infectious and rheumatic disease in children 박 수 성 울산대학교 의과대학...

Infectious and Rheumatic Infectious and Rheumatic Disease in ChildrenDisease in Children

박 수 성박 수 성

울산대학교 의과대학 서울아산병원 정형외과울산대학교 의과대학 서울아산병원 정형외과

1.1. Infectious disease in childrenInfectious disease in children• Acute hematogenous osteomyelitis (AHO)Acute hematogenous osteomyelitis (AHO)

• Acute septic arthritisAcute septic arthritis

• Special conditionsSpecial conditions

2.2. Rheumatic disease in childrenRheumatic disease in children• Juvenile Idiopathic Arthritis (JIA)Juvenile Idiopathic Arthritis (JIA)

IntroductionIntroduction

• A relatively common problem in childrenA relatively common problem in children

– Peak incidence in the first decade Peak incidence in the first decade

– Can cause severe disabilityCan cause severe disability

• Pediatric orthopedic emergenciesPediatric orthopedic emergencies

– A timely & accurate diagnosis is essential for effective tx.A timely & accurate diagnosis is essential for effective tx.

– Early diagnosis & treatment !Early diagnosis & treatment !

Early Dx. & Tx. Early Dx. & Tx.

Pre opPre op Post op 10 MPost op 10 M

Delayed Dx. & Tx. Delayed Dx. & Tx.

Pre opPre op Post op 2 MPost op 2 M

AnatomyAnatomy

• Cortical boneCortical bone– metaphysis ; easy communication btw. subperiosteal metaphysis ; easy communication btw. subperiosteal

& medullary space& medullary space– diaphysis ; dense compact bonediaphysis ; dense compact bone

• Cancellous boneCancellous bone (more pronounced in long bone)(more pronounced in long bone)

– medullary cavity ; rich RES, little bonemedullary cavity ; rich RES, little bone– metaphyseal region ; few RES, more bonemetaphyseal region ; few RES, more bone

• PeriosteumPeriosteum– thick, easily separated, not easily penetratedthick, easily separated, not easily penetrated

• Vessels beneath the physeal plateVessels beneath the physeal plate– small arterial loops into venous sinusoids (turbulence)small arterial loops into venous sinusoids (turbulence)

– gaps in the endothelial wallgaps in the endothelial wall

Changing anatomy of interosseous blood supplyChanging anatomy of interosseous blood supplyChanging anatomy of interosseous blood supplyChanging anatomy of interosseous blood supply

• In infantIn infant

• Before the ossific nucleus is formedBefore the ossific nucleus is formed

• Metaphyseal vessel penetrate into eMetaphyseal vessel penetrate into e

piphysispiphysis

• Early destruction and growth distuEarly destruction and growth distu

rbancerbance

Changing anatomy of interosseous blood supplyChanging anatomy of interosseous blood supplyChanging anatomy of interosseous blood supplyChanging anatomy of interosseous blood supply

• After the ossific nucleus is formedAfter the ossific nucleus is formed

• Epiphysis & Metaphysis have separEpiphysis & Metaphysis have separ

ate blood supplyate blood supply

• Physeal plate provide barrier to the Physeal plate provide barrier to the

spread of infection into epiphysisspread of infection into epiphysis

Pathogenesis of OsteomyelitisPathogenesis of Osteomyelitis

• Causes remain unknown

• Bacteremia a frequent (daily) event

– 50% occurrence following tooth brushing

• Begins in metaphysis of long bone

• Portals of EntryPortals of Entry

Why does acute hematogenous osteomyelitisWhy does acute hematogenous osteomyelitis

begin in the metaphysis ? begin in the metaphysis ?

• Local edema and hematoma limits blood supply and provides medium for bacterial proliferation

• Trauma to metaphysis delays macrophage migration into area

• Poorly developed RES with lack of tissue-based macrophages

• Sluggish circulation favoring deposition of bacteria

Subsequent course of metaphyseal abscessSubsequent course of metaphyseal abscess

Metaphysis within the joint : early septic arthritis Metaphysis within the joint : early septic arthritis Metaphysis within the joint : early septic arthritis Metaphysis within the joint : early septic arthritis

Risk factors Risk factors

• Diabetes Mellitus

• Hemoglobinopathies

• Chronic renal disease

• Rheumatic arthritis

• Immune compromise

Pathogenesis of Septic ArthritisPathogenesis of Septic Arthritis

• Bacteremia

Synovium (RES absence)

Subperiosteal spread

• Direct innoculation

• Bacteremia

Synovium (RES absence)

Subperiosteal spread

• Direct innoculation

• Synovitis & fibrinous exudate

• Synovial necrosis

• Cartilage destruction

– Articular cartilage lacks blood supply,

– Enzymes degrade matrix &collagen

– Immune response even after the bacteria are eliminated.

– Process continues until debris removed from joint

PathogensPathogens

• S. aureus -- still the predominant (60~90%)

• Beta Hemolytic streptococcus -- esp. Group B

• G(-) organisms -- less than 5%

– H. influenzae: esp those cases with negative cultures

if below 3 yrs of ages– P. aeruginosa: after age nine, most common G(-) org.

from puncture wound

DiagnosisDiagnosis• Suspicion – key to Dx.

• History

• Physical Examination

• Laboratory

• Imaging study

• Aspiration - essential

• History History

– fever, malaise, limping

: Refusal to walk, to bear weight or disuse

– history of other infectious disease

– conditions that impair host immunity

eg. Chicken Pox…

– recent trauma

– risk factors; DM, CRD, RA…

• Physical ExaminationPhysical Examination

– Swelling, erythema & warmth

– Tenderness, LOM.

– Pseudoparalysis, limp

cf. Inability to “log roll” the hip (IR, ER) is 90% predictive of hip joint effusion

• Laboratory testLaboratory test

– WBCWBC ; ; not reliable esp. in early stagenot reliable esp. in early stage• only 15% abnormal, shift to left in 65%only 15% abnormal, shift to left in 65%

– ESRESR ; ; best single test (reliable indicator, in 90%)best single test (reliable indicator, in 90%)• not reliable in neonate, anemia, steroid, less than 48-72hrsnot reliable in neonate, anemia, steroid, less than 48-72hrs• return normal within 2- 4 wksreturn normal within 2- 4 wks

– CRPCRP ; ; helpful in early diagnosishelpful in early diagnosis• rise within 6 hrs & return normal within 1 wkrise within 6 hrs & return normal within 1 wk

– Blood cultureBlood culture ; ; even after antibioticseven after antibiotics• 30 ~ 50% positive culture30 ~ 50% positive culture

• Imaging studiesImaging studies

1. Plain Radiographs

2. Ultrasound

3. Bone Scan

4. Computed Tomography

5. Magnetic Resonance Imaging

1. Plain Radiographs1. Plain Radiographs

• Minimal usefulness early in infections

– Bone changes take 7~14 days to appear

• Soft tissue edema may obliterate soft tissue planes

(3days)

• Bone resorption & periosteal new bone formation

• Joint space widening seen in only 40% septic

arthritis

• Most useful to rule out tumor, trauma, other

bony pathology

2. Ultrasound2. Ultrasound

• Useful in detecting joint effusions, subperiosteal abscess, soft tissue swelling

• Best useful when diagnosis in question or need to confirm soft tissue edema or abscess

• Should not delay aspiration

( sono-guided aspiration )

3. Bone scans3. Bone scans

• Test of choice when multiple sites are in question or the site is unknown

• Technetium 99m diphosphonate bone scan

• 3 phase scan, pin hole or magnification

• Can rule out multifocal osteomyelitis & malignancy

• Cold scan; asso with devasc. & subperiosteal abscess

• Should not delay aspiration

Pin hole viewPin hole viewPin hole viewPin hole view

Scans may be misleadingScans may be misleading

• Very early stage < 24hours after onset• Neonate• Patient with sickle cell disease

4. CT4. CT

• Decreased bone density, soft tissue masses

or intraosseous gas

• Good for documentation of sequestration, abscess, S-I joint, spine

• Poor for early acute osteomyelitis, septic arthritis

5. MRI5. MRI

• Useful for detecting soft tissue and marrow abnormalities

• Poor bone detail, high cost, time consuming, may

need sedation

• Probably best used when other data is conflicting

or confusing

F / 20D

F / 6M

F / 14Y

Incision & Drainage instead of arthrotomyIncision & Drainage instead of arthrotomyIncision & Drainage instead of arthrotomyIncision & Drainage instead of arthrotomy

• AspirationAspiration

Ultimate Diagnostic TestUltimate Diagnostic Testforfor

Osteomyelitis and septic arthritisOsteomyelitis and septic arthritis

• Indications for aspirationIndications for aspiration

• Bone tenderness

• Deep soft tissue swelling

• Bone changes on radiographs – periosteal new bone, bone destruction

• Joint effusion

• Fluid analysisFluid analysis

1. Joint aspirate

Nl. Infl. (JIA) SepticClarity clear translucent opaque

Color clear yellow(clear) white(turbid)

Mucin clot good good to poor poor

WBC <200(mm³) 2K-100K 50K->100K

PMN’s <25% 50% >75%

Gram S. Neg. Neg. 30-40% pos.

Septic ArthritisSeptic Arthritis

• WBC > 80,000WBC > 80,000

• Diff. count > 75% neutrophilsDiff. count > 75% neutrophils

• Mucin poorMucin poor

• Sugar 50 mg%Sugar 50 mg%

• Gram stain 1/3 positiveGram stain 1/3 positive

• culture positive in 70-80%culture positive in 70-80%

2. Osteomyelitis

– Metaphysis

• Subperiosteal & bone aspiration

– Gram Stain, cultures• Cultures positive 85-90 % of cases

• Gram stain positive in 30-40%

Differential Diagnosis (AHO)Differential Diagnosis (AHO)

• Rheumatic fever

• Septic arthritis

• Cellulitis

• Malignancy (Ewing’s sarcoma and leukemia)

• Thrombophlebitis

• Sickle cell crisis

• Gaucher’s disease

• Toxic synovitis

Differential diagnosis (Septic arthritis)Differential diagnosis (Septic arthritis)

• Transient synovitis of the hip• Pelvic, sacroiliac, vertebral osteomyelitis• LCP• SCFE• Appendicitis• Rheumatic fever• Leukemia• JIA…….

• History of fever greater than 38.5History of fever greater than 38.500

• Inability to bear weightInability to bear weight• ESR greater than 40mm/hESR greater than 40mm/h• WBC count greater than 12000/WBC count greater than 12000/μμLL

• History of fever greater than 38.5History of fever greater than 38.500

• Inability to bear weightInability to bear weight• ESR greater than 40mm/hESR greater than 40mm/h• WBC count greater than 12000/WBC count greater than 12000/μμLL

• Principles of treatment Principles of treatment (AHO)(AHO)

1.1. Identify the organismIdentify the organism

2.2. Select the correct antibiotics Select the correct antibiotics

3.3. Deliver the antibiotics to the organismDeliver the antibiotics to the organism• IV for 5-7days, oral for 4-5 wks.IV for 5-7days, oral for 4-5 wks.

4.4. Stop the tissue destructionStop the tissue destruction• OP Ix. --- presence of pusOP Ix. --- presence of pus

bone destruction radiologicallybone destruction radiologically

failure to resolve within 36 to 48 hrsfailure to resolve within 36 to 48 hrs

1. Identify the organism

Best done with cultures of aspirate, blood and tissue. This must be done before administering antibiotics.

2. Select the correct antibiotics• Based upon Gram stain, cultures and antimicrobial sensitivities.

• “ Best Guess ” guided by several factors - Gram stain

- Age

- Predisposing causes

- Probable sensitivities of the suspected organism

3. Deliver the antibiotic to the organism3. Deliver the antibiotic to the organism

• Initially all antibiotics should be intravenousInitially all antibiotics should be intravenous

• Oral antibiotics can be used when Oral antibiotics can be used when

– Resolving clinical course

– Adequate surgical debride. of all necrotic tissue

– Adequate serum levels with oral antibiotics

– Reliable parents to assure compliance

– GI tolerance

• IV antibiotics must be continued– Inability to swallow or retain medication

– Lack of identification of etiologic agent

– Inability of lab. to obtain serum bactericidal levels

– Infection caused by an organism for which no effective oral antibiotics exists (e.g. Pseudo.)

– Lack of clinical response to IV antibiotics

• Duration of treatment– Depend on characters of infection

– In AHO, Intravenous antibiotics therapy for 1 week if the clinical response is adequate Oral medication for at least 4 to 6 weeks

– In SA, IV antibiotics for 1week, oral antibiotics for additional 2 to 3 weeks

4. Stop the Tissue Destruction4. Stop the Tissue Destruction- Surgery • remove all of dead bone and inflammatory products • preserve blood supply to bone • preserve periosteum and its attachment to the bone as best as possible

• Treatment of septic arthritisTreatment of septic arthritis

• Aspiration and irrigationAspiration and irrigation• AntibioticsAntibiotics• ArthrotomyArthrotomy

– in deep joint such as hip or shoulderin deep joint such as hip or shoulder

• Repeated aspiration and irrigationRepeated aspiration and irrigation– in superficial joint in superficial joint

• Some facts about septic arthritisSome facts about septic arthritis

– Delay in Dx & Tx is the most signif. cause of poor resultsDelay in Dx & Tx is the most signif. cause of poor results

– Results associated with osteomyelitis are worseResults associated with osteomyelitis are worse

– poorer prognosis in neonate than older childrenpoorer prognosis in neonate than older children

– The hip is more likely to have poor result than other Jt.The hip is more likely to have poor result than other Jt.

– Hip infection is more common in neonate & young infantHip infection is more common in neonate & young infant

– Septic arthritis secondary to osteomyelitis is more commoSeptic arthritis secondary to osteomyelitis is more commo

n in the hipn in the hip

• Open surgical vs arthroscopic debridementOpen surgical vs arthroscopic debridement

– Arthroscopy ; shoulder, knee, elbow ankle Arthroscopy ; shoulder, knee, elbow ankle

– Efficacy of arthroscopic vs open drainage : controversialEfficacy of arthroscopic vs open drainage : controversial

– Repeated US guided aspiration : good result in hipRepeated US guided aspiration : good result in hip

(Givon U 2004)(Givon U 2004)

– Anterior or medial approach > posterior app. in hip jt.Anterior or medial approach > posterior app. in hip jt.

Special Conditions

• Neonatal osteomyelitis

• Subacute osteomyelitis

• Chronic recurrent multifocal osteomyelitis

• Pyogenic infection of spine

• Pelvic infection

• Tuberculosis

Neonatal osteomyelitisNeonatal osteomyelitis

• Definition– first 4 ~8 weeks of life

• Immature immune system – susceptible to less virulent organism

– less able to produce inflammatory response

– difficult early diagnosis

2 types of infection2 types of infection

• Premature infant

– In hospital, sick neonate, systemically ill

– invasive monitoring : Staph. aureus or gram negative

– multiple sites > 40 %

• Full term neonate

– After discharge, healthy infant not ill, normal development an

d feeding

– group B streptococcus

– single site

• Transphyseal vessels

– until 12 to 18 Mos.

– contiguous bone and joint

infection

– damage to physis

• Diagnosis is not easy– lack of sign & symptoms

– Laboratory evaluation is of little value

• ESR not specific finding

• Blood culture 50%

– Bone scan may be normal

– Swelling, psudoparalysis, tenderness

• Aspiration is mandatory– esp. at both hip joint

• Multiple sites common

• The proximal & hip are frequently involved

• Symptom & sign are subtle

• The hip is most difficult to exam

• The window of opportunity for effective tx. is small

• The hip is the most frequent site of permanent sequelae

• Subacute osteomyelitis Subacute osteomyelitis

– No previous acute attack

– Insidious onset of pain

– Absence of systemic signs

– Radiographic bony lesion at presentation(King & Mayo 1969)(King & Mayo 1969)

PathogenesisPathogenesis

• Reduced virulence of organism

• Increased host resistance

• Previous administration of antibiotic agents

• Differential diagnosis is important step

• S. aureus most common organism

• Single course of antibiotics and curettage, but longer

course IV therapy in compairing to AHO

• Positive culture or failure to respond to antibiotics i

ndicates the need for curettage, drainage of abscess,

and sequestrectomy

Chronic Recurrent Multifocal OsteomyelitisChronic Recurrent Multifocal Osteomyelitis

• Relatively rare condition of unknown etiology affect

ing children

• Characterized by symmetric juxtaphyseal sclerosis,

pain and tenderness of insidious onset

• ESR mildly elevated

• Culture negative. No organism identified

• Avoid biopsy if possible

• Symptomatic treatment. No indication for

antibiotics

• May spontaneously resolve following skeletal

maturity

• Growth arrest (+/-)

Pyogenic infection of the spinePyogenic infection of the spine

• Vertebral osteomyelitis and discitis are

the result of hematogenous infection beg

inning in the bone adjacent to cartilage

nous vertebral end plate

Three patterns of clinical presentationThree patterns of clinical presentation

1. Younger than 3 years of age

hip pain w/ walking difficulty

D/D : septic hip

2. 7 to 15 years of age

abdominal pain

D/D : intraabdominal condition

3. Back pain

• Pelvic infectionPelvic infection

Osteomyelitis of Pelvis & SI jointOsteomyelitis of Pelvis & SI joint

• 3 clinical types

– Gluteal syndrome

– Abdominal syndrome

– Lumbar disc syndrome

• DDx with septic hip joint

• MRI

• BR & Antibiotics

• Surgery

TuberculosisTuberculosis• Common under age of 5 years old

• Lung - the most common site

• If untreated, involvement of bone and joint occurs in 5-10%

• Epiphysis or metaphysis - initial focus

• Spine - the most common skeletal tuberculosis (50~60%)

TreatmentTreatment

Curettage (with or without bone graft)

+

Combined antituberculosis chemotherapy (is

oniazid, ethambutol, rifampin) should be co

ntinued for 1 year

Juvenile Idiopathic Arthritis (JIA)Juvenile Idiopathic Arthritis (JIA)

• Juvenile chronic arthritis: JCA

– EULAR (European League Against Rheumatism)

• Juvenile rheumatoid arthritis: JRA

– ACR (American College of Rheumatology)

• Juvenile idiopathic arthritis: JIA

– ILAR (International League of Associations of Rheumatology)

– Durban Criteria (Petty, 1998)

Etiology-unknownEtiology-unknown

InfectiousInfectious

Immunologic Immunologic

Age at onset : before 16Age at onset : before 16thth birthday birthday

Arthritis in one or more jointsArthritis in one or more joints

Duration of disease : at least 6 weeksDuration of disease : at least 6 weeks

• Oligoarthritis

• Polyarthritis

• Systemic Arthritis

• Psoriatic Arthritis

• Enthesitis-related Arthritis

• Other Juvenile Idiopathic Arthritides

OligoarthritisOligoarthritis

1.Persistent oligoarthritis :

no more than four joints involved

2.Extended oligoarthritis :

affects a cumulative total of five or more joints after the first 6 months of disease

OligoarthritisOligoarthritis

– Most common type ; 50% – No more than 4 joints during first 6 months – < 6 yrs old– Girl : Boy=4:1 – Knee, Ankle, Elbow joint.. – ESR, CRP : slightly increased or normal– RA factor (-)– Antinuclear antibody (+) 40-80% ; risk of ant. uveitis

– Benign clinical course in most cases

• Joint destruction in 15%

• Chronic uveitis (13-34%)

PolyarthritisPolyarthritis

• five or more joints during the first 6 Months• 20% of JIA• Girl : boy = 3:1• Symmetric involvement : knee, wrist, ankle… • PIP, MTP joint : 20% • ESR: disease activity • ANA(+): risk of uveitis• 2 types : RF(+) & RF(-) types

Polyarthritis RF(-)

• Any age (av. 6.5 yr)

• Uveitis risk (+) 5%

Polyarthritis RF(+)

• Over 8 yrs old

• Persistent and severe

• Uveitis risk (-)

• Joint destruction 30%

Systemic ArthritisSystemic Arthritis

• Arthritis with or preceded by daily fever of at least 2 wee

ks’ duration, accompanied by one or more of the followin

g:

1. Evanescent, nonfixed erythematous rash

2. Generalized lymph node enlargement

3. Hepatomegaly or splenomegaly

4. Serositis

Psoriatic ArthritisPsoriatic Arthritis

• Arthritis & psoriasis, or Arthritis & at least two of

a. dactylitis

b. nail abnormalities (pitting or onycholysis)

c. family history of psoriasis confirmed

by a dermatologist in at least one first- degree relative

Enthesitis-related ArthritisEnthesitis-related Arthritis

• Arthritis & enthesitis, or arthritis or enthesitis with at leas

t two of :

1. Sacroiliac joint tenderness and/or inflam. spinal pain

2. Presence of HLA-B27

3. Family history of HLA-B27-associated disease

in at least one first- or second-degree relative

4. Anterior uveitis that is usually associated with

pain, redness, or photophobia

5. Onset of arthritis in a boy after the age of 8 years

Other ArthritisOther Arthritis

Children with arthritis of unknown cause that persists for at least 6 weeks, but that either

1. Does not fulfill criteria for any of the other categories, or

2. Fulfills criteria for more than one of the other categories

Differential DiagnosisDifferential Diagnosis

• Leukemia • Acute rheumatic fever • Pigmented villonodular synovitis • Hypermobility syndrome • Septic arthritis • Lyme disease • Henoch-Schönlein purpura • Systemic lupus erythematosus

TreatmentTreatment

• Control inflammation

• Prevent contractures in nonfunctional position

• Encourage movement

Medical therapyMedical therapy

NSAIDNSAID

GlucocorticoidGlucocorticoid

DMARDDMARD

Step Down Step Down Step Up Step Up

- usually given for minimum 6 weeks if in 6 weeks all signs of arthritis are gone, medication should be discontinued if one fails, change to different NSAIDs naproxen ( 10 to 20 mg/kg/day, bid ) indomethacin for systemic CBC, renal & liver function test, urinalysis : every 6 months

NSAIDsNSAIDs

severe or systemic oral steroid intra-articular steroid 0.1-1mg/kg/day for uncontrolled systemic disease

SteroidSteroid

Methotrexate (MTX)Methotrexate (MTX)

• Most commonly used DMARD• 0.5 to 1mg/kg ( with maximum 20 to 30 mg) • Not systemic arthritis• Decrease severity of uveitis• Side effect gastrointestinal complication folic acid (1mg/day) liver fibrosis and cirrhosis

SulfasalazineSulfasalazine

• Oligo and polyarticular JRA

• 50mg/kg/day bid

• Serious side effect in systemic

Orthopadic surgical treatmentOrthopadic surgical treatment

• Synovectomy - arthroscopic

• Soft tissue release

• Osteotomy

• Epiphysiodesis

• Arthroplasty

• Arthrodesis

• Joint excision

대단히 감사합니다 .