general measures and m

easures to control both the muscle disease aneasures to control both the muscle disease and the skin disease. d the skin disease.

Bed rest, and a program of physical therapy is Bed rest, and a program of physical therapy is useful to help prevent contractures.useful to help prevent contractures.

Calcinosis:Calcinosis: This complication of the disease affects childreThis complication of the disease affects childre

n and adolescents. n and adolescents. Prevention: Prevention: Skin disease is exacerbated by sunlight and othSkin disease is exacerbated by sunlight and oth

er sources of ultraviolet light. er sources of ultraviolet light.

SlerodermaSleroderma Scleroderma: a chronic disease, unknowScleroderma: a chronic disease, unknow

n etiology, affects microvasculature and n etiology, affects microvasculature and connective tissue. connective tissue.

Two types of sclerodermaTwo types of scleroderma 1. localized scleroderma (morphea):1. localized scleroderma (morphea): 2. systemic sclerosis (SSc): 2. systemic sclerosis (SSc):

limited SSc and diffuse SSc limited SSc and diffuse SSc

SlerodermaSleroderma Localized scleroderma:Localized scleroderma: is not a life-threatening disea is not a life-threatening disea

se but can cause disfigurement. se but can cause disfigurement. Several clinical forms: Several clinical forms: 1. Morphea: the most common type, poorly defined area1. Morphea: the most common type, poorly defined area

s of nonpitting edema, surface smooth and shiny with s of nonpitting edema, surface smooth and shiny with the loss of hair follicles. the loss of hair follicles.

2. Generalized morphea: absence of Raynaud's phenom2. Generalized morphea: absence of Raynaud's phenomenon, acrosclerosis, and organ involvement differentienon, acrosclerosis, and organ involvement differentiates generalized morphea from SSc.ates generalized morphea from SSc.

3. Guttate morphea: small and superficial3. Guttate morphea: small and superficial4. Subcutaneous morphea (morphea profunda)4. Subcutaneous morphea (morphea profunda)5. Linear scleroderma5. Linear scleroderma6. Frontal or frontoparietal linear scleroderma, called co6. Frontal or frontoparietal linear scleroderma, called co

up de sabreup de sabre

MorpheaMorphea Diagnosis:Diagnosis: no diagnostic laboratory test no diagnostic laboratory test

s are available for morphea. s are available for morphea. Treatment: Treatment: No proven effective treatmeNo proven effective treatme

nts for morphea exist.nts for morphea exist. Most patients with plaque-type morphea Most patients with plaque-type morphea

experience very gradual spontaneous reexperience very gradual spontaneous remission. mission.

Systemic sclerodermaSystemic scleroderma Classification of Systemic Scleroderma Subsets: Classification of Systemic Scleroderma Subsets: Diffuse cutaneous SSc (dSSc)Diffuse cutaneous SSc (dSSc)

Onset of skin changes (puffy or hidebound) within 1 year of onset of Raynaud's Onset of skin changes (puffy or hidebound) within 1 year of onset of Raynaud's phenomenonphenomenon

Truncal and acral skin involvement Truncal and acral skin involvement Tendon friction rubs Tendon friction rubs Early and significant interstitial lung disease, oliguric renal failure Early and significant interstitial lung disease, oliguric renal failure Diffuse gastrointestinal disease Diffuse gastrointestinal disease Myocardial involvement Myocardial involvement Nail fold capillary dilatation and drop out Nail fold capillary dilatation and drop out Antitopoisomerase-l (Scl-70) antibodies (30% of patients) Antitopoisomerase-l (Scl-70) antibodies (30% of patients)

Limited cutaneous SSc (lSSc)Limited cutaneous SSc (lSSc) Raynaud's phenomenon for years (occasionally decades) Raynaud's phenomenon for years (occasionally decades) Skin involvement limited to hands, face, feet, and forearms (acral) Skin involvement limited to hands, face, feet, and forearms (acral) A significant late incidence of pulmonary hypertension, with or without A significant late incidence of pulmonary hypertension, with or without

interstitial lung disease, skin calcification, telangiectasia, and gastrointestinalinterstitial lung disease, skin calcification, telangiectasia, and gastrointestinal involvementinvolvement

High prevalence (70-80%) of ACA (anticentromere Ab) High prevalence (70-80%) of ACA (anticentromere Ab) Dilated nail fold capillary loops, usually without capillary drop out Dilated nail fold capillary loops, usually without capillary drop out

Scleroderma sine sclerodermaScleroderma sine scleroderma Raynaud's phenomenon Raynaud's phenomenon No skin involvement No skin involvement Presentation with pulmonary fibrosis, scleroderma, renal crisis, cardiac or Presentation with pulmonary fibrosis, scleroderma, renal crisis, cardiac or

gastrointestinal diseasegastrointestinal disease Antibodies may be present (Scl-70, ACA, nucleolar) Antibodies may be present (Scl-70, ACA, nucleolar)

Systemic sclerodermaSystemic scleroderma CREST Syndrome: CREST Syndrome: 1.1. Calcinosis cutis Calcinosis cutis 2.2. Raynaud's phenomenon Raynaud's phenomenon 3.3. Esophageal dysfunctionEsophageal dysfunction4.4. Sclerodactyly Sclerodactyly 5.5. Telangiectasia Telangiectasia

Systemic sclerodermaSystemic scleroderma Treatment:Treatment: In pruritus: topical steroid and emollients, PUVAIn pruritus: topical steroid and emollients, PUVA Calcinosis: anticoagulant, colchicine, intralesionCalcinosis: anticoagulant, colchicine, intralesion

al steroid, calcium-channel blockersal steroid, calcium-channel blockers Raynaud’s phenomenon: avoiding exposure to Raynaud’s phenomenon: avoiding exposure to

cold temperature, smoking cessation is advised.cold temperature, smoking cessation is advised. Complications:Complications: neoplastic diseases may compl neoplastic diseases may compl

icate the disease course.icate the disease course. Prognosis:Prognosis: depends on the type of SSc. depends on the type of SSc.

Sjögren's syndromeSjögren's syndrome Sjögren's syndrome: a rheumatologic disease,Sjögren's syndrome: a rheumatologic disease,

dryness of the mucous membranes of the eyes,dryness of the mucous membranes of the eyes, mouth. mouth.

The etiology is unknown. The etiology is unknown. Primary Sjögren's syndrome: occur alonePrimary Sjögren's syndrome: occur alone Secondary Sjögren's syndrome: association wiSecondary Sjögren's syndrome: association wi

th other connective tissue diseases such as rheth other connective tissue diseases such as rheumatoid arthritis, progressive systemic sclerosumatoid arthritis, progressive systemic sclerosis, and SLE.is, and SLE.

Sjögren's syndromeSjögren's syndrome European Epidemiology Center CriteriaEuropean Epidemiology Center Criteria Ocular symptoms (at least one)Ocular symptoms (at least one)

– Daily, persistent, troublesome dry eyes for more than 3 monthsDaily, persistent, troublesome dry eyes for more than 3 months – Recurrent sensation of sand or gravel in the eyesRecurrent sensation of sand or gravel in the eyes – Use of a tear substitute more than 3 times/dayUse of a tear substitute more than 3 times/day

Oral symptoms (at least one)Oral symptoms (at least one) – Daily feeling of dry mouth for at least 3 monthsDaily feeling of dry mouth for at least 3 months – Recurrent feeling of swollen salivary glands Recurrent feeling of swollen salivary glands – Drinking liquids to help wash down dry foodsDrinking liquids to help wash down dry foods

Objective evidence of dry eyes (at least one)Objective evidence of dry eyes (at least one) – Schirmer I test 5 mm or below/5 minutesSchirmer I test 5 mm or below/5 minutes – Rose bengal score of 4 or greater according to van Bijsterveld systemRose bengal score of 4 or greater according to van Bijsterveld system

Histopathologic signsHistopathologic signs – Minor salivary gland biopsy with focus score of 1 or greaterMinor salivary gland biopsy with focus score of 1 or greater

Objective evidence of salivary gland involvement (at least one)Objective evidence of salivary gland involvement (at least one) – Salivary gland scintigraphySalivary gland scintigraphy – Parotid sialographyParotid sialography – Unstimulated whole sialometry 1.5 ml/15 minutes or belowUnstimulated whole sialometry 1.5 ml/15 minutes or below

Laboratory abnormality (at least one)Laboratory abnormality (at least one) – Anti-SS-A or anti-SS-B antibodyAnti-SS-A or anti-SS-B antibody – ANAANA – IgM rheumatoid factorIgM rheumatoid factor

Exclusion criteria: preexisting lymphoma, acquired immunodeficiency Syndrome, sarcoidosiExclusion criteria: preexisting lymphoma, acquired immunodeficiency Syndrome, sarcoidosis, graft-versus-host disease.s, graft-versus-host disease.

Sjögren's syndromeSjögren's syndrome Cutaneous manifestations:Cutaneous manifestations: Xerosis, palpable and nonpalpable purpXerosis, palpable and nonpalpable purp

ura, urticaria-like vasculitic lesions, erytura, urticaria-like vasculitic lesions, erythema multiforme-like, erythema perstahema multiforme-like, erythema perstans, erythema nodosum lesions, cutaneons, erythema nodosum lesions, cutaneous lymphoma, nodular amyloidosis, Swus lymphoma, nodular amyloidosis, Sweet's syndrome, Annular erythematosus eet's syndrome, Annular erythematosus lesion (donut lesion) described in Japanlesion (donut lesion) described in Japanese patientsese patients

Relapsing polychondritisRelapsing polychondritis Relapsing polychondritis: a rare disease, recurRelapsing polychondritis: a rare disease, recur

ring episodes of inflammation in cartilagenous ring episodes of inflammation in cartilagenous tissues throughout the body.tissues throughout the body.

Auricular chondritis and arthritis: the most coAuricular chondritis and arthritis: the most common.mmon.

The chondritis: sudden onset, redness, warmtThe chondritis: sudden onset, redness, warmth, swelling, and tenderness limited to the cartih, swelling, and tenderness limited to the cartilagenous portion of the external ears, the ear llagenous portion of the external ears, the ear lobe is typically uninvolved. obe is typically uninvolved.

Lab: ESR increase, Ab to type II collagen (1/3 to Lab: ESR increase, Ab to type II collagen (1/3 to 1/2).1/2).

Raynaud’s phenomenonRaynaud’s phenomenon Raynaud's phenomenon: the occurrence of episRaynaud's phenomenon: the occurrence of epis

odic attacks of digital ischemia provoked by exodic attacks of digital ischemia provoked by exposure to cold or emotional stress. posure to cold or emotional stress.

The classic episode of Raynaud's phenomenon:The classic episode of Raynaud's phenomenon: A triphasic color change of pallor, cyanosis, and A triphasic color change of pallor, cyanosis, and

hyperemia of the fingers. hyperemia of the fingers. Symptoms of numbness or tingling during the atSymptoms of numbness or tingling during the at

tack or actual pain with recovery are common.tack or actual pain with recovery are common. Primary (idiopathic) and secondary forms.Primary (idiopathic) and secondary forms.

connective tissue disease 國泰醫院皮膚科. connective tissue diseases lupus erythematosus...

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