1. Viral infections
Asma El-Howati BDS, Mclin Oral Medicine

2. Objectives Be aware of the viruses which can cause oral lesions
Recognize the oral manifestations of viral infections
Understand how to manage these infections

3. Introduction
Viruses are vey small ( nm) obligate intracellular parasites that require host cells protein synthesising components
Many viruses have property of latency and reside in host asymptomatically
90% of adults have viruses acquired early in life

4. Introduction
Oral mucosa frequent location for primary viral infection and subsequent reactivation
Reactivation occurs during periods of immuno-compromization

5. Viral infections potentially involving oral mucosa
Herpes simplex type 1 (HSV1)
Herpes simplex type 2 (HSV2)
Varicella zoster virus (VZV)
Epstein-Barr virus (EBV)
Human Cytomegalovirus (HCMV)
Coxsackie viruses
Other human herpes viruses eg; HHV8 (HHV)
Human papilloma virus (HPV)
HIV

6. HSV1 and HSV2 HSV1: most herpetic infection above the belt
Primary herpetic gingivostomatitis
Virus lies dormant in dorsal root ganglion
reactivation –herpetic labialis
Reactivation triggered by: sunlight, trauma, immunosuppression
HSV2: herpetic infections below the belt are mainly caused by this type and cause ano-genital herpes

7. HSV infection
Endemic
By age 12 years 40% of children have HSV1 antibody
By age 60 years, 90% have HSV 1 antibody
Decreasing numbers with increasing prosperity
Infection maybe sub clinical (teething) or florid (up 10%)
Maybe sign of immunosuppression

8. Primary herpetic gingivostomatitis
Caused by HSV1 or 2 and spread by saliva
Clinical features
Incubation period 4-7 days
Primary infection; intra epithelial vesicles
Multiple herpetic mouth ulcers
Diffuse gingivitis
Cervical lympadenitis
Fever
Malaise, irritability and fever

10. Natural history Prodromal symptoms of fever and malaise
Vesicles 2-3 mm on keratinised tissue only
Rupture leaving painful ulcers which heal 7-10 days
Lip erosions, lymphadenopathy, pharyngotonsillitis present in severe cases
Infection usually in childhood, but an increasing number are being encountered in young adults

11. How would you manage primary HSV?
Basic principles
Specific treatment

12. Management of primary HSV
Usually clinical diagnosis
Large numbers of virions in ulcers and saliva
Viral culture, electron microscopy
serology
PCR- raising titre of antibody is confirmatory
Treatment largely supportive
Antiviral therapy if severe

13. Management of primary HSV
Reassurance and advise on nature of disease
Limit contact with lips and mouth
Antiseptic mouthwash to prevent secondary bacterial infection(chlorahexidine MW)
Encourage fluid intake (dehydration state)
Simple analgesics, antipyretic (paracetamol, ibuprofen)
Admission sometimes required if dehydrated
Prevention of spread, avoid close contacts
Acyclovir suspension 200mg in 5ml five times a day for 5 days (or tablets, 200mg) – half dose for children <2yrs. Prescribed at early stage

14. Recurrent herpes labialis
Cold sore or fever blisters
Mucocutaneous junction of the lip
40% of infected persons have recurrence
Prodromal tingling or burning prior to appearance of lesion (~24)
25% episodes have no prodromal symptoms

15. Recurrent herpes labialis
Vesicular eruption, breaks down to crusting lesion
Vesicular enlarge, coalesce, weep, rupture (2-3 days), crust, heal (10 days)

16. Reactivation of latent HSV1
Breakdown in local or systemic immuno-surveillance
Previously accepted that HSV1 migrates from trigeminal ganglion to site of peripheral reactivation
HSV may also be found in local neural tissue
HSV1 may be asymptomatically shed periodically > once/ month by up to 70%

17. HSV recurrence- trigger factors
Ultraviolet light exposre-snow, sea
Infection eg; pneumonia, upper respiratory tract infection
Menstruation
Reduced immunity eg; HIV, chemotherapy, transplants
Trauma, post operative

18. Prevention Sunscreen- reduces frequency of recurrence
Topical aciclovir- can reduce duration of attack
Severe or frequent recurrences systemic aciclovir prophylaxis

19. treatment Educate patients regarding infectivity of the lesion
Topical aciclovir will reduce duration and severity

20. Additional topical agents for RHL
1% penciclovir apply every 2 hours for 4 days
5% idoxuridine; little value

21. HSV recurrence (Herpetic whitlow)
Recurrence involving skin and digits
Health care workers at risk
HSV acquired from patients saliva
Highly infective
Intensely painful
Warn about shared utensils

22. Recurrent herpes simplex-intraoral
Keratinised tissue
Often on hard palate near the greater palatine foramen
Attached gingiva
Usually after dental treatment
Preceded by prodromal tingling
Area appears as localised collection of vesicles which ulcerate
Differential is anesthetic necrosis

23. Erythema multiforme EM is mucocutaneous blistering condition
Mucosal erosions and lip blistering with skin lesions
Some cases triggered by recurrent HSV infection
Continuous systemic antiviral therapy to suppress recurrence eg; Aciclovir 400mg bd

24. Erythema multiforme Age <30 (50% <20)
Aetiology: drugs, infections (HSV, HIV, Hepatitis, mycoplasma), Idiopathic.
Immune mediated type III (immune complex)
Target/ iris lesions, erythematoys papules and blisters
Extremities (palma and soles) and mucous membranes

25. EM features
Oral lesions; bullae or erythematous base break rapidly into irregular ulcers, bleed, form crusts
Lips more frequently involved, rare for gingiva to be affected
Skin macules and papules, central, pale area surrounded by oedema and bands of erythema; iris type but can be bullae
Varied appearance

26. EM causes
Infection; HSV 70%, hepatitis viruses, mycoplasma, bacterial, fungal, parasites
Drugs; NSAIAs, antifungal, barbiturates
Systemic; SLE, malignancy, pregnancy
Idiopathic 50%

27. Aciclovir Topical agent; Aciclovir cream 5%
Limited evidence for its effectiveness in reduction of pain and limited effect on reducing time to resolution
Systemic aciclovir is effective both as prophylaxis and treatment and some evidence on decreased healing time; level evidence A

28. Action of aciclovir
Nucleoside analogue drug active against herpes viruses particularly HSV
Aciclovir triphosphate is produced in HSV infected cell by viral enzymes
Acts by inhibiting viral DNA synthesis and blocking viral replication
Similar agents include valaciclovir (longer intracellular half life), penciclovir (topical) and famciclovir (oral prodrug of penciclovir)
Docosonal alters cell membranes preventing viral entry used for orofacial herpes

29. Varicella zoster virus (HHV3)
Herpes virus causing chickenpox and shingles
Primary infection; chickenpox in nonimmune, may affect up to 90% of children
Recurrence; reactivation as shingles; maybe sign of underlying malignancy, immunosuppression

30. Primary infection- chicken pox
Common childhood infection
Itchy maculopapular rash back, chest, face, 2-3 weeks after initial infection
Initial site upper respiratory tract- droplet infection
May have areas of oral vesicles, ulceration, palate and fauces
Usually present to GMP rather than GDP

32. Complication of chicken pox
Complication more common in adults, smokers and those with chronic lung infection
Bacterial superinfection of vesicles (usually staphylococcal or streptococcal) occurs in 1-4%, can lead to cellulitis, toxic shock syndrome (TSS) or bacterial pneumonia
Varicella pneumonitis
Cerebellar ataxia in children
Bacterial pneumonia (more common in adults, smokers and those with pre-existing lung disease)
Rare: Encephalitis, iritis, thrombocytopenia, myocarditis, osteomyelitis, orchitis, reyes syndrome.

33. Herpes zoster recurrence
Shingles; usually appears on trunk, affecting single dermatome
Occasionally underlying immunosuppression eg; AIDS, Hodgkins lymphoma, organ transplant
Often misdiagnosed in prodromal phase
Predilection for cranial nerves V and VII

34. Shingles
Herpes zoster (shingles) affects 50% of patients who live to 85%
Recrudescence of latent varicella zoster virus from DRG or cranial nerve ganglia present since initial infection as chicken pox
Probably many reactivation during life time but controlled by competent immune system cmi
Incidence; per year and expected to increase

35. Complications of herpes zoster
Postherpetic neuralgia
Ophthalmic shingles
Ramsay-Hunt syndrome
Encephalitis
Secondary bacterial infection
Scarring
Muscular weakness

36. VII- Ramsay-Hunt syndrome
Herpes zoster affecting geniculate ganglion
Lower motor neuron facial paralysis
Vesicular lesions on external auditory meatus, (pinna, fauces)
Altered taste
deafness

37. What is this? And why do you need to recognise it quickly?
V1- ophthalmic herpes zoster
Corneal scarring with result lost of vision
Urgent referral to ophthalmology

38. Herpes zoster V2 &3; maxillary and mandibular divisions:
Vesicles affecting facial skin and mucosa up to midline affected
Maybe preceded pain in teeth and gingivae
Lymphadenopathy
Malaise and pyrexia

39. Potential long term effects of herpes zoster affecting the trigeminal nerve?
Corneal scarring; impaired vision
Post herpetic neuralgia

40. Management of herpes zoster
Treatment often suboptimal
>50 yrs greater risk of PHN; antiviral treatment with aciclovir/ famciclovir/ valaciclovir
Treatment ideally commenced within 72 hours of rash onset
Decrease duration of viral shedding, rash healing hastened, decrease severity and duration of acute pain
Reduction in neural damage should decrease PHN

41. Management of herpes zoster
Immunocompromised patients IV antiviral
V1 (nasociliary) ophthalmic assessment and antivirals
Pain relief; follow analgesic ladder, opioids maybe required
Risk of complication increases with age, immuno-compromisation, lack of appropriate treatment

42. Post-herpetic neuralgia
Highest risk in the elderly over 65 years
Occurs in zone of eruption
Burning continuous pain/ intervals sever shooting pain
Prevention: systemic aciclovir (800mg x5/ day 10/7), famciclovir used during an attack of zoster also TCA
Treatment: gabapentin, TCA

43. Epstein-barr virus
Cause of infectious mononucleosis (glandular fever); gives positive Paul Bunnel and monospot tests.
Also involved in number of other conditions eg; Non Hodgkins and Burkitts lymphoma, oral hairy leukoplakia, nasopharyngeal carcinoma
70% carry virus by 30 years
Spread through saliva; “teenage kissing disease”
Concurrent treatment with penicillin causes erythematous skin rash (not penicillin allergy)

44. Infectious mononucleosis
Oral involvement in 30% of patients
Incubation of days followed by; fever
Anorexia
Malaise and lassitude
Generalized tender lymphadenopathy
Sore throat, faucial oedema creamy tonsillar exudate
Oral petechiae; at hard and soft palate junction

45. Glandular fever management
No specific treatment
Symptomatic management maintain fluid intake
Antiseptic mouthwashes
analgesics

46. EBV and OHL Not pathognomonic of HIV Immunocompromised patients
Use of potent oral and inhaled corticosteroids
Transplant patients

47. Measles (rubeola)
Acute contagious infection with paramyxovirus, rubella virus (droplet)
Incubation period: 7-10 days
Fever, sore throat, rhinitis, cough, conjunctivitis
Then maculopapular rash- forhead first then behind ears

48. 1-2 days prior to onset of rash develop Koplik’s spots on buccal mucosa and soft palate (small whitish lesions resembling grains of salt)

49. Mumps
Paramyxovirus
Painful swelling of major salivary glands- often asymmetrical
Spread: close contact respiratory route
Incubation period: days
Other symptoms: headache, joint pain, nausea, dry mouth, mild abdominal pain, fatigue, loss of appetite, pyrexia of >38◦C
Complications: Orchitis (20-30% of adults men affected may cause sterility), Oophritis, pancreatitis, meningitis.

50. Cytomegalovirus (CMV, HHV5)
~80% adults serological evidence of exposure
Salivary inflammation/ sialadenitis- cytomegalic inclusion disease
Uncommon and limited to immuno-compromised and newborn
May cause a glandular fever-like illness
HIV- widespread, shallow mucosal ulcers responds to ganciclovir

52. Coxsackie viruses Enteroviruses Several subspecies of type A and B
Some cause oral infections
Highly infectious
Transmission by faecal-oral route or by nasopharyngeal secretions

53. Hand, foot and mouth disease
Coxsackie virus, particularly subspecies A16 (also A4, A5, A9, A10)
Infection in childhood (rarely in adults)
Highly infectious
Incubation period 3-10 days
Viral prodrome; mild systemic upset
Triad of manifestations; macular and vesicular eruptions involving hands, feet and oropharyngeal mucosa

54. Hand, foot and mouth - oral
Multiple shallow relatively painless, oral vesicles/ ulcers
Pharynx, soft palate, buccal mucosa and tongue
Rarely severe enough for dental opinion, resolve in 7-10 days
No lymphadenopathy
Gingivae spread

55. Hand, foot and mouth - skin
Erythematous macules and vesicles on hands and feet
Maybe deep and blister
Transient- last only 1-3 days

56. Management Treatment supportive, antiseptic mouthwash
Serology needed for confirmation but usually not performed as self resolving
Differential from primary herpetic gingivostomatitis
Not related to cattle

57. Herpangina Coxsackie subtypes A2, A4, A5, A6 and A8 Chldhood infection
Sudden onset of pyrexia and sore throat
Oral lesions within 2 days
Multiple papules, vesicles and ulcers on soft palate and fauces
Pain and swelling in salivary glands
Symptoms mild
No active treatment needed
Resolution within 10 days

58. Human Papilloma Virus HPV
Warts virus
Over 100 different types- HPV types 2 and 4 typically cause mucosal warts
HPV-related lesions on hands and fingers (eg; Butcher’s warts),
genital mucosa (condyloma)
and skin maybe transferred to oral cavity producing cauliflower like appearance in labial mucosa, palate or lingual frenum (verruca vulgaris)
Important to treat both sites at same time

59. May resolve spontaneously
Diagnosis clinically and by histopathology; large clear koilocyte, Immunostaining.
Possible treatment: surgical excision, cryotherapy, laser treatment, medical treatment

60. HHV and HPV
Have been implicated in, or are suspected of causing many and various conditions
Many HHV’s ad HPV’s are associated with neoplasias
E.g. HPV16 is found in 22% of oral SCC’s
E.g. HPV18 is found in 14% of oral SCC’s
Association and causation are not the same thing, but there is some evidence to suggest HHV and HPV’s are implicated in SCC

61. HHV8 and Kaposi’s sarcoma
HHV8 implicated in Kaposi’s sarcoma
Skin, mucosa-eye, mouth, nose
May spread systemically eg lung, GIT
KS/HHV8 promotes angiogenesis
KS prevalence reduced since introduction of antiviral therapy
M:F =8:1

62. Oral Kaposi’s Sarcoma Human herpes virus 8? True clonal malignancy
Typically affects palate but also periodontal tissues
Reddy-blue or purple macules or nodules which may ulcerate
Oral KS pathognomonic of AIDS- mouth affected in 50% of patients with mucocutaneous KS

63. Kaposi’s Sarcoma Seen with CD4 counts below 200
Other features of HIV may be present such as candidiasis, linear gingiva erythema, advanced periodontal disease
Treatment:
Usually respon to initiation antiretroviral treatment
If not then alitretinoin gel, liposomal daunorubicin/ oloxorubicin, paclitaxel, IFN-α
Intra-lesional treatment/ localised radiotherapy

64. Oral lesions associated with HIV
Candidiasis
Oral hairy leukoplakia
Kaposi’s sarcoma
Lymphoma
Periodontal disease
Oral ulcers

65. Summary Viral diseases affecting the oral mucosa are common
Most common infections are HSV recurrences (cold sore)
Recurrent zoster in the mouth must be considered as a differential for unexplained dental pain
Immuno-suppressed patients at risk of reactivation of normally nonvirulent dormant viruses e.g: EBV, CMV