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Recurrence of Herpes Simplex Virus Blepharitis After Cesarean Section and Epidural Morphine Christopher F. James, MD Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida N umerous case reports and a few studies have After magnesium sulfate was administered as a 4-g bolus associated the recurrence of oral herpes simplex followed by a 2-g/h infusion, the patient underwent epi- virus (HSV) infections involving the third divi- dural anesthesia and cesarean section. Epidural lidocaine 2% with epinephrine (1:200,000) in divided doses for a total of sion of the trigeminal nerve with epidural or spinal 18 mL was administered; epidural fentanyl, 100 pg, was opiates, especially morphine (l-8). Two recent pro- added prior to incision. The patient tolerated the procedure spective studies, however, had conflicting results: In well, and the l- and 5-min Apgar scores for the neonate were one, the effects of neuraxial morphine and parenteral both 9. Prophylactic cefazolin, 2 g, was administered intra- opioids did not differ significantly (9). In the other, the venously. Toward the end of the procedure, epidural mor- incidence of HSV was 11 times higher with epidural phine, 3.5 mg, was administered for postoperative pain con- morphine than with parenteral morphine (10). Fur- trol. The next morning, approximately 18 h after epidural morphine had been administered, the patient had mild facial thermore, two large retrospective reports also had pruritus of unknown duration that did not require treat- conflicting results: The incidence of HSV was zero ment. At that time, the patient was not aware of itching, only with intrathecal morphine (0.2 mg) in one (11) and that she was rubbing her face. The pruritus was not localized 3.5% with epidural morphine in the other (12). Despite to any one side or area.A second dose of epidural morphine, the reported cases of oral HSV infection, however, 3 mg, was administered 24 h after the first dose, and the there have been no reported cases of recurrent HSV epidural catheter was removed. The patient reported no itching or any other side effects on the second postoperative blepharitis involving the first and second divisions of day. She was pain free until 30 h after the second dose of the trigeminal nerve without third division involve- epidural morphine, when she complained of abdominal ment after epidural morphine. This report describes a cramping and mild incisional pain, which was treated with parturient who experienced recurrent HSV blepharitis ibuprofen, 600 mg orally. three days after surgery and two days after the second Three days after surgery and 2 days after the second dose dose of epidural morphine for pain control after ce- of epidural morphine, the patient developed right-sided sarean section. vesicular lesions involving the lower eyelid, the upper cheek area, and the area lateral to the lateral palpebral fissure; early erythematous lesions of the upper eyelid; and injected Case Report A 28-yr-old woman, gravida 1 para 0, at 39 wk gestation was admitted for cesarean section. On the day of admission, she had an acute increase in blood pressure of 140/95 mm Hg and a routine positive contraction stress test with an unfa- vorable cervix (closed and ~30% effacement). During a clinic visit 3 days earlier, her blood pressure was 130/80 mm Hg. During gestation, her blood pressure ranged from 120 to 130 systolic mm Hg and 70 to 82 mm Hg diastolic. Except for gestational diabetes mellitus, which was diet controlled, the patient had a benign gestational course up to the day of admission. Her medical history was unremarkable except for pilonidal cyst removal at 15 yr of age and right-sided periorbital cellulitis of unknown origin that was treated with antibiotics at 24 yr of age. Accepted for publication January 26, 1996. Figure 1. Photograph of early erythematous (A) and vesicular (B) Address correspondence to Editorial Office, Department of An- lesions of a herpes simplex virus infection that developed 3 days esthesiology, University of Florida College of Medicine, Box 100254, after surgery and 2 days after the second dose of epidural morphine Gainesville, EL 32610-0254. administered for pain control after cesarean section. 01996 by the International Anesthesia Research Society 10% An&h Anal8 1996;82:1094-6 0003-2999/96/$5.00 ANESTH ANALG CASE REPORTS 1095 1996;82:10944 Table 1. Reports of the Incidence of Herpes Simplex Virus (HSV) After Neuraxial Morphine Compared with After Parenteral dpioids Incidence of HSV (% [total n in group]) Year of Population Neuraxial morphine Parenteral opioids Neuraxial Parenteral report size (n) (route, dose) (drug, route, dose) morphine opioids 1987 (1) 44 Epidural, 5 mg initially Morphine, IM, 10 mg every 34.6 (26) 0 (18) and 3-5 mg repeated 6 h as needed 1988 (2) Retrospective 291 Epidural, 4-5 mg Unknown 9.7 (134) 0.6 (157) Prospective 729 Epidural, 4-5 mg Unknown 4.9 (146) 0.5 (583) 1990 (3) 187 Epidural, 4-5 mg Meperidine, IM, 50-100 mg, 14.6(96) 0 (91) or morphine, IM, 7.5-10 mg 1994 (9) 357 Epidural, 3-5 mg, or Unknown 3.5 (201) 2.6 (156) spinal, 0.15-0.25mg 1995 (10) 811 Epidural, dose Morphine, IV or IM, dose 5.2 (425) 0.5 (386) unknown unknown IM, intramuscular; IV, intravenous. conjunctiva of the right eye (Figure 1). Out of concernfor eye one of many contributing factors (such as the hor- involvement, an ophthalmologic consultation was obtained. monal effects of pregnancy, immunosuppression, and The diagnosisof recurrent HSV infection was confirmed by stress of the procedure), is not clear. Many have at- Tzanck smear.The patient reported having suffered a HSV infection of the right upper eyelid and cheek2 yr earlier after tempted to associate pruritus, a common side effect of excessiveexposure to sunlight. At that time, the lesionshad neuraxial opiates (especially morphine), with the sub- been confined to the upper eyelid and upper cheek. During sequent development of HSV (l-3,8,9). Opioid-related the most recent infection, the conjunctiva was cultured and pruritus can be generalized or can be localized-either found not to be infected and the cornea was clear. Trifluri- to the dermatome where the injection was adminis- dine 1% was administered as drops to the eyes, and acyclo- vir ointment was used to treat the affected skin. The patient tered or, more commonly, to the facial region, proba- was discharged from the hospital the next day. A follow-up bly involving the trigeminal ganglion (15,16). Except ophthalmologic examination revealed that her lesionshad for two studies reporting no correlation between oral resolved. lesions and either generalized or facial pruritus (9,10), most studies report that the majority of women who experience recurrent HSV infection complain of facial Discussion itching. Extensive facial pruritus may cause significant Recurrent HSV infection can be exacerbated by exog- skin trauma, which, in turn, may incite recurrent HSV enous factors, such as sunlight, wind, trauma, and lesions. However, because pruritus and a burning fever, or by endogenous sources related to physiologic pain are classic prodromes to erythema and subse- states, such as stress. Although not necessarily causal, quent grouped vesicular eruptions, pruritus could recurrent HSV infection has followed the use of also just be an early manifestation of HSV reactivation neuraxial opiates for analgesia after cesarean section and not an inciting factor. (l-8,10,12). In most cases, epidural and spinal mor- This report describes a term pregnant patient who phine were used, but epidural fentanyl (7) and spinal had recurrent HSV blepharitis three days after sur- meperidine (5) have also been implicated. gery. Unlike those in other reports, this patient man- Up to 40%-50% of the US population may suffer ifested recurrent HSV in the first and second divisions recurrent HSV infections (13). Moreover, in one study of the trigeminal nerve alone (ophthalmic and maxil- of women with a history of HSV infection from the lary), as opposed to the more typical third division fifth month of gestation until delivery, up to 84% had (mandibular). Extension of HSV lesions to the nose a documented recurrence during pregnancy (14), and infraorbital areas from preexisting and more typ- which renders the association between neuraxial opi- ical oral lesions has been mentioned (3,8). The other ates and recurrent infection during this period more possible contributing factor in this case was that the suspect. patient received two separate doses of epidural mor- The incidence of recurrent HSV infection has been phine totaling 6.5 mg. Most of the other reports also compared between those who did and did not have involved large doses of neuraxial opioids (1,4-7). In epidural or spinal opiates (Table 1). Whether neuraxial the original study, there was a 34.6% incidence of HSV morphine and other opiates are the main cause of in patients receiving multiple doses of epidural mor- recurrent HSV infection after cesarean section, or just phine (1). Whether this large dose had any bearing on 1096 CASE REPORTS ANESTH ANALG 1996;82:1094-6 the present case is uncertain. Although epidural mor- 6. Pennant JH, Wallace D. Intrathecal morphine and reactivation of oral herpes simplex [correspondence]. Anesthesiology 1991; phine and reactivation of HSV appeared to be associ- 75:167. ated in this case, it is unclear whether the relationship 7. Valley MA, Bourke DL, McKenzie AM. Recurrence of thoracic was causal. Unfortunately, the information about the and labial herpes simplex virus infection in a patient receiving patient’s history of HSV was not obtained until after epidural fentanyl. Anesthesiology 1992;76:1056-7. 8. Douglas MJ, McMorland GH. Possible association of herpes the reactivation. simplex type I reactivation with epidural morphine administra- A history of HSV infection involving less common tion [correspondence]. Can J Anaesth 1987;34:426. areas should be viewed with more caution than peri- 9. Norris MC, Weiss J, Carney M, Leighton BL. The incidence of oral infections due to the potentially more harmful herpes simplex virus labialis after cesarean delivery. Int J Obstet Anesth 1994;3:127-31. sequelae of ophthalmic and central nervous system 10. Boyle RK. Herpes simplex labialis after epidural or parenteral manifestations, such as HSV keratoconjunctivitis and morphine: a randomized prospective trial in an Australian ob- meningitis (13,17). stetric population. Anesth Intensive Care 1995;23:433-7. 11. Abouleish E. Intrathecal morphine as a cause for herpes simplex should be scratched out [correspondence]. Anesthesiology 1991; 75:919. References 12. Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural 1. Gieraerts R, Navalgund A, Vaes L, et al. Increased incidence of morphine for analgesia after Caesarean section: a report of 4880 itching and herpes simplex in patients given epidural morphine patients. Can J Anaesth 1990;37:636-40. after cesarean section. Anesth Analg 1987;66:1321-4. 13. Fiumara NJ. Herpes simplex. Clin Dermatol 1989;7:23-36. 2. Crone LA, Conly JM, Clark KM, et al. Recurrent herpes simplex 14. Vontver LA, Hickok DE, Brown Z, et al. Recurrent genital virus labialis and the use of epidural morphine in obstetric herpes simplex virus infection in pregnancy: infant outcome patients. Anesth Analg 1988;67:318-23. and frequency of asymptomatic recurrences. Am J Obstet Gy- 3. Crone LA, Conly JM, Storgard C, et al. Herpes labialis in par- necol 1982;143:75-84. turients receiving epidural morphine following cesarean sec- 15. Scott PV, Fischer HBJ. Spinal opiate analgesia and facial tion. Anesthesiology 1990;73:208-13. pruritus: a neural theory. Postgrad Med J 1982;58:531-5. 4. Cardan E. Herpessimplex after spinal morphine [correspon- 16. Ballantyne JC, Loach AB, Carr DB. Itching after epidural and dencel. Anaesthesia 1984:39:1031. spinal opiates. Pain 1988;33:149-60. 5. Acalovschi I. Herpes simplex after spinal pethidine [correspon- 17. Beriault M. Herpes virus infections and intraspinal opioids [cor- dence]. Anaesthesia 1986;41:1271-2. respondence]. Anesthesiology 1991;74:199.
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