Detection and Treatment of Unsuspected Tuberculous Endometritis

DETECTION AND TREATMENT OF UNSUSPECTED TUBUOULOUS ENDOMETRITIS* WILLIAM LEVINE,

M.D., :F'.A.C.S.,

AND IRVIN"G

BROOKLYN,

I.

KuRLAND,

M.D.,

N. Y.

( Jhom the Department of Gynecology and Obstetrics and the Gynecological Endocri;ne Clinic, Beth·El Hospital)

T THE turn of the century, tuberculosis was widespread and led all other diseases as a cause of death. While it remained a major scourge in Europe, it continued to show a steady downward trend in this country as a result of the improved standard of living, efficient methods of prevention, and earlier detection and treatment. However, genital tuberculosis has always been, and still is. a rare gynecologic finding, because of the elusive clinical manner in which it masquerades and simulates other pelvic conditions. With the advent of infertility studies and the routine use of endometrial biopsy, more cases of UJlsuspected tuberculous endometritis have now come to light. Thus attention is focused on genital tuberculosis as a possible cause of female infertility.

A

It is generally agreed that the commonest lesion in genital tuberculosis i:-tubal involvement. Sharman 1 (1944) reports tubal occlusion in 62 per cent of patients with a Koch lesion in the endometrium as compared to only 26 per cent of 1,500 nontuberculous sterile women. Halbreeht2 (1946) found endometrial tuberculosis in 5.5 per cent of 820 infertile patients, but aroused comment when he reported 37.5 per cent of tuberculous endometritis in 48 sterile women who had partially or completely occluded Fallopian tubes. Rabau 3 (1950) found endometrial tuberculosis in 3.5 per cent of 2,000 infertile patient~. He coneluded that, since tubal tuberculosis is 2 to 3 times a~ frequent as endometrial involvement, genital tuherrulosis is the cau~e of infertility in 10 to 12 per cent of his cases. In Great Britian, Sutherland/ Sharman/ and 0 'Brien and Lawler·; t'E'· ported the incidence of endometrial tuberculosis in all curettage specimens to vary from 0.6 per cent to 1.1 per eent. However, in women coming under ob~ervation and study for infertility, the percentages vary from 2.8 per cent to fi.3 per cent. This indicates that it is fi times more common in barren women than in fertile women. In this country, Israel and 1\leranze'; ( 1950) stimulated by Halbrecht 's report of such a hig-h incidenre of tuberculous endometritis in women who hac] partially or completely occluded tubes, reviewed their curettage specimens of 172 sterile women with similar tubal occlusion. 'l'he;v could not find a single cast> of tuberculous endometritis. This controversial issue was discussed furt.her at the 1H5l session of tiH' American Soeiety for the Study of Sterility. Sharman reported 154 cases of endometrial tuberculosis in 2,962 cases of primary sterility investigated over a period of 16 years in Glasgow. This was an incidence of fi.2 per cent. In n·· viewing the literature he Rtressed the global character of this disease. Israel, however, took issue and again stresse
befor~;

the BrooklYn (;yneeological Sodety, Oet. 17. 1951.

421

UNSUSPECTED TUBERCULOUS ENDOMETRITIS

Volume 63 Number 2

The relative infrequency of this form of genital tuberculosis in the American literature is attested by the single case reports of Aranson and Dwight 7 (1949), Schaupp 8 (1949), Herring and King 9 (1950), Lubin and Waltman 10 (1950), and Keettel1 1 (1951).

Material The following report is based on the study of 5 cases of tuberculous endometritis observed during the course of infertility investigation. 'l'hese were found among 794 patients who had 529 endometrial biopsies during the past 15 years, an incidence of 0.65 per cent. Table I summarizes all five cases. 'l'reatment in all the patients was not standardized, but follows advances in the therapy of tuberculosis with antibiotics. 'l'ABLE

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SUMMARY OF CASES

---~-'======:===·-­

CASE

1. M.

AGE

TYPE OF STERILITY

DURATION OF STERILITY

METHOD OF DETECTION

w-.- 3;cc3c--"_,.S-ec-ondary--To-End.ometrial years

biopsy

2. C. L.

30

Secondary

1 year

Endometrial biopsy, follow· up; menstrual culture, Ny· lon tampon

3. J. F.

28

Primary

4 years

4. T.M.

20

Primary

Endometrial biopsy Endometrial biopsy

6

months 5. M.. G.

26

Primary

6

TREATMENT

RESULT

-Streptomy-c.,-in-,---'-~s-u_r_gl.,_,c-a~l-c-u-re--

Curettage

pre-op. 21 grams in 3 wks. followed by pelvic surgery *Combined therapy

Latest basal body temperature readings show normal pattern. Biopsies negative

None Streptomycin 50 mg. in 10 weeks *Combined therapy

Unimproved, repeated biopsies, positive Still under treatment

*Combined therapy, streptomycin, 1 Gm. three times weekly, para-aminosalicyclic acid. 12·week course.

12 Gm. daily,

Case Reports CASE 1.-M. W., aged 33 years, was first seen at the Gynecological Endocrine Clinic on Nov. 8, 1949, eomplaining of involuntary sterility for past 10 years. Past History.-One induced abortion 12 years ago. Menstruation began at age of 12 years, every 28 days, lasting four days. The pelvic examination on initial visit to the outpatient department revealed a cystic mass the size of a lemon in the left fornix, causing that fornix to become .shortened. 'l'he remainder of the pelvic findings were negative. Endometrial biopsy taken on the twenty-fifth day of a 28-day cycle revealed tuberculous endometritis. The patient was then admitted to the hospital for a complete study on Feb. 14, 1950. X-ray examination disclosed no evidence of pulmonary diMase. All extrapulmonary tests were reported negative for tuberculosis. The patient was placed on the following therapy preoperatively for 21 days: strepto· mycin, 1 Gm., given daily intramuscularly, together with vitamins and a high caloric diet. A supracervic-al hysterectomy with bilateral salpingectomy and left oophorectomy was performed. The pathological report was bilateral tuberculous salpingitis. There was no residual tuberculosis in the endometrium. The patient's c.ourse, postoperatively, was afebrile and she was discharged on the twelfth postoperative day.

422

Am . .J. Obst. & Gynct . February, 1952

LEVINE AND KURL AND

CASE 2.-C. L., aged 30 years, was first seen at the Gynecologi cal Endocrine Clini" on Aug. 22 , 1950, complaining .of secondary sterility of one year 's dura tion. Past History.-Her last delivery was five and one-half years ago. During her pro:· na tal and post natal period, she lived under adverse conditions. She developed pleurisy for which she was hospitalized for a period of six month·g. She was discharged completely r:u reil, an d r epeated chest plates were report ed negative. In 1947, up.on a rriving in this country, she had a ~ omp l ete examinatio n as well as chest plates which wer e all reported negative. C'Yfi~E I

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General physical examination was essentially negative and pelvic examination wa ~ normal except f or some tenderness in t he right fornix. Basal tempe rature readings were ~tarted on Oct . 3, 1950, and continued for th e next ten month s. The p rogr ess of this case can best be followed by the changes in the t emperat ure charts, which will give a more comprehensive picture of the progress made (Fig. 1) . Uterotubal insufflation performed on the ninth day of the firs t Oct ober cycle re vealed patency of the tubes. An endomet rial biopsy t aken on the twenty-second day r evealed t uberc ulous endometritis. During the second October cycle the patient was r eferred to the chest clinic for a complete survey. X -ray of the chest disclosed no evidence of pulmonary disease and the sputum was negative for tuberculosis. All extrapulmonary tests were reported negative for tuber culosis. It is interesting to note that, while a biphasic curve was obtained with basal tempera ture r eadings, the whole pat tern was aoove the b ase line of 98° F . F or the next.

Volume 63 Number 2

UNSUSPECTED TUBERCULOUS ENDOMETRITIS

423

three months (November and December, 1950, and January, 1951) the patient received 1 gram of streptomycin intramuscularly three times weekly, together with 12 Gm. of para-aminosalicylic acid daily, administered orally. After six weeks of therapy, a second endometrial biopsy was performed soon after the close of the December menses. A proliferative endometrium was obtained, but no tuberculous lesion was found. Guinea pig inoculation of the endometrial tissue failed to reveal any tubercle bacilli. During the course of treatment, the temperature curve still remained above the base line of 98° F., but it assumed a normal pattern soon after completion of therapy (February, 1951). A third biopsy taken at the end of this cycle failed to reveal any tuberculous le.sion. During the March and April periods, the patient was placed on a high caloric diet with vitamin supplements and the temperature curves observed. They remained at a normal level. At the end of the May cycle menstrual blood was cultured on Petragnani 's medium and sent for guinea pig inoculation according to the method of Halbrecht.l2 At the end of the June period, in lieu of a biopsy, we used Doyle's Nylon tampon method to recover endometrial tissue.1s Menstrual blood obtained daily was again sent for culture and guinea pig inoculation. These tests were repeated at subsequent menses. To date all reports have been negative for tuberculosis. The basal temperature readings have remained at a normal level.

Comment Case 1 was managed surgically because she presented an adnexal mass in addition to the positive biopsy. Preoperatively, a course of streptomycin was given as advocated by J:i'alls and associates. 14 Her postoperative course was smooth, and she was discharged on the twelfth postoperative day. This is in sharp contrast to the experience of Lahmann and Schwartz/ 5 who, before the advent of streptomycin therapy, reported an average hospital stay of 43.4 days in 15 cases of genital tuberculosis treated by surgery. Case 2 was treated medically as she presented no gross pelvic pathology_ It afforded us an opportunity to observe the effect of combined treatment with streptomycin and para-aminosalicylic acid. Before treatment the basal body temperature curve was entirely above the base line of 98° F. After treatment it assumed a normal pattern, and has continued as such up to the present time. While it is not positive proof of a cure, it may serve as a useful guide. Recovery of endometrial tissue containing the lesion is not always possible since it is focal in character, the remainder o:f the endometrium being clear. The negative biopsies obtained in this case must be interpreted in this light. A refinement in technique, therefore, would be serial biopsy whereby tissue is obtained from each surface of uterine cavity. 'fhe commonest method of detection of unsuspected tuberculous endometritis during infertility studies has been endometrial biopsies. Since repeated biopsies are not without danger, we sought other means of diagnosis. Halbrecht used menstrual blood taken daily during the menses. This was cultured on Petragnani medium and colonies obtained inoculated into guinea pigs. By this method he discovered latent tuberculosis in nine suspected cases whjch had negative endometrial biopsies. It also confirmed twelve other cases in which endometrial biopsies were positive. Doyle's nylon tampon is another means of avoiding the repeated use of the endometrial biopsy curette. An alkaline douche is used at the start of the menses. The tampon is inserted into the vagina and held in place with a special plastic spoon. The Nylon acts as a filter holding back the desquamated endometrial tissue, but allowing the fluid part of the menses to be absorbed by the cotton padding of the tampon. The latter is removed within twenty-four hours and the tissue recovered for study.

424

LEVINE AND KUR.LAND

Am.]. Obst. ll< Gy11ec Febru~ry,

l9S2

Streptomycin is the most reliab.le antibiotic· agent in the present-day treatment of tuberculosis. It is most effective in <·ases under medical care and as n preoperative therapeutic agent. Beeanse it is only haeteriostatic it should not be used where the lesion is inactive. 'l'he destructive nature of tuherculon" chan!!eR limits the arressihi1itv of this a!tent to the mieroor~;mnisms. Ohief•· tions" to prolonged st1·eptom;v~·in therapy" m·£>, first, the t~·JH1~ney to p!·ot(~wc drug resistant strains of the tubercle bacilli and, He<·ond, the development ol' neurotoxic side reactions. Lehmann, 16 in 1946,
Summary 1. Endometrial biopsy and cmettage have been the usual methods of detection of unsuspected tuberculous endometritis. Culture of menstrual blood mu.I the Nylon-tipped tampon may now be added to our armamentarium. 2. Five cases of latent tuberculous endometritis are herein reported. Two are discussed in detaiL 3. The effectiveness of streptomyc.in as a pre-operative agent is demonstrated in one of the cases. 4. The effectiveness of the combined use of streptomycin and para-aminosalicylic acid (PAS) is demonstrated in the second case reported. The effect is not only cumulative hut may even be synergistic with minimal side reactions. 5. This combined therapy may effect a eure in some cases of genital tuberculosis, heretofore not considered amenable to medical treatment. 6. Basal body temperature readings proved to be a valuable guide i11 (~valuating therapy and cure. The authors wish to express their appreciation to Dr. ,T, S. Beil!y and Dr. B. Diamond for permission to use their material in this report.

References 1.

2. 3. 4. 5. 6. 7. 8. 9. 10. l l. 12. 13. H. 15. 16. 17.

Sharman, A.: .T. Obst. & Gynaec. Brit. Emp. 5.1: 85, 1944. Halbrecht, I.: Steril. & Fertil. 2: 267, 1951. Rabau, E.: Steril. & Fertil. 1: 517, 1950. Sutherland, A. M.: J. Obst. & Gynaec. Bri.t. Emp. 50: 161, 1943. O'Brien, J. R., and Lawlor, M. K.: J. Obst. & Gynaec. Brit. Emp. 54: 636, 1947. Israel, 8. L., and Meranze, D. R.: Steril. & Fertil. 1: 523, 1950. Aranson, A., and Dwight, R. W.: New England J. Med. 240: 294, 1949. Schaupp, K. L.: West .T. Surg. 57: 243, 1949. Herring, J. S., and King, J. A.: AM. J. OBST. & GYNEC. 60: 925, 1950. Lubin, S., and Waltman, R.: AM. J. 0BST. & GYNEC. 60: 1176, 1950. Keettel, W. G.: AM. J. 0BST. & GYNEC. 61; 1382, 1951. Halbrecht, I.: .T. A. M. A. 142: 331, 1950. Doyle, J. B.: New England J. Med. 243: 121, 1050. Falls, F. H., Sered, H., and Zuma, B. P.: .T. A. 1\'L A. 142: 547, 1950. Lahmann, A. A., and Schwartz, S. F.: AM • •T. OBST. & GYNEC. W: 439, 1940. Lehmann, J.: Lancet 1: 15, 1946. Carr, A.: Proe. Staff Meet., Mayo Clin. 24: 213, 1949. 960

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STERI,ING PLACE PRESIDENT 8TREE1'