patient, we decided to treat her with metyrapone because of her gestational age and severe preeclampsia. Metyrapone, an 11-b-hydroxylase inhibitor, reduces serum cortisol levels in patients with Cushing syndrome and has been used safely during pregnancy. However, reduced cortisol levels stimulate corticotropin, which increases the production of mineralocorticoids, resulting in hypertension. Metyrapone has not been demonstrated to cause preeclampsia, but an association does exist.7 Oral antihypertensive therapy may be used to manage blood pressures; however, if superimposed severe preeclampsia is diagnosed and blood pressures become refractory to medication, delivery may be warranted. In patients with a history of bilateral adrenalectomy, mineralocorticoid and glucocorticoid replacement must be carefully monitored and stress dose steroids administered at the time of delivery. Screening the neonate for inherited disease is recommended because most cases are familial. Cardiac and cutaneous myxomas and primary pigmented nodular adrenocortical disease are the most common tumors during infancy,4 and an annual clinical work-up for all manifestations is recommended.4 Screening with baseline echocardiography is recommended by age 6 months and then annually.4,5 In families with a known PRKAR1A mutation, genetic testing can be performed to eliminate this screening for noncarriers. Genetic counseling is recommended in subsequent pregnancies and should
include discussion of autosomal-dominant inheritance and neonatal screening.4 It is important to recognize severe elevations of blood pressure and signs of hypercortisolism in pregnancy as abnormal. Although Carney complex is a rare cause of Cushing syndrome, and although Cushing syndrome is a rare diagnosis during pregnancy, it should be promptly identified so it can be treated to optimize maternal and fetal outcomes.
Cogan Syndrome in Pregnancy
known about whether it affects pregnancy or whether pregnancy affects the disease.
Christopher M. Tarney, MD, Karen Wilson, MD, and Mark F. Sewell, MD BACKGROUND: Cogan syndrome is a rare, multisystem, autoimmune disorder of unknown etiology. Little is From the Department of Obstetrics and Gynecology and Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Womack Army Medical Center, Fort Bragg, North Carolina. The opinions or assertions contained herein are the private views of the authors and are not to be construed as the official policy of the Department of the Army, Department of Defense, or the U.S. Government.
REFERENCES 1. Schulz S, Redlich A, Koppe I, Reschke K, Weise W. Carney complex—an unexpected finding during puerperium. Gynecol Obstet Invest 2001;51:211–3. 2. Kalelioglu I, Mert M, Has R, Kale T, Iyibozkurt C, Aral F. Carney’s complex: a successful pregnancy after bilateral adrenalectomy. Arch Med Sci 2012;8:175–7. 3. Stratakis CA, Sarlis N, Kirschner LS, Carney JA, Doppman JL, Nieman LK, et al. Paradoxical Response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease. Ann Intern Med 1999;131:585–91. 4. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and Recommendations for patient evaluation. J Clin Endocrinol Metab 2001;86:4041–6. 5. Bertherat J. Carney complex (CNC). Orphanet J Rare Dis 2006;I:21. 6. Nader S. Other endocrine disorders of pregnancy. In: Creasy and Resnik’s Maternal-fetal medicine. 6th ed. Philadelphia (PA): Saunders Elsevier; 2009. p. 1041–58. 7. Lim WH, Torpy DJ, Jeffies WS. The medical management of Cushing’s syndrome during pregnancy. Eur J Obstet Gyencol Reprod Biol 2013;168:1–6.
CASE: A 24-year-old primigravid woman with Cogan syndrome diagnosed 3 years before her pregnancy presented to our clinic for prenatal care. During pregnancy she experienced no worsening of symptoms of her disease but reported subjective improvement in vision and hearing. Cesarean delivery was performed at term because of nonreassuring fetal status. There were no obstetric or postpartum complications. CONCLUSION: Cogan syndrome requires close monitoring. If it worsens, then the disease process can be similar to both physiologic and pathologic changes of pregnancy. However, unlike the former, worsening Cogan syndrome can have irreversible maternal consequences.
Corresponding author: Christopher M. Tarney, MD, Womack Army Medical Center, Department of Obstetrics and Gynecology, 2817 Reilly Road, Fort Bragg, NC 28307; e-mail: [email protected].
(Obstet Gynecol 2014;124:428–31)
Financial Disclosure The authors did not report any potential conflicts of interest.
ogan syndrome was first described in 1934, with a later review of five cases by the ophthalmologist David Cogan who described this syndrome as a rare autoimmune disorder characterized by nonsyphilitic
© 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
428
Tarney et al
Cogan Syndrome During Pregnancy
DOI: 10.1097/AOG.0000000000000390
C
OBSTETRICS & GYNECOLOGY
interstitial keratitis associated with vestibuloauditory dysfunction, which is similar to Meniere disease and may lead to bilateral hearing loss within 2 years.1,2 This chronic inflammatory disorder affects young Caucasian adults with no gender predominance and has a range of diagnosis between the ages of 2.5 and 60 years.3 Twelve to 15% of patients with Cogan syndrome can have development of vasculitis involving vessels of all sizes and within different organ systems.4 More importantly, 10% of cases can be life-threatening secondary to aortic insufficiency.5 Initial theories speculated this disease was secondary to infection because 20% of patients had respiratory infections at the initial onset of symptoms; however, current theories postulate an autoimmune process with previous detection of this syndrome in patients with antiphospholipid antibodies or Crohn disease.3 Since 1934, there have been fewer than 300 reported patients described in the literature with Cogan syndrome. A computerized MEDLINE search of the period 1943 to March 2014 using the key words “Cogan’s syndrome” and “pregnancy” revealed only two previous reports of Cogan syndrome during pregnancy in the English literature. We present the third documented case of Cogan syndrome during pregnancy.
CASE A 24-year-old primigravid woman presented to our department at 14 0/7 weeks of gestation determined by last menstrual period. The patient’s medical history revealed that she had Cogan syndrome diagnosed at age 21 years. The patient reported that she first noticed a loss of hearing at the age of 9 years. Her hearing loss and tinnitus were initially attributed to Meniere disease. However, at age 20 years progressive vision loss developed, at which point Cogan syndrome was diagnosed by her rheumatologist. Serum antinuclear antibody testing performed before pregnancy, with the exception of antinuclear antibodies and p-ANCA, were negative (SSA-Ab, SSB-Ab, anticardiolipin antibodies, lupus anticoagulant, beta-2 glycoprotein, double-stranded DNA, Smith autoantibody, and Smith ribonucleic protein). During the year before pregnancy, the patient had three episodes of acute anterior uveitis that were successfully treated with both oral and ophthalmic steroids. A baseline echocardiogram demonstrated no abnormalities and an ejection fraction of 65%. The patient was followed-up during her pregnancy by obstetricians, optometrists, and otolaryngologists. She had an uncomplicated prenatal course with no acute exacerbations of her disease. She reported that her tinnitus had significantly improved and that she experienced improvement in her vision loss, which were confirmed by objective findings on both visual and auditory examinations. Induction of labor was initiated at 40 5/7 weeks of gestation with oxytocin. The intrapartum course was complicated by multiple episodes of fetal bradycardia for
VOL. 124, NO. 2, PART 2, AUGUST 2014
which a cesarean delivery was performed, resulting in the delivery of a vigorous newborn weighing 3,680 g. Gross inspection of the placenta demonstrated multiple calcifications with meconium-stained membranes and a three-vessel cord. Histologic examination demonstrated acute chorioamnionitis and funisitis with no findings of vasculitis among the placental vessels. The patient did well intraoperatively and postoperatively. The patient and newborn were discharged to home on postoperative day 2 with no postoperative complications. The newborn passed auditory brainstem response testing on the second day of life, and follow-up for auditory testing was planned for 3month follow-up. After delivery, the newborn demonstrated no findings concerning for a cardiac arrhythmia. Eight weeks after delivery, the patient reported no relapse of symptoms of her Cogan syndrome.
COMMENT Cogan syndrome is a rare inflammatory disease that occurs in young adults and is characterized by systemic vasculitis with ocular and vestibuloauditory findings. Other systemic symptoms can include headache, fever, and arthralgias. Our MEDLINE search revealed only two documented cases in the English literature of this rare disease during pregnancy.6,7 Table 1 summarizes the important findings of the three known cases of Cogan syndrome during pregnancy.6,7 Permanent hearing loss and cardiovascular disease are the gravest sources of morbidity for Cogan syndrome.8 The exact cause of Cogan syndrome is unknown, but current theory postulates an underlying autoimmune etiology. One theory postulates IgG antibodies against the protein DEP-1/CD148, a protein responsible for cellular differentiation and inhibition of cell growth, may be responsible for the autoimmune process8; however, Cogan syndrome is primarily a clinical diagnosis. In general, approximately 30% of pregnant patients with autoimmune disease will have worsening of their disease and the rest will have stability or improvement.9 Given the rarity of this disease, it is difficult to assess the course of disease during pregnancy and its possible effects on pregnancy outcomes. Treatments utilized to control ocular and vascular symptoms in Cogan syndrome include corticosteroids with consideration of immunosuppressive drugs such as hydroxychloroquine in patients who demonstrate no improvement with corticosteroids.7 The two previous reported cases and our case show a variation in the progression of Cogan syndrome during pregnancy. Our patient was not using suppressive therapy for her Cogan syndrome during the pregnancy. The patient never expressed or demonstrated worsening
Tarney et al
Cogan Syndrome During Pregnancy 429
Table 1. Key Findings of Cogan Syndrome During Pregnancy Currie et al Age (y) Medications
Maternal serum analysis
33 Hydroxychloroquine 200 mg twice daily during entire pregnancy None provided
Deliveliotous et al
Tarney et al
39 Ophthalmic steroids for 3 weeks (12–15 wk of gestation)
24 None
Positive antinuclear antibodies and p-ANCA Negative SSA-Ab, SSB-AB, Negative SSA-Ab, SSB-AB, anticardiolopin antibodies, anticardiolopin antibodies, double-stranded DNA, Smith double-stranded DNA, Smith autoantibody, Smith autoantibody, Smith ribonucleic protein ribonucleic protein Change in symptoms No change Interstitial keratitis developed at Subjective improvement in 12 wk of gestation auditory and visual symptoms Timing of delivery Induction of labor at 38 0/7 wk 38 0/7 wk of gestation presented Induction of labor at 40 5/7 wk of gestation for in labor of gestation for expert opinion oligohydramnios Mode of delivery Cesarean delivery for Spontaneous vaginal delivery Cesarean delivery for nonreassuring fetal status and nonreassuring fetal status arrest of dilation Neonatal weight (g) 3,410 3,820 3,680 Apgar scores (1-min, 5-min) 8, 9 None provided 4, 9 Postpartum complications None None None
of her symptoms; in fact, she reported subjective improvement in her baseline ocular and auditory symptoms, which were confirmed by objective measures. This is in contrast with the two previously reported case reports in which one woman was administered hydroxychloroquine therapy with no change in symptoms and the other woman required a 3-week treatment of ophthalmic steroids for acute interstitial keratitis. Recommendations regarding the management of Cogan syndrome during pregnancy are limited given the paucity of information. Based on the three cases of Cogan syndrome during pregnancy, it would be reasonable to obtain baseline ophthalmologic examination, peripheral vascular examination, auditory examination, and maternal echocardiography. Given the association of this disease with vasculitis and possible concern for uteroplacental insufficiency, antepartum surveillance similar to that of other autoimmune conditions is reasonable. Close evaluation of maternal hearing and vision is needed to separate common changes in pregnancy from worsening Cogan syndrome because worsening symptoms left untreated have the potential for permanent hearing loss. Clinicians must be cognizant that findings in preeclampsia may be similar to acute exacerbations in Cogan syndrome. In general, women with autoimmune disease are at higher risk for preeclampsia. As a result, we recommend that pregnant women with
430
Tarney et al
Cogan Syndrome During Pregnancy
Positive antinuclear antibodies
Cogan syndrome with development of symptoms that may be consistent with worsening of their disease or preeclampsia (vision changes, headaches, increased blood pressure) should be carefully evaluated. Mistaking an exacerbation of Cogan syndrome for a diagnosis of preeclampsia could lead to significant morbidity for the patient. Women found to have an exacerbation of Cogan syndrome should be administered prompt treatment to avoid permanent hearing loss, because previous studies have demonstrated that symptoms in these women respond well to corticosteroids.6,7
REFERENCES 1. Cogan DA. Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Arch Opthalmol 1945;33:144. 2. Vollersten RS, McDonald TJ, Younge BR, Banks PM, Stanson AW, Ilstrup DM. Cogan’s syndrome: 18 cases and a review of the literature. Mayo Clin Proc 1986;61:344. 3. Bakalianou K, Salakos N, Iavazzo C, Danilidou K, Papadias K, Kondi-Pafiti. A rare case of uneventful pregnancy in a woman with Cogan’s syndrome. Clin Exp Obstet Gynecol 2008;35: 201–302. 4. Vollertsen RS. Vasculitis and Cogan’s syndrome. Rheum Dis Clin North Am 1976;60:549. 5. Garcia Berrocal JR, Vargas JA, Vaquero M, Ramon Y Cajal S, Ramirez-Camacho RA. Cogan’s syndrome: an oculoaudiovestibular disease. Postgrad Med J 1999;75:262.
OBSTETRICS & GYNECOLOGY
6. Deliveliotous A, Moustakarias T, Argeitis J, Vaggos G, Vitoratos N, Hassiakos D. Successful full-term pregnancy in a woman with Cogan’s syndrome: a case report. Clin Rheumatol 2007;26:2181–3.
8. Lunardi C, Bason C, Leandri M, Navone R, Lestani M, Millo E, et al. Autoantibodies to inner ear and endothelial antigens in Cogan’s syndrome. Lancet 2002; 360:915–21.
7. Currie C, Wax JR, Pinette MG, Blackstone J, Cartin A. Cogan’s syndrome complicating pregnancy. J Matern Fetal Neonatal Med 2009;22:928–30.
9. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse D, Spong CY. Connective-tissue disorders. Williams obstetrics. 23rd ed. New York: McGraw-Hill; 2010. p. 1146.
Influenza A Hepatitis in Pregnancy
diagnosed, which resolved spontaneously during a period of 10 to 14 days, with favorable maternal and perinatal outcomes. This case was uniquely challenging because of the broad differential of deranged liver function tests in pregnancy and their maternal and perinatal implications.
Sarah Morocco, MD, Andrew Korman, MD, and Janet Stein, MD
CASE
© 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
A 32-year-old woman, gravida 3 para 2002, presented to her obstetrician’s office at 31 4/7 weeks of gestation with a 3-day history of a flu-like illness (fever, rhinorrhea, and cough). Influenza A was diagnosed by rapid nasal swab and her obstetrician recommended oseltemavir, but she declined treatment. Over the next several days, progressive pruritis of the palms and soles of her feet developed and she was sent to the labor and delivery unit because of the concern for cholestasis of pregnancy. She had been using 2,000 mg/day of acetaminophen in divided doses for continued body aches and fevers. She reported normal fetal movement. On evaluation, her SaO2 was 93% on room air; she was afebrile and normotensive (blood pressure 110/65). She had no rashes or jaundice. A transabdominal ultrasonogram showed the fetus in cephalic presentation with a biophysical profile of 10 out of 10, a normal-appearing anterior placenta, an amniotic fluid index of 8 cm, and an estimated fetal weight of 1,631 g, which was in the 55th percentile for this gestational age. Laboratory values obtained on the day of presentation revealed elevated liver enzymes (alanine aminotransferase 115 international units/L, aspartate aminotransferase 120 international units/L) and total bilirubin 2.2 mg/dL (Table 1). Coagulation study (prothrombin time, partial thromboplastin time, fibrinogen, fibrin split products) results were normal. She had a normal platelet level (191 K/uL), a normal acetaminophen level (less than 10), as well as negative screen results for viral hepatitis (including herpes simplex virus 1 and 2, cytomegalovirus, Epstein–Barr virus, parvovirus, and hepatitis A, B, C, and E) and autoimmune hepatitis (including alpha-1-antitrypsin level, antiliver kidney microsomal antibody, antinuclear antibody, and ceruloplasmin). Bile acids were also measured at this time, and a 24hour urine protein collection was initiated. The patient was admitted and treated supportively with intravenous fluids and administered ursodiol and diphenhydramine for pruritis, which provided minimal relief. Betamethasone was administered for fetal lung maturity.
VOL. 124, NO. 2, PART 2, AUGUST 2014
Morocco et al
BACKGROUND: Influenza A has been described in association with hepatitis. We present a case of complicated influenza A hepatitis in a pregnant woman, adding to the broad differential of liver disease in pregnancy. CASE: A 32-year-old woman, gravida 3 para 2002, at 31 4/7 weeks of gestation had influenza A diagnosed and subsequent development of severe pruritis and elevated liver enzymes (aspartate aminotransferase 659 international units/L, normal 15–46 micromoles/L; alanine aminotransferase 933 international units/L, normal 13–69 micromoles/L; and total bile acids 249.7 micromoles/L, normal 4.5–19.2 micromoles/L). She was treated supportively, and fetal surveillance was normal. Her symptoms resolved over the subsequent 2 weeks, and she delivered a healthy term newborn. CONCLUSION: Influenza A infection can be associated with hepatitis in pregnancy, which in our case resolved spontaneously over 10 to 14 days with favorable maternal and perinatal outcomes. (Obstet Gynecol 2014;124:431–3) DOI: 10.1097/AOG.0000000000000348
A
pregnant woman had influenza A infection and concomitant and clinically significant hepatitis
From the Departments of Obstetrics and Gynecology and Gastroenterology, Mount Sinai Beth Israel, New York, New York. The authors thank Men-Jean Lee, MD, and Stephanie Lam, DO, for their editorial assistance. Corresponding author: Sarah Morocco, MD, 350 East 17th Street, 9 Baird Hall, Department of Obstetrics and Gynecology, Mount Sinai Beth Israel, New York, NY 10003; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest.
Influenza A Hepatitis in Pregnancy 431
include discussion of autosomal-dominant inheritance and neonatal screening.4 It is important to recognize severe elevations of blood pressure and signs of hypercortisolism in pregnancy as abnormal. Although Carney complex is a rare cause of Cushing syndrome, and although Cushing syndrome is a rare diagnosis during pregnancy, it should be promptly identified so it can be treated to optimize maternal and fetal outcomes.
Cogan Syndrome in Pregnancy
known about whether it affects pregnancy or whether pregnancy affects the disease.
Christopher M. Tarney, MD, Karen Wilson, MD, and Mark F. Sewell, MD BACKGROUND: Cogan syndrome is a rare, multisystem, autoimmune disorder of unknown etiology. Little is From the Department of Obstetrics and Gynecology and Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Womack Army Medical Center, Fort Bragg, North Carolina. The opinions or assertions contained herein are the private views of the authors and are not to be construed as the official policy of the Department of the Army, Department of Defense, or the U.S. Government.
REFERENCES 1. Schulz S, Redlich A, Koppe I, Reschke K, Weise W. Carney complex—an unexpected finding during puerperium. Gynecol Obstet Invest 2001;51:211–3. 2. Kalelioglu I, Mert M, Has R, Kale T, Iyibozkurt C, Aral F. Carney’s complex: a successful pregnancy after bilateral adrenalectomy. Arch Med Sci 2012;8:175–7. 3. Stratakis CA, Sarlis N, Kirschner LS, Carney JA, Doppman JL, Nieman LK, et al. Paradoxical Response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease. Ann Intern Med 1999;131:585–91. 4. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and Recommendations for patient evaluation. J Clin Endocrinol Metab 2001;86:4041–6. 5. Bertherat J. Carney complex (CNC). Orphanet J Rare Dis 2006;I:21. 6. Nader S. Other endocrine disorders of pregnancy. In: Creasy and Resnik’s Maternal-fetal medicine. 6th ed. Philadelphia (PA): Saunders Elsevier; 2009. p. 1041–58. 7. Lim WH, Torpy DJ, Jeffies WS. The medical management of Cushing’s syndrome during pregnancy. Eur J Obstet Gyencol Reprod Biol 2013;168:1–6.
CASE: A 24-year-old primigravid woman with Cogan syndrome diagnosed 3 years before her pregnancy presented to our clinic for prenatal care. During pregnancy she experienced no worsening of symptoms of her disease but reported subjective improvement in vision and hearing. Cesarean delivery was performed at term because of nonreassuring fetal status. There were no obstetric or postpartum complications. CONCLUSION: Cogan syndrome requires close monitoring. If it worsens, then the disease process can be similar to both physiologic and pathologic changes of pregnancy. However, unlike the former, worsening Cogan syndrome can have irreversible maternal consequences.
Corresponding author: Christopher M. Tarney, MD, Womack Army Medical Center, Department of Obstetrics and Gynecology, 2817 Reilly Road, Fort Bragg, NC 28307; e-mail: [email protected].
(Obstet Gynecol 2014;124:428–31)
Financial Disclosure The authors did not report any potential conflicts of interest.
ogan syndrome was first described in 1934, with a later review of five cases by the ophthalmologist David Cogan who described this syndrome as a rare autoimmune disorder characterized by nonsyphilitic
© 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
428
Tarney et al
Cogan Syndrome During Pregnancy
DOI: 10.1097/AOG.0000000000000390
C
OBSTETRICS & GYNECOLOGY
interstitial keratitis associated with vestibuloauditory dysfunction, which is similar to Meniere disease and may lead to bilateral hearing loss within 2 years.1,2 This chronic inflammatory disorder affects young Caucasian adults with no gender predominance and has a range of diagnosis between the ages of 2.5 and 60 years.3 Twelve to 15% of patients with Cogan syndrome can have development of vasculitis involving vessels of all sizes and within different organ systems.4 More importantly, 10% of cases can be life-threatening secondary to aortic insufficiency.5 Initial theories speculated this disease was secondary to infection because 20% of patients had respiratory infections at the initial onset of symptoms; however, current theories postulate an autoimmune process with previous detection of this syndrome in patients with antiphospholipid antibodies or Crohn disease.3 Since 1934, there have been fewer than 300 reported patients described in the literature with Cogan syndrome. A computerized MEDLINE search of the period 1943 to March 2014 using the key words “Cogan’s syndrome” and “pregnancy” revealed only two previous reports of Cogan syndrome during pregnancy in the English literature. We present the third documented case of Cogan syndrome during pregnancy.
CASE A 24-year-old primigravid woman presented to our department at 14 0/7 weeks of gestation determined by last menstrual period. The patient’s medical history revealed that she had Cogan syndrome diagnosed at age 21 years. The patient reported that she first noticed a loss of hearing at the age of 9 years. Her hearing loss and tinnitus were initially attributed to Meniere disease. However, at age 20 years progressive vision loss developed, at which point Cogan syndrome was diagnosed by her rheumatologist. Serum antinuclear antibody testing performed before pregnancy, with the exception of antinuclear antibodies and p-ANCA, were negative (SSA-Ab, SSB-Ab, anticardiolipin antibodies, lupus anticoagulant, beta-2 glycoprotein, double-stranded DNA, Smith autoantibody, and Smith ribonucleic protein). During the year before pregnancy, the patient had three episodes of acute anterior uveitis that were successfully treated with both oral and ophthalmic steroids. A baseline echocardiogram demonstrated no abnormalities and an ejection fraction of 65%. The patient was followed-up during her pregnancy by obstetricians, optometrists, and otolaryngologists. She had an uncomplicated prenatal course with no acute exacerbations of her disease. She reported that her tinnitus had significantly improved and that she experienced improvement in her vision loss, which were confirmed by objective findings on both visual and auditory examinations. Induction of labor was initiated at 40 5/7 weeks of gestation with oxytocin. The intrapartum course was complicated by multiple episodes of fetal bradycardia for
VOL. 124, NO. 2, PART 2, AUGUST 2014
which a cesarean delivery was performed, resulting in the delivery of a vigorous newborn weighing 3,680 g. Gross inspection of the placenta demonstrated multiple calcifications with meconium-stained membranes and a three-vessel cord. Histologic examination demonstrated acute chorioamnionitis and funisitis with no findings of vasculitis among the placental vessels. The patient did well intraoperatively and postoperatively. The patient and newborn were discharged to home on postoperative day 2 with no postoperative complications. The newborn passed auditory brainstem response testing on the second day of life, and follow-up for auditory testing was planned for 3month follow-up. After delivery, the newborn demonstrated no findings concerning for a cardiac arrhythmia. Eight weeks after delivery, the patient reported no relapse of symptoms of her Cogan syndrome.
COMMENT Cogan syndrome is a rare inflammatory disease that occurs in young adults and is characterized by systemic vasculitis with ocular and vestibuloauditory findings. Other systemic symptoms can include headache, fever, and arthralgias. Our MEDLINE search revealed only two documented cases in the English literature of this rare disease during pregnancy.6,7 Table 1 summarizes the important findings of the three known cases of Cogan syndrome during pregnancy.6,7 Permanent hearing loss and cardiovascular disease are the gravest sources of morbidity for Cogan syndrome.8 The exact cause of Cogan syndrome is unknown, but current theory postulates an underlying autoimmune etiology. One theory postulates IgG antibodies against the protein DEP-1/CD148, a protein responsible for cellular differentiation and inhibition of cell growth, may be responsible for the autoimmune process8; however, Cogan syndrome is primarily a clinical diagnosis. In general, approximately 30% of pregnant patients with autoimmune disease will have worsening of their disease and the rest will have stability or improvement.9 Given the rarity of this disease, it is difficult to assess the course of disease during pregnancy and its possible effects on pregnancy outcomes. Treatments utilized to control ocular and vascular symptoms in Cogan syndrome include corticosteroids with consideration of immunosuppressive drugs such as hydroxychloroquine in patients who demonstrate no improvement with corticosteroids.7 The two previous reported cases and our case show a variation in the progression of Cogan syndrome during pregnancy. Our patient was not using suppressive therapy for her Cogan syndrome during the pregnancy. The patient never expressed or demonstrated worsening
Tarney et al
Cogan Syndrome During Pregnancy 429
Table 1. Key Findings of Cogan Syndrome During Pregnancy Currie et al Age (y) Medications
Maternal serum analysis
33 Hydroxychloroquine 200 mg twice daily during entire pregnancy None provided
Deliveliotous et al
Tarney et al
39 Ophthalmic steroids for 3 weeks (12–15 wk of gestation)
24 None
Positive antinuclear antibodies and p-ANCA Negative SSA-Ab, SSB-AB, Negative SSA-Ab, SSB-AB, anticardiolopin antibodies, anticardiolopin antibodies, double-stranded DNA, Smith double-stranded DNA, Smith autoantibody, Smith autoantibody, Smith ribonucleic protein ribonucleic protein Change in symptoms No change Interstitial keratitis developed at Subjective improvement in 12 wk of gestation auditory and visual symptoms Timing of delivery Induction of labor at 38 0/7 wk 38 0/7 wk of gestation presented Induction of labor at 40 5/7 wk of gestation for in labor of gestation for expert opinion oligohydramnios Mode of delivery Cesarean delivery for Spontaneous vaginal delivery Cesarean delivery for nonreassuring fetal status and nonreassuring fetal status arrest of dilation Neonatal weight (g) 3,410 3,820 3,680 Apgar scores (1-min, 5-min) 8, 9 None provided 4, 9 Postpartum complications None None None
of her symptoms; in fact, she reported subjective improvement in her baseline ocular and auditory symptoms, which were confirmed by objective measures. This is in contrast with the two previously reported case reports in which one woman was administered hydroxychloroquine therapy with no change in symptoms and the other woman required a 3-week treatment of ophthalmic steroids for acute interstitial keratitis. Recommendations regarding the management of Cogan syndrome during pregnancy are limited given the paucity of information. Based on the three cases of Cogan syndrome during pregnancy, it would be reasonable to obtain baseline ophthalmologic examination, peripheral vascular examination, auditory examination, and maternal echocardiography. Given the association of this disease with vasculitis and possible concern for uteroplacental insufficiency, antepartum surveillance similar to that of other autoimmune conditions is reasonable. Close evaluation of maternal hearing and vision is needed to separate common changes in pregnancy from worsening Cogan syndrome because worsening symptoms left untreated have the potential for permanent hearing loss. Clinicians must be cognizant that findings in preeclampsia may be similar to acute exacerbations in Cogan syndrome. In general, women with autoimmune disease are at higher risk for preeclampsia. As a result, we recommend that pregnant women with
430
Tarney et al
Cogan Syndrome During Pregnancy
Positive antinuclear antibodies
Cogan syndrome with development of symptoms that may be consistent with worsening of their disease or preeclampsia (vision changes, headaches, increased blood pressure) should be carefully evaluated. Mistaking an exacerbation of Cogan syndrome for a diagnosis of preeclampsia could lead to significant morbidity for the patient. Women found to have an exacerbation of Cogan syndrome should be administered prompt treatment to avoid permanent hearing loss, because previous studies have demonstrated that symptoms in these women respond well to corticosteroids.6,7
REFERENCES 1. Cogan DA. Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Arch Opthalmol 1945;33:144. 2. Vollersten RS, McDonald TJ, Younge BR, Banks PM, Stanson AW, Ilstrup DM. Cogan’s syndrome: 18 cases and a review of the literature. Mayo Clin Proc 1986;61:344. 3. Bakalianou K, Salakos N, Iavazzo C, Danilidou K, Papadias K, Kondi-Pafiti. A rare case of uneventful pregnancy in a woman with Cogan’s syndrome. Clin Exp Obstet Gynecol 2008;35: 201–302. 4. Vollertsen RS. Vasculitis and Cogan’s syndrome. Rheum Dis Clin North Am 1976;60:549. 5. Garcia Berrocal JR, Vargas JA, Vaquero M, Ramon Y Cajal S, Ramirez-Camacho RA. Cogan’s syndrome: an oculoaudiovestibular disease. Postgrad Med J 1999;75:262.
OBSTETRICS & GYNECOLOGY
6. Deliveliotous A, Moustakarias T, Argeitis J, Vaggos G, Vitoratos N, Hassiakos D. Successful full-term pregnancy in a woman with Cogan’s syndrome: a case report. Clin Rheumatol 2007;26:2181–3.
8. Lunardi C, Bason C, Leandri M, Navone R, Lestani M, Millo E, et al. Autoantibodies to inner ear and endothelial antigens in Cogan’s syndrome. Lancet 2002; 360:915–21.
7. Currie C, Wax JR, Pinette MG, Blackstone J, Cartin A. Cogan’s syndrome complicating pregnancy. J Matern Fetal Neonatal Med 2009;22:928–30.
9. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse D, Spong CY. Connective-tissue disorders. Williams obstetrics. 23rd ed. New York: McGraw-Hill; 2010. p. 1146.
Influenza A Hepatitis in Pregnancy
diagnosed, which resolved spontaneously during a period of 10 to 14 days, with favorable maternal and perinatal outcomes. This case was uniquely challenging because of the broad differential of deranged liver function tests in pregnancy and their maternal and perinatal implications.
Sarah Morocco, MD, Andrew Korman, MD, and Janet Stein, MD
CASE
© 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
A 32-year-old woman, gravida 3 para 2002, presented to her obstetrician’s office at 31 4/7 weeks of gestation with a 3-day history of a flu-like illness (fever, rhinorrhea, and cough). Influenza A was diagnosed by rapid nasal swab and her obstetrician recommended oseltemavir, but she declined treatment. Over the next several days, progressive pruritis of the palms and soles of her feet developed and she was sent to the labor and delivery unit because of the concern for cholestasis of pregnancy. She had been using 2,000 mg/day of acetaminophen in divided doses for continued body aches and fevers. She reported normal fetal movement. On evaluation, her SaO2 was 93% on room air; she was afebrile and normotensive (blood pressure 110/65). She had no rashes or jaundice. A transabdominal ultrasonogram showed the fetus in cephalic presentation with a biophysical profile of 10 out of 10, a normal-appearing anterior placenta, an amniotic fluid index of 8 cm, and an estimated fetal weight of 1,631 g, which was in the 55th percentile for this gestational age. Laboratory values obtained on the day of presentation revealed elevated liver enzymes (alanine aminotransferase 115 international units/L, aspartate aminotransferase 120 international units/L) and total bilirubin 2.2 mg/dL (Table 1). Coagulation study (prothrombin time, partial thromboplastin time, fibrinogen, fibrin split products) results were normal. She had a normal platelet level (191 K/uL), a normal acetaminophen level (less than 10), as well as negative screen results for viral hepatitis (including herpes simplex virus 1 and 2, cytomegalovirus, Epstein–Barr virus, parvovirus, and hepatitis A, B, C, and E) and autoimmune hepatitis (including alpha-1-antitrypsin level, antiliver kidney microsomal antibody, antinuclear antibody, and ceruloplasmin). Bile acids were also measured at this time, and a 24hour urine protein collection was initiated. The patient was admitted and treated supportively with intravenous fluids and administered ursodiol and diphenhydramine for pruritis, which provided minimal relief. Betamethasone was administered for fetal lung maturity.
VOL. 124, NO. 2, PART 2, AUGUST 2014
Morocco et al
BACKGROUND: Influenza A has been described in association with hepatitis. We present a case of complicated influenza A hepatitis in a pregnant woman, adding to the broad differential of liver disease in pregnancy. CASE: A 32-year-old woman, gravida 3 para 2002, at 31 4/7 weeks of gestation had influenza A diagnosed and subsequent development of severe pruritis and elevated liver enzymes (aspartate aminotransferase 659 international units/L, normal 15–46 micromoles/L; alanine aminotransferase 933 international units/L, normal 13–69 micromoles/L; and total bile acids 249.7 micromoles/L, normal 4.5–19.2 micromoles/L). She was treated supportively, and fetal surveillance was normal. Her symptoms resolved over the subsequent 2 weeks, and she delivered a healthy term newborn. CONCLUSION: Influenza A infection can be associated with hepatitis in pregnancy, which in our case resolved spontaneously over 10 to 14 days with favorable maternal and perinatal outcomes. (Obstet Gynecol 2014;124:431–3) DOI: 10.1097/AOG.0000000000000348
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pregnant woman had influenza A infection and concomitant and clinically significant hepatitis
From the Departments of Obstetrics and Gynecology and Gastroenterology, Mount Sinai Beth Israel, New York, New York. The authors thank Men-Jean Lee, MD, and Stephanie Lam, DO, for their editorial assistance. Corresponding author: Sarah Morocco, MD, 350 East 17th Street, 9 Baird Hall, Department of Obstetrics and Gynecology, Mount Sinai Beth Israel, New York, NY 10003; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest.
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