Pavla Doležalová Klinika dětského a dorostového lékařství 1 · Pavla Doležalová Klinika...

Rheumatic diseases in children

Pavla Doležalová

Klinika dětského a dorostového lékařství 1.LFUK

Ke Karlovu 2, Praha 2

•Pain or limb dysfunction - various

organ system involvement

•Musculoskeletal pain - common in

chidren (4-30% otherwise healthy

kids)

• Arthritis - small proportion:

108,5/100000 children under 16

(transitory conditions in most cases,

duration shorter than 6 weeks)

• Chronic (idiopathic) arthritis (over

6 weeks duration):

5,3 - 19,6/100000 dětí

History

• Pain characteristics:

– type of the pain (dull, sharp, colicky…)

– Intenzity, duration, localisation, radiance

– Predisposing and relieving factors (relation to activity)

– Time location of the most intensive pain (morning,

evening, night)

• Presence of stiffness? (eg early morning)

• Limb dysfunction?

• Age-appropriate activities?

• Presence of visible changes? (skin colour, oedema)

Joint symptoms

Příznaky Souvislosti Preferenčnílokalizace

Specifické příznaky

Mechanické Po tělesnéaktivitěČastěji ustarších dětí

KolenoKotník

Blokáda,instabilitaBolest:ostrá,náhlá,přechodná,úlevapo odpočinkuPřechodná synovitida

Zánětlivé Po klidu Jakýkolikloub

Časná ranní ztuhlostBolest: palčivá nebo tupá,přetrvávající kolísavě, nezmizí zcelapři odpočinku, může probudit zespaní. Otok, kožní teplota zvýšená

Idiopatické PředcházejícítraumaStres

KončetinaGeneralizované potíže

Bolest:trvalá, zneschopňujícíUnavitelnost, školní absence, výraznádysfunkce, poruchy spánku

Basic joint exam

• Color

• Bone structures

• Muscle bulk

• Length and width discrepancy

• Limb position

• Appearance of the painful site

Joint exam: Palpation

• Skin temperature

• Oedema

– soft tissues, effusion, bone overgrowth

• Site of maximum pain

– joint space, soft tissues, bone

Joint exam: ROM

• ROM

– passive

– active

• Compensatory movements

• Pain with motion

Differencial diagnosis of

musculoskeletal pain Avascular necrosis and degenerative conditions:

Perthes,osteochondritis,chondromalacia patellae,hypermobility

Reactive arthritis: post:-streptococcal,-enteritic, -viral

Trauma, non-accidental injury

Hematological diseases: hemoblastosis,hemofília,lymphoma

Rachitis, other metabolic disorders and endocrinopathies

Infections: septic arthritis, osteomyelitis

Tumors: cartilage, bone, muscle, synovium, blood vessels

Idiopathic pain: localised, generalised

Systemic connective tissue diseases: SLE, vasculitis,

dermatomyositis, scleroderma

Osteochondritis and similar disorders

• „Avascular necrosis“

– Etiology unclear

• Localisation

– Femoral head (Legg-Calvé-Perthes)

– Tuberositas tibiae (Osgood-Schlatter)

– Os naviculare (Köhler)

– Vertebral bodies (Scheuermann)

• Patelo-femoral syndrome (anterior knee pain syndrome, chondromalacia)

Post-infectious arthropathies

• Acute rheumatic fever, poststreptococcal reactive

arthritis

• Postenteritic arthritis: gut infections symptomatic

and asymptomatic (Salmonella, Shigella, Yersinia,

Helicobacter), acute anterior uveitis, mucous

membrane ulcerations, often HLA B-27+

(+urethritis=Reiter´s syndrome; Chlamydia)

• Postviral arthritis (EBV, CMV,rubella,

ADV,VZV,parvoB19)

Trauma

• Osteochondritis dissecans (transchondral

fracture with fragment separation)

• Traumatic arthropathy (following haemarthros)

• Non-accidental trauma

Hemato-oncological diseases

• Generalised

– Haemofilia

– Hemoblastsis

– Lymphoma

– Neuroblastoma

• Localised tumors

– Osteosarkoma

– Ewing sarkoma

– Synovial tumors (villonodular synovitis?)

Infection

• Lyme disease

• Viral arthritis (rubella, parvovirus, HB, herpesvirus)

• Septic arthritis

– Staph, HIB, Pneumococcus, Salmonella

– Haematogeneous

– Acte - systemic signs, subacute, chronic – difficult dg (TB!!!)

• Osteomyelitis acute, subacute, chronic

• Chronic recurrent multifocal osteomyelitis (CRMO), SAPHO syndrome

Idiopathic pain syndromes

• Localised

– RSD (Reflex Sympathetic Dystrophy, Sudeck

atrophy)

– „Growing pains“

– Fibromyalgia

• Chronic pain syndrome

Diseases affecting musculoskeletal

system: infants and toddlers

• Septic arthritis and osteomyelitis

• Kawasaki disease

• Discitis: ?etiology, back pain, often preceded

by trauma or infection. XR, bone scan

• Non-accidental trauma: child abuse

• CINCA/NOMID

• Periodic fever syndromes (HIDS, TRAPS)

Diseases affecting musculoskeletal

system: Preschool and school children

• Transient coxitis, postinfectious arthropathy

• Lyme disease

• Henoch - Schönlein purpura

• Benign hypermobility syndrome

• Growing pains

• Perthes disease

• Acute haemoblastosis, bone tumours, pigmented

villonodular synovitis, sarcoidosis

• Genetically-determined disorders: bone dysplasias,

collagen disorders, metabolic diseases

Diseases affecting musculoskeletal

system: adolescence • Back pain

• Patelofemoral pain

• Slipped upper femoral epiphysis

• Diffuse connective tissue diseases: SLE,

JDM,MCTD,SS

• Systemic diseases with joint symptoms: IBD,

CF, hemofilia, DM

• Idiopathic pain syndromes: localised (RSD),

generalised (fibromyalgia)

Chronic inflammatory diseases

• Vasculitides

– Henoch-Schönlein purpura

– Kawasaki disease

• Juvenile Idiopathic Arthritis

• SLE, JDM, scleroderma, MCTD…

Rheumatic diseases in children-

epidemiology

Incidence Prevalence

JIA 5,3 - 19,6 minim. 1/1000

JSLE 0,5 - 0,6 10% new dg.

JDM/JPM 0,2 - 0,5 (0,15)

SS 0,45 - 1,2 total. ?

1,0-9,0% do 20 let

HSP 13,5 ?

KD 5,95 - 7,6 do 5 let ?

JUVENILE IDIOPATHIC

ARTHRITIS:

Diagnosis per exclusionem

Classification of Juvenile Idiopathic

Arthritis

2nd revision-Edmonton 2001

Definition: Arthritis of unknown origin affecting a

person younger than 16 years of age of minimum 6

weeks duration in at least one joint

JIA classification

Clinical features during first 6 months

Criteria, descriptors, exclusions

1. Systemic arthritis

2. Polyarthritis IgM RF-

3. Polyarthritis IgM RF+

4. Oligoarthritis: persistent, extended

5. Arthritis with enthesitis

6. Psoriatic arthritis

7. Other arthritis

Systemic JIA

Still’s disease: epidemiology

• sJIA: 10-15% of all JIA (annual incidence

2-20/100.000) Cassidy and Petty, 2000

– any age, peak onset 2 years

– boys and girls equally affected

Definition and classification: sJIA Petty et al, 1998

• Arthritis with or preceded by daily fever of at least 2 weeks’ duration

(documented as quotidian for minimum 3 days) accompanied with

one or more of:

-Evanescent, non-fixed erythematous rash

– Generalised LNpathy

– Hepato or splenomegaly

– Serositis

Laboratory features of sJIA

• Non-specific inflammatory activity – high ESR, CRP, neutrophilia, thrombocytosis

• Activation of coagulation pathways

• Endothelial activation

• Increased levels of circulating pro-inflammatory cytokines and their inhibitors (IL-6, IL-18, TNF-R, IL-1Ra, IL-10)

• Increased ferritin concentration

Complication: Macrophage

activation syndrome - MAS

• Persistent fever and malaise, neurological abnormalities, rash

• Acute hepatopathy, multi-organ failure

• Cytopenia with haemophagocytosis in marrow aspirate

• Consumptive coagulopathy with DIC

fibrinogen and ESR, d-dimer, FDP, APTT

• Drop in ESR and fibrinogen

• Raised ferritin and IL-18

sJIA disease course and outcome

• 3 clinical subtypes

– Monocyclic (11%)

– Intermittent (34%)

– Persistent (55%) Lomater et al 2000

• Active disease after >10 years follow-up in 23-58 % of sJIA patients

• 81 adults with JIA, med 21 years duration: 39% active disease, significantly higher HAQ and lower SF-36 than controls Foster et al 2003

• Mortality all JRA: <0.29% (0.08% standardised death rate USA), 2/3 sJRA Wallace and Levinson 1991

Oligoarticular JIA

• No affected joints < 5

• Frequency: 60% of all JIA

• Subtypes:

– Persistent

– Extended

Clinical picture • Onset 2-3 years, girls predominate

• Knee, ankle

• Limp, stiffness, swelling, flexion deformity

• Lab often normal

• Fever and general symptoms – careful differential dg

– Malignancies (leukemia, neuroblastoma)

– Infections, other systemic diseases

• CAVE: ANA

• eyes

• psoriasis

• local growth disturbancies

Prognosis

• Excellent if treated early and appropriately

• Chronic uveitis – limits favourable prognosis

Oligoarthritis extended

• Initial 6 months less than 5 joints affected,

polyarticular course later on

• Often elevated inflammatory activity

• Prognosis varies, similar to poly-JIA

• Therapy similar to poly-JIA

Polyarthritis RF negative

• More than 4 affected joints

during initial 6 mo

• ↑ nonspecific inflammation

• Often foot, wrist, hip

involvement – negative

prognostic factor

Polyarthitis RF positive

• 1-2% JIA

• Often adolescent girls

• Similar to adult RA

• Rapidly progressive

destruction, symmetrical

small joint disease

Arthritis with enthesitis

• „Enthesis“ = insertion of tendon or ligament into

bone

• Plantar, Achilles tendon, knee, pelvis

• Lower extremities, SI

• Often HLA B-27, enteropathogen-triggered

• Exclude IBD

• Therapy: local CS, Salazopyrin, (MTX, Enbrel)

JIA – therapy principles

• Multidisciplinary approach

• Drug treatment

– NSAID

– Corticosteroids – intraarticular, systemic

– Methotrexate, Sulphasalazine

– Biologics – TNFα, IL-1, CTLA blockade

– Osteoporosis prevention, topical eye treatment

• Physical and occupational therapy

• Education, supportive/social care

Juvenile idiopathic

inflammatory myopathies

Epidemiology

Incidence Prevalence

JIA 5,3 - 19,6 minim. 1/1000

JSLE 0,5 - 0,6 10% nových dg.

JDM/JPM 0,2 - 0,5 (0,15)

SS 0,45 - 1,2 celk. ?

1,0-9,0% do 20 let

HSP 13,5 ?

KD 5,95 - 7,6 do 5 let ?

Classification (Rider a Miller, 1997)

IIM = Idiopathic Inflammatory Myopathies:

Chronic striated muscle inflammation of

unknown origin

JDM: 85% JPM: 8%

DG criteria JDM/JPM (Bohan a Peter, 1975)

• Typical skin manifestations

• Symmetrical proximal muscle

weakness

• Muscle enzymes

• EMG changes

• Histopathology

JDM investigations

Labs

• Inflammatory markers

• Muscle enzymes (all)

• Immunology: Ig,C, ANA, ENA, immunoblot

(MAS, MSA) B-ly (CD 19), CD3+CD8+ T-ly

• Endothelial damage (vWF, neopterin, adhesion

molecules)

• Metabolic screening

JDM investigations

• Muscle MRI - T2W, STIR

• EMG - directed

• Muscle biopsy - directed

Early signs of JDM

• Most common: Muscle weakness +

characteristic skin rash (100%,Pachman, J

Rheumatol. 1998)

• Less common: Myopathic syndrome plus

other vasculitis or „dermatomyositis sine

myositis“

• Warning signs: dyslalia, voice change,

dysphagia, fluid regurge

CAVE:

• Muscle enzymes normal in up to 10% (Pachman

1998)

• Inflammatory parameters can be normal, ANA

neg

• Typical skin changes may be initially absent

• Non-targeted biopsy or EMG may be

noninformative in up to 20% (Pachman 1998)

JDM /JPM - DIF. DG.

• Postinfectious myositis (influenza A,B, coxackievirus B, toxoplasmsis, trichinosis, staph pyomyositis)

• Neuromuscular disorders (spinal atrophy, myastenia)

• Metabolic and heritable myopathies (glykogen storage dis, lipidoses, carnitin def, -oxidation disorders, dystrophinopathies…)

• Secondary myopathies (endocrinopthies, steroid induced )

• Other CTD (MCTD, SLE, vasculitis..)

THERAPY

• Drug treatment:

- CS (+ osteoporosis prevention, K suppl)

- immunosuppressive (hydroxychloroquine, MTX,

CFM, CyA, IVIG)

• Multi-discipliplinary: PT/OT, supportive,

alimentation, hydration (myoglobinuria)

PROGNOSIS

Disease course:

• monocyclic : limited, steroid responsive (27%)

• persistent (chronic ulcerative (33%)

• polycyclic (chronic nonulcerative): (40%)

Vasculitides

• Primary systemic vasculitis

New classification of childhood vasculitis Ozen et al 2006

I Predominantly large vessel vasculitis

• Takayasu arteritis

II Predominantly medium sized vessel vasculitis

• Childhood polyarteritis nodosa

• Cutaneous polyarteritis

• Kawasaki disease

III Predominantly small vessels vasculitis

(A) GRANULOMATOUS

• Wegener’s granulomatosis

• Churg-Strauss syndrome

(B) NON-GRANULOMATOUS

• Microscopic polyangiitis

• Henoch-Schönlein purpura

• Isolated cutaneous leucocytoclastic vasculitis

• Hypocomplementic urticarial vasculitis

IV Other vasculitides

• Behçet disease

• Vasculitis secondary to infection (including hepatitis B associated polyarteritis nodosa), malignancies, and drugs, including hypersensitivity vasculitis

• Vasculitis associated with connective tissue diseases

• Isolated vasculitis of the central nervous system

• Cogan syndrome

• Unclassified

Etiopathogenesis of PSV

• Etiology

– Unknown

– Suspected infectious triggers: HB, strep,CMV, Staph aureus, others

• Pathogenesis - principles

– Pathogenic IC formation and deposition

– Autoantibodies (AECA, ANCA)

– Cellular and molecular immune responses (cytokines, adhesion molecules)

– Granuloma formation

– Alteration/damage to EC (infection, toxins, tumors)

Henoch-Schönlein purpura

• Most common PSV in children, typically

school-aged children

• Small vessels, IgA deposits

• Usually benign course

• Prognosis limited by organ involvement

• Predomint localisations

– Skin (typically distributed purpura)

– Acute, self-limited arthritis

– GI vasculitis

– Nephritis

Henoch-Schönlein purpura Ozen et al 2006

Palpable purpura (mandatory criterion) in the presence of at least

one of the following four features:

• Diffuse abdominal pain

• Any biopsy showing predominant IgA deposition

• Arthritis* or arthralgia

• Renal involvement (any haematuria and/or proteinuria)

*Acute, any joint.

Kawasaki disease

• 2nd most common PSV

• Medium-vessel involvement

• Most common in children below 5 years of age, ethnicity important

• Acute, dramatic onset of systemic disease with variable organ manifestations

• Predominant involvement of heart and coronary arteries with aneurysm formation

• Prognosis limited by presence of aneurysms

Kawasaki disease • Fever (100%)

– >5 days

• A: Conjunctivitis (85%) – Bilat., bulbar, non-exsudative

• B,C: Mucosal changes (90%)

– Red lips, strawberry tongue, oropharyngeal erythema

• D: Lymphadenopathy(70%) – Cervical, acute, non-

suppurative, >1,5 cm

• E: Rash (80%)

– Polymorphous

• F,G: Extremity changes.(70%)

– Erythema palms and soles, edema, peeling

Classification criteria for

Kawasaki disease Ozen et al 2006 Fever persisting for at least 5 days (mandatory criterion) plus

four of the following five features:

• Changes in peripheral extremities or perineal area

• Polymorphous exanthema

• Bilateral conjunctival injection

• Changes of lips and oral cavity: injection of oral and pharyngeal

mucosa

• Cervical lymphadenopathy

In the presence of coronary artery involvement(detected on echocardiography)and

fever, fewer than four of the remaining five criteria are sufficient (the exact number

of criteria required is to be defined in the validation phase).

KD – other symptoms

• Musculoskeletal: arthralgia, arthritis

• CNS: aseptic meningoencephalitis, palsies, stroke

• GIT: abd pain, hepatopathy, hydrops of

gallbladder, pancreatitis

• Urinary: urethritis, interstic. Nephritis

• Cardiopulmonary:

– acute - peri/myocarditis, valvulitis, CA dilatation, heart

failure,

– subacute-CA aneurysms, ischemia,

– convalescent-angina, IM

KD – course and therapy

Phase Week Therapy

Acute 1-2 IVIG 2g/kg

(pulse IVMP)

Subacute 3-6 ASA 80-100 mg/kg 14d.

Convalescent 4-10 ASA 3-5 mg/kg 6-8 wk

Dipyridamole

Anticoagulation

Angioplasty, bypass,

transplant

Juvenile polyarteritis - cPAN

• Necrotising inflammation of medium and/or small arteries

• Epidemiology

– worldwide, rare

– equal sex distribution

– peak age at onset 10 years

• Histopathology

– fibrinoid necrosis

– pleiomorphic infiltration

– disarranged wall architecture

– healing with fibrosis.

cPAN – general principles

• Vessel type and size, site (predilection for renal and

GI arteries, severity: brain, CA x skin)

• Extent of vessel involvement

– Focal - aneurysm, rupture

– Segmental – stenosis, occlusion

• Quantity (organ-specific symptoms, systemic

features, multiorgan failure)

cPAN – clinical characteristics (Cassidy and Petty 2001)

• Fever (84%)

• Arthritis/arthralgia (74%)

• Abdominal pain (68%)

• Myalgia (67%)

• Skin:

– rash (58%)

– edema (20%)

– petechiae (17%)

• Renal (25%)

• Cardiac (21%)

• Nervous system

– seizures (16%)

– other (10%)

• Mucous memb (17%)

• Respiratory (7%)

• Cervical LN(<5%)

• Splenomegaly (6%)

Treatment principles • Induction of remission

– Corticosteroids (CS) (i.v.)

– Cyclophosphamide i.v. pulse 500-1000mg/m2 or oral 2-3 mg/kg/day 2-3 months (cum dose up to 7(-10) g/m2 )

– Plasmapheresis, IVIG, MTX, AZA, CyA, colchicine, thalidomide in combinations

• „Standard“ therapy failure

– antiTNF (infliximab) (Bartolucci et al 2002), ASCT (Wedderburn et al 2001)

• Remission maintenance

– Azathioprin or MTX, slow CS withdrawal

Additional therapy • Vasodilation (prostacyclin analogues for

peripheral ischaemia) (Gianviti et al 1996, Zulian et al 1998)

• Antihypertensives

• Antithrombotic therapy (ASA, LMWH)

• Prevention and therapy of secondary osteoporosis

• Antimicrobial/antimycotic therapy and prophylaxis (PCP, strep), IVIG replacement

• Physical therapy (neurological deficits, musculoskeletal)

Granulomatous vasculitis

• Wegener´s granulomatosis (WG)

• Churg-Strauss syndrome

Classification criteria for Wegener´s

granulomatosis Ozen et al 2006

3 of the following:

• Abnormal urinanalysis

• Granulomatous inflammation on biopsy

• Nasal sinus inflammation

• Subglottic, tracheal or endobronchial stenosis

• Abnormal CXR or CT

• PR3 ANCA or C-ANCA staining

TAKAYASU ARTERITIS

• Segmental arteritis causing stenoses of large

muscular arteries, prediminantly aorta and

its main branches

• Abdominal aorta more often involved in

children, often systemic hypertension

• Non-specific symptoms common

– Fevers, elevation of ESR/CRP, malaise, weight

loss, palpitations, headaches

– Vascular bruits, pulse and BP assymetry

Classification criteria for

Takayasu arteritis

• Angiographic abnormalities (conventional,

CT, MR) of the aorta or its main branches +

at least one of:

– Decreased peripheral artery pulse(s) and/or

claudication of extremities

– Blood pressure difference >10 mm Hg

– Bruits over aorta and/or its major branches

– Hypertension (related to childhood normative

data)

Isolated CNS vasculitis/vasculopthy

• GANS, PACNS, BACNS (Calabrese 2001, Gallagher et al 2001, Stone et al 2001)

• Acquired focal CNS symptoms – Acute severe headache, focal neurologic deficit, gross motor

deficit, hemiparesis, cranial nerve involvement, cognitive dysfunction, seizures (Benseller and Schneider 2004)

• Angiographic or histopathologic features of CNS angiitis

• Absence of systemic disease (clinical and laboratory)

Systemic lupus erythematosus

Definition: ..“episodic, multisystem

autoimmune disease characterised by

inflammation of blood vessels and

connective tissue and presence of

antinuclear antibodies“

Clinical course - variable, unpredictable,

potentially life threatening

Epidemiology: adolescence, 4-5x more

frequent in girls

SLE - DG CRITERIA (ACR) • Malar rash

• Discoid lupus

• Mucocutaneous ulceration

• Non-erosive arthritis

• Nephritis (proteinuria >0,5g/d, cel.casts)

• Encefalopathy (seizures, psychosis)

• Pleuritis or pericarditis

• Cytopenia

• Positive immune serology

• Positive ANA

SLE - clinical I

• Constitutional: fever, fatigue, weight loss

• Mucocutaneous: malar, discoid lupus, periungual erythema, photosensitivity, maculopap.exant., alopecia, ulcerations

• Musculoskeletal: arthritis/arthralgia, myopathy, asept.necrosis

• Vascular: arterioles, venules. Lupus crisis - acute generalised vasculitis, RS, thromboflebitis, livedo, purpura

SLE - clinical II

• Heart: pericarditis, myocarditis, veruccous

endocarditis (Libmann-Sachs)

• Lungs: pleuritis, pneumonitis,

pulm.haemorrhage, thromboembolism

• GIT: dysmotility, malabsorption, colitis,

peritonitis, ascites, pancreatitis, thrombosis

• RES: Hepatosplenomegaly, lymphadenopathy

• Autoimunne endocrinopathy

SLE - clinical III

• NS: 20-35% children. Psychosis (organic or

functional), seizures, chorea, vascular accident,

neuropathy, pseudotumor cerebri

• Eyes: retinal vasculitis (cytoid bodies),

papilloedema, retinopathy, episcleritis

• Kidneys: 75% children. Main long-term

prognostic factor. Often asymptomatic, rarely

nephrotic syndrome, haematuria, hypertension,

renal failure

SLE - investigations

• LABORATORY: non-specific

inflammatory activity, anemia, cytopenia,

autoantibodies (ANA, dsDNA, ENA,

ACLA), C3,C4, renal and hepatic

• IMAGING: organ involvement (XR, US,

MRI, EEG, SPECT)

• BIOPSY: skin, renal

• Disease activity and damage evaluation:

SLEDAI, BILAG..

SLE - therapy

• Multidisciplinary approach

• Drug: NSAID, glucocorticoid, antimalarials,

immunosupressives (azathioprine, CYC,

MTX, CyA, MMF, rituximab),

anticoagulation, Ca and vitD supplementation

• Prevention and management of infectious

complications

• Regime (stress, diet, sun exposure)

• Education and councelling

SLE - prognosis

• Protracted course with remissions and

exacerbations

• Mortality - approx. 15%

• Bad prognostic factors: diffuse proliferative

GNF, persistent CNS disease

• Main causes of death: 1) sepsis 2) renal

insufficiency

NEONATAL LUPUS

• Maternal autoantibodies (mainly anti-Ro) in

foetal circulation from 12th-16th wk gestation,

bind to skin and myocardial structures (AV

node mainly)

• Clinical picture: CCHB, skin manifestations

(erythema annulare, discoid lupus), cytopenia

• Antiphospholipid syndrome (APLS)

• Drug-induced lupus (anticonvulsants, infliximab) - often associated with anti-histone ANA

• Overlap syndromes: MCTD (SLE,JIA,JDM,SS), posit. ENA (anti U1RNP)

• Sjögren syndrome primary and secondary

(xerostomy, keratoconjunctivitis sicca, antiRo,La)

Scleroderma I

• Systemic sclerosis: diffuse (proximal skin,

multiorgan involvement), limited ( CREST:

Calsinosis, RS, Esophageal dysmotility,

Sclerodaktyly, Teleangiectasia)

• Clinical features: oedema-induration-sclerosis-

skin atrophy, calcinosis, RS (90%), ischemic

fingertip ulceration, contractures, weakness,

arthralgia, abd pain, GI dysmotility and

malabsorption, dysphagia, pericarditis, pulm

fibrosis, PH, renal vasculitis with hypertension

Scleroderma II • Localised:

- morphea-oval shaped, circumscripted induration

variable in size, depth and number

- linear scleroderma-often deep tissues involved

incl muscle and bone, epilepsy, organ involvement

• Eosinophilic fasciitis: skin induration with

flexion contractures, eosinophilia,

hypergamaglobulinemia, usually no organ

involvement