Stevens-Johnson syndrome is a severe mucocutaneous reaction typically caused by drugs involving skin and mucous membranes. It begins with flu-like symptoms followed by distinctive target lesions. Complications can include blindness, infections, and death. Treatment focuses on stopping the causative agent, supportive care, corticosteroids, IVIG, and antibiotics for secondary infections.

1. Stevens-Johnson
Syndrome
BY
DR.TOSIF AHMAD
TMO-PEDS

2. Stevens-Johnson Syndrome
• Stevens-Johnson syndrome (SJS) is an immune-
complex–mediated hypersensitivity complex that
typically involves the skin and the mucous
membranes. While minor presentations may
occur, significant involvement of
oral, nasal, eye, vaginal, urethral, gastrointestinal,
and lower respiratory tract mucous membranes
may develop in the course of the illness. GI and
respiratory involvement may progress to necrosis.
Stevens-Johnson syndrome is a serious systemic
disorder with the potential for severe morbidity
and even death.

3. Stevens-Johnson Syndrome
• The syndrome was first described in
1922, when the American pediatricians Albert
Mason Stevens and Frank Chambliss Johnson
reported the cases of 2 boys aged 7 and 8
years with "an extraordinary, generalized
eruption with continued fever, inflamed
buccal mucosa, and severe purulent
conjunctivitis." Both cases had been
misdiagnosed by primary care physicians as
hemorrhagic measles.

4. Stevens-Johnson Syndrome
• Although several classification schemes have
been reported, the simplest breaks the disease
down as follows:
• Stevens-Johnson syndrome - A "minor form of
TEN," with less than 10% body surface area (BSA)
detachment
• Overlapping Stevens-Johnson syndrome/toxic
epidermal necrolysis (SJS/TEN) - Detachment of
10-30% BSA
• Toxic epidermal necrolysis - Detachment of more
than 30% BSA

5. Pathophysiology
• An idiosyncratic, delayed hypersensitivity
reaction has been implicated in the
pathophysiology of Stevens-Johnson syndrome.
Certain population groups appear more
susceptible to develop Stevens-Johnson
syndrome than the general population. Slow
acetylators, patients who are
immunocompromised and patients with brain
tumors undergoing radiotherapy with
concomitant antiepileptics are among those at
most risk.

6. Pathophysiology
• Antigen presentation and production of tumor
necrosis factor (TNF)–alpha by the local tissue
dendrocytes results in the recruitment and
augmentation of T-lymphocyte proliferation and
enhances the cytotoxicity of the other immune
effector cells.A "killer effector molecule" has
been identified that may play a role in the
activation of cytotoxic lymphocytes.The activated
CD8+ lymphocytes, in turn, can induce epidermal
cell apoptosis via several mechanisms, which
include the release of granzyme B and perforin.

7. Pathophysiology
• The death of keratinocytes causes
separation of the epidermis from the
dermis. Once apoptosis ensues, the dying
cells provoke recruitment of more
chemokines. This can perpetuate the
inflammatory process, which leads to
extensive epidermal necrolysis.

8. Etiology
• Various etiologic factors have been implicated
as causes of Stevens-Johnson syndrome.
Drugs most commonly are blamed. The 4
etiologic categories are as follows:
• Infectious
• Drug-induced
• Malignancy-related
• Idiopathic

9. Infectious causes
• Viral diseases that have been reported to cause
Stevens-Johnson syndrome include the following:
• Herpes simplex virus (possibly; remains a debated
issue)
• AIDS
• Coxsackie viral infections
• Influenza
• Hepatitis
• Mumps

10. Infectious causes
• Bacterial etiologies include the following:
• Group A beta-hemolytic streptococci
• Diphtheria
• Brucellosis
• Lymphogranuloma venereum
• Mycobacteria
• Mycoplasma pneumoniae
• Rickettsial infections
• Tularemia
• Typhoid

11. Infectious causes
• Possible fungal causes include
coccidioidomycosis, dermatophytosis
, and histoplasmosis. Malaria and
trichomoniasis have been reported
as protozoal causes.

12. Drug-induced
• Antibiotics are the most common cause
of Stevens-Johnson syndrome, followed
by analgesics, cough and cold
medication, NSAIDs, psychoepileptics, an
d antigout drugs. Of
antibiotics, penicillins and sulfa drugs are
prominent; ciprofloxacin has also been
reported.

13. Drug-induced
• The following anticonvulsants have been
implicated:
• Phenytoin
• Carbamazepine
• oxcarbazepine
• Valproic acid
• Lamotrigine
• Barbiturates

14. Drug-induced
• Antiretroviral drugs implicated in
Stevens-Johnson syndrome include
nevirapine and possibly other non-
nucleoside reverse transcriptase
inhibitors.Indinavir has been mentioned.

15. Drug-induced
• Stevens-Johnson syndrome has also been
reported in patients taking the following drugs:
• Modafinil
• Allopurinol
• Mirtazapine
• TNF-alpha antagonists
• Cocaine
• Sertraline
• Pantoprazole
• Tramadol

16. Genetic factors
• There is strong evidence for a genetic
predisposition to severe cutaneous
adverse drug reactions such as Stevens-
Johnson syndrome. Carriage of the
certain human leukocyte antigens has
been associated with increased risk.

17. Idiopathic
• Stevens-Johnson syndrome is idiopathic
in 25-50% of cases.

18. Epidemiology
• The incidence rate is 7 cases per million
population per year.
• Cases tend to have a propensity for the early
spring and winter.
• Stevens-Johnson syndrome has been
described worldwide in all races, although it
may be more common in whites.
Interestingly, disease is not limited to humans;
cases have been reported in dogs, cats, and
monkeys.

19. Epidemiology
• SJS occurs with a worldwide distribution
similar in etiology and occurrence to that in
the United States. However, a study from
Germany reported only 1.1 cases per 1 million
person-years.
• Cases have been reported in children as young
as 3 months.

20. Clinical Presentation
• Typically, Stevens-Johnson syndrome (SJS) begins
with a nonspecific upper respiratory tract
infection. This usually is part of a 1- to 14-day
prodrome during which fever, sore
throat, chills, headache, and malaise may be
present. Vomiting and diarrhea are occasionally
noted as part of the prodrome.
• Mucocutaneous lesions develop abruptly.
Clusters of outbreaks last from 2-4 weeks. The
lesions are typically nonpruritic.

21. Clinical Presentation
Typical prodromal symptoms are as
follows:
• Cough productive of a thick purulent
sputum
• Headache
• Malaise
• Arthralgia

22. Clinical Presentation
In addition to the skin, lesions in Stevens-Johnson
syndrome may involve the following parts of the body:
• Oral mucosa
• Esophagus
• Pharynx
• Larynx
• Anus
• Trachea
• Vagina
• Urethra

23. Clinical Presentation
Ocular symptoms include the following:
• Red eye
• Tearing
• Dry eye
• Pain
• Blepharospasm
• Itching
• Grittiness

24. Clinical Presentation
• Foreign body sensation
• Decreased vision
• Burn sensation
• Photophobia
• Diplopia

25. Clinical Presentation
• The rash can begin as macules that develop into
papules, vesicles, bullae, urticarial plaques, or
confluent erythema. The center of these lesions may
be vesicular, purpuric, or necrotic.
• The typical lesion has the appearance of a target; this is
considered pathognomonic. However, in contrast to
the typical lesions of erythema multiforme, these
lesions have only two zones of color. The core may be
vesicular, purpuric, or necrotic; that zone is surrounded
by macular erythema. Some have called these
targetoid lesions.

26. Clinical Presentation
• Lesions may become bullous and later
rupture, leaving denuded skin. The skin
becomes susceptible to secondary infection.
• Although lesions may occur anywhere, the
palms, soles, dorsum of the hands, and
extensor surfaces are most commonly
affected.

27. Clinical Presentation
The following signs may be noted on examination:
• Fever
• Tachycardia
• Hypotension
• Altered level of consciousness
• Epistaxis
• Conjunctivitis
• Corneal ulcerations
• Erosive vulvovaginitis or balanitis
• Seizures
• Coma

28. Complications
Of patients with Stevens-Johnson syndrome, 27-
50% progress to severe ocular disease. Ocular
complications of Stevens-Johnson syndrome
include the following:
• Chronic cicatrizing conjunctivitis
• Corneal epithelial defects
• Corneal stromal ulcers
• Corneal perforation
• Endophthalmitis

29. Complications
Other complications may include the following:
• Gastroenterologic - Esophageal strictures
• Genitourinary - Renal tubular necrosis, renal
failure, penile scarring, vaginal stenosis
• Pulmonary - Tracheobronchial shedding with
resultant respiratory failure
• Cutaneous - Scarring and cosmetic
deformity, recurrences of infection through slow-
healing ulcerations

30. Differential Diagnoses
• Staphylococcal scalded skin syndrome
• Irradiation
• Trauma
• Progressive systemic sclerosis (scleroderma)
• Erythroderma ichthyosiform congenita
• Porphyria cutanea tarda
• Epidermolysis bullosa acquisita
• Linear immunoglobulin A bullous disease

31. Differential Diagnoses
• Paraneoplastic pemphigus
• Bullous systemic lupus erythematosus
• Corynebacterium diphtheriae conjunctivitis
• Sebaceous cell carcinoma
• Adenoviral conjunctivitis
• Intraepithelial epithelioma
• Acute generalized exanthematic pustulosis

32. Workup
There are no specific laboratory studies (other than biopsy)
that can definitively establish the diagnosis of Stevens-
Johnson syndrome.
• Serum levels of the following are typically elevated in
patients with Stevens-Johnson syndrome:
• Tumor necrosis factor (TNF)-alpha
• Soluble interleukin 2-receptor
• Interleukin 6
• C-reactive protein
• However, none of these serologic tests is used routinely in
diagnosing and managing Stevens-Johnson syndrome.

33. Workup
• Skin biopsy specimens demonstrate that
the bullae are subepidermal.
However, skin biopsy is not an
emergency department (ED) procedure.
Epidermal cell necrosis may be noted.
Perivascular areas are infiltrated with
lymphocytes.

34. Treatment & Management
• Management of patients with Stevens-
Johnson syndrome is usually provided in
intensive care units or burn centers. No
specific treatment of Stevens-Johnson
syndrome is noted; therefore, most patients
are treated symptomatically. In principle, the
symptomatic treatment of patients with
Stevens-Johnson syndrome does not differ
from the treatment of patients with extensive
burns.

35. Treatment & Management
• Identify and stop the offending agent.
• Isolate the patient.
• Give IV fluids.
• Give corticosteroids.
• IVIG if available.
• Antibiotic to treat secondary infection.
• Use minimum drugs for its treatment.

36. Treatment & Management
• Manage oral lesions with mouthwashes.
Topical anesthetics are useful in reducing
pain and allowing the patient to take in
fluids.
• Skin lesions are treated as burns. Areas
of denuded skin must be covered with
compresses of saline.
• Address tetanus prophylaxis.

37. Treatment & Management
• Treatment of acute ocular manifestations
usually begins with aggressive lubrication
of the ocular surface. As inflammation
and cicatricial changes ensue, most
ophthalmologists use topical
steroids, antibiotics, and symblepharon
lysis.

38. Prognosis
• Individual lesions typically should heal within 1-2
weeks, unless secondary infection occurs. Most
patients recover without sequelae.
• Mortality is determined primarily by the extent of
skin sloughing. When body surface area (BSA)
sloughing is less than 10%, the mortality rate is
approximately 1-5%. However, when more than
30% BSA sloughing is present, the mortality rate
is between 25% and 35%, and may be as high as
50%. Bacteremia and sepsis appear to play a
major role in increased mortality.

39. Prognosis
• The SCORTEN score (a severity-of-illness score for toxic
epidermal necrolysis) calculates the risk for death in
both SJS and TEN on the basis of the following
variables:
• Age >40 years
• Malignancy
• Heart rate >120
• Initial percentage of epidermal detachment >10%
• Blood urea nitrogen (BUN) level >10 mmol/L
• Serum glucose level >14 mmol/L
• Bicarbonate level < 20 mmol/L

40. Prognosis
• Each variable is assigned a value of 1 point.
Mortality rates are as follows:
• 0-1 points, ≥3.2%
• 2 points, ≥12.1%
• 3 points, ≥35.3%
• 4 points, ≥58.3%
• 5 or more points, ≥90%

41. Prognosis
• Other negative prognostic factors include
persistent neutropenia (defined as
neutropenia lasting more than 5
days), hypoalbuminemia (usually < 2
g/dL), and persistent azotemia.

42. Prognosis
Survivors of Stevens-Johnson syndrome may experience
numerous long-term sequelae; the most disabling are
those of the eye. Cicatrization of conjunctival erosions
may lead to the following:
• Inverted eyelashes
• Photophobia
• A burning sensation in the eyes
• Watery eyes
• A siccalike syndrome
• Corneal and conjunctival neovascularization

43. images

44. images

45. images

46. images

47. images

48. images

49. images