Rheumatic Diseases in Rheumatic Diseases in ChildrenChildren

ObjectivesObjectives

Review Rheumatic Diseases Discuss the medications utilized to treat

Rheumatic Conditions

By the end of this presentation you will:

The Immune SystemThe Immune System 101101

AntibodiesLymphocytes

T-cellsB-cells

PhagocytoesNatural killer cells

Granulocytesmacrophils

Skin, mucus membranes, enzymesNatural microbial floraComplement proteins

B and T cells and their productsare the target for many of the

treatmentsfor

Autoimmune diseases seen in

Rheumatology

3rd line

2nd line

1st line

The FactorsThe Factors of Autoimmune of Autoimmune DiseaseDisease

Genetic predisposition

Environment Timing

Rheumatic Rheumatic ConditionsConditions Systemic Lupus Erythematosus

(SLE) Juvenile Arthritis

UveitisLinear Scleroderma Systemic Sclerosis

Juvenile Dermatomyositis Vasculities

Juvenile ArthritisJuvenile Arthritis•85,0000-115,000 children in the United States have Juvenile Arthritis

•Most Common Rheumatic Disorder in Children

•Diagnostic Criteria •Age at onset <16•Arthritis in one or more joints•Duration of disease 3 months or longer (6weeks for ACR)

Criteria Juvenile Criteria Juvenile ArthritisArthritis

• Types defined by characteristics of disease

• Pauciarticular (Oligoarthritis for JIA) <5 joints

• Polyarticular: >5 joints• Systemic:arthritis with characteristic

fever (rash) • Juvenile Psoriatic arthritis• Spondyloarthropathies

• Juvenile Anklylosing Spondyloarthritis • Enthesitis-related arthritis

Clinical Clinical Manifestations Manifestations Juvenile ArthritisJuvenile ArthritisJoint specificMorning stiffnessPain on motionLoss of motionTenosynovitisJoint inflammation: Swelling, redness, heat, pain, loss of function

Extra-articular Abnormalities in growth and developmentOsteopenia

Organ-Specific Nodules*** Systemic or rare involvement=vasculitis, cardiac disease, pleuropulmonary disease, GI tract, Lympadenopathy and splenomegaly, hepatosplenomegaly, neurologic, renal

Systemic JA – RashSystemic JA – Rash

Juvenile ArthritisJuvenile Arthritisprior to the age of methotrexate and prior to the age of methotrexate and biologicsbiologics

Treatment JATreatment JA NSAIDS Intra-articular injection: Ibuprofen Aristospan Naprosyn Diclofenac

Glucocorticosteroids DMARDS Prednisone Methotrexate Methylprednisolone Sulfasalazine Leflunomide

Biologic Response Modrifiers Etanercept(Enbrel);

Adalimumab (Humira)Infliximab (Remicade);

Anakinra (Kineret)/systemicAbatacept (Orencia)Rituximab(Rituxan)

Tocilizumab(in study)

Laboratory StudiesLaboratory StudiesNo laboratory testing is diagnostic

for JA

Used for evidence of inflammation, determine pathogenesis, support diagnosis, and monitor treatment

Laboratory StudiesLaboratory Studies • Antinuclear antibody (ANA)

– Pauciarticular disease (+) demonstrates increase risk of uveitis• Rheumatoid Factor

– More indicative erosive disease 3% (Cassidy, 2005) • Sedimentation rate (ESR)

– Non specific measure of inflammation • C reactive protein (CRP)

– more reliable monitor of inflammatory response• CBC • Chem 14

– monitoring potential side effects NSAIDS and methotrexate increased LFT’s

UVEITISUVEITISInflammation of uveal tract

◦ Iris, ciliary body, and/or choroid Asymptomatic until very late stagesUveitis is often progressive & difficult to

control◦ Possible Symptoms: synichiae, reduced vision,

glaucoma, increased inflammation in the other eye, and blindness

Slit Lamp examination for diagnosis and follow-up

Uveitis

Treatment UveitisTreatment Uveitis Opthalmology: Topical steroid drops

Systemic Treatment

DMARD Methotrexate

Corticosteroids Prednisone

Methylprednisonlone

Biologic Response Modifiers

Infliximab (Remicade)

Etanercept(Enbrel); Adalimumab (Humira)

Diclizumab (Zenapak)

Systemic Lupus Systemic Lupus Erythematosus (SLE)Erythematosus (SLE)• Incidence: 0.5 -0.6/100,000 children• Prevalence: 5-10,000 children in the USA• Onset: 15% in childhood• Female to Male ratio

– Higher female onset post pubescent– Equal pre pubescent

• Affects multiple systems • Characterized by inflammation of the

small blood vessels and connective tissue

Diagnosis of SLEDiagnosis of SLE• 4 out of 11 criteria

◦ Malar rash◦ Discoid rash◦ Photosensitive rash◦ Mucosal ulcers◦ Serositis◦ Arthritis ◦ Renal disease/cellular casts◦ CNS: Seizure or psychosis◦ Hematology: Leukopenia <4000/cubic mm; lymphopenia <

1500/cubic mm; thrombocytopenia <100,000/mm3

◦ Immunoserology: anti double stranded DNA (anti ds DNA), anti Smith - specific marker for active SLE, false + (VDRL)

◦ Positive AntiNuclear Antibody test (ANA) (95%, typical pattern is homogeneous)

SLE rashes

Upper Malar

Lower left Discoid

Lower rightMixed rashes

Laboratory Studies: Laboratory Studies: DiagnosticDiagnostic Cytopenia

◦ Thrombocytopenia ◦ Anemia: hemolytic (Coombs +) ◦ Leucopenia

Positive Immunoserology◦ dsDNA: (+) presence of antibodies◦ Sm nuclear antigen: (+) presence of antibodies◦ Antiphospholipid antibodies: (+) risk of clotting◦ VDRL (syphilis) false (+)

Antinuclear antibody (ANA)◦ antibody most commonly found in SLE

Laboratory Studies: Laboratory Studies: MonitoringMonitoring• CBC • Chem 14• Antinuclear Antibody• dsDNA:• Complement 3 and 4

– low in most active SLE disease, used for tracking not diagnostic

• Urinalysis with micro– initial indication of renal disease– usually shows lots of blood, protein and high specific

gravity!!!• Spot urine protein and creatinine

– monitoring of renal disease (UP/UC ratio)

Treatment SLETreatment SLEPlaquenil Aspirin NSAIDS

Prednisone Methotrexate

Imuran Rituximab IVIG

Orencia

Cellcept Cytoxan IV

Daily Cytoxan

Plasmapheresis

Nitrogen MustardCampath

BMT

Heliotrope RashGottran’s Papules

Features of Juvenile Dermatomyositis

Juvenile Dermatomyositis: Radiographical features

Thigh of 12yr old maleInflammation is bright white

Calcinosis

Laboratory JDMSLaboratory JDMSCBCChem 14: monitoring medication side effects Aldolase: elevated with muscle

inflammation: monitoring and confirmation not diagnostic

Neopterin: same as aldolaseCPK: same as aldolase and NeopterinESR: inflammation unspecified locationUrinalysis

Treatment Treatment DermatomyositisDermatomyositis

Glucocorticosteroids

Hydroxychloroquine

IVIG

Biologics Infliximab Etanercept

AbataceptMethotrexate

Cyclosporin

Stem Cell Transplant

Cyclophosphamide

Campath

Linear SclerodermaLinear Scleroderma11 yr old girl

Coupe de Sabre

10 year old girlDiagnosis age 4

Systemic Sclerosis Systemic Sclerosis ChildrenChildren

0.2-0.9% of the Major Mixed Connective Tissue Disorders

•Prevalence: 0.8/100,000 children in the USA•Onset: 3 % in childhood•Female to Male ratio: 1:1= <8yrs old and 3:1 = >8yrs old•Average age onset in childhood: undefined •Affects multiple systems connective tissue disorder•Characterized by thickening and hardening of the skin in conjunction with fibrous and degeneration of multiple organsCassidy, 2005

Systemic Sclerosis: Systemic Sclerosis: Clinical Clinical ManifestationsManifestations• Raynaud’s phenomenon

• Skin changes– Sclerosis, edema, atrophy, Telangiectases, calcinosis

• Sclerodactyly• Musculoskeletal Disease estimated 35%

– Morning stiffness, joint pains, contractures, tendon tightening• Gastrointestinal Disease 25%

– Ulcerations of the mouth• Digestive problems• Kidneys

– high blood pressure– kidney failure

• Heart and lung– arrhythmias, heat failure– scaring of the lung tissue

Scleroderma: Scleroderma: Acrolysis and Acrolysis and calcinosiscalcinosis

Unaffected

SclerodermaSclerodermaRenal arteriogram:

Left is normalRight is renal insufficiency

Pulmonary x-rayInterstitial Fibrosis

Laboratory Laboratory SclerodermaSclerodermaCBCChem. 14UrinalysisSCL70 antibody (diagnostic for SSc <30% of children, >70% in adults)

Treatment Treatment SclerodermaScleroderma

Glucocorticosteroids

Hydroxychloroquine

IVIGMethotrexate

Cyclosporin

Stem Cell Transplant

Cyclophosphamide

CampathMycophenolate Mofetil

Classification of Classification of VasculitidesVasculitides• Small Vessel Vasculitis

– ANCA associated• microscopic polyangitis; Wegener’s granulomatosis; Churg-Strauss Syndrome; Drug induced

– Immune complex• Henoch-Schonlein purpura; (SLE,JIA, Sjogrens); Bechets; Drug associated; Infection associated

– Paraneoplastic• lymphoproliferative neoplams induced, myeloproliferative neoplasm induced, carcinoma induced

– Inflammatory Bowl Disease (IBD)

Classification of Classification of VasculitidesVasculitides

Medium Vessel Vasculitides

◦ Polyarteritis nodosa◦ Kawasaki disease

Large Vessel Vasculitides

◦ Giant Cell arteritis◦ Takayasus’s arterititis

Wegener’s Wegener’s GranulomatosisGranulomatosis

•Prevalence: 0.1/100,000 children•Onset: 3 % in childhood•Female to Male ratio: undefined•Average age onset in childhood: 15.4•Characterized by granulomatous vasculitis in the upper and lower respiratory tracks •Criteria for diagnosis: 2 of 4 must be present

• Nasal of Oral Inflammation• Abnormal appearing chest radiograph• Abnormal urinary sediment

• Granulomatous inflammation Cassidy, 2005

Wegeners Wegeners GranulomatosisGranulomatosisSaddle Nose Saddle Nose

Wegener Wegener Granulamotosis Granulamotosis granulomas and cavitations granulomas and cavitations

Treatment Treatment Wegener’s Wegener’s GranulomatosisGranulomatosis

GlucocorticosteroidsIVIG

Methotrexate

Cyclophosphamide

Takayasu’s ArteritisTakayasu’s Arteritis•Most common in young women of Japanese origin

•Classification criteria for diagnosis• Sub clavian or aortic bruit • Decreased brachial artery pulse• Blood pressure difference of >10mm between arms• Claudication of extremities• Arteriographic evidence of narrowing or occlusion of aorta, its primary branches

or large arteries in the proximal, upper, or lower extremities

Cassidy, 2005

Takayasu: Takayasu: AngiogramsAngiograms

Treatment Treatment Takayasu’s ArteritisTakayasu’s Arteritis

Glucocorticosteroids

Methotrexate

Infliximab

Cyclophosphamide