Recrudescent herpes labialis mimicking primary herpes labialis in pregnancy.

CONTEXT: Herpes simplex virus (HSV) infection is prevalent worldwide. Herpes labialis is caused predominantly by HSV-1, and herpes vulvo-vaginitis is caused predominantly by HSV-2. HSV-2 may result in significant morbidity and mortality for infected neonates exposed during delivery. Due to this fact, a large amount of literature exists for HSV-2 but data for HSV -1 is scanty. CASE REPORT: We report two cases of recrudescent herpes labialis in 3(rd) trimester of pregnancy with extensive peri-oral lesions resembling primary herpes labialis. There was no obvious cause of immunosupression. The patients were followed up with a normal outcome of pregnancy and no fetal abnormality.
CONCLUSIONS: The reasons for such extensive perioral lesions are uncertain. Immunosupression of pregnancy may be a factor in a sub group of patients.

Introduction

HSV (herpesvirus hominis) is subdivided into types 1(HSV-1) and 2(HSV-2), which have distinct but overlapping antigenic and epidemiologic patterns. HSV-1 mostly causes infections above the waist, and HSV-2 those below. The primary infection with both is usually mucosal but, even though the clinical lesions heal, the virus persists in sensory root ganglia, most frequently in the trigeminal (HSV-1) or the sacral (HSV-2) ganglia. The virus probably persists for life with periodic reactivation in the form of cold sores at the muco-cutaneous junctions of the face or as genital lesions. Virus may also be shed asymptomatically from mucosal surfaces on which there are no visible lesions[1]. Recurrent infections differ from primary infections in the smaller size of the vesicles and their close grouping, and in the usual absence of constitutional symptoms.

Two cases of extensive recrudescent herpes labialis are reported in pregnant females. Pregnancy is associated with decreased cell mediated immunity and this might be responsible for extensive mucocutaneous lesions of recrudescent herpes labialis.

Case Report

Case 1

A 26 year old primigravida of 34 weeks gestation was referred from the department of obstetrics to the department of Oral medicine in February 2007 with complaint of multiple perioral blisters associated with fever for the last 2 days. Examination revealed multiple, grouped vesicular lesions over the right angle of mouth and the vermilion border of both upper as well as lower lips. The oral mucosa was normal. Submandibular and cervical lymph nodes were enlarged. Opinion was taken from dermatologist. Routine investigations including Hb, TLC, DLC, Urine examination were normal. Tzanck smear showed multinucleated giant keratinocytes. ELISA for HIV was negative. On serological analysis at the time of presentation herpes simplex virus (HSV)-specific IgG and IgM were negative. Serum analysis on day 14 was positive for HSV-specific IgM only. There was history of 5-6 similar episodes in the past 2-3 years usually following a febrile illness. According to the patient slight pain preceeded lesions by 1-2 days. The lesions were not so severe in the previous episodes as in this episode. The lesions used to heal within 5-6 days without any residual scarring. The patient was diagnosed as case of recrudescent herpes labialis and given tab. Acyclovir 400 mg 5 times a day for 7 days. The lesions healed completely within 7-8 days.

The patient was put on regular follow up by her obstetrician. The spatient delivered at 40 weeks without any adverse outcome for the mother or the child. On follow up visits the child was in perfect physical and mental health.

Case 2

Another similar case, a 32 year old multigravida (G3,P2,L2) of 38 weeks gestation reported to the department of Dermatology in October 2009.The patient had fever, burning around the mouth along with blisters over both the angles of the lips as well as on the upper lip. Examination revealed multiple fluid filled lesions on an erythematous base over angles of mouth and the upper lip. Oral mucosa was normal. Submandibular lymph nodes were palpable. Cytological smear revealed typical features of herpetic infection i.e. multinucleated giant cells. Serological analysis demonstrated herpes simplex virus (HSV)-specific IgG at initial presentation while sera on 12th day exhibited HSV-specific IgG as well as IgM. Patient gave history of frequent episodes of similar lesions in the past but of lesser intensity usually following fever. The patient was offered Tab Acyclovir but she refused due to her pregnancy. The lesions healed completely within 10 days.

The patient underwent regular monitoring and gave birth to a normal healthy baby. The baby is normal on follow up visits.

Discussion

HSV-1 and HSV-2 are DNA viruses that belong to Alphaherpesvirinae, a subfamily of the Herpesviridae family. Both viruses, transmitted across epithelial mucosal cells as well as through skin interruptions, migrate to nerve tissues, where they persist in a latent state. HSV-1 predominates in oro-facial lesions and it is typically found in the trigeminal ganglia, whereas HSV-2 is most commonly found in the lumbo-sacral ganglia. Nevertheless these viruses can infect both oro- facial areas and the genital tract[2].

Literature on the subject of oral HSV infections in pregnancy is particularly scarce, probably because of relative rarity of oral HSV infection in pregnancy[3]. Brown et al[4] reported that two percent or more of susceptible women acquire HSV infection during pregnancy.

Herpetic gingivostomatitis and pharyngitis are most commonly associated with a primary HSV-1 infection. The symptoms of primary oral herpes may resemble those of aphthous stomatitis and include ulcerative lesions involving the hard and soft palate, tongue and buccal mucosa, as well as neighbouring facial areas.

By definition asymptomatic viral reactivation is regarded as a recurrence whereas an episode of viral reactivation that leads to clinical signs of herpetic disease is referred to as a recrudescence[5].

After initial HSV-1 infection of the oro-facial region, there are three well-recognized sequelae resulting from reactivation of HSV from latency, namely 1)Recrudescent herpes labialis, 2)Asymptomatic shedding of HSV-1 in saliva, and 3)Localised intraoral recrudescences. Christie et al[6] reported a fourth sequelae that of , recrudescent intraoral herpes simplex infection mimicking primary herpetic gingivostomatitis.

Reactivation of the virus from the primary infections involves the perioral area mainly the outer third of the lower lip. In patients with frequent recurrences, the lesion may differ slightly in location with each episode. Immunocompetent patients tend not to experience recurrent intraoral lesions. Prodormal symptoms precede herpes labialis in 45 to 60 percent episodes. Patients experience pain, burning or itching at the site of subsequent eruption[7].

Even in the immunocompetent patient, the severity of recurrent herpes labialis is extremely variable, and may vary from that of prodromal symptoms alone without the subsequent development of lesions (aborted episodes ), to extensive disease induced by severe local sunburn[7].

Following primary infection, humoral and cell mediated immune responses take place ,the latter being probably more important[8].

Sridama et al[9] found a significant decrease in the percentage and absolute number of T lymphocytes in the second and third trimesters of pregnancy. This decrease in total T cells may be explained by a decrease in the proportion and absolute number of helper T cells (T4+ cells) throughout pregnancy. This evidence supports the hypothesis of decreased cell mediated immune responsiveness during pregnancy and this mechanism may be important in non-rejection of the fetal allograft by the mother.

A decrease in T4+ cells may be a consequence of the hormonal changes associated with pregnancy. Human chorionic gonadotropin, estrogen, progesterone, corticosteroids, α-fetoprotein, prolactin and α-globulin have been shown to have immunosuppressive effects during in vitro studies[10].

In a large study of 3738 women of recrudescent herpes labialis prior to and during the first trimester of pregnancy, Scott et al[11] reported that 28.55% women had a history of RHL with reduced incidence during pregnancy. Those who had lesions during pregnancy experienced them at a higher monthly rate, than before pregnancy. According to them the common manifestation of RHL is an isolated oro-labial lesion with very distinctive clinical characteristics, often referred to as ‘cold sore’. They also reported that there was no relationship between a history of herpes simplex recrudescence either before or during pregnancy and adverse pregnancy outcome (miscarriage, pre-term delivery, or low birth weight).

In both of our cases, the lesions, although recrudescent, were more florid having extensive eruptions around the oral orifice as compared to the more common ‘cold sores’ reported by Scott et al[11]. The reasons for recrudescent herpes labialis with extensive muco-cutaneous lesions are unclear. We postulate that due to immune suppression of pregnancy the lesions of RHL may become more florid especially in 3rd trimester of pregnancy in a particular subset of patients. Although RHL in late pregnancy is unlikely to cause any adverse fetal outcome it may cause a fulminant disease mimicking primary herpes simplex. Further studies are required to identify the cause of such extensive lesions.