CASE REPORT

STEVEN JOHNSON SYNDROME PADA ANAK

Pembimbing:
dr. Ulynar Marpaung, SpA

Penulis:
Gina Maharani (1102012099)

KEPANITERAAN KLINIK ILMU KESEHATAN ANAK

FAKULTAS KEDOKTERAN UNIVERSITAS YARSI
RUMAH SAKIT BHAYANGKARA TK. I RADEN SAID SUKANTO
PERIODE 11 SEPTEMBER 18 NOVEMBER 2017
Table of contents

Identity of patient.......................................................................................................................2

Anamnesis .................................................................................................................................2

Physical Examination.................................................................................................................6

General Status.........................................................................................................................6

Antropometry Status...............................................................................................................7

Head to Toe Examination.......................................................................................................9

Neurological Examination....................................................................................................11

Meningeal Sign.................................................................................................................11

Motoric Examination........................................................................................................11

Autonom Examination......................................................................................................12

Laboratory Investigation...................................................................................................12

Follow Up.............................................................................................................................14

Literature Review.....................................................................................................................16

Definition..............................................................................................................................16

Etiology................................................................................................................................17

Pathophysiology....................................................................................................................18

Clinical Manifestations.........................................................................................................17

Diagnosis..............................................................................................................................19

Treatment..............................................................................................................................19

References................................................................................................................................24

2
 I. Identity of Patient

Name : Child AC
Birth Date : May 23th 2017
Age : 4 months old
Gender : Female
Address : Komplek Hankam, East Jakarta
Nationality : Indonesia
Religion : Islam
Date of admission : Oktober 15th 2017
Date of examination : Oktober 15th 2017

Father Mother
Name Mr. F Mrs. V
Age 27 years old 25 years old
Job Police Housewife
Nationality Javanese Javanese
Religion Islam Islam
Education High School High School
Earning/month Approximately Rp 3.500.000,- -
Address Komplek Hankam

II. Anamnesis

The anamnesis was taken on Oktober 15th 2017 by alloanamnesis from patients mother.
Chief complain : Rash on the face area 4 day before admission to the hospital
Additional complains: Fever

3
History Of Present Ilness

A 4-month-old girl came to Raden Said Sukanto Police Center emergency room with
rash on the face area 4 day before admission to the hospital.

5 day ago, patient had fever right after she took DPT vaccination. The fever slowly
increased, and the temperature wasnt measured by her parents. Patient then took medicine
Paracetamol Drop 3 times a day given by her mother.

1 day after (4 days before admission) patient got rash on the face area. The rash
appear on the face, then her neck and slightly on her arms and the genitalia area. The rash
become like blister. The day after that it become crustae and the skin tone around the crustae
became darker than before. Defecate and urinate within normal limits.

History Of Past Illness

Pharyngitis/Tonsili -
tis
Bronchitis -
Pneumonia -
Morbilli -
Pertussis -
Varicella -
Diphteria -
Malaria -
Polio -
Enteritis -
Bacillary Dysentry -
Amoeba Dysentry -
Diarrhea -
Thypoid -
Worms -

4
 Surgery -
Brain Concussion -
Fracture -
Drug Reaction -

Allergic History

The patient didnt have asthma, allergic rhinitis, and atopic dermatitis
The patient didnt have allergic to medicine
The patient didnt have allergic to dust, pollen, etc

Birth History
Mothers Pregnancy History
The mother routinely checked her pregnancy to the midwives in the local clinic. She denied
any problem noted during her pregnancy. She took vitamins routinely given.
Childs Birth History

Labor : Healthcare
Birth attendants : Doctor
Mode of delivery : Sectio Caesarea
Gestation : 38 weeks
Infant state : Healthy
Birth weight : 2900 grams
Body length : 49 cm
According to the mother, the baby started to cry and the baby's skin is red, no
congenital defects were reported

Development History
Psychomotor development
Head Up : 1 month old
Smile : 1 month old
Laughing : 1- 2 month old
Slant : 2,5 months old
Speech Initation : 5 months old

5
 Mental Status: Normal
Conclusion: Growth and development status is still within normal limit and was
appropriate according to the patients age.

6
 Immunization History
Immunizatio Frequenc Time
n y

BCG 1 time 1 month old

Hepatitis B 2 times 0, 1 month old

DPT 2 times 2, 4 months old

Polio 3 times 0, 2, 4 months

old

Family History
Patients both parents were married when they were 24 years old and 27 years old,
and this is their first marriage
There are not any significant illnesses or chronic illnesses in the family declared
Born died : ( - )
Child dies : ( - )
Miscarriage : ( - )

History of Disease in Other Family Members

There is no one living around their home known for having the same condition as the patient.

III. Physical Examination

General Status
- General condition : Moderately ill
- Awareness : Compos Mentis
- Pulse : 130 x/min, regular, full, strong.
- Respiratory rate : 38x/min
- Temperature : 37,2oC (per axilla)
- Saturation O2 : 100%

Antropometry Status
- Weight : 5,8 kilograms
- Height : 60 centimeters

Nutritional Status based NCHS (National Center for Health Statistics) year 2000:
WFA (Weight for Age): 5,8/6 x 100 % = 96 % ( good nutrition)

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HFA (Height for Age): 60/61 x 100 % = 98 % (good nutrition)
WFH (Weight for Height): 5,8/60 x 100 % = 94 % (normal)

Conclusion: The patient has good nutritional status.

Head to Toe Examination

Head

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 Normocephaly, hair (black, normal distribution, not easily removed ) sign of
trauma (-)
Eyes
Icteric sclera -/-, pale conjunctiva -/-, hyperaemia conjunctiva -/- , lacrimation -/-,
sunken eyes -/-, pupils 3mm/3mm isokor, direct light +/+ and indirect light response
+/+
Ears
AD: Normal shape, no wound, no bleeding, secretion or serumen
AS: Normal shape, no wound, , no bleeding, secretion or serumen
Nose
Normal shape, midline septum, secretion -/-
Mouth

Lips: dry, crustae

Teeth: -
Mucous: moist
Tongue: no dirty, normal
Tonsils: T2/T2, hyperemia
Pharynx: hyperemia (+)

Neck
Lymph node enlargement (-), scrofuloderma (-), crustae (+)

Thorax :
i. Inspection : symmetric when breathing , no retraction, ictus cordis is not visible
ii. Palpation : mass (-), tactile fremitus -/-
iii. Percussion : sonor on both of lungs
iv. Auscultation :
1. Cor : regular S1-S2, murmur (-), gallop (-)
2. Pulmo : vesicular +/+, Wheezing -/- , Rhonchi -/-

Abdomen :
i. Inspection : Convex, epigastric retraction (-), there is no a widening of the veins,
no spider nevi
ii. Palpation : supple, hepar and lien not palpable, fluid wave (-),abdominal mass (-)
iii. Percussion : The entire field of tympanic abdomen, shifting dullness (-)
iv. Auscultation: normal bowel sound

Vertebra : There are no scoliosis, kyphosis, and lordosis, no mass along the
vertebral line
Extremities : warm, capillary refill time < 2 seconds, edema(-)
Skin : petechie, purpura, ecchymosis

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Neurological Examination

Meningeal Sign

Motoric Examination

Power
Hand 5 5 5 5/ 5 5 5 5
Feet 5 5 5 5/ 5 5 5 5
Tonus
Hand Normotonus / Normotonus
Feet Normotonus / Normotonus
Trophy
Hand Normotrophy / Normotrophy
Feet Normotrophy / Normotrophy
Physiologic Reflex
Upper extrimities
Biceps +/+
Triceps +/+
Lower extrimities
Patella +/+
Achilles +/+
Pathologic Reflex
Upper extrimities
Hoffman -/-
Trommer -/-
Lower extrimities
Babinsky -/-
Chaddock -/-
Oppenheim -/-
Gordon -/-
Schaeffer -/-
Clonus
Patella -/-
Achilles -/-

Autonom Examination

Defecation Normal
Urination Normal ( 3-4 times daily )

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 Sweating Normal

IV. Laboratory Findings

Routine complete blood count

Oktober 15th 2017

Hematology Results Normal Value

Haemoglobin 10,1 g/dL 12-14 g/dL
Leukocytes 10.900 /L 5,000 10,000/L
Hematocrits 30 % 40 48 %
Trombocytes 730.000/ L 150,000 400,000/L
Glucose 98 mg/dL <200 mg/dL
Sodium 134 mmol/L 135-145 mmol/L
Kalium 5,0 mmol/L 3,5-5 mmol/L
Chloride 101 mmol/L 98-108 mmol/L

V. Working Diagnosis
Steven Johnson Syndrome

VI. Differential Diagnosis

TEN

VII. Management

IVFD RL 600cc / day

Inj. Methylprednisolone 3 x 2 mg

Floxamini Dose 6 x 1 drop

VIII. Prognosis
Quo ad vitam : dubia ad bonam
Quo ad functionam : dubia ad bonam
Quo ad sanationam : dubia ad malam

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FOLLOW UP September 20th 2017 - September 23rd 2017
September 16th 2017. Second day of hospitalization

S Fever (-)
Blister and rash on the face, neck, arms and genitalia

O General condition: Compos mentis.

Heart rate = 120 x/min
Respiratory rate = 24x/min
Temperature = 36.5C
Eye: anemic conjunctiva -/-
Cardio : S1/S2, reguler, murmur (-) , no gallop
Pulmonary : vesiculer +/+, rhonchi -/-, wheezing -/-
Skin : Crustae and makuloeritema on the face, neck, arms and genitalia

A Steven Johnson Syndrome

P IVFD RL 600cc / day

Inj. Methylprednisolone 3 x 2 mg

Floxamini Dose 6 x 1 drop

September 17st 2017. Third day of hospitalization

S Blister and rash on the face, neck, arms and genitalia

O General condition: Compos Mentis

Heart rate = 120 x/min
Respiratory rate = 26 x/min
Temperature = 36.9C
Eye: anemic conjunctiva -/-
Cardio : S1/S2, reguler, no murmur, no gallop
Pulmonary : vesiculer +/+, rhonchi -/-, wheezing -/-
Skin : Crustae and makuloeritema on the face, neck, arms and genitalia

A Steven Johnson Syndrome

P IVFD RL 600cc / day

Inj. Methylprednisolone 3 x 2 mg

Zalf Betamethasone

Zalf Cendocitrol 2x1 ODS

Drop Tobroson 4x1 OD

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 Zalf Mupirocin 4x1

September 22nd 2017. Fourth day of hospitalization

S Skin

O General condition: Compos Mentis

Heart rate = 110 x/min
Respiratory rate = 24 x/min
Temperature = 36.6C
Eye: anemic conjunctiva -/-
Cardio : S1/S2, reguler, no murmur, no gallop
Pulmonary : vesiculer +/+, rhonchi -/-, wheezing -/-
Skin : Crustae and makuloeritema on the face, neck, arms and genitalia

A Steven Johnson Syndrome

P Discharge from hospital

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 LITERATURE REVIEW

I. Definition

SJS and TEN are variants of the same process, presenting as severe mucosal erosions
with widespread erythematous, cutaneous macules or atypical targets. The cutaneous lesions
often become confluent and show a positive Nikolsky sign and epidermal detachment. In SJS,
epidermal detachment involves less than 10% of the total body skin area; transitional SJS-
TEN is defined by an epidermal detachment between 10 and 30%; TEN is defined by a
detachment greater than 30%. Full-thickness epidermal necrosis is observed on pathological
examination. This clinical definition separates SJS-TEN from erythema multiforme major.

II. Epidemiology

Certain infectious diseases may have an impact on the incidence of TEN, and this is
clearly the case for HIV where the annual incidence is approximately 1000-fold higher than
in the general population, with approximately 1 case per thousand per year in the HIV-
positive population. In a study of HIV positive patients of the greater Paris area in the late
eighties and early nineties, 15 cases of SJS/TEN were reported in patients with AIDS
compared to 0.04 expected cases. In another study only ten out of 50 cases of SJS/TEN in
HIV patients could be clearly attributed to the use of medications, whereas in the other cases
a cause could not be determined due to lack of data of drug intake or details. Regional
differences in drug prescription, the genetic background of patients (HLA, metabolizing
enzymes), the coexistence of cancer, or concomitant radiotherapy can have an impact on the
incidence of SJS and TEN. To a lesser extent, other infections have occasionally been
reported as the sole cause. Mycoplasma pneumoniae infections are widely documented to
cause SJS and TEN without initial exposure to drugs. Furthermore, Herpes simplex virus was
recognized in several cases of SJS, especially in children. Single case reports describe Lupus
erythematodes or reactivation of Herpes simplex under treatment with azithromycine as
potential causes of SJS. The occurrence of TEN in a patient with severe aplastic anaemia
after allogeneic haematopoietic stem cell transplantation has also been reported. However
there are still cases of SJS/ TEN without any obvious identifiable cause.

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III. Pathophysiology

The pathogenesis of SJS/TEN is not fully understood but is believed to be immune-

mediated, as re-challenging an individual with the same drug can result in rapid recurrence of
SJS/TEN. The histopathology of SJS/TEN lesions show that keratinocyte apoptosis followed
by necrosis is the pathogenic basis of the widespread epidermal detachment observed in
SJS/TEN. The clinical, histopathological and immunological findings in SJS/TEN support the
currently prevalent concept, that SJS and TEN are specific drug hypersensitivity reactions in
which cytotoxic T lymphocytes (CTL) play a role in the initiation phase. Indeed, in the early
phase of disease, blister fluid contains mainly cytotoxic CD8+T lymphocytes, suggesting that
a major histocompatibility (MHC) class-I restricted drug presentation leads to clonal
expansion of CD8+ CTLs, and the subsequent - to date only incompletely understood -
immune reaction that causes SJS/TEN. These CD8+ T cells express common cutaneous
leukocyte antigen (CLA) and are negative for CD45RA and CD28. Nassif et al. were able to
demonstrate that blister T cells from patients exert drug specific cytototoxic activity against
both autologous B-lymphocyte cell lines and keratinocytes, and furthermore demonstrated
that this cellmediated cytotoxicity was mediated by granzyme B. The discrepancy between
the paucity of the infiltration of immune cells (including CTLs) in the skin of patients with
SJS/TEN and the overwhelming keratinocyte apoptosis has however lead to the search for
cytotoxic proteins and/or cytokines that may amplify the extent of keratinocyte apoptosis
that CTLs alone could induce upon cell-cell contact. To date, the strongest evidence suggests
a key contribution of the cytotoxic molecules FasL and granulysin as molecules responsible
for the disseminated keratinocyte apoptosis in SJS/TEN.

The role of the membrane form of the death ligand FasL and its cognate death
receptor Fas in the signalling that triggers keratinocyte apoptosis is supported by research
performed using an ex-vivo experimental set up with TEN lesional skin biopsy cryostat
section overlays with Fas-expressing lymphoid target cells. However, the functional
relevance of up-regulated keratinocyte membrane FasL, and thus its ability to induce
keratinocyte cell death, has been questioned by some as the above ex-vivo demonstration of
the lytic ability of keratinocyte FasL in TEN was limited in its effect on lymphoid target cells
and not demonstrated with keratinocytes as target cells. It is well known that primary
keratinocytes are sensitive to the cytolytic effect of FasL in vitro, and this sensitivity can be
further enhanced by interferon gamma, a cytokine known to be present in the skin during

15
TEN. However, it is still not fully understood what causes the up-regulation of FasL Fas on
keratinocytes, and how the immune system, including T cells found in blister fluid at the
onset of disease may regulate this.

The role of soluble FasL (sFasL) in SJS/TEN remains controversial. It appears clear
now that increased levels of sFasL can be found in the serum of patients with SJS/ TEN, and
levels of sFasL are consistently elevated when analysis is performed preceding skin
detachment [48]. Soluble FasL as opoposed to membrane-bound FasL is, however, very
poorly cytolytic, and it is therefore unlikely to be a cause of keratinocyte apoptosis in TEN
[49]. Nevertheless, one study showed that sera of SJS/ TEN were able to induce abundant
keratinocyte apoptosis and furthermore that peripheral blood monuclear cells of patients
stimulated by the causative drug excreted high levels of sFasL [50], but it should be noted
that sera can contain small membrane vesicles with membarne bound FasL that can account
for the observed activity.

Gene expression analysis of blister fluid cells, and analysis of blister fluid from
patients with SJS/TEN has also recently identified secretory granulysin (a cationic cytolytic
protein secreted by CTLs, NK cells and NKT cells) as a key molecule responsible for the
induction of keratinocyte death in TEN. Blister fluid cells express high levels of granulysin
mRNA, the protein is found in increased concentrations in blister fluid, and most importantly,
recombinant granulysin mimicks features of SJS/TEN when injected intradermally in mice.
The finding that elevated serum granulysin levels apparently discriminate between serious
and non-blistering adverse drug reactions, serum granulysin levels being normal in the latter,
lends further support an important role of granulysin in SJS/TEN.

In conclusion, and based on our knowledge to date, CD8 T-cells as well as the
cytolytic molecules FasL and granulysin are key players in the pathogenesis of SJS/ TEN.
How a culprit drug in a given patient who will develop SJS/TEN regulates the function of
these key players is the subject of ongoing research.

IV. Clinical Manifestations

The clinical features of SJS/TEN are characteristic and the diagnosis is primarily clinical. The
initial symptoms or prodrome include fever, upper respiratory tract symptoms and
conjunctivitis mimicking febrile illness of infective origin. This is followed by the
detachment of mucous membranes (oropharyngeal, conjunctival, anogenital and nasal).

16
Usually, more than two mucous membranes are involved. Cutaneous lesions, in the form of
dusky erythematous macules/purpura and/or flat typical/atypical target lesions, erupt in
association with pain and burning sensation. Typical raised target lesions, characteristic of the
erythema multiforme spectrum, are usually absent. The lesions extend symmetrically,
predominantly on the trunk and proximal limbs over a period of hours to 23 days. There is
an appearance of flaccid blisters followed by sheet-like detachment of epidermis. Shearing
pressure on the involved erythematous skin may cause epidermal detachment (pseudo-
Nikolsky's sign). Peri-lesional erythema is a sign of disease activity and helps to monitor
response to treatment.[16] Systemic symptoms are almost always associated with SJS/TEN
overlap and toxic epidermal necrolysis. Involvement of the mucosae can lead to impaired
alimentation, painful micturition, photophobia, diarrhea and respiratory distress.
Thermoregulation is impaired and energy expenditure is increased. Re-epithelialization
begins in a few days after the cessation of disease activity and is usually complete in about 3
weeks, barring mucosae and pressure sites which take longer.

V. Diagnosis

The diagnosis relies on the one hand on clinical symptoms and on the other hand on
histological features. Typical clinical signs initially include areas of erythematous and livid
macules on the skin, on which a positive Nikolsky sign can be induced by mechanical
pressure on the skin, followed within minutes to hours by the onset of epidermal detachment
characterized by the development of blisters. It should be noted, however, that the Nikolsky
sign is not specific for SJS/TEN. Mucosal, including ocular, involvement develops shortly
before or simultaneously with skin signs in almost all cases. To distinguish SJS, SJS-TEN
and TEN the surface area of the detachment is the main discriminating factor (Figure 1).
Histological work up of immediate cryosections or conventional formalin-fixed sections of
the skin revealing wide spread necrotic epidermis involving all layers confirms the diagnosis.
In order to rule out autoimmune blistering diseases, direct immune fluorescence staining
should be additionally performed and no immunoglobulin and/or complement deposition in
the epidermis and/ or the epidermal-dermal zone should be detected.

VI. Treatment
Early management The management of patients must be prompt; early diagnosis with the
early recognition and withdrawal of all potential causitive drugs is essential to a favorable
outcome. Morbidity and mortality increase if the culprit drug is withdrawn late. We observed

17
that death rates were lower when causative drugs with short elimination half-lives were
withdrawn no later than the day when blisters or erosions first occurred. No difference was
seen for drugs with long half-lives. Second, intravenous fluid replacement must be initiated
using macromolecules or saline solutions. Third, the patient must be transferred to an
intensive care unit or a burn center. Prompt referral reduces risk of infection, mortality rate
and length of hospitalization. Symptomatic treatment General principles. The main types of
symptomatic treatment are the same as for burns, and the experience of burn units is helpful
for the treatment of TEN: environmental temperature control, careful and aseptic handling,
sterile field creation, avoidance of any adhesive material, maintenance of venous peripheral
access distant from affected areas (no central line when possible), initiation of oral nutrition
by nasogastric tube, anticoagulation, prevention of stress ulcer, and medication administration
for pain and anxiety control are all essential.

However, TEN and burned patients are not identical: burns happen in a very short time period
(a few seconds) and do not spread thereafter; the TEN-SJS progress occurs during several
days, including after hospital admittance. Cutaneous necrosis is more variable and often
deeper in burns than in TEN. These differences induce a some important management
specificities. Subcutaneous edema is a very uncommon feature of TEN, in contrast with
burns, probably because of milder injury to blood vessels. Therefore the fluid requirements of
TEN patients are habitually two-thirds to three-fourths of those of patients with burns
covering the same area. Since the lesions are restricted to the epidermis and usually spare the
hair follicles, the regrowth of epidermis is quick in patients with SJS-TEN. This supports a
different approach of topical treatment.

Systemic management. Pulmonary care includes aerosols, bronchial aspiration and physical
therapy. If the trachea and bronchi are involved, intubation and mechanical ventilation are
nearly always necessary. Early and continuous enteral nutrition decreases the risk of stress
ulcer, reduces bacterial translocation and enterogenic infection, and allows earlier
discontinuation of venous lines. Phosphorus levels must be measured and corrected, if
necessary. Profound hypophosphoremia is frequent and may contribute to altered regulation
of glycemia and to muscular dysfunction. Most authors do not use prophylactic antibiotics.
Catheters are changed and cultured regularly. Bacterial sampling of the skin lesions is
performed the first day and every 48 hours. Indications for antibiotic treatment include an
increased number of bacteria cultured from the skin with selection of a single strain, a sudden

18
drop in temperature, and deterioration in the patient's condition. S. aureus is the main bacteria
present during the first days, and gram negative strains appear later.

Environmental temperature is raised to 30 to 32 degrees,C. This reduces caloric losses

through the skin and the resultant shivering and stress. Heat loss can also be limited by
raising the temperature of antiseptic baths to 35v' to 38(C and by using heat shields, infrared
lamps, and air-fluidized beds. Some drugs are needed. Thromboembolism is an important
cause of morbidity and death; effective anticoagulation with heparin is recommended for the
duration of hospitalization. Although this results in increased bleeding from the skin, it is
usually limited in amount and does not require additional transfusion. Antacids reduce the
incidence of gastric bleeding. Emotional and psychiatric support must not be forgotten.
Tranquilizers such as diazepam and morphinic analgesics can be used liberally if the
respiratory status permits. Insulin is administered when hyperglycemia leads to overt
glycosuria or to increased osmolarity. Many reviews have been published about intravenous
and oral supplementation on burn care: oxandrolone and human growth factor are effective
for decreasing hypercatabolism and net nitrogenous loss; ornithine alpha-ketoglutarate
supplementation of enteral feeding is effective to reduce wound healing time; high dose
ascorbic acid (66 mg/kg per hour) given during the first 24 hours reduces fluid volume
requirements. The usefulness of these treatments is not established in TEN/SJS and is
probably lower than for burns because of a shorter duration of skin detachment.

Topical management. No consensus exists about topical care. Possible approaches may be
conservative or more aggressive (large operative debridement). In our opinion, conservative
care is better than any surgical method. Even though we did not perform any study, it has
been our experience that the areas with a positive Nikolski, potentially detached by any
trauma healed much more rapidly where the epidermis stayed on site than on similar areas
where the epidermis had been detached. We leave in place the involved "detachable"
epidermis and use dressings only to protect it. Topical antiseptics (0.5% silver nitrate or
0.05% chlorhexidine) are used to paint, bathe, or dress the patients. Dressings may be gauzes
with petrolatum, silver nitrate, polyvidoneiodine, or hydrogels. Some authors use biologic
skin covers after epidermal stripping (cadaveric allografts, cultured human allogeneic or
autologous epidermal sheets). New dressings are being investigated: Apligraft(r), Biobrane(r),
TransCyte(r) (human newborn fibroblasts cultured on the nylon mesh of Biobranee). In
burns, topical recombinant bovine basic fibroblast growth factor allowed faster granulation
tissue formation and epidermal regeneration than placebo.

19
Prevention of ocular sequelae requires daily examination by an ophtalmologist. Eye drops,
physiologic saline, or antibiotics if needed, are instilled every 2 hours and developing
synechiae are disrupted by a blunt instrument. It is suggested that wearing gas-permeable
scleral contact lenses reduces photophobia and discomfort; these lenses improve visual acuity
and heal corneal epithelial defects in half of patients. Oral and nasal crusts are removed, and
the mouth is sprayed with antiseptics several times a day.

Specific treatment Corticosteroids. Corticosteroid use is highly debated. These drugs are a
mainstay in some units, bur other investigators consider systemic corticosteroids to provoke
prolonged wound healing, increased risk of infection, masking of early signs of sepsis, severe
gastrointestinal bleeding and increased mortality. A review of the literature shows only
patients series and no randomized clinical trials. Several articles reported corticosteroids
benefit: Tegelberg used 400 or 200 mg prednisone/day, gradually diminished over a 4 to 6
week period, and observed a single death among eight patients . Others series claimed also
excellent results but the diagnosis of SJS-TEN was debatable for most of the cases. In two
retrospective studies, no difference in mortality rates or infectious complications was noted in
patients who received steroids before or after referral. By contrast, other studies claimed that
corticosteroid use was detrimental. Thirty patients with SJS or TEN were included in an
uncontrolled prospective study. The first 15 patients received corticosteroids and the
mortality rate was 66%. Therefore, the next 15 patients were treated without corticoids and
the mortality rate was 33%. Both groups were similar in other described aspects. However, 11
of the 15 patients "without corticosteroids" had received corticosteroids prior to referral. Thus
no conclusion may be made about exclusive early administration of corticosteroids. In a
retrospective study, a multivariate analysis of prognostic factors showed that corticosteroid
therapy was an independent factor for increased mortality. Other series provided the same
conclusion. Moreover, many TEN cases have occurred during treatment with high doses of
corticosteroids for preexistent disease. In conclusion, today, according to most authors,
systemic corticosteroids are of unproven benefit in early forms and are clearly deleterious in
advanced forms of TEN/SJS.

Intravenous immunoglobulin (IVIG) One uncontrolled clinical trial pointed out the possible
usefullness of IVIG. It was based on in vitro demonstration that intravenous
immunoglobulins can inhibit Fas-Fas ligand mediated apoptosis. Ten consecutive patients
with TEN of moderate severity were treated with different doses of IVIG (0.2 to 0.75 g/kg of
body weight per day for four consecutive days); all survived. However, no randomized

20
clinical trial is published on this, and other authors have not obtained the same results.
Rational evaluation of the benefit of this treatment cannot currently be done.

Immunomodulating agents Some case reports claimed a benefit of plasmapheresis for

treatment of TEN/SJS. However, according to an open trial (8 consecutive patients with
historical controls), plasma exchange produces no significant difference in mortality, length
of hospital stay, or time to re-epithelialization. Cyclophosphamide was also proposed. Eight
patients with TEN were treated by only cyclophosphamide (initial dose: 300 mg per day); all
survived. Other series are not interpretable, on account of concomitant therapy by
cyclophosphamide and corticosteroids. Anecdotally, some cases of cyclophosphamideinduced
TEN were reported; one included a positive rechallenge test. In a retrospective comparative
study, cyclosporin was safe and was associated with a more rapid re-epithelialization rate and
a lower mortality rate (0/11 vs. 3/6) than treatment with cyclophosphamide and
corticosteroids. Cyclosporin has also received attention as a useful drug for treatment of TEN,
however, further investigations are needed to evaluate the real value of cyclosporin. N-
acetylcysteine . NAC increases the clearance of several drugs and their metabolites and in
vitro inhibits production of TNF-oc and IL- I P. We found no evidence of clinical
effectiveness in TEN. A randomized trial has shown lack of effectiveness of NAC in
prevention of hypersensitivity reactions to trimethoprim-sulfamethoxazole in patients with
HIV infection. Moreover, high doses of NAC may inactivate not only the culprit drug but
also other drugs, potentially useful for the patient. Other medications. We found only case
reports but no good evidence on the use of granulocyte colony stimulating factor, heparin,
monoclonal antibodies against cytokines and pentoxifylline. Thalidomide. Thalidomide has
been proposed as a treatment of TEN because it is a potent inhibitor of TNF-a action. This
drug was tested in the only randomized clinical trial ever published in TEN. It was a double-
blind, randomized, placebo-controlled study; the regimen was a 5-day course of thalidomide
400 mg daily. The study was stopped after the inclusion of only 22 patients because there was
an unexplained significant excess of mortality in the thalidomide group (10 of 12 patients
died, compared with 3 of 10 in the placebo group). Based on this unique trial, thalidomide
seems to be detrimental in TEN. In conclusion, we believe that no specific treatment has been
proven to be beneficial for TEN/SJS, which is a self-limited disease. For us, to date, the best
management is supportive care alone

21
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