INTRODUCTION

Women can rarely become sensitized to their own hormones.Sensitivity to progesterone is termed autoimmune proges-terone dermatitis and is now a well-documented conditionwith a number of cases being reported.1–4 Oestrogen sensitivityhas only rarely been reported.5–10 Both present as recurrentskin eruptions premenstrually. We report a case of oestrogendermatitis that had a positive intradermal test with oestrogenand was negative with progesterone.

CASE REPORT

A 36-year-old woman had a 5 year history of a recurrent itchyeruption involving mainly her face and upper trunk. The rashfollowed a cyclic pattern flaring 3 days premenstrually andimproving spontaneously 5–10 days after the onset of herperiod, with minimal involvement at other times. She had aregular menstrual cycle of 28 days. There was a history ofusing a low-dose oestrogen pill for contraception from 19 to29 years of age without experiencing any rash during thatperiod. She had two children at 30 and 35 years of age. During

her first pregnancy she described a generalized itchy erup-tion from early pregnancy, which settled spontaneously withdelivery. The rash did not recur in her second pregnancy.There was no history of atopy, photosensitivity or any signi-ficant medical illness, and she was not on any regular medi-cation. The current eruption responded partially to topicalcorticosteroids.

Physical examination revealed mainly erythematous maculopapules, a few vesicles and crusting distributed sym-metrically over the face, neck, upper chest, axilla and infra-mammary areas with minimal involvement of the arms andabdomen (Fig. 1).

Skin biopsy from a papule on the neck revealed spongioticepidermis with moderate to marked perivascular dermal infil-trate that was mainly lymphocytic. Investigations revealed fullblood count, urea, electrolytes and liver function tests to benormal. Her erythrocyte sedimentation rate was 15 mm/h(normal range, 0–12 mm/h) and anti-nuclear antibody testwas negative. Follicle stimulating hormone, luteinizing hor-mone, free testosterone, dehydroepiandrosterone acetate, sexhormone-binding globulin, and oestradiol levels were in thenormal range in both follicular and luteal phase. Progesteronewas normal in the follicular phase but reduced at 2.2 nmol/L(normal range, 3.1–5.5 nmol/L) in the luteal phase.

Given that the patient described premenstrual worseningof her rash with each cycle, sensitization to endogenous hor-mones was suspected and intradermal testing was carried outwith medroxyprogesterone acetate and premarin (conjugatedoestrogen). Each of these was used in dilutions of 1, 10 and100 µg/mL in sterile normal saline that also served as con-trol. A 27 gauge needle was used to inject 0.1 mL each time.The test was positive for oestrogen in all three dilutions withan urticarial response, and negative for progesterone and nor-mal saline at 30 min (Fig. 2). The test remained positive formore than 24 h. This confirmed the diagnosis of oestrogendermatitis.

She was commenced on tamoxifen 10 mg twice daily for 7 days premenstrually for each period, and complete clear-ance of her rash was noted after two cycles. Tamoxifen wasstopped after three cycles, which resulted in the minimalreturn of premenstrual symptoms prior to the next two periods. She was thus advised tamoxifen for a further 3 months, which cleared her rash.

DISCUSSION

Allergy to endogenous sex hormones was first demonstratedin 1945 in women who had symptoms related to menstrua-

Australasian Journal of Dermatology (1999) 40, 96–98

CASE REPORT

Oestrogen dermatitis

Ajay Kumar and Katherine Evelyn Georgouras

Department of Dermatology, Liverpool Hospital, Liverpool, New South Wales,Australia

SUMMARY

A 36-year-old woman presented with a recurrent itchyeruption mainly involving her face and upper trunk for5 years. The rash flared cyclically 3 days before hermenstruation and improved 5–10 days after the onsetof her period. Examination revealed erythematousmaculopapules, vesicles and crusting mainly on herface and upper trunk. Biopsy from a papule revealedspongiotic dermatitis. Intradermal testing with oestro-gen was positive. There was marked improvement withtamoxifen. Sensitivity to oestrogen and progesterone israre in women and the clinical presentation may besimilar. Positive intradermal testing is diagnostic.Tamoxifen is effective in treating oestrogen sensitivity.

Key words: cyclical, intradermal testing, oestrogensensitivity, premenstrual skin rash, tamoxifen.

Correspondence: Assoc. Prof. Katherine Georgouras, 87 CecilAvenue, Castle Hill, NSW 2154, Australia.

Ajay Kumar, MBBS. Katherine Evelyn Georgouras, FACD.Submitted 29 April 1998; accepted 4 October 1998.

tion, and positive intradermal tests with oestrogens and prog-esterones.5

Autoimmune progesterone dermatitis was first described in1964.1 The woman who was described presented with gener-alized erythema multiforme, which settled with oöpherectomy.It is characterized by recurrent cyclic eruptions includingeczema, urticaria, papules, vesicles and erythema multiformeduring the luteal phase of the menstrual cycle. Diagnostic cri-teria include positive intradermal skin testing, demonstrationof serum progesterone antibodies in some patients, andimprovement with agents that inhibit ovulation and decreaseserum progesterone.3

Sensitivity to oestrogens has only rarely been described.5–7

In 1995 Shelley and colleagues described a series of womenwho had a skin eruption with cyclic premenstrual flare andpositive intradermal tests to oestrogen.8 All six women wereof child-bearing age and showed clinical features that includedpapules, vesicles, urticaria, generalized pruritus, and handdermatitis. Four of them showed premenstrual worsening of

symptoms and, of the remaining, one was on oestrone andanother on premarin as oestrogen replacement therapy.These two women responded to discontinuation of these med-ications. The other four women responded to tamoxifen.Intradermal testing showed a wheal and flare response thatpersisted for more than 24 h. They named the condition oestro-gen dermatitis as the criteria for inclusion of the disorderwithin the strict immunological definition of autoimmunityhad not been met. Yet another woman who presented with pre-menstrual papules on the face, which cleared with tamoxifen,has been reported.9 A series of 14 women sensitive to oestro-gen has been described recently.10 They presented with clin-ical features including pruritus, urticaria, papulovesicles andeczema, and responded to tamoxifen 20 mg daily for 7 dayspremenstrually.

Oestrogen dermatitis 97

Figure 1 Erythematous maculopapules and vesicles over the face,neck and anterior chest.

Figure 2 Positive intradermal test with premarin.

Oestrogen dermatitis presents characteristically with lesionsthat cyclically appear or flare premenstrually and improvewith the onset of menstruation. The clinical manifestationsvary and include macules, papules and vesicles involving theface, neck, upper arms and trunk. This distribution may reflectoestrogen receptor density.11 The condition may also presentas localized or generalized pruritus or urticaria that flares pre-menstrually. Thus clinically both oestrogen and autoimmuneprogesterone dermatitis may be similar. To distinguish these,intradermal testing with a progesterone and an oestrogen isrequired. We used mederoxyprogesterone acetate and pre-marin (conjugated oestrogen) in dilutions of 1, 10 and 100µg/mL in sterile normal saline. Persistence of a papule formore than 24 h is considered positive.8 When the clinical pic-ture is that of urticaria, the intradermal test is a wheal thatfades in hours.8 The test site may be reactivated during sub-sequent periods. Although oestrogen levels reach a peak justbefore ovulation, it is unclear why the symptoms appear onlyin the luteal phase when oestrogen levels attain a second butsmaller peak.

The condition responds to tamoxifen, which is a syntheticanti-oestrogen that is structurally similar to diethylstilbesterol.It possibly acts through competitive binding of the oestrogenreceptor12 and thus interferes with the clinical expression ofoestrogen sensitivity. The dose used for this condition is usu-ally 10 mg two to three times daily for 7–14 days premen-strually for each cycle. Tamoxifen therapy has been linked toendometrial hyperplasia, endometrial cancer and cervicalpolyps.13–15 Intermittent use of tamoxifen for 7–14 days eachcycle may reduce the potential side-effects, moreover, it maynot be necessary to give it over a prolonged number of cycles,a view shared by other authors.8 We feel that a minimum ofthree cycles is required but some patients may require longertreatment. Some authors have used tamoxifen for long peri-ods of time for the condition. We feel that, in order to avoidexcessive use of tamoxifen, it would be appropriate to give abreak after three cycles and that the therapy should be tailoredto the individual situation.

Other treatments that have been successfully used to treat

oestrogen dermatitis include progesterone therapy, desensi-tization with oestrogens, and oöpherectomy.

In conclusion, oestrogen and progesterone dermatitis pre-sent similar clinical pictures. Women with recurrent flare ofskin eruptions premenstrually should be tested intradermallywith oestrogen and progesterone to confirm the diagnosis andto initiate specific therapy.

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14. Neven P, De Muylder X, Belle YV, Vanderick G, De Muylder E.Tamoxifen and the uterus and endometrium. Lancet 1989; i: 375–6.

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98 A Kumar and KE Georgouras