Insights into the DX of Pediatric SLE Dr. John H. Yost Pediatric Rheumatology Children s Hospital at Dartmouth Assistant Professor of Medicine Geisel School of Medicine at Dartmouth john.h.yost@hitchcock.org
A DIAGNSOSIS of SLE is RARELY OBVIOUS
Pediatric Systemic Lupus Erythematosus (SLE) INTRODUCTION More to Come!
Diseases Resembling SLE RHEUMATOLOGIC JIA (JRA systemic)** MCTD** Psoriatic arthritis** Sjogren s Syndrome** Polymyalagia rheumatica Polymyositis Juvenile Dermatomyositis** Overlap Syndrome ** Vasculitis/Kawasaki s ** Fibromyalgia** NEOPLASTIC and OTHER Myeloma Neuroblastoma** Lymphoma** Infections** Reactive arthritis** Lyme disease** Autoimmune thyroid** Autoimmune neurologic (MS,MG) disease ** PEDIATRIC DISEASE
Common Conditions Co-Existing with SLE Fibromyalgia Hypothyroidism Osteoarthritis Bursitis LUPUS Anemia Infection Tendonitis Migraine Cardiovascular Disease
EVOLUTION of COLLAGEN VASCULAR DISEASES over TIME RA LUPUS Overlap: RHUPUS LUPUS RA Transformation
MCTD: Mixed Connective Tissues Disease A Lupus-Like Disease with (+) Anti-RNP Antibody
SLE: Systemic Lupus Erythematosis Grey wolf The great masquerader The angry bite Canis lupus
Historical Descriptions of Lupus 14 th century skin lupus 16 th century - "Leprosy is more clearly recognized in the nose, where it shows well-defined symptoms. Sometimes it is also called wolf because it can contaminate all of a man's limbs as does cancerous lupus 1808 lupus vulgaris TB 1878 Kaposi discoid and disseminated lupus. 1894 Osler - 29 patients who presented "erythema with visceral injuries". From "Diseases of the skin. An Outline of the principles and practice of Dermatology Malcolm Morris, Cassel & Co., London, 1894
SLE -- EPIDEMIOLOGY Prevalence: 1 in 2000 Americans Peak incidence: 15 to 40 years 8:1 female:male ratio Increased incidence: African-Americans, Hispanics, Native Americans Greater frequency in urban areas
FREQUENCY OF SLE CLINICAL MANIFESTATIONS Fatigue 80-100% Cutaneous Arthritis >90% Butterfly Rash >50% Arthralgia >90% Photosensitivity >50% Renal Oral ulceration 30% Nephrosis 18% Alopecia 70% Nephritis 30% Raynaud s 30% Pulmonary Purpura 15% Pleurisy 40% Urticaria 8% Effusion 25% Cardiac CNS Pericarditis 40% Functional 90% Myocarditis 5% Psychosis 20-30% Seizures 15%
ACR Classification Criteria of SLE S erostis O ral ulcers A rthritis P hotosensitivity B lood (heme) R enal A NA I mmune tests N eurologic disorder M alar rash D iscoid rash
DIAGNOSIS of SLE Definite Lupus Probable Lupus Possible Lupus Overlap or Undifferentiated CTD
SOAPBRAIN MD SCLE : Subacute Cutnaeous Lupus Malar Rash
SCLE : Subacute Cutnaeous Lupus
SOAPBRAIN MD DLE: Discoid Lupus Erythematosis
MALAR (butterfly) RASH Seborrhea
SLE Interphalyngeal Dermatitis
DDx- dorsal joint Dermatitis in JDM
Lupus Vasculitic Lesions
SOAPBRAIN MD Oral Ulceration Photosensitivity
SOAPBRAIN MD Lupus - arthritis Inflammatory Low-grade swelling Non-erosive Symptoms out of proportion to exam Sometimes deformining Rare: Jacoud s Arthropathy
SOAPBRAIN MD SLE - Serositis Pleuritis/Pericarditis Libmann-Sachs Endocarditis Pneumonitis
SLE - Renal 1. Normal (by light micro but deposits on IF or EM). 2. Mesangial GN 3. Focal GN 4. Diffuse membranous GN 5. Diffuse proliferative GN >>>>>> 6. Advanced sclerosing GN RBC casts, Proteinuria > SOAPBRAIN MD
SLE: Neurologic-Psych Seizures Psychosis Cognitive dysfunction Depression Stroke Transverse myelitis Cerebritis Aseptic meningitis Peripheral neuropathy MS/ lupoid sclerosis Myesthenia gravis SOAPBRAIN MD
20 yr-old female with 4-year Hx of mild SLE complicated by Longitudinal Myelitis
SOAPBRAIN MD ANA Immunologic Tests Rim & Homogeneous >>> dsdna Ab Speckled pattern >>> >> ENA pannel anti Sm anti Ro anti - La anti - RNP
ANA Testing in the General Population False (+) or clinically insignificant ANA occurs in 10-15 % of healthy individuals
Anti-Nuclear Antibodies SOAPBRAIN MD TITER PATTERNS
Autoantibody-disease associations: SLE and drug-induced lupus Antigen SLE Drug-Induced LE dsdna 40% No ssdna 70% 75%-80% Histone 70% >95% Sm antigen 30% No Nuclear RNP 30% No Ribosomal RNP 10% SS-A/Ro 35% No SS-B/La 15% No Copyright 1972-2004 American College of Rheumatology Slide Collection. All rights reserved.
The Utility of ANA Testing depends on the Pre-Test Probability of Disease
SLE Immunologic Tests SOAPBRAIN MD LE Cell Low C3 and/or C4 C2 deficiency (males)
MCTD: Mixed Connective Tissues Disease A Lupus-Like Disease with (+) Anti-RNP Antibody
Anti-Phospholipid Antibodies syndrome AP is present if more than 1 clinical and 1 lab criteria met.ar thrombosis Clinical Criteria 1 arterial, venous, or small-vessel thrombosis and/or Pregnancy morbidity > 1 fetal death > 10th week gestation or > 1 premature birth > 34th week with preeclampsia or placental insufficiency or > 3 consecutive spontaneous abortions < 10th week gestation Laboratory criteria Anticardiolipin antibody IgG or IgM present medium or high titers > 2 times at least 6 weeks apart or Lupus anticoagulant present > 2 times at least 6 weeks apart False (+) VDRL Thrombocytopenia Copyright 1972-2004 American College of Rheumatology Slide Collection. All rights reserved.
SLE Blood SOAPBRAIN MD Hemolytic Anemia Leukopenia Immune Thrombocytopenia
Pathogenesis disruption in apoptosis programmed cell death
NSAIDs