628 Brief reports
APRIL 2003
icant and persistent facial scarring, atrophy, and hy-
perpigmentation resulting from NLE. In this case,
bleaching agents, tretinoin, and photoprotection
provided substantial cosmetic improvement.
REFERENCES
1. Franco HL, Weston WL, Peebles C, Forstot SL, Phanuphak P. Au-
toantibodies directed against sicca syndrome antigens in the
neonatal lupus syndrome. J Am Acad Dermatol 1981;4:67-72.
2. Dugan EM, Tunnessen WW, Honig PJ, Watson RM. U1RNP anti-
body-positive neonatal lupus. Arch Dermatol 1992;128:149-4.
3. Provost TT, Watson R, Gammon WR, Radowsky M, Harley
JB, Reichlin M. The neonatal lupus syndrome associated with
U1RNP antibodies. N Engl J Med 1987;316:113-8.
4. Miyagawa S, Kitamura W, Yoshioka J, Sakamoto K.
Placental transfer of anticytoplasmic antibodies in annular
erythema of newborns. Arch Dermatol 1981;117:569-72.
5. Furukawa F, Lyons MB, Lee LA, Coulter SM, Norris DA. Estradiol
Nonpigmenting solitary fixed drug eruption
caused by a Chinese medicine, ma huang (Ephedra
Hebra), mainly containing pseudoephedrine and
ephedrine
Kazuhiko Matsumoto, MD, PhD, Hajime Mikoshiba, MD, and Toshiaki Saida, MD, PhD
Matsumoto, Japan
We describe a case of nonpigmenting solitary fixed drug eruption appearing on the right thigh of a 31-year-old
woman in Japan. The causative drug was determined by closed patch test on postlesional skin as a Chinese traditional
herbal medicine, ma huang (Ephedra Hebra), mainly containing pseudoephedrine and ephedrine. (J Am Acad Dermatol
2003;48:628-30.)
A Chinese traditional herbal medicine, ma huang
(Ephedra Hebra), mainly containing pseudoephedrine and
ephedrine, has been widely used in the Oriental world for
hundreds of years. Currently, herbal mixtures containing
Ephedra Hebra are often used as health foods and
supplements. We describe a patient in Japan with a solitary
From the Department of Dermatology, Shinshu University
School of Medicine.
Funding sources: None.
Conflict of interest: None identified.
Reprint requests: Kazuhiko Matsumoto, MD, PhD, Department
of Dermatology, Shinshu University School of Medicine, 3-
1-1, Asahi, Matsumoto 390-8621, Japan. E-mail:
dermatsu@hsp. md.shinshu-u.ac.jp.
Copyright © 2003 by the American Academy of Dermatology, Inc.
0190-9622/2003/$30.00 0
doi:10.1067/mjd.2003.192
J AM ACAD DERMATOL
binding to cultured human keratinocytes of antibodies specific
for SSA/Ro and SSB/La. J Immunol 1988;141:1480-8.
6. McCune AB, Weston WL, Lee LA. Maternal and fetal outcome in
neonatal lupus erythmatosus. Ann Intern Med 1987;106:518-23.
7. Weston WL, Morelli JG, Lee LA. The clinical spectrum of
anti-Ro positive cutaneous neonatal lupus erythematosus.
J Am Acad Dermatol 1999;40:675-81.
8. Thornton CM, Eichenfield LF, Shinall EA, Siegfried E, Rabinowitz
LG, Esterly NB, et al. Cutaneous telangiectases in neonatal lupus
erythematosus. J Am Acad Dermatol 1995;33:19-25.
9. Crowley E, Frieden IJ. Neonatal lupus erythematosus: an unusual
congenital presentation with cutaneous atrophy, erosions, alope-
cia, and pancytopenia. Pediatr Dermatol 1998;15:38-42.
10. Lee LA, Weston WL. Cutaneous lupus erythematosus during
the neonatal and childhood periods. Lupus 1997;6:132-8.
11. Chung-E T, Buyon JP. Neonatal lupus syndromes. Rheum
Dis Clin North Am 1997;23:31-54.
12. Silverman ED, Laxer RM. Neonatal lupus erythematosus.
Rheum Dis Clin North Am 1997;23:599-618.
lesion of nonpigmenting (NP) fixed drug eruption
(FDE) (NPSFDE) caused by Ephedra Hebra.
CASE REPORT
On 2 consecutive evenings, a 31-year-old woman in
Japan took an herbal medicine (Sepi Gold, Zeria
Pharmaceutical Co, Tokyo, Japan) containing Ge-Gen-
Tan (Formula puerariae) for a common cold. On the
morning after the second dose, she noticed slightly
tender erythema on her right thigh and vis-ited our clinic.
The eruption was diagnosed as FDE and she was treated
with topical clobetasol propi-onate 0.05% ointment. The
eruption cleared gradu-ally without residual
pigmentation. She had taken Sepi Gold several times and
the same eruption had appeared on the same region
twice in the last 6 months. Three months later, after she
took the herbal medicine Xiao-Qing-Long-Tang
(Formula di-vinitalis caeruleae minor), a slightly tender
erythema
J AM ACAD DERMATOL Brief reports 629
VOLUME 48, NUMBER 4

reappeared on the same site as the previous FDE lesion.

She visited our clinic the next day.
A palm-sized, red erythema with reddish papules was
seen on her right thigh (Fig 1). She was treated with
topical clobetasol propionate 0.05% ointment again. The
eruption cleared without pigmentary changes in 7 days.

The patient refused oral provocation with herbal

medicines Formula puerariae and Formula divini-talis
caeruleae minor. The occlusive patch tests were
performed both on the site of previous FDE lesion and
on unaffected skin (back) using 25% of Formula
puerariae and Formula divinitalis caeruleae minor in
petrolatum and the eluate of the components of them.
Formula puerariae and Formula divinitalis caer-uleae
minor, and the common constituent of them, Ephedra
Hebra, clearly produced erythematous reac-tion solely on
the previous lesion (Fig 2). The result of open patch test
of 10% of l-ephedrine hydrochloride in petrolatum was
negative on the NPFDE lesion. Pseudoephedrine Fig 1. Palm-sized, red erythema with reddish papules was seen
hydrochloride, a raw ingredient of a stimulant drug, on patient’s right thigh.
could not be obtained in Japan.
Fig 2. Positive reaction of occlusive patch test on nonpig-
menting fixed drug eruption: 25% of Formula puerariae (H1)
DISCUSSION Abramowitz and Noun1 first proposed the con-cept of NPFDE in 1937. Fifty years later, Shelly and Shelly2 described a distinctive type of NPFDE that consisted of symmetric,
and Formula divinitalis caeruleae minor (H2) in pet-rolatum.
tender, large, erythematous plaque. Since then, there have been 15 reported cases of NPFDE: 9 caused by pseudoephedrine,

Third position of right side, eluate of Ephedra Hebra. Eluate was

prepared by putting dried Ephedra Hebra into boiled water in 15
1 by tetrahydrozoline,2 1 by piroxicam,11 1 by
minutes.
thiopental,12 1 by radiopaque contrast media
(iothalamate),13 1 by diflunisal,14 and 1 by ephed-rine and
pseudoephedrine.15 In our case, Ephedra Hebra, the2-10 fects by traditional Chinese herbal medicines are rare, but
common constituent of a herbal med-icine, Formula recently, various cases of adverse side effects by Ephedra
puerariae and Formula divinitalis caeruleae minor, was Hebra have been reported. Haller and Be-nowitz16
determined as the cause of NPSFDE. The main reviewed 140 reports of adverse events re-lated to the
components of Ephedra Hebra are d-pseudoephedrine use of supplements that contained ephedra alkaloids that
and l-ephedrine. Pseudo-ephedrine may have been the were submitted to the Food and Drug
causative agent of the eruption in our case, because
pseudoephed-rine is the most common drug causing
NPFDE. Although we could not perform patch tests
with pseudoephedrine, the result of open patch test with
ephedrine was negative. Other minor com-ponents of
Ephedra Hebra such as tannin, maoko-mine, ephedroxane,
ephedradine, monacosane, monacosane-10-ol, and
tricosane-1-ol, could not be excluded as the causative
reagent.
2 Formulation
Pseudoephedrine 60 mg/5 ml active subtance
Metyleparaben 0,015% preservative
Tartrazine 0,005% coloring
Sucrose 30% sweeting,thickener
Sorbitol 15% anticaplockin
Aquadest ad 100 ml solvent

NPFDE has been characterized by multiple sym-

metric distributed eruptions.2 Only 3 reports5,11,13 of
NPSFDE were found in the literature. Recognition of
this clinical entity is important, because NPSFDE could
not be so unusual.
Physicians and laypersons believe that advers
630 Brief reports
Administration. According to this report, 47% were
cardiovascular symptom such as hypertension, myo-
cardial infarction, and stroke, and 18% were central
nervous system events such as seizures. Furthermore,
hepatotoxic effects have also been reported.17 As these
medicines containing Ephedra Hebra are now popular in
the world, NPFDE or other forms of drug eruption
caused by Chinese traditional herbal medicines should be
taken into consideration in any country.
REFERENCES
1. Abramowitz EW, Noun MH. Fixed drug eruptions. Arch
Derma-tol Syphil 1937;35:875-92.
2. Shelley WB, Shelley ED. Nonpigmenting fixed drug
eruption as a distinctive reaction pattern: examples
caused by sensitivity to pseudoephedrine hydrochloride
and tetrahydrozoline. J Am Acad Dermatol 1987;17:403-7.
3. Alanko K, Kanerva L, Mohell-Talolahti B, Jolanki R,
Estlander T. Nonpigmented fixed drug eruption from
pseudoephedrine. J Am Acad Dermatol 1996;35:647-8.
4. Quan MB, Chow WC. Nonpigmenting fixed drug eruption
after pseudoephedrine. Int J Dermatol 1996;35:367-70.
5. Hindioglu U, Sahin S. Nonpigmenting solitary fixed drug
erup-tion caused by pseudoephedrine hydrochloride. J Am
Acad Der-matol 1998;38:499-500.
6. Vidal C, Prieto A, Perez-Carral C, Armisen M. Nonpigmenting
Dermatobia hominis myiasis among travelers returning
from South America
Jeremy Tamir, MD,a Josef Haik, MD,a Arie Orenstein, MD,a and Eli Schwartz, MD, DTMHb
Tel Aviv, Israel
Dermatobia hominis is the most common cause of myiasis in Central and South America, affecting mammals and
humans, causing nonhealing furuncle-like lesions. During the years 1994 to 1999, 14 Israeli travelers returning from
South America were diagnosed with D hominis myiasis. The approach consists of correct diagnosis and a proper
removal of the larvae, after which the patients heal with no complications. (J Am Acad Dermatol 2003;48:630-2.)
M yiasis is an infestation of human tissue by larvae
of higher flies. Dermatobia hominis (the human botfly) is the
most common localized myiasis in tropical America.1 The
usual
From the Plastic and Reconstructive Surgery Department, a
and the Center for Geographic Medicine and Department of
Medicine C,b Chaim Sheba Medical Center, The Sackler
School of Medicine, Tel Aviv University.
Funding sources: None.
Conflict of interest: None identified.
Reprint requests: Jeremy Tamir, MD, Department of Plastic and
Re-constructive Surgery, Chaim Sheba Medical Center, Tel
Hashomer 52621, Israel. Email: irmidana@inter.net.il.
Copyright © 2003 by the American Academy of Dermatology, Inc.
0190-9622/2003/$30.00 0
doi:10.1067/mjd.2003.37
J AM ACAD DERMATOL
APRIL 2003
fixed drug eruption due to pseudoephedrine. Ann Allergy
Asthma Immunol 1998;80:309-10.
7. Anibarro B, Seoane FJ. Nonpigmenting fixed exanthema
in-duced by pseudoephedrine. Allergy 1998;53:902-3.
8. Krivda SJ, Benson PM. Nonpigmenting fixed drug
eruption. J Am Acad Dermatol 1994;31:291-2.
9. Camisa C. Fixed drug eruption due to pseudoephedrine.
Cutis 1988;41:339-40.
10. Hauken M. Fixed drug eruption and pseudoephedrine.
Ann Intern Med 1994;120:442.
11. Valsecchi R, Cainelli T. Nonpigmenting fixed drug reaction to
piroxicam. J Am Acad Dermatol 1989;21:1300.
12. Desmeules H. Nonpigmenting fixed drug eruption after
anes-thesia. Anesth Analg 1990;70:216-7.
13. Benson PM, Giblin WJ, Douglas DM. Transient,
nonpigmenting fixed drug eruption caused by radiopaque
contrast media. J Am Acad Dermatol 1990;23:379-81.
14. Roetzheim RG, Herold AH, Van Durme DJ.
Nonpigmenting fixed drug eruption caused by diflunisal. J
Am Acad Dermatol 1991;24:1021-2.
15. Garcia Ortiz JC, Terron M, Bellido J. Nonpigmenting fixed
exan-thema from ephedrine and pseudoephedrine.
Allergy 1997;52: 229-30.
16. Haller CA, Benowitz NL. Adverse cardiovascular and central
nervous system events associated with dietary supplements
containing ephedra alkaloids. N Engl J Med 2000;343:1833-8.
17. Stickel F, Egerer G, Seitz HK. Hepatotoxicity of
botanicals. Pub-lic Health Nutr 2000;3:113-24.
host of D hominis is livestock mammals; humans are
accidentally infested.2 The fly deposits its packet of eggs
on a mosquito or other blood-feeding insect, which
unknowingly transfers the eggs to a warm-blooded
animal. When the mosquito lands on the skin, the eggs
hatch and penetrate the feeding site. The larva develops
in the skin for 4 to 14 weeks, reaching a length of about
2 cm, exits, and drops to the ground to pupate. After 14
to 30 days the adult fly emerges and the life cycle
resumes. In humans the skin lesions are most frequently
seen on unpro-tected areas including the hands, legs,
head, and neck. At first the lesions resemble a pruritic
mos-quito bite, but as the larva begins to move it pro-
duces severe pain and itching. The inflammatory