Part 16. Rheumatic Disorders of Childhood

PART XVI Rheumatic Diseases Of Childhood

PART XVI Rheumatic Diseases Of Childhood (Inflammatory Diseases of Connective Tissue, Collagen Diseases)

Chapter 146. Autoimmunity

Autoimmunity ; self antigen에 대해 무반응을 유지하는 self tolerance (inhibition of immunce system)의 이상으로 발생.

(1) Mechanism of autoimmunity

·development of active auto immunity; require a predisposing genetic background

·determining ds. susceptibility; MHC gene + multiple gene + environment factor(diet, toxin, infectious agent, susceptible individuals)

·Fig 146-1

(2) Tx

·corticosteroid; most widely used drug for controlling autoimmune ds.

i) enhancing the barrier function of vascular endothelium

ii) decreased cell migration into sites of active inflammation

iii) preventing continued antigen uptake by APC

iv) block- macrophage와 T lymphocyte와의 상호 작용 억제, antigen-specific T lymphocyte 증식과 활성 억제

·Fig 146-1

Chapter 147. Laboratory Studies In The Rheumatic Diseases

Table 147-1

tests of diagnostic or specific for rheumatic diseases

* acute phase phenomena, rheumatoid factors, antinuclear & other autoAb, total serum complement & individual complement components, immune complexes, serum protein & immunoglobulins, histocompatibility Ag.

tissue histology

* may provide tissue involvement or aid in classification but, rarely diagnostic of any specific disease

Acute-Phase Reactants

appear or increase during the inflammatory state

ESR, CRP, serum mucoproteins, various alpha-globulins, gamma globulins, some complement components, transferrin

of little diagnostic usefulness

follow up the course of ds

ESR; most readily available test

Rheumatoid Factors

; *group of Ab. that react with Fc portion of IgG

; ★IgM detected by agglutination techniques

- IgG, A, E는 다른 방법으로 발견된다.

; ★Positive

- classic adult rheumatoid arthritis

- RF(+) polyarticular JRA, SLE, scleroderma, chronic active hepatitis - chronic infection (Toxocara canis, congenital infection, bacterial endocardiatis)

- leukemia, lymphoma, viral infection, immunization, open heart op., organ transplantation, normal aging human being

- previous viral infection

; not cause diseases nor necessary for chronic synovitis

; *play a role in perpetuation of synovial inflammation with RA

Antinuclear Antibodies

a group of Ab. that react with various nuclear protein

including deoxyribonucleoprotein (DNP)

DNA

ribonucleoprotein (RNP)

ribonucleic acid (RNA) and Sm Ag

detect by immunofluorescent staining technique

positive : SLE, JRA, chronic active hepatitis, scleroderma

drug- anticonvulsant, procainamide, oral pills

infection- Epstein Barr viral inf., malignancy, normal human being

* high titer; SLE, mixed connective ts ds (RNP)

pattern; speckled, homogenous, peripheral,& nucleolar --limited clincal use

Ab reactive with double stranded DNA

-specific for SLE & indicative of active disease .

Ab to Ag. called Ro(SSA) & La(SSB)

- neonatal lupus syndrome

Lupus erythematosus (LE) cell⇒ ANA보다 예민도 높다.

-핵내 물질인 DNP가 ANA와 혼합되어 백혈구에 의해 phagocytosis 된것

-LE, CAH, RA

Antineutrophil Cytoplasmic Ab (ANCA)

; react with the granules of neutrophil

; *1st found in Wegener granulomatosis

; ★2 pattern of staining

- diffuse activity of granules(c-ANCA)

/ *W. granulomatosis, Kawasaki ds.

- perinuclear pattern(p-NCA)

/ less specific

/ *glomerulonephritis, UC, cholangitis, CAH, H-S vasculitis

- *HIV : both pattern

Antiphospholipid Ab

; class of autoantibody that react with several phospholipid antigen

; *so-called lupus anticoagulant, anticardiolipin Ab, Ab for VDRL test for syphilis

; *prolongation of aPTT but associated with thrombosis

; 30-40% of SLE

Clinical Manifestation

; thrombosis, thrombocytopenia, hemolytic anemia, stroke, chorea, tranv. myelitis, valvular herat ds.

; other positive condition

- malignancy, infection

; primary antiphospholipid syndrome

- no underlying ds.

- thrombotic event, thrombocytopenia, recurrent abortion, stroke

Complement

·useful in indicating the activity of SLE and other disease with immune complex mech.

·low serum level - reflec. complement consumption by immune complex & thus indicate active disease

·most useful test - measurement of total serum hemolytic complement activity

Immune Complex Determinations

responsible for tissue damage in some rheumatic dis.

Serum Proteins & Immunoglobulins

gamma-globulin and alpha2-globulin ↑in actvie inflammation

The Histocompatibility (HLA) System

valuable insight into genetically determined susceptibility to disease

located on the surface of most human cell

loci determing HLA Ag.-located on the 6th chromosome

:A, B, C, D, & DR DP, DQ loci are recgnized

biologic role of HLA

1. determing tissue compatibility

2. determing synthesis of various component of complement

3. determing immune responsi~eness

4. information about disease association

5. // // // linkage

SLE (HLA B8, DR2, DR3), childhood dermatomyositis (HLA B8, DR3)

DR4; IDDM, classic adult onset rheumatic arthritis, RF(+)-polyarticular JRA

HLA haplotype B8/DR3

1. chronic active hepatitis

2. celiac sprue

3. dermatitis herpetiformis with malabsorption

4. IDDM 5. thyroiditis 6. Graves disease

7. addison disease 8. myasthenia gravis

9. Sjogren syndrome 10. childhood dermatomyositis 11. SLE

# ♥HLA-B27

1) *ankylosing spondylitis(AS)

; *▲strongest associated of human ds.

; 95% HLA-B27

2) Reiter syndrome

3) spondylitis of inflammatory bowel dis. & psoriasis

4) acute iridocyclitis

5) *pauciarticular arthritis of older child & adult : pauciarticular JRA type II

6) reactive arthritis following salmonella, shigella, Y.enterocolitica, campylobacter

Chapter 148. Juvenile Rheumatoid Arthritis

a disease or group of diseases characterized by chronic synovitis & associated uith a number of extra-articular inflammatory manifestation

( = juvenile arthritis, Still disease, juvenile chronic polyarthritis, chronic childhood arthritis)

RF(+)polyarticular disease, most resemble with adult-onset rheumatoid arthritis

RF(+) // // , occurs in adult

pauciarticular type II, adult as spondyloarthropathy

// type I with chronic iridocyclitis, not described in adult

systemic onset type, occasionally in adult

Etiology & Epidemiology

1) 2 hypotheses of chronic synovial inflammation

1. result from infection with as yet unidentified micro-organism

i) viral; rubella, parvovirus 19

ii) borrelia burgdorferi, spirochete of lyme ds

⇒ cause ch. pauciarthritis but no etiologic agnet

iii) mycoplasma

2. hypersensitivity or an autoimmune reaction to unknown stimuli

; RF, low complement

2) i) pauciarticular type II frequently associated with

family history for ankylosing spodylitis

Reiter syndrome

acute iridocyclitis

pauciarticular arthritis

ii) pauciarticualr I and RF(+) polyarthritis- 이 환아의 1st degree relative에 나타날수 있음.

㉿Table 148-1 subgroups of JRA

Pathology

characterized by chronic nonsuppurative inflammation of the synovium

⇒ pannus formation

duration of synovitis before joint damage become permanent varies;

articular cartilage damage occur later in the course of JRA than in adult-onset

joint destruction occur more often RF(+) disease or systemic-onset disease

many children with JRA never incur permanant joint damage despite prolonge synovitis

Rheumatoid nodule; less frequent in children

Clinical Manifestations

Polyarticular-Onset Disease

(35%)

involvement of multiple joints typically including small joint of the hand

2 subgroups ; more girl

i) RF (-) polyarthritis- 20-30% of all

소아기 어느 시기나, 경하고 Rh nodule없다.

ii) RF (+) polyarthritis- 5-10%

late chiIdhood, more severe arthritis, frequent rheumatoid nodule, occasional vasculitis

rheumatoid factor test & poly articular pattern

estahlished early in the course of the disease (within 6month)

arthritis

-onset : incidious,

-gradual development of joint stiffness, swelling, loss of motion

or fulminant, with sudden appearance of symptomatic arthritis

-swollen & warm, rarely red

-painless joint stiffness & discomfort before objective changes appear

-severe pain & tenderness- unusual

-morning stiffness and gelling following inactivity

typical posture of anxious guarding against movement

-joint involvement

i) begin in the large joint , knee, ankle, wrist, & elbow; initial--symmetric

ii) PIP jt의 inflammation; spindling or fugiform change of fingers

MCP, DIP jt도 involve

iii) cervical spine- 50%, neck stiffness and pain

iv) TM jt; 입여는데 장애

v) severe hip disease; major cause of disability in late JRA

growth disturbance

- overgrowth & undergrowth of the affected joints

- growth spurts often occur with remission

extra-articular manifestations

-not as dramatic as systemic type

-malaise, anorexia, irritability, mild anemia, low-grade fever,

slight hepatosplenomegaly, lymphadenopahty,

pericarditis, iridocyclitis- rare

# late hallmark of JRA

; increased leg length

; micrognathia after TM arthritis

Pauciarticular-Onset Disease

characterized arthritis that remains limited to four or fewer joints for the first

6 mo after disease onset (large jt가 主, asymmetric)

* 2 distinct subgroup

type I : primarily girl who are young at onset, risk for chronic iridocyc itis

type II : primarily boy who are older at onset, risk for spondyloarthropathy

Pauciarticular Type I

TMC form, 35-40% of all JRA

begin before the 4th birthday

ANA- 90%, but rheumatoid factor & HLA-B27; negative

TMC affected joint- knee, ankle, elbow

the hips & hip girdle- spared, sacroiliitis- not associated

serious disability or joint destruction- uncommon : 80%

20%- severe polyarthritis

eye complication

i) chronic iridocyclitis- 30% (첫 10년간)

unassociated with early sx and activity of arthritis, or elevated ESR

ii) sequale; post synechia, cataract, glaucoma, phthisis bulbi, blindness

iii) if initial involement is unilateral, the other eye remains uninvolved

iv) follow the onset of joint complaints by month to years

v) detectable only by slit-lamp exam; 첫 5년간 3-4년/1년 (ds. activity와 관계없이)

·extra-articular manifestation; mild

Pauciarticular Diseaes Type II

boys older than 8 yr, 10-15%

family history - pauciarticular arthritis, ankylosing spondylitis,

Reiter disease. or acute iridocyclitis

ANA & rheumatoid factor - negative, HLA B27- 75% (+)

affected joint - large joint, esp. lower ext.

hip girdle involvement - frequent early in the course

with time, some pt;

i) typical ankylosing spondylitis with involvement of lumbosacral jt.

ii) manifestation of Reiter syndrome

( hematuria, urethritis, acute iridocyclitis, mucosal sx)

iii) sign of inflammatory bowel disease

acute iridocyclitis- 20-30%, self-limited

follow up phy. exam; back flexion, chest expansion 측정

Systemic-Onset JRA

★Table 148-2

; *characterized by prominent extra-articular manifestation, high fever & rheumatoid rash

; 20% of all JRA

; males

; begin with systemic symptom

- Fever

/ high & intermittent, daily or twice-daily elevation to 39℃ or higher

/ rapid return to normal or subnormal level usually in the evening & morning

/ asso. shaking chill

; rheumatoid rash

- small, pale, red-pink macule, often with central pallor

- frequently found trunk & prox. extremity

- appear during febrile periods

; *hepatosplenomegaly, generalized lymphadenopathy

- mild hepatic dysfunction

; pleuritis, pericarditis

- 1/3

; *leukocytosis, leukemoid reaction

; DIC, acute hepatic failure

; joint manifestation

-at or within a few months of onset

-resemble for polyarticular disease

-midcarpus & midtarsus- characteristically affected with dorsal swelling in the wrist & ankle

- self-limited course for several months but may recur

- systemic manifetation rarely recur after pt. reach adulthood. even though chronic arthritis may persist

Course & Prognosis

·major cause of morbidity in polyarticular & systemic JRA- chronic joint disease · pauciarticular type I - chronic iridocyclitis

pauciarticular type II- spondyloarthropathy

less commonly, severe arthritis that progresses to joint destruction & permanent deformity

· poorest px for jt. function

i) RF(+) polyarthritis

ii) systemic-onset disease

Laboratory Findings

1) -ESR, CRP; increased

-anemia, low reticulocyte, negative Coombs test, IDA

-leucocytosis, thrombocytosis; esp systemic JRA

2) antinuclear Ab(ANA)

·RF(-); 25%, RF(+); 75%, pauciarticular type I; 90%

·rarely, systemic or pauciarticular type II

·correlate with presenxe of chronic iridocyclitis but not with presence of chronic iridocyclitis

3) rheumatoid factor

·5% of all

·correlate with older age at onset

·positive results

1. polyarticular disease

2. late childhood onset

3. severe destructive arthritis

4. rheumatoid nodule

5. rheumatoid vasculitis

6. Sjogren syndrome

4) synovial fluid

·cloudy, may clot spontaneously, increase amount of protein ·leukocytosis (neutrophil), glucose- may be low, complement- normal or decrease

5) roentgenographic findings

i) early change - 1. soft tissue swelling

2. osteoporosis

3. periostitis about the affected joint

ii) long-active joint disease (late change) in wrist and hand

1. subchondral erosion

2. narrowing of cartilage spaces

3. bony destruction & fusion

Diagnosis And Differential Diagnosis

Table 148-3, 148-4 (next page)

) Dx; depend on

i) persistence of arthritis or typical systemic manifestation for 3 consecutive mo↑ ii) exclusion of other disease

) DDx

i) early in ds.시 감별

1. pyogenic or tuberculous joint infection

2. osteomyelitis 3. sepsis

4. arthritis asso. with other acute infection

ii) 1. Lyme disease - children with pauciarticular diseaes

2. viral inf- parvo inf.

3. acute leukemia, malignancy

4. acute RF

5. SLE

6. ankylosing spondylitis 7. Reiter syn.

8. vasculitis, dermatomyositis 9. UC, RE, psoriasis, sarcoidosis

10. jt truma, acute toxic synovitis

Treatment

# Aims Of Immediate & Long-Term Treatment

1) to preserve joint function & provide adequate care for extra-articular manifestations without causing iatrogenic harm

2) to support the family & child in achieving an optimal psychosocial adjustment

# Changes in drug therapy

; NSAIDs are more frequently used

; low-dose methotrexate is increasingly used in patients who not responded to NSAIDs

; gold salts, antimalarials, D-penicillamine are less frequently used

Acetylsalicylic Acid (Aspirin) ;Main

·blood level : 20-30 mg/dl (아침 복용 2시간후 25mg/dl 유지)

·25kg 이하, 100 mg/kg/24 hr, heavier children - 2.4-3.6 gm , 최소 6주에 치료효과

혹은 활동성 없어진후 1-2년 더

·chronic therapeutic salicylate administration is relatively safe

·intoxications -

① rapid or heavy breathing

② drowsiness & other CNS change : 1,2 earliest signs in chiIdren

③ tinnitus : common complaint in adult

④ gastric irritation/ hemorrhagic phenomena

⑤ elevated serum levels of hepatic enzymes

⑥ Reye syndrome in children with either chickenpox & influenza

Nonsteroidal Anti-Inflammatory Agents

; 주로 성인

; *tolmetin, ibuprofen, naproxen (미국에서 소아에 인정)

; indomethacin, fenoprofen. & sulindac

The Disease-Modifying Agents

·Gold therapy

i) oral therapy; given on a daily basis

less effective than IM therapy

ii) signs of toxiciy; skin rash, mucosal ulcer, lekopenia, thrombocytopenia anemia, proteinuria

iii) intramuscular therapy;

- weekly injection, oral 보다 효과적

- 치료 반응을 얻기까지 수개월 요함.

- 24주이내 반응없으면 D/C

·hydroxychloroquine; retinal toxicity, 3개월 간격으로 안과 검사

·D-penicillamine; BM suppression, MG, renal damage

·methotrexate; given on a weekly basis, heptic toxicity

·IV gamma globulin

Corticosteroid

; dramatically suppress but do not induce permanant remission or prevent the occurrence of damage

# disadventages

1) long-term 사용시 cartilage destruction & aseptic necrosis of bone 초래

2) therapeutic dose에서도 adrenal suppression, growth suppression, S/E 초래

# ♥Indications

1) severe systemic disease unresponsive to adequate trial of salicylates

2) iridocyclitis uncontrolled by topical steroid

3) cardiac decompensation due to pericarditis or myocarditis

# joint manifestation을 위해서는 거의 사용하지 않음.

; ♥Why ?

- neither cure arthritis nor prevent joint damage

- chronic side effect less tolerable than joint diseaes

Physical And Occupational Therapy

; tricycle and swimming

Synovectomy

-helpful but curative

7. Iridocyclitis시

;opthal slit lamp exam⇒ 1번/년 in systemic and polyart. ds.

4번/년 in pauciarticular (2년간)

# functional calssificaltion of JRA

class I ; performs all activity

II ; performs adequately with some limitation

III ; limitied activiy, self-care only

IV ; wheelchair-bound or bedridden

Chapter 149. Ankylosing Spondylitis And Other Spondyloarthropathies

Ankylosing Spondylitis

- characterized by stiffness and pain in the back,

- involvement of the sacroiliac jt., progression to the jt and periarticular tissue of lumbodors. and cervical spine

· males older than 8yr

·differ from rheumatoid arthritis by its

i) characteristic involvement of the sacroiliac jt and lumbosacral spine

ii) predilection for male

iii) lack of association with rheumatoid factor or rheumatoid nodules (-)

iv) association with acute iridocyclitis

v) occurence of aortitis with resulting aortic insufficiency

vi) significant familial incidence (HLA B27)

Clinical Manifestatlos

i) peripheral arthritis - may be the first manifestation( 1/2 pt)

ii) large joint, esp, lower extremity; most frequently

iii) enthesopathy; bone에 부착되는 tendon, ligament 의 통증

iv) heel pain : common

v) sacroiliac joint & lumbodorsal spine - characteristic involvement

vi) pain in the low back & hip girdle, & thigh - characteristic

- more severe at night & relieved by movement

vii) stiffness in the lower back with loss of normal spinal mobility

viii) spinal involvement

- begin in the sacroiliac joint & ascend. finally cervical spine

(JRA에서는 neck이 잘 침범되고 lumbosacral spine은 spare)

ix) family Hx - similar arthritis or acute iridocyclitis

x) prognosis; usually good outcome (if good posture is maintained)

- acute iridocyclitis; 25% of pt

- aortitis; rare in children but adult ↑

Laboratopy Findings

·HLA-B27 : 95% of patient

·rheumatoid factor & ANA :negative

·X-ray 상 sacroiliac joint involvement : usually the first 3-4 y에 나타남.

Differential Diagnosis

·spinal cord tumor & other childhood malignancy

·anatomic defect

·infection of the vertebrae & intervertebral disk

·Scheuermann disease

·Legg-Perthes disease

·slipped capital femoral epiphysis

·Reiter syn.

Treatment

·relieve pain and maintain good posture and function

·salicylate

·indomethacin or NSAIDs

·gold salt; not considered

·corticosteroid; rarely indicated

·radiation therapy; contra Ix

·firm bed, thick pillow; avoided

Other Spondyloarthropathies In Children

-described in adults inclucle those seronegative types of arthritis asso. with sacroilitis & spinal arthritis :

① ankylosing spondylitis.

② Reiter disease. ; ①, ② misleaded JRA

③ psoriatic arthritis

④ the arthritis of inflammatory bowel disease

⑤ the reactive arthritis of yersinosis & other gastrointestinal infections

-all asso. with HLA-B27, not asso. writh rheumatoid factor & ANA except for psoriatic arthritis.

- boy & girl equally or male predominance

Table 149-1

Reiter Disease

; *consist of sterile urethritis, arthritis, ocular inflammation(uveitis) & others

- gastroenteritis, skin rash

; male predominance

; after infection with shigella, Y.enterocolitica, comphylobacter, chlamydia

- may follow sexual intercourse

; *strongly asso. with HLA-B27

; *arthritis : pauciarticular

; *achilles tendinitis, other enthesopathies

; Treatment

- *salicylate, NSAID

Arthritis Of Inflammatory Bowel Ds.

·Above 10% of IBD in children

·generally older than 8yr

·arthritis; pauciarticualr pattern

·2 form; i) peripheral arthritis; waxe and wanes with activity of bowel ds and

never jt destruction or deformity

ii) inseparable from ankylosing spondylitis; progressive to disability asso. with HLA-B27

Reactive Arthritis

·sterile arthrritis; may follow Gl infection with Y. enterocolitica, shigella , sa!monella or campylobacter

·outcome : good

may develop spondyloarthropathy

Psoriatic Arthrits

· uncommon during children

· classification may not be appropriate

i) difference in sex ratios of affected pt & patterns of arthritis : girl dominant

ii) less strong asso. with HLA-B27

·arthrilis : begin in one or several ,joint

asymmetric fashion

·nail pitting

Chapter 150. Systemic Lupus Erythematosus

children ; more acute and severe

Etiology And Epidemiology

; unknown

-- disease of altered immune regulation

-- association between inflammation and circulating immune complexes

; exacerbation due to intercurrent infections

; lupus-like disease

-- drugs (hydralazine, sulfonamides, procainamide, anticonvulsants)

; incidence

- unknown

- begins in childhood in 20%

- *usually over 8yr in childhood

- *female :male = 8 :1 in all age but 3:1 in prepubertal age

Pathology

; hematoxylin bodies

-- degenerated cell nuclei similar to the the inclusions of LE cells

-- extracellular material with hmatoxylin staining

; vasculitis

-- in spleen, "onion ring" lesions

; granuloma

; deposition of immune complexes

Clinical Manifestations

; most frequent early symptoms -- fever, malaise, arthritis or arthralgia and rash

★Table 150-1

; cutaneous manifestations

-- butterfly rash : bluish or scaly erythematous patches

-- discoid rahses

-- erythematous macules or punctate lesions on the palms, soles, fingertips, extremities, trunk

-- vasculitic rashes

-- livedo reticularis

-- nailbed changes

-- macular and painless ulcerative lesions on palate and mucous membranes

-- purpura due to thrombocytopenia

-- erythema nodosum and erythema multiforme

-- alopecia : patchy or generalized

; arthralgia and joint stiffness

-- persistent deforming arthritis is rare

-- aseptic necrosis in femoral heads

-- tenosynovitis and myositis

; polyserositis

; hepatosplenomegaly and generalized lymphadenopathy

; cardiac manifestations

-- variable murmurs, friction rubs, cardiomegaly, electrocardiolgraphic changes

-- congestive heart failure

-- myocarditis

-- pericarditis

-- verrucous endocarditis (Libman-Sacks endocarditis)

-- myocardial infarctions

; lung manifestations

-- acute pneumonia

-- pulmonary hemorrhage

-- chronic pulmonary fibroisis

; CNS manifestations

-- personality changes, seizures, cerebrovaascular accidents, chorea, peripheral neuritis

; GI manifestations

-- abdominal pain, vomiting, diarrhea, melena, bowel infarctions due to vasculitis

; ocular manifestations

-- episcleritis, iritis, retinal vascular changes with hemorrhages or exudates(cystoid bodies)

; *clinical renal involvements

- *common in childhood

Laboratory Manifestations

; ANA

-- screening tests

; Ab to Sm

-- specific for SLE

; Ab to Ro/SSA and La/SSB

-- neonatal lupus syndrome

; *Ab to double-stranded DNA

- *ass. with active disease, esp. nephritis

- useful index of severity & activity

; complements ( esp. C3 )

- decreased in severe active SLE

; anticardiolipin(antiphospholipid) or lupus anticoagulant antibodies

- ass. with thrombotic events

- false-positive serologic tests for syphilis

; increased serum gamma globulin and α2-globulin

; decreased albumin

; prevalence of HLA-B8, -DW3/DR3, -DW2/DR2

; anemia

; thrombocytopenia and leukopenia

-- ITP 를 첫증상으로 오는 경우도 있다.

Diagnosis

㉿Table 150-2

Drug-induced SLE

; less severe

; fever, arthritis, rash, serositis

-- most common Sx

; nephritis, CNS Sx,

-- unusual

; responds to symptomatic therapy and discontinuance of the offending agents

; cytopenias and autoantibodies such as FA factors

; antihistone Ab

Treatments

치료는 extents and severity of disease에 따라 달리 한다.

충분한 검사가 실시된 후 실시한다. 예를들면 major organ involvements

no specific therapy이며, 치료의 목적은 suppress inflammation and immune reactivity하므로 써 clinical well-being and serologic normality을 위해 실시한다.

active lupus 는 emergency 로서 prompt evaluation과 vigorous therapy가 필요하다.

1. mild disease without nephritis

; NSAID for arthritis and other discomfort

; hydroxychloroquine for discoid and cutaneous manifestations

; topical corticosteroid preparations

2. significant disease without nephritis

; corticosteroids

-- prs 1-2mg/24hr 으로 시작하여 lowest dose 로 tapering

; antimalarial agents

3. significant disease with nephritis

; large dose of corticosteroids

-- prs 1-2mg/24hr 으로 시작하여 증량

-- IV pulse therapy

; cyclophosphamide

; azathioprine

4. seizures and other CNS manifestations

; severe, active disease 을 의미하므로 vigorous control이 요함.

5. patients with antiphospholide antibodies(lupus anticoagulants)

; venous and arterial thrombosis, recurrent fetal loss, migraine, stroke, transient ischemic attacks, avascular bone necrosis, transverse myelitis, pulmonary hypertension, pulmonary embolism, livedo reticularis, leg ulcers, thrombocytopenia의 증상을 보일 수 있다.

; steroid or cytotoxic therapy가 요함.

; antiplatelet or anticoagulants

Prognosis

; potentially or uniformly fatal childhood disease

; prolonged spontaneous remission 는 children에는 드물다.

; *90% 5-yr survival rate

; major cause of death

-- nephritis, CNS complications, infections, pulmonary lupus, myocardial infarctions

Chapter 151. Neonatal lupus

; *Ab to Ro/SSA, La/SSB을 가진 산모에서 태어난 환아의 소수에서 발생

Clinical manifestations

; rash, thrombocytopenia, congenital heart block, liver disease, hemolyti anemia, leukopenia

; Rash

- 생후 1주 혹은 수개월이내에 사라진다.

- erythematous, circinate form

; Congenital heart block

- Ab to Ro/SSA을 가진 산모에서 주로 발생

Chapter 152. Vasculitis Syndromes

Table 152-1

152.1 Henoch-Schonlein Purpura Or Vasculitis

(Anaphylactoid purpura)

unknown origin

follow an URI, sometimes streptococcal

any age : more common in children

children 2-8 yr

boys more common

Pathology

; small vessels surrounded by an acute leukocytoclastic inflammatory reaction of polymorphonuclear and round cells; eosinophils and red blood cells

; dermal IgA deposits

; capillaries more common involved

-- small arterioles and venules also

Clinical Manifestations

; acute onset

; *sequential appearance of different manifestations over a period of weeks

; *significant renal disease가 없으면, excellent outcome

; serious affected children -- 4-6wks의 average duration

; malaise and low-grade fever in half in patients

# skin lesions

; small wheal or erythematous maculopapule

- initially blanch on pressure

- later petechial or purpuric

; *usually on lower extremities and buttocks

- maybe upper extremities, trunk, face

; erythema multiforme and erythema nodosum rarely

; angioedema

-- scalp, eyelids, lips, ears, dorsa of the hands and feet, back, scrotum, perineum

# arthritis

; *two thirds

; large joints -- knees and ankles in common

; serous joint fluids

; resolve after a few days without residual deformity

# GI manifestations

; *more than 50%

; *colicky abdominal pain - ▲common complaints

; gross or occult blood in stool

; X-ray finding

-- decreased motility, segmental narrowing, submucosal edema and hemorrhage

; Cx -- intussusception, obstruction, infarction with bowel perforation

# renal manifestations

; *25-50% during acute phase

; hematuria with or without casts or proteinuria during first few weeks of illness

- sometimes renal involvement first appears later

; occasionally nephrotic syndrome, moderate azotemia, hypertension, oliguria, hypertensive encephalopathy

; a few -- CRF

# CNS manifestations

; seizures, paresis, coma

# others manifestations

; hepatosplenomegaly and lymphadenopathy

; intramuscular hemorrhage, rheumatoid-like nodules, cardiac involvement, eye involvements, testicular swelling and hemorrhage

Laboratory Findings

; increased ESR

; leukocytosis, eosinophilia

; normal coagulation studies

; ANA, RA factor -- negative

Diagnosis And Differential Diagnosis

; full-blown picture of rash, arthritis, GI nd renal manifestations 로서 진단

Treatments

; specific allergen이 증명된 경우에는 avoid therapy

; bacterial infections에 뒤따라 온 경우에는 특히 streptococcal infections 후에 오는 경우에는 organism elimination이 선행되어져야한다.

; symptomatic treatments

-- NSAID

; corticosteroids therapy

-- intestinal hemorrhage, obstruction, intussusception, perforation 등의 life-threatening complication이 있는 경우

-- CNS manifestations and nephrotic syndrome을 보이는 경우

-- prs 1-2mg/24hr

Prognosis

; death

-- acute phase 동안

-- due to GI complication, ARF, CNS manifestations

152.2 Kawasaki Disease

(=Mucocutaneous Lymph Node Syndrome, Infantile Polyarteritis)

Definition

; a febrile condition affecting chiIdren

; is notable for its association with vasculitis of the large coronary blood vessels and a constellation of other systemic complaints

Epidermiology

; 2 차 세계 대전 이후 일본에서 처음으로 발표

; 5세 이하의 소아에서 주로 발생

; 인종적으로 일본인에게서 흔하며, sub-Saharan Africa에서는 드물다.

; no person-to-person transmission

Etiology

; unknown

; bacterial toxins similar to the staphylococcal toxins of TSS

; increased T-cell subsets(Vβ-positive T cells)

cf. 1) retroviruses or rickettsiae 는 증명되지 않았다.

2) no evidence of autoimmunity

Clinical Manifestations

㉿Table 152-2, 152-3

1) 1세 이하의 atypical 환자는 gastroenteritis, viral syndrome, sepsis으로 오진하여 입원하기도 하며, 이러한 경우에는 high mortality 을 보인다.

2) abrupt high sustained fever

; 1wks 이상 지속하며, unresponsive to antibiotic therapy

; 104 ℉이상을 보임.

3) erythematous skin eruptions

; maculopapular, morbiliform, or erythema multiforme form

; nonspecific erythematous, desquamating perineal eruption

--> 1wks 이내

4) edematous, swollen, painful hands and feet

; several days

5) desquamation

; durine the 2nd-3rd wk of illness

6) transient arthritis

; 특히 older children

; symmetric in distribution and affect both large and small joints

7) other acute manifestations

; diarrhea, vomiting, abdominal pain, hydrops of the gallbladder, myositis, meatitis with sterile pyuria, tympanitis, ulcerative stomatitis, cough, rhinorrhea, aseptic meningitis, seizures, cranial or peripheral nerve palsies, hepatosplenomegaly

8) iridocyclitis

9) peripheral large arterial aneurysms(axillary, popliteal)

10) cardiac involvement

; most important manifestation

; untreated children의 경우 1주이내에 10-40%에서 발생

; at presentation and during the first 2wk of disease 에 2D ECHO가 시행되어져야 함.

; myocardial ischemia, myocardial infarction, rupture of an aneurysm, pericarditis, myocarditis, endocarditis, heart failure, arrythmias

Laboratory Findings

no diagnostic tests

; leukocytosis, thrombocytosis, anemia

; increased ESR, CRP

; negative autoantibody (e.g. ANA, rheumatoid factors)

; mild proteinuria, pyuria

; CSF pleocytosis

; increased hepatic transaminases and bilirubin

; cardiac study

-- coronary vascular dilatation or aneurysm formation

; histologic changes

-- intense inflammatory cell infiltrates of the media and intima of large coronary vessels

-- central vessels and arterial obstruction by platelet

Diagnosis

rests on the clinical features

Prognosis

; coronary vasculitis가 없는 환아는 usually complete recovery

; cardiac involvement을 한 경우에는 long-term prognosis 는 unknown이지만 do well

; 일본 통계에 의하면 1-2%가 cardiac complication으로 사망한다고 함.

Treatment

# IV gamma globulin

; 24시간이내에 fever와 other attendant systemic Sx이 사라짐.

; *초기에 투여하면 cardiac involvement을 예방

; 2g/kg a single dose over 10-12hr

; side effect -- anaphylaxis, chills, fever, headache, myalgia

# Salicylate therapy

; therapeutic serum concentration 20-30mg/dl

; 100mg/kg/day

; 5mg/kg/day -- active disease가 subside 되고 한후에 6-8주간

# Heparine or warfarin therapy

; persistent large or multiple nonobstructive or obstructive aneurysm 에 사용

# Corticosteroid therapy

; contraversy

# Thrombolytic therapy

; streptokinase

; active coronary thrombosis or peripheral artery ischemia

# Aterrial bypass surgery

152.3 Rare Forms of Vasculitis

Polyarteritis Nodosa

vasculitis in medium-sized and small arteries

rare in childhood

common in male

Etiology

unknown

; drug exposure, streptococcal infections, serous otitis media, hepatitis B infection

Clinical Maifestration

Wegener Granulomatosis

(=Lethal Midline Granuloma)

systemic necrotizing vasculitis

--> destructive granulomatous lesions of the upper respiratory tract and lungs

vasculitis는 lung, kidney에 흔함.

male (2:1) in common

Laboratory Finding

; no specific laboratory findings

; *often positive serum antineutrophil cytoplasmic antibodies(ANCA)

Takayasu arteritis

(=Pulseless Disease)

vasculitis in the aorta and its major branches

young women in common

childhood에 some cases, infants에 a few cases

Etiology

; unknown

; congenital defects of the great vessels

Charper 153. Dermatomyositis

nonsuppurative inflammation of striated muscle and distinctive cutaneous lesions

Etiology and Epidemiology

; unkown

; cellular immune mechanisms

-- activated lymphocytes 가 lymphotoxins을 분비

-- immunoglobulin, complements deposition in blood vessels in affected muscle

; childhood dermatomyositis

-- HLA-B8/DR3와 연관

; viral infections

-- Coxsackie virus

; adult dermatomyositis

-- 20%에서 malignacy 와 연관

; 8-9세에서 흔함

; female in common (3:1)

; no familial or racial predilection

Pathology

; skin, subcutaneous tissues, gastrointesinal tract, striated muscles을 침범

Clinical Manifestations

; insidious

1) slowly developing muscle weakness

; first proximal muscles of extremities, trunk

2) awkward gait, difficulties on climbing stairs, rising from the floor, riding a bicycle, combing hair, dressing

3) weak neck flexors, weak abdominals, Gower sign

4) nonpitting edema, thickening of the skin and subcutaneous tissue

5) palatorespiratory involvements

; respiratory difficulty, nasal regurigitation, nasal voice, aspiration

; severe case로 사망

6) cardiac involvements

; conduction defects, myocarditis

7) ★Skin Lesion

; *distinctive violaceous (heliotrope) erythma

- *upper eyelids : pathognomonic

; periorbital and facial edema

; butterfly rash or malar rash

; *rash (erythematous, atrophic, scaly)

- *on the extensor surfaces of the joints, esp. knuckles(Gottron papules), knees, elbow, medial malleoli

--> later hyperpigmentation or hypopogmentation

; dusky erythma

; tight and glossy

; cutaneous atrophy with binding to underlying structure longstanding disease

8) calcinosis in subcutaneous tissues

; 20-50% of children

; slowly progression to contractures, focal atrophy of muscle, poorly healing ulcers

9) Gastrointestinal involvements

; swalling difficulties, abdominal pain, perforation, melena, constipation

10) low-grade fever

11) arthritis or other systemic Sx

; lymphadenopathy, hepatosplenomegaly

Laboratory Finding

; *elevated transaminases, creatine kinase, aldolase, lactase dehydrogenase

; EMG

- combination of myopathic and neuropathic changes

; NCV -- normal

; RA factor -- negative

; *ANA -- positive

; *myiositis-specific autoantibodies -- positive

Diagnosis and Differential Diagnosis

; proximal and axial muscle weakness, characteristic rash, elevated serum levels, abnormal findings on EMG or MRI

; muscle biopsy 는 대부분 불필요

Treatment

1) management of palatorespiratory function and respiratory muscle

; constant nursing cae

; soft or liguid diets

; nasopharyngeal suction

; endotracheal intubation, trachiostomy

; artificial ventilation

2) cortiocosteroid therapy

; prs 1-2mg/kg/24hr or 60mg/m2/24hr

- enzyme level이 정상이 될 때까지

- 대부분 1-2주내에 정상으로 된다.

; iv high-dose steroid pulse

; 대부분 2년이후에는 임상적인 증상 호전으로 stop steroid therapy

; triamicinolone, dexamethasone

- *steroid induced myopathy 을 일으킬 수 있으므로 사용하지 않는다.

3) immunosuppressive agents

; methotrexate, azathioprine, cyclosporine

4. iv immunoglobulin therapy

5. physical therapy

; bed rest, immobilization은 불필요하다.

Prognosis

adequately treated children is good

untreated children ; 40% mortality, 2년 이내

late complication ; lipodystrophy with insulin resistance and hyperandrogenism

Chapter 154. Scleroderma

chronic fibrotic disturbance of connective tissue

skin(classically), GI tract, heart, lung, kidney, synovium

Table 154-1

Etiology and Epidemiology

; unpredictable slow progression or remission

; girl in common

; no familial predisposition

; unknown etiology

Clinical Manifestations

1. Morphea and Linear xcleroderma

; patchy lesions of skin and subcutaneous tissues

; distribution of peripheral nerves and one side of the body

; early phase

-- erythematous, edematous, atrophic

-- pain or prickly sensation

; at progressing

-- indurated with violaceous

-- elevated borders and pale, waxy-appering centers

; at terminal

-- extensive scarring and fibrosis of the involved area

-- "hide-binding"

2. Systemic sclerosis

; raynaud phenomenon

-- first manifestation

; cutaneous involvement

-- symmetric

-- hands, feet, trunk, face

-- induration, pigmentary changes, telangiectasia, hide-binding

-- cutaneous ulcers

; synovitis

-- esp. small hand joints

; GI tract, heart, lungs, kidney involvements

; severe hypertension

Laboratory Findings

; ESR is normal

; positive RA factors and ANA

Diagnosis and Differential diagnosis

; eosinophilic fasciitis

; dermatomyositis

; subcutaneous fat necrosis

; Weber-Christian nonsuppurative panniculitis

; Scleredema adultrum (or Buschke)

Treatment

1. penicillamine or cytotoxic drugs

; severe systemic disease에 사용

2. corticosteroid therapy

; active phase에 효과

; fibrotic phase에는 효과가 없다

3. topical corticosteroid therapy

4. management of hypertension

; captopril이 효과

5. physiotherapy

6. management of Raynaud phenomenon

; 불필요

; nifedipine drugs 사용 불가

Chapter 155. Mixed Connective Tissue Disease(=Overlap syndrome)

; combined features of SLE, rheumatoid arthritis, dermatomyositis, sclerderma

; *high serum titers of speckled ANA, antibody to RNA

; 6세 이상의 girls

Chapter 156. Erythema Nodosum

; painful, indurated, shiny, red, hot, elevated, ovoid nodules 1-3 cm in diameter

; symmetric distribution over the shins

- calves, thighs, buttocks, upper extremities

; fever, malaise, arthralgia 가 선행하거나 동반됨.

; hilar adenopathy on chest X-ray

; skin progression

- several days : protuberant and violaceous

- 1-2 wks : decreased induration, dull purple discoloration

- 3-6 wks : large bruise, brown residuum without ulceration or scar formation 으로 사라진다

; *6세이전의 소아에서는 드물다. -- 20대에 peak

; female in common

※Etiology

; precipitating infection

- streptococcal infection, leptospirosis, tularemia, psittacosis, Yersinia infection, cat-scratch disease, tuberculosis

- Epstein-Barr virus

- histoplasmosis, coccidiodomycosis

- sarcoidosis

; drug

- sulfonamides, birth control pills

; underlying disease

- SLE, vasculitis, regional enteritis, ulcerative colitis, Behcet syndrome

Treatment

; salicylates

; corticosteroids

- not warranted

- *원인질환의 규명이 더중요

Chapter 157. Pain Syndromes

musculoskeletal pain syndromes that have no demonstrable organic cause

; growing pains, fibromyalgia syndrome, hypermotility syndromes, reflex sympathetic dystrophy syndrome

157.1 Fasciitis(=Diffuse Fasciitis, Eosinophilic Fasciitis)

; *blood eosinophilia

157.2 Raynaud Phenomenon

ischemic blanching of distal phalanges by vasospasm

; cyanosis and then reactive hyperemia

symmetric involved

precipitated by cold, pressure, stress

primary Raynaud phenomenon

; no underlying disease

secondary Raynaud pbhenomenon

; scleroderma, SLE, mixed connective tissue disease, cryoglobulinemia

Therapy

; underlying disease 치료

; maintain central and peripheral body temperatures

; biofeedback technique

; vasodilating agents -- nifedipine

Chapter 158. Relapsing Nodular Nonsuppurative Panniculitis (=Weber-Christian Syndrome)

; subcutaneous inflammation

; unknown causes

- infection, drug reation(esp. bromides, iodides), abnormal fat metabolism, hypersensitivity

Clinical Manifestation

; *crops of subcutaneous nodules on any parts of body

- thigh, legs, abdomen, breasts, arms : ▲frequently

- *painful with redness, warmth of overlying skin

- size from mm to cm

; fever

Chapter 159. Relapsing Polychondritis

; *pain, swelling, destruction, deformation of external and internal cartilaginous elements of ear, nose, eyes, joints, laryngotracheobronchial system, heart, large blood vessels

Chapter 160. Syndrome Of Neonatal Fever, Rash, And Arthropathy

high intermittent fevers, maculopapular rash, systemic illness

출생후 1주이내에 발생

other Cl/M

; meningoencephalitis, progressive mental retardation, chronic iridocyclitis, hepatosplenomegaly, lymphadenopathy, arthropathy

patellar enlargement is striking

characteristic facies ; prominent foreheads

Treatment

; NSAID

; physiotherpy

long-term prognosis는 알려지지 않았지만 1년이내 혹은 10세이내에 사망한 보고가 있다.

Chapter 161. Behcet Syndrome

; *recurrent oral and genital ulcers and ocular inflammation

; associated Cl/M

- arthritis, thrombophlebitis, neurologic abnormalities, skin lesions, fever, colitis

; unknown origin

Pathology

; vasculitis of small and medium-sized arteries with cellular infiltrations

--> fibrinoid necrosis, narrowing and obliteration of the vessels lumens

Chapter 162 Sjogren syndrome

; chronic inflammatory autoimmune disease

; *dry eyes (keratoconjunctivitis sicca, xerophthalmia), dry mouth(xerostomia), asso. with connective tissue disorders

Clinical Manifestation

Chapter 163 Nonrheumatic Conditions Mimicking Rheumatic Diseases Of Childhood

Table 163-1

163.1 Benign Rheumatoid Nodules

unassociated with rheumatic disese

pretibial areas, dorsa of the feet, scalp, hands, elbows

unknown cause

no associated rheumatic complaints

laboratory test ; normal

RA factor and ANA ; negative

wax, wane and recur

Chapter 164. Amyloidosis

deposition in various body tissues of a homogeneous-appearing eosinophilic materials(Amyloid material ; binds Congo red dye)