Volume 4 Issue 6, June 2017

Editorial

Chauhan AR

Uterine leiomyomas are mesenchymal tumors of smooth muscle origin and are the commonest benign tumors that affect women of reproductive age. They may be subserosal, intramural or submucous in location. This article looks at this common tumor at uncommon sites. Extrauterine fibroids are rare, may present at any age, and pose a diagnostic challenge mainly because of the unusual sites they are found in. They may primarily arise from the uterus or parauterine structures like broad, round and utero-ovarian ligaments or fallopian tube; subserous pedunculated fibroids may lose their vascular connection to the uterus and attach to other intraperitoneal structures like omentum, and become parasitic. Other locations are bladder or urethra; rectus sheath, labia or vaginal wall (anterior being more common); or virtually any site where smooth muscle is present. Very rarely, spontaneous occurrence may be seen with congenital Mullerian anomalies, where a fibroid can develop from a rudimentary or non-functioning uterus. Of all the extrauterine sites, intraligamental (broad ligament) fibroids are the commonest and constitute between 6 - 10% of all fibroids. 
"Iatrogenic parasitic fibroids" have been increasingly reported in recent times following either laparoscopic myomectomy or hysterectomy, where use of power morcellator has dispersed small tissue fragments in the peritoneal cavity, which subsequently implant over omentum or bowel.
Mode of presentation varies depending on the location. Many patients may be asymptomatic. Small round ligament or fallopian tube leiomyomas may be incidentally found at surgery for some other pathology. Bladder and urethral fibroids may present with urinary symptoms or mass protruding from the urethral meatus. Labial fibroids may initially be mistaken for a Bartholin cyst. Large broad ligament or giant retroperitoneal fibroids may present with pain, lump and pressure effects. Like all other fibroids, extrauterine fibroids are also hormone-responsive. Differential diagnosis for parasitic fibroid includes leiomyosarcoma, ovarian tumor and lymphadenopathy. Though rare, malignant transformation can occur even in extrauterine fibroids and should be borne in mind.
Irrespective of location, or rather because of unusual locations, the mainstay of diagnosis is imaging with ultrasonography, CT scan or MRI, where the fibroid will show low signal intensity similar to smooth muscle. However, even MRI may sometimes fail to diagnose a large fibroid in the retroperitoneal space or broad ligament, especially if it has undergone degeneration; the commonest differential is ovarian neoplasm. Due to the relatively small number of cases of extrauterine fibroid that the average gynecologist will encounter, diagnosis may often only be made intraoperatively. Confirmatory diagnosis is by histopathological examination.
Surgical excision is the mainstay of treatment for all extrauterine leiomyomas, and may be via laparotomy or laparoscopy, depending on the location. Bladder fibroids should be excised transurethrally, laparoscopically or via open surgery. There is a greater risk of ureteric and uterine artery injury when operating large broad ligament fibroids as compared to any other type of fibroid; hence laparoscopy for broad ligament fibroid should only be undertaken by a skilled and experienced laparoscopic surgeon. In cases with widespread peritoneal deposits, GnRH analogues have been tried preoperatively.
It is the responsibility of the laparoscopic surgeon to make all efforts to prevent iatrogenic parasitic fibroids, either at myomectomy or hysterectomy where the specimen is morcellated. Ideally, preoperative counselling should include an explanation of the risk of dissemination or seeding of fibroids at extrauterine sites despite the surgeon's best efforts, and also the potential risk of dissemination of malignant cells. Intraoperatively,  careful identification and complete removal of all fragments and thorough peritoneal lavage with saline should be performed; if morcellation is used, it should be "in-bag" using an endobag.
Another form of extrauterine fibroids is diffuse or disseminated peritoneal leiomyomatosis, which is extremely rare. The hallmark of this condition is the presence of multiple smooth muscle peritoneal nodules resembling peritoneal carcinomatosis, usually seen in young women. Benign metastasizing leiomyoma may manifest as multiple nodules or masses in the lungs or other sites, mimicking metastases from malignant tumors. It is recommended that these patients are followed up long- term; lesions regress after menopause. 
Fibroids at unusual locations such as rectus sheath and utero-ovarian ligament, and multiple parasitic fibroids following morcellation have been reported in previous issues of this journal. The June issue carries a case report of an anterior vaginal wall fibroid, which we hope will be of interest to our readers.

Herlyn Wurner Wunderlich Syndrome : A Rare Mullerain Anomaly

Author Information 

Jaybhaye SB
(Consultant Obstetrician And Gynecologist, Department Of Advanced Gynaec. Endoscopy. Om Sai Hospital, Kamothe, Panvel, Maharashtra, India.)

Abstract

A syndrome complex consisting of didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis is one of the most complex and rare congenital anomaly of the female urogenital system. In most of the cases patients remain asymptomatic till puberty only to present with dysmenorrhea, pelvic pain, inter menstrual bleeding and or abdominal cramps in the period following menarche. We present one of the atypical, delayed presentation of this syndrome who was diagnosed at 26 years of age because of dysmenorrhea and irregular vaginal bleeding. Appropriate combination of imaging, clinical examination and hysteroscopic evaluation confirmed the diagnosis that was followed by appropriate surgical correction to relieve her of her complaints . 

Introduction

Herlyn Werner Wunderlich syndrome also known as OHVIRA (Obstructed Hemivagina, Ipsilateral Renal Agenesis) syndrome is typically found to be associated with uterine didelphys but sometimes it has been encountered in association with septate uterus.[1] Most patients present after menarche with severe dysmenorrhea due to outflow tract obstruction.

Case Report

A 26 year old, unmarried female presented in the out patient department with complaints of severe dysmenorrhea, pain in abdomen since 6 to 7 years along with complaints of inter menstrual bleeding not responding to multiple attempts of hormonal treatment attempted by the primary general practitioner. She gave history of foul smelling vaginal discharge since last 2 months. There was no history of fever and burning micturition. She was sexually active since last 2 years. There were no coital complaints. Her menstrual history consisted of heavy menstrual flow for 7 days, every 30 days and it was associated with dysmenorrhea. Proper menstruation was followed by inter menstrual bleeding of altered brownish color almost daily throughout the month since the last 6 to 7 years. Ultrasonography (USG) features were suggestive of bicornuate uterus with minimal hematometra on the right side (Figure 1) with absent right kidney. (Figure 2). She gave history of undergoing hystero-laparoscopy at another center 18 months ago to evaluate her problem. It confirmed the presence of a bicornuate uterus. There was no evidence of endometriosis on laparoscopy. Right uterine horn could not be negotiated during last hysteroscopic attempt but there was discharge of hematometra collection from a small fistulous opening in the vaginal wall. Dilatation of fistulous opening was attempted during last surgery as mentioned in the operative notes.
Her general clinical examination was unremarkable. Per speculum examination revealed a bulge in the right anterolateral vaginal wall. Purulent discharge was noted from a fistulous opening in the vaginal wall bulge on pressing the bulge. (Figure 3). Cervix was more clearly seen on the left side and it was normal looking. On this clinical evaluation a clinical diagnosis of Herlyn Werner Wonderlich syndrome was made and she was posted for hysteroscopic confirmation of the diagnosis followed by surgical correction.
Intraoperatively on vaginoscopic examination the findings of per speculum examinations were confirmed. Since pus discharge was noted on clinical examination, low pressure hysteroscopy was planned under higher antibiotic cover to prevent the entry of purulent material into the peritoneal cavity and subsequent development of pyo peritoneum. Left sided cervix could be negotiated with the hysteroscope and a banana shaped left hemiuterine cavity with centrally placed ostium was noted. Hysteroscope was withdrawn and pushed through a small fistulous opening on the bulging right anterolateral vaginal wall. Hysteroscope entered into a blind vaginal pouch with pus collection. Right sided cervix was  located inside the vaginal pouch and on negotiating the cervix right hemiuterine cavity could be visualized hysteroscopically. Uterine cavity was also draining purulent material. This confirmed the suspected diagnosis of Herlyn Wurner Wonderlich syndrome. The oblique obstructing vaginal septum was excised. (Figure 4) The excised edges were marsupialized with the vaginal wall to relieve the obstruction as well as to prevent reocclusion of the outflow track. After complete excision of the septum, two distinct cervices could be visualized clearly and confirmed by passage of hegar’s dilator in the cervix. (Figure 5) Final picture after completion of excision as well as marsupialization resulted in formation of a single vagina with two cervices sharing a common medial wall. (Figure 6) Postoperative course was uneventful. She reported complete cure of her symptoms on 2 month followup postoperative visit.


Figure 1. Preoperative ultrasound showing bicornuate uterus


Figure 2. Preoperative ultrasound showing right renal agenesis


Figure 3. Intraoperative photograph showing pus discharge from blind vaginal pouch (arrow)


Figure 4. Intraoperative photograph showing septum excision in progress.


Figure 5. Passage of dilators through both cervices sharing common medial wall amongest them


Figure 6. Final intraoperative look showing single vagina with two cervices sharing common medial wall.

Discussion 

Herlyn Werner Wunderlich syndrome is included in class III of American Fertility Society (AFS) classification, as well as class U3C2V2 of mullerian anomaly according to European Society of Human Reproduction and Embryology (ESHRE) classification of mullerian anomalies. Overall incidence of this condition is very rare and is found to be seen in 0.1-3.8 % as reported by various case series reports across the world.[1] Ipsilateral renal agenesis on the side of obstructed hemivagina is the most commonly encountered renal anomaly in OHVIRA syndrome, although few other malformations, like renal duplication and multicystic dysplastic kidney, have also been reported in some papers.[2, 3] Acien proposed that while uterus and cervix were derived from fused-paired paramesonephric ducts (2nd part) and divergent distal paramesonephric ducts (3rd part), the vagina development is completely mesonephric in origin.[4] Hence, paramesonephric ducts don’t have any role in the embryonic development of the vagina but mullerian tubercle plays a role in the formation of vagina because it has been found that the cells in the vaginal lining have originated from the mullerian tubercle. 
Development of metanephric diverticulum from mesonephric duct with normally occurs around 5 weeks of pregnancy fails due to some unknown mechanism and because of that the ureteric bud doesn’t develop leading to renal and ureteric agenesis on the side of the blind vagina. Anatomical defect is created because of failed lateral fusion of mullerian ducts (didelphys/ septate uterus and double vagina) in combination with complete or partial failure of longitudinal fusion between the mullerian duct and the urogenital sinus (hemivaginal septum) on the side of the renal agenesis. In a reported case series of 27 cases, the age at diagnosis varied from 10 to 29 years, with a median age of 14 years.[3] Earliest reported case in the literature is one day old neonate at birth.[7] Defective development of both the  mullerian and wolfian ducts has been proposed as one of the theory in development of this malformation.[5] 
Patients complaints of dysmenorrhea or recurrent painful menses that occurs due to the outflow tract obstruction and pressure generated by the increasing distension of the obstructed hemivagina. Early and accurate diagnosis of this clinical entity is crucial because prompt surgical correction can relieve symptoms and prevent further complications related to chronic obstructive hematocolpos (such as endometriosis and pelvic adhesions), and maintain reproductive capacity. Delays in diagnosis were usually attributed to lack of knowledge of this clinical entity, occurrence of regular menstruations because of an incomplete vaginal outlet obstruction, and slow extension of the hematocolpos. Surgical correction not only relieves pain with immediate effect but also reduces chances of pelvic endometriosis due to retrograde menstruation. In postoperative phase patient is capable of having a normal sexual and reproductive life. In the earlier days hemi hysterectomy was the treatment chosen in many patients. Further addition of knowledge about this condition in the last few years has changed the treatment plans from hemi hysterectomy to a simple excision of the oblique complete vaginal septum relieving the obstruction.

Conclusion

Herlyn Wurner Wunderlich syndrome is a one of the rare forms of complex congenital female urogenital malformation. It does exhibit a wide range of clinical manifestations. Prompt diagnosis with appropriate surgical management is the key to a good outcome. Diagnosis is often missed clinically but investigations like MRI scan can identify the condition very easily.[6] Very high index of suspicion on part of the treating clinician is required to pick up this clinical condition either on clinical examination or with the help of appropriate investigations. Excision or complete division of the septum with marsupialization of the cut edges of the excised septum corrects the problem. Early and correct diagnosis is required to relieve the symptoms, preserve sexual functions and fertility and prevent complications caused by retrograde menstruation which may result in endometriosis. 

References
  1. Resetkova N, Christianson M, Kolp L : Uterine didelphys with obstructed hemivagina and ipsilateral renal agenesis with hydronephrosis. Fertil Steril 2012;97(3): 30-31.
  2. Li S, Qayyum A, Coakley FV, Hricak H. Association of renal agenesis and mullerian duct anomalies. J Comput Assist Tomogr. 2000;24(6):829-34.
  3. Vercellini P, Daguati R, Somigliana E, Viganò P, Lanzani A, Fedele L. Asymmetric lateral distribution of obstructed hemivagina and renal agenesis in women with uterus didelphys: institutional case series and a systematic literature review. Fertil Steril. 2007;87(4):719-24.
  4. Acién P. Embryological observations on the female genital tract. Hum Reprod. 1992;7(4):437-45.
  5. Orazi C, Lucchetti MC, Schingo PM, Marchetti P, Ferro F. Herlyn-Werner-Wunderlich syndrome: uterus didelphys, blind hemivagina and ipsilateral renal agenesis. Sonographic and MR findings in 11 cases. Pediatr Radiol. 2007;37(7):657-65.
  6. Marten K, Vosshenrich R, Funke M, Obenauer S, Baum F, Grabbe E. MRI in the evaluation of müllerian duct anomalies. Clin Imaging. 2003;27(5):346-50.
  7. Tsung-Hsin Wu, Trang-Tiau Wu, Yan-Yan Ng, Soo-Cheen Ng, Pen-Hua Su, Jia-Yuh Chen, et al. Herlyn-Werner-Wunderlich Syndrome Consisting of Uterine Didelphys, Obstructed Hemivagina and Ipsilateral Renal Agenesis in a Newborn. Pediatrics & Neonatology 2012;53(1),68–71.
Citation

Jaybhaye SB. Herlyn Wurner Wunderlich Syndrome : A Rare Mullerain Anomaly. JPGO 2017. Volume 4 No.6. Available from: http://www.jpgo.org/2017/06/herlyn-wurner-wunderlich-syndrome-rare_1.html

Omphalocoele: An Interesting Case

Author Information

Mahanti S*, Parulekar SV**.
(* Second Year Resident, ** Professor and Head, Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)

Abstract

The significance of prenatal ultrasonography lies greatly in the detection of fetal anomalies and to determine fetal prognosis. Fetal, placental and umbilical cord anomalies can both be detected on antenatal ultrasonography and determine fetal prognosis. Body wall defects such as anterior abdominal wall defects that include omphalocoele, cloacal and bladder exstrophy can also be detected on routine antenatal ultrasonography. This helps to ascertain post-delivery course and treatment of the neonate.

Introduction

Omphalocoele is characterized by failure of return of viscera into the abdomen after physiological mid-gut herniation.[1] It can be reliably detected on routine anomaly scans done between 16-18 weeks and the prognosis of the baby is fairly good. Here is a case of omphalocoele in a baby with unusual content of fundus of urinary bladder.   

Case Report

A 22 year old, third gravida, first para G3P1L1MTP1 with previous one full-term normal delivery and one first trimester medical termination of pregnancy was referred to us at 22 weeks of gestation from a peripheral maternity home in view of 2nd trimester anomaly scan showing polyhydramnios with ventral hernia defect, suspected to be an omphalocoele. The fetus was of 22 weeks on biometry. The amniotic fluid index was 20. There were multiple umbilical cord cysts.  She registered with us and followed up regularly for antenatal check-ups until term. She had no significant history of major medical or surgical illness in the past and all her other antenatal investigations were within normal limits. She presented at 37 weeks with complaints of pain abdomen and leaking per vaginum since 4 hours. On examination vitals were stable, cardiovascular and respiratory system examination was within normal limits. On per abdomen examination, the uterus was full term cephalic presentation with activity of 2-3 contractions per 10 minutes, each lasting for 20-30 seconds . She progressed spontaneously in labor and delivered  vaginally a female child weighing 2.120 kg with Apgar of 9/10. On post-delivery examination, the umbilical cord was found to be grossly dilated and edematous, with three vessels visible on gross examination. Umbilical cord at maternal end was normal in morphology for around 5-6 cm followed by gross dilatation up to full length of umbilical cord that is around 40 cm. There were no cysts in the umbilical cord. Placenta and membranes were expelled spontaneously. Active management of third stage of labor given and no postpartum hemorrhage was noted.

The baby was suspected to have loop of intestine at the fetal end of cord - an omphalocoele major - that was covered with amnion and membranes. A pediatric surgical reference was made. A diagnosis of an omphalocoele major was made. It was repaired on day 4 of life. The upper end of the urinary bladder was found in the omphalocele. The baby made an uneventful recovery and was discharged on day 10 of life with a per-urethral catheter in-situ. Histopathlogy report of the wall tissue as excised during the surgery of the neonate revealed features consistent with bladder wall. The Wharton’s jelly in the umbilical cord was found to be edematous. There were increased syncytial knots.


Figure 1. The neonate with edematous cord and the proximal end of the cord showing omphalocoele sac with contents.

Discussion

The contents of omphalocoele include loops of intestine and liver in 1/10000 and loops of intestine alone in 1/5000.[1] In the above-mentioned case, immediate post-delivery the presence of loop of intestine was suspected in the omphalocoele. In the case presented here, the contents of the omhalocele was the fundus of the urinary bladder. The presence of the urinary bladder in the omphalocoele sac is incredibly rare and has hardly ever been documented. Other unusual features in this case were edematous Wharton’s jelly and increased syncytial knots.
Omphalocoele must be differentiated from gastroschisis. It is seen in 1:20000 cases. It has the paramedian body wall defect and is associated with a worse prognosis than the former. Gastroschisis lacks the protective membrane over the intestinal contents and hence is associated with intestinal atresia.[2]
Abdominal wall defects involving the urinary bladder almost always show an extrophy of the bladder rather than inclusion of the urinary bladder in the omphalocele sac,[3] as was found in our case. The other possible differential diagnosis could be persistent urachus which results from the failure of closure of allantoic duct and is usually associated with bladder outlet obstruction. It is also associated with edematous umbilical cord as in the case presented.[4] However that is usually associated clear yellow urine-like fluid discharging from the umbilicus which was absent in this case.[4] 
Majority of omphalocoele have been associated with congenital syndromes such as Beckwith-Wiedemann Syndrome, chromosomal anomalies such as trisomy 13 and 18 or multiple non-chromosomal anomalies such as musculoskeletal or cardiovascular defects. Isolated omphalocoele, as in this case, has a good prognosis with survival rates as good as more than ninety percent. [5] Gastroschisis, on the other hand, usually doesn’t have associated anomalies.[1]

Conclusion

The presence of bladder fundus in omphalocoele sac is extremely rare. The presence of omphalocoele with anomalies of the umbilical cord should raise the suspicion of associated chromosomal anomalies such as trisomy 13 and 18.

References
  1. Weber T, Au-Fliegner M, Downard C, Fishman S. Abdominal wall defects. Curr Opin Pediatr. 2002;14:491–497.
  2. Boyd  PA,  Haeusler  M,  Barisic  I.  EUROCAT  report  9: surveillance of congenital anomalies in Europe 1980-2008. Birth Defects Res A Clin Mol Teratol 2011;91(suppl 1):S1.
  3. Swartz KR, Harrison MW, Campbell TJ. Selective management of Gastroschisis. Ann Surg. 1996;203:214–218.
  4. Schiesser M, Lapaire O, Holzgreve W, et al. : Umbilical cord edema associated with patent urachus. Ultrasound Obstet Gynecol. 2003;22(6):646–7.
  5. Chen CP. Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, diaphragmatic defects and others. Taiwan J Obstet Gynecol. 2007 Jun;46(2):111-20.
Citation

 Mahanti S, Parulekar SV. Omphalocoele: An Interesting Case. JPGO 2017. Volume 4 No.6. Available from: http://www.jpgo.org/2017/06/omphalocoele-interesting-case.html

Genital Tuberculosis - An Unusual Presentation

Author Information

Bijapur S*, Parulekar SV**.
(* Second Year Resident, ** Professor and Head, Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)

Abstract

Endometrial tuberculosis is a condition that can be asymptomatic, or can be present even in the absence of any physical findings both on clinical examination as well as endoscopic evaluation. We present a case of a 37 year old parous woman with hypomenorrhea followed by secondary amenorrhea due to end organ defect. She was ubusual in that she had no physical findings of tuberculosis and had amenorrhea despite the endometrium not being replaced by fibrous tissue, and which was cured with antituberculous therapy for just 2 months.

Introduction

Genital tuberculosis can cause a variety of symptoms like amenorrhea, abnormal uterine bleeding, pelvic pain, infertility, pelvic masses, abdominal masses, ascites etc. It can be suspected on investigations like hemogram, pelvic ultrasonography, hysterosalpingography, hysteroscopy and laparoscopy. The diagnosis can be confirmed by tests like TB-PCR, microbiologic studies on endometrium, and endometrial histopathology. It is unusual to have a case with secondary amenorrhea in presence of normal hysteroscopy and laparoscopy findings and the diagnosis being made by both TB-PCR test and histopathology. It is even more unusual to have the amenorrhea in the absence of replacement of the endometrium by fibrous tissue and reversal of the amenorrhea by antituberculous therapy for just two months. We present here such an unusual case.

Case Report

A 37 year old female , married for 13 years, para 2 living 2 MTP 1 presented with complaints of hypomenorrhea for 2 years , cycles every month lasting for 1 day, changing 1 pad per day and amenorrhea for 3 months. There was no pain in abdomen, foul smelling discharge, fever, loss of weight, loss of appetite. She was otherwise well and had no significant medical history. She had no history of tuberculosis or contact with tuberculosis. History of check curettage done in September 2016. General and systemic examination revealed no abnormality except mild enlargement of thyroid . On per speculum examination vagina was healthy and  cervix congested. On bimanual pelvic examination the uterus was anteverted, bulky, deviated to left and bilateral fornices were free. Pap smear showed inflammatory cells. Her rpogesterone and estrogen challenge tests were negative, and endometrial tuberculosis was suspected. Her chest radiograph, hemogram, liver and renal function tests were normal. Her thyroid function tests showed mild hypothyroidism, for which she was put on thyroid replacement therapy. Hysterroscopy, laparoscopy and cervical dilatation and endometrial curettage were performed. Hysteroscopy showed normal cervical canal, uterine cavity and tubal ostia. The endometrium was pale and flat.  Laparoscopy revealed normal abdominal and pelvic findings. Her endometrium was sent for TB-PCR and histopathological examination. Both tests confirmed the diagnosis of endometrial tuberculosis. She was put on category 1 antituberculous therapy, which she tolerated well, and started menstruating in two months.

Discussion

Genital tuberculous infection is usually caused by hematogenous spread from a primary site, usually in the lungs. [1]. The commonest site is the fallopian tubes (100%), followed by endometrium (50%), ovaries (20%), cervix (5%), and vagina and vulva in (<1%). [2,3] The patients present with infertility, pelvic pain, abnormal vaginal bleeding, amenorrhea, and vaginal discharge in 44%, 25%, 18%, 5%, 4% cases respectively. [4] Less common features include include abdominal mass, tuboovarian mass or abscess and ascites. [5]
The case presented by us was unusual in many respects. The patient was healthy and well, except having hypomenorrhea in the past and amenorrhea at present. Her general and systemic examination and investigations did not reveal anything suggestive of pelvic tuberculosis. It is usual to find some feature of tuberculosis on hysteroscopy and laparoscopy. In this patient all endoscopic findings were normal. Amenorrhea in a case of genital tuberculosis is usually due to replacement of endometrium by fibrous tissue (Asherman syndrome). It has been stated that the general toxemia of tuberculosis can cause amenorrhea in the absence of endometrial disease. However there is no evidence to support this statement. A negative estrogen challenge test strongly suggested the diagnosis. Hence the endometrium was sent for TB-PCR as well as histopathological examination, even though the findings on hysteroscopy and laparoscopy were normal, and there was no evidence of tuberculosis. It was surprising that both the tests were positive for tuberculosis. PCR is far more sensitive in detecting genital tuberculosis than microbiologic smear and culture methods. [6,7,8] But it is not usual to find the TB-PCR test positive when there are no gross features of tuberculosis on endoscopy. TB-PCR can be false negative as well as false positive. [9]
Endometrial tuberculosis can be present even when chest radiography, hemogram, hysteroscopy and laparoscopy do not show any feature suggestive of genital tuberculosis. In presence of other supportive evidence, a positive PCR test can be considered to be diagnostic of tuberculosis. In our case the endometrial histopathology confirmed the diagnosis, and the TB-PCR test turned out to be unnecessary in hindsight. However the likelihood of having a positive diagnosis on histopathology was considered to be low, and hence TB-PCR test was asked for. The patient started normal menstruation within two months of starting antituberculous therapy, which suggests presence of some factor in the endometrium that causes amenorrhea in the absnce of fibrosis replacing the endometrium, and even a short course of antituberculous therapy can remove this factor so that menstruation can start again. Thus an early diagnosis is important and hence TB-PCR test should be done in suspected cases.

References
  1. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. JAMA 1999;282:677–686.
  2. Chow TWP, Lim BK, Vallipuram S. The masquerades of female pelvic tuberculosis: case reports and review of literature on clinical presentations and diagnosis. Journal of Obstetrics and Gynaecology Research 2012;28:203– 210.
  3. Antonucci G, Girardi E, Raviglione MC, Ippolito G. Risk factors for tuberculosis in HIV-infected persons: a prospective cohort study. JAMA 1995;274:143–148.
  4. Carter JR. Unusual presentation of genital tract tuberculosis. Int J  Gynecol Obstet 1990;33:171–176.
  5. Saracoglu OF, Mungan T, Tanzer F. Pelvic tuberculosis. Int J  Gynecol Obstet 1992;37:115–120.
  6. Shrivastava G, Bajpai T, Bhatambare GS, Patel KB. Genital tuberculosis: Comparative study of the diagnostic modalities. J Hum Reprod Sci. 2014; 7(1): 30–33.
  7. Baxi A, Neema H, Kaushal M, Sahu P, Baxi D. Genital Tuberculosis in Infertile Women: Assessment of Endometrial TB PCR Results with Laparoscopic and Hysteroscopic Features. The Journal of Obstetrics and Gynecology of India 2011;61:301-306.
  8. Goel G, Khatuja R, Radhakrishnan G, Agarwal R, Agarwal S, Kaur I. Role of newer methods of diagnosing genital tuberculosis in infertile women. 2013;56:155-157.
  9. Thangappah RPB, Paramasivan CN,  Narayanan S. Evaluating PCR, culture & histopathology in the diagnosis of female genital tuberculosis. Indian J Med Res 2011;134:40-46.
Citation

Bijapur S, Parulekar SV. Genital Tuberculosis - An Unusual Presentation. JPGO 2017. Volume 4 No.6. Available from: http://www.jpgo.org/2017/06/genital-tuberculosis-unusual.html

Arcuate Uterus And Ectopic Kidney With Pregnancy

Author Information

Shah A*, Shende D**, Chaudhari HK***.
(* Second year Resident, ** Assistant Professor, *** Associate Professor, Department of Obstetrics and Gynecology, Seth GS Medical College and KEM Hospital, Mumbai, India.)

Abstract 

The female genital tract develops from müllerian ducts that forms the fallopian tube, uterus, cervix and the upper two-thirds of the vagina. Usual growth of the müllerian ducts is determined on the completion of three stages that is organogenesis, fusion and septal resorption. Fusion is characterized by joining of the ducts to form the uterus and its lack  leads in the development of a bicornuate or didelphys uterus. Renal anomalies occur in 29% of mullerian duct anomalies and are more commonly associated with unicornuate uteri than with other mullerian duct anomalies. Renal agenesis is the usually reported anomaly. Additional anomalies refer to the occurrence of an ectopic kidney, horseshoe kidney and renal dysplasia .

Introduction 

Mullerian duct anomalies (MDA) are uncommon but can be a treatable form of infertility. They are known to have higher incidences of infertility, repeated first trimester spontaneous abortions, fetal intra-uterine growth retardation, fetal malposition, preterm labor and retained placenta. The particular role of imaging is to discover and classify these MDA so that suitable treatment is undertaken. The group involving arcuate uterus is characterized by mild indentation of the endometrium at the uterine fundus. It is the outcome of a near total resorption of the uterovaginal septum. There is no difference in clinical pregnancy rate between women with arcuate uteri and women with a normal uterus. Meta analysis of congenital anomalies and its effect on reproduction showed that arcuate uterus was associated with second trimester miscarriage and increased rate of fetal malpresentation at delivery.[1,2] We present a case of arcuate uterus with breech presentation and ectopic kidney with a successful outcome of pregnancy.

Case Report

A 22 year old, primigravida at 34 weeks of gestation was referred from a private hospital with ultrasound suggestive of uterine anomaly;  most likely a subseptate uterus and an ectopic right kidney. She was admitted in ward for safe confinement and evaluation of the ectopic kidney. Ultrasonography was done from our hospital. It reported the presence of the right kidney measuring 9.5x4.5 cm in the right iliac fossa in the rectouterine pouch with normal echogenicity and corticomedullary differentiation.  Left kidney was 11.7x5.6 cm with anterioposterior dimension of the renal pelvis measuring 1.8 cm indicating mild hydronephrosis and hydroureter. Bladder was normally distended. Obstetric ultrasonography (USG) reported a single live intrauterine gestation of 34 weeks 6 days with breech presentation and effective fetal weight of 2209 grams, amniotic fluid index adequate, placenta in posterior position and S/D ratio of 1.96.
Urology reference was sort for and urine routine with culture and ultrasound was performed to rule out hydroureter and hydronephrosis. Urine routine was normal and urine culture showed no growth. Fitness for lower segment cesarean section was obtained from the nephrologist. At 37 weeks of gestation she complained of vaginal leaking.  Cervical Os  was 2.5 cm dilated, 60% effaced,  station was high, amniotic  membrane were absent, liquor was clear and litmus test was positive. It was a breech presentation. It was decided to deliver her by an emergency lower segment cesarean section. A Healthy male baby of 2.75 kg with 1 minute APGAR score of 9/10 was delivered. Intra operative findings confirmed the arcuate uterus with right kidney in the rectouterine pouch.


Figure 1. Arcuate Uterus


Figure 2. Ectopic kidney (arrow) 

Discussion

The female reproductive tract develops from a pair of müllerian ducts . Defect in the stage of septal resorption  results in subseptate or arcuate uterus.[2] Mullerian anomaly is associated with high chances of infertility and poor pregnancy outcome. The most widely accepted method of categorizing mullerian duct anomalies is the American Fertility Society (AFS) classification (1988). This system organizes mullerian anomalies according to the major uterine anatomic defect and allows for standardized reporting methods. The AFS classification system is based on the clinically useful scheme of Buttram and Gibbons, which combined the degree of developmental failure and its clinical manifestations.[3] Our case falls in the 6th class as it is an arcuate uterus. Interestingly in our case we had an ectopic right kidney with a normally located left kidney.
The mesonephric ducts connect with the urogenital sinus but by the 5th week of fetal life the ureteric buds appear on either side of the müllerian tubercle and the metanephrogenic mass of cells (the future kidney) appears. At the same time the primordial germ cells are migrating from the hindgut to form the primitive gonads along the urogenital ridge. The kidneys develop in the pelvis and begin as a metanephrogenic mass of intermediate mesoderm around the ureteric bud. As the kidneys develop they migrate toward the head of the embryo. This is chiefly the result of the growth of the embryo caudal to the kidneys.
An ectopic kidney is a birth anomaly in which a kidney is situated below, above, or on the opposite side of its regular place. An ectopic kidney may be asymptomatic and may function normally. It may be detected incidentally on USG, CT or MRI.  Possible complications of an ectopic kidney includes problems with urine drainage from that kidney. Abnormal urine flow can lead to difficulties like infection, stones and kidney damage.
Ectopic kidney may obstruct labor but unexpected degree of mobility permits them to be moved into the lower portion of the abdomen and allows normal vaginal delivery.[4] Ectopic kidney is more likely to suffer from certain complications than a normally located kidney.[4] Pelvic kidneys are more likely to get injured because they are unprotected by thoracic ribs and situated in a more anterior position.[4] Always consider a renal malformation in a differential diagnosis of a “pelvic mass.”[4]

Conclusion 

No treatment for an ectopic kidney is needed if urinary function is normal and no blockage of the urinary tract is present. Surgery or alternative treatment may be required if there is 
blockage, reflux, or extensive damage to the kidney. During gynecological surgery precautions should be taken to avoid iatrogenic injury to the ectopic kidney. 

References
  1. Acién P. Reproductive performance of women with uterine malformations. Hum Reprod. 1993;8(1):122-6.
  2. Chandler TM, Machan LS, Cooperberg PL, Harris AC, Chang SD. Müllerian duct anomalies: from diagnosis to intervention. Br J Radiol.2009;82(984):1034-1042.
  3. Buttram VC Jr, Gibbons WE. Müllerian anomalies: a proposed classification. (An analysis of 144 cases). Fertil Steril. 1979;32(1):40-6.
  4. Salvanos G, Papoutsas D, Bouropoulos C, Tsironis I. Ectopic kidney. Consultant. 2012;52(5). Available from: http://www.consultant360.com/article/ectopic-kidney
Citation

Ankita S, Shende D, Chaudhari HK. Arcuate Uterus And Ectopic Kidney With Pregnancy. JPGO 2017. Volume 4 No.6. Available from: http://www.jpgo.org/2017/06/arcuate-uterus-and-ectopic-kidney-with.html

Anterior Vaginal Wall Leiomyoma

Author Information

Ostwal P*,  Kale K**, Chauhan AR***
(* Second Year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynaecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)

Abstract

Leiomyomas are common tumors of the female genital tract, more commonly arising from the uterus and the cervix. Primary vaginal wall leiomyomas are rare, with only 300 reported cases in the literature. They are more commonly located in the anterior vaginal wall and present with a variety of symptoms which leads to difficult diagnosis. Surgical excision is the treatment of choice, preferably by vaginal route. Here we report a case of primary vaginal wall leiomyoma in a 37-year-old female presenting with mass protruding out of the introitus. Vaginal excision was performed and diagnosis was confirmed on histopathology.

Introduction

Vagina is a rare site for the occurrence of leiomyoma. Vaginal masses commonly include polyp, papilloma and hemangioma. Only few cases of vaginal leiomyoma have been reported in literature, of which anterior wall is the most commonly affected site.[1] Here we discuss one such rare case of primary vaginal wall leiomyoma which posed a diagnostic challenge.

Case Report

A 37-year-old parous woman with one living issue, presented to the outpatient department with something coming out per vaginum since 3 - 4 months duration associated with dyspareunia and increased frequency of urination. There were no associated menstrual complaints. Past medical and surgical history was not significant. Abdominal examination was within normal limits. Local examination of the perineal region revealed a mass protruding out of the introitus (Figure 1A), which bulged on coughing. On speculum examination, the mass was elongated, 4 x 5 cm in size, confined to the anterior vaginal wall. Cervix was seen separately below the mass (Figure 1B).  On per vaginal examination, uterus was anteverted, normal in size and mobile. The mass was firm in consistency, mobile, non-tender and was felt separate from the uterus. Overlying vaginal mucosa was free and healthy. Urethral opening was seen well away from the site of the mass.


Figure 1. (A) Mass protruding out of the introitus. (B) Mass seen arising from anterior vaginal wall with cervix seen separately below the mass.

Ultrasonographic examination showed a 5 x 6 cm mass in the upper part of vagina, most probably a pedunculated cervical fibroid. However, a clinical diagnosis of primary vaginal wall fibroid seemed more likely. After complete evaluation, patient underwent vaginal excision of the mass. Consent was also taken for abdominal exploration and hysterectomy if required. Under all aseptic precautions, bladder was catheterised. Base of the mass near the cervix was infiltrated with saline-adrenaline solution. A longitudinal incision was taken at the most inferior part of the mass to avoid injury to bladder (Figure 2). Plane was identified and the mass was dissected off the anterior vaginal wall using blunt and sharp dissection (Figure 3). The mass was removed completely and there was no evidence of a connecting pedicle to the uterus. Base of the myoma was obliterated using multiple sutures in figure of eight manner with no. 1 polyglactin. The excess vaginal mucosa was cut and sutured back in two layers using no. 2-0 polyglactin sutures (Figure 4).


Figure 2. Base of the mass infiltrated and a small vertical incision taken over the vaginal mucosa.


Figure 3. Mass held with a tenaculum and dissected off the vaginal mucosa by blunt and sharp dissection.


Figure 4. Final view after closure.

Grossly, the excised mass resembled a fibroid with characteristic whorling appearance on cut section. Microscopy showed a well circumscribed leiomyoma, thus confirming the diagnosis. The postoperative period was uneventful and patient was discharged on the third postoperative day.

Discussion

Leiomyomas are benign mesenchymal tumors of smooth muscle origin and are commonly found in the female genital tract, especially the uterus and the cervix. Vaginal leiomyomas are very rare and till date only 330 cases have been reported in the literature.[2] They commonly occur in females in the late reproductive age and/or nearing menopause, although rare cases have been reported in pubertal and postmenopausal females. They are more commonly located in the anterior vaginal wall as compared to the lateral and posterior vaginal walls. Vaginal leiomyomas are usually single, well circumscribed, firm in consistency and <5 cm in size. They may be asymptomatic initially or present with symptoms such as mass protruding from the vagina, bleeding, dyspareunia and lower abdominal pain. Compression of the bladder may lead to symptoms such as urinary retention and increased frequency of micturition.[3] Gupta et al have reported a rare case of large vaginal leiomyoma growing into the abdomen and masquerading as ovarian tumor.[2] Gowri et al have reported vaginal leiomyoma presenting as gluteal swelling and pus discharging per vagina.[4]
Vaginal leiomyomas present a diagnostic challenge owing to their rarity. Clinical features of the mass are such as consistency and mobility can point towards the diagnosis and were primarily relied upon in our case. Transabdominal and transvaginal ultrasonography may be useful but often leads to a misdiagnosis of cervical fibroids.[5] MRI is a better modality with greater delineation and may be used where the diagnosis is doubtful. Histopathology is confirmatory and gold standard for diagnosis of vaginal leiomyomas.[1]
Treatment of choice for vaginal leiomyomas is surgical excision, preferably by vaginal route. In some cases with large leiomyomas, an abdomino-perineal approach may be used. Urethral catheterisation is a must for avoiding bladder injury, which is usually rare and occurs when the myomas are large and indenting the bladder.[3, 4] Some authors have suggested hysterectomy for perimenopausal females.[2] In our opinion, the choice and route of surgery should be based on age, clinical presentation and size and extent of the vaginal leiomyoma. Recurrence may occur rarely and hence complete excision of the tumor and regular follow up is important. Malignant change is very rare, but reported.[3, 6]
Thus vaginal leiomyoma, although rare, is an important differential diagnosis of vaginal masses and should be kept in mind by the treating clinicians.

References
  1. Chakrabarti I, De A, Pati S. Vaginal leiomyoma. J Midlife Health. 2011; 2(1): 42-3.  
  2. Gupta V, Arya P, Gupta V, Rawat DS. A rare case of vaginal fibroid presenting as ovarian tumor. J Obstet Gynecol India. 2006; 56(6): 537-8.
  3. Nidhanee SV, Maiti S, Shareef D, Holland N. An unusual presentation of a vaginal leiomyoma in a postmenopausal hysterectomised woman: a case report. Cases J. 2009; 2: 6461.
  4. Gowri R, Soundararaghavan S, Oumachigui A, Sistla SC, Iyengar KR. Leiomyoma of the vagina: an unusual presentation. J Obstet Gynaecol Res. 2003; 29(6): 395-8.
  5. Bansal N, Jain VJ, Gupta V, Bharadwaj A. A case of vaginal leiomyoma: a rare entity. J South Asian Feder Obst Gynae. 2015; 7(3): 231-233.
  6. Goyal LD, Kaur H, Kaur K, Kaur S. An unusual case of vaginal myoma presenting with postmenopausal bleeding. J Family Reprod Health. 2013; 7(2): 103–104.
Citation

Ostwal P,  Kale K, Chauhan AR. Anterior Vaginal Wall Leiomyoma. JPGO 2017. Volume 4 No.6. Available from: http://www.jpgo.org/2017/06/anterior-vaginal-wall-leiomyoma.html

Use Of Eltrombopag In Immune Thrombocytopenic Purpura In Pregnancy

Author Information

Desai A*, Tiwari N**, Chauhan AR***.
(* Second Year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)

Abstract

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder that is secondary to accelerated destruction of platelet or impairment of thrombopoiesis by anti-platelet antibodies. We present a case of a 26-year-old primigravida with 33 weeks’ gestation with ITP, where thrombopoietin (TPO) analogue Eltrombopag (Revolade®) was used successfully. Patient had a falling platelet count despite injection methyl prednisolone and intravenous immunoglobulin (IVIG), and transfusions of Single Donor Platelets (SDP) and Random Donor Platelets (RDP), hence was started on eltrombopag. Though a category C drug, it was used when all other treatments failed and only in the third trimester; no adverse maternal or neonatal outcomes were noted.

Introduction

Immune thrombocytopenic purpura (ITP) affects 1 in 10000 persons in the general population and the reported incidence in pregnancy is 1-2 per 1000 deliveries.[1] ITP is responsible for 4% pregnancy associated thrombocytopenia.[2] 
Because of the side effects of drugs on the fetus and possible effects on course of pregnancy, the approach to treatment of ITP in pregnancy is different from that in non-pregnant state. Glucocorticoids are the initial drug of choice in the absence of major bleeding symptoms. Intravenous immunoglobulin (IVIG) and immunosuppressants are used in severe cases of ITP or those with bleeding. TPO mimetics like Eltrombopag and Romiplostim have been successfully used in non-pregnant patients but data regarding their effects on pregnancy are limited.[3]

Case Report

A 26-year-old primigravida 33 weeks of gestation was referred to us in view of low platelet count (45000 per cmm at the time of admission) and petechiae over the thigh. She was admitted in the intensive care unit in view of severe thrombocytopenia. 
Diagnosis of ITP was made after complete hematological investigations, and bone marrow aspiration and biopsy, which was suggestive of hypercellular marrow consistent with peripheral destruction of platelets. The patient was jointly managed by the hematologist and obstetrician. Platelet counts were monitored on a daily basis and patient was given platelet transfusion twice in the pregnancy, 1 SDP and 2 RDP given at platelet count of 10000 cu mm. At platelet count of only 1000 cu mm, patient was given intravenous immunoglobulin, injection methyl prednisolone and azathioprine, after which counts improved. Patient was started on tablet eltrombopag 50 mg along with tab prednisolone 60 mg once daily when platelet count was 36000 per cu mm. Eltrombopag was continued throughout pregnancy and the dose was tapered to 25 mg once a day. Tab Prednisolone was also continued throughout pregnancy and then tapered and omitted in the postnatal period. 
After starting treatment with eltrombopag, platelet counts initially fell below 30000 cu mm only once and she was given 1 SDP. After 1 week of treatment with eltrombopag, platelet counts rose and subsequently were always above 100,000 cu mm; she did not require further transfusions. 
At 40 weeks 2 days of gestation, a decision for planned induction of labor was taken, after confirming availability of adequate platelets. However, the NST was non-reactive, hence patient underwent emergency LSCS. The outcome was a female child weighing 3420 gm with an Apgar score of 9/10. The peripartum and postpartum periods were uneventful and the platelet count at the time of discharge was above 100,000 cu mm. Patient was continued on tablet eltrombopag at the same dose (25 mg) in the postnatal period, for 6 weeks.

Discussion

ITP is caused by antiplatelet antibodies also known as platelet associated immunoglobulin (PAIg) which bind to the glycoprotein complex on the platelet surface. These antibody- coated platelets are destroyed by tissue macrophages.  The autoantibodies also affect megakaryocytic maturation thus reducing platelet production.[4] Management decisions in cases of ITP depend on the platelet count and presence of bleeding symptoms. Glucocorticoids are the first line of treatment if the patient does not have major bleeding symptoms. Though safe for the fetus, they may induce gestational diabetes or hypertension in the mother. Cytotoxic drugs like azathioprine are teratogenic and thus not safe in early pregnancy. In our patient azathioprine was given only in third trimester. In case of life threatening bleeding the treatment of choice is IVIG, which is safe for the fetus but may cause adverse reactions in the mother; however, its effect is short lasting and not cost effective. Eradication of H. pylori with antibiotics has a positive impact on the platelet count in a patient with ITP.[5]
Eltrombopag is a nonpeptide TPO receptor agonist. Mode of administration is oral. Eltrombopag is of benefit in patients who have not responded to steroids or IVIG. It increases platelet production by acting on the cMpl receptor.[2] Eltrombopag belongs to pregnancy category C, to be used only when the benefits outweigh the risks, as in our case. Eltrombopag is usually started at a dose of 50 mg per day and modified as per the platelet count so as to keep the count above 50000 cu mm.[3,6] Daily dose should not exceed 75 mg as the most common complication is hepatotoxicity; the dose should be reduced in cases with liver disease. Side effects like rash, nausea, backache, diarrhea and upper respiratory tract infection may sometimes be seen. The main limitation at present to the use of eltrombopag, is the lack of studies in pregnant women and its prohibitively high cost.

References
  1. McCrae KR. Thrombocytopenia in pregnancy: differential diagnosis, pathogenesis, and management. Blood Rev 2003; 17(1): 7–14.
  2. Kelton JG. Idiopathic thrombocytopenic purpura complicating pregnancy. Blood Rev 2002; 16(1): 43-6.
  3. Kuter DJ. Thrombopoietin and thrombopoietin mimetics in treatment of thrombocytopenia. Annu Rev Med 2009; 60:193-206.
  4. Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS et al. ITP plasma and purified ITP monoclonal antibodies inhibit megakaryocytopoiesis in vitro. Blood 2003; 102(3): 887-95.
  5. Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of helicobacter pylori eradication on platelet count in ITP. A systematic review and meta analysis. J Antimicrob Chemother 2007; 60(2): 237-46.
  6. Psaila B, Bussel JB. Refractory immune thrombocytopenic purpura: current strategies for investigation and management. Br J  Haematol 2008; 143(1):16-26.
Citation

 Desai A, Tiwari N, Chauhan AR. Use Of Eltrombopag In Immune Thrombocytopenic Purpura In Pregnancy. JPGO 2017. Volume 4 No.6. Available from: http://www.jpgo.org/2017/06/use-of-eltrombopag-in-immune.html

Posterior Reversible Encephalopathy Syndrome Postpartum

Author Information

Sowpari R*, Warke HS**.
(* Second year resident, ** Associate Professor, Department of Obstetrics and Gynecology, Seth GS Medical college and KEM Hospital, Mumbai, India.)

Abstract

Preeclampsia is an insidious disease occurring in 4-7% of all pregnancies. It can develop anytime during pregnancy, delivery or postpartum. Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiological diagnosis. It rarely occurs without seizures or after delivery. Here we present a case of a patient with history of severe preeclampsia with term pregnancy, complicated by posterior reversible encephalopathy syndrome (PRES) with seizures seven days after delivery in her postpartum period. Clinical improvement with complete resolution without any complications was observed within one week.

Introduction

Preeclampsia can affect multiple systems, including the central nervous system. Posterior reversible leukoencephalopathy syndrome is a clinical and radiological syndrome. It is also called as reversible posterior cerebral edema syndrome, brain capillary leak syndrome or hyper perfusion syndrome.[1] PRES can clinically associated with a number of medical conditions such as preeclampsia, eclampsia, hypertensive encephalopathy, acute renal diseases, hemolytic uremic syndrome, cytotoxic drugs and immunosuppressant drugs, blood transfusion and electrolyte imbalance.
Clinically patient may present with headache, confusion, visual disturbances, blindness, photophobia or seizures. Parieto-occipital white matter changes are observed on imaging studies due to vasogenic edema.
If early diagnosis is established and appropriate treatment is started without delay, clinical symptoms of PRES can reverse.

Case Report

A 25-year-old married since 2 years P1L1 day7 of emergency caesarean was admitted in the emergency medical ward in view of post partum eclampsia. Patients’ antenatal registration was at seven months of gestation at a primary health centre and had 8 antenatal visits. Throughout her antenatal period her Blood Pressure was within the normal range and urine albumin was nil. There was no past history of any seizure disorder or any medical or surgical high risk. Patient was not compliant with hematinics. The patient was admitted at a private hospital  in view of pain abdomen at 40.3 weeks of gestation. On examination, high BP of 150/100 mm of hg was recorded. There were no premonitory symptoms and urine albumin was nil. Patient was started on tablet Labetalol 100mg OD and tablet Atenlol 50 mg OD.  Patient’s hemoglobin was 7.8mg% and one unit packed cell transfusion was given.  Emergency LSCS was done in view of cephalopelvic disproportion in labor under spinal anesthesia. Patient delivered a healthy female child of 3.5kg. Post LSCS patient was stable. There were no premonitory symptoms or seizures observed and urine albumin was nil. Patient was discharged on antihypertensives(labetalol and atenolol) and BP was controlled at 130/80 mm of hg. Patient was not compliant with her antihypertensive medications. On day 7 after delivery, patient complained of headache and vomiting followed by one episode of generalized tonic clonic convulsions followed by unconsciousness for 30 minutes. After regaining consciousness patient was drowsy. Patient came to the emergency medical ward at our tertiary care centre. On admission patient had generalized headache with drowsiness. General condition was moderate, pulse was 96/min, BP was 180/130 mm of Hg, on auscultation chest was clear and heart sounds were normal Labetalol 20mg was given intravenously . Repeat  BP was 160/110 mm of Hg. On per abdominal examination uterus was well contracted and on per vaginal examination there was no bleeding. Bilateral knee jerks were normal and urine albumin was +1. CT scan done was suggestive of PRES (posterior reversible encephalopathy syndrome). Patient was started on intravenous mannitol and levitiracetam. Labetalol 100mg thrice daily and nifedepine 10mg four times daily was started. Complete blood count revealed a hemoglobin of 11.4g/dL, platelet count of 162.000/mm3. Renal and liver function tests, serum electrolytes and electrocardiogram were normal. On day 8, post LSCS patient had second episode of convulsion followed by post ictal confusion and drowsiness. Injection Magnesium sulphate was given as per Pritchard regimen. Mannitol, levitiracetam and labetalol were continued. MRI brain was done which was suggestive of PRES. Neurology evaluation was done and injection eptoin was added. Patient was continued with these medications. No further convulsions were observed. Four days after starting treatment, her blood pressure was controlled. Meanwhile the patient had no episodes of seizures and on day 18 postpartum, there was complete recovery and was discharged without any recurrent symptoms.

Discussion

PRES is a rare and serious clinical entity of central nervous system. It can present with headache, altered mental status, seizures and visual loss. The most common presentation is with generalized tonic clonic seizures. In our case PRES occurred with seizures one week after LSCS in a preeclamptic woman with no history of visual complaints. We are reporting this case as this was a delayed presentation of PRES. 
Possibility of PRES must be kept in mind when a postpartum patient presenting with headache, mental confusion after seizures with high blood pressure with history of severe preeclampsia antenatally. The possibilities that must be kept in mind include eclampsia, cerebrovascular hemorrhage and PRES. If patient presents with visual complains, then ophthalmological examination must be done to rule out hypertensive retinopathy, exudative retinal detachment and cortical blindness must be ruled out as these can occur in preeclampsia and eclampsia.
The pathophysiological mechanism underlying PRES is still not clear. Two different theories have been considered. The first is the hyper perfusion or the vasogenic theory. It can be due to disordered cerebral autoregulation and endothelial dysfunction. The combination of acute hypertension and endothelial damage can lead to vasogenic edema elicited by the capillary leak of serum into the brain interstitium.[2] The reason for the primary involvement of the posterior brain regions (parietoccipital lobes) is not well understood. It can be due to the regional heterogenicity of sympathetic innervations of intracranial arterioles. This is due to better auto regulation of the anterior circulation due to better sympathetic innervations as compared to the posterior circulation.[3] Acute hypertension can cause hyper perfusion and edema in posterior circulation in PRES. The second theory is the hypoperfusion-ischemic theory or the cytotoxic theory in which the toxic cytokines playing a role is still uncertain.
It is thought that patients with chronic hypertension have hypertrophic arterial walls, including the central nervous system causing reduced permeability of blood brain barrier. Patients with preeclampsia do not have this compensatory effect and even a small increase in blood pressure can lead to increased permeability of the blood-brain barrier.[4,5]
Neuroimaging is impotant for the diagnosis of PRES and radiological abnormalities encountered in PRES are best demonstrated by magnetic resonance imaging (MRI). MRI shows symmetrical white matter edema in the posterior cerebellar hemispheres that particularly involves the parieto-occipital regions bilaterally.[6] T2- weighted MRI shows areas of hyper intense signal.
The goal of therapy is to rapidly lower the blood pressure. Once the blood pressure is controlled, neurological symptoms and cerebral lesions disappear completely within days to weeks. Magnesium therapy should be started if eclampsia or PRES in pregnancy is suspected.[7]
The prognosis of PRES is usually benign. Clinical improvement always follows the treatment of elevated blood pressure and it is important to avoid irreversible damage to the central nervous system.

References
  1. Pedraza R, Marik PE, Varon J. Posterior reversibl encephalopathy syndrome: a review. Crit. Care Shock 2009; 12: 135-143.
  2. Schwartz RB, Feske SK, Polak JF. Preeclampsia-eclampsia: clinical and neuroradiographic correlates and insights into the pathogenesis of hypertensive encephalopathy. Radiology 2000; 217: 2: 371-376.
  3. Bartynski WS. Posterior reversible encephalopathy syndrome-part 1: fundamental imaging and clinical features. American Journal of Neuroradiology 2008; 29: 6: 1036-1042.
  4. Hinchey J, Chaves C, Appignani B, Breen J. A reversible posterior leukoencephalopathy syndrome. N. Engl. J. Med 1996; 334: 494-500.
  5. Cipolla M J. Cerebrovascular function in pregnancy and eclampsia. Hypertension 2007; 50: 14-24.
  6. Lamy C, Oppenheim C, Meder JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome.  Journal of Neuroimaging 2004; 14: 2: 89-96.
  7. Striano P, Sitriano S, Tortea F. Clinical spectrum and critical care management of posterior reversible encephalopathy syndrome (PRES). Medical Science Monitor 2005; 11: 11: CR549-CR553.
Citation

Sowpari R, Warke HS. Posterior Reversible Encephalopathy Syndrome Postpartum. JPGO 2017. Volume 4 No. 6. Available from: http://www.jpgo.org/2017/06/posterior-reversible-encephalopathy.html

Chronic Myeloid Leukemia With Rheumatic Heart Disease In Pregnancy

Author Information

Shaikh A*, Mayadeo NM**, Warke HS***.
(* Second Year Resident, ** Professor, *** Associate Professor, Department of Obstetrics and Gynecology, Seth GS Medical college and KEM Hospital, Mumbai, India.)

Abstract

We describe the successful management of a 35-year-old gravida 3 para 2 living 2 woman who was diagnosed with chronic myeloid leukemia (CML) in the third trimester of pregnancy, with rheumatic heart disease (RHD) with severe mitral stenosis (MS) with moderate mitral regurgitation (MR) with trivial tricuspid regurgitation (TR) with pulmonary hypertension. She was started on hydroxyurea 500 mg twice daily and Inj Interferon 50 gm twice a week. Post-delivery she was started on Tab Imatinib 400 mg daily and hydroxyurea was stopped. Though hydroxyurea and imatinib are classified as category D drugs and interferon is category C drug in pregnancy, they were used only in third trimester due to CML, with a successful outcome.

Introduction

Chronic myeloid leukemia is a clonal hematopoietic disorder characterized by the translocation and resultant production of the activated bcr-abl tyrosine kinase. This arises due to an exchange of genetic material between chromosomes 9 and 22. Pregnancy and CML is an uncommon event as CML occurs mostly in elderly females. Management of CML is difficult because of the detrimental effects on the mother and fetus.[1] In our case, the condition was further aggravated by rheumatic mitral stenosis. We describe the successful management of pregnancy with hydroxyurea and imatinib in a case of rheumatic mitral stenosis in a patient who was diagnosed to have CML in the third trimester of her pregnancy. 

Case Report

A 35 year old female gravida 3, para 2 with previous 2 normal deliveries, was referred from a regional hospital with 35- 36 weeks’ gestation, in view of myeloid leukemoid reaction diagnosed for the first time during routine evaluation for right limb edema. Her WBC count was 87,900/cu mm with increased number of immature leucocyte series. Patient had a history of limb edema aggravated since last 15 days. Patient was referred to the regional cancer hospital and was advised observation till delivery, but was not started on any treatment.
On examination, she was averagely built and nourished; her vital parameters and systemic examination were unremarkable. On obstetric examination, uterus was 36 weeks’ size, cephalic presentation and fetal heart sounds were 148 beats per minute. Vaginal examination revealed a multiparous cervix; patient was not in labor. She was admitted and evaluated.   
Hematology consultation was obtained and she was investigated. Her routine investigations showed hemoglobin of 9.9 gm %, severely elevated total WBC count of 56,900 /cu mm with differential leucocyte count as follows: neutrophils 45 %, basophils 3 %, eosinophils 1 %, lymphocytes 12 %, myeloblasts 6 %, and myelocytes and metamyelocytes 30 %. Her platelet count was 2.4 lakh/ cu mm. Peripheral blood smear and bone marrow aspiration showed presence of chronic myeloid proliferative disorder with myeloid leukemoid reaction. Molecular cytogenetics (FISH) showed presence of single fusion in 93% of total interphase cells.
Over the course of one week, her WBC count increased from 56,900 to 86,000/ cu mm hence she was started on cap hydroxyurea 500 mg twice daily with inj interferon 50 gm twice a week. 
While investigating the cause of bilateral pedal edema with which the patient had presented, ECG was done which showed sinus tachycardia with right axis deviation and T wave inversion in lead III. Hence cardiology consultation was done and 2 D echo was performed; patient was detected to have RHD with severe MS with moderate MR with trivial TR with pulmonary hypertension with an ejection fraction of 60%; she was asymptomatic. She was started on inj furesemide 40 mg daily. As her serum TSH was 7.5, patient was also started on tab thyronorm 50 mcg daily. 
Patient went in spontaneous labor; full term outlet forceps application was done to cut short second stage of labor. She delivered a healthy female child of 2.7 kg.  Post-delivery there were no complications. She was started on tab imatinib 400 mg daily and cap hydroxyurea and inj interferon were stopped. Tab furesemide 40 mg daily was continued and tab metoprolol 50 mg daily was initiated. Breastfeeding was withheld as she was on imatinib, after consultation with neonatologist. Her further stay in the ward was uneventful and she was discharged on day 8 after delivery.

Discussion

Chronic myeloid leukemia has low occurrence in pregnancy. It is mostly diagnosed in the second or third trimester in pregnancy.[2]. Because of its chronic course, CML it is usually managed conservatively. Hydroxyurea and imatinib are classified as category D drugs and interferon is category C drug in pregnancy. However, nonteratogenic treatments during pregnancy are not very well defined hence leukapheresis, hydroxyurea, interferon alfa [3,4] and imatinib [5] can be used in the second or the third trimester. Our patient was an undiagnosed case of CML with rheumatic heart disease with severe MS with moderate MR with trivial TR with pulmonary hypertension for which she did not take any treatment until 35 weeks of pregnancy. Hydroxyurea is an S-phase antineoplastic agent which decreases the production of deoxyribonucleotides and causes release of free radicals due to their involvement in reduction of nucleoside diphosphates. There are no fetal malformations reported with hydroxyurea.[6] Our patient received this in third trimester, along with interferon. Interferons, which are proteins secreted by the immune system, boost the immune system response and reduce the growth of cancer cells. She was started on imatinib therapy post- delivery, and she delivered a healthy baby. Imatinib is a bcr-abl tyrosine kinase inhibitor frequently used and is a better treatment for patients with CML. It inhibits the abl protein of non-cancer cells leading to tumor cell death. Leukapheresis is not currently recommended as maintenance therapy for these diseases as it is inconvenient, costly and time consuming.[7]

Conclusion

Even though hydroxyurea and imatinib [5] are not considered totally safe for the treatment of CML in pregnancy and there is no effective data available about imatinib and breastfeeding in humans, it is still a necessary treatment in select cases[1]. The result in our case was good and shows that even if started late in pregnancy and continued thereafter, there is a good maternal and fetal outcome.

References
  1. Ali R, Ozkalemkas F, Kimya Y, Koksal N, Ozkocaman V, Gulten T et al. Imatinib use during pregnancy and breastfeeding: a case report and review of the literature. Arch Gynecol Obstet. 2009; 280(2):169–75.
  2. Lichtman M, Liesveld J. Acute myelogenous leukemia. In Beutler E, Lichtman M, Coller B, et al. Williams Hematology 6th edition, Vol. 1047. New York, USA: McGraw-Hill; 2001. pp. 1074-84.  
  3. O’Dwyer M. First-line treatment of chronic myeloid leukaemia. Therapeutic Advances in Hematology. 2010;1(1):15-22. 
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Citation

Shaikh A, Mayadeo NM, Warke HS. Chronic Myeloid Leukemia With Rheumatic Heart Disease In Pregnancy. JPGO 2017. Volume 4 No. 6. Available from: http://www.jpgo.org/2017/06/chronic-myeloid-leukemia-with-rheumatic.html