Juvenile Idiopathic Arthritis Ankylosing Spondylitis and Other Spondyloarthritides Systemic Lupus Erythematosus Juvenile Dermatomyositis

Pathogenesis  Most common rheumatic disease in children
 Characterized by dysregulation of the innate immune system with a lack of
autoreactive T cells and autoantibodies
 All these immunologic abnormalities cause inflammatory synovitis, characterized
pathologically by villous hypertrophy and hyperplasia with hyperemia and edema of the
synovial tissue.
 Vascular endothelial hyperplasia is prominent and is characterized by infiltration of
mononuclear and plasma cells with a predominance of T lymphocytes
 <16 yr old
 Spondyloarthritis are classified in the juvenile  Presence of circulating autoantibodies directed against self-antigens - Hallmark of SLE  Most common inflammatory myositis in children
idiopathic arthritis (JIA) categories of enthesitis-  Disproportionately affecting females of reproductive age.  Proximal muscle weakness and a characteristic rash.
related arthritis (ERA) or psoriatic arthritis  Female sex - strongest risk factor for SLE  Inflammatory cell infiltrates result in vascular inflammation - underlying pathology in
 ERA accounts for 10–20% of JIA  25 – 60% among monozygotic twins this disorder
 Mean age at onset - 12 yr.  Environmental exposures:  (HLA) alleles such as B8, DRB1*0301, DQA1*0501 and DQA1*0301
 Males > females = 60% of ERA cases. o Viral infection (EBV)  History of infection in the 3 mo before disease onset is usually reported
 Influence of human leukocyte antigen (HLA)-B27: o UV light exposure  Constitutional signs and upper respiratory symptoms predominate, but one third of
o 90% of JAS  Median age at diagnosis of 11-12 yr patients report preceding gastrointestinal (GI) symptoms.
o 50% of ERA  Time to diagnosis of SLE from onset of symptoms is variable and can range from 1 month to 5 years 9  Postulated as possible pathogens:
 30% of heritability (median 4 to 8 months) o Group A streptococcus, Upper respiratory infections
 HLA-B27 responsible for two thirds of the total  Diffuse proliferative glomerulonephritis (class IV) - increases risk for renal morbidity. o GI infections, Coxsackievirus B
 Immune complexes - “full house” deposition of immunoglobulin and complement. o Toxoplasma, Enteroviruses Parvovirus B19
 Discoid rash:  Peak age of onset is 4-10 yr
o Hyperkeratosis  2nd peak of onset - late adulthood (45-64 yr
o Follicular plugging  Girls to boys with 2: 1.
o Infiltration of mononuclear cells into the dermal-epidermal junction (DEJ).  Familial
 Both B and T cells demonstrate functional impairments in SLE  Upregulation of gene products controlled by type I IFNs - clinical biomarker

 Most commonly involves:  Extreme photosensitivity to

o Skin ultraviolet (UV) light exposure
o Joints with generalized erythema in
o Kidneys sun-exposed areas.
o Bloodforming cells o If seen over the chest
Clinical o Blood vessels and neck, this erythema
manifestations is known as the shawl
o CNS
sign.
 Systemic signs of inflammation:
o Heliotrope rash
o Fever o Malar rash - Facial
o Lymphadenopathy erythema crossing the
 Deficiences of C1q, C2, C4 nasolabial folds
 Increased frequency of HLA-B8, HLA-DR2,  Classic Gottron papules:
and HLA-DR3  Rash of JDM:
 Cytokine profile, known as the type I o Develops as the first
interferon symptom in 50% of
 Neutrophil signature can be identified in patients
65% of adult SLE patients and has recently o Concomitant with
been rec- ognized as a potential weakness - 25%
biomarker for active lupus nephritis o Thickened
 Most common presenting complaints of erythematous and
children with SLE : scaly rash develops in
o Fever children over the
o Fatigue palms (known as
o Hematologic abnormalities mechanic’s hands)
Enthesitis-Related Arthritis o Arthralgia and soles along the
o Arthritis. flexor tendons,
 Arthritis in SLE: o Associated with anti–
o Usually present in the 1st yr of Jo-1 antibodies.
diagnosis;  Small-vessel inflammation is
o May be painful or painless swelling, often visible in the nail folds
o Often with stiffness in the morning, and gums as individual capillary loops that are thickened, tortuous, or absent
o Symmetric polyarthritis affecting  Telangiectasias
large and small joints.  Severe vascular inflammation causes cutaneous ulcers on toes, fingers, axillae, or
o Tenosynovitis is often epicanthal folds
o Joint erosions or other radiographic
changes are rare. Proximal muscle weakness
 During the 1st 6 mo of disease :  Often characterized by periods of flare and disease quiescence or may follow a more smoldering disease  Half of children exhibit muscle tenderness as a result of muscle inflammation
o The arthritis is typically asymmetric course  Affecting proximal muscles such as the neck flexors, shoulder girdle, and hip flexors.
o Involves ≤4 joints  Jaccoud arthritis  Difficulty climbing stairs, combing hair, and getting out of bed
o Most frequently: o Deforming arthritis associated with ligament and tendon laxity is rarely seen in pSLe  Examination;
 Knees  Rhupus o Inability to perform a sit-up
 Ankles o Destructive arthritis associated with a positive rheumatoid factor (rare in children) o Head lag in a child after infancy
 Hips.  Multiorgan disease is the hallmark of SLE o Gower sign (use of hands on thighs to stand from a sitting position).
 Inflammation of the small joints of the foot, or  Circulating antihistone antibodies are often present in drug-induced SLE; these antibodies are only detected
tarsitis, is highly suggestive of ERA. in up to 20% of individuals with SLE Amyopathic JDM or dermatomyositis sine myositis:
 Enthesitis :  Long-term complications of SLE and its therapy, including accelerated atherosclerosis and osteoporosis,  Classic rash but no apparent muscle weakness or inflammation;
o Typically symmetric become clinically evident in young to middle adulthood  More severe muscle involvement with long-term sequelae such as calcinosis and
o Typically affects the lower limbs lipodystrophy if untreated
 Sacroiliac or other axial joints are involved: Rule of 4 remains but new principle: there must be at least ONE clinical and ONE immunologic AND if there is
o Inflammatory back pain (Table 181.4) lupus nephritis by biopsy in the setting of ANA or anti- dsDNA, no further criteria is required Serologic testing results are divided into 2 groups:
o Hip pain 1. Myositis-associated antibodies (MAAs)
o Alternating buttock pain 2. Myositis-specific antibodies (MSAs) - Specific for myositis.
Psoriatic Arthritis
MSAs (Myositis-specific antibodies)
 SSA, SSB, Sm, ribonucleoprotein (RNP), and double-stranded (ds) DNA may increase
the likelihood of overlap disease or connective tissue myositis.
 Antibodies to Pm/Scl - Complicated by pulmonary interstitial fibrosis and cardiac
 Onset peaks - preschool and early adolescent years. involvement.
 Preschool years:  anti–Jo-1, anti–Mi-2, anti-p155/140, anti-NXP2 - predict the development of
o More often female complications.
o Antinuclear antibody (ANA) positive  Anti-p155/140 antibodies also known as TIF-1-γ
o Risk for asymptomatic ocular inflammation. o Associated with photosensitive rashes, ulceration, and lipodystrophy.
 Majority of children:  Anti-MJ antibodies, also known as NXP2
o Arthritis is asymmetric o Associated with cramps, muscle atrophy, contractures, and dysphonia.
o ≤4 joints  Anti-MDA5 antibodies
 Large (knees and ankles) and small (fingers and toes) joints may be involved o Concerning for development of interstitial lung disease.
 Axial (sacroiliac) and root (hip) joints - 30% of children
Radiographic studies
 MRI using T2-weighted images and fat suppression
o Identifies active sites of disease
 Rheumatoid nodules:  Contrast swallow study:
o On the extensor surfaces of the elbows o Palatal dysfunction and risk of aspiration.
o Spine
o Over the Achilles tendons
Pulmonary function testing
o Exclusively occur in RF-positive individuals (polyarthritis)
 Evanescent salmon-colored lesion
o Classic for sJIA
o Llinear or circular
 o Usually distributed over the trunk and proximal extremities Juvenile Ankylosing Spondylitis
o The classic rash is nonpruritic and migratory with lesions lasting <1 hr
 Koebner phenomenon
 Arthritis:
 Macrophage activation syndrome (MAS):
o Predominantly in the lower
o Fatal complication of sJIA
extremities
 Also referred to as secondary hemophagocytic syndrome or hemophagocytic o Often involves the hips
 Sacroiliitis of grade 2 or greater
bilaterally or at least grade 3
unilaterally
 At least 1 clinical criterion
involving:
o Inflammatory back pain
o Limitation of motion in the
lumbar spine
o Limitation of chest
expansion.
 JAS is present if the patient is <16 yr old

lymphohistiocytosis (HLH)

 No specific diagnostic laboratory test Imaging  Immunofluorescence examination of both Table 184.1
 MRI is more sensitive than radiography to detect early change  Show erosions or bony spurs (enthesophytes). affected and nonaffected skin may reveal Electromyography (EMG)
Diagnosis  Radiographic changes in cervical spine, most frequently in the neural arch joints at C2-  Squaring of the corners of the vertebral bodies and syndesmophyte formation resulting in the classic “bamboo deposition of immune complexes within the  Myopathy (increased insertional activity, fibrillations, sharp waves)
C3, may progress to atlantoaxial subluxation spine” characteristic of advanced AS is rare in early disease, particularly in childhood. DEJ.  Muscle fiber necrosis (decreased action potential amplitude and duration).
 MRI o This finding is called the lupus band test,
o Gold standard for early visualization of sacroiliitis which is specific for SLE Muscle biopsy
o Bone marrow edema adjacent to the joint  Antibodies to dsDNA:  Focal necrosis and phagocytosis of muscle fibers
o With fluid-sensitive sequences such as short-T1 inversion recovery (STIR). o Specific for SLE  Fiber regeneration
o Correlate with disease activity,
particularly in those with significant  ALT - usually elevated on initial presentation, whereas CK level may be normal.
nephritis.  ESR - often normal
 Hypergammaglobulinemia  (RF) test - negative.
 Antiphospholipid antibodies:  Anemia consistent with chronic disease.
o Increase clotting risk  (ANA) - >80% of children with JDM.
o 66% of children and adolescents with
SLE.
o Include the presence of:
 Anticardiolipin
 Anti–β2-glycoprotein antibodies
 Prolonged phospholipid-
dependent coagulation test results
(partial thromboplastin time, dilute
Russell viper-venom time), and
circulating lupus anticoagulant

Treatment  NSAIDs, such as naproxen (15-20 mg/ kg/day):  Sunscreen and avoidance of prolonged direct sun exposure & other ultraviolet light Intravenous (IV) gamma globulin
o Frequently used initially  Corticosteroids (1-2 mg/kg/day):  Frequently used as an adjunct for treatment of severe disease
o May slow the progression of structural damage (syndesmophyte formation and growth) if used o Mainstay of treatment
continually. o Adverse effects: Corticosteroids
 Mild disease  Growth disturbance, Weight gain  Mainstay of treatment.
o Intraarticular corticosteroids (e.g., triamcinolone acetonide/hexacetonide)  Striae ,Acne  Oral prednisone
o Also help to control peripheral joint inflammation.  Hyperglycemia, Hypertension o Clinically stable child without debilitating weakness
 Cataracts, Avascular necrosis  IV administration
 Moderate disease and JAS:  Osteoporosis o Children with GI involvement have decreased absorption of oral corticosteroids
o Typically necessary to add a second-line agent. o Severe disease - high doses of intravenous (IV) methylprednisolone  High-dose pulse methylprednisolone
o DMARDs such as sulfasalazine (up to 50 mg/kg/day; maximum 3 g/day) or methotrexate (10 mg/m2) o Steroid-sparing immunosuppressive medication - limit cumulative steroid exposure. o In more severe cases with respiratory or oropharyngeal weakness
may be beneficial for peripheral arthritis, but these medications have not been shown to improve axial  NSAID : arthralgias and arthritis  Corticosteroid dosage is slowly tapered over 12 mo, after indicators of inflammation
disease in adults.  Hydroxychloroquine: (muscle enzymes) normalize and strength improves.
o Effective in controlling rash and mild arthritis, Prevents SLE flares
 Tumor necrosis factor (TNF) inhibitors (e.g., etanercept, infliximab, adalimumab): o Should never be prescribed at doses >6.5 mg/kg (maximum 400 mg daily) Methotrexate
o Efficacious in reducing symptoms and improving function in adults with AS, and there is evidence that o Potential toxicities: retinal pigmentation & color vision impairment  Decreases the length of treatment with corticosteroids
similar responses are seen in children.  Steroid-sparing immunosuppressive agents:  Often used as a steroid-sparing agent in JDM.
o It remains unclear whether TNF inhibitors have an impact on structural damage in established AS o Methotrexate, leflunomide & azathioprine: treat persistent moderate disease, including arthritis,  Folic acid is typically given with methotrexate starting at a dose of 1 mg daily to
significant cutaneous or hematologic involvement, and pleural disease reduce toxicity
o MMF and rituximab - hematologic manifestations
o Cyclophosphamide: reserved for the most severe Hydroxychloroquine
o Mycophenolate mofetil: effective as CYC for inducing remission  Secondary disease-modifying agent to reduce rash and maintain remission.
o Belimumab: improves multiple markers of disease severity
 CARRA treatment plans advise 6 mo of induction therapy with either cyclophosphamide (given per NIH Ophthalmologic follow-up
Protocol as 500-1000 mg/m2 IV monthly) or MMF (600 mg/m2, up to 1500 mg, twice daily), used in  Monitor for rare retinal toxicity
combination with 1 of 3 standardized glucocorticoid regimens.
 Switch agents - Fail to achieve a partial response in 6 mo Nasogastric or gastrostomy feedings
 Oral medication adherence is very poor in pediatric SLE, which must be considered when weighing the  Children with pharyngeal weakness
benefits of an IV infusion vs a twice-daily oral medication such as MMF.  To avoid aspiration
Maintenance therapy of lupus nephritis  Rarely, children with severe respiratory weakness require ventilator therapy and
 Cyclophosphamide every 3 mo, or MMF even tracheostomy until the respiratory weakness improves.
 Azathioprine, typically for 36 mo after completion of induction therapy.
 Attention to cholesterol levels, smoking status, body mass index, blood pressure, and other traditional Full bowel rest
cardiovascular risk factors is warranted.  GI vasculitis
Long-term anticoagulation
 SLE patients with antiphospholipid antibody syndrome Physical therapy and occupational therapy
 Prevent thrombotic events.  Integral in the management
 Antiphospholipid antibody positive without a history of clot - aspirin (81 mg daily).  Passive stretching in the disease; direct reconditioning
 Adequate intake of calcium and vitamin D is necessary to prevent future osteoporosis, particularly as  Bed rest is NOT indicated
vitamin D levels are lower in pediatric SLE patients compared to age-matched healthy controls.
 Recommended, including the annual influenza vaccination.
 Hydroxychloroquine is recommended throughout the pregnancy of all SLE patients
  50% of patients with JIA have active disease persisting into early adulthood, often with  >5 yr in juvenile spondyloarthritis predicts disability.  Mortality rate 1%
severe limitations of physical function Neonatal Lupus  Children with JDM generally respond well to therapy.
 Persistent oligoarticular disease: majority achieve disease remission  Not an autoimmune disease of the fetus  At 7 yr of follow-up, 75% of patients have little to no residual disability
 Extended oligoarticular disease: poorer prognosis  Results from passively acquired autoimmunity, when maternal immunoglobulin G autoantibodies cross the
 Predictors of severe and persistent disease: placenta and enter the fetal circulation
Prognosis o Young age at onset  The vast majority of NLE cases are associated maternal :
o RF seropositivity or rheumatoid nodules o anti-Ro (also known as anti-SSA)
o (+) anti-cyclic citrullinated peptide antibodies o anti-La antibodies (also known as anti-SSB)
o Large numbers of affected joints o anti-RNP (antiribo- nucleoprotein) autoantibodies
 Disease involving the hip, hand & wrist: poorer prognosis Risk Factors
 sJIA: most difficult to control  Siblings of infants with NLE - 15–20% chance of developing NLE.
 Poorer prognosis:  A mother with history of a born child with congenital heart block has a 15%
o Polyarticular distribution of arthritis  Hereditary: Sjögren syndrome or SLE.
o Fever lasting >3 mo  Conduction system abnormalities - detected in utero beginning at 16 wk of gestational age
o Increased inflammatory markers for >6 mo
 Orthopedic complications include leg length discrepancy and flexion contractures Annular or macular rash typically affecting the face (especially the periorbital area), trunk, and scalp
o Management: shoe lift on the shorter side to prevent secondary scoliosis  Can be present at birth
 More often appears within:
o The first 6-8 wk of life
o After exposure to UV light
o Typically lasts 3-4 mo.
 Most feared complication is congenital heart block.
 Third-degree congenital heart block is permanent

Conduction system abnormalities

 Prolongation of the PR interval to complete heart block

Diagnosis
 Regular fetal ECG from 16th week until delivery
 Screening fetal echocardiography
o Performed weekly from 16-26 wk of gestation and then biweekly through 34 wk
 Screening for maternal anti Ro and anti La
o If fetal bradycardia is found during in utero monitoring
o If fetal echocardiography confirms a conduction defect
Treatment
 Cardiac pacing
 Cardiac transplantation - Severe cardiomyopathy
 Fluorinated steroids (betamethasone and dexamethasone) - Improve cases of hydrops fetalis
 Addition of β-agonist therapy - increase fetal heart rate
o In combination with corticosteroids or IVIG - help prevent hydrops in cases of severe fetal heart block
 IVIG-limited studies at 1–2 g/kg maternal weight - Cytopenias
 Reassurance - Usual approach to management of C-NLE
 Topical corticosteroids - moderate to severe NLE rash.
 Supportive care - hepatic and neurologic manifestation.
 Hydroxychloroquine - Reduce the frequency and recurrence of congenital heart block.
 Plasmapheresis
 The most common causes of death in SLE patients are infection and complications of glomerulonephritis and Calcinosis
neuropsychiatric disease  Dystrophic deposition of:
 Most common causes of mortality are complications of atherosclerosis and malignancy. o Calcium phosphate
 5-year survival rate: 95% o Hydroxyapatite
Others  10 yr survival rate - 80-90% o Fluoroapatite crystals
(Complications)
Lipodystrophy
 10–40% of patients with JDM
 Difficult to recognize.
 Progressive loss of subcutaneous and visceral fat, typically over the face and upper
body
 Scleroderma and Raynaud Phenomenon Behçet Disease Sjögren Syndrome Kawasaki Disease
Pathogenesis  Presence of fibrosis of the skin.  Primary variable vessel vasculitis  Characterized by progressive lymphocytic and plasma cell infiltration of the  Formerly known as mucocutaneous lymph node syndrome and infantile polyarteritis nodosa
 2 major categories:  Involvement of any size and type (arterial, venous) of blood vessel exocrine glands, especially salivary and lacrimal  Vasculitis with a predilection for the coronary arteries.
o Juvenile localized scleroderma (JLS, also known as morphea) :  Autoinflammatory disease.  Rare in children  20–25% of untreated children develop coronary artery abnormalities (CAA) including aneurysms
 Largely limited to the skin  Originally described with recurrent oral ulcerations, uveitis, and skin abnormalities, the  Affects middle-age women  KD is the leading cause of acquired heart disease in children in most developed countries, including the United States
 More common BD spectrum is much broader  Classic symptoms of dry eyes (keratoconjunctivitis sicca) and dry mouth and Japan
 Predominant type seen in pediatric populations (>95%),  Onset : 8-12 yr of age (xerostomia).  Higher susceptibility to KD in boys
o Juvenile systemic sclerosis (JSSc)  HLA-B5101  Manifests at 35-45 yr of age  Children age <5 yr had the highest annual hospitalization rates
 Multisystem organ involvement.  People along the Silk Road  90% of cases among women  Body surface area (BSA)–adjusted coronary artery dimensions on baseline echocardiography in the 1st 10 days of
 Associated with mortality and severe multiorgan morbidity  Co-association with the MEFV (Mediterranean fever) gene.  Mean age at diagnosis in children is 9-10 yr; illness appear to be good predictors of involvement during follow-up.
 Autoimmunity :  Infectious agent genetically predisposed host:  75% are girls.  Baseline z scores may provide a useful imaging biomarker
o Key process in the pathogenesis of both localized and systemic scleroderma  Streptococci  Can occur as an isolated disorder, referred to as primary Sjögren syndrome
o Localized disease:  Herpes simplex virus type 1 (sicca complex) Infectious triggers:
 Positive antinuclear antibody (ANA) test result (42%)  Parvovirus B19.  Infrequent occurrence of the illness in infants <3 mo old
 47% have antihistone antibodies.
 Children with JSSc have higher rates of ANA positivity (80.7%) and may have anti–Scl-70  Affects the medium-size arteries.
antibody (34%, antitopoisomerase  Coronary arteries are most often involved
 Linear scleroderma :  A 3-phase process to the arteriopathy of KD has been described.
o Most common subtype o 1st phase;
o 65% of patients diagnosed before age 18 yr.  Neutrophilic necrotizing arteritis
o After age 8 yr the female/male ratio for both LS and SSc is approximately 3 : 1, whereas in  1st 2 wk of illness
patients younger than 8 yr,  Saccular aneurysms may form from this arteritis.
 No sex predilection o 2nd phase:
 Subacute/chronic vasculitis
 Driven by lymphocytes, plasma cells, and eosinophils
 May last weeks to years and results in fusiform aneurysms.
o 3rd phase
 Progressive stenosis .

Clinical Localized Scleroderma  Painful oral ulcer - The most  Recurrent parotid gland enlargement and parotitis are the most common Fever of KD
manifestations  Onset is insidious frequent initial symptom manifestations in children (>70%)  High spiking (≥38.3°C [101°F])
 Initial skin manifestations of localized disease:  Sicca syndrome (dry mouth, painful mucosa, sensitivity to spicy foods, halitosis,  Remitting
o Erythema BD oral ulcers widespread dental caries) predominates in adults.  Unresponsive to antipyretics.
o Bluish hue seen around an area of waxy induration  May be single or multiple  Duration of fever without treatment is
o Subtle erythema may be the only presenting sign  From 2-10 mm Children with Sjögren syndrome generally 1-2 wk but may be as short as 5
o Edema and erythema are followed by indurated, hypopigmented or hyperpigmented  Any location in the oral cavity  Recurrent parotitis (72%) days
atrophic lesions  Often very painful  Sicca symptoms (38%)  May persist for 3-4 wk.
 Oral ulcers last 3-10 days and  Polyarthritis (18%)
Extracutaneous manifestations: heal without scarring. 5 principal clinical criteria of KD
 Arthritis (47%) 1. Bilateral nonexudative conjunctival injection
 ANAs and SSA and SSB antibodies in children are 78%, 75%, and 65%,
 Neurologic symptoms (17%) associated with en coup de sabre. Genital ulcers with limbal sparing
respectively, with rheumatoid factor present in 67%.
 Heal with scars 2. Erythema of the oral and pharyngeal mucosa
Systemic Scleroderma  60–85% of the patients with strawberry tongue and red, cracked lips;
 Skin manifestations of SSc:  Occur after puberty 3. Edema (induration) and erythema of the hands
o Early phase of edema that spreads proximally from the dorsum of the hands and fingers and Bilateral eye involvement and feet;
4. Rash of various forms (maculopapular, erythema multiforme, scarlatiniform or less often psoriatic-like, urticarial or
includes the face.  30–60% of pediatric patients
o Eventual decrease in edema is followed by induration and fibrosis of skin, micropustular)
 Main symptoms of anterior uveitis:
o Later, atrophic skin becomes shiny and waxy in appearance. 5. Nonsuppurative cervical lymphadenopathy, usually unilateral, with node size >1.5 cm
o Blurred vision
o As lesions spread proximally, flexion contractures develop at the elbows, hips, and knees o Redness
o In the face, small oral stoma with decreased mouth aperture.  Perineal desquamation is common in the acute phase.
o Often in the form of panuveitis
o Skin ulceration over pressure points, such as the elbows, may be associated with o Anterior uveitis may be seen in females.  Gastrointestinal (GI): >60% of patients,
subcutaneous calcifications. o Uveitis : more common in males.  1 respiratory symptom: 35%.
o Severe Raynaud phenomenon causes ulceration of the fingertips with subsequent loss of o Vitreitis and retinal vasculitis - most prominent features of posterior involvement.  Arthritis may occur early in the illness or may develop in the 2nd or 3rd wk.
tissue pulp and tapered fingers (sclerodactyly) o Complications of uveitis include blindness (unusual with treatment), glaucoma, and  Small or large joints may be affected
o Resorption of the distal tufts of the distal phalanges may occur (acroosteolysis). cataracts.  Arthralgias may persist for several weeks.
o Salt-and-pepper appearance to skin.
Cardiac involvement
 Pulmonary disease Skin lesions of BD
 Most important manifestation of KD.
 Erythema nodosum (50%)
o Most common visceral manifestation of SSc  Myocarditis:
o Includes both arterial and interstitial involvement (alveolitis).  Papulopustular acneiform lesions (85%) o Occurs in most patients with acute KD
o Neutrophilia or eosinophilia on BAL suggest active alveolitis.  Pathergy (50%):  Cardiogenic shock (KD shock syndrome)
 Gastrointestinal tract disease : o Pustular reaction occurring 24-48 hr after a sterile needle puncture or saline o Greatly diminished left ventricular function.
injection;
o 25% of children with SSc  Develop CAA in the 2nd to 3rd week of illness ungreated
o Common manifestations: o It is not pathognomonic of BD
 Almost all the morbidity and mortality in KD occur in patients with large or giant coronary artery aneurysms
 Esophageal and intestinal dysmotility o z score ≥10 or an absolute dimension of ≥8 mm.
 Mortality from JSSc is usually a result of cardiopulmonary disease. Vasculitis of BD  Occasionally KD initially presents with only fever and lymphadenopathy (node-first KD).
 Involves both arteries and veins o Children with node-first KD tend to be older (4 vs 2 yr) and have more days of fever and higher CRP levels
Raynaud Phenomenon  Deep venous thrombosis of the lower limbs - most frequent vasculitic feature. Suggest the diagnosis of KD
 Most frequent initial symptom in pediatric systemic sclerosis  Budd-Chiari syndrome may occur.  Persistence of high fever
 70% of affected children months to years before other manifestations.  Lack of response to antibiotics
 Classic triphasic sequence: (induced by cold exposure and/or emotional stress)  Pulmonary aneurysms are the most severe feature of pediatric BD, associated with the  Subsequent development of other signs of KD
o Blanching - Initial arterial vasoconstriction, resulting in hypoperfusion and pallor highest mortality.
o Cyanosis - Venous stasis 3 clinical phases
o Erythema of the digits - Reflex vasodilation caused by the factors released from the ischemic Central nervous system (CNS)  Acute febrile phase
phase  Dural sinus thrombosis is the most common CNS manifestation in children o Fever and the other acute signs of illness
 Color change is classically reproduced by immersing the hands in iced water and reversed by o Elevated ESR or CRP value
warming. Gastrointestinal (GI) o Usually lasts 1-2 wk
 Abdominal pain, diarrhea, and intestinal ulcerations, most often in the ileocecal region.  Subacute phase
Raynaud disease  Oligoarticular arthritis/arthralgia is present in >50% of patients and can be recurrent, but o Associated with desquamation, thrombocytosis, development of CAA,
 Often begins in adolescence is nondeforming. o The highest risk of sudden death in patients who develop aneurysms;
 Symmetric occurrence o Generally, lasts 3 wk
 Absence of tissue necrosis and gangrene  Require the presence of oral ulcers (at least 3 times per year) along with 2 other major  Convalescent phase
 Children have normal nail fold capillaries (absence of periungual telangiectasias). features, including genital ulcers, a positive pathergy test, uveitis, and the characteristic o Begins when all clinical signs of illness have disappeared and continues until the erythrocyte sedimentation rate
 RP should be distinguished from acrocyanosis and chilblains. skin lesions (ESR) returns to normal
 Incomplete or partial Behçet disease - If only 1 of the criteria is present along with oral o Typically 6-8 wk after the onset of illness.
ulcerations  In the presence of ≥4 principal criteria, particularly when redness and swelling of the hands and feet are present,
Kawasaki disease diagnosis can be made on day 4 of illness

Diagnosis  Diagnosis of JLS is based on the distribution and depth of characteristic lesions.  There are no specific laboratory tests.  The diagnosis is based on clinical features  Table 191.1
 Biopsy is helpful to confirm the diagnosis.  Acute-phase reactants are often mildly elevated  Biopsy of salivary or parotid glands:  There is no diagnostic test for KD
 No laboratory studies are diagnostic of either localized or systemic scleroderma. o Current gold standard for diagnosis.  Two-dimensional echocardiography is the most useful test to monitor for development of CAA.
 Elevated ESR, eosinophilia, or hypergammaglobulinemia, all of which normalize with treatment. o Demonstrating foci of lymphocytic infiltration,  Adjusted for BSA (z scores), may be increased in the 1st 5 wk after presentation, and as previously noted, baseline z
 Elevated aldolase, can be seen with muscle involvement. scores may offer prognostic information regarding ultimate coronary artery dimensions.
 Anemia, leukocytosis, and eosinophilia and autoantibodies (ANA, anti–Scl-70).  Anti–β-fodrin autoantibodies  Aneurysms:
 MRI is useful in en coup de sabre and Parry-Romberg syndrome (facial hemiatrophy) for o Useful diagnostic marker for juvenile Sjögren syndrome. o Small (≤4 mm internal diameter [ID])
determination of CNS or orbital involvement.  Schirmer test detects abnormal tear production (≤5 mm of wetting of filter o Medium (>4 to ≤8 mm ID)
paper strip in 5 min). o Giant (>8 mm ID).
  2 of 20 minor criteria (see Table 185.2).  Rose bengal staining detects damaged ocular epithelial conjunctival and The AHA z-score classification system is as follows:
corneal cells. 1. No involvement: always <2
2. Dilation only: 2 to <2.5; or if initially <2, a decrease in z score during
Symptomatic treatment follow-up ≥1
 Use of artificial tears 3. Small aneurysm: ≥2.5 to <5
 Massage of the parotids 4. Medium aneurysm: ≥5 to <10, and absolute dimension <8 mm
 Oral lozenges 5. Large or giant aneurysm: ≥10, or absolute dimension ≥8 mm
 Fluids to limit the damaging effects of decreased secretions.
 Cardiologic follow-up every 5 yr.
Corticosteroids, nonsteroidal antiinflammatory drugs, and hydroxychloroquine  Diagnosis of KD should be made within 10 days, and ideally within 7
 Among the more commonly used agents for treatment days, of fever onset to improve coronary artery outcomes.
 In atypical or incomplete KD, - persistent fever but <4 of the 5 characteristic clinical signs.
 Any infant age ≤6 mo with fever for ≥7 days without explanation undergo echocardiography to assess the coronary
Methotrexate and etanercept
arteries
 Treatment of arthritis.

Cyclosporine and cyclophosphamide

 Life-threatening complications

Treatment  Superficial morphea - topical corticosteroids or ultraviolet therapy. Azathioprine  Aspirin is continued for its antithrombotic effect until 6-8 wk
 Inflammatory eye disease. after illness onset and is then discontinued in patients who
Anti–tumor necrosis factor (TNF) treatment and interferon (IFN)-α have had normal echocardiography findings
Methotrexate + corticosteroids : o Antithrombotic medications are the cornerstone of
 Considered for refractory eye disease.
o Effective in treating JLS by preventing lesion extension and resulting in significant skin therapy for the child with coronary disease.
softening and improved range of motion of affected joints. Sucralfate, corticosteroids  Corticosteroids have been used as primary therapy with the
o Eosinophilic fasciitis  For oral and genital ulcers 1st dose of IVIG in hopes of improving coronary outcomes
 The treatment plan for JLS includes Colchicine  Coronary artery stenosis and inducible ischemia - coronary
1. Weekly subcutaneous (SC) methotrexate  For erythema nodosum or arthritis in males and females artery bypass grafting (CABG)
2. Weekly SC methotrexate plus either 3 mo of high-dose intravenous (IV) corticosteroids for 3  For genital ulcers in females
consecutive days a month or weekly corticosteroids at the same dose for 3 mo;  Skin features, and disease activity.
3. High-dose daily oral corticosteroids with a slow taper over 48 wk. Thalidomide, sulfasalazine, corticosteroids, azathioprine, and anti-TN
 GI disease
Mycophenolate mofetil (MMF) Corticosteroids, azathioprine, cyclophosphamide, and IFN-α
 Second- line agent for recalcitrant disease.  For CNS disease.
Corticosteroids and azathioprine
 RP is treated with cold avoidance, and pharmacologic interventions are reserved for severe
 Vascular involvement with venous thrombosis
disease.
o Calcium channel blockers -most common pharmacologic interventions. Cyclophosphamide
 Angiotensin- converting enzyme (ACE) inhibitors (captopril, enalapril) - hypertension associated  Pulmonary arterial or cardiac involvement
with renal disease.
 Methotrexate or MMF -r- skin manifestations.
 Cyclophosphamide and MMF - pulmonary alveolitis and prevent fibrosis.
 Corticosteroids should be used cautiously in SSc because of an association with renal crisis

 The treatment of RP begins with avoiding cold stimuli, using hand and foot warmers, and avoiding
carrying bags by their handles (impairs circulation).

Prognosis  JLS is generally self-limited,  Early diagnosis and effective treatment improve the outcome of BD.  Symptoms of Sjögren syndrome develop and progress slowly.  Vast majority of patients with KD return to normal health;
 Period of stabilization = 3-5 yr, although there are reports of active disease lasting up to 20 yr.  Diminished salivary flow typically remains constant for years.
 Death from a en coup de sabre lesion with progressive neurologic decline has been reported.

Others  The most common cause of death is heart failure caused by myocardial and pulmonary fibrosis  Myocardial infarction
(Complications,  Angina
Tables)  Sudden death