Upload
apocru
View
119
Download
8
Embed Size (px)
Citation preview
Antinuclear autoantibodies in CTD. Autoantibidy Antigen Disease Anti-ss-DNA Single strand DNA SLE, MCTD, RA, SS,
Drug induced LE, morphea
Anti-ds-DNA* Double strand DNA SLE
Anti-Sm* complex of proteins rich on RNA
SLE
Anti Histonové Histones SLE, lékový LE, RA, SSc, morphea
Anti-U1RNP complex of proteins rich on uridineé
RNA
SLE, MCTD, SS
Anti-rRNP ribosomal phosphoproteins
SLE
Antinuclear autoantibodies in CTD.Autoantibody Antigen Disease Anti-Ro/SSA complex protein/RNA SLE, SS, SSc, RA
Anti-La/SSB complex phosphoprotein/ RNA-polymerase III
SLE, SS
Anti-Jo1* histidyl tRNA syntetase PM/DM
Anti-Mi-2* nuclear protein DM
Anti-RNA pol* complex proteins/ RNA polymerase I-III
SSc
Anti-PM-Scl nucleolar proteins SSc/PM
Anti-Scl-70* DNA topoizomerase I SSc
Anti-Centromere* kinetochore proteins SSc
Anti-Fibrilarin* Part of U3RNP SSc
Specific cutaneous lesions of LE (ie. with typical histopahtological picture of LE)
Acute (systemic) LE: erythema, maculopapular localized - diseminated
Subacute LE:
annular
papulosquamous (psoriasis-like)
Chronic LE:
discoid: - localized - disseminated
hypertrophic (verrucous)
LE panniculitis (profundus)
mucous LE
lupus tumidus
lupus pernio
Chronic (discoid, cutaneous, scarring) LE
Chronic (discoid) LE - annular
Chronic (discoid) LE – cicatricial alopecia
Chronic (discoid) LE – cicatricial alopecia
Chronic LE – photosensitivity, inappropriate profession: roofer (tile layer)
Diagnostic criteria of SLE
(American Rheumatology Association = ARA) 1. butterfly erythema2. Cutaneous manifestations of LE (subacute, chronic)3. photosensitivity4. Mucous ulcerations (mouth, nose)5. polyarthritis, arthralgia, joint swelling6. serositis (pleuritis, perikariditis)7. renal (proteinuria > 0,5g/24 h, casts in urine sediment)8. CNS (spasms, neuropsychiatric symptoms)9. hematologic (hemolytic anemia, leukopenia, lymfopenia, thrombocytopenia)10. imunology (anti-ds-DNA, anti-Sm ab., positive BWR)11. Antinuklear autoantibodies
Note. 4 criteria sufficient for diagnosis of SLE
Lupus band test (direct immunofluorescence) – Ig (G)+ C3
SLE - urticaria -vasculitis
more burning and painful than itchy pertaine longer than 24 hleaving pigmentations.
splinter hemorrhagia
Subacute LE – annular+anti-SSA/Ro and/or anti-SSB/La
bullous
Neonatal lupus erythematosus - Mother (may be asymptomatic) positivity of anti-SSA/Ro and/or anti-SSB/La. Congenital heart block in 70% - anti SS-A52 cross react with conduction system - cardiostimulator
Subacute LE – papulosquamous-psoriasiform
THERAPY – cutaneous LE Topical: photoprotection, cortikosteroids (external, intralesional),
retinoids (tazaroten), pime/tacro-limus, lasersSystemic: if necessary First choice: antimalarics (OH-chlorochin, chlorochin,
chlorochin+quinacrine) Second choice: retinoids, dapsone (vasculitis) Third choice: methotrexate, thalidomide, gold, clofazimine, Fourth choice: corticosteroids, azathioprine, cyclosporine, cyclofosfamide, IV imunoglobulins Experimental: alfa-interferon, UVA-1 fototerapy, anti-CD4 ab., topical tacrolimus…
Classification
dermatomyositis/polymyositis (DM/PM)
1. primary idiopathic PM
2. primary idiopathic adult DM
3. paraneoplastic DM (PM)
4. juvenile DM (PM)
5. DM (PM) accompanying other connective tissue diseases – overlap syndrome
6. clinically amyopathic DM
Diagnostic criteria (Bohan a Peter) dermatomyositis (DM) a polymyositis (PM)
1. muscle weekness - symetric proximal (shoulder and hip girdle muscles-combing hairs, climbing stairs), other- dysfagia, ptosis, hoarse voice
2. In serum signs of muscle damage: raised kreatinkinase (MM-izoenzymu), aldolase, transaminases, myoglobin
3. EMG: elektromyografic signs of myopathy 4. biopsy muscle with inflammatory myopathy (sono, MRI)3. Cutaneous typical lesions in dermatomyositis
Note: sure diagnosis = 1.-4. in PM, at least 3 criteria plus 5. criterium in DM, probable diagnosis = 3 criteria in PM, 2 criteria plus 5. Criterium in DM.
Eyelid edema andLivid erythema
„Shawl“ sign
Papules and erythema over finger joints and knuckles
Nailfold teleangiectasia:On capilaroscopy - giant capilaries avascular areas, bushy proliferation
Mechanic´s hands - hyperkeratosis, fissures, ulcers
Muscle atrophy and weakness
Therapy - dermatomyositis Systemic:
cortikosteroids – drug of choice
combination with immunosupresives (mostly
methotrexate), IV imunoglobulins
Of cutaneous lesions: similar to lupus erythematosus
Course and progonosis:
Better with early diagnosis and treatment.
In children in 50% complete remission, in 40 %
prolonged therapy
In adults mostly chronic therapy. Malignancy deteriorate prognosis.
Classification of scleroderma:
Localized scleroderma (morphea)
systemic scleroderma
Overlap syndromes
Undifferentiated connective tissue diseases
Scleroderma-like diseases (pseudoscleroderma)
MORPHEASCLERODERMIA CIRCUMSCRIPTA
LOCALIZED SCLERODERMAClassification
I. Morphea PLAQUE
one(several) plaques
disseminated, generalized
II. Morphea LINEAR
"en coup de sabre"
hemiatrophia progressiva faciei
III. Morphea PROFUNDA – SUBCUTANEOUS
morphea profunda
fasciitis eosinophilica
I. MORPHEA plaque
• Plaque (to few plaques)• Generalized• Large plaque• Guttate• Bullous• Nodular (keloid)• Morphea pansclerotica• Atrophodermia idiopathica progressiva Passini-
Pierini
MorpheaInflammatory phaseOrange peel appereance Livid erythema
Peripheral red-violet erythema („Lilac ring)Central ivory induration
Generalized morphea
Generalized morphea
Linear morphea
Linear morphea
Linear morphea
Linear morphea - flexion contracture
Linear morphea
Linear morphea
Linear morphea
Facial hemiatrophy
Deep morphea –
Eosinophilic fasciitis
Deep morphea
Deep morphea
THERAPY - morphea Topic: corticosteroids, vitamin D analogs emolients fysiotherapySystemic: in extensive involvement, functional defect phototherapy: PUVA therapy,, UVA1 methotrexate Corticosteroids (deep morphea) Others: vitamine E, penicillin, penicillamine,
antimalarics… Surgical: contracturesCourse and prognosis: duration 3-5 years. In deep and
extensive morphea can be longer. Rarely flare (linear in 13 %). Persistent hyperpigmentation, disability,
Classification of scleroderma:
localized scleroderma (morphea)
systemic scleroderma
overlap syndromes
Undifferentiated connective tissue diseases
Scleroderma-like disease
SYSTEMIC SCLERODERMA CLASSIFICATION (acc. skin involvement)
LIMITED
DIFFUSE
Typ I - fingers (acroscleroderma digitalis)
Typ II - fingers, forearms,
arms
(acrosclerodermia proximalis) - intermedial
Typ III - trunk
diffuse
MINIMAL (PRE-) SSc (Raynaud + capilaroscopy and/or ANA+)CREST (calcinosis,oesofagus,Raynaud, sklerodactyly, teleangiectasia)SCLERODERMIA SYSTEMICA SINE SCLERODERMIA
(acrosclerosis)
GIT involvement SYSTEMIC SCLERODERMA
• oropharynx (mikro-stomie-glossie, shortened frenulum, alveolar resorption etc.)
• hypomotility/90%/ • gastroesofageal reflux• esophagitis • Barrett.metaplasia • stricture • gastroparesis • malabsorption
• dysmicrobia• diarrhoea• bleeding • Perforation, volvulus • pneumatosis cystoides
intestinalis • INVESTIGATION • rx barium • manometry • scinti 99m Tc • stools - fats, blood
LUNG INVOLVEMENT systemic scleroderma
- alveolitis
- interstic. Fibrosis /53% rx,
92% functional/
- pulmonary hypertension
- pleura (fluid,fibrosis..)
- spontaneous pneumothorax
- coincidence with pneumoconiosis
- carcinoma
- drug pneumonitis (CF, PNCA)
-aspiration pneumonia
INVESTIGATION- rx
- spirometry-restriction
- DLCO
- blood gas
- BAL
- HRCT
- scinti (67GA,99mTc-DTPA)
- biopsy
HEART INVOLVEMENT systemic scleroderma
(in 50% on non-invasive investigation)
- pericarditis – (autopsy 71%, symptomatic 7- 20%)
- focal fibrosis of heart muscle – (autopsy 89%)
- fibrosis of conduction system - arythmias /ECG 50%/
- myocarditis
- concentric intimal hypertrophy of coronary a.
INVESTIGATION:
ecg, echokardio, Holter, scintigraphy thalium 201, catetrization
KIDNEY INVOLVEMENT systemic scleroderma
mild : 15 – 45% pacients
- proteinuria 500mg/24h- hypertension 140/90- azotemia 9 mmol/1
serious : 3 – 10%
- chronic renal insufficiency - sklerodermic hypertensive renal crisis (8%)
ANTICENTROMERIC antibodies (in 12-46% SSc)
(Antigenem jsou centromerové nehistonové proteiny:
CENP-A 14-19kD, B 80, C 140, D 47)• HLA-DR 1, 4, 5, DRw8, DQB1• Milder, chronic course• no renal involvement• Less lung, heart and skin• May be serious pulmonary hypertension
a GIT• previous Raynaud phenomena • Role in chromosamal breaks ?
SCL-70 antibodies (in 18-83%)
antigen: DNA topoizomerase I (non-histone protein 70-100kD)
HLA-DR 2, 5, DQB1
• more serious, shorter course• more extensive skin involvement• more frequent lung, heart, renal involvement
Systemic sclerodermaclassification criteria (ARA)
MAIN: (one is sufficient)
proximal scleroderma
OTHER: ( 2 of 3)
sklerodactyly
Pitting scars on fingers
Bilateral interstitial lung fibrosis
(rx) Masi AT, et al., Arthritis Rheum, 1980, 23, 581
THERAPY- systemic scleroderma:
no causal drug - symptomatic, organ directed therapy
Vasoactive drugs: rheological (pentoxiphyllin), vasodilatation (calcium chanel blocators, prostaglandins), antihypertensives (ACE).
Antiinflammatory: NSA, glukokortikosteroids, imunosupresives (cyclophosphamide, azamune, methotrexate).
Antifibrotic: penicillamine, interferons, penicilin, extrakorporal phtopheresis.
General care of pacient: positive approach to disesase, stop smoking, warm enviroment, massage, exercise, prevention of řed trauma and cold.
Course and prognosis: limeted SSc 5 years survival from diagnosis 75-84%, diffuse SSc 34-50%.
Klasifikace sklerodermie:
lokalizovaná sklerodermie (morphea)
systémová sklerodermie
překryvné syndromy
nediferencovaná onemocnění pojiva
pseudosklerodermie
SYSTÉMOVÁ SKLERODERMIE
• je difuzní onemocnění pojiva a drobných cév
charakterizované vznikem fibrózy a vaskulární
obliterace postihující především kůži,
gastrointestinální trakt, plíce, srdce a ledviny.
Tuhá kůže je přitom jeho hlavním klinickým
příznakem, orgánové postižení nejdůležitějším
prognostickým ukazatelem.
Limitovaná systémová sklerodermie
(acrosclerosis)
Raynaudův fenomén trvající roky a desetiletí, tužší kůže aker (ruce, nohy, předloktí, bérce,
hlava, krk) – může i chybět pozdní výskyt plicní hypertenze (s či bez
intersticiální plicní fibrózy), kožní kalcifikace, teleangiektazie, GIT postižení,
kapilaroskopie - ektazie kapilár bez výrazné redukce počtu
anticentromerové protilátky
Štork J: Sklerodermie, Galén, 1996
Difúzní systémová sklerodermie
Raynaudův fenomén – trvá krátce do 1 roku
tuhá kůže - trupu, paží a aker, krepitace šlach orgány - časná a výrazná intersticiální plicní fibróza,
GIT, ev. ledvin, srdce kapilaroskopie - výrazné ektazie, redukce počtu,
avaskulární zóny anti Scl-70 protilátky
Štork J: Sklerodermie, Galén, 1996
Subacute LE – annular+anti-SSA/Ro and/or anti-SSB/La