1. Viruses Causing Vesicular Rash By: Dr.Mona Badr Assistant Professor & Consultant Virologist College of Medicine & KKUH

2. Viruses Causing Vesicular Rash   What is the meaning of vesicular rash?   It is a temporary vesicular eruption on the skin   Vesicle:Is a small circumscribed elevation of the epidermis containing serious fluid   The two main viruses causing vesicular rash are: 1. 1.Herpes viruses 2. 2.Coxsackie A viruses

3. Herpes Virus   The herpesvirus family known to be pathogens for human: 1. 1.Herpes simplex virus type 1 2. 2.Herpes simplex virus type 2 3. 3.Varicella / zoster VZ 4. 4.Cytomegalovirus CMV 5. 5.Epstein Barr virus EBV 6. 6.Human Herpes virus type 6 7. 7.Human Herpes virus type 7 8. 8.Human Herpes virus type 8

4. Herpes Virus (Continued) Special Features of Herpes Virus  Are large in size, ds, DNA, icosahedral, enveloped virus.  The herpes viruses has the ability to induce latent infection HSV and VZV Nerve cell EBV B-lymphocyte CMV lymphocyte and macrophage

6. Electron Microscopy of Herpes Virus

7. Herpes Viruses (Continued)  The infection with all herpes virus has very characterized feature, there are 2 types of presentation: 1.Primary:  When the virus invade the body for the first time 2.Reactivation (Recurrent):  When the Latent (Hidden) virus, reactivated  The predisposing factors of reactivation, if any situation lead to decrease the immune system of the body e.g. diabetes, pregnancy, menstruation, stress or …. Cancer, AIDS, …

8.  Also, some herpes virus has oncogenic potential as EBVBurkitt’s lymphoma B-cell lymphoma Aplastic Nasopharyngeal carcinoma Herpes virus 8 Kaposi Sarcoma  Herpes viruses can cause high morbidity and mortality in immunocompromised patients.  Herpes viruses susceptible to antiviral treatment due to presence of thymidine kinase enzyme in the viruses. Herpes Virus (Continued)

9. Herpes Simplex Virus Type-I Herpes Simplex Type -II Pathogenesis and Immunity:  Both viruses are initially infect and replicate in mucoepithelial cells and then become latent (hidden) at trigeminal ganglia (HSV-I), at sacral ganglia (HSV-II)  Humoral and cellular immunity are necessary for HSV infection to be controlled and resolve.

10. Diseases of HSV1,HSV2

11. Herpes Simplex Viruses Herpes Virus (Continued) Herpes Simplex Virus 1  Spread through saliva and respiratory droplets. Herpes Simplex Virus 2  Spread by sexual contact Or new born during birth  Usually primary presentation seen in young adult.  Primary presentation usually painful. Latency occur in Sacral ganglia  Usually primary presentation seen in children 2-4 years.  Primary presentation usually asymptomatic Latency occur in trigeminal ganglia

12. Herpes Virus (Continued) A.Primary Infection of HSV1:  Leasions begin as vesicles, then rapidly become ulcerated which resolve spontaneously.  Gingivostomatitis  Pharyngitis  Kerato-conjunctivitis  Herpetic whitlow  Dendritic ulcer (cornea)  Herpetic encephalitis

13. Clinical Syndrome of Herpes Simplex Type-I A.Primary Presentation:  Most primary infection are symptomless but disease can be presented primary as: 1.Gingivostomalitis  Seen mostly in children from 1-5 years, with 4 days duration.  Vesicles inside the mouth and bucal mucosa and on the gum, fever, sore throat and submandibular lymph nodes enlarged can be seen. 2.Kerato-conjunctivitis  Usually in children, due to autoinoculation  Very severe situation can lead to corneal ulcer.

14. Gingivostomatitis Primary HSV-I

15. Dendritic ulcer (corneal ulcer) can be primary or reactivation can lead to blindness

16. Clinical Syndrome of Herpes Simplex Type-I (Continued) 3.Herpetic Whitlow  Is an infection of the finger, or infection at any site of the body.  The virus can enter through cut or abrasion in the skin.  Herpetic whitlow usually occur in nurses, physician and dentists 4.Acute herpetic encephalitis  The disease can occur at any age can be primary or reactivation  Very rare presentation of HSV-I usually limited to one lobe.  Started as acute fever, headache, mental confusion and lack of coordination.  Can lead to severe morbidity and mortality 5.Disseminated herpes Very rare disseminated vesicular lesions on skin and internal

17. Herpetic Whitlow

18. A. Latent Infection OF HSV- I:  From the primary lesion virus travels through nerves and then remain latent in trigeminal ganglia (HSV 1)  Virus persist for life time  Recurrent occur if immunity  Cold sore: vesicless at mucocutaneous function of nose and mouth  Dendritic ulcer Virus reach the cornea via ophthalmic branch of Trigeminal nerve very serious conditions can lead to blindness Herpes Virus (Continued)

19. Cold Sore 2 nd Presentation of HSV-I

20. Dendritic ulcer (corneal ulcer) can be primary or reactivation can lead to blindness

21. B.Primary infection of HSV-2:  Genital herpes, Vesiculo ulcerative Leasion associated with fever and lymphadenopathy.  I.P. one week after sexual contact  Lesion on the external genitalia as on penis, vulva and also in the cervix which is very painful.  HSV II proctitis lession on the anus in homosexual  Associated with fever and lymphadenopathy Herpes Virus (Continued)

22. HSV2 on Penis

23. HSV2 on Vulva

24. B.Primary infection of HSV-2:  Neonatal herpes: can occur with great risk (50%) if mother have the primary presentation around time of delivery when there is no maternal antibody is present to protect the baby. If mother has recurrent herpes the transmission (8%). The affected infants have jaundice, hepatosplenomegaly, thrombocytopenia and large vesicular lesions on the skin with high fatality rate. To avoid neonatal infection we do Caesarean section.  Meningitis: as a complication of genital HSV2 Herpes Virus (Continued)

25. Latent Infection OF HSV- 2:  From the primary lesion virus travel to be latent in sacral ganglia.  Virus persist for life time  Recurrent occur if immunity  Recurrent HSV2 are shorter and less severe than primary Herpes Virus (Continued)

26. Treatment and Prevention  Acyclovir is used for treatment of serious lesions as herpetic encephalitis, immunocompromised patient, dendritic ulcer, neonatal herpes, primary genital herpes. Prevention  Avoid contact with infected cases, droplet or vesicular lesion.  Avoid venereal transmission sex education.  Caesarian section to prevent transmission to baby during contact with birth canal.

27. Herpes Simplex Type-I and Type-II Laboratory Diagnosis Viral detectionAntibody detection 1)Culture Specimen: Vesicular fluid infected cell become enlarged and produce multinucleated giant cell (appear after 1- 3 days)  Serum IgM Ab is diagnostic of Acute infection.  Serum IgG Ab is diagnostic of pat infection. 2)Direct immunofluorescent:detect the virus directly from scraping of base vesicle. Neonatal herpes diagnosed by the detection of IgM Ab from the serum of the baby.

28. Varicella-Zoster These are two distinct (different) diseases caused by the same virus. Herpes Virus (Continued) Primary Presentation Varicella - Chickenpox 2 nd Presentation Or Reactivation Herpes Zoster

29. Herpes Vesicles Chickenpox

30. Primary presentation:(ckickenpox)  This is a high infectious disease of children, occur in Epidemic with seasonal variation late winter and early spring with 21 days I.P.  Transmitted by respiratory droplet and direct contact, patients are contagious before and during symptoms.  Fever, vesicular rash started on trunk, then extremities, face and even Scalp.  Recovery is the rule without scar formation.  Solid immunity develop after chickenpox  The disease is very severe in adult and immunocopromized patient.  Complication: are rare as encephalitis, pneumonia may seen in adult, disseminated disease in immunocompromized patient. Herpes Virus (Continued)

31. Chickenpox

34. Dark SkinLight Skin

35. Chickenpox

36.  Congenital varicella Limb – hypoplasia, muscular atrophy and cerebral retardation very rare complication can occur in baby born to mother infected with varicella early in pregnancy.  Peri-natal varicella (neonatal) If mother develop chickenpox within 7 days before delivery there is no maternal antibody and the baby is liable to develop severe disease.

37. 2 nd Presentation of Chickenpox (Zoster):  Zoster means belt  Viral DNA is present in dorsal root ganglia during latency for years.  Zoster result as reactivation of latent varicella (chickenpox) usually as sporadic cases occur in old adult Or immunocompromised patients.  Virus affect sensory nerve and ganglia leading to severe pain of area of skin supplied with this nerve.  Followed by appearance of very painful vesicles.  Uni-lateral, usually in the trunk, less common cranial, thoracic  Disseminated zoster can be seen in immunocompromized patient. Herpes Virus (Continued)

39. Herpetic Zoster on trunk

40. Herpetic Zoster

42. Herpetic Zoster in immunocompromized dessiminated

43. Herpes Virus (Continued) Laboratory Diagnosis  Virus isolation from vesicles on cell cultureCPE.  Detection of IgM or rising titer of IgG. Prophylaxis  Vaccine: live attenuated varicella vaccine given to high risk group patient e.g. hospitalized patient exposed to varicella. To be given as wide scale still under studies.  Varicella-Zoster immunoglobulin can be given to protect immunosuppressed patient within 3 days of exposure is protective.

44. Herpes Virus (Continued) Treatment  Acyclovir Interferonare used in immunocompromised children with varicella. Also used for adult developing complication as encephalitis or adult with reactivation as Zoster.

45. These are two diseases caused by Coxsackie A viruses  Coxsackie A virus is one of the picornaviridae family  Small, RNA virus  Stable at acid pH  Both disease are transmitted mainly by Fecal oral route and rarely by aerosol droplet  Incubation period from 3-7 days. Viruses Causing Vesicular Rash Herpangina and Hand, Foot and Mouth Disease

46. Fever, Cervical lymphadenopathy, sore throat and multiple small vesicles on the tonsils, pharynx and soft palate. These vesicles become ulcers later on. Viruses Causing Vesicular Rash Herpangina and Hand, Foot and Mouth Disease (Continued) Multiple small vesicles and ulcers seen on the  Tongue, and buccal mucosa.  Palm of the hands  Plantar of the foot also vesicles become ulcers Both are self-limiting diseases with complete recovery. No vaccine available No specific treatment Diagnosed by virus isolation in tissue culture. Complication Aseptic meningitis HerpanginaHand, foot & Mouth Dis.

47. Laboratory Diagnosis of Coxsackie Viruses  Control: by improving the standard of hygiene.  No vaccine available.  Diagnosis:Culture: Specimen from: Stool, CSF, Vesicular fluid and eye secretion, throat swab Some enterivorus fail to grow in tissue culture only in newborn mice. Some enterovirus can gro on several tissue culture CPE after few days neutralization. Serology: By ELISA to detect IgM, IgG and neutrilization PCR detect RNA test for identification

48. Herpangina caused by Coxsackivirus A

49. Hand foot and mouth diseases