Viral Infections

Viral Infections4th year by Hidayah BahrinViral Infections Herpes simplex virus Varicella zoster virus Epstein -Barr virus Coxsackie virus Paramyxovirus Human papilloma virus HIV

Diagnostic TestsClinical Diagnosis, remember that the diagnosis of most viral infections is primarily made on clinical grounds. Tissue Culture(24 hours) is most useful but it is lengthy and expensive. It requires incubate the tissue for 24 hours before u get the results. Serologic tests (10-24) days are a lengthy process; it takes longer duration before we have an established diagnosis. And in most cases it is retrospective, although in sometimes we have to establish the diagnosis based on serologic tests. Cytology it is direct & rapid test that can be used in the clinic or at least can be used in the lab probably, you will have the results within 12 hours if you have a lab close to your clinic. Molecular techniques, which look at the DNA of each virus, and in some cases it is the only technique that distinguish between HSV type 1 and HSV type 2 and Varicella zoster virus.1.Herpes SimplexType 1 : Oral mucosa, pharynx, skin, Bells palsy. The most common disease with type 1 HSV is primary herpetic gingivostomatitis can affect the skin and cause recurrent infection. Type 2 : genital lesions, and rarely oral lesions HHV 6 & 7 : Roseola Infantum condition which is very similar to measles, occur in infantsHHV 8 : Kaposis sarcomaCMV : associated with salivary gland disease and oral ulcers especially in the new borns and immune compromised patients. EBV :remember the 4 lesions associated with EBV. Varicella zoster virus: cause chickenpox &shinglesPrimary Herpetic GingivostomatitisThe most common viral infection of the mouth 95% are subclinical, that means that the patients can transmit the disease without showing any signs or symptoms Reaches a peak between 2-3 years of age It affects mainly children and toddlers but still you can find them in adults (in 40s and 50s) who have no previous contact with the virus. 2-3 days of prodromal symptoms; malaise, sore throat, submandibular lymphadenopathy. When the disease progresses oral and perioral vesicles appears Gingivitis is the whole mark of this infection, means that you cannot make a diagnosis of Primary herpetic gingivostomatitis without involvement of the gingival. Thats a hint to distinguish between erythema multiforme a very simple condition, and Primary herpetic gingivostomatitis. Some books could refer to erythema multiforme as a condition that might involve the gingival but this is not true,at least vesicles and ulceration will not be seen on the gingival. Recovery over 10-14 days, without treatmentSelf-limiting disease unless pt. immunocompromised Malaise(/mlez/ muh-LAZE) is a feeling of general discomfort or uneasiness,5Primary Herpetic GingivostomatitisDiagnosis Clinical Most rapid,straight forwardTissue Culture (most positive method)the best test to be used in the diagnosis of Primary herpetic gingivostomatitis not used routinely because it takes long durationThe medium will include cells that are used to keep the virus. And then cellular changes will be seen under microscope. This technique is a 100% specific, sensitivity is less than that. Primary Herpetic GingivostomatitisDiagnosisSerology. Serology implies the detection of the antibody to the virus. Serology deals with identification of IgM & IgG when you want to confirm a diagnosis of viral infection. Is a lengthy lengthy and expensive process, not all labs are equipped with required instruments and devices to perform that test. And it is retrospective diagnosis. What does that means? It probably needs 3 weeks to confirm a diagnosis of Primary herpetic gingivostomatitis, by the time you will have a diagnosis, the lesion will be healed and the symptoms have subsided. In serology we need to observe a fourfold rise in IgM antibody. (Correct the mistake in your book). IgM rises in acute infection. As the patient develops symptoms the titer of that antibody will raise. You have to have two specimens, one specimen in the first week of infection and then the other specimen after three weeks and compare. If the titer increased by fourfold you can make a diagnosis of acute Primary herpetic gingivostomatitis. If IgG is detected without IgM, that is not an indicative of acute Primary herpetic gingivostomatitis. It means that the patient had the virus before and now he has immunity to that virus. But in certain patients that should be done, especially patients who are immune-compromised, patient who wants to undergo stem cells transplant, or patients who receives an organ transplant, the titer of HSV should be determined before the procedure, because those patients are in risk of developing complications, and in that case they should be given systemic anti-viral treatment to prevent the complications. Cytology. You are going to see Tzanck cells which are multinucleated giant cells and ballooning degeneration of the nucleus. This is a comparison between viral and serological classification of infection with genital (HSV) *

ComplicationsEncephalitis (inflammation of the brain, caused by infection or an allergic reaction.) Hepatitis (a disease characterized by inflammation of the liver) Adrenals can be involved Lung complications such as pneumonia Infants born to asymptomatic carriers and immune-compromised patients are at risk.This is how primary herpetic gingivostomatitis presents, pts usually have vesicles, ulcerations. Earliest lesions start as an erythema and then to vesicles, then these vesicles disrupt causing ulceration. And if you look at the gingival you will observe gingivitis, vesicles and ulcerations. Tongue is also involved. Severity differs among individuals.

Eating is extremely painful in those patients, and you have to advice your patient how to maintain their nutrition. It can cause dehydration in infants and children, and have consequences.

Management Supportive Antiseptic mouthwashes Antipyretics,patients who have fever can be given paracetamol or Acetomeniphen. However this is debatable Foscarnet is prescribed for patients with resistance cases to Acyclovir Patient who are immune-suppressed systemic anti-virals are prescribed like Acyclovir Systemic Acyclovir is not routinely given as treatment of choice for patients with primary herpetic gingivostomatitis unless they are immune-compromised, and they are not recommended for patients who are under 12 years of age. Valacyclovir, famciclovirRecurrent HerpesHSV-1 remains latent thereafter in the trigeminal ganglion but can be reactivated. Occurs in 20-40% of patients: reactivation of latent herpes virus (recurrent attack -> resolve -> attack again)Most commonly seen on keratinized mucosa: lips, palate, gingivae, skin Prodromal symptoms include itching, burning before vesicular eruptions We use topical acyclovirRecurrent lesion are localized

Triggers What reactivates HSV? Sunlight Mechanical trauma Common cold (avoid contact with people who have cold)Emotional factors (stress-usually the most triggering factor)Menstruation

Clinical ManifestationProdromal Stage: burning, itching, irritation Vesicle stage (highly infectious) remember that when you educate your patient about his disease, that although it doesnt have severe complications but it can have serious implications on other family members who are immune-suppressed. Healing without scarring in 10 daysLesions tend to involve the same area in successive episodes Although these lesions heal within 14 days, large chronic lesions are seen in immunocompromised patients that lasts for 2 months or more than that.In some cases,we must make biopsy to exclude other disease. Clinical ManifestationThe prodromal symptoms are more severe in primary herpetic gingivostomatitis than in recurrent herpes.Primary herpetic gingivostomatitis -> fever, malaise,fatigue,lymph node enlargementRecurrent herpes -> itching&burning sensation at the site where herpetic lesion will appear (there are no systemic manifestation) its localizedDiagnosis and ManagementDiagnosis: Cytology, viral cultures, clinical(most common)

Management: Avoidance of triggers, sunblock, acyclovir, penciclovir cream

Acyclovir 400mg twice daily for frequent deforming lesions is recommended but not all patients. Specially for famous people (e.g. Nancy Ajram :P) or whose work requires good appearance can take prophylactically treatment. That will not treat the disease but Acyclovir will prevent virus replication, so those patients will still develop latencies but the periodicity of those latencies is reduced.

Frequent means more than 5 times a year.

Diagnosis and ManagementPatients especially infants or nurses can develop herpetic lesions of the fingers that get in contact with a fresh viral lesion, and these lesions are called herpetic whitlow.May be transmitted from the mouth / genitaliaContagious and very painful

How to differentiate between recurrent oral herpes and other ulcerative conditions? Recurrent herpes occurs on keratinized mucosa, preceded by vesicles. Apthous ulcers do not affect keratinized mucosa, is not preceded by vesicles.

Kaposi sarcoma is caused by HHV8, it is observed in HIV patients, especially oral Kaposi sarcoma, and is more commonly observed in Males rather than females. 2. Varicella Zoster Infections Chicken pox is the primary infection with VZ, while the latent condition is called Shingles

Varicella Zoster Chicken pox Incubation period of 14-21 days Oral small ulcers appear before skin rash-Usually not diagnosed Maculopapular itchy lesions develop into vesicles Fever, lymphadenopathy (systemic symptoms) Treatment: supportive (symptomatic) Complications: encephalitis, pneumonia*pt. Should avoid itching the lesion because scrap will develop then scars are formed*this disease is highly contagious, now it has vaccine *Dermatologist distinguished between chicken pox lesions from other lesions on the skin, by observing the stages of chicken pox, so the earliest stage is dew drop on a rose petal and then in late stages while include crusted lesions and ruptured vesicles. Varicella Zoster - Shingles The recurrent lesion 70% of affected patients are above 50 years of age Few neonates and young patients but with very mild symptoms. Debilitating diseases and immune-suppression are predisposing factors (stress may also be a predisposing factor)

Clinical manifestation Prodromal sever pain for 2-3 days precede vesicular eruptions. Vesicular eruptions in the area of distribution of a sensory nerve 15% affect the trigeminal nerve (ophthalmic division in most cases) Oral lesions in some cases resemble herpetic lesions Recovery in 2-4 weeks Complications: corneal ulceration, post herpetic neuralgia

The lesions are unilateral, in most doesnt cross the midline, and it follows the sensory distribution of the trigeminal nerve.

Treatment of Varicella Zoster Antivirals within 48-72 hours of rash onset.If you were late in introducing the medication, dont start the patient on these medications Acyclovir 800mg 5 times for 7 days Valacyclovir 1000 mg 3 times for 7 days Famicyclovir 500mg 3 times for 7 days Control the symptoms by Analgesics and tricyclic antidepressants (amitriptyline 25 mg qhs), mainly those who developed post herpetic neuralgia.

*Post herpetic neuralgia is difficult to treat and the symptoms are usually sever, and it is caused by scarring of the nerve, through which the virus was reactivated, and therefore controlling their symptoms should include tricyclic antidepressant *Bells palsy is caused by HSV-1 and Varicella zoster both viruses are implicated in the etiology. *If a patient has ear rashes and vesicles without facial nerve involvement the diagnosis will be shingles not Ramsay Hunt syndrome. 3. Epstein Barr Infections Infectious mononucleosis *kissing disease*Burkitts lymphoma Nasopharyngeal carcinoma Hairy leukoplakia

a. Infectious mononucleosis Synonyms: glandular fever, kissing disease Affects young adults and they presents with Febrile illness Sore throat, tonsillitis Oral ulcerations Petechiae on the palate They may develop generalized lymphadenopathy, similar to that in lymphoma. Blood test to confirm the diagnosis which is called the WBC monospot, so if it is positive in a patient with lymphoma like symptoms then a diagnosis of infectious mononucleosis is established.Treatment : supportive Some patients with infectious mononucleosis develops symptoms that can last up to 6 months with organomegaly (hepato-megaly, generalized lymph node enlargement) *50% of patients with infectious mononucleosis develop petechiae of the soft palate *Patients with Sore throat and tonsillitis symptoms, If they were misdiagnosed and were given amoxicillin antibiotics they will develop skin rash

b. Burkitts lymphoma Is a malignant tumor Affects African children It is also caused by EBV

c. Hairy leukoplakia Usually at the lateral borders of the tongue In most cases it is bilateral white lesionIt is seen in patients with immune-suppression (HIV or organ transplant or those on corticosteroids systemic therapy) *If you are dealing with bilateral lesion of the tongue then you are likely to diagnose it as hairy leukoplakia.*one of the most common oral disorders in persons infected with HIV, occurring in approximately 15 to 20% ofpatients.

4. Coxsakievirus infections Group A: 24 types: causes hand, foot and mouth disease, herpangina, acute lymphonodular pharyngitis

Group B: 6 types: hepatitis, meningitis, myocarditis, pericarditis and acute respiratory disease a.Hand Foot and Mouth Disease Caused by mostly by (A16) , A5,A7, A9, A10,B2, B5 Fever, oral vesicles and ulcers Macules, papules, vesicles on hands and feet Diagnosis: clinical Treatment: supportive The disease lasts five to eight days.

*These lesion looks like the herpetic lesion but there will be vesicles,macules,papules on the hands&feets*there is no available antiviral medication to treat coxsakie lesion. Acyclovir is a antiviral medication only to herpetic lesion. Hand Foot and Mouth Disease

b. HerpanginaCoxsakie A1 to A10, A16 to A22Occurs in epidemicsmore common in childrenpatients may be affected more than once

Clinical ManifestationsIncubation: 2-10 daysFever, chills and anorexiaSore throat, dysphagia(difficulty in swallowing) and sore mouthRecovery in one week (in 95% of the cases is self-limiting)Diagnosis: smearTreatment: supportiveDeaths were related to non coxsackie virus causing similar symptoms*Acyclovir is not effective in herpangina, because coxsackie virus is not a herpes virus

Coxsakievirus affect the posterior part of the soft palate ,posterior part of the buccal mucosa and the posterior part of the tongue.

HSV affect anterior part of the oral cavity

5. Paramyxovirus InfectionsMeasles Caused by morbilli virusNasal discharge, kopliks spots intraorally (that is very similar to fordyces granules) and conjunctivitis, skin rashComplications: encephalitis, pneumoniaTreatment: supportive

*Patient will be severely ill*Those patients develop oral kopliks spots before skin rash, so if you have a patient with conjunctivitis, cough and sever fever with Fordyces granules like on the buccal mucosa you can make a diagnosis of measles.*But there is a difference between Fordyces granules and Kopliks spots which is the erythematous base is associated with kopliks spots. Kopliks spots Small white spots on the buccal mucosa during measles prodrome.

Fordyces spots, also known as Fordyce granules, are creamy yellowish soft granules beneath the oral mucosa, usually seen along the border between the vermilion and the oral mucosa of the upper lip and in the buccal mucosa particularly inside the commissures, and also in the retromolar regions and lips. They are sebaceous glands containing neutral lipids similar to those found in skin sebaceous glands, but they are not associated with hair follicles.36MumpsViral infection affecting the salivary glands.Incubation 14-21 daysBilateral parotid enlargement, trismus, dry mouth,fever, headache. not always bilateral, some patients develop unilateral enlargements.Diagnosis: clinical, serum amylase levels, serologyComplications: deafness, orchitis (inflammation of the testes), myocarditis and oophoritis (inflammation of the ovaries), encephalitisTreatment: symptomatic

6.Human papilloma virusCommon warts (verruca vulgaris)Hecks disease (self-limiting, associated with multiple lesions, focal epithelial hypoplasia, it tends to affect certain families American-latin in origin)Condyloma acuminatum (its significance, if you see it in children that means the child may be sexually abused)Carcinoma of the cervix

*Nowadays there is a vaccine against HPV, which has been used to vaccinate young girls primarily and young boys against HPV, in an attempt to prevent cervical cancer*And now there is a discussion about preventing oral squamous cell carcinoma which can be induced by HPV, but the efficacy of that vaccine is questionable.7. HIV and AidsStages of HIV infectionInitial stages are asymptomatic and when we say that a pt is HIV positive, that means that his blood shows antibody to HIV.Oral manifestations of HIV infectionCandidosis, hairy leukoplakia, periodontal disease, kaposis sarcoma, lymphoma, mycobacterial infection, Melanotic pigmentation, salivary gland disease, purpura, viral infections,necrotizing stomatitis