- Email: [email protected]
Erythema nodosum associated with pregnancy
EUROP. J. OBSTET. GYNEC. REPROD. BIOL., 1979,9/6,399-401 0 Elsevier/North-Holland Biomedical Press
Erythema nodosum associated with pregnancy Case reports
R. Langer, I. Bukovsky, I. Lipshitz, S. Ariely and E. Caspi Department of Obstetricsand Gynecology, Assaf Harofeh Hospital (AffiWed to Sackler School of Medicine, Tel-Aviv University),Zerifin, Israel Accepted for publication 26 April 1979 LANCER, R., BUKOVSKY, I., LIPSHITZ, I., ARIELY, S. and CASPI, E. (1979): Erythema nodosum associated with pregnancy. Case report. Europ. J. Obstet. Gynec. reprod. Biol., 916, 399-401. Four cases of erythema nodosum associated with pregnancy are reported and the literature reviewed. Erythema nodosum in pregnancy is a self-limited condition requiring minimal supportive treatment. No adverse effects upon pregnancy course or fetal outcome were noted. It is suggested that pregnancy may serve as an etiological basis for the disease. erythema nodosum; pregnancy
stitutes less than 0.5% of cases seen in private or clinical practice (de Moragas, 1971; Ryan and Wilkinson, 1972). Although it has been stated that EN is common in association with pregnancy (Lancet, 1962), this association is not mentioned in the textbooks of dermatology, while the pertinent references in the literature are very scarce. Therefore, it seemed very interesting to report here 4 cases of EN associated with pregnancy and to review the literature.
Introduction
Erythema nodosum (EN) is a well-known selflimited condition, characterized by the occurrence of tender, red inflammatory nodules, mostly localized on the extensor sides of the lower part of the legs. There is a predominance of the female sex in the reproductive age. The condition can be considered as a specific, allergic skin reaction provoked by a great variety of factors (de Moragas, 1971; Ryan and Wilkinson, 1972), such as bacterial (streptococcal, mycobacterial: tuberculosis and leprosy, yersinia), fungal and viral infections, internal diseases (sarcoidosis, ulcerative colitis, Behcet’s syndrome, lupus erythematosus etc.), and drugs (sulfonamides, oral contraceptives). In a number of cases no causative factor can be found (idiopathic EN). The prevalence was given as 2.4 per 10,000 population per year (Ryan and Wilkinson, 1972). Its incidence varies in different countries; the condition con-
Case reports Case I.
F.C., A 24-yr-old primigravida, was hospitalized at the 18th wk of gestation because of fever of 38’C!, low abdominal pain and bilateral hip pain. Past history was noncontributory, physical examination revealed tender, red nodules measuring 1-3 cm in diameter distributed over both shins. There was limitation of motion in both hips. Laboratory data: 399
400
erythrocyte sedimentation rate 60 mm/h, Hb 13.9 g%, leucocytes 13,5OO/ml with normal differentiation. Electrolytes, urea, blood glucose, uric acid, total proteins, urine samples, renal function tests and hematologic profile were all within normal limits. Urine culture, throat culture and feces for parasites were negative. Complement fixation test, L.E. cell phenomenon, antinuclear factor test, Latex futation test, C.R.P., anti-streptolysin titer, tuberculin test all reported negative. X-ray of the chest and electrocardiogram were normal. Treatment consisted of bed rest and administration of salicylates. By 22 wk gestation, the eruption had gradually disappeared and the patient was symptom-free. The remaining pregnancy course was uneventful, and the patient spontaneously delivered a healthy female of 3650 g at term. Her second pregnancy was uneventful until 17 wk gestation, when similar tender, red nodules appeared on both shins accompanied by fever of 38’C and malaise. A complete laboratory work-up revealed no evidence of any underlying cause. Drug therapy was not required, but elastic support bandages and bed rest provided adequate symptomatic relief. The skin condition was completely resolved by 20 wk gestation without further recurrence. A healthy male infant of 3450 g was spontaneously delivered at term. Case II. A.Z., a 26-yr-old oligomenorrheic patient, conceived after treatment with human menopausal gonadotropins and human chorionic gonadotropins. No pertinent past history was present. Aside from iron therapy for mild anemia, the patient reached 20 wk gestation uneventfully. At that time she com.plained of fever of 38.2”C, malaise and bilateral pain of hips and knee joints. Clinical examinations revealed an eruption marked by red, tender nodules over both shins. Bilateral limitation of motion was present in both hip and knee joints. Extensive laboratory investigations (as in case I) revealed no evidence of any underlying cause for this erythema nodosum. Treatment consisted of bed rest and administration of salicylates. Subjective improvement was noted after 2 wk, with marked reduction of pain. Objective evidence of disappearance of the skin condition continued gradually until complete resolution at 24 wk gestation. A term infant was delivered uneventfully with an uncomplicated pre- and postnatal course.
R. Langer et al.: Erythema nodosum associated with pregnatzcy
Three years later, the patient conceived again after treatment with human menopausal gonadotropins and human chorionic gonadotropins. Triplets were diagnosed, and the patient had long hospitalization until delivery in the third trimester. No recurrence of erythema nodosum was noted. Case III. G.R., a 34-yr-old gravida III, para II, was administered at 8 wk gestation with complaints of fever, malaise and painful, itching, red nodules over both shins. Two previous pregnancies were complicated by similar tender, red nodules on both shins, which resolved after 3-4 wk without medical treatment. No further information was available concerning these admissions. Laboratory investigations (see case I) revealed no underlying cause. Bed rest and salicylates provided adequate symptomatic relief, and the eruption gradually disappeared by 27 wk gestation. A healthy female infant weighing 3520 g was spontaneously delivered at term. Case IV.
I.N., a 26-yr-old gravida II, para I, was admitted at 19 wk gestation because of complaints of fever up to 37.8”C, malaise, and painful nodules over both shins. Her first pregnancy was uneventful. Findings on examination revealed red, tender nodules on both shins. As in the 3 other cases, extensive laboratory investigations did not reveal any underlying infections or other cause. After bed rest for 2 wk, the eruption gradually dissolved. Two days after her discharge, the patient was readmitted for inevitable late abortion. The fetus and placenta showed no abnormalities.
Discussion
It has been mentioned that EN can be induced by various factors. Although the association between pregnancy and EN is known (Lancet, 1962), the actual frequency of this relationship is not wellestablished. It is a well-known fact that EN is common in young women in their reproductive phase of life (Loefgren, 1953; Geraint, 1961; Siltzbach, 1961; de Moragas, 1971; Ryan and Wilkinson, 1972). However, reports in the literature on the association of EN with pregnancy are extremely scarce. We found only two communications on the occur-
R. Langer et al.: Erythema nodosum associated with pregnancy
rence of EN in successive pregnancies (Daw, 1971; Wetherill, 1971). In a recent review paper on the possible etiology of EN (Debois et al., 1978), the authors observed an association with pregnancy in only one out of 54 patients (10 males, 44 females). The observations that pregnancy may form an etiological basis for the occurrence of EN may be strengthened by the fact that EN can be provoked by contraceptive agents. Several studies (Holcomb, 1965; Matz, 1967; Baden and Holcomb, 1968; Kirby and Kraft, 1972; Kariher, 1973; Berant, 1974) showed that estrogens or progesterones alone were unable to cause erythema nodosum, but that only the combination of estrogens and progesterones was causative. The likely action, therefore, seems to be exerted through the pseudopregnancy effect of the contraceptive pill. Our cases lend support to the idea that pregnancy itself may serve as an etiological basis for EN. In this respect it should be noted that 2 out of 6 reported cases (2 literature cases plus 4 own cases) failed to recur in successive pregnancies. Since in all cases but one (case IV) pregnancy terminated in term delivery of a normal fetus, it seems very likely that the condition does not adversely affect the pregnancy or the fetus. In that one case, where late abortion followed the appearance of erythema nodosum, no evidence of fetal or placental involvement were noted. This case, therefore, may represent an incidental event unrelated to erythema nodosum. In summary, it can be concluded that EN may be associated, although in rare instances, with pregnancy. Here, as in other instances, it is a self-limited condition, requiring at most such symptomatic treatment as bed rest and pain-relieving medication. No adverse
effect on maternal pated.
or fetal systems should be antici-
References Baden, H.P. and Holcomb, F.O. (1968): Erythema nodosum from oral contraceptives. Arch. Dermatol., 98,634. Berant, N. (1974): Erythema nodosum associated with oral contraception. Harefuah, 87, 19. Daw, E. (1971): Recurrent erythema nodosum of pregnancy. Brit. med. J., 2,44. Debois, J., Vandepitte, J. and Degreef, H. (1978): Yersinia enterocolitica as a cause of erythema nodosum. Dermatologica, 156, 65. de Moragas, SM. (1971): Nodules on the leg syndromes. In: Dermatology in General Medicine, pp. 1471-1475. Editors: Th.B. Fitzpatrick et al. McGraw-Hill Inc., New York. Geraint, D.G. (1961): Erythema nodosum. Brit. med. J., I, 853. Holcomb, F.D. (1965): Erythema nodosum associated with the use of contraceptives. Obstet. Gynec., 25,156. Kariher, D.H. (1973): Erythema nodosum and oral contraception. Obstet. Gynec., 42, 323. Kirby, J.F., Jr. and Kraft, G.H. (1972): Oral contraceptives and erythema nodosum. Obstet. Gynec., 40,409. Lancet (1962): Erythema nodosum. Lancet, I, 256. Loefgren, S. (1953): Primary pulmonary sarcoidosis. Acta med. stand., 145,424. Matz, M.H. (1967): Erythema nodosum and contraceptive medication. New Engl. J. Med., 276,351. Ryan, T.J. and Wilkinson, D.S. (1972): Erythema nodosum. In: Textbook of Dermatology, Vol. I, 2nd edn., pp. 950958. Editors: A. Rooh, D.S. Wilkinson and F.J.G. Ebllne. Blackwell, Oxford. Siltzbach, L.E. (1961): Current status of the NickersonKvien reaction. Amer. Rev. Resp. Dis., 84,89. Wetherill, J.H. (1971): Recurrent erythema nodosum of pregnancy. Brit. med. J., 3,535.
Erythema nodosum associated with pregnancy Case reports
R. Langer, I. Bukovsky, I. Lipshitz, S. Ariely and E. Caspi Department of Obstetricsand Gynecology, Assaf Harofeh Hospital (AffiWed to Sackler School of Medicine, Tel-Aviv University),Zerifin, Israel Accepted for publication 26 April 1979 LANCER, R., BUKOVSKY, I., LIPSHITZ, I., ARIELY, S. and CASPI, E. (1979): Erythema nodosum associated with pregnancy. Case report. Europ. J. Obstet. Gynec. reprod. Biol., 916, 399-401. Four cases of erythema nodosum associated with pregnancy are reported and the literature reviewed. Erythema nodosum in pregnancy is a self-limited condition requiring minimal supportive treatment. No adverse effects upon pregnancy course or fetal outcome were noted. It is suggested that pregnancy may serve as an etiological basis for the disease. erythema nodosum; pregnancy
stitutes less than 0.5% of cases seen in private or clinical practice (de Moragas, 1971; Ryan and Wilkinson, 1972). Although it has been stated that EN is common in association with pregnancy (Lancet, 1962), this association is not mentioned in the textbooks of dermatology, while the pertinent references in the literature are very scarce. Therefore, it seemed very interesting to report here 4 cases of EN associated with pregnancy and to review the literature.
Introduction
Erythema nodosum (EN) is a well-known selflimited condition, characterized by the occurrence of tender, red inflammatory nodules, mostly localized on the extensor sides of the lower part of the legs. There is a predominance of the female sex in the reproductive age. The condition can be considered as a specific, allergic skin reaction provoked by a great variety of factors (de Moragas, 1971; Ryan and Wilkinson, 1972), such as bacterial (streptococcal, mycobacterial: tuberculosis and leprosy, yersinia), fungal and viral infections, internal diseases (sarcoidosis, ulcerative colitis, Behcet’s syndrome, lupus erythematosus etc.), and drugs (sulfonamides, oral contraceptives). In a number of cases no causative factor can be found (idiopathic EN). The prevalence was given as 2.4 per 10,000 population per year (Ryan and Wilkinson, 1972). Its incidence varies in different countries; the condition con-
Case reports Case I.
F.C., A 24-yr-old primigravida, was hospitalized at the 18th wk of gestation because of fever of 38’C!, low abdominal pain and bilateral hip pain. Past history was noncontributory, physical examination revealed tender, red nodules measuring 1-3 cm in diameter distributed over both shins. There was limitation of motion in both hips. Laboratory data: 399
400
erythrocyte sedimentation rate 60 mm/h, Hb 13.9 g%, leucocytes 13,5OO/ml with normal differentiation. Electrolytes, urea, blood glucose, uric acid, total proteins, urine samples, renal function tests and hematologic profile were all within normal limits. Urine culture, throat culture and feces for parasites were negative. Complement fixation test, L.E. cell phenomenon, antinuclear factor test, Latex futation test, C.R.P., anti-streptolysin titer, tuberculin test all reported negative. X-ray of the chest and electrocardiogram were normal. Treatment consisted of bed rest and administration of salicylates. By 22 wk gestation, the eruption had gradually disappeared and the patient was symptom-free. The remaining pregnancy course was uneventful, and the patient spontaneously delivered a healthy female of 3650 g at term. Her second pregnancy was uneventful until 17 wk gestation, when similar tender, red nodules appeared on both shins accompanied by fever of 38’C and malaise. A complete laboratory work-up revealed no evidence of any underlying cause. Drug therapy was not required, but elastic support bandages and bed rest provided adequate symptomatic relief. The skin condition was completely resolved by 20 wk gestation without further recurrence. A healthy male infant of 3450 g was spontaneously delivered at term. Case II. A.Z., a 26-yr-old oligomenorrheic patient, conceived after treatment with human menopausal gonadotropins and human chorionic gonadotropins. No pertinent past history was present. Aside from iron therapy for mild anemia, the patient reached 20 wk gestation uneventfully. At that time she com.plained of fever of 38.2”C, malaise and bilateral pain of hips and knee joints. Clinical examinations revealed an eruption marked by red, tender nodules over both shins. Bilateral limitation of motion was present in both hip and knee joints. Extensive laboratory investigations (as in case I) revealed no evidence of any underlying cause for this erythema nodosum. Treatment consisted of bed rest and administration of salicylates. Subjective improvement was noted after 2 wk, with marked reduction of pain. Objective evidence of disappearance of the skin condition continued gradually until complete resolution at 24 wk gestation. A term infant was delivered uneventfully with an uncomplicated pre- and postnatal course.
R. Langer et al.: Erythema nodosum associated with pregnatzcy
Three years later, the patient conceived again after treatment with human menopausal gonadotropins and human chorionic gonadotropins. Triplets were diagnosed, and the patient had long hospitalization until delivery in the third trimester. No recurrence of erythema nodosum was noted. Case III. G.R., a 34-yr-old gravida III, para II, was administered at 8 wk gestation with complaints of fever, malaise and painful, itching, red nodules over both shins. Two previous pregnancies were complicated by similar tender, red nodules on both shins, which resolved after 3-4 wk without medical treatment. No further information was available concerning these admissions. Laboratory investigations (see case I) revealed no underlying cause. Bed rest and salicylates provided adequate symptomatic relief, and the eruption gradually disappeared by 27 wk gestation. A healthy female infant weighing 3520 g was spontaneously delivered at term. Case IV.
I.N., a 26-yr-old gravida II, para I, was admitted at 19 wk gestation because of complaints of fever up to 37.8”C, malaise, and painful nodules over both shins. Her first pregnancy was uneventful. Findings on examination revealed red, tender nodules on both shins. As in the 3 other cases, extensive laboratory investigations did not reveal any underlying infections or other cause. After bed rest for 2 wk, the eruption gradually dissolved. Two days after her discharge, the patient was readmitted for inevitable late abortion. The fetus and placenta showed no abnormalities.
Discussion
It has been mentioned that EN can be induced by various factors. Although the association between pregnancy and EN is known (Lancet, 1962), the actual frequency of this relationship is not wellestablished. It is a well-known fact that EN is common in young women in their reproductive phase of life (Loefgren, 1953; Geraint, 1961; Siltzbach, 1961; de Moragas, 1971; Ryan and Wilkinson, 1972). However, reports in the literature on the association of EN with pregnancy are extremely scarce. We found only two communications on the occur-
R. Langer et al.: Erythema nodosum associated with pregnancy
rence of EN in successive pregnancies (Daw, 1971; Wetherill, 1971). In a recent review paper on the possible etiology of EN (Debois et al., 1978), the authors observed an association with pregnancy in only one out of 54 patients (10 males, 44 females). The observations that pregnancy may form an etiological basis for the occurrence of EN may be strengthened by the fact that EN can be provoked by contraceptive agents. Several studies (Holcomb, 1965; Matz, 1967; Baden and Holcomb, 1968; Kirby and Kraft, 1972; Kariher, 1973; Berant, 1974) showed that estrogens or progesterones alone were unable to cause erythema nodosum, but that only the combination of estrogens and progesterones was causative. The likely action, therefore, seems to be exerted through the pseudopregnancy effect of the contraceptive pill. Our cases lend support to the idea that pregnancy itself may serve as an etiological basis for EN. In this respect it should be noted that 2 out of 6 reported cases (2 literature cases plus 4 own cases) failed to recur in successive pregnancies. Since in all cases but one (case IV) pregnancy terminated in term delivery of a normal fetus, it seems very likely that the condition does not adversely affect the pregnancy or the fetus. In that one case, where late abortion followed the appearance of erythema nodosum, no evidence of fetal or placental involvement were noted. This case, therefore, may represent an incidental event unrelated to erythema nodosum. In summary, it can be concluded that EN may be associated, although in rare instances, with pregnancy. Here, as in other instances, it is a self-limited condition, requiring at most such symptomatic treatment as bed rest and pain-relieving medication. No adverse
effect on maternal pated.
or fetal systems should be antici-
References Baden, H.P. and Holcomb, F.O. (1968): Erythema nodosum from oral contraceptives. Arch. Dermatol., 98,634. Berant, N. (1974): Erythema nodosum associated with oral contraception. Harefuah, 87, 19. Daw, E. (1971): Recurrent erythema nodosum of pregnancy. Brit. med. J., 2,44. Debois, J., Vandepitte, J. and Degreef, H. (1978): Yersinia enterocolitica as a cause of erythema nodosum. Dermatologica, 156, 65. de Moragas, SM. (1971): Nodules on the leg syndromes. In: Dermatology in General Medicine, pp. 1471-1475. Editors: Th.B. Fitzpatrick et al. McGraw-Hill Inc., New York. Geraint, D.G. (1961): Erythema nodosum. Brit. med. J., I, 853. Holcomb, F.D. (1965): Erythema nodosum associated with the use of contraceptives. Obstet. Gynec., 25,156. Kariher, D.H. (1973): Erythema nodosum and oral contraception. Obstet. Gynec., 42, 323. Kirby, J.F., Jr. and Kraft, G.H. (1972): Oral contraceptives and erythema nodosum. Obstet. Gynec., 40,409. Lancet (1962): Erythema nodosum. Lancet, I, 256. Loefgren, S. (1953): Primary pulmonary sarcoidosis. Acta med. stand., 145,424. Matz, M.H. (1967): Erythema nodosum and contraceptive medication. New Engl. J. Med., 276,351. Ryan, T.J. and Wilkinson, D.S. (1972): Erythema nodosum. In: Textbook of Dermatology, Vol. I, 2nd edn., pp. 950958. Editors: A. Rooh, D.S. Wilkinson and F.J.G. Ebllne. Blackwell, Oxford. Siltzbach, L.E. (1961): Current status of the NickersonKvien reaction. Amer. Rev. Resp. Dis., 84,89. Wetherill, J.H. (1971): Recurrent erythema nodosum of pregnancy. Brit. med. J., 3,535.