Musculoskeletal disorders 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 painAvascular 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

Mechanical arthropaties

Osteochondritis and similar disorders

• „Avascular necrosis“

– Etiology unclear

• Sites

– Femoral head (Legg-Calvé-Perthes)

– Tuberositas tibiae (Osgood-Schlatter)

– Os naviculare (Köhler)

– Vertebral bodies (Scheuermann)

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

• Hypermobility-related pain

– Overuse injury

Trauma

• Osteochondritis dissecans (transchondral

fracture with fragment separation)

• Traumatic arthropathy (following haemarthros)

• Non-accidental trauma

Inflammatory disorders

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

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)

Hemato-oncological diseases

• Generalised

– Haemofilia

– Hemoblastsis

– Lymphoma

– Neuroblastoma

• Localised tumors

– Osteosarkoma

– Ewing sarkoma

– Synovial tumors (villonodular synovitis?)

Idiopathic/chronic pain

syndromes

• „Pain amplification“ syndromes

• Localised

– CRPS (Complex Regional Pain Syndrome,

RSD Reflex Sympathetic Dystrophy, Sudeck´satrophy)

• Generalised

– Fibromyalgia

• „Growing pains“

• http://www.pmmonline.org/

Chronic inflammatory diseases

• Vasculitides

– Henoch-Schönlein purpura

– Kawasaki disease

• Juvenile Idiopathic Arthritis

• Rare connective tissue diseases

– 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 the first 6 months

– „onset“ types

• Re-classification later on

• Each group

– Criteria, descriptors, exclusions

JIA classification

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

Disease assessment – disease

activity and damage

• Core set of outcome measures

– Global assessments physician and patient

– Active and limited joint counts

– Disability score

– ESR

• ACRpedi, JADAS – composite disease

activity score

• Definitions of improvement and relapse

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: sJIAPetty 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

Clinical features of sJIA

• Fever often preceding arthritis, systemic unwellness

• Arthritis – variable, often destructive polyarthritis

• Pericarditis

• High non-specific inflammation, activation of coagulation pathways

• Acute complication: MAS

• Chronic complications

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

Complications: osteoporosis

Ca and Vitamin D3 supplementation

• calcitonin, bisphosphonates (oral alendronate, i.v.

pamidronate) Noguera et al 2003, Steelman and Zeitler 2003

Complications: growth retardation

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

• Therapy

– Corticosteroids, cytokine inhibitors – IL-1 and IL-6 blockade (anakinra, tocilizumab)

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

Psoriatic arthritis

• Artritida + psoriasis or arthritis + nail

pitting/psoriasis in 1st degree

relative/dactylitis (2 of 3)

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)

Acute anterior uveitis (iridocyclitis)

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

Boy, 8 y

Boy, 5 let

„Kissing“ ulcers –

necrotising skin vasculitis

Boy, 12 y

• Angiopathy

Angiopathy

Angiopathy: nailfolds

Nailfold capillaroscopy

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

19.9.2000 – before therapy

20.5.2001 – after 8 months

→

HE 10x, intermysial and perivasculůar infiltration (mo/ma CD68+, Tly

CD3+CD4+, CD3+CD8+), fiber size variation, degener/regener.

Late complications of JDM

• Lipoatrophy Calcinosis

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

Chapel Hill Consensus vasculitis

nomenclature

Jennette JC et al, A&R 2013

Distributopn of vessel involvement

Jennette JC et al, A&R 2013

IgA Vasculitis (Henoch-Schönlein)

• Most common paediatric vasculitis

Definition :

- vasculitis with IgA1 dominant imune deposits affecting small blood

vessels

- typically skin, GIT, joints, kidneys

- glomerulonephritis indistinguishable from IgA nephropathy

Jennette JC…:Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

Arthritis Rheum.2012: 20143 (65):1-11

IgAV

Classification criteria:

- palpable purpura with predominant distribution overlower extremities

+ at least 1 of: - abdominal pain

- histopathology

- arthritis/arthralgia

- renal involvement

Ozen S et al.: EULAR/PRINTO/PRES criteria for HSP, childhood PN, WG a TA: Ankara 2008: Part II: Final classificationcriteria. Ann Rheum Dis 2010: 69: 798-806

IgAV – course and prognosis

• Variable, often relapsing– 1/3 – acute disease, ovet wwithin 2 wks

– 1/3 – within 1 month

– 1/3 – recurrent course for several months

• IgAV nephritis– 1,6-3% terminal renal disease

Eleftheriou and Brogan : Therapeutic advances in the treatment of vasculitis, Pediatric Rheumatology (2016) 14:26

Therapy

• Analgesia– NSA

• Corticosteroids– Indicated in case of: Orchitis, CNS vasculitis or other major organ disease.

– Severe abdominal pain, enterorrhagia

– 1-2mg/kg/day

• IgAV– Pediatric nephrology consult

– ACE inhibitor when persistent proteinuria

– Renal biopsy result informs therapeutic decision

Nienke de Graeff et al:Evidence Based Recommendations for Diagnosis anf Treatment of KD and HSP, SHARE – Complete

list of recommendations (publikace v přípravě)

Kawasaki disease (KD)

• 2nd most common primary paediatric vasculitis

• Asian ethnicity prevails

• Systemic vasculitis affecting medium-sized arteries

• 85% of patients are < 5 yrs (max. incidence 18-24 months)

• Most frequent cause of acquired heart disease in developed countries

• 15-25% untreated patients develop coronary aneurysms (CAA)

• 2-3% untreated patients die

Elephteriou D..: Management of KD, Arch Dis Child 2014 , 99:74-83

Kawasaki disease (KD)

Diagnostic criteria (AHA) :

Fever at least 5 days + at least 4 of :

1. erythema and induration of palms and soles→ desquamation duringconvalescent phase

2. rash - polymorphous

3. conjunctivitis

4. mucous membrane changes

5. cervical lymphadenopathy often asymetrical >1,5 cm

Klasifikační kriteria KD Ozen et al 2006

Horečka alespoň 5 dnů (mandatorní) + 4 z:

• Změny na periferii končetin nebo perineálně

• Polymorfní exantém

• Oboustranná injekce spojivek

• Změny rtů a dutiny ústní: erytém orální a

faryngeální sliznice

• Krční lymfadenopatie

V přítomnosti postižení CA (dle ECHO) a horečky stačí

méně než 4 kritéria (přesný počet vyžaduje validační

studii).

Labs

•ESR, CRP, FBC, LFTs (AST/ALT), renální function,

albumin.

•Dif. Dg. From other (infection, HLH…):

–Feritin, lumbar tap

•Risk stratification:–Na, ALT, PLT, CRP, albumin.

•Monitoring:–ESR (prior to IVIG), CRP, FBC

Other investigations

•Echo in ALL suspects immediately

•F/U ECHO 2 wks post 1st IVIG –When initially normal

–Ijn ALL another F/U 6-8 wks later

•Persistent inflammation–ECG + ECHO weekly

•Abnormal 1st echo–F/U weekly until stable

Therapy

•Start as soon as possible

IVIG

•IVIG 2 g/kg

ASA

•30-50 mg/kg/day until–Afebrile for 48h

–Clinically improving

–Dropping CRP

•Reduction to 3-5 mg/kg o.d.

•When CAA–longterm

Corticosteroids

•Indications: – IVIG Resistence

– Kobayashi score ≥5 [Sleeper et al.]

– HLH

– KSS

•Consider to add to IVIG immediately:– Infants

– Aneurysms identified at onset

Additional therapies

•Anti TNF-alpha (infliximab, adalimumab)

•Anticoagulation

•Angioplasty…

•Adjustment of vaccination scheme

–No vaccines for 6 months

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.

PAN: Deep skin biopsy

• Types of vessel wall involvement:

Focal Segmental

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(

cPAN – cutaneous findings

• Livedo reticularis Purpura

cPAN: Evolution of skin ulcers

Granulomatous vasculitis

• GPA – granulomatosis with polyangiitis

• EGPA

Classification criteria GPA 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)

Pulmonary angiography in 10-years old girl

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)

PACNS / GANS

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

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

Linear scleroderma