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Hormonal evaluation and autoimmune background in pruritic urticarial papules and plaques of pregnancy
Hormonal evaluation and autoimmune background in pruritic urticarial papules and plaques of pregnancy Joseph Alcalay, MD, Arieh Ingber, MD, Datia Kafri, MD, Jacob Segal, MD, Hayuta Kaufmann, PhD, Bilha Hazaz, BSc, and Miriam Sandbank, MD Petah Tiqva and Tel Aviv, Israel There is little insight into the pathogenesis of most of the dermatoses specifically associated with pregnancy. We evaluated the hormonal profile and the autoimmune background in 11 pregnant women with pruritic urticarial papules and plaques of pregnancy. No statistically significant difference was found between the serum levels of the ~-subunit of human chorionic gonadotropin, estradiol, cortisol, and urinary estriol of the patients and gestational age-matched control subjects. No autoantibodies were found in the patients' group. We conclude that patients with pruritic urticarial papules and plaques of pregnancy have no hormonal alterations when compared with normal pregnant women and that no known major autoimmune background plays a part in the pathogenesis of the disease. (AM J OesTET GvNECOL 1988;158:417-20.)
Key words: Pruritic urticarial papules and plaques of pregnancy, hormonal profile, autoantibodies
Pregnant patients may develop skin disease that is seen in the nonpregnant state. However, a small group of dermatoses occur predominantly, if not exclusively, during pregnancy. These dermatoses include herpes gestationis, impetigo herpetiformis, prurigo gestationis, papular dermatitis of pregnancy, and pruritic urticarial papules and plaques of pregnancy. 1 The pathogenesis of most of the specific dermatoses of pregnancy, except for herpes gestationis, is still an enigma. We present here a prospective study in which the hormonal profile and autoimmune backgrounds were studied in patients with pruritic urticarial papules and plaques of pregnancy. To the best of our knowledge, no such study has previously been done.
Material and methods Patients. The study population consisted of 11 pregnant women with pruritic urticarial papules and plaques of pregnancy with ages ranging from 18 to 36 years and an average age of 27 years. The patients'
From the Departments of Dermatology and Obstetrics and Gynecology, The Endocrine Laboratory, and the Immunopathology Unit, Beilinson Medical Center, and Sackler School of Medicine, Tel Aviv University. Received for publication January .15, 1987; revised August 31, 1987; accepted September 9, 1987. Reprint requests: Joseph Alcalay, MD, Department of Immunology, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 1515 HolcOmbe Blvd., Box 178, Houston, TX 77030. .
Fig. 1. Erythematous papules and large urticarial plaques on the thighs.
417
418 Alcalay et al.
February 1988 Am J Obstet Gynecol
Fig. 2. Erythematous, edematous papules along the striae distensae.
Table I. Case histories Case No.
Age
Gestational age at diagnosis
(yr)
I
26 18 23 31 31 31 25 36 26 26 22
2 3 4 5 6 7 8 9 10 11
Ultrasound findings
Labor
(wk)
Gravidity and parity
(wk)
Fetal outcome
29 27 30 39 38 42 40 25 21 40 36
Gl/PO Gl/PO Gl/PO G2/PO G2/PO G1/PO G2/P1 G4/P3 G2/PO Gl!PO Gl/PO
Normal Normal Normal Large for dates Normal Normal Normal Normal Normal Normal Normal
41 42 40 40 41 41 40 41 42 40 39
Normal Normal Normal Large for dates Normal Normal Normal Normal Normal Normal Normal
past history showed no eruptions or any other skin or systemic diseases in previous pregnancies. The diagnosis of pruritic urticarial papules and plaques of pregnancy was made on clinical examination. The criteria included symmetrical eruption, mainly on the arms, forearms, abdomen, and thighs, consisting of erythematous papules and urticarial plaques with pruritus (Figs. 1 and 2). All patients underwent laboratory investigations and skin biopsy for histopathologic arid immunofluorescent studies during hospitalization. Ultrasonographic examination was done before the laboratory measurements were done. Controls. The control group consisted of 11 healthy pregnant women (aged 22 to 43 years) matched with the .patients according to gestational age. The women in the control group had suffered no rashes in previous pregnancies. Endocrine evaluation. Serum levels of the 13-subunit of human chorionic gonadotropin (13-hCG), estradiol, and cortisol, were measured by radioimmunoassay
(AmerLex-M hCG radioimmunoassay kit, Amersham, UK; Iodine 125-coated tubes, DPC). Urinary estriol levels were measured by the modified direct Ittrich method. 2 Autoantibodies. Sera were screened (at a 1 : 20 dilution) for antinuclear, anti-smooth muscle, antithyroid, antimitochondrial, and antigastric parietal cell antibodies, by indirect immunofluorescence on cryostat sections of rat liver, human thyroid, rat kidney, and mouse stomach. Positive sera were tested by titration. Statistical analysis. Differences between the hormone levels of the patients and the control group were evaluated by Wilcoxon's rank sum test. Results
The case histories are summarized in Table I. Six patients were primigravid (55%). Except for Patient No. 4, all of the patients demonstrated normal ultrasohographic findings and normal fetal outcome. The histopathologic findings were compatible with those of
Hormones and autoantibodies in pruritic urticarial papules and plaques 419
Volume 158 Number 2
Table II. Hormonal evaluation in patients with pruritic urticarial papules and plaques of pregnancy Patient No.
Total {3-hCG (m!Uiml)
Estradiol (pglml)
Cortisol (mgldl)
Urinary estriol (mg/24 hr)
1 2 3 4 5 6 7 8 9 10 11
12,600 2,050 5,000 9,000 13,500 9,407 9,198 10,005 8,328 3,148 3,602
9,350 6,340 11,930 10,080 12,498 6,136 10,830 7,667 4,987 10,820 14,760
34.8 28.6 30.8 25 34.8 57.7 41 20.3 29.3 38.9 27
26.6 26 19.6 33 20.4 28.3 23.5
Mean± SD
7,803 ± 3,831
9,581 ± 3,023
33.47 ± 10.06
21.96 ± 6.44
ll
15 16 22.2
Table III. Hormonal evaluation in healthy pregnant women Patient No.
Total {3-hCG (m!VIml)
Estradiol (pglml)
Cortisol (mgldl)
Urinary estriol (mg/24 hr)
1 2 3 4 5 6 7 8 9 10 11
2,753 6,451 9,582 13,500 9,197 2,500 10,812 41,988 14,497 13,893 14,537
7,646 21,010 13,030 5,039 27,840 13,380 16,140 10,301 6,990 31,670 6,451
39.2 29.9 24.9 23.7 27.5 34.5 38.3 26.6 20.1 33.1 32.7
7.8 22.6 21.2 6 31.2 20.1 13.4 17.8 7.7 48.6 25.8
Mean± SD
12,701 ± 10,649
14,499 ± 8,925
30.04 ± 6.1
20.2 ± 12.36
the patients with pruritic urticarial papules and plaques of pregnancy. Direct immunofluorescent findings were negative. The hormone levels of the patients and the control group are summarized in Tables II and III. No significant differences in the levels of !3-hCG, estradiol, estriol, and cortisol were observed between the patients with pruritic urticarial papules and plaques of pregnancy and the control group. No specific autoantibody was found in any of the patients.
Comment Since its original description in 1979,' pruritic urticarial papules and plaques of pregnancy has been recognized as a distinct clinical entity. No severe maternal complications or cases of prematurity, postmaturity, or spontaneous abortion have been documented.• We have recently demonstrated that no immunofluorescent findings are typical for patients with pruritic urticarial papules and plaques of pregnancy. 5 The etiologic and pathogenetic conditions of pruritic urticarial papules and plaques of pregnancy are not known. Dermatoses of pregnancy usually raise questions about their direct relationship to pregnancy. However,
in most of these cases no hormonal evaluation was carried out. The only hormonal evaluation in papular dermatitis of pregnancy was done by Spangler et al.,6 who found an elevated urinary chorionic gonadotropin level during the last trimester, a lowered plasma hydrocortisone level, and a shortened hydrocortisone half-life in pregnant women. 6 Spangler and Emerson later demonstrated low values of estrogen in 24-hour urine specimens from patients with papular dermatitis of pregnancy.7 No control patients were included in that study. Our study demonstrated that there is no hormonal alteration in patients with pruritic urticarial papules and plaques of pregnancy when compared with normal pregnant women. Also, since no autoantibodies were found in the patients in this study, we conclude that no known major autoimmune background is responsible for the eruption of pruritic urticarial papules and plaques of pregnancy. Although further investigation is needed to understand the pathogenesis of pruritic urticarial papules and plaques of pregnancy, the results of our study confirm that no maternal or fetal morbidity or mortality is found in patients with pruritic urticarial papules and plaques of pregnancy.
Alcalay et al.
We thank Ms. Alice Burnett for preparing the manuscript. REFERENCES 1. Holmes RC, Black MM. The specific dermatoses of pregnancy. JAm Acad Dermatol1983;8:405. 2. Ittrich G. Eine neue Methode zur chemischen Bestimmung der oestrogenen Hormone in Harn. Hoppe Seyler Z Physiol Chern 1958;312:1. 3. Lawley TJ, Hertz KC, Wade TR, et a!. Pruritic urticarial papules and plaques ofpregnancy.JAMA 1979;241:1696.
February 1988 Am J Obstet Gynecol
4. Yancey KB, Hall RP, Lawley TJ. Pruritic urticarial papules and plaques of pregnancy: clinical experience in twentyfive patients. JAm Acad Dermatol 1984;10:473. 5. Alcalay J, Ingber A, David M, Hazaz B, Sandbank M. Pruritic urticarial papules and plaques of pregnancy-a review of twenty one cases. J Reprod Med 1987;32:315. 6. Spangler AS, Reddy W, Bardawil WA, Roby CC, Emerson K. Papular dermatitis of pregnancy. A new clinical entity? JAMA 1962;181:577. 7. Spangler AS, Emerson K. Estrogen levels and estrogen therapy in papular dermatitis of pregnancy. AM J 0BSTET GYNECOL 1971;110:534.
Legal abortion mortality and general anesthesia Hani K. Atrash, MD, MPH, Theodore G. Cheek, MD, and Carol). R. Hogue, PhD, MPH Atlanta, Georgia, and Philadelphia, Pennsylvania Legal abortion-related mortality as reported to the Centers for Disease Control declined eightfold between 1972 and 1981. However, the causes of legal abortioo mortality have changed over time. We reviewed all legal abortion-related deaths that occurred between 1972 and 1985 in the United States. We found that, although the absolute number of legal abortion-related deaths caused by general anesthesia complications did not increase, the proportion of such deaths increased significantly, from 7.7% between 1972 and 1975 to 29.4% between 1980 and 1985. Women who died of general anesthesia complications did not differ by age, presence of preexisting medical conditions, or type of facility from women who died of other causes. However, the proportion of deaths from general anesthesia complications was significantly higher among women of black and other races, women obtaining abortions during the first trimester, and women obtaining abortions in the Northeast. Our results indicate that at least 23 of the 27 deaths were due to hypoventilation and/or loss of airway resulting in hypoxia. Persons administering general anesthesia for abortion must be skilled in airway management as well as the provision of general anesthesia. (AM J 0BSTET GYNECOL 1988;158:420-4.)
Key words: Abortion mortality, general anesthesia, maternal mortality Legal abortion-related mortality as reported to the Centers for Disease Control experienced an eightfold decline between 1972 and 1981, falling from 4.1 deaths per 100,000 abortions in 1972 to 0.5 deaths per 100,000 abortions in 1981. 1 The number of legal abortionrelated deaths also declined, from 24 in 1972 to seven in 1981. However, the New York City Department of Health recently reported seven legal abortion-related deaths that occurred between 1980 and 1985. The cause of death in all cases was attributed directly to general anesthesia. 2 Moreover, during our investigation of legal abortion-related deaths we have noted that an increasing proportion of these were anesthesia-related
From the Division of Reproductive Health, Center for Health Promotion and Education, Centers for Disease Control, and the Department of Anesthesia, University of Pennsylvania. Received for publication April20, 1987; revised August 11, 1987; accepted September 14, 1987. Reprints not available.
420
deaths, and that most deaths resulting from cardiopulmonary arrest associated with general anesthesia occurred in the recovery room. We reviewed all legal abortion-related deaths that occurred between 1972 and 1985 to determine the role of general anesthesia in legal abortion mortality and to identify factors that place women seeking abortion at higher risk of dying from general anesthesia complications. Methods
Legal abortion-related deaths were identified by the Centers for Disease Control's Nationwide Surveillance of Abortion Mortality initiated in 1972, details of which have been previously reported. 1 All reported cases were investigated by medical epidemiologists and the causes of death were determined based on data collected from death certificates, medical records and autopsy reports (when available). In our study, deaths were classified as related to general anesthesia (or caused by general an-
Key words: Pruritic urticarial papules and plaques of pregnancy, hormonal profile, autoantibodies
Pregnant patients may develop skin disease that is seen in the nonpregnant state. However, a small group of dermatoses occur predominantly, if not exclusively, during pregnancy. These dermatoses include herpes gestationis, impetigo herpetiformis, prurigo gestationis, papular dermatitis of pregnancy, and pruritic urticarial papules and plaques of pregnancy. 1 The pathogenesis of most of the specific dermatoses of pregnancy, except for herpes gestationis, is still an enigma. We present here a prospective study in which the hormonal profile and autoimmune backgrounds were studied in patients with pruritic urticarial papules and plaques of pregnancy. To the best of our knowledge, no such study has previously been done.
Material and methods Patients. The study population consisted of 11 pregnant women with pruritic urticarial papules and plaques of pregnancy with ages ranging from 18 to 36 years and an average age of 27 years. The patients'
From the Departments of Dermatology and Obstetrics and Gynecology, The Endocrine Laboratory, and the Immunopathology Unit, Beilinson Medical Center, and Sackler School of Medicine, Tel Aviv University. Received for publication January .15, 1987; revised August 31, 1987; accepted September 9, 1987. Reprint requests: Joseph Alcalay, MD, Department of Immunology, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 1515 HolcOmbe Blvd., Box 178, Houston, TX 77030. .
Fig. 1. Erythematous papules and large urticarial plaques on the thighs.
417
418 Alcalay et al.
February 1988 Am J Obstet Gynecol
Fig. 2. Erythematous, edematous papules along the striae distensae.
Table I. Case histories Case No.
Age
Gestational age at diagnosis
(yr)
I
26 18 23 31 31 31 25 36 26 26 22
2 3 4 5 6 7 8 9 10 11
Ultrasound findings
Labor
(wk)
Gravidity and parity
(wk)
Fetal outcome
29 27 30 39 38 42 40 25 21 40 36
Gl/PO Gl/PO Gl/PO G2/PO G2/PO G1/PO G2/P1 G4/P3 G2/PO Gl!PO Gl/PO
Normal Normal Normal Large for dates Normal Normal Normal Normal Normal Normal Normal
41 42 40 40 41 41 40 41 42 40 39
Normal Normal Normal Large for dates Normal Normal Normal Normal Normal Normal Normal
past history showed no eruptions or any other skin or systemic diseases in previous pregnancies. The diagnosis of pruritic urticarial papules and plaques of pregnancy was made on clinical examination. The criteria included symmetrical eruption, mainly on the arms, forearms, abdomen, and thighs, consisting of erythematous papules and urticarial plaques with pruritus (Figs. 1 and 2). All patients underwent laboratory investigations and skin biopsy for histopathologic arid immunofluorescent studies during hospitalization. Ultrasonographic examination was done before the laboratory measurements were done. Controls. The control group consisted of 11 healthy pregnant women (aged 22 to 43 years) matched with the .patients according to gestational age. The women in the control group had suffered no rashes in previous pregnancies. Endocrine evaluation. Serum levels of the 13-subunit of human chorionic gonadotropin (13-hCG), estradiol, and cortisol, were measured by radioimmunoassay
(AmerLex-M hCG radioimmunoassay kit, Amersham, UK; Iodine 125-coated tubes, DPC). Urinary estriol levels were measured by the modified direct Ittrich method. 2 Autoantibodies. Sera were screened (at a 1 : 20 dilution) for antinuclear, anti-smooth muscle, antithyroid, antimitochondrial, and antigastric parietal cell antibodies, by indirect immunofluorescence on cryostat sections of rat liver, human thyroid, rat kidney, and mouse stomach. Positive sera were tested by titration. Statistical analysis. Differences between the hormone levels of the patients and the control group were evaluated by Wilcoxon's rank sum test. Results
The case histories are summarized in Table I. Six patients were primigravid (55%). Except for Patient No. 4, all of the patients demonstrated normal ultrasohographic findings and normal fetal outcome. The histopathologic findings were compatible with those of
Hormones and autoantibodies in pruritic urticarial papules and plaques 419
Volume 158 Number 2
Table II. Hormonal evaluation in patients with pruritic urticarial papules and plaques of pregnancy Patient No.
Total {3-hCG (m!Uiml)
Estradiol (pglml)
Cortisol (mgldl)
Urinary estriol (mg/24 hr)
1 2 3 4 5 6 7 8 9 10 11
12,600 2,050 5,000 9,000 13,500 9,407 9,198 10,005 8,328 3,148 3,602
9,350 6,340 11,930 10,080 12,498 6,136 10,830 7,667 4,987 10,820 14,760
34.8 28.6 30.8 25 34.8 57.7 41 20.3 29.3 38.9 27
26.6 26 19.6 33 20.4 28.3 23.5
Mean± SD
7,803 ± 3,831
9,581 ± 3,023
33.47 ± 10.06
21.96 ± 6.44
ll
15 16 22.2
Table III. Hormonal evaluation in healthy pregnant women Patient No.
Total {3-hCG (m!VIml)
Estradiol (pglml)
Cortisol (mgldl)
Urinary estriol (mg/24 hr)
1 2 3 4 5 6 7 8 9 10 11
2,753 6,451 9,582 13,500 9,197 2,500 10,812 41,988 14,497 13,893 14,537
7,646 21,010 13,030 5,039 27,840 13,380 16,140 10,301 6,990 31,670 6,451
39.2 29.9 24.9 23.7 27.5 34.5 38.3 26.6 20.1 33.1 32.7
7.8 22.6 21.2 6 31.2 20.1 13.4 17.8 7.7 48.6 25.8
Mean± SD
12,701 ± 10,649
14,499 ± 8,925
30.04 ± 6.1
20.2 ± 12.36
the patients with pruritic urticarial papules and plaques of pregnancy. Direct immunofluorescent findings were negative. The hormone levels of the patients and the control group are summarized in Tables II and III. No significant differences in the levels of !3-hCG, estradiol, estriol, and cortisol were observed between the patients with pruritic urticarial papules and plaques of pregnancy and the control group. No specific autoantibody was found in any of the patients.
Comment Since its original description in 1979,' pruritic urticarial papules and plaques of pregnancy has been recognized as a distinct clinical entity. No severe maternal complications or cases of prematurity, postmaturity, or spontaneous abortion have been documented.• We have recently demonstrated that no immunofluorescent findings are typical for patients with pruritic urticarial papules and plaques of pregnancy. 5 The etiologic and pathogenetic conditions of pruritic urticarial papules and plaques of pregnancy are not known. Dermatoses of pregnancy usually raise questions about their direct relationship to pregnancy. However,
in most of these cases no hormonal evaluation was carried out. The only hormonal evaluation in papular dermatitis of pregnancy was done by Spangler et al.,6 who found an elevated urinary chorionic gonadotropin level during the last trimester, a lowered plasma hydrocortisone level, and a shortened hydrocortisone half-life in pregnant women. 6 Spangler and Emerson later demonstrated low values of estrogen in 24-hour urine specimens from patients with papular dermatitis of pregnancy.7 No control patients were included in that study. Our study demonstrated that there is no hormonal alteration in patients with pruritic urticarial papules and plaques of pregnancy when compared with normal pregnant women. Also, since no autoantibodies were found in the patients in this study, we conclude that no known major autoimmune background is responsible for the eruption of pruritic urticarial papules and plaques of pregnancy. Although further investigation is needed to understand the pathogenesis of pruritic urticarial papules and plaques of pregnancy, the results of our study confirm that no maternal or fetal morbidity or mortality is found in patients with pruritic urticarial papules and plaques of pregnancy.
Alcalay et al.
We thank Ms. Alice Burnett for preparing the manuscript. REFERENCES 1. Holmes RC, Black MM. The specific dermatoses of pregnancy. JAm Acad Dermatol1983;8:405. 2. Ittrich G. Eine neue Methode zur chemischen Bestimmung der oestrogenen Hormone in Harn. Hoppe Seyler Z Physiol Chern 1958;312:1. 3. Lawley TJ, Hertz KC, Wade TR, et a!. Pruritic urticarial papules and plaques ofpregnancy.JAMA 1979;241:1696.
February 1988 Am J Obstet Gynecol
4. Yancey KB, Hall RP, Lawley TJ. Pruritic urticarial papules and plaques of pregnancy: clinical experience in twentyfive patients. JAm Acad Dermatol 1984;10:473. 5. Alcalay J, Ingber A, David M, Hazaz B, Sandbank M. Pruritic urticarial papules and plaques of pregnancy-a review of twenty one cases. J Reprod Med 1987;32:315. 6. Spangler AS, Reddy W, Bardawil WA, Roby CC, Emerson K. Papular dermatitis of pregnancy. A new clinical entity? JAMA 1962;181:577. 7. Spangler AS, Emerson K. Estrogen levels and estrogen therapy in papular dermatitis of pregnancy. AM J 0BSTET GYNECOL 1971;110:534.
Legal abortion mortality and general anesthesia Hani K. Atrash, MD, MPH, Theodore G. Cheek, MD, and Carol). R. Hogue, PhD, MPH Atlanta, Georgia, and Philadelphia, Pennsylvania Legal abortion-related mortality as reported to the Centers for Disease Control declined eightfold between 1972 and 1981. However, the causes of legal abortioo mortality have changed over time. We reviewed all legal abortion-related deaths that occurred between 1972 and 1985 in the United States. We found that, although the absolute number of legal abortion-related deaths caused by general anesthesia complications did not increase, the proportion of such deaths increased significantly, from 7.7% between 1972 and 1975 to 29.4% between 1980 and 1985. Women who died of general anesthesia complications did not differ by age, presence of preexisting medical conditions, or type of facility from women who died of other causes. However, the proportion of deaths from general anesthesia complications was significantly higher among women of black and other races, women obtaining abortions during the first trimester, and women obtaining abortions in the Northeast. Our results indicate that at least 23 of the 27 deaths were due to hypoventilation and/or loss of airway resulting in hypoxia. Persons administering general anesthesia for abortion must be skilled in airway management as well as the provision of general anesthesia. (AM J 0BSTET GYNECOL 1988;158:420-4.)
Key words: Abortion mortality, general anesthesia, maternal mortality Legal abortion-related mortality as reported to the Centers for Disease Control experienced an eightfold decline between 1972 and 1981, falling from 4.1 deaths per 100,000 abortions in 1972 to 0.5 deaths per 100,000 abortions in 1981. 1 The number of legal abortionrelated deaths also declined, from 24 in 1972 to seven in 1981. However, the New York City Department of Health recently reported seven legal abortion-related deaths that occurred between 1980 and 1985. The cause of death in all cases was attributed directly to general anesthesia. 2 Moreover, during our investigation of legal abortion-related deaths we have noted that an increasing proportion of these were anesthesia-related
From the Division of Reproductive Health, Center for Health Promotion and Education, Centers for Disease Control, and the Department of Anesthesia, University of Pennsylvania. Received for publication April20, 1987; revised August 11, 1987; accepted September 14, 1987. Reprints not available.
420
deaths, and that most deaths resulting from cardiopulmonary arrest associated with general anesthesia occurred in the recovery room. We reviewed all legal abortion-related deaths that occurred between 1972 and 1985 to determine the role of general anesthesia in legal abortion mortality and to identify factors that place women seeking abortion at higher risk of dying from general anesthesia complications. Methods
Legal abortion-related deaths were identified by the Centers for Disease Control's Nationwide Surveillance of Abortion Mortality initiated in 1972, details of which have been previously reported. 1 All reported cases were investigated by medical epidemiologists and the causes of death were determined based on data collected from death certificates, medical records and autopsy reports (when available). In our study, deaths were classified as related to general anesthesia (or caused by general an-