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SYSTEMIC LUPUS

ERYTHEMATOSUS
INTRODUCTION
WHAT IS PAEDIATRIC SLE?

Systemic lupus erythematosus is a chronic, multisystem, inflammatory,


autoimmune disorder characterized by formation of autoantibodies directed
against self-antigens and immune-complex formation resulting in damage to
essentially any organ.

EPIDEMIOLOGY
Although SLE affects primarily women of childbearing age, approximately
5% of cases present in childhood, mainly around puberty. SLE is rare in
children younger than 9 years of age. Although there is a female
predominance of this disease in adolescence and adulthood, there is an
equal gender distribution in children. The overall prevalence of SLE in the
pediatric population is 10 to 25 cases per 100,000 children.
A LITTLE BIT OF HISTORY

Lupus is the Latin word for wolf. Erythematosus means red rashes. In 1851, Dr.
Cazenave discovered red rashes on a patient’s face that looked like wolf bites.
He named the rash Discoid Lupus Erythematosus (DLE).

In 1885, Sir William Osler recognized that many people with lupus had a disease
involving not only the skin but many other organs or systems. He named the
disease Systemic Lupus Erythematosus (SLE).
TYPES OF LUPUS
1. Systemic Lupus Erythematosus (SLE)

One that most people refer to when they say “lupus”. The symptoms of SLE
may be mild or serious. Although SLE usually first affects people between the
ages of 15 and 45, it can occur in childhood or later in life as well.

2. Discoid Lupus Erythematosus (DLE)


A chronic skin disorder in which a red, raised rash appears on the face, scalp,
or elsewhere. The raised areas may become thick and scaly and may cause
scarring. The rash may last for days or years and may recur. A small
percentage of people with discoid lupus have or develop SLE later.
TYPES OF LUPUS
3. Neonatal Lupus

A rare disorder that can occur in newborn babies. Scientists suspect that
neonatal lupus is caused by auto-antibodies in the mother’s blood called
anti-Ro (SSA) and anti-La (SSB). Auto-antibodies (“auto” means “self”) are
blood proteins that act against the body’s own parts.

At birth, the babies have a skin rash, liver problems, and low blood counts.
These symptoms gradually go away over several months, although in rare
cases, babies with neonatal lupus may have a heart problem that slows down
the natural rhythm of the heart.

Some drugs may cause SLE-like features and hence this condition is called
“drug-induced lupus”. The features typically go away completely when the
drug is stopped. The kidneys and brain are rarely involved.
CLINICAL FEATURES
CARDIAC
 Endocarditis
 Myocarditis
 Pericarditis

CONTITUTIONAL
 Fatigue
 Fever
 Weight loss

GASTROINTESTINAL
 Abdominal pain
 Nausea & vomiting
CLINICAL FEATURES
DERMATOLOGICAL
 Alopecia
 Butterfly rash
 Mucous membrane lesion
 Photosensitivity
 Purpura
 Raynaud’s phenomenon
 Urticaria
 Vasculitis
CLINICAL FEATURES
HEMATOLOGIC
 Anemia
 Leukopenia
 Thrombocytopenia

MUSCULOSKELETAL
 Arthralgia
 Arthritis
 Myositis

PULM ONARY
 Pleurisy
 Pulmonary hypertension
 Pulmonary parenchyma
CLINICAL FEATURES
NEUROPSYCHIATRIC
 Cranial neuropathies
 Organic brain syndrome
 Peripheral neuropathies
 Psychosis
 Seizures
 Transverse myelitis

RENAL
 Casts
 Hematuria
 Nephrotic syndrome
 Proteinuria
CLINICAL FEATURES
RETICULOENDOTHELIAL
 Hepatomegaly
 Lymphadenopathy
 Splenomegaly

Clinical presentation varies in different patients & the disease activity varies
over time in a single patient

1. Majority of patients have arthralgia of the hand


2. Most frequent manifestations in children include fever, rash, alopecia,
arthritis & renal involvement
3. Compared with adults, children have a higher incidence of malar rash,
anemia, leukopenia, neurologic & renal involvement
WHAT CAUSES SLE?
WHAT CAUSES SLE?
SLE is an autoimmune disorder that develops when the body’s immune system
begins to attack its own tissues. Its cause is unknown, but it is likely that a
combination of genetic, environmental, and, possibly, hormonal factors work
together to cause SLE.

This occurs through the production of “auto-antibodies” that attack a person’s


own cells thus contributing to the inflammation of various parts of the body,
and may cause damage to organs and tissues.

The most common type of auto-antibody that develops in people with SLE is
called an antinuclear antibody (ANA) because it reacts with parts of the cell’s
nucleus (command centre).
WHAT CAUSES SLE?
The fact that SLE can run in families indicates that its development has a genetic
basis; however, no specific “lupus gene” has been identified yet.

Studies suggest that several different genes may be involved in determining a


person’s likelihood of developing the disorder, which tissues and organs are
affected, and the severity of disease. However, it is believed that genes alone do
not determine who gets SLE and that other factors also play a role.

Some of the other factors scientists are studying include sunlight, stress, certain
drugs, and agents such as viruses.
DIAGNOSIS
Diagnosis of systemic lupus erythematosus (SLE) is based on clinical symptoms &
lab findings

Diagnosis based on the American College of Rheumatology criteria for the


diagnosis of definite lupus in children

 ≥4 criteria on the list either at the present time or at some time in the past,
there is a strong chance that you have lupus.
 11 common criteria, or measures that was developed by the American
College of Rheumatology (ACR):
1. Malar rash – a rash over the cheeks & nose, often in the shape of a butterfly
2. Discoid rash – a rash that appears red, raised, disk-shaped patches
3. Photosensitivity – a reaction to sun or light that causes a skin rash to appear
or get worse
4. Oral Ulcers – sores appearing in the mouth
5. Arthritis – joint pain & swelling of 2 or more joints in which the bones
around the joints do not become destroyed
DIAGNOSIS
6. Serositis – inflammation of the lining around the lungs
(pleuritis) or inflammation of the lining around the heart that
causes chest pain which is worse with deep breathing
(pericarditis)
7. Kidney disorder – persistent protein or cellular casts in the
urine.
8. Neurological disorder – seizures or psychosis
9. Blood disorder – anemia, leukopenia, lymphopenia, or
thrombocytopenia
10. Immunologic disorder – anti-DNA or anti-Sm or positive
antiphospholipid antibodies
11. Abnormal antinuclear antibody (ANA)
DIAGNOSIS
Diagnosis of systemic lupus erythematosus (SLE) is based on clinical symptoms &
lab findings

Diagnosis based on the Systemic Lupus International Collaborating Clinics


(SLICC) classification criteria for systemic lupus erythematosus (SLE)

 ≥4 criteria (at least 1 clinical & 1 immunologic criteria)


or
Biopsy-proven lupus nephritis with positive antinuclear antibody (ANA)
or
Anti-double stranded deoxyribonucleic acid (dsDNA)

 Symptom/finding need not be present all at the same time


DIAGNOSIS
C L I N I C A L C R I T E R I A:

Acute cutaneous lupus, including:


 Lupus malar rash (do not count if malar discoid)
 Bullous lupus
 Toxic epidermal necrolysis variant of systemic lupus erythematosus (SLE)
 Maculopapular lupus rash
 Photosensitive lupus rash (In the absence of dermatomyositis) or
 Subacute cutaneous lupus (nonindurated psoriaform &/or annular polycyclic
lesions that resolve w/out scarring, although occasionally w/ post-
inflammatory dyspigmentation or telangiectasias)
DIAGNOSIS
C L I N I C A L C R I T E R I A:

Chronic cutaneous lupus, including:


 Classic discoid rash: localized (above the neck) or generalized (above & below
the neck)
 Hypertrophic (verrucous) lupus
 Lupus panniculitis (profundus)
 Mucosal lupus
 Lupus erythematosus tumidus
 Chilblains lupus
 Discoid lupus/lichen planus overlap

Oral Ulcers or Nasal Ulcers


 Oral: palate, buccal, tongue
 In the absence of other causes, such as vasculitis, Behcet’s disease, infection
(herpesvirus), inflammatory bowel disease, reactive arthritis, & acidic foods
DIAGNOSIS
C L I N I C A L C R I T E R I A:

Nonscarring alopecia
 Diffuse thinning or hair fragility w/ visible broken hairs
 In the absence of other causes such as alopecia areata, drugs, iron deficiency,
& androgenic alopecia

Synovitis involving ≥2 joints


 Characterized by swelling or effusion
 Or tenderness in ≥2 joints & at least 30 minutes of morning stiffness

Renal
 Urine protein–to-creatinine ratio (or 24-hour urine protein) representing 500
mg protein/24 hours or red blood cell casts
DIAGNOSIS
C L I N I C A L C R I T E R I A:

Serositis
 Typical pleurisy for >1 day or pleural effusions or pleural rub
 Typical pericardial pain (pain w/ recumbency improved by sitting forward) for
>1 day or pericardial effusion or pericardial rub or pericarditis by
electrocardiography
 In the absence of other causes, such as infection, uremia, & Dressler’s
pericarditis
DIAGNOSIS
C L I N I C A L C R I T E R I A:

Neurologic
 Seizures
 Psychosis
 Mononeuritis multiplex (in the absence of other known causes such as
primary vasculitis)
 Myelitis
 Peripheral or cranial neuropathy (in the absence of other known causes such
as primary vasculitis, infection, & diabetes mellitus)
 Acute confusional state (in the absence of other causes, including
toxic/metabolic, uremia, drugs)
DIAGNOSIS
C L I N I C A L C R I T E R I A:

Hemolytic anemia

Leukopenia (<4000/mm3)
 at least once, in the absence of other known causes such as Felty’s syndrome,
drugs, & portal hypertension or Lymphopenia (<1000/mm3) at least once, in
the absence of other known causes such as

Corticosteroids, drugs, & infection

Thrombocytopenia (<100,000/mm3)
 At least once in the absence of other known causes such as drugs, portal
hypertension, & thrombotic thrombocytopenic purpura
DIAGNOSIS
I M M U N O L O G I C A L C R I T E R I A:

 Antinuclear antibodies (ANA) level above laboratory reference range

 Anti-double stranded deoxyribonucleic acid (dsDNA) antibody level above


laboratory reference range [or >2-fold the reference range if tested by
enzyme-linked immunosorbent assay (ELISA)]

 Anti-Smith (Anti-Sm): presence of antibody to Smith (Sm) nuclear antigen


DIAGNOSIS
I M M U N O L O G I C A L C R I T E R I A:

 Antiphospholipid antibody positivity, as determined by:


o Positive test for lupus anticoagulant
o False-positive test result for rapid plasma reagin
o Medium- or high-titer anticardiolipin antibody level [Immunoglobulin A
(IgA), immunoglobulin G (IgG) or immunoglobulin M (IgM)]
o Positive test result for anti-B2-glycoprotein I [Immunoglobulin A (IgA),
immunoglobulin G (IgG) or immunoglobulin M (IgM)]

 Low complement (C3, C4, or CH50)

 Direct Coombs’ test (in the absence of hemolytic anemia)


MANAGEMENT
MONITORING
Monitoring during clinic visit should include:
1. History-taking
2. Physical exam
3. Lab tests
4. Complete blood count (CBC)
5. Creatinine measurement
6. Urinalysis
MANAGEMENT
MONITORING
Results of lab tests that may precede a disease flare:

1. Decrease in serum complement levels


2. Increase in anti-double stranded deoxyribonucleic acid (dsDNA)
3. Increase in erythrocyte sedimentation rate (ESR)
4. Decrease in hemoglobin level, leukocyte or platelet counts
5. Increase in creatine phosphokinase (CPK) levels
6. Appearance of microscopic hematuria or proteinuria
TREATMENT
GOALS OF THERAPY:

 Control disease manifestation


 Allow child to have a good quality of life without major exacerbations
 Prevent serious organ damage that adversely affects function or lifespan
 Prevent adverse effects of the drugs used

PHARMACOTHERAPY

Corticosteroids Immunosuppressants NSAIDs Sunscreen


TREATMENT
CORTICOSTEROIDS

Oral corticosteroids
 Patients w/ mild SLE do not normally require use of systemic corticosteroids
but there are patients who has low quality of life if not given low-dose
corticosteroids
 Lowest possible dose should be used for maintenance therapy
 High-dose corticosteroids are necessary for refractory manifestations of SLE
& for severe organ systems’ manifestations especially CNS, renal &
hematologic manifestations
 Decreases inflammation by suppression of the immune system

Topical corticosteroids
 Helpful for discoid lesions especially on the scalp
 Use a less potent steroid on the face because it is more prone to atrophy
TREATMENT
CORTICOSTEROIDS

Parenteral corticosteroids
 Pulse therapy with IV corticosteroids in combination with
immunosuppressive therapy is recommended for Class III and IV SLE patients
with confirmed glomerulonephritis
TREATMENT
HYDROXYCHLOROQUINE

 Used for skin & joint manifestations

 Also used for preventing flares & other constitutional symptoms

 Inhibits chemotaxis of eosinophils & locomotion of neutrophils & impairs


complement-dependent antigen-antibody reactions

 Recommended as background treatment for Class III and IV SLE patients with
nephritis
TREATMENT
IMMUNOSUPPRESSANTS

These agents act as immunosuppressive, cytotoxic & anti-inflammatory agents

 In the treatment of severe CNS & severe glomerulonephritis,


thrombocytopenia & hemolytic anemia, high dose glucocorticoids &
immunosuppressantS are used

 Concomitant use with corticosteroids allows lower doses of


immunosuppressants

1. Azathioprine
2. Belimumab
3. Cyclophosphamide
4. IV Immune Globulin (IVIg)
5. Methotraxate
TREATMENT
NSAIDS

 These drugs provide symptomatic relief of fever, arthritis & mild serositis

 Inhibit inflammatory reactions & pain by decreasing prostaglandin synthesis

 SLE patients have a high incidence of NSAID-induced hepatotoxicity

SUNSCREEN

Patients with SLE should apply sunscreen with at least an SPF of 15 to prevent
dermal or systemic disease flares upon exposure to ultraviolet light
COMPLICATIONS
Some degree of long term and often permanent organ dysfunction from
either SLE or its treatment has been found in 88% of patients.

 Hypertension
 Growth retardation
 Chronic pulmonary impairment
 Ocular abnormalities
 Permanent renal damage
 Neuropsychiatric symptoms
 Musculoskeletal damage
 Gonadal impairment
PROGNOSIS
Outcomes for SLE have improved significantly over the past several decades
and depend largely on the organ systems that are involved. Worse prognoses
are seen in patients with severe lupus nephritis or cerebritis, with risk of
chronic disability or progression to renal failure. With current therapy for the
disease and the success of renal transplantation, however, most patients live
well into adulthood.