Coccidioidomycosis complicating pregnancy

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Coccidioidomycosis complicating pregnancy MICHAEL

J. McCOY, M.D.,

CAPTAIN (MC) USA JOHN F. ELLENBERG, M.D., CAPTAIN (MC) USA ALLEN P. KILLAM, M.D., COLONEL

(MC) USA

(RET.)

Department of Obstetrics and Gynecology, WiUiam Beaumont Army Medical Center, El Paso, Texas INCREASED SEVERITY of infections such as coccidioidomycosis, herpes, and influenza and the likelihood of dissemination during pregnancy (especially in the third trimester) is thought to be due to the depressed immune status associated with pregnancy. The treatment of pregnant patients with toxic medications is hazardous but may be necessary if the disease has a higher potential risk.

A 28-year-old woman, gravida 3, para 2, was admitted at 27 weeks' estimated gestation, complaining of right upper quadrant pain, nausea, and vomiting. Physical examination on admission revealed a temperature of 37.6° C and marked right upper quadrant abdominal direct and rebound tenderness. Fundal height was 27 em and fetal heart tones were present. Initial white blood cell count was 14,000/cu min, with 75% polymorphonuclear leukocytes, 17% bands, and 1% eosinophils. A chest x-ray film showed right costophrenic angle blunting. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Reprint requests: Captain Michael J. McCoy, MC, Department of Obstetrics and Gynecology, William Beaumont Army Medical Center, El Paso, Texas 79920.

Exploratory laparotomy for suspected appendicitis revealed no pathologic condition. Postoperatively, decreased breath sounds were noted and chest films confirmed im:reasing consolidation and effusion in the left lower lung. Thoracocentesis was performed. Pleural biopsies grew Coccidioide-1 immit~1. Serum complement fixation (CF) titers were 1: 4. Skin tests were nonreactive with 1: 100 and I: 10,000 dilutions of coccidioidin, while a Candida control skin test was positive. In view of the titer, an increased eosinophil count to 10%, and a rapidly reaccumulating pleural effusion, the patient was begun on a regimen of intravenous amphotericin B at 32 weeks' gestation, the final dosage regimen being 0.6 mg/kg every other dav. Serial amniocenteses beginning at !~31;2 weeks' gestation were performed by means of real-time sonography and yielded immature lecithin/sphingomyelin (LIS) ratios. In an effort to hasten fetal lung maturity, SoluCortef (500 mg every 8 hours for 4 doses) was given and delivery was planned as soon as the infant was mature. Good fetal renal output by fetal bladder filling times was demonstrated by sonography, allaying fears of fetal renal damage while definite maternal renal impairment existed. The fetal antenatal course was monitored with nonstress tests twice each week until 37 weeks. Thereafter, oxytocin challenge tests (OCT) were performed weekly, as it was felt this test was a more reliable indication of fetal well-being. During an OCT at 42 weeks, spontaneous amniorrhexis occurred, with the subsequent uncomplicated vacuum extraction of a 3,189 gram male infant with Apgar scores of 8 and 9. The patient received postpartum amphotericin B therapy for l week to complete a 10-week course. The pleural effusion markedly improved by the time of discharge. Coccidioidin skin tests remained negative until2 months postpartum, when a 7 mm reaction was noted. Neonatal outcome was excellent, with no neurological or renal impairment noted at 8 months of age. Amphotericin B levels were determined during the treatment course (Table 1). Trough levels determined immediately prior to infusion and peak levels 1 hour after infusion were comparable to those of nonpregnant female subjects.

Coccidioidomycosis is usually a benign fungal infection with little effect on pregnancy without dissemina-

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740 Communications in brief Am.

Table I. Levels of amphotericin B in maternal blood, fetal cord blood, and amniotic fluid Amphotericin B levels (meg lml) * Maternal blood Trough

9/28 9/30 11/1 11/20 (delivery) 11/24

0.08 0.32 0.60

I

Peak

0.64 2.60 2.60

Fetal cord blood (arterial)

Amniotic fluid

J

J•d1 I''· l\lHO Ob.>teL ( ;ill<'c·ol

course in adequate therapeutic doses. This case. unique in that coccidioidomycosis has not been reported to present in pregnancy as a pleural effusion. furnished the first simultaneous amniotic fluid and maternal and fetal blood amphotericin B levels and represents our management of a relatively rare disease complicating pregnancy. REFERENCES

2.60

0.08

5.10

*The minimum inhibitory serum concentration is reported to be 0.5 mcg/ml in the nonpregnant state. tion. Many factors interact in assigning a risk of dissemination. Low CF titers are related to uncomplicated courses, with significant increases in titers occurring in patients with pleural effusions without subsequent dissemination. Anergy may be associated with increased risk of dissemination in coccidioidal pleural effusion, 1 and peripheral eosinophilia (greater than 5%) may rise in accompaniment with progression and/or dissemination. The predisposition to systemic involvement increases in pregnancy, with concomitantly higher risks as the pregnancy progresses. In the pre-amphotericin B era, 90% of pregnant patients with dissemination died (and 90% of third-trimester coccidioides disseminated), compared to only a 50% mortality rate in the nonpregnant state. 2 Some consultants recommended termination of the pregnancy at 28 to 32 weeks because of the risk of fatal dissemination. Prophylactic treatment with amphotericin B has been condemned. Aggressive intervention at the earliest indication of dissemination and careful monitoring for toxicity related to amphotericin B therapy allowed the delivery of a healthy infant. Use of alternate-day administration of amphotericin B reduced the maternal toxicity. The effect on the fetus was unknown, but no signs of permanent renal damage have appeared in the infant. Simultaneous maternal and fetal blood levels of amphotericin B had not been previously established to aid in determining relative fetal exposure to the drug, nor has fetal response to amphotericin B, in terms of organ maturity, vulnerability, and metabolism, been established. Short-term, low-dose corticosteroids have not been shown to significantly increase the risk of dis· semination and were used to enhance fetal lung maturity. The effect of amphotericin B on lung maturity is unknown and the LIS ratio of this infant remained immature late in pregnancy. The high risk of maternal death and fetal wastage in disseminated coccidioidomycosis compels aggressive management. Amphotericin B. a potentially toxic drug, may allow maternal and fetal salvage in a previously highly fatal systemic illness if given early in the

I. Lonky, S. A., et al.: Acute coccidioidal pleural effusion, Am. Rev. Respir. Dis. 114:681, 1976. 2. Smale, L E., and Waechter, K. G.: Dissemination of coccidioidomycosis in pregnancy, AM. ]. OssTET. GYNECOL. 107:356, 1970.

Chorea associated with oral contraceptive therapy DOUGLAS J. DOVE, M.D. Departments of Pediatrics and Neurology, Southern Illinois

University School

of Medicim, Springfield, Illinois

THE ASSOCIATION between chorea and oral contraceptives was described by Fernando and Chii· 1 in 1966. Since then 23 cases have been described, mostly in the British literature. 1- 13 The purpose of this report is to further emphasize this association. A 20-year-old white woman was seen for evaluation of a movement disorder manifested by irregular uncontrollable movements of the face, tongue, and upper and lower extremities, which had been present for 5 weeks. She also noted slurred speech and unsteady gait and frequently was "dropping things." Since the initial symptoms, she had consulted four physicians, including a neurosurgeon, who failed to tee• ognize the reason for her difficulty. The following laboratory examinations had been performed: throat culture, negative; erythrocyte sedimentation rate (ESR), 22 mm/ hour; antistreptolysin 0 (ASO) titer, 166 Todd units; and complete blood count, normal. Treatment with diazepam and with propranolol had been ineffective. Her past history revealed that at age 11 years she had had a febrile, arthritic illness, diagnosed as rheumatic fever without chorea. Prophylactic penicillin therapy was given until she was 14 years of age. At the age of 17, the patient was started on the oral contraceptive agent Norinyl 1-80 (norethindrone plus mestranol) following the birth of her first child. Three months later she was hospitalized for uncontrollable movements resulting in slurred speech, unsteady gait, and extreme "nervousness." Concomitantly she had pharyngitis, a cardiac murmur, and a fine generalized macular rash noted over the medial aspects of both upper extremities. Skull radiographs and brain scan were negative. Serial ASO titers were 166, 250, Reprint requests: Dr. Douglas]. Dove, P.O. Box 3926, Department of Pediatrics, Springfield, Illinois 62708. 0002-9378/80/140740+03$00.30/0

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1980 The C. V. Mosby Co.