INTRODUCTION
Due to the lack of protective vaccines, both primary and recurrent disease related to infection with Herpes Simplex Virus types 1 and 2 (HSV-1, HSV-2) remain common, although the precise incidence and prevalence vary geographically and due to host factors (such as age, gender and immune status).1 HSV-1, in particular, appears to be quite ubiquitous worldwide, reaching about 40% seroprevalence by age 15 and subsequently rising to a seroprevalence of 60-90% among adults.2,3 The major therapeutic goals in HSV-1 therapy are to reduce the duration and symptomatology of acute primary or recurrent outbreaks, as well as to decrease the frequency of future recurrent episodes. Because acyclovir-resistant strains remain rare in immunocompetent hosts, oral and various formulations of topical acyclovir and its analogues (valacyclovir and famciclovir) form the mainstay of both chronic suppressive and episodic therapy.4 A relatively new muco-adhesive formulation of acyclovir was approved in 2013 for the treatment of recurrent oro-labial HSV-1 infections (“cold sores” or “fever blisters”; this agent delivers a single 50 mg acyclovir dose which decreases time to healing, increases the number of aborted attacks, and notably provides a decrease in future outbreaks, probably due to a diminution of herpes virus load in all reservoir sites.5,6 We report herein the successful off-label use of muco-adhesive acyclovir in the setting of an acute, severe episode of oro-labial HSV-1.
CASE REPORT
A 32-year-old Caucasian female presented with refractory constipation in June, 2012, which was ultimately found due to Stage IIA, moderately well-differentiated adenocarcinoma of the rectosigmoid. Pertinent past medical history included pan-colonic Crohn’s disease since high school age, managed with periodic infliximab infusions. Colon cancer treatment consisted of: pre-operative chemoradiotherapy, complete colectomy with ileo-anal anastomosis and J-pouch formation, as well as post-operative capecitabine chemotherapy. The anastomosis was reversed due to a perforated J-pouch during a colonoscopy that led to a septic intra-abdominal abscess. Three years later, the patient developed peristomal pyoderma gangrenosum and concomitant recurrent Crohn’s disease involving the residual J-pouch. She was initially placed an adalimumab, which was discontinued after approximately 8 months due to the rare development of alopecia areata. Although the peristomal pyoderma gangrenosum resolved, she continued to experience severe abdominal pain and cramping with rectal bleeding due to active Crohn’s disease affecting the J-pouch. She was subsequently treated with certolizumab. Despite the latter, the J-pouch continued as a source of symptomatic inflammation. She then underwent major abdomino-pelvic surgery to remove the J-pouch, convert her temporary ileostomy into a permanent one, remove the now non-functional rectum, lyse adhesions, and remove peri-ureteral scar tissue. Two days following an 11 hour surgical procedure, she developed multiple painful, vesiculo-bullous lesions on the soft and hard palate, gingiva, tongue, and lips (Figure 1). This was presumed to be herpetic gingivostomatitis likely precipitated by trauma from the endotracheal tube placed during her protracted surgery, and possibly worsened by recent certolizumab therapy. Tzanck smear of one lesion was positive for multinucleated giant and balloon cells; polymerase chain reaction analysis of vesicle fluid was positive for HSV-1.At this point, the patient could not consume a regular diet, could barely ingest soft/liquid food, and was having sleep disturbance due to oral discomfort. Due to the need for rapid relief of truly debilitating herpetic gingivostomatitis, administration of intravenous acyclovir was contemplated. However, the patient was unshakably insistent on avoiding yet another intravenous line. Thus, off-label use of muco-adhesive acyclovir 50 mg tablet was instituted. A single tablet was placed, as approved, on the upper canine fossa. This single tablet constituted monotherapy. No other topical or systemic antiviral was co-administered. The patient experienced remarkably rapid pain reduction and similarly rapid resolution of vesiculo-bullous lesions within five
