165
ht. J. Gynecol. Obstet.. 1990,33: 165-169 International Federation of Gynecology and Obstetrics
Pregnancy
and complicated
familial Mediterranean
fever
Y. Shimoni and E. Shalev Department of Obstetrics and Gynecology, Central Emek Hospital, Afula (Israel) (Received March 13th, 1989) (Revised and accepted July 26th, 1989)
Abstract
Familial Mediterranean Fever (FMF) is an inherited disease, closely following the pattern of autosomal recessive inheritance. Amyloidosis is the most severe complication of the disease. The prevalence of pregnancy loss in women with FMF is considered to be high. There is no information to support the possibility of increase risk of late pregnancy complications or change in the natural course of the disease. Two cases are presented with complicated FMF. One case with proved amyloidosis and the second patient with ascites. Pregnancy and neonatal outcome were uneventful in both. No further deterioration in the systemic disease occurred.
synovitis and erysipelas-like erythema [27]. Amyloidosis is the most severe complication of the disease, which fortunately develops in a small percentage of cases [5]. Patients with amyloidosis are advised not to conceive [2,21]. There are only a few articles in the literature about the recurrent peritonitis and the development of ascites in patients suffering from FMF [25,27]. No report of ascites during pregnancy due to FMF has been reported. We report of two cases of young women with complicated FMF in pregnancy. The literature is reviewed with discussion on the possible implication of the disease on fertility and on pregnancy outcome. Case reports
Keywords: Amyloidosis; Familial Mediterranean fever; Pregnancy complications. Introduction
Familial Mediterranean fever (FMF) is an inherited disease almost exclusively confined to populations originating on the south and east coasts of the Mediterranean Sea. Genetic analysis of several hundred families has shown that the disease closely follows the pattern of autosomal recessive inheritance. The syndrome consists of recurrent attacks of fever with peritonitis, pleuritis, pericarditis, 0020-7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
Case 1 A 35year-old woman, gravida 2, para 1, born in Algeria, was followed in the outpatient high risk clinic with the diagnosis of amyloidosis due to FMF. The disease was suspected when she was 9 years old, after several attacks of abdominal pain and fever and with a family history of FMF. At the age of 23 she conceived and delivered her first child. A year later she was placed on prophylactic colchicine therapy. The attacks of abdominal pain and fever were less frequent and milder. At the age of 34, rectal biopsy revealed amyloidosis. The present pregnancy Case Report
166
Shimoni and Shalev
was unplanned, colchicine was taken prior to conception and was continued during the whole gestation. A genetic amniocentesis performed at 17 weeks revealed a normal karyotype. The patient was admitted to the high risk pregnancy unit at 24 weeks gestation when gestational diabetes was diagnosed. During the rest of the pregnancy she was readmitted several times to control the blood glucose. Renal function tests were as follows: blood urea nitrogen 15-26070, uric acid 5.96.2 mg%, creatinine 0.6-0.7 mg%, the amount of urine collected in 24 h ranged from 1900 ml to 2400 ml with urine protein secretion of 240-450 mg. The creatinine clearance was 88-96 ml/min. All function tests remained normal through the whole period. Even though the blood glucose was adequately controlled with insulin, sonographic follow-up indicated the fetus to be on the 95th percentile. On the 40-week of gestation after failed induction she had a cesarean section, and gave birth to a 4300 g male newborn. Case 2 A 25year-old nullipara, born in Morocco, was admitted to the high risk pregnancy unit in the 37th week of her first pregnancy with the diagnosis of fetal intrauterine growth retardation. The patient’s past medical history revealed that at the age of 21 she was operated for suspected acute appendicitis. An uninflammed appendix was found and removed. The peritoneal cavity contained 500 ml of serotic fluid and the ileum was covered with serotic sheath. Following the operation the patient had several attacks of abdominal pain for which she attended the emergency ward. In the present pregnancy serial sonographic examinations have pointed out the existence of a symmetrical growth retarded fetus. The last sonogram done at 37 weeks gestation also revealed a large amount of maternal ascites. The patient was admitted to the hospital and paracenthesis was performed. The fluid was gloomy. Cytological examination revealed many foam cells. Within the foam cells there Int J Gynecol Obstet 33
were inclusion bodies filled with dark hemosiderin like pigment. There were also many lymphocytes. Bacterial cultures were negative including special cultures for tuberculosis and chlamydia. Chemical analysis revealed a high protein content (6.0 golo), mostly albumin (4.0 go/o). At 38th week of gestation labor was induced and a 2400 g girl with Apgar score 10 was delivered. The postpartum period was uneventful. Postnatal ultrasound scan of the pelvis revealed a normal uterus. Fluid was found in the Douglas area and there were also many cystic areas along the right psoase. With the diagnosis of unexplained pelvic cysts and ascites, an explorative laparotomy was performed. In the operation, many cysts filled with clear fluid were found in the peritoneal cavity. There were multiple and extensive adhesions between the small intestinal colon and uterus to the abdominal wall. Otherwise the pelvic organs appeared normal. The fluid aspirated from the cysts was cytologically identical to the ascites found in the paracenthesis performed during the pregnancy. Diagnosis of FMF was raised and treatment with colchicine was started. A subjective relief from the abdominal pain attacks was mentioned by the patient. Later, under colchicine treatment, she had an uncomplicated pregnancy. Discussion Familial Mediterranean fever (FMF) Attacks of FMF begin in childhood. More than half of those affected have had an attack by the age of 10 years and 80-90% by the age of 20 years [ 191. The attacks are unpredictable and can be varied in their nature, often once a month or more, with occasional remissions lasting for a few months. Remissions are some times associated with pregnancy and may continue through lactation [6,20,23,27]. There is an increased number of cases among males compared to females in a ratio of 3:2 [25].
Familial Mediteranean fever in pregnancy
The most common type of attack, abdominal pain, may begin in any part of the abdomen and spread rapidly, then peritonism, fever, vomiting and absence of bowel sounds develop within a few hours. The patient usually recovers within 48 h [ 13,25,27]. Laparotomy and appendectomy are- often performed during the first attack for suspected acute appendicitis. Patients occasionally have tender enlarged ovaries on pelvic examination and pain on motion of the cervix [6]. Some patients have had attacks coincident with menstruation and may appear to have endometriosis [24]. No underlying cause of FMF has been discovered so far, despite extensive research for infective, metabolic and toxic agents. During acute attacks the erythrocyte sedimentation rate is raised but no specific diagnostic test is yet available [25]. Effusion fluids may contain polymorphonuclear leucocytes, and occasionally these cells have small inclusion bodies thought to be triglyceride [27]. Prognosis of FMF is indicated by the associated amyloidosis [ 14,181. A variable proof patients with FMF have portion amyloidosis. Amyloidosis of the amyloid type AA [la] is manifested clinically by a nephropathy that passes through proteinuric, nephrotic and uremic stages to death from renal failure. The approximate duration of the disease from onset of proteinuria or the nephrotic syndrome to end-stage renal failure is 7 and 3 years, respectively. Renal vein thrombosis has been proposed to be a major cause of rapid deterioration of renal function [14.27]. A rectal or renal biopsy has been the usual method for obtaining pathologic confirmation of the presence of amyloid [ 191. Continuous prophylaxis with colchicine has been proved to be effective in the suppression of the attacks in most patients [12,17]. Furthermore it has been shown recently that colchicine prevents both the development of amyloidosis and additional deterioration of renal function in patients with early amyloidosis [26,29]. Colchicine is thought to inhibit
167
the activation and release of lysosomes from phagocytic cells [17]. The drug interacts with microtubules and is a well-known mitotic inhibitor destroying germ cells in animals (in doses 30-50 times higher than conventional doses used in FMF) [l]. Side effects of colchicine given in therapeutic doses are usually minor and include abdominal pain, loose stool and vomiting [4]. Fertility FMF occurs in patients of child-bearing age. Infertility has been reported in up to 30% of women with FMF [15]. Peritoneal adhesions [6] and ovulatory disfunction [15] have been implicated. Since the introduction of long-term colchicine therapy concern from possible adverse effects on fertility have been raised. In a follow-up of 36 women, 13 (36%) had periods of infertility. Four suffered from primary infertility and only one of them conceived. In 10 of the 13 women (770/o), cause of infertility could be determined. Ovulatory disturbances were found in 6 (46%) and pelvic adhesions in 4 (30%) [7]. The infertility rate is high but close to that reported for women with FMF before colchitine therapy was introduced. Male fertility was initially suggested not to be affected by colchicine [18]. In a more recent report, azoospermia or impairment of sperm penetration was found in 20% of male FMF patients on long-term colchicine therapy [ 181. Pregnancy The prevalence of pregnancy loss in women with FMF appears to be high. Miscarriage, being the major cause, was reported in 26.6% of pregnancies (4 out of 15) in untreated FMF patients [6]. Similar high percentage (25%) of miscarriage was reported in women who conceived while on colchicine treatment [7]. Early miscarriage has been also reported after cessation of colchicine therapy [28]. Mutagenicity of colchicine deserves special consideration. A significant increase of cells with abnormal numbers of chromosomes was found in lymphocyte cultures from three gout Case Report
168
Shimoni and Shalev
patients under colchicine treatment. Patients of the same sex and age served as the control group. Out of 54 children with trisomy 21, two were born to patients with gout on continuous colchicine treatment [lo]. It must be stressed that patients with gouty arthritis are relatively old, thereby having an increased risk of trisomy. In a cytogenetic study of 38 FMF patients on colchicine therapy no important changes could be detected [3]. Still, out of 52 women who conceived while on daily colchicine treatment, one woman gave birth to a child with trisomy 21 [28]. Furthermore, reviewing 55 pregnancies associated with colchicine therapy, one pregnancy was found to be aborted after trisomy 23 was detected by amniocentesis [22]. It is strongly recommended that in pregnant patients on colchicine therapy, fetal karyotyping should be assessed. There is no information to support the possibility of increased risk for late pregnancy complications nor in changing of the disease’s natural course by pregnancy, with the exception of patients with renbal amyloidosis. In patients with mild to moderate nephropathy during pregnancy proteinuria was found to disappear in one third while in one third, the disease deteriorated despite colchicine treatment. Most patients with nephrotic syndrome go on to terminal renal failure while some may experience complete clinical recovery. It was suggested that in these patients, as pregnancy may result in either abortion, stillbirth or deterioration of renal funciton, pregnancy should be avoided [2,7,21]. This suggestion should be individualized and restricted to those patients with severe disease or those who have complicated their family planning. References 1 2
Bremner WJ, Paulsen CA: Colchicine and testicular function in man. N Engl J Med 294: 1384, 1976. Cabili S, Rabinovitch 0, Zemer D, Pras M, Gafni J: Effect of pregnancy on amyloid nephropathy in FMF (Abstract). XXII Congress of the EDTA, European Renal Association, 1985.
Int .I Gynecol Obstet 33
6
8
9
10 11 12 13
14
15
16
17 18
19
20
21
22
Cohen MM, Levy M, Eliakim MA: A cytogenetic evaluation of long-term colchicine therapy in the treatment of FMF. Am J Med Sci 274: 147, 1977. Dinarello CA, Wolff SM, Goldfinger SE, Dale DC, Alling DW: Colchicine therapy for familial Mediterranean fever. A double-blind trial. N Engl J Med 291: 934, 1974. Ehrenfeld EN, Eliakim M, Rachmilewitz M: Recurrent polyserobsitis (familial Mediterranean fever; periodic disease). A report of fifty-five cases. Am J Med 31: 107, 1981. Ehrenfeld EN, Polishuk WZ: Gynecological aspects of recurrent polyserositis (familial Mediterranean fever; periodic disease). lsr J Med Sci 6: 9, 1970. Ehrenfeld M, Brzezinski A, Levy M, Eliakim M: Fertility in obstetric history in patients with familial Mediterranean fever on long-term colchicine therapy. Br J Obstet Gynaecol94: 1186,1987. Ehrenfeld M, Levy M, Margalioth EJ, Eliakim M: The effects of long-term colchicine therapy on mate fertility in patients with familial Mediterranean fever. Andrology 18: 420, 1986. Eliakim M: Incidence of amyloidosis in recurrent polyserositis (familial Mediterranean fever). lsr J Med Sci 6: 2, 1970. Ferreira NR, Buoniconti A: Trisomy after colchicine therapy (Letter). Lancet 2: 1304, 1968. Gafni J, Ravid M, Sohar E: The role of amyloidosis in familial Mediterranean fever. lsr J Med Sci 4: 995, 1968. Goldfinger SE: Colchicine for familial Mediterranean fever. N Engl J Med 287: 1302, 1970. Heller H, Gafni J, Michaeli D, Shahin N, Sohar E, Ehrlich G, Karten I, Sokoloff L: The arthritis of familial Mediterranean fever (FMF). Arthritis Rheum 9: 1, 1966. Heller H, Sohar E, Gafni J, Heller J: Amyloidosis in familial Mediterranean fever: an independent genetically determined character. Arch Intern Med 107: 539, 1961. lsmajovitch B, Zemer D, Revach M, Serr DM, Sohar E: The causes of infertility in females with familial Mediterranean fever. Fertil Steril24: 844, 1973. Levin M, Franklin EC, Frangione B, Pras M: The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. J Clin Invest 51: 2773, 1972. Levy M, Eliakim M: Long-term prophylaxis in familial Mediterranean fever. Br Med J ii: 808, 1977. Levy M, Yaffe C: Testicular function in patients with familial Mediterranean fever on long term colchicine treatment. Fertil Steril29: 667, 1978. Meyerhoff J: Familial Mediterranean fever: report of a large family, review of the literature and discussion of the frequency of amyloidosis. Medicine 59: 66, 1980. Nixon RK, Priest RJ: Familial recuring polyserositis simulating acute surgical condition of the abdomen. N Engl J Med 263: 18, 1960. Pennigton JC, Pfaner DN: Familial Mediterranean fever, amyloidosis and pregnancy. Aust NZ J Obstet Gynaecol 13: 51,1973. Pras M, Gafni J, Jacob ET, Cabili S, Zemer D, Sohar E:
Familial Mediteranean fever in pregnancy
23
24 25 26
27
Recent advances in familial Mediterranean fever. Adv Nephrol 13: 261, 1984. Reimann HA, Moadie J, Semerdjian S, Sahyoun PF: Periodic perperitonitis - heredity and pathology. Report of seventy-two cases. J Am Med Assoc 154: 1254, 1954. Schwartz J: Periodic peritonitis, onset simultaneously with menstruation. Ann Intern Med 53: 407, 1960. Siegal S: Familial paroxysmal peritonitis. Analysis of fifty cases. Am J Med 36: 893, 1964. Skrinskas G, Bear RA, Majil A, Lee KY: Colchicine therapy for nephrotic syndrome due to familial Mediterranean fever. Can Med Assoc J 117: 1416, 1977. Sohar E, Gafni J, Pras M, Heller H: Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 43: 227, 1967.
28
169
Zemer D, Pras M, Shemer Y, Sohar E, Gafni J: Daily prophylactic colchicine in familial Mediterranean fever. In: Amyloid and Amyloidosis, Proceedings of the Third International Symposium on Amyloidosis. Excerpta Medica, Amsterdam, 1980, pp. 580-583.
Address for reprints: E. Shaiev Department of Obstetrics and Gynecology Central Emek Hospital Afuln 18 101 Israel
Case Report
ht. J. Gynecol. Obstet.. 1990,33: 165-169 International Federation of Gynecology and Obstetrics
Pregnancy
and complicated
familial Mediterranean
fever
Y. Shimoni and E. Shalev Department of Obstetrics and Gynecology, Central Emek Hospital, Afula (Israel) (Received March 13th, 1989) (Revised and accepted July 26th, 1989)
Abstract
Familial Mediterranean Fever (FMF) is an inherited disease, closely following the pattern of autosomal recessive inheritance. Amyloidosis is the most severe complication of the disease. The prevalence of pregnancy loss in women with FMF is considered to be high. There is no information to support the possibility of increase risk of late pregnancy complications or change in the natural course of the disease. Two cases are presented with complicated FMF. One case with proved amyloidosis and the second patient with ascites. Pregnancy and neonatal outcome were uneventful in both. No further deterioration in the systemic disease occurred.
synovitis and erysipelas-like erythema [27]. Amyloidosis is the most severe complication of the disease, which fortunately develops in a small percentage of cases [5]. Patients with amyloidosis are advised not to conceive [2,21]. There are only a few articles in the literature about the recurrent peritonitis and the development of ascites in patients suffering from FMF [25,27]. No report of ascites during pregnancy due to FMF has been reported. We report of two cases of young women with complicated FMF in pregnancy. The literature is reviewed with discussion on the possible implication of the disease on fertility and on pregnancy outcome. Case reports
Keywords: Amyloidosis; Familial Mediterranean fever; Pregnancy complications. Introduction
Familial Mediterranean fever (FMF) is an inherited disease almost exclusively confined to populations originating on the south and east coasts of the Mediterranean Sea. Genetic analysis of several hundred families has shown that the disease closely follows the pattern of autosomal recessive inheritance. The syndrome consists of recurrent attacks of fever with peritonitis, pleuritis, pericarditis, 0020-7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
Case 1 A 35year-old woman, gravida 2, para 1, born in Algeria, was followed in the outpatient high risk clinic with the diagnosis of amyloidosis due to FMF. The disease was suspected when she was 9 years old, after several attacks of abdominal pain and fever and with a family history of FMF. At the age of 23 she conceived and delivered her first child. A year later she was placed on prophylactic colchicine therapy. The attacks of abdominal pain and fever were less frequent and milder. At the age of 34, rectal biopsy revealed amyloidosis. The present pregnancy Case Report
166
Shimoni and Shalev
was unplanned, colchicine was taken prior to conception and was continued during the whole gestation. A genetic amniocentesis performed at 17 weeks revealed a normal karyotype. The patient was admitted to the high risk pregnancy unit at 24 weeks gestation when gestational diabetes was diagnosed. During the rest of the pregnancy she was readmitted several times to control the blood glucose. Renal function tests were as follows: blood urea nitrogen 15-26070, uric acid 5.96.2 mg%, creatinine 0.6-0.7 mg%, the amount of urine collected in 24 h ranged from 1900 ml to 2400 ml with urine protein secretion of 240-450 mg. The creatinine clearance was 88-96 ml/min. All function tests remained normal through the whole period. Even though the blood glucose was adequately controlled with insulin, sonographic follow-up indicated the fetus to be on the 95th percentile. On the 40-week of gestation after failed induction she had a cesarean section, and gave birth to a 4300 g male newborn. Case 2 A 25year-old nullipara, born in Morocco, was admitted to the high risk pregnancy unit in the 37th week of her first pregnancy with the diagnosis of fetal intrauterine growth retardation. The patient’s past medical history revealed that at the age of 21 she was operated for suspected acute appendicitis. An uninflammed appendix was found and removed. The peritoneal cavity contained 500 ml of serotic fluid and the ileum was covered with serotic sheath. Following the operation the patient had several attacks of abdominal pain for which she attended the emergency ward. In the present pregnancy serial sonographic examinations have pointed out the existence of a symmetrical growth retarded fetus. The last sonogram done at 37 weeks gestation also revealed a large amount of maternal ascites. The patient was admitted to the hospital and paracenthesis was performed. The fluid was gloomy. Cytological examination revealed many foam cells. Within the foam cells there Int J Gynecol Obstet 33
were inclusion bodies filled with dark hemosiderin like pigment. There were also many lymphocytes. Bacterial cultures were negative including special cultures for tuberculosis and chlamydia. Chemical analysis revealed a high protein content (6.0 golo), mostly albumin (4.0 go/o). At 38th week of gestation labor was induced and a 2400 g girl with Apgar score 10 was delivered. The postpartum period was uneventful. Postnatal ultrasound scan of the pelvis revealed a normal uterus. Fluid was found in the Douglas area and there were also many cystic areas along the right psoase. With the diagnosis of unexplained pelvic cysts and ascites, an explorative laparotomy was performed. In the operation, many cysts filled with clear fluid were found in the peritoneal cavity. There were multiple and extensive adhesions between the small intestinal colon and uterus to the abdominal wall. Otherwise the pelvic organs appeared normal. The fluid aspirated from the cysts was cytologically identical to the ascites found in the paracenthesis performed during the pregnancy. Diagnosis of FMF was raised and treatment with colchicine was started. A subjective relief from the abdominal pain attacks was mentioned by the patient. Later, under colchicine treatment, she had an uncomplicated pregnancy. Discussion Familial Mediterranean fever (FMF) Attacks of FMF begin in childhood. More than half of those affected have had an attack by the age of 10 years and 80-90% by the age of 20 years [ 191. The attacks are unpredictable and can be varied in their nature, often once a month or more, with occasional remissions lasting for a few months. Remissions are some times associated with pregnancy and may continue through lactation [6,20,23,27]. There is an increased number of cases among males compared to females in a ratio of 3:2 [25].
Familial Mediteranean fever in pregnancy
The most common type of attack, abdominal pain, may begin in any part of the abdomen and spread rapidly, then peritonism, fever, vomiting and absence of bowel sounds develop within a few hours. The patient usually recovers within 48 h [ 13,25,27]. Laparotomy and appendectomy are- often performed during the first attack for suspected acute appendicitis. Patients occasionally have tender enlarged ovaries on pelvic examination and pain on motion of the cervix [6]. Some patients have had attacks coincident with menstruation and may appear to have endometriosis [24]. No underlying cause of FMF has been discovered so far, despite extensive research for infective, metabolic and toxic agents. During acute attacks the erythrocyte sedimentation rate is raised but no specific diagnostic test is yet available [25]. Effusion fluids may contain polymorphonuclear leucocytes, and occasionally these cells have small inclusion bodies thought to be triglyceride [27]. Prognosis of FMF is indicated by the associated amyloidosis [ 14,181. A variable proof patients with FMF have portion amyloidosis. Amyloidosis of the amyloid type AA [la] is manifested clinically by a nephropathy that passes through proteinuric, nephrotic and uremic stages to death from renal failure. The approximate duration of the disease from onset of proteinuria or the nephrotic syndrome to end-stage renal failure is 7 and 3 years, respectively. Renal vein thrombosis has been proposed to be a major cause of rapid deterioration of renal function [14.27]. A rectal or renal biopsy has been the usual method for obtaining pathologic confirmation of the presence of amyloid [ 191. Continuous prophylaxis with colchicine has been proved to be effective in the suppression of the attacks in most patients [12,17]. Furthermore it has been shown recently that colchicine prevents both the development of amyloidosis and additional deterioration of renal function in patients with early amyloidosis [26,29]. Colchicine is thought to inhibit
167
the activation and release of lysosomes from phagocytic cells [17]. The drug interacts with microtubules and is a well-known mitotic inhibitor destroying germ cells in animals (in doses 30-50 times higher than conventional doses used in FMF) [l]. Side effects of colchicine given in therapeutic doses are usually minor and include abdominal pain, loose stool and vomiting [4]. Fertility FMF occurs in patients of child-bearing age. Infertility has been reported in up to 30% of women with FMF [15]. Peritoneal adhesions [6] and ovulatory disfunction [15] have been implicated. Since the introduction of long-term colchicine therapy concern from possible adverse effects on fertility have been raised. In a follow-up of 36 women, 13 (36%) had periods of infertility. Four suffered from primary infertility and only one of them conceived. In 10 of the 13 women (770/o), cause of infertility could be determined. Ovulatory disturbances were found in 6 (46%) and pelvic adhesions in 4 (30%) [7]. The infertility rate is high but close to that reported for women with FMF before colchitine therapy was introduced. Male fertility was initially suggested not to be affected by colchicine [18]. In a more recent report, azoospermia or impairment of sperm penetration was found in 20% of male FMF patients on long-term colchicine therapy [ 181. Pregnancy The prevalence of pregnancy loss in women with FMF appears to be high. Miscarriage, being the major cause, was reported in 26.6% of pregnancies (4 out of 15) in untreated FMF patients [6]. Similar high percentage (25%) of miscarriage was reported in women who conceived while on colchicine treatment [7]. Early miscarriage has been also reported after cessation of colchicine therapy [28]. Mutagenicity of colchicine deserves special consideration. A significant increase of cells with abnormal numbers of chromosomes was found in lymphocyte cultures from three gout Case Report
168
Shimoni and Shalev
patients under colchicine treatment. Patients of the same sex and age served as the control group. Out of 54 children with trisomy 21, two were born to patients with gout on continuous colchicine treatment [lo]. It must be stressed that patients with gouty arthritis are relatively old, thereby having an increased risk of trisomy. In a cytogenetic study of 38 FMF patients on colchicine therapy no important changes could be detected [3]. Still, out of 52 women who conceived while on daily colchicine treatment, one woman gave birth to a child with trisomy 21 [28]. Furthermore, reviewing 55 pregnancies associated with colchicine therapy, one pregnancy was found to be aborted after trisomy 23 was detected by amniocentesis [22]. It is strongly recommended that in pregnant patients on colchicine therapy, fetal karyotyping should be assessed. There is no information to support the possibility of increased risk for late pregnancy complications nor in changing of the disease’s natural course by pregnancy, with the exception of patients with renbal amyloidosis. In patients with mild to moderate nephropathy during pregnancy proteinuria was found to disappear in one third while in one third, the disease deteriorated despite colchicine treatment. Most patients with nephrotic syndrome go on to terminal renal failure while some may experience complete clinical recovery. It was suggested that in these patients, as pregnancy may result in either abortion, stillbirth or deterioration of renal funciton, pregnancy should be avoided [2,7,21]. This suggestion should be individualized and restricted to those patients with severe disease or those who have complicated their family planning. References 1 2
Bremner WJ, Paulsen CA: Colchicine and testicular function in man. N Engl J Med 294: 1384, 1976. Cabili S, Rabinovitch 0, Zemer D, Pras M, Gafni J: Effect of pregnancy on amyloid nephropathy in FMF (Abstract). XXII Congress of the EDTA, European Renal Association, 1985.
Int .I Gynecol Obstet 33
6
8
9
10 11 12 13
14
15
16
17 18
19
20
21
22
Cohen MM, Levy M, Eliakim MA: A cytogenetic evaluation of long-term colchicine therapy in the treatment of FMF. Am J Med Sci 274: 147, 1977. Dinarello CA, Wolff SM, Goldfinger SE, Dale DC, Alling DW: Colchicine therapy for familial Mediterranean fever. A double-blind trial. N Engl J Med 291: 934, 1974. Ehrenfeld EN, Eliakim M, Rachmilewitz M: Recurrent polyserobsitis (familial Mediterranean fever; periodic disease). A report of fifty-five cases. Am J Med 31: 107, 1981. Ehrenfeld EN, Polishuk WZ: Gynecological aspects of recurrent polyserositis (familial Mediterranean fever; periodic disease). lsr J Med Sci 6: 9, 1970. Ehrenfeld M, Brzezinski A, Levy M, Eliakim M: Fertility in obstetric history in patients with familial Mediterranean fever on long-term colchicine therapy. Br J Obstet Gynaecol94: 1186,1987. Ehrenfeld M, Levy M, Margalioth EJ, Eliakim M: The effects of long-term colchicine therapy on mate fertility in patients with familial Mediterranean fever. Andrology 18: 420, 1986. Eliakim M: Incidence of amyloidosis in recurrent polyserositis (familial Mediterranean fever). lsr J Med Sci 6: 2, 1970. Ferreira NR, Buoniconti A: Trisomy after colchicine therapy (Letter). Lancet 2: 1304, 1968. Gafni J, Ravid M, Sohar E: The role of amyloidosis in familial Mediterranean fever. lsr J Med Sci 4: 995, 1968. Goldfinger SE: Colchicine for familial Mediterranean fever. N Engl J Med 287: 1302, 1970. Heller H, Gafni J, Michaeli D, Shahin N, Sohar E, Ehrlich G, Karten I, Sokoloff L: The arthritis of familial Mediterranean fever (FMF). Arthritis Rheum 9: 1, 1966. Heller H, Sohar E, Gafni J, Heller J: Amyloidosis in familial Mediterranean fever: an independent genetically determined character. Arch Intern Med 107: 539, 1961. lsmajovitch B, Zemer D, Revach M, Serr DM, Sohar E: The causes of infertility in females with familial Mediterranean fever. Fertil Steril24: 844, 1973. Levin M, Franklin EC, Frangione B, Pras M: The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. J Clin Invest 51: 2773, 1972. Levy M, Eliakim M: Long-term prophylaxis in familial Mediterranean fever. Br Med J ii: 808, 1977. Levy M, Yaffe C: Testicular function in patients with familial Mediterranean fever on long term colchicine treatment. Fertil Steril29: 667, 1978. Meyerhoff J: Familial Mediterranean fever: report of a large family, review of the literature and discussion of the frequency of amyloidosis. Medicine 59: 66, 1980. Nixon RK, Priest RJ: Familial recuring polyserositis simulating acute surgical condition of the abdomen. N Engl J Med 263: 18, 1960. Pennigton JC, Pfaner DN: Familial Mediterranean fever, amyloidosis and pregnancy. Aust NZ J Obstet Gynaecol 13: 51,1973. Pras M, Gafni J, Jacob ET, Cabili S, Zemer D, Sohar E:
Familial Mediteranean fever in pregnancy
23
24 25 26
27
Recent advances in familial Mediterranean fever. Adv Nephrol 13: 261, 1984. Reimann HA, Moadie J, Semerdjian S, Sahyoun PF: Periodic perperitonitis - heredity and pathology. Report of seventy-two cases. J Am Med Assoc 154: 1254, 1954. Schwartz J: Periodic peritonitis, onset simultaneously with menstruation. Ann Intern Med 53: 407, 1960. Siegal S: Familial paroxysmal peritonitis. Analysis of fifty cases. Am J Med 36: 893, 1964. Skrinskas G, Bear RA, Majil A, Lee KY: Colchicine therapy for nephrotic syndrome due to familial Mediterranean fever. Can Med Assoc J 117: 1416, 1977. Sohar E, Gafni J, Pras M, Heller H: Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 43: 227, 1967.
28
169
Zemer D, Pras M, Shemer Y, Sohar E, Gafni J: Daily prophylactic colchicine in familial Mediterranean fever. In: Amyloid and Amyloidosis, Proceedings of the Third International Symposium on Amyloidosis. Excerpta Medica, Amsterdam, 1980, pp. 580-583.
Address for reprints: E. Shaiev Department of Obstetrics and Gynecology Central Emek Hospital Afuln 18 101 Israel
Case Report
