EUROP. J. OBSTET. GYNEC. REPROD. BIOL., 1979,9/6,399-401 0 Elsevier/North-Holland Biomedical Press

Erythema nodosum associated with Case reports

R. Langer, I. Bukovsky, I. Lipshitz, S. Ariely and E. Caspi

pregnancy

Department of Obstetrics and 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

Introduction

Erythema nodosum (EN) is a well-known self- limited 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, mycobacte- rial: tuberculosis and leprosy, yersinia), fungal and viral infections, internal diseases (sarcoidosis, ulcera- tive 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 popu- lation per year (Ryan and Wilkinson, 1972). Its inci- dence varies in different countries; the condition con-

399

stitutes less than 0.5% of cases seen in private or clin- ical practice (de Moragas, 1971; Ryan and Wilkinson, 1972).

Although it has been stated that EN is common in association with pregnancy (Lancet, 1962), this asso- ciation is not mentioned in the textbooks of derma- tology, 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.

Case reports

Case I. F.C., A 24-yr-old primigravida, was hospi- talized 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 limi- tation of motion in both hips. Laboratory data:

400 R. Langer et al.: Erythema nodosum associated with pregnatzcy

erythrocyte sedimentation rate 60 mm/h, Hb 13.9 g%, leucocytes 13,5OO/ml with normal differentiation. Electrolytes, urea, blood glucose, uric acid, total pro- teins, urine samples, renal function tests and hema- tologic profile were all within normal limits. Urine

culture, throat culture and feces for parasites were negative. Complement fixation test, L.E. cell phe- nomenon, antinuclear factor test, Latex futation test, C.R.P., anti-streptolysin titer, tuberculin test all

reported negative. X-ray of the chest and electro- cardiogram were normal. Treatment consisted of bed

rest and administration of salicylates. By 22 wk gesta- tion, 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 gesta- tion 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 labo-

ratory investigations (as in case I) revealed no evi- dence of any underlying cause for this erythema nodosum. Treatment consisted of bed rest and admin-

istration of salicylates. Subjective improvement was noted after 2 wk, with marked reduction of pain. Ob- jective evidence of disappearance of the skin condi-

tion continued gradually until complete resolution at 24 wk gestation. A term infant was delivered unevent- fully with an uncomplicated pre- and postnatal

course.

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 compli- cated by similar tender, red nodules on both shins, which resolved after 3-4 wk without medical treat- ment. No further information was available concern-

ing 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 gesta-

tion. 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. Find- ings on examination revealed red, tender nodules on

both shins. As in the 3 other cases, extensive labora- tory investigations did not reveal any underlying

infections or other cause. After bed rest for 2 wk, the

eruption gradually dissolved. Two days after her dis- charge, the patient was readmitted for inevitable late

abortion. The fetus and placenta showed no abnor- malities.

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 well- established. It is a well-known fact that EN is com- mon in young women in their reproductive phase of life (Loefgren, 1953; Geraint, 1961; Siltzbach, 1961; de Moragas, 1971; Ryan and Wilkinson, 1972). How- ever, 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 pos- sible 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 combina- tion of estrogens and progesterones was causative.

The likely action, therefore, seems to be exerted

through the pseudopregnancy effect of the contra- ceptive 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 fol- lowed the appearance of erythema nodosum, no evi-

dence 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 condi- tion, requiring at most such symptomatic treatment as bed rest and pain-relieving medication. No adverse

effect on maternal or fetal systems should be antici- pated.

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. Derma- tologica, 156, 65.

de Moragas, SM. (1971): Nodules on the leg syndromes. In: Dermatology in General Medicine, pp. 1471-1475. Edi- tors: 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 contra- ception. 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. 950- 958. Editors: A. Rooh, D.S. Wilkinson and F.J.G. Ebllne. Blackwell, Oxford.

Siltzbach, L.E. (1961): Current status of the Nickerson- Kvien reaction. Amer. Rev. Resp. Dis., 84,89.

Wetherill, J.H. (1971): Recurrent erythema nodosum of preg- nancy. Brit. med. J., 3,535.