ARTICLE
Autoimmune progesterone dermatitis (APD) is a rare clinical condition
characterized by the cyclic skin rash which develops premenstrually. APD
is a hypersensitivity reaction to endogenous or exogeneous progesterones
with variable cutaneous manifestations [1-3]. In 1964, Shelley et al.
first described APD in a 27 year-old woman with pruritic vesicular eruption
[4]. Since then, more than 40 cases have been reported in the English
language literature.
We describe a patient with typical findings of APD who was successfully
treated with conjugated estrogen.
Case report
A 27-year old woman was admitted to our clinic because of a recurrent
facial eruption which had been ongoing for 3 years. The patient's dermatitis
always occurred approximately 3 days before the onset of menses and resolved
spontaneously within 7 days. She reported that her attacks happened every
month and never occurred without a close association to her menses. The
lesions cleared spontaneously without any residual markings until the
next premenstrual time. She had never taken or been given exogeneous progesterone,
or received any hormonal therapy. She was otherwise healthy, and her family
history was not contributory.
During the previous months, the patient had had no change in her diet,
cosmetics, medications, or soaps that could account for the dermatitis.
The patient's menstrual cycle was regular. Dermatologic examination revealed
scaly, erythematous and edematous patches and papules distributed over
the face (Fig. 1). She
was initiallly treated with antihistamines and a topical corticosteroid
treatment which failed to suppress her eruption. The results of routine
laboratory analysis were normal. Hormonal analysis revealed normal levels
of serum progesterone, estrogen, FSH, LH, TSH, T3 and T4.
On histopathologic examination an epidermis
showing minimal hyperkeratosis, focal parakeratosis and minimal irregular
acanthosis was observed. The dermis contained minimal mononuclear inflammatory
cells around capillaries. A focus of inflammation composed entirely of
multinuclear giant cells was also present (Fig.
2). A biopsy performed at the two next presentations revealed the
same findings again.
The diagnosis of APD was suspected and an intradermal skin test was
performed, using an aqueous progesterone suspension of 0.1 mg/ml, and
normal saline. The same procedure was carried out on a healthy woman as
a control, and she displayed no reactions. Urticaria was the initial immediate
response at thirty minutes, followed by a delayed reaction at forty-eight
hrs of erythema at the sites of the progesterone injections in the patient,
whereas no reaction was observed with the saline injections. The skin
test with progesterone confirmed the diagnosis. Her lesions were also
exacerbated by the administration of intramuscular progesterone. These
findings were consistent with the diagnosis of APD. For six months the
patient was treated with conjugated estrogen with improvement in her dermatitis.
At one year follow-up, the patient had had no recurrence of the facial
eruption.
Discussion
The criteria for the diagnoses of APD includes [1] cylic skin lesions
related to the menstrual cycle [2] a positive progesterone skin test or
a positive oral/intramuscular challenge to progesterone and [3] demonstration
of a circulating antibody to the progesterone or basophil degranulation
tests [1, 3, 5, 6]. Most reported cases have been described in the light
of the first two criteria. APD usually occurs in adult life after menarche
and rarely during pregnancy or the postmenopausal period [1, 7, 8]. A
case of APD has also been documented after receiving oral progesterone
for the treatment of persistent amenorrhoea [9].
APD can present in different morphological forms such as pruritus, vesicular,
papular, eczematous, and bullous eruption, erythema multiforme, urticaria,
life-threateining angioedema, and mucosal lesions [1-14]. The histopathologic
diagnoses are variable, ranging from nonspecific, consistent with erythema
multiforme, allergic dermatitis, to prurigo simplex/lichen simplex chronicus
[1].
The pathogenesis of APD is unclear, although possibly related to the
development of antigenicity to endogeneous, or exogenous progesterones
by antibodies or cell-mediated reactions [1-5]. Miura et al. reported
that serum IgG from APD patients bound to the cytoplasm of rat corpus
luteum, and suggested that the formation of immune complexes between antibodies
and progesterone might be significant in the pathogenesis of this disease
[6]. The mechanism by which the endogeneous progesterone becomes antigenic
is unknown. Hart et al. suggested that previous exposure to exogenous
progesterone may induce hypersensitivity to endogenous progesterone [15].
It has been postulated that the patients may produce an altered form of
progesterone that induces an immunologic response [16]. The majority of
reported patients had a history of exposure to exogenous progesterone
such as oral contraceptives [1, 19, 22]. To our knowledge, there are only
nine previous cases of APD without exposure to exogenous progesterone
(Table I).
APD must be differentiated from perimenstrual
flares of skin diseases such as acne, dermatitis herpetiformis, erythema
multiforme, lichen planus, lupus erythematosus, psoriasis and estrogen
dermatitis. A positive intradermal skin test reaction to progesterone
is essential to establish the diagnosis of APD [1, 18].
The mainstay of treatment is to inhibit the secretion of endogenous
progesterone by the suppression of ovulation. The therapeutic modalities
of APD include prednisolone, luteinizing hormone releasing hormone agonists,
danazol, tamoxifen, and conjugated oestrogens [1, 19-22]. The majority
of reported patients with APD who are treated with estrogenic preparations
which supress ovulation, and therefore postovulation rise of progesterone
production, show an improvement in their condition as in our case [1].
Oophorectomy has been reported as a valuable treatment in intractable
cases [4, 17, 22]. APD was also reported to resolve without treatment
[1, 15] or during pregnancy in few patients [7, 14, 16].
Article accepted on 23/7/02
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