Part 16. Rheumatic Disorders of Childhood
PART XVI Rheumatic Diseases Of Childhood (Inflammatory Diseases of Connective Tissue, Collagen Diseases)
Chapter 146. Autoimmunity
Autoimmunity ; self antigen¿¡ ´ëÇØ ¹«¹ÝÀÀÀ» À¯ÁöÇÏ´Â self tolerance (inhibition of immunce system)ÀÇ ÀÌ»óÀ¸·Î ¹ß»ý.
(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- macrophage¿Í T lymphocyte¿ÍÀÇ »óÈ£ ÀÛ¿ë ¾ïÁ¦, antigen-specific T lymphocyte Áõ½Ä°ú Ȱ¼º ¾ïÁ¦
¡¤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
;
¡ÚIgM detected by agglutination techniques
- IgG, A, E´Â ´Ù¸¥ ¹æ¹ýÀ¸·Î ¹ß°ßµÈ´Ù.
;
¡ÚPositive
- 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¢¡ ANAº¸´Ù ¿¹¹Îµµ ³ô´Ù.
-ÇÙ³» ¹°ÁúÀÎ DNP°¡ ANA¿Í È¥ÇÕµÇ¾î ¹éÇ÷±¸¿¡ ÀÇÇØ phagocytosis µÈ°Í
-LE, CAH, RA
Antineutrophil Cytoplasmic Ab (ANCA)
; react with the granules of neutrophil
;
*1st found in Wegener
granulomatosis
;
¡Ú2 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 ¡èin 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
# ¢¾HLA-B27
1)
*ankylosing spondylitis(AS)
;
*¡ãstrongest
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- ÀÌ È¯¾ÆÀÇ 1st degree relative¿¡ ³ªÅ¸³¯¼ö ÀÖÀ½.
¢ÞTable
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
¼Ò¾Æ±â ¾î´À ½Ã±â³ª, °æÇϰí Rh nodule¾ø´Ù.
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 jtÀÇ inflammation; spindling or fugiform change of fingers
MCP, DIP jtµµ involve
iii) cervical spine- 50%, neck stiffness and pain
iv) TM jt; ÀÔ¿©´Âµ¥ Àå¾Ö
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 jt°¡ ñ«, 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% (ù 10³â°£)
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; ù 5³â°£ 3-4³â/1³â (ds. activity¿Í °ü°è¾øÀÌ)
¡¤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 ÃøÁ¤
Systemic-Onset JRA
¡ÚTable
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¡É 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¡è ii) exclusion of other disease
) DDx
i) early in ds.½Ã °¨º°
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 (¾ÆÄ§ º¹¿ë 2½Ã°£ÈÄ 25mg/dl À¯Áö)
¡¤25kg ÀÌÇÏ, 100 mg/kg/24 hr, heavier children - 2.4-3.6 gm , ÃÖ¼Ò 6ÁÖ¿¡ Ä¡·áÈ¿°ú
ȤÀº Ȱµ¿¼º ¾ø¾îÁøÈÄ 1-2³â ´õ
¡¤chronic therapeutic salicylate administration is relatively safe
¡¤intoxications -
¨ç rapid or heavy breathing
¨è drowsiness & other CNS change : 1,2 earliest signs in chiIdren
¨é tinnitus : common complaint in adult
¨ê gastric irritation/ hemorrhagic phenomena
¨ë elevated serum levels of hepatic enzymes
¨ì Reye syndrome in children with either chickenpox & influenza
Nonsteroidal Anti-Inflammatory Agents
; ÁÖ·Î ¼ºÀÎ
;
*tolmetin, ibuprofen, naproxen (¹Ì±¹¿¡¼
¼Ò¾Æ¿¡ ÀÎÁ¤)
; 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 º¸´Ù È¿°úÀû
- Ä¡·á ¹ÝÀÀÀ» ¾ò±â±îÁö ¼ö°³¿ù ¿äÇÔ.
- 24ÁÖÀ̳» ¹ÝÀÀ¾øÀ¸¸é D/C
¡¤hydroxychloroquine; retinal toxicity, 3°³¿ù °£°ÝÀ¸·Î ¾È°ú °Ë»ç
¡¤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 »ç¿ë½Ã cartilage destruction & aseptic necrosis of bone ÃÊ·¡
2) therapeutic dose¿¡¼µµ adrenal suppression, growth suppression, S/E ÃÊ·¡
# ¢¾Indications
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 manifestationÀ» À§Çؼ´Â °ÅÀÇ »ç¿ëÇÏÁö ¾ÊÀ½.
;
¢¾Why ?
- 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. Iridocyclitis½Ã
;opthal slit lamp exam¢¡ 1¹ø/³â in systemic and polyart. ds.
4¹ø/³â in pauciarticular (2³â°£)
# 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; bone¿¡ ºÎÂøµÇ´Â tendon, ligament ÀÇ ÅëÁõ
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
(JRA¿¡¼´Â neckÀÌ Àß Ä§¹üµÇ°í lumbosacral spineÀº 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 ¡è
Laboratopy Findings
¡¤HLA-B27 : 95% of patient
¡¤rheumatoid factor & ANA :negative
¡¤X-ray »ó sacroiliac joint involvement : usually the first 3-4 y¿¡ ³ªÅ¸³².
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 :
¨ç ankylosing spondylitis.
¨è Reiter disease. ; ¨ç, ¨è misleaded JRA
¨é psoriatic arthritis
¨ê the arthritis of inflammatory bowel disease
¨ë 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
¡ÚTable
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 ¥á2-globulin
; decreased albumin
; prevalence of HLA-B8, -DW3/DR3, -DW2/DR2
; anemia
; thrombocytopenia and leukopenia
-- ITP ¸¦ ùÁõ»óÀ¸·Î ¿À´Â °æ¿ìµµ ÀÖ´Ù.
Diagnosis
¢ÞTable
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
Ä¡·á´Â extents and severity of disease¿¡ µû¶ó ´Þ¸® ÇÑ´Ù.
ÃæºÐÇÑ °Ë»ç°¡ ½Ç½ÃµÈ ÈÄ ½Ç½ÃÇÑ´Ù. ¿¹¸¦µé¸é major organ involvements
no specific therapyÀ̸ç, Ä¡·áÀÇ ¸ñÀûÀº suppress inflammation and immune reactivityÇϹǷΠ½á clinical well-being and serologic normalityÀ» À§ÇØ ½Ç½ÃÇÑ´Ù.
active lupus ´Â emergency ·Î¼ prompt evaluation°ú vigorous therapy°¡ ÇÊ¿äÇÏ´Ù.
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 À¸·Î ½ÃÀÛÇÏ¿© lowest dose ·Î tapering
; antimalarial agents
3. significant disease with nephritis
; large dose of corticosteroids
-- prs 1-2mg/24hr À¸·Î ½ÃÀÛÇÏ¿© Áõ·®
-- IV pulse therapy
; cyclophosphamide
; azathioprine
4. seizures and other CNS manifestations
; severe, active disease À» ÀǹÌÇϹǷΠvigorous controlÀÌ ¿äÇÔ.
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, thrombocytopeniaÀÇ Áõ»óÀ» º¸ÀÏ ¼ö ÀÖ´Ù.
; steroid or cytotoxic therapy°¡ ¿äÇÔ.
; antiplatelet or anticoagulants
Prognosis
; potentially or uniformly fatal childhood disease
; prolonged spontaneous remission ´Â children¿¡´Â µå¹°´Ù.
;
*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/SSBÀ» °¡Áø
»ê¸ð¿¡¼ žî³
ȯ¾ÆÀÇ ¼Ò¼ö¿¡¼
¹ß»ý
Clinical manifestations
; rash, thrombocytopenia, congenital heart block, liver disease, hemolyti anemia, leukopenia
; Rash
- »ýÈÄ 1ÁÖ È¤Àº ¼ö°³¿ùÀ̳»¿¡ »ç¶óÁø´Ù.
- erythematous, circinate form
; Congenital heart block
- Ab to Ro/SSAÀ» °¡Áø »ê¸ð¿¡¼ ÁÖ·Î ¹ß»ý
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 disease°¡ ¾øÀ¸¸é, excellent outcome
; serious affected children -- 4-6wksÀÇ 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 - ¡ãcommon 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 ·Î¼ Áø´Ü
Treatments
; specific allergenÀÌ Áõ¸íµÈ °æ¿ì¿¡´Â avoid therapy
; bacterial infections¿¡ µÚµû¶ó ¿Â °æ¿ì¿¡´Â ƯÈ÷ streptococcal infections ÈÄ¿¡ ¿À´Â °æ¿ì¿¡´Â organism eliminationÀÌ ¼±ÇàµÇ¾îÁ®¾ßÇÑ´Ù.
; symptomatic treatments
-- NSAID
; corticosteroids therapy
-- intestinal hemorrhage, obstruction, intussusception, perforation µîÀÇ life-threatening complicationÀÌ ÀÖ´Â °æ¿ì
-- CNS manifestations and nephrotic syndromeÀ» º¸ÀÌ´Â °æ¿ì
-- prs 1-2mg/24hr
Prognosis
; death
-- acute phase µ¿¾È
-- 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 Â÷ ¼¼°è ´ëÀü ÀÌÈÄ ÀϺ»¿¡¼ óÀ½À¸·Î ¹ßÇ¥
; 5¼¼ ÀÌÇÏÀÇ ¼Ò¾Æ¿¡¼ ÁÖ·Î ¹ß»ý
; ÀÎÁ¾ÀûÀ¸·Î ÀϺ»Àο¡°Ô¼ ÈçÇϸç, sub-Saharan Africa¿¡¼´Â µå¹°´Ù.
; no person-to-person transmission
Etiology
; unknown
; bacterial toxins similar to the staphylococcal toxins of TSS
; increased T-cell subsets(V¥â-positive T cells)
cf. 1) retroviruses or rickettsiae ´Â Áõ¸íµÇÁö ¾Ê¾Ò´Ù.
2) no evidence of autoimmunity
Clinical Manifestations
¢ÞTable
152-2, 152-3
1) 1¼¼ ÀÌÇÏÀÇ atypical ȯÀÚ´Â gastroenteritis, viral syndrome, sepsisÀ¸·Î ¿ÀÁøÇÏ¿© ÀÔ¿øÇϱ⵵ Çϸç, ÀÌ·¯ÇÑ °æ¿ì¿¡´Â high mortality À» º¸ÀδÙ.
2) abrupt high sustained fever
; 1wks ÀÌ»ó Áö¼ÓÇϸç, unresponsive to antibiotic therapy
; 104 ¢µÀÌ»óÀ» º¸ÀÓ.
3) erythematous skin eruptions
; maculopapular, morbiliform, or erythema multiforme form
; nonspecific erythematous, desquamating perineal eruption
--> 1wks À̳»
4) edematous, swollen, painful hands and feet
; several days
5) desquamation
; durine the 2nd-3rd wk of illness
6) transient arthritis
; ƯÈ÷ 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 childrenÀÇ °æ¿ì 1ÁÖÀ̳»¿¡ 10-40%¿¡¼ ¹ß»ý
; at presentation and during the first 2wk of disease ¿¡ 2D ECHO°¡ ½ÃÇàµÇ¾îÁ®¾ß ÇÔ.
; 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 vasculitis°¡ ¾ø´Â ȯ¾Æ´Â usually complete recovery
; cardiac involvementÀ» ÇÑ °æ¿ì¿¡´Â long-term prognosis ´Â unknownÀÌÁö¸¸ do well
; ÀϺ» Åë°è¿¡ ÀÇÇϸé 1-2%°¡ cardiac complicationÀ¸·Î »ç¸ÁÇÑ´Ù°í ÇÔ.
Treatment
# IV gamma globulin
; 24½Ã°£À̳»¿¡ fever¿Í other attendant systemic SxÀÌ »ç¶óÁü.
;
*Ãʱ⿡
Åõ¿©Çϸé cardiac involvementÀ»
¿¹¹æ
; 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 disease°¡ subside µÇ°í ÇÑÈÄ¿¡ 6-8ÁÖ°£
# Heparine or warfarin therapy
; persistent large or multiple nonobstructive or obstructive aneurysm ¿¡ »ç¿ë
# 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
vasculitis´Â lung, kidney¿¡ ÈçÇÔ.
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
childhood¿¡ some cases, infants¿¡ 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 °¡ lymphotoxinsÀ» ºÐºñ
-- immunoglobulin, complements deposition in blood vessels in affected muscle
; childhood dermatomyositis
-- HLA-B8/DR3¿Í ¿¬°ü
; viral infections
-- Coxsackie virus
; adult dermatomyositis
-- 20%¿¡¼ malignacy ¿Í ¿¬°ü
; 8-9¼¼¿¡¼ ÈçÇÔ
; female in common (3:1)
; no familial or racial predilection
Pathology
; skin, subcutaneous tissues, gastrointesinal tract, striated musclesÀ» ħ¹ü
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 case·Î »ç¸Á
6) cardiac involvements
; conduction defects, myocarditis
7)
¡ÚSkin 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 ´Â ´ëºÎºÐ ºÒÇÊ¿ä
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 levelÀÌ Á¤»óÀÌ µÉ ¶§±îÁö
- ´ëºÎºÐ 1-2ÁÖ³»¿¡ Á¤»óÀ¸·Î µÈ´Ù.
; iv high-dose steroid pulse
; ´ëºÎºÐ 2³âÀÌÈÄ¿¡´Â ÀÓ»óÀûÀÎ Áõ»ó È£ÀüÀ¸·Î stop steroid therapy
; triamicinolone, dexamethasone
-
*steroid induced myopathy À»
ÀÏÀ¸Å³ ¼ö
ÀÖÀ¸¹Ç·Î »ç¿ëÇÏÁö
¾Ê´Â´Ù.
3) immunosuppressive agents
; methotrexate, azathioprine, cyclosporine
4. iv immunoglobulin therapy
5. physical therapy
; bed rest, immobilizationÀº ºÒÇÊ¿äÇÏ´Ù.
Prognosis
adequately treated children is good
untreated children ; 40% mortality, 2³â À̳»
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 disease¿¡ »ç¿ë
2. corticosteroid therapy
; active phase¿¡ È¿°ú
; fibrotic phase¿¡´Â È¿°ú°¡ ¾ø´Ù
3. topical corticosteroid therapy
4. management of hypertension
; captoprilÀÌ È¿°ú
5. physiotherapy
6. management of Raynaud phenomenon
; ºÒÇÊ¿ä
; nifedipine drugs »ç¿ë ºÒ°¡
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
; 6¼¼ ÀÌ»óÀÇ 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 °¡ ¼±ÇàÇϰųª µ¿¹ÝµÊ.
; 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 À¸·Î »ç¶óÁø´Ù
; *6¼¼ÀÌÀüÀÇ
¼Ò¾Æ¿¡¼´Â µå¹°´Ù. -- 20´ë¿¡ peak
; female in common
¡ØEtiology
; 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
-
*¿øÀÎÁúȯÀÇ
±Ô¸íÀÌ ´õÁß¿ä
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 Ä¡·á
; 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 : ¡ãfrequently
-
*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
Ãâ»ýÈÄ 1ÁÖÀ̳»¿¡ ¹ß»ý
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 prognosis´Â ¾Ë·ÁÁöÁö ¾Ê¾ÒÁö¸¸ 1³âÀ̳» ȤÀº 10¼¼À̳»¿¡ »ç¸ÁÇÑ º¸°í°¡ ÀÖ´Ù.
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)