Background

Herpes zoster infections (HZIs) or, shingles are painful eruptions, usually unilateral, caused by the re-activation of varicella zoster virus (VZV) showing dermatomal distribution. Following primary varicella zoster virus (VZV) infection, VZV remains latent in the sensory nerve ganglion. The re-activation of the virus may take place years to decades after the primary infection of VZV (Kasahara et al., 2011). Herpes Zoster Infections (HZIs) are more common in people with reduced cell mediated immunity. This includes primarily the elderly people, patients undergoing cancer treatments, patients with chronic immuno-suppression, patients on prolonged drug therapies or, steroids and the ones with HIV and lymphoma etc (Greenberg et al., 2003; Wareham et al., 2007; Handa et al., 2016). The infection commonly presents with prodrome of dermatomal pain that precedes the appearance of the characteristic unilateral eruptions characterized by the presence of crops of vesicles in the skin and mucosa which are unilaterally and linearly distributed alongside the distribution of the affected nerve (Schmader et al., 2011). The most commonly affected dermatomes are the thoraco/lumbar (45%), cervical (23%) and trigeminal (15%) (Cohrs et al., 2004). Post-herpetic neuralgia (PHN) is the most debilitating complication of VZV infections (Wadhawan et al., 2015). The pain associated with herpes zoster can be devastating with a serious impact on the quality of life (QOL) of the affected patients (Schmader et al., 2011). Managing the disease and prevention of serious complications represents an important burden on both the health care providers and the society leading to long-term and/or, permanent morbidities in the affected patients. Re-activation of infection is infrequent in younger people and children (Wadhawan et al., 2015). Herewith, we are reporting cases of herpes zoster infections (HZIs) involving the maxillary division of trigeminal nerve (V2) showing manifestations in the middle third of face and oral cavity in the affected patients.

1 Case Series

1.1 Case 1

A 28 years old female patient came with the chief complaint of pain in the upper jaw in left side since two days and discomfort in taking food (Figure 1a). The patient revealed a history of appearance of 3-4 vesicles two days back on the hard palate following their rupture to form ulcer which were associated with pain. The pain as reported by the patient was severe in nature in the upper jaw and was not localized and attended with fever three days back. Intra-oral examination revealed multiple ulcers in an erythematous background in relation to left side of the hard palate not crossing midline. Based on the above findings, a provisional diagnosis of herpes zoster infection (HZI) of left maxillary division of trigeminal nerve (V2) was considered. The patient was prescribed Acyclovir 800mg 5 times a day for 7 days and kept on follow-up. After 7 days, the patient reported with resolution of the lesions with minor erythema that was asymptomatic. The patient was prescribed Acyclovir 1% for topical applications in the affected region till complete resolution of the erythema and to report in case of any symptoms (Figure 1b). After 4 days, the patient reported with complete resolution of the lesions (Figure 1c).

1.2 Case 2

Another 23 years old female patient reported with the chief complaint of ulcers on right side of the palate since two days (Figure 2a). The patient gave history of pain in right side of the palate since seven days which got aggravated since last three days. The pain was continuous but not severe and attended with discomfort and pain in the right eye since three days. There was no history of fever and malaise. There was no evidence of any vesiculation or, ulceration extra-orally. On intra-oral examination, multiple small ulcers, approximately 8-10 in number, were observed on the right side of the palate with a unilateral arrangement in linear pattern. The ulcers were irregular in shape extending anteriorly in the palatal rugae region towards the mid of the hard palate posteriorly and from the midline of the palate medially extending to the interdental gingiva in relation to teeth #13, 14 and 15 laterally. No such lesions were observed anywhere else in oral cavity. Based on the abovementioned clinical findings, a provisional diagnosis of herpes zoster infection (HZI) of right maxillary division of trigeminal nerve (V2) was considered. The patient was prescribed Acyclovir 600 mg 5 times a day for 7 days and kept on follow-up. The patient was, then, prescribed Acyclovir 1% for topical applications in the affected region till complete resolution of the erythema (Figure 2b). After 2 days, the patient reported with complete recovery (Figure 2c).

1.3 Case 3

A 65 years old female patient reported with the chief complaint of pain and swelling in the right upper and middle third of face along with burning sensation in the oral cavity since five days (Figure 3a). The pain was severe and throbbing in nature. There was history of multiple small vesicular eruptions on nose, middle third of face and upper lip on the right side since two days which were painful. The patient, also, presented with extra-oral swelling in the right upper and middle third of face involving right eye, right ala of nose and upper lip. The eruptions were limited to right side only. A slight redness involving the right eye was, also, observed. On palpation, the overlying skin was tender. On intra-oral examination, multiple crops of irregular, small, shallow ulcers arranged in a linear distribution and associated with an erythematous patch were observed on right side of the hard palate, not crossing the midline, and extending from the posterior third of hard palate towards the soft palate posteriorly and from the midline of the palate medially (along the line of mid palatine raphe) to around 1cm away from the interdental gingiva in relation to teeth #16, 17 (Figure 3b). There was, also, observed slight swelling on right side of the hard palate. There was no evidence of vesiculation or, ulceration anywhere else extra-or, intra-orally. Based on the above mentioned cardinal features of unilateral pain and eruptions involving one side of the face and unilateral intra-oral involvement, a provisional diagnosis of herpes zoster infection (HZI) of right maxillary (V2) division of trigeminal nerve was considered. The patient was immediately prescribed Acyclovir 800 mg 5 times a day for 7 days and follow-up appointment was scheduled after 5 days (Figure 3c). After 5 days, the patient reported with complete resolution of the extra-oral lesions while in the next follow-up appointment after 2 days, the patient reported with almost complete resolution of the intra-oral lesions with minor erythema that was reported to be asymptomatic (Figure 3d). The patient was prescribed Acyclovir 1% for topical applications in the affected region till complete resolution of the erythema and to report in case of any symptoms. After 2 more days, the patient reported with complete resolution of the lesions (Figure 3e).

2 Discussion

Herpes zoster infections (HZIs) or, shingles are unilateral eruptions caused by the re-activation of varicella zoster virus (VZV) showing dermatomal distribution. It is a DNA virus with the primary infection caused being chickenpox and recurrent infection resulting in herpes zoster infections (HZIs) (Katz et al., 1989). The virus after the primary infection may remain in a dormant state in the body, usually, in the dorsal root ganglion of peripheral nerves that control sensation. In one out of five patients previously infected with chickenpox, the virus gets re-activated, often after years or, decades of the primary infection and then, causes shingles resulting in inflammation in the dorsal root ganglia and/or, extra-medullary cranial nerve ganglia (Wadhawan et al., 2015). The prevalence of herpes zoster increases with advancing age and there is observed a marked increase in its incidence with aging (Schmader et al., 2011). The reason behind this is attributed to age-related diminished virus-specific and cell-mediated immunity (Thomas and Hall, 1987; Johnson and Dworkin, 2003). Under certain circumstances (predisposing factors) including emotional stress, immuno-suppression, cancer therapy (chemotherapy and radiotherapy), HIV infection, underlying malignancy, immunosuppressant drugs and dental manipulations, the virus gets re-activated and causes shingles. The disease is more common in adult life and affects males and females in equal frequency. The disease process can be grouped into three phases as 1) Prodrome, 2) Acute, and 3) Chronic phases. Herpes zoster infection (HZI) usually starts with a deep aching or, burning pain (Neville et al., 2009). The prodrome begins 2-4 days before the appearance of the muco-cutaneous rashes or, vesicles. The presentation of prodromal pain is dermatomic in nature and may be associated with fever, malaise and headache (Neville et al., 2009; Wadhawan et al., 2015). Thoraco/lumbar dermatomes are the most commonly affected sites in herpes zoster infections (HZIs) and account for 50% to 70% of the cases reported; followed by followed by cervical and trigeminal and sacral dermatomes (Schmader et al., 2011; Cohrs et al., 2004). The prodromal pain might show variations, such as, cases without painful prodromes typically show occurrence of pain at the first onset of rashes or, shortly afterwards (Schmader et al., 2011). The acute phase begins as the involved area develops clustered vesicles in a dermatomal pattern which are unilateral and usually follow a linear fashion alongside the affected nerve. This acute herpes zoster pain gradually resolves before or, shortly after the rashes heal. Within a period of 3-4 days, the vesicles become pustular and ulcerate followed by formation of scab usually in 7-10 days, although, it might take around 2-3 weeks for the lesions to go for complete resolution in otherwise healthy patients (Neville et al., 2009). The disease is not infectious in the chronic phase, especially, after the development of scab. After complete healing ensues, scarring with areas of hypo-pigmentation or, hyper-pigmentation can be seen. Occasionally, dermatomal pain of herpes zoster infections (HZIs) might occur without appearance of rashes being referred to as zoster sine herpete. It is difficult to identify this condition due to absent obvious clinical signs (Kasahara et al., 2011). Oral lesions occur with trigeminal nerve involvement. Ophthalmic division (V1) of the trigeminal nerve is most often affected being called as herpes zoster ophthalmicus with the common signs being lesions on upper eyelid, forehead and scalp. The common attending symptoms may comprise conjunctivitis, keratitis, uveitis and optic nerve palsies causing chronic ocular inflammation, loss of vision and debilitating pain. The maxillary division (V2) of trigeminal nerve leads to formation of vesicles on hard palate and/or, buccal gingiva on one side which is preceded by prodrome. Involvement of the mandibular division (V3) results in formation of vesicles and ulcers on mandibular gingivae and tongue. Ulcers are 1-5mm in size and often, coalesce to form larger ulcers with scalloped borders (Greenberg et al., 2003). The most common and debilitating complication of herpes zoster infections (HZIs) is post-herpetic neuralgia (PHN) which is characterized by pain that persists for almost 3 months after the initial presentation of the rash. Pain is severe, burning, throbbing, aching, itching and often, elicits on light touch. Most of the post-herpetic neuralgias (PHNs) resolve within 1 year with half of the patients experiencing resolution in the first 2 months after resolution of the lesions. Incidence of post-herpetic neuralgias (PHNs) is upto 50% in patients above 60 years of age (Neville et al., 2009). There are 4 independent predictors for post-herpetic neuralgias (PHNs): old age, severe acute pain, severe rash and a shorter duration of rash before consultation indicating more severity of the lesions (Johnson and Dworkin, 2003). An uncommon complication called James Ramsay Hunt syndrome results due to the virus spreading from the facial nerve to the vestibulo-cochlear nerve. It is, also, known as Herpes zoster oticus. The syndrome clinically manifests as facial paralysis, pain in external acoustic meatus (EAM), pinna and vesicles of external ear attended with loss of taste sensation in the anterior 2/3^rd of the tongue, tinnitus, vertigo (Jan et al., 2006). Diagnosis of herpes zoster infections (HZIs) can often be made from clinical presentation because of its unique unilateral distribution of the lesions (Wareham et al., 2007; Wadhawan et al., 2015). Other procedures may be necessary in atypical cases such as zoster sine herpete characterized by severe pain without any evidence of vesicular eruptions (Wadhawan et al., 2015). Identification of the virus in the cell culture of human fibroblasts is still the best diagnostic modality which reveals multinucleated epithelial cells, although, it takes 24 hours for the concluding statement and does not distinguish between herpes simplex virus (HSV) and varicella zoster virus (VZV). The other methods with higher sensitivity and rapid diagnosis are direct immuno-fluorescence antibody detection against varicella zoster virus (VZV). This technique gives positive results in upto 80% of the cases. Polymerase chain reaction (PCR) detects viral antigen (Neville et al., 2009; Wadhawan et al., 2015). In recurrent cases, increased IgM levels are detectable in serum ten days after the appearance of the vesicles and increased IgG and IgA four days after the vesicles. The treatment of acute herpes zoster infections (HZIs) in younger, healthy patients is generally limited to symptomatic therapy. However, in elderly or, immuno-compromised patients, an early, aggressive therapy is indicated (Katz et al., 1989). There are non-invasive approaches that include the use of anti-viral agents, systemic steroids, analgesics, anti-depressants and topical treatment modalities (Katz et al., 1989). Acyclovir, valacyclovir, famciclovir or, brivudin are the agents administered systemically (Katz et al., 1989; Johnson and Dworkin, 2003; Wadhawan et al., 2015). Systemic steroids, also, have been reported to decrease the incidence as well as the severity of pain during the first few weeks of treatment (Katz et al., 1989). There are no promising evidences, although, regarding the reduction in risk of developing post-herpetic neuralgias (PHNs) as one of the most dreaded complication with either anti-viral agents and/or, systemic steroids (Johnson and Dworkin, 2003; Opstelten et al., 2008).

3 Conclusion

Post-herpetic neuralgia (PHN) is the most dreaded complication of herpes zoster infections (HZIs). The incidence of HZIs and PHN increases with increasing age of the patients. An early diagnosis of HZIs, thus, becomes mandatory in decreasing the risk of PHN as well as decreasing the duration and severity and in early resolution of the lesions.

References

Cohrs R.J., Gilden D.H., and Mahalingam R., 2004, Varicella zoster virus latency, neurological diseaseand experimental models: An update, Frontiers in Bioscience, 9: 751-762

https://doi.org/10.2741/1275

PMid:14766405

Greenberg M.S., Michael G., and Ship J.A., 2003, Burket's Oral Medicine, 11^thed, pp.46-49

Handa H., Dara B.G., Naidu G.S., and Deshpande A., 2016, Zoster and its lurking shadow, Journal of Indian Academy of Oral Medicine and Radiology, 28: 337-341

https://doi.org/10.4103/0972-1363.195652

Johnson R.W., and Dworkin R.H., 2003, Treatment of herpes zoster and post-herpetic neuralgia, British Medical Journal, 326: 748-750

https://doi.org/10.1136/bmj.326.7392.748

PMid:12676845 PMCid:PMC1125653

Jan A.M., Mc Guire T.P., Clokie C.M., and Sándor G.K., 2006, Unilateral facial swelling caused by Ramsay Hunt syndrome resembles odontogenic infection, Canadian Dental Association, 72: 829-832

Katz J.A., Phero J.C., and McDonald J.S., 1989, Herpes Zoster Management, Anesthesia Progress, 36: 35-40

Kasahara M., Ichinohe T., Sano T., Fukuda K., and Kaneko Y., 2011,Acaseofzoster sine herpete of the trigeminal nerve, The Bulletin of Tokyo Dental College, 52: 47-51

https://doi.org/10.2209/tdcpublication.52.47

PMid:21467781

Neville B.W., Damm D.D., Allen C.M., and Bouquot J.E., 2009, Oral and Maxillofacial Pathology, 3^rded, pp.250-253

Opstelten W., Eekhof J., Neven A.K., and Verheij T., 2008, Treatment of herpes zoster: Clinical review, 54: 373-377

Schmader K.E., and Dworkin R.H., 2011, Herpes Zoster and Post-herpetic Neuralgia. In. Essentials of Pain Medicine. 3^rded, pp.358-364

Thomas S.L., and Hall A.J., 1987, What does epidemiology tell us about risk factors for herpes zoster? British Journal of Ophthalmology, 71: 806-809

Wadhawan R., Luthra K., Reddy Y., Singh M., Jha J., and Solanki G., 2015, Herpes zoster of right maxillary division of trigeminal nerve along with oral manifestations in a 46 year old male, International Journal of Advanced Biological Research, 5: 281-284

Wareham D.W., and Breuer J., 2007, Clinical review: Herpes zoster. British Medical Journal, 334: 1211-1215

https://doi.org/10.1136/bmj.39206.571042.AE

PMid:17556477 PMCid:PMC1889999