7. [Alergi-Imunologi] SLE - Dr. Galuh

PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS

Department of Child Health Faculty of Medicine Diponegoro University – Kariadi Hospital Semarang

BACKGROUND Systemic Lupus Erythematosus (SLE) A rheumatic disease characterized by autoantibodies directed against self-antigens, immune complex formation, and immune dysregulation, resulting in damage to essentially any organ.

Kidneys, skin, blood cells, and nervous system

Flare

Remission

Unpredictable  many years of symptoms or with acute (life threatening disease)

EPIDEMIOLOGY • Incidence rates among children younger than age 15 years have been reported to be 0.5-0.6 case per 100,000 persons. • Prevalence rates of 4-250 cases per 100,000 persons have been reported, with greater prevalence in Native Americans, Asian Americans, Latin Americans, and African Americans.

• A female-to-male ratio of approximately 4:1 occurs before puberty and after menopause, with a ratio of 8:1 between onset and loss of estrogen cycles. • Uncommon in children younger than age 8 years

Lupus in Children • Uncommon before age 4 • Incidence 0.5-0.6 /100,000 per year

• Females>males • Children have more organ involvement than adults

• Compliance issues in adolescence dangerous • Prognosis guarded; 30% may progress to renal

insufficiency depending on treatment

LE CELL • The LE cell is a neutrophil that

has

engulfed

the

antibody-coated nucleus of another neutrophil. • LE

cells

rosettes

may

where

appear

in

there

are

several neutrophils vying for an

individual

covered protein.

complement

PROTEAN MANIFESTATIONS

Differential Diagnosis  Fever of Unknown Origin  Arthralgia  Anemia  New Onset kidney disease  Psycosis  Fatique

Early diagnosis & careful treatment  improved the prognosis

CHARACTERISTIC • Episodic : pleurisy,

symptoms appear intermittent (arthritis,

dermatitis

may appear months

or years

previously) • Multisystem disease : especially in children

• Characterized by antinuclear antibody (especially to dsDNA)

CHRONIC, UNPREDICTABLE, CHARACTERIZED WITH EXCACERBATIONS & REMISSION

ETIOLOGY

Specific cause  remains undefined

APOPTOSIS Protease (caspase) cascade

Receptor ligation ex: TNF, Fas DNA fragmentation Chromatin condensation Cytoplasmic blebbing Clearance by phagocytes

Y AUTOREACTIVITY

Apoptotic bodies

Y

PATHOPHYSIOLOGY

• Autoimmune

reactions

directed

against

constituents of cell nucleus, DNA • Antibody

response

T cell hyperactivity

related

to

B

and

MAIN PATHOLOGY

• The plasma cells are producing antibodies that are specific for self proteins, namely ds-DNA

• Overactive B-cells • Suppressed regulatory function in T-cells

• Lack of T-cells • Activation of the Complement system

PATOFISIOLOGI • timbul sebagai ekspresi klinis sebab ?? • Diawali : sistem imun

tak mampu kenali struktur antigen diri

AutoAb + AutoAg = Komplek imun mengendap berupa depot di jaringan  aktivasi komplemen  sehingga terjadi Rx Inflamasi  timbullah LESI !!

mekanisme autoimun

Clinical Features of SLE • • • • • • • •

Constitutional symptoms Musculoskeletal disease Mucocutaneous involvement Renal Disease Central nervous system disease Cardiopulmonary disease Hematologic abnormalities Gastrointestinal involvement

SYMPTOMS •

Non-specific: – Fatigue – Weight loss – Malaise = generally feeling ill – Fever – Anorexia (over time) – Arthritis • 90% of patients experience arthritic symptoms • Symmetrical • Appears in hands, wrists, and knees mainly

General symptoms The most common symptoms listed as initial complaints are fatigue, fever, and weight loss. •

Fever: fever secondary to active disease was recorded from 50% to 86%. No fever curve or pattern is characteristic. It can be difficult, but very important to distinguish the fever of SLE from that caused by complicating infections.

Mucocutaneous Manifestations • Frequency: 76% – – – – – – – – –

Malar rash Discoid lupus Vasculitis (purpura, petechiae) Raynaud’s phenomenon Nail involvement Alopecia Periungual erythema/ Livedo reticularis Photosensitivity Oral/ nasal ulcers

CLASSIC MALAR RASH

 Distribution

over

the

cheeks and nasal bridge  Fixed erythema  Sometimes



mild

induration Butterfly Rash

 Nasolabial folds  Photosensitivity” noted in patients antibodies

with

anti-Ro

• Vasculitic skin lesin

• Alopecia

MUSKULOSKELETAL Swan Neck Deformity

joint and muscle pains, small joints of hands, synovitis (pain

may appear disproportionate to the degree of swelling), joint erosion (unusual)

Meniscus

Cardiovascular system : • Pericarditis, pericardial effusion (10%) • Myocardial involvement  conduction defect, arrhythmias, cardiac

failure • “libman-sacks” endocarditis (mitral valve)valvular incompetence

Respiratory system : • Pleural effusion, pleurisy, pleuritic pain • “shrinking lung syndrome” • Recurrent pneumonitis (may be due to immunosupresive therapy)

Renal involvement : • 60% develops renal involvement • May be due from immune complex deposition in the glomerulus • Renal biopsy : mesangial deposits of immunoglobulin and complement (direct immunofluorescent) • Proliferative glomerulonephritisnephrotic syndrome, hypertension, renal failure • Mortality 60% (untreated) at 3 years

Haematological features : • Autoimmune haemolytic syndrome

• Lymphopenia,neutropenia, thrombocytopenia • Normochromic anaemia of chronic disease

The anti-phospholipid syndrome : • Recurrent thrombosis (arterial or venous) • Thrombocytopenia • Recurrent fetal loss (2nd trimester) • Heart valve lesions • High-titre IgG anti-phospholipid autoantibodies and/or a related autoantibody, the lupus anticoagulant

Features of SLE FEATURES

%

Constitutional symptoms

50

Joints/muscles

62

Skin

50

Blood

8

Brain

15

Kidney

25

Cumulative organ involvement in SLE patient Organ/tissue Skin Joints/muscles Lung/pleura Blood Brain Kidney Heart

Patient (%) 80 80 30 60 30 40 15

INVESTIGATION

• Anti-nuclear antibodies : mostly present (anti-dsDNA

antibodies, anti-ENA) • Disease activity : measuring C3, C4 • ESR elevated during acute flares • CRP normal. If CRP +, consider infection, serositis, synovitis, vasculitis

Autoantibodies in SLE • Antibodies to cell nucleus component ANA, anti-dsDNA, antibodies to extracellular nuclear antigen (ENA, anti-Sm, anti-RNP, anti-Jo1) • Antibodies to cytoplasmic antigens anti-SSA, anti-SSB • Cell-specific autoantibodies lymphocytotoxic antibodies, anti-neurone antibodies, anti-erythrocyte antibodies, anti-platelet antibodies • Antibodies to serum components antiphospholipid antibody anticoagulants antiglobulin (rheumatoid factor)

Diagnostic Studies • Antinuclear antibodies – ANA and other antibodies indicate autoimmune disease – Anti-DNA and anti-Smith antibody tests most specific for SLE

– LE prep can be positive with other rheumatoid diseases – ESR & CRP are indicative of inflammatory activity

LABORATORY • Peripheral blood smear • Titer IgM, IgG, IgA

• Krioglobulin

• • • • • • • •

Coagulation study VDRL Combs test Electrophoresis protein Ureum, creatinin Prot urin ( 24 jam ) Urine and blood culture Chest X Ray

Diagnostic Tests • CBC for hematologic problems

• UA for lupus nephritis • X-rays of affected joints

• Chest x-ray for pulmonary problems • ECG for cardiac problems

DIAGNOSIS

CLINICALLY

LABORATORY

• Episodic disease • Multisystem disease • Usually with ANA (antibody antinuclear) positive

American College of Rheumatology

CRITERIA FOR DIAGNOSING LUPUS

The diagnosis of lupus is a clinical one made by observing symptoms. Lab tests provide only a part of

the

picture.

The

American

College

of

Rheumatology has designated 11 criteria for diagnosis. To receive the diagnosis of lupus, a person must have 4 or more of these criteria:

CLINICAL FEATURE NO

1982 American College of Rheumatology (ACR) criteria CRITERIA DEFINITION

1

Malar rash

Fixed erythema over the cheeks and nasal bridge, flat or raised, butterfly rash

2

Discoid rash

Erythematous raised-rimmed lesions with keratotic scaling and follicular plugging, often scarring

3

Photosensitivity

Unusual skin reaction to light exposure

4

Oral ulcers

Oral or nasopharyngeal, usuallly painless, palate is most specific

5

Arthritis

Nonerosive, two or more peripheral joints with tenderness or swelling

6

Serositis

Pleurisy, pericarditis on examination or diagnostic ECG or imaging

7

Renal involvement

Proteinuria (>0,5 g/d or 3+ on dipstick testing) or cellular cast

8

Neurologic disorder

Seizures of psychosis in the absence of other causes

9

Blood disorder

Leukopenia (1 occasion Lymphopenia (1 occasion Thrombocytopenia (1:160), must be in the absence of medications associated with druginduced lupus

MANAGEMENT

• Individual approach • Avoidance of exposure (sunlight, drugs, infection) • Sun-blocking creams, NSAIDs • Awareness of long-term drugs therapy

• Effects of therapy for women

1. Monitoring the lupus patients • It cannot be emphasized too strongly that lupus is a disease requiring regular and careful follow-up. • Important initial advice should be given about avoiding UV light, infections, extreme stress or fatigue • Laboratory test—blood test, ESR, C3,IC, liver function tests and anti-dsDNA.

2. Grading clinical activity • The highly variable nature of the syndrome • Evaluation of lupus activity is the base or beginning of therapy.

• Non-life-threatening features such as arthralgia, skin rash, RP, alopecia

• Severe complication such as renal, cerebral and heart involvement.

SLE disease activity index (SLEDAI) Clinical feature

score

seizure , psychosis , organ brain syndrome visual disturbance, cranial nerve disorder lupus headache, cerebrovascular accidents, vasculitis arthritis myositis urinary casts, hematuria, proteinure, pyuria rash, alopecia, mucosal ulcers, pleurisy, pericarditis low complement, increased DNA binding fever thrombocytopenia, leucopenia

8 8 8 8 4 4 4 2 2 2 1 1

3. Clinical therapy • There are four main groups drugs useful in the treatment of lupus:

the non-steroid anti-

inflammatory drugs, anti-malarials, corticosteroid

and cytotoxic drugs. • How to treat lupus is a kind of art. Which and the

dosage of drugs will be used to treat the patient depend on lupus activity.

Collaborative Care • Drug therapy – NSAIDs – Antimalarial drugs – Steroid-sparing drugs – Corticosteroids – Immunosuppressive drugs

SLE - Treatment • MILD DISEASE: Rashes, arthralgias, leukopenia, anemia, arthritis, fever, fatigue – Treatment: NSAIDs, low dose corticosteroids (