Surachai Likasitwattanakul, M.D.
|CC : Fever and rash
prior to admission.
PI : A 13-year-old boy was admitted to our hospital with fever,
and a rash all over the body. The patient was known to have had complex
partial seizure with secondarily generalization for four years. A combination
of phenytoin and phenobarbital was tried for 4 years without any benefit.
Four weeks before this admission, the parents decided to stop phenobarbital
because of its ineffectiveness and the patient's recent weakness. After
initial evaluation at our institution, phenobarbital was represcribed
and carbamazepine was added, while phenytoin was tapered off. Twelve days
after starting carbamazepine, the patient developed fever and painful
edematous red eyes followed by painful, swollen lips. The next day, a
red rash occurred initially on both wrists and ankles, spread rapidly
to the scrotal area and then all over the body.
Temp= 36.5 o C Pulse rate= 80/ min Respiratory rate= 24/ min BP= 110/60
Body weight= 30 kg.
A boy with good consciousness.
Skin findings: Generalized symmetrical
discrete purpuric macules, papules and patches including the palms,
soles and scrotal area (Figure 1). Dry hemorrhagic crusts, edema and
redness of the lips and external nares were seen (Figure 2). Multiple
necrotic membranous patches were noted on the buccal mucosa. Mild erosion
of the glans penis and a few crusts on the eyelids were seen. Otherwise,
the patient was normal.
|Figure 1. Multiple
sharply demarcated purpuric macules and patches of Stevens-Johnson syndrome.
Dry hemorrhagic crusts on red lips and anterior nares on the 7th day of
|Diagnosis : Stevens-Johnson
Various cutaneous eruptions associated with antiepileptic drugs include
SJS, toxic epidermal necrolysis and hypersensitivity syndrome (1).
The patient was diagnosed as SJS because of the skin findings
and mucosal involvement. The most important aspect was to identify the
causative medication. The "length of exposure" rule is a useful
method for suspecting the presence of an adverse drug reaction. The
medications received in a 7-21 day period are a most likely cause and
those within a 2-month duration are considered a possible cause (2-5).
This patient had obviously taken carbamazepine for twelve days before
developing fever and a rash that rapidly became purpuric macules, patches
and areas of denudation. He also had more than two painful areas of
mucosal surface involvement. Therefore, the causative medication was
most likely carbamazepine. He had been on phenobarbital and phenytoin
for many years without any allergic problem.
1. Toxic epidermal necrolysis which is fever and inflammation of the
eyelids, conjunctivae, mouth, and genitalias, may precede diffuse tender
erythema. Flaccid bullae may develop. Characteristically, full-thickness
epidermis is lost in large sheets. Conjuntivitis and oral lesions are
usually not as severe as in SJS (3-5).
2. Antiepileptic drug hypersensitivity syndrome is characterized by
fever, skin rash and internal organ involvement (6).
Fever is usually an initial manifestation, followed by skin eruptions
and lymphadenopathy. However, it rarely has mucous membrane involvement.
The patient may develop hepatitis, eosinophilia, blood dyscrasia, nephritis
or lung involvement. Hepatitis is usually the leading cause of death.
1. Specific treatment.
There is no specific treatment for SJS. It is important to discontinue
the causative medication (carbamazepine in this patient). However, crossreactivity
among phenobarbital, carbamazepine, and phenytoin is as high as 70-80%
|2. Supportive treatment (2-5).
- Evaluate the degree of dehydration, correction of fluid and electrolyte
imbalance. Intravenous fluid may be necessary. Monitor urine output
and serum osmolality.
- Evaluate the nutritional disturbance. Caloric replacement is necessary.
Liquid to soft diet is encouraged.
- Local skin care, especially for the lips and genitalia, is required.
Denuded skin lesions can be cleansed with saline or Burow solution compresses.
Mouth rinses and antacids are an important aspect of care. Vaginal lesion
should be observed closely and treated to prevent vaginal stricture
- Other early complications should be looked for such as secondary bacterial
infection of the skin, diarrhea, otitis, gastrointestinal bleeding,
hepatitis, pneumonia, pneumothorax, myocarditis and eye complication.
The prevention of such complications includes periodic culture of the
skin, eyes and mucosal sites, and pulmonary toilet.
- Late complications are hypo-/ hyperpigmentation of the skin; alopecia
and nail shedding; angular web of the lips; strictures of the vagina,
anus, urethra and hematocalpos; symblepharon, synechiae; trichiasis;
corneal opacities; corneal scar; pseudomembrane and permanent blindness;
esophageal stenosis and stricture; progressive bronchiolitis obliterans;
progressive vanishing bile duct syndrome; and renal failure.
- Physical therapy to prevent contractures is needed.
- Systemic corticosteroid has been controversial. SJS developed in patients
with systemic lupus erythematosus who were on a high-dose of corticosteroid
1. Tennis P, Stern RS. Risk of serious cutaneous disorders after initiation
of use of phenytoin, carbamazepine, or sodium valproate: a record linkage
study. Neurology 1997;49:542-6.
2. จุฬาภรณ์ พฤกษชาติคุณากร. Update on erythema multiforme and Stevens-Johnson
syndrome.ใน : เกวลี อุณจักร, เสาวลักษณ์ โอภาสถิรกุล, อรวรรณ เลาห์เรณู,
ณัฐพงษ์ อัครผล, บรรณาธิการ. Update on Common Pediatric Problems. เชียงใหม่
:ธนบรรณการพิมพ์ 2543: 157-163.
3. Weston W. Erythema multiforme, Stevens-Johnson syndrome and Toxic epidermal
necrolysis. In: Harper J, Oranje A, Prose N. Textbook of Pediatric Dermatology.
Oxford: Blackwell Science. 2000: 628-636.
4. Fritsch PO, Ruiz-Maldonado R. Stevens-Johnson syndrome-TEN. In: Freedberg
IM, Eisen AZ, Wolff K, et al. Fitzpatrick's Dermatology in General Medicine.5th
edn. New York. McGraw-Hill. 1999: 644-654.
5. Weston WL, Hogan PA. Vascular reactions. In: Schachner LA, Hansen RC,editors.
Pediatric Dermatology, 2ndedition. New York: Churchill Livingstone. 1995:
6. Schlienger RG, Shear NH. Antiepileptic drug hypersensitivity syndrome.
Epilepsia 1998;39(Suppl 7):S3-S7.
7. Samimi SS, Siegfried E. Stevens-Johnson syndrome developing in a girl
with systemic lupus erythematosus on high-dose corticosteroid therapy.
Pediatr Dermatol 2002; 19: 52-55.