Journal of the
576 Correspondence
brahe, resulting after the transduction of the signal, in
the expression of a function. The lag time observed in
response to phorbol myristate acetate is considered as
a reliable index of activaton and is only slightly cor-
rected, in this case, by clofazimine. This molecule
might, therefore, act more by modifying the physico-
chemical properties of the membrane than by improving
the intracellular activation mechanisms. A grossly el-
evated IgE serum level in association with pyoderma
gangrenosum to the best of our knowledge has been
reported in only a single previous case)
Sharply elevated IgE serum levels, above 5,000
IU/ml, are seldom encountered except in the hyper-
immunoglobulin E recurrent infections syndrome. 4 De-
spite a permanent IgE serum level above 10,000
IU/ml, this patient was not thought to present a hyper
IgE recurrent infections syndrome. By definition, the
onset of the disease occurs in early childhood. Hyper
IgE recurrent infections syndrome is, moreover, char-
acterized by the occurrence of large subcutaneous staph-
ylococcal abscesses associated with recurrent infections
of the sinopulmonary tract and other viscera not ob-
served in our patient.
The role of the sharply elevated IgE serum levels in
the pathogenesis of this case of pyoderma gangrenosum
is unclear. A coincidental association is possible: heal-
ing of the lesions, obtained with clofazimine, was not
correlated by a significant decrease of the serum IgE
levels. However, the exposure of neutrophils and other
inflammatory cells to the high tissular levels of hista-
mine and other mediators released from basophils and
mast cells (after the interaction between cytophilic IgE
in excess and the various antigens that penetrate the
skin) could lead to a complex immunomodulator effect
that could be responsible, at least partially, for the de-
velopment of the ulcers, The recent report by de Cock
and Thorne5of successful treatment of two patients with
pyoderma gangrenosum by means of topical sodium
cromoglycate could plead, as in our patient, in favor
of a pathogenetie role of both basophil and mast cell
degranulation in some cases of pyoderma gangrenosum.
Additional reports, including determination of IgE se-
rum levels and in vitro studies of histamine release from
pyoderma gangrenosum patients' basophils and mast
cells, should further help clarify this hypothesis.
Ph. Berbis,* M.D., J. L. Mege,** M.D.,
C. Capo,** Ph.D., S. Kaplanski.** M.D.,
P. Bongrand,** M.D., Ph.D., and Y. Privat, * M.D.
Hotel-Dieu* and H@ital Sainte-Marguerite**
Marseille, France
American Academy of
Dermatology
REFERENCES
1, Lehrer RI, Cohen L. Receptor mediated regulation of su-
peroxide production in human neutrophils stimulated by
phorbol myristate acetate. J Clin Invest 1978;68:1314-20.
2. Mege JL, Capo C, Benoliel AM, Bongrand P. Determi-
nation of binding strength and kinetics of binding initia-
tion. A model study made on the adhesive properties of
P388D1 macrophage like cells. Cell Biophys 1986;8:
148-50.
3. Robinson HF, McGregor R, Collins R, Cheung K. Com-
bined neutrophil and T cell deficiency. Initial report of a
kindred with features of hyperimmunoglobulin E syn-
drome and chronic granulomatous disease. Am I Med
1982;73:63-70.
4. Bucldey RH, Wray BB, Blemaker EZ. Extreme hyper-
immunoglobulin E and undue susceptibility to infections.
Pediatrics 1972;48:59-70.
5. De Cock KM, Thome MG. The treatment of pyoderma
gangrenosum with sodium cromoglycate. Br J Dermatol
1980;102:231-3.
Roaccutane and menorrhagia
To the Editor: Isotretinoin (Roaceutane, Europe; Ac-
cutane, United States and Canada) is a very effective
oral treatment for recalcitrant nodulocystic acne. It is,
however, recognized as highly teratogenic' and is ab-
solutely contraindicated in women of childbearing age
unless adequate contraception is used, usually in the
form of an ora) contraceptive.
Abnormal menses with isotretinoin therapy have
only rarely been reported to the Roche Basle Drug Sec-
tion in Switzerland. Only four cases of menorrhagia or
prolonged menstrual bleeding have been reported.* In
two of these cases the dosage of isotretinoin was de-
creased and the patients had no further difficulties with
their menses, lsotretinoin therapy was stopped and the
symptoms resolved in the remainder of the cases also.
We report another case briefly.
Case report. A 17-year-old woman with moderate to se-
vere papulopustular acne encountered a problem of prolonged
menstrual bleeding while being treated with isotretinoin. Prior
to administration she had normal menstrual periods lasting
5 days every 28 days and requiring two or three tampons per
day. Her periods started at the age of 15 and had been regular
ever since. She was currently taking the oral contraceptive
Synphasic (norethisterone, 0.5 mg; ethinyl estradiol, 0.03
rag). She was commenced on isotretinoin, 0.5 mg/kg (30
mg/day) but experienced prolonged menstrual bleeding re-
quiting two or three tampons per day and persisting for 20
days; the bleeding ceased 2 days after isotretinoin was
*RocheBasle Drug Safety Section, Roche case reports, September
1986 [personalcommunication].
Volume 18
Number 3 Correspondence 577
March 1988

stopped. Eight days later she had a lighter than normal period
lasting 5 days. Her oral contraceptive was changed to Mar-
velon (0.035 mg ethinyl estradiol; 0.15 mg desogestrel) at
this stage. Ten days later the isotretinoia was reintroduced;
however, her subsequent menstrual period, although occurring
at a normal time, persisted longer than her normal priod and
ceased 1 day after the isotretinoin was stopped. This was a
total of 10 days. Since she stopped the isotretinoin the sub-
sequent menstrual period occulted at the normal time and was
of normal volume and length and her periods have since
returned to normal.

Comment. Menstrual irregularities are common in

young women due to physiologic hormone changes?
However, this patient had a regular menstrual cycle
prior to commencement of isotretinoin, and it is be-
lieved to be the cause of her irregularity. No adverse Fig. 1. The scalp at the first visit.
effects on hormone levels have been noted in those
patients treated with isotretinoin, suggesting another
mechanism for menstrual dysfunction?
Amenorrhea is the most commonly recognized men-
strual irregularity in patients treated with isotretinoin.
This has also been observed in patients treated with
vitamin A, and some workers have used it in the treat-
ment o f menorrhagia. 4 The association of our patients
taking isotretinoin and having prolonged menstrual
bleeding therefore appears to be a paradox and the
mechanism is unclear.
7". Christmas, F.R.A.C.P.
Auckland Public Hospital, Auckland, New Zealand

REFERENCES
1. Ward A, Brogden EN, Neff RC, Speight TM, Avery GS.
Isotretinoin: a review of the pharmacological properties
and therapeutic efficacy in acne and other skin disorders.
Drugs 1984;28:6-37.
2. Jones DL. Abnormal uteline bleeding. In: Llewellyn-
Jones D. Fundamentals of obstetrics and gynaecology.
Vol 2: Gynaecology. London: Faber & Faber, 1986:75-82.
3. Peck GL, Olsen TG, Yoder FW, et al. Prolonged remission
of cystic and conglobate acne with 13-cis-retinoic acid.
N Engl J Med 1979;300:329-33.
4. Lithgow DM, Poliztzer WM. Vitamin A in treatment of
menorrhagia. S Aft Med J 1977;51:191-3.
Fig. 2. Granulematous inflammation in the scalp.
(Hematoxylin-eosin stain; x 250.)
Lupus vulgaris with Michaelis-Gutmann-like
bodies in an immunologically compromised
digestion of bacteria by macrophages, characterizes
patientmcutaneous malacoplakia of,
malacoplakia, a local inflammatory lesion described in
tuberculous origin? almost every organ, t Coexistence of a significant im-
To the Editor: Concentric laminated calcified intracel- munosuppressive disease or treatment and the cuta-
lular Michaelis-Gutmann body, a result of incomplete neous malacoplakia has been notable in the majority of