Sjögren’s syndrome (SS)Sjögren’s syndrome (SS)

Definition: Autoimmune inflammation of the exocrine (lacrimal,salivary, etc) glands resulting in decreased production of tears and saliva (xerophthalmia és xerostomia).Primary and secondary forms (the latter accompanies otherautoimmun diseases (e.g.: RA, SLE, etc).

Epidemiology: One of the most frequent autoimmune diseases; estimated incidence: 1-10/1000, prevalence: 1%. Male: femaleratio cca 1:9.

Pathogenesis: Lymphoid infliltration of exocrine glands(infiltrating lymphocytes are mostly CD4+ T cells); with concomitant inflammation and slow destruction.

Histology of salivary gland in Sjögren’s syndrome

Parotitisin SS

Keratoconjunctivitis sicca (rose bengal test) in SS

Schirmer’s test

Vasculitis (purpura)in Sjögren’s syndrome

Diagnostic criteria of SS Diagnostic criteria of SS (E(ECSGCSG, 1993), 1993)1. Ocular symptoms (at least one the following):

a/ symptomatic dry eyes for at least 3 monthsb/ repeated sensation of foreign bodies in the eyesc/ artificial tears are required at least 3 times a day

2. Mouth symptoms (at least one of the following):a/ symptomatic dry mouth for at least 3 monthsb/ recurrent salivary gland enlargementc/ requirement of frequent drinking while swallowing dry food

3. Positive Schirmer’s test ( 5mm/5 min) (or positive rose bengal test)4. Positive salivary gland (lower lip) biopsy. In histology at least 1 lymphoid

follicle ( 50 cells) / 4 mm2 tissue)5. Salivary gland involvement (at least one of the following):

a/ positive scintigraphyb/ positive parotid sialographyc/ unstimulated salivary flow ( 1.5 ml/15 min)

6. Autoantibodies (at least one of the following):a/ SS-A (Ro) or SS-B (La) antibodyb/ antinuclear antibody (ANA)c/ rheumatoid factor (RF)

Definite diagnosis requires at least 4 criteria. In the absence of other (systemic) autoimmune disease, the diagnosis is primary SS.

Therapy of SS1) symptomatic: artificial tears, physostigmine (?)2) systemic manifestations: myositis, pneumonitis, neuritis –

corticosteroid and/or Imuran or other immunosuppressivedrugs

3) parotitis: NSAID or corticosteroid (sialolithiasis or suppurative parotitis should be excluded!)

4) B cell lymphoma with moderate malignity

SclerodermaScleroderma

Definition: Inflammatory/degenerative disease of the connectivetissues with consecutive fibrosis. Skin, vessels, and muscles areinvolved, less commonly also internal organs (GI system, lungs, heart,kidney).Classification:1. Diffuse cutaneous scleroderma (progressive systemic

sclerosisnak; PSS)2. Limited cutaneous scleroderma (acrosclerosis forms, e.g. CREST)3. Overlap syndromes, mixed connective tissue disease (MCTD) and

undifferentiated connective tissue disease (UCTD) 4. Localized scleroderma (morphea & linear scleroderma)

Epidemiology: not rare; incidence: 19/1 million; prevalence 19-75/100,000. More common in women; in the 30-55 ys age group, male:female ratio is 7-12:1.

Raynaud’s phenomenon

Nailfold capillaries in scleroderma

Morphea (generalized)

Severe acrosclerosis

Calcinosis insclerodermaCalcinosis in scleroderma

Teleangiectasia in scleroderma

PSS

PSS

Centromere antibodies in acrosclerosis

Nucleolar antibodies in scleroderma

Bibasilar pulmonaryfibrosis in PSS

Classification criteria of sclerodermaClassification criteria of scleroderma (ARA, 1980)(ARA, 1980)

A/ Major criterium:1. Proximal scleroderma: symmetric thickening, tightening, and induration of the skin of the fingers and the skin proximal to the MCP or MTP joints. The changes may affect the entire extremity, face, neck, and trunk (thorax and abdomen).

B/ Minor kritériumok:2. Sclerodactyly: as above limited to the fingers3. Digital pitted scars or loss of substance from the fingerpad: depressed areas at tips of fingers or loss of digital pad tissue as a result of ischemia.4. Bibasilar pulmonary fibrosis: bilateral reticular pattern of linear or lineonodular densities most pronounced in basilar portions of the lungs on standard chest roentgenogram: may assume appearance of diffuse mottling or “honeycomb” lung. These changes should not be attributable to primary lung disease.

Definite diagnosis requires the major and 2 minor criteria.

SCLERODERMA-SCLERODERMA-LIKELIKE DISEASESDISEASES EOSINOPHILIC FASCIITIS: (Shulman’s syndrome)diffuse fasciitis with eosinophilia) MIXED CONNESTIVE TISSUE DISEASE (MCTD ) (Sharp’s syndrome): A mixture of SLE, scleroderma, PM, RA (SS).Clinical picture: most prominent symptoms are:

Raynaud’s phenomenon,synovitis: arthritis/arthralgia,„sausage-like" fingers, hands and/or sclerodactyly,esophagus motility disorder (dysphagia),myositis (CPK elevation),pneumonitis, pulmonary fibrosis.

Laboratory: U1-RNP antibodies

"OVERLAP" SYNDROMES AND UCTDUCTD = in most cases, preceding SLE or scleroderma

Therapy of scleroderma:1) systemic: penicillamine (ineffective)2) vasodilators (Ca-channel blockers, prostacyclin)3) GI system: reflux - metoclopramide, slow motility –

octreotid, antibiotics4) pulmonary hypertension: ACE-inhibitors are ineffective,

prostacyclin infusion5) pneumonitis/fibrosis: corticosteroid/cytostatics6) kidney: ACE-inhibitors

Polymyositis/Dermatomyositis(Idiopathic inflammatory myopathies)

Definition: a heterogenic group, characterized byproximal muscle weakness (involvement of shoulder and pelvic girdle).

Classification:I. Adult polymyositis (PM)II. Adult dermatomyositis (DM)III. Myositis associated with malignancyIV. Childhood myositisV. Myositis associated with systemic autoimmune diseaseVI. Other (inclusion body, eosinophilic and localized)

Gottron’s sign in DM

Gottron’s sign in PM

Splinter haemorrhage sign in PM/DM

Heliotrope rash in DM

DM – shawl sign

Lymphocytic infiltration in early PM

Classification criteria of PM/DM (Bohan & Peter, 1975)

1. symmetrical proximal muscular weakness2. elevated serum enzymes (CPK, LDH, transaminases, aldolase)3. Characteristic triad by EMG:

a) small amplitude, short polyphasic waves, b) fibrillation, irritability, c) spontaneous, bizarre discharges

4. Biopsy (=infiltration, necrosis, degenerative-regenerative signs5. Heliotrope rash*--------* Gottron’s papules or Gottron’s sign are thought to be more specificDiagnosis: PM = 4 criteria; DM = 5th criterium + 4 other)

Autoantibodies specific for PM/DM

a) anti- ‘synthetase’ antibodies, specific for ‘anti-synthetasesyndrome’anti-aminoacyl-tRNA synthetase antibodies:

anti-histidyl- (= Jo-1)anti-alanyl- (= PL-12)anti-threonyl- (= Pl-7)anti-isoleucyl-(= OJ)anti-glicyl- (= EJ)

b) anti- SRP (signal recognition particle), specific for anothersubgroup

c) other autoantibodies:anti-Mi-2 (antibody against a 220 kD nuclear protein)anti-MAS (antibody against a 4S sedimentation RNA)

Therapy of PM/DM:1) early diagnosis – early treatment!2) high dose corticosteroid (CS)3) in DM, especially when CS resistant: IVIG4) Imuran or methotrexate5) Other: e.g. cyclosporin

Relapsing Polychondritis

Definition: Rare destructing inflammatory disorder, frequently in relapsing form, affecting cartilages in many organs.

Pathogenesis: directly pathogenic autoantibodies against type II collagen and proteoglycan.

Diagnostic criteria of polychondritis (McAdam et al, 1976)1. 1. symmetrical auricular chondritis2. 2. nonerosive, seronegative polyarthritis3. 3. nasal chondritis3. 4. eye involvement (conjunctivitis, keratitis, scleritis/episcleritis,

uveitis)5. 5. Upper airway (larynx-, trachea-) chondritis6. 6. Cochlear and/or vestibular functional impairment (hearing loss,

tinnitus, vertigo)Diagnosis: 3 (or more) criteria present.

Therapy: CS, cyclosporine

Polychondritis ofthe ear