British Journal of Dermatology (1982) 106, 511-516.

Late prurigo of pregnancy

W.R.FABER*, TH.VAN JOOST*, R.HAUSMANt AND G.H.WEENINK:|:* Department of Dermatology, f Department of Pathology, and X Department of Gynaecology and Obstetrics,

University Hospital of Amsterdam, Amsterdam, The Netherlands

Accepted for publication 20 August 1981

SUMMARY

Seven patients who developed a characteristic pruritic rash in late pregnancy are described.Clinically the lesions consisted of erythematous urticaria! papules and plaques, with vesicles insome cases. The eruption started in the striae on the abdomen and spread over the thighs and inmost cases also over the arms and buttocks. Biopsy showed lymphocytic vasculitis with avarying admixture of eosinophils and only minor epidermal changes. Immunofluorescenceexamination of six cases showed C3 deposition along the dermoepidermal junction in only onecase. The lymphocytes, identified by a specific anti-T-cell serum, appeared to be mostly T-cells.

The nomenclature of pruritic skin disease in late pregnancy is confusing, but the term 'lateprurigo of pregnancy' seems appropriate for this condition.

Several pruritic dermatoses occur in association with pregnancy, e.g. herpes gestationis (Russel& Thorne, 1957), papular dermatitis of pregnancy (Spangler et al., 1962) and impetigoherpetiformis (Katzcnellcnbogen & Feuerman, 1966). These diseases are all rather uncommon.Perhaps more common, although exact figures are lacking, is a pruritic skin condition whichmay have been described by various authors under different names.

Vignes (1937) mentioned a skin condition which Besnier had called prurigo gestationis. Itbegan in the third or fourth month of pregnancy on the dorsal aspects of hands and feet. Costello(1941) described a papular rash under the name of prurigo gestationis of Besnier, which began inthe later months of pregnancy and which was confined to the extensor surfaces of theextremities. Bourne (1962) reported on a toxaemic rash of pregnancy, consisting of raisederythematous patches, sometimes with an urticarial aspect and a central papule, which started inthe striae on the abdomen and afterwards spread over the thighs, arms and buttocks. Nurse(1968) divided what he called prurigo of pregnancy into an early and a late type. The early typestarted in the second trimester and consisted of papules with excoriations, mainly localized onthe proximal parts of the extremities and upper trunk. The late type started in the last weeksbefore delivery, initially in the striae on the abdomen and it spread to the extremities and trunk.

Correspondence: W.R.Faber, MD, Department of Dermatology, Ziekenhuis 'De Lichtenberg', Utrechtseweg 160,3818 ES Amersfoort, The Netherlands.

0007-0963/82/0500-0511S02.00 (V) 1982 British Association of Dermatologists

512 W.R.Faber et al.Clinically, these lesions ranged from erythema multiforme to maculopapular erythema andurticaria.

Recently, Lawley et al. (1979) described a rash starting in the third trimester of pregnancywhich consisted of urticarial papules and plaques. It began on the abdomen and spread over thethighs and occasionally the buttocks and arms. They proposed the rather cumbersome name,pruritic urticarial papules and plaques of pregnancy (PUPPP).

MATERIALS AND METHODS

Seven patients who suffered from a similar pruritic dermatosis in the later stage of pregnancywere investigated.

Histopathological examination was performed in all cases. Direct immunofluorescence (DIF)examination on biopsies from lesional skin was performed in six cases. Monospecific fluorcsceinisothiocyanate (FTC) labelled antisera against human IgG, IgA, IgM, IgD, IgE and C3 (C3band C3C) were used in working dilutions i :6o or i: 120. The sections were examined with afluorescence microscope with blue narrowband excitation, equipped with epi-illumination.Moreover, sections were incubated with rabbit anti-human T-cell serum (working dilution1:20) (kindly provided by the Red Cross Blood Transfusion Service, Amsterdam, TheNetherlands) and with a FTC-labelled goat anti-rabbit immunoglobulin (GAR-FTC) anti-serum (working dilution r:2o). Controls consisted of incubating with GAR-FTC only or byusing normal rabbit serum as the first layer instead of the anti-T-cell serum. In these cases alsoindirect immunofluorescence (IIF) examination was performed (substrate rat tongue) as well asinvestigation for the herpes gestationis (HG) factor according to the method of Jordon cr al.(1976).

After delivery, epicutaneous tests were performed with the routine battery of the Interna-tional Contact Dermatitis Research Group (ICDRG) (Malten, Nater & van Ketel, 1976).Intraeutaneous tests were performed with o i ml of o 001",, aqueous solution of oestradiol ando-i ml of oi^o aqueous solution of progesterone as well as epicutaneous tests with oestradiol20",, and 50",) in petrolatum and progesterone 20",, and 50",, in petrolatum according to Jones& Gordon (1969). Intracutaneous tests were read at 20 min and 48 and 72 h; epicutaneous testswere read at 48 and 72 h.

RESULTS

In all patients tbe eruption started rather abruptly on the abdomen usually in the striae and itspread afterwards to the thighs and also over the arms and buttocks in most cases (Fig. i). Thelesions consisted of erythematous urticarial papules and plaques on which vesicles weresometimes present.

The disease generally started late in pregnancy, but in one case it started at 28 weeks and inone case 2 days after delivery.

There appeared to be no relation with drug intake as three patients took no drugs at all, threetook only iron tablets and one took anti-hypertensive medication.

There was no relation to the sex of the babies.Generally, there was a good response to local treatment with corticosteroids, but the eruption

cleared completely only after delivery. One patient showed a flare up at the first menstruationafter delivery. One patient had noted a similar eruption in previous pregnancies. In the two

Late prurigo of pregnancy 513

FIGURE I. Papular-urticarial lesions on the leg.

other patients having a second pregnancy, the previous pregnancies had been terminated at 22and 23 weeks respectively.

The histopathological findings are summarized in Table i. Slight focal parakeratosis, varyingfrom a few nucleated squames to small mounds, was seen in all cases. The epidemiis itself,except for a slightly irregular distribution of melanin pigment in the basal layer, was virtuallynormal. The dcrmis presented a moderate superficial and at times also a mild deep infiammatoryreaction consisting of perivascular lymphocytic aggregations. In most cases these assumed theform of a lymphocytic vasculitis as judged by either the involvement of the vessel walls, or thepresence of fibrin thrombi. The number of eosinophils varied considerably. There were minorindividual histological changes. These consisted of occasional slight compact hyperkeratosis,slight to moderate exocytosis, vacuolization of the basal cell layer, variation in the extent ofdermal involvement, occasionally accompanied by superficial oedema, admixture of a fewmacrophages in the lymphocytic accumulation and the occasional presence of melanophages inthe upper dermis.

Immunofluorescence studies were performed in six cases. Direct IF examination showed C3deposits in the vessel walls in one case and linear C3 deposition along the dermo-epidermaljunction in another case. Indirect IF examination for anti-epithelial antibodies as well asinvestigation for the HG factor was negative in all these cases.

Examination with the anti-T-cell serum showed accumulation of cells with a positive

514 W.R.Faber et al.TABi-E I. Histology of late prurigo of pregnancy

Patent no.

I

2

34367

P

+-1-++

++

±

BV

+++++

IP

++++

EX

++-f

-(-

-HI

+

l-l-

DIR

SS/DSS/DS/DS/DS

LV

+++++ *-1-+

E

+ +++++ +±

* = Thickening and fibrinoid changes of the walls of small bloodvessels; ± =mild; + = definite; + + = strong.

P—Parakeratosis; BV—basal layer vacuolization; IP—irregularbasal pigment distribution; EX—exocytosis (inflammatory cellsin the epidermis); DIR—dermal inflammatory reaction; L V ^lymphocytic vasculitis; E—eosinophils; S—superficial;D—deep.

membrane staining in and around the vessel walls, and also some positive staining cells in theepidermis.

Skin tests were performed in five patients. Epicutaneous tests with the routine ICDRG serieswere negative in three cases, a positive reaction (+ +)tO2'5'^,i nickel sulphate in petrolatum wasfound in one case and a positive ( + ) reaction to i5'\, parabens in petrolatum was found inanother case. Epicutaneous and intracutaneous tests with oestradiol and progesterone werenegative in these cases.

DISCUSSION

Our patients clinically resemble to a great extent those described by Bourne (1962) and Lawleyet al. C1979) and those described as late type of prurigo of pregnancy by Nurse (1968). In ourpatients the skin lesions generally started in the third trimester of pregnancy, although notespecially in the last weeks before delivery, and in one case they even appeared 2 days afterdelivery.

Contrary to Lawley er al. (1979), the histological features in all our patients were essentiallythe same and were fairly distinctive. The common denominator appeared to be a lymphocyticvasculitis with a variable admixture of eosinophils. These cells were rather numerous in threecases, but could easily be found in the other eases by examining multiple sections of the biopsies.In most cases two biopsies were taken (one for histological and one for immunofluorescenceexamination) and we found that the number of eosinophils varied between the two biopsies inseveral cases. Hxocytosis in slight and varying degree was found in all cases.

It appeared from the examination using anti-T-cell serum that the mononuclear infiltrates, aswell as the cells penetrating into the epidermis, were mainly T-cells.

Since several cases had vesicles, we investigated the possibility of contact sensitization as apossible cause of the skin eruption. In two out of five patients examined by the routine ICDRGseries we found positive delayed type reactions to nickel sulphate and parabens respectively, butthese reactions appeared to be unrelated to the occurrence of the skin lesions.

Since profound hormonal changes take place in pregnancy and since a disease called

Late prurigo of pregnancy 515autoimmune progesterone dermatitis of pregnancy has been described (Bierman, 1973), we alsotested five patients epicutaneously and intracutancously with oestradiol and progesterone butthese tests were negative.

In one patient we found linear C3 along the dermo-epidermal junction. In this case weinitially considered the possibility of herpes gestationis. The HG factor was not present, thoughthis may be lacking in some cases of herpes gestationis (Lawley, Stingl & Katz, 1978), but theclinical and histological features persuaded us that all our cases had an identical condition.

We believe that the patients described in the present study as well as those described astoxaemic rash of pregnancy (Bourne, 1962), latetypeof prurigo of pregnancy (Nurse, 1968) andpruritic urticarial papules and plaques of pregnancy (Lawley et al.^ 1979) have the samecondition. The clinical features of the patients described as prurigo of pregnancy of Besnier byCostello (1941) are more compatible with the early type of prurigo of pregnancy as reported byNurse (1968), although Costello states that in his cases the eruption started in the later months ofpregnancy.

In our opinion, until more insight is gained into the aetiology of this condition, the term lateprurigo of pregnancy seems to be the most appropriate. The possibility that this condition is a'forme fruste' of herpes gestationis merits further consideration.

ADDENDUM

The original description of prurigo of pregnancy, attributed to Besnier (Vignes, 1937) is that of amarked oedematous papular eruption localized on the extensor sides of hands and feet, startingin the third and fourth month of pregnancy. This seems to be more compatible with the earlytype of prurigo of pregnancy described by Nurse (1968).

Recently, we saw three patients suffering from a pruritic papular dermatosis which started inthe second trimester of pregnancy and which was predominantly localized on the extremities.These patients may belong to this early type of prurigo of pregnancy. Direct immunofluores-cence examination was negative in these cases. The histological picture was very similar to thatfound in our patients with the late type of prurigo of pregnancy, though in one case thehistological picture was blurred by a slight psoriasiform reaction (Pinkus & Mehregan, 1976).

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LAWLEV, T.J., STINGL, G , & KATZ, S.I. (1978) Fetal and maternal risk factors in herpes gestationis. Archives ofDermatology, 114, 552.

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