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592 Pediatric Dermatology Vol. 23 No. 6 November ⁄ December 2006
3. Niiyama S, Katsuoka K, Happle R, Hoffmann R. Multiple
eruptive dermatofibroma: a review of the literature. Acta
Derm Venereol 2002;82:241–244.
TOSHIYUKI YAMAMOTO, M.D.
YASUYUKI SAWADA, M.D.
KAZUYA MINATOHARA, M.D.
Ibaraki,
Japan
METHEMOGLOBINEMIA AND CNS TOXICITY
AFTER TOPICAL APPLICATION OF EMLA TO
A 4-YEAR-OLD GIRL WITH MOLLUSCUM
CONTAGIOSUM
To the Editor:
The eutectic mixture of 2.5% lidocaine and 2.5%
prilocaine (EMLA) is an anesthetic gel frequently used
by pediatricians and dermatologists. It is very useful in
preventing pain in painful superficial procedures in
children, and specifically, curettage of molluscum contagiosum (1). Contraindication for its use is a prior history of sensitivity to type amida local anesthetics and
special precaution must be taken in any application to
mucosa or injured skin (such as in atopic dermatitis or
molluscum contagiosum). In these situations the time of
application should be shorter because absorption is faster and plasma concentrations higher (2). The side effects
of EMLA are usually very mild but the application of an
excessive amount to a compromised cutaneous barrier
can cause potentially life-threatening complications such
as methemoglobinemia and central nervous system toxicity (3–5).
We report a 4-year-old girl with atopic dermatitis and
extensive molluscum contagiosum (left anterior hemithorax, axilla, and left arm). Ninety minutes prior to
arrival in our pediatric emergency department, her dermatologist had applied 30 g of EMLA to the affected
regions for the curettage of the molluscum contagiosum,
covering them with an occlusive dressing. Fifty minutes
after the application of EMLA, the girl had headache,
instability in walking, and blurry vision, and her mother
transported her to our emergency room.
When the girl arrived, she was not able to walk
without help, and had perioral cyanosis and considerable
amounts of EMLA on her skin. No respiratory distress
was noted and cardiopulmonary auscultation was normal. She was afebrile and oxygen saturation was 88%.
The EMLA cream was immediately washed off and the
girl was placed on 100% oxygen via a non-rebreather
facemask. Co-oxymetry revealed a level of methemoglobin of 19.0%. A complete blood count and electrolyte
concentrations were within normal limits.
She was given an intravenous dose of methylene blue
(1 mg/kg) and a few minutes later, her cyanosis had
disappeared and she was able to walk alone. Her
methemoglobin level dropped to 2.5%. The patient
remained in the Observation Unit, did not present with
additional problems, and was sent home 12 hours later.
Very few occurrences of methemoglobinemia secondary to the application of EMLA have been previously
reported. Most of them have been in young children with
previous skin injury and were associated with incorrect
use of the anesthetic agent (3–5). In our patient, the dose
of the EMLA applied, the skin lesions the girl had, and
the physical examination strongly suggested toxicity due
to an overdose of EMLA.
Methemoglobinemia is a rare cause of cyanosis in
childhood. Methemoglobin is the consequence of oxidation of normal hemoglobin. The intraerythrocytic
system reduces methemoglobin and maintains its level
under 2% of the total hemoglobin. Two types of methemoglobinemia are seen: one hereditary, and the other
acquired, usually resulting from exposure to toxic substances. The most common cause of methemoglobinemia is ingestion or skin exposure to an oxidizing agent. In
our environment this is usually caused by nitrate exposure, mainly from ingestion of home-made purées of
mixed vegetables not immediately consumed (6).
Clinical symptoms and signs of methemoglobinemia
are related to the level of methemoglobin. Cyanosis
becomes apparent at levels over 15% to 20%. Dyspnea,
lethargy, irritability, dizziness, headache, and weakness
can be noted at higher levels. Levels above 50% can
produce respiratory depression, heart arrhythmia, convulsion, or coma, and those higher than 70% are
potentially lethal. Because methemoglobin is generally
expressed as a percentage of total hemoglobin, levels may
not correspond with symptoms in some patients. Anemia, acidosis, respiratory compromise, and cardiac disease may make patients more symptomatic than
expected for a given methemoglobin level. In the three
published cases of methemoglobinemia produced by
EMLA the level of methemoglobin was lower than 21%,
but the patients presented with neurologic effects.
Methemoglobinemia should be suspected in every
patient with central cyanosis that does not improve with
oxygenotherapy, and a methemoglobin level measurement should be obtained. Initial treatment should be
supportive, with administration of supplementary
oxygen and decontamination (cleaning of the skin, gastric emptying, or activated charcoal). The elimination
half-life of methemoglobin is around 15–20 hours, and
this is reduced to 40–90 minutes if methylene blue is
administered. Thus, if the methemoglobin level is above
30% or clinical signs of hypoxia exist, intravenous 1%
Correspondence
methylene blue (1–2 mg/kg) should be administered, and
can be repeated in an hour if the symptoms persist. If the
methemoglobin level is above 70%, exchange transfusion and hyperbaric oxygen should be considered (7).
REFERENCES
1. Ronnerfalt L, Fransson J, Wahlgren CF. EMLA cream
provides rapid pain relief for the curettage of molluscum
contagiosum in children with atopic dermatitis without
causing serious application-site reactions. Pediatr Dermatol
1998;15:309–312.
2. Juhlin L, Hagglund G, Evers H. Absorption of lidocaine and
prilocaine after application of a eutectic mixture of local
anesthetics (EMLA) on normal and diseased skin. Acta
Derm Venereol 1989;69:18–22.
3. Parker J, Vats A, Bauer G. EMLA toxicity after application
for allergy skin testing. Pediatrics 2004;113:410–411.
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4. Rincón E, Baker RL, Iglesias AJ et al. CNS toxicity after
application of EMLA cream on a toddler with molluscum
contagiosum. Pediatr Emerg Care 2000;16:252–254.
5. Toum S, Jackson JB. Lidocaine and prilocaine toxicity in a
patient receiving treatment for mollusca contagiosa. J Am
Acad Dermatol 2001;44:399–400.
6. Sánchez J, Benito J, Mintegui S. Methemoglobinemia and
consumption of vegetables in infants. Pediatrics
2001;107:1024–1028.
7. Naguib M. Adverse effects of local anesthesia. Drug Saf
1998;18:222–250.
S. MINTEGI RASO, M.D.
J. BENITO FERNANDEZ, M.D.
E. ASTOBIZA BEOBIDE, M.D.
A. FERNÁNDEZ LANDALUCE, M.D.
Bizkaia,
Spain