PLENO SCENARIO 4

HEMATOIMUNOLO
GI

TUTORIAL
6
STEVENS-JOHNSON SYNDROME
 ETIOLOGY

Infection
Drug-induced
Malignancy-related
Collagen vascular disease
Idiopathic

25-50% of cases
 SYMPTOMS
Typical symptoms are as follows:
Cough productive of a thick purulent
sputum
Headache
Malaise
Arthralgia
 The following signs may be noted on
exam:

Fever
Epistaxis
Tachycardia, hypotension
Conjunctivitis, corneal ulcerations
Erosive vulvovaginitis or balanitis
Altered level of consciousness, Seizures, coma
 Ocular symptoms

Red eye Foreign body

Tearing sensation
Dry eye Decreased vision
Pain Burn sensation
Itching Photophobia
Diplopia
 PHYSICAL EXAMINATION

Triad Disorder : Skin ,Mucosal ,Eyes

Skin : Rash , Lesion has the apperance of a
targed (occur in the palm , soles , dorsum of the
hand, extensor surface)
Mucosal : erythema , edema , sloughing ,
blistering , ulceration , necrosis
Eyes : Conjuncitivitis , Trichiasis , blepharitis ,etc
Fever , Orthostatis , Tachycardia , Hypotension ,
Epistaxis , Conjunctivitis , Corneal Ulceration ,
etc
 LABORATORY CONSIDERATIONS
Complete Blood Count (CBC)
1. Normal white blood cell (WBC) count
or a non specific leukocytosis or
2. A severely elevated WBC Count
super imposed bacterial infection
Imunologic Examination
(imunoglobulin value , C3 and C4
complement, imun kompleks )
 LABORATORY CONSIDERATIONS

Skin and Blood Cultures

Skin Biopsy
Imunofluoresen
 TREATMENT
Early diagnosis - biopsy
Immediate discontinuation of offending agent
Supportive care pay close attention to ocular
complications
IV hydration (e.g. Parkland formula)
Antihistamines
Analgesics
Local v. systemic corticosteroids
Think about nursing requirements!
Possible treatment in burn unit, wound care
IVIg?
SYSTEMIC LUPUS ERITOMATOSUS
PATHOGENESIS AND PATHOPHYSIOLOGY
 Immune responses against endogenous
nuclear antigens are characteristic of SLE.
Autoantigens released by apoptotic cells
are presented by dendritic cells to T cells
leading to their activation. Activated T
cells in turn help B cells to produce
antibodies to these self-constituents by
secreting cytokines such as interleukin 10
(IL10) and IL23 and by cell surface
molecules such as CD40L and CTLA-4.
In addition to this antigen-driven T cell-
dependent production of autoantibodies,
recent data support T cell-independent
mechanisms of B cell stimulation via
combined B cell antigen receptor (BCR)
and TLR signalling. The pathogenesis of
SLE involves a multitude of cells and
molecules that participate in apoptosis,
innate and adaptive immune responses.
 ETIOLOGY OF SLE

Genetic factors
The rate of gene discovery in SLE has
increased during the past few years
thanks to large genome-wide association
studies (GWAS) using hundreds of
thousands of single nucleotide
polymorphism (SNP) markers.
 EPIGENETIC EFFECTS

The risk for SLE may be infl uenced by

epigenetic effects such as DNA
methylation and post-translational
modifi cations of histones, which can
be either inherited or environmentally
modified.
 ENVIRONMENTAL FACTORS

Candidate environmental triggers of

SLE include ultra violetlight,
demethylating drugs, and infectious or
endogenous viruses or viral-like
elements
 HORMONAL FACTORS

In murine models, addition of estrogen

or prolactin can lead to an autoimmune
phenotype with an increase in mature
high-affi nity autoreactive B cells. Oral
contraceptive use in the Nurses Health
Study was associated with a slightly
increased risk of developing SLE
 CLINICAL MANIFESTATIONS
Systemic symptoms : weakness, anorexia,
fever, weakness, and weight loss.
Symptoms of skin : malar rash (butterfly
rash), skin and mucosal ulcers, purpura,
alopecia (baldness), Raynaud's
phenomenon, and photosensitivity.
Symptoms of joint : Joint symptoms are
often found to be symmetric and not
cause joint disorders
 Lupus nephritis is generally not symptomatic
at the time of onset, but often develops into
a progressive and lead to death
Symptoms include edema, hypertension,
electrolyte disorders, and acute renal failure.
Renal biopsy is indicated in patients who are
not responsive to corticosteroid therapy
Hepatosplenomegaly (enlarged liver and
spleen) may occur but are rare
manifestations include
 Involvement of the central nervous
system may be convulsions, coma,
hemiplegia (paralysis on one side of
the body), neuropathy (nerve
disorder) focal, and behavioral
disorders
DIAGNOSIS OF SLE
 THERAPY OF SYSTEMIC LUPUS ERITOMATOSUS

Conservative therapy

To cope with arthritis, arthralgia, and myalgia can be given

simple analgesics or anti-inflammatory non steroid drugs .If
analgesic and non-steroidal anti-inflammatory drugs do not
respond, can be considered the provision of anti-malarial drugs,
such as hydroxychloroquine 400 mg / day. within 6 months when
the drug had no effect, then it should stop.
Local glucocorticoids such as creams, ointments, or injection can
be considered in lupus dermatitis
anti-malarial drugs are very good to deal cutaneous lupus,
(subacute cutaneous lupus or discoid lupus). Antimalarial have
sunsblocking effects, anti-inflammatory and immunosuppressant
 To cope serositis, can be given
salicylates, non-steroidal anti-
inflammatory drugs, anti-malarial or
low-dose glucocorticoids (15mg/hari)
 AGGRESSIVE THERAPY

Aggressive therapy is initiated with high-dose

glucocorticoid administration if serious
manifestations of SLE, for example, vasculitis,
severe cutaneous lupus, polyarthritis, poly
serositis, lupus pneumonitis, myocarditis,
glomerulonephritis, hemolytic anemia,
thrombocytopenia
Administration of glucocorticoids that has
long effect such as dexamethasone, should
be avoided
 Prednisone administration is more selected
cause it more easily to set the doses.In minor
manifestations of SLE, can be given
prednisone 0.5 mg /kgBB/day, while the major
manifestations of SLE, can be given
prednisone 1-1.5 mg /kgBB/day
After the administration of high-dose
glucocorticoids for 6 weeks, then it should
start do decrease the dose gradually, starting
with 5-10% every week if not raised acute
exacerbation
 If within 4 weeks after administration of high-
dose glucocorticoids showed no real
improvement then considered to provide another
immunosuppressant or other aggressive
therapy, such as intravenous cyclophosphamide
bolus (0.5-1 g / m2 in 250 ml of 0.9% NaCl for 60
min followed by administration of fluid 2-3 liters /
24 hours after drug administration)
Besides cyclophosphamide, other drugs that
may be used are azathioprine (1-3 mg /kgBB
/day for 6-12 months were orally)
 Another immunosuppressant that
can be used is cyclosporin A low dose
(3-6 mg/kgBB/day) and
mycophenolate mofetil
TOXIC EPIDERMAL NECROLYSIS
 Toxic epidermal necrolysis (TEN) is a potentially life-
threatening dermatologic disorder characterized by
widespread erythema, necrosis, and bullous
detachment of the epidermis and mucous
membranes, resulting in exfoliation and possible
sepsis and/or death. Mucous membrane
involvement can result in gastrointestinal
hemorrhage, respiratory failure, ocular
abnormalities, and genitourinary complications.
 ETIOLOGY
TEN can be induced by drugs or infection or can be idiopathic.
Medications are the major precipitating cause. Numerous
medications have been implicated, including antibiotics,
antiepileptic drugs, nonsteroidal anti-inflammatory drugs
(NSAIDs), ampicillin, allopurinol, corticosteroids (topical and
systemic), and the antiretroviral drugs nevirapine and abacavir.
Antibacterial drugs associated with TEN include the following:
Sulfonamides (4.5 cases per million users per week)
Chloramphenicol
Macrolides (eg, erythromycin)
Penicillins
Quinolones (eg, ciprofloxacin, trovafloxacin)

Infectious agents (ie, Mycoplasma pneumoniae, herpes virus,

hepatitis A), immunizations, and bone marrow or solid organ
transplantation have also been associated with TEN
 PATHOPHYSIOLOGY
The pathophysiology of TEN has not been fully elucidated;
however, various theories have received wide acceptance. TEN
is believed to be an immune-related cytotoxic reaction aimed
at destroying keratinocytes that express a foreign antigen.
TEN mimics a hypersensitivity reaction, with its characteristic
delayed reaction to an initial exposure and an increasingly
rapid reaction with repeated exposure.
The widespread epidermolysis and blistering of TEN results
from keratinocyte apoptosisan organized series of
biochemical reactions leading to cell changes and cell death.
However, the number of inflammatory T cells in the skin of
patients with TEN is variable and perhaps too low to explain
the widespread destruction.
There is evidence supporting several
immunopathologic pathways leading to
keratinocyte apoptosis in TEN, including the
following:
1. Fas ligand activation on keratinocyte
membranes leading to death receptor
mediated apoptosis
2. Release of destructive proteins (perforin and
granzyme B) from cytotoxic T lymphocytes
(CTLs) generated from an interaction with cells
expressing major histocompatability complex
(MHC) class I
3. Overproduction of T cell and/or macrophage-
derived cytokines (interferon- [INF-], tumor
necrosis factor- [TNF-], and various
interleukins)
4. Drug-induced secretion of granulysin from
 PHARMACOLOGIC THERAPY
Corticosteroid therapy

Intravenous immunoglobulin

Cyclosporine
JUVENILLE RHEUMATOID ARTHRITIS
 Juvenile rheumatoid arthritis (JRA) is the
most common chronic rheumatologic disease
in children and is one of the most common
chronic diseases of childhood. The etiology is
unknown, and the genetic component is
complex, making clear distinctions between
the various subtypes difficult. A new
nomenclature, juvenile idiopathic arthritis
(JIA), is being increasingly used to provide
better definition of subgroups.
 SYMPTOMS
History findings in children with JIA may include the following:
Arthritis present for at least 6 weeks before diagnosis
(mandatory for diagnosis of JIA)
Either insidious or abrupt disease onset, often with morning
stiffness or gelling phenomenon and arthralgia during the day
Complaints of joint pain or abnormal joint use
History of school absences or limited ability to participate in
physical education classes
Spiking fevers occurring once or twice each day at about the
same time of day
Evanescent rash on the trunk and extremities
Psoriasis or more subtle dermatologic manifestation
 Arthritis: Defined either as intra-articular swelling on
examination or as limitation of joint motion in association
with pain, warmth, or erythema of the joint; physical
findings in JIA reflect the extent of joint involvement
Synovitis: Characterized by synovial proliferation and
increased joint volume; the joint is held in a position of
maximum comfort, and range of motion often is limited
only at the extremes

Types of JIA include the following:

Systemic-onset juvenile idiopathic arthritis
Oligoarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis
Psoriatic arthritis
Enthesitis-related arthritis
Undifferentiated arthritis
 Diagnosis
Diagnosis of JIA is based on the history and physical
examination findings. When physical findings do not
document definite arthritis, further evaluation is warranted.
Laboratory studies that may be considered include the
following:

Inflammatory markers: Erythrocyte sedimentation rate (ESR) or

CRP level
Complete blood count (CBC) and metabolic panel
Liver function tests and assessment of renal function with
serum creatinine levels
Antinuclear antibody (ANA) testing
Additional studies: Total protein, albumin, fibrinogen, ferritin,
D-dimer, angiotensin-converting enzyme (ACE),
antistreptolysin 0 (AS0), anti-DNAse B, urinalysis
 When only a single joint is affected,
radiography is important to exclude other
diseases. Basic radiographic changes in JIA
include the following:

Soft tissue swelling

Osteopenia or osteoporosis
Joint-space narrowing
Bony erosions
Intra-articular bony ankylosis
Periosteitis
Growth disturbances
Epiphyseal compression fracture
Joint subluxation
Synovial cysts
 Other imaging modalities that may be helpful
include the following:

Computed tomography
Magnetic resonance imaging
Ultrasonography and echocardiography
Nuclear imaging
Other studies and procedures that may be
considered include the following:

Dual-energy radiographic absorptiometry (DRA)

Arthrocentesis and synovial biopsy
Pericardiocentesis
 THERAPY
Pharmacologic therapy with nonsteroidal anti-
inflammatory drugs (NSAIDs), disease-modifying
antirheumatic drugs (DMARDs), biologic agents,
or intra-articular and oral corticosteroids
Psychosocial interventions
Measures to enhance school performance (eg,
academic counseling)
Improved nutrition
Physical therapy
Occupational therapy
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