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UNIVERSITY PELITA HOPE 23 Literature review Varicella zoster CHILDRENMartin Kurniawan 1 , Norberta Dessy 2 , Matheus Tatang 3 1 Faculty of Medicine, Universitas Pelita Harapan 2 Department of Clinical Pathology, University of Pelita Harapan 3 Department for Children, Univeritas Pelita Harapan ABSTRACT Varicella is a viral infectious disease roomates a the caused by the varicella-zoster virus. It manifests as chickenpox and its latent reactivation will manifests as herpes zoster (shingles). The clinical signs of varicella begin as soon Becomes macule that itchy vesicles on the scalp, face, and trunk. On the other hand, herpes zoster infection is commonly manifests as vesicular lesions roomates distributed unilaterally According to the infected sensory nerves. The diagnosis of varicella should be made clinically rather than laboratory (virology and serology). Vaccination and administration of immunoglobulin are recommended for prophylaxis. Acyclovir has been the the drug of choice for both varicella and herpes zoster infection. Complications may vary from bacterial infection until hemorrhage and neurologic disorder. Key words: varicella - the virus - infection ABSTRACT Pox is an infectious disease caused by the virus Varicella-Zoster virus which can manifest as varicella (chickenpox) and reactivation of latent cause herpes zoster (shingles). Clinical symptoms of varicella can be found on the skin head, face, body, usually very itchy, reddish macules, which then can turn into lesions vesicles. Meanwhile, herpes zoster generally cause vesicular lesions are distributed in accordance with the unilateral sensory nerve travels infected. Varicella diagnosis is made clinically and laboratory (virology techniques and serology). Precautions that can be used against this disease is vaccination and immunoglobulin. The drug of choice against varicella and herpes zoster disease is antiviral acyclovir types. Complications that may occur is a bacterial infection, bleeding, and neurological disorders. Keywords: Varicella - Virus - infection PRELIMINARY Chicken pox (varicella) may already familiar and is a disease that worldwide 1 , Varicella is a disease contagious which can affect anyone, -------------------------------------------------- - Martinus Kurniawan ( ) Faculty of Medicine, University of Pelita Harapan Jl. Boulevard Jend.Sudirman, Lippo Karawaci, Tangerang, Indonesia. Tel: + 62-21-54210130; Fax: + 62-21-54210133; e-mail: martinz0203@yahoo.com especially those who have not received immunization. In Indonesia, not a lot of data which recorded cases of varicella or chickenpox nationally. The recorded data is Data epidemic of chicken pox in certain areas only. Data DHO Banyumas mentioned, during the period January to November 2007, at least 691 residents exposed to measles or Varicella. Number of patients most at Twinning districts with 155 patients, then districts Kalibagor 79 patients, and sub Karanglewas 75 people. Head Of Communicable Diseases and Environmental Health said the health office

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varicella zoster 30 UNIVERSITY PELITA HOPE 9. Drew WL. Herpes Viruses. In: Ryan KJ, Ray CG. Editor. Sherris Medical Microbiology. 4th edition. New York: McGraw Hill; 1994. h.562-565. 10. Whitley RJ. Varicella-Zoster Virus Infections. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Harrison's Principles of Internal Medicine. 16th edition. New York: McGraw Hill; 2005. h.1042-1045. 11. Parker SP, Quinlivan M, Y Taha, Breuer J. Genotyping of Varicella-Zoster Virus and The Discrimination of Oka Vaccine Strains by TaqMan Real-Time PCR. Journal of Clinical Microbiology 2006; 44: 3911-3914. 12. Warenham DW, Breuer J. Herpes Zoster. BMJ 2007; 334: 1211-1215. 13. Murray PR, Rosenthal KS, Kobayashi GS, Pfaller MA. Medical Microbiology. 3rd ed. St. Louis: Mosby; 1998. h.427-430. 14. Grose C. Variation on a Theme by Fenner: The Pathogenesis of Chickenpox. Pediatrics 1981; 68: 735-737. 15. Joklik WK, Willet HP, DB Amos, Willfert CM. Zinsser Microbiology. 20th edition. Connecticut: Appleton & Lange; 1992. h.959-961. 16. Gilden DH, Demasters BKK, Laguardia JJ, Mahalingam R, Cohrs RJ. neurologic Complications of The reactivation of the Varicella-Zoster Virus. NEJM 2000; 342: 635-645. 17. RW Johnson. Herpes Zoster-Predicting and Minimizing the Impact of postherpetic neuralgia. Journal of Antimicrobial Chemotheraphy 2001; 47: 1-8. 18. Center for Disease Control. Varicella (Chickenpox) Photos. 11 September 2007. Derived from http://phil.cdc.gov. Accessed on June 19, 2008. 19. Gilchrest B, Baden HP. Photodistribution of Viral Exanthems. Pediatrics 1974; 54: 136-138. 20. Vasquez M, Shapiro ED. Varicella Vaccine and Infection with Varicella-Zoster Virus. NEJM 2005; 352: 439-440. 21. Johnson CE, Stancin T, Fattlar D, Rome LP, ML Kumar. A Long-Term Prospective Study of Varicella Vaccine in Healthy Children. Pediatrics 1997; 100: 761-766. 22. Fisher RG, Edwards KM. Varicella-Zoster. Pediatrics in Review 1998; 19: 62-67. 23. English R. Varicella. Pediatrics in Review 2003; 24: 372-379. 24. Reynolds L, Struik S, Nadel S. Neonatal Varicella: Varicella-Zoster Immunoglobulin (VZIG) Does Not Prevent Disease. Arch. Dis. Child. Fetal Neonatal Ed. 1999; 81: 69-70. 25. Enright AM, Prober CG. Herpesviridae Infections in newborns: Varicella-Zoster Virus, Herpes Simplex Virus, and Cytomegalovirus. Pediatr Clin N Am 2004; 51: 889- 908. 26. Lokeshwar MR. Varicella-Zoster Virus. 25 May 2007. be obtained from: http://www.pediatriconcall.com. Accessed on July 4, 2008. 27. Gershon AA. Varicella-Zoster Infections. Pediatrics in Review 2008; 29: 5-11. 28. Hay WW, Hayward AR, Levin MJ, Sondheimer JM. Current Pediatric Diagnosis & Treatment. 16th edition. New York: McGraw Hill; 2003. h.1117-1119.

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MEDICINUS Vol. 3 No. February 1, 2009 - May 2009 UNIVERSITY PELITA HOPE 29 Reactivation of VZV in the trigeminal nerve may cause occurrence conjunctivitis, keratitis dendritic, anterior uveitis, iridosiklitis, and panoftalmitis. Blindness Herpes is usually rare. If until blindness occurs typically caused due to retrobulbar neuritis and atrophy optic. 34 lesions on tongue could indicate an infection of the nerves cranial 7 and associated with loss the sense of taste. Herpes zoster 2 and 3 against a branch of the nerve can 5 Oral cause paralysis. On the other hand, reactivation of the virus in the ganglion genikulatum the cranial nerves to 7 and 8 to be cause occurrence Ramsay Hunt syndrome. If the virus infects the lumbosacral ganglia, then it can happen dysfunction of the bladder and ileus. 34 PROGNOSIS The primary varicella infection levels of 2-3 deaths per 100,000 cases with case fatality rate in children aged 1-4 years and 5-9 years (1 death per 100,000 cases). In babies the average risk of death is about 4 times larger and in adults about 25 times greater. Average of 100 death happen in USA before the discovery of varicella vaccine, complications the main cause of death, among others: pneumonia, complications of CNS, secondary infection, and bleeding. 1,5,6 CONCLUSION Varicella is an infectious disease caused by the Varicella Zoster virus until now still become an epidemic in world and in Indonesia. although infection Varicella Zoster belongs to the infection lightweight, yet in a state of immune deficiency the disease can be severe and not rule led to death. administration vaccinations and immunoglobulin already proven effective provide protection from virus infection this. Until now, fixed oral acyclovir be the main drug for treatment varicella and herpes zoster. BIBLIOGRAPHY 1. Arvin AM. Varicella-Zoster Virus. Clinical Microbiology reviews 1996; 9: 361-381. 2. on the Committee on Infectious Diseases. Varicella Vaccine Update. Pediatrics 2000; 105: 136-141. 3. Soedarmo SSP, Garna H, Hadinegoro SRS. Textbook of Pediatrics and Infectious Diseases Tropical. 1st edition. Jakarta: Balai Publisher FMUI; 2002. h.152-159. 4. Data and Information Ministry of Health of the Republic of Indonesia. 22 November 2007. Obtained from www.depkes.go.id. Accessed on June 14, 2008. 5. Hambleton S, Gershon AA. Preventing Varicella-Zoster Disease. Clinical Microbiology reviews 2005; 18: 70-80. 6. Kliegman RM, Marcdante KJ, Jenson HB, Behrman RE. Nelson Essentials of Pediatrics. Edition 5th. Philadelphia: Saunders Elseviers; 2006. h.470-472. 7. Myers MG, Stanberry LR, Seward JF. Varicella-Zoster Virus. In: Behrman RE, Kliegman RM, Jenson HB. Nelson Textbook of Pediatrics. 17th edition. Philadelphia: Saunders Elseviers; 2004. h.1057-1062. 8. Ludwig H, HG Haines, Biswal N, Melnick MB. The characterization of Varicella-Zoster Virus DNA. J. gen. Virol 1972; 14: 111-114.

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varicella zoster 28 UNIVERSITY PELITA HOPE lymphocyte count ranges above 700, can reduce about 13% of the instances of attacks. However, children with leukemia who have received the vaccine difficult to gain increased cell-mediated imunity against VZV. It should be stressed that vaccines are not recommended to be given on patient that moderate experience immunodeficiency because precisely could cause activation of disease after 1 month immunizations. However, need remember on basically prevention is better to reduce mortality rather than treat disease which is already happening. 1 COMPLICATIONS varicella The most frequent complications found due to varicella infection is a bacterial infection S. aureus or Streptococcus pyogenes (group A beta hemolytic streptococcus). 6,45,46 Antibiotics can actually be used for reduce the risk of death, but in sepsis circumstances be less useful. 47 Infection secondary to bacteria usually marked with the advent of bullae or cellulitis, regional lymphadenitis and subcutaneous abscess can appears. S. pyogenes generally cause Varicella gangrenous invasive. Another manifestation is pneumonia, arthritis, and osteomyelitis. 48 Reye's syndrome, which is a non-inflammatory encephalopathy with fatty degeneration of the liver can a complication that makes it difficult. Children who suffer from varicella should not be given aspirin, because it can improve the risk of Reye's syndrome. 49,50 complication neurologic as meningoensefalitis and cerebellar ataxia is the main symptom is common. Complications of the central nervous system usually occur in children under 5 years and more from the age of 20 years. varicella encephalitis usually be gone by itself within 24 to 72 hours. So as with cerebellar ataxia, usually missing in some time. 6 symptoms such as bleeding, petechiae, purpura, epistaxis, hematuria, gastrointestinal bleeding, and DIC due complications such as thrombocytopenia, occurring 1 to 2 weeks after varicella infection. 5.6 can also the occurrence of arthritis virus, which caused because the varicella virus in the joint. Joint infections usually heal within 3 to 5 days. Other complications may also occur, but rarely found is myocarditis, pericarditis, pancreatitis, and orchitis. 1 herpes Zoster A common complication of shingles is PHN (post herpetic neuralgia). of some Data, obtained information that 9% of cases of herpes zoster associated with PHN for 4 weeks for up to 10 years. Persistent pain is felt by 22% of patients who get this syndrome. risk of PHN in fact related with increasing age and immunodeficiency conditions of patients. The risk of prolonged PHN increase, 40 to 50% by age of 60 years. 6.34 Shingles also can attack the system central nervous and cause encephalitis, however this is very rare roughly only 0.2-0.5% of the total patients. Radiation from the skin to cause encephalitis occurs within 9 days to 6 Sunday. The symptoms can appear, among others: the disruption of sensory function, pain head, photophobia, meningismus, and looks abnormal electroencephalogram. paresis cranial and peripheral nerves can occur from complications of herpes zoster in the arrangement Central nervous. Usually encephalitis due varicella only occurs about 16 days. 143 Encephalitis due to herpes zoster rarely cause death, most patients cured without a specific disability. Encephalitis is also usually associated with acute vasculitis. Other symptoms are usually happen is cerebral angitis, that is a syndrome consisting of vasculitis, thrombosis, and the mikroinfark associated with herpes zoster ophthalmic and reactivation cranial nerve in individuals aged further. In the CT scan is usually obtained their results see infarction in areas perfused by the middle cerebral artery. It was also reported can occur transverse myelitis, symptoms rare, but if there can be pose a higher risk of death. 1.6

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MEDICINUS Vol. 3 No. February 1, 2009 - May 2009 UNIVERSITY PELITA HOPE 27 prevented, and transformed the prognosis of infection varicella in children who are at high risk. Acyclovir therapy in children immunodeficiency should begin in 24 to 72 hours after skin rash appears. Because of the low oral absorption, the drug is given intravenously with each administration of a dose of 500 mg / m 2 in 8 hours. Treatment was continued for 7 days or until no new lesions appearing in 48 hour. 31,35,36 Efficacy of famciclovir and valacyclovir has not been well evaluated in patients who healthy and imonudefisiensi. BvaraU (sorivudine) given the 40 mg / day for 5 days have been studied to reduce fever, skin lesions, although administration postponed until 24 to 96 hours after the appearance of the first lesions. 1 Prevention Passive with Antibody Varicella zoster immunoglobulin (VZIG) IgG antibodies against VZV is with the dosage of one vial to 10 kg weight body by intramuscular (IM). VZIG prophylaxis is indicated for individuals at risk high, including children immunodeficiency, pregnant women ever having direct contact with patients varicella, neonatal exposed by mother infected with varicella, at least given the in no more than 96 hours. 37,38 Antibodies were administered after the onset of symptoms can reduce the severity of the happen. 5.6 Prophylaxis with Antiviral Therapy Test the efficacy of prophylactic acyclovir leave the results were quite good in people Bone marrow transplants are risky high VZV infection. but in clinical, prophylactic acyclovir as VZV infection prevention rarely used, because VZV therapy would be more effective if symptoms have appeared. 39 Vaccine Indications and Contraindications varicella: 1 Indication: Age 12 months-13 years. given one dose Age 13 years old to adult. Two dose, interval 4-8 weeks Infections Acute lymphoblastic leukemia in remission and HIV CD4> 25%, the vaccine is given in 2 dose with a distance of 3 months. Contraindication: Congenital immunodeficiency Leukemia, lymphoma, or malignancy other symptomatic HIV infection High-dose corticosteroids Pregnancy Allergy neomycin Salicylic acid is more than 6 weeks There are no clinical symptoms arising from vaccine doses 9000 PFU infectious virus. This vaccine can induce protection to more than 95% against the occurrence of transmission. 41,42 immunological Studies show that administration vaccine Live attenuated varicella can increasing seroconversion (approximately 95%), as good as antibody VZIG after 1 year. This vaccine can increasing the T lymphocytes that recognize VZV antigen or virus proteins. Circulation T lymphocytes specific to VZV may appear peripheral blood about 2 to 6 weeks after administration of varicella vaccine. Immunization with vaccine varicella also could increasing cytotoxic T cells that can lysis of VZV protein. T lymphocyte proliferation against VZV antigen can be maintained up to 6 years in children with immunity good and has been given the varicella vaccine. In some studies also mentioned that cell mediated immune stimulation index response against VZV dosing dual vaccine for 1 year is 22.2 6:42 compared to dosing ie single 9.3 1:39. The higher it is antigen contained in the vaccine more and more big contribution in increase the level of immunity. Immunization with varicella vaccine may increase of memory T lymphocytes useful for memproliferasi and produce lymphokines the IE62 proteins and glycoproteins virus. 43.44 Oka vaccine given to children with leukemia in remission with

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varicella zoster 26 UNIVERSITY PELITA HOPE LABORATORY DIAGNOSIS Laboratory tests are very important to diagnose patients with suspected suffered varicella or herpes zoster and to determine antiviral therapies corresponding. 26 Leukopenia occurred in 72 hours first, followed by lymphocytosis. Examination function heart (75%) also increased. Patients with impaired neurology due to varicella usually experience lymphocytic pleocytosis and increased protein in the cerebrospinal fluid and glucose generally within normal limits. 5.6 PCR techniques Virological Methods to detect DNA viruses or viral proteins used as one method of diagnosis of VZV infection. Specimens should be stored on ice or refrigerant with temperature -70C if storage is done on time longer. 26 techniques Serology One method used serological to diagnose VZV infection in base on examination of acute serum and konvalesens ie IgM and IgG. VZV IgM examination has a sensitivity and specificity. reactivation of VZV IgM spur that is sometimes difficult to distinguish with the presence of IgM in primary infection. 28 One of the interests of antibodies IgG is to determine the immune status someone, Where history disease varicelanya unclear. examination IgG have interest clinical, in order to knowing passive antibody or never received active vaccine against varicella. The existence of IgG, basically a markers of latent infection with the exception of patients already receive antibody passive from immunoglobulin. Another technique is to using fluorescent-antibody membrane antigen assay, this examination can detecting antibodies bound to cells infected with VZV. This test is very sensitive and specific, almost similar with examination enzyme immunoassay or immunoblotting. 29 Serology Another that support is latex agglutination, to determine the immune status of the VZV. 29.30 TREATMENT AND PROPHYLAXIS Acyclovir, famciclovir and valacyclovir are antiviral agents that have been recognized for handling to infection varicella. Nucleotides have replaced vidarabin and IFN-, which is the first antivirus which is known to have a clinical effect to address the primary and recurrent infections of VZV. 31 Phosphorylated acyclovir only when met by thymidine kinase of the virus, this drug tend to be inactive in the body unless sensitized with VZV-infected cells or who have a viral enzyme. After the merger between acyclovir with timidine kinase, then the cellular kinase would metabolizes into adenosine monophosphate which is a competitive inhibitor and be chain termination of the viral DNA polymerase. The concentration normally required for inhibit VZV is about 1 to 2 mg / ml. 32 Other drugs are famciclovir are is diacetyl, 6-deoxy penciclovir ester, which is an analog of guanosine nucleotides. The metabolism of this drug begins of uptake in intestinal cells and settled in the liver. How it works is similar to acyclovir. 33 Valaciclovir is acyclovir with derivatives valine ester which allows absorption Oral acyclovir is better than usual, valaciclovir change back into acyclovir during the process of absorption and have a way of working together against VZV with acyclovir derivatives outstanding. Other than that, there are also BvaraU which is nucleosides other that also have ability high for menginhibisi VZV activity in vitro. 1 For those who develop resistance to acyclovir then could be given foscarnet as successor. 6 Treatment Giving acetaminophen to reduce discomfort due to fever; antipruritus such as diphenhydramine 1.25 mg / kg hidroksin every 6 hours or 0.5 mg / kg every 6 hour. Topical and systemic antibiotics can be given to overcome superinfection bacteria. 34 Therapy anti virus lower mortality due to progressive pneumonia can

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MEDICINUS Vol. 3 No. February 1, 2009 - May 2009 UNIVERSITY PELITA HOPE 25 Symptomatic can cause vesicular lesions on the skin that is distributed only on certain dermatom follow nerve certain sensory. 17 Inflammatory process, necrosis, and disruption of cell morphology nonneuron neurons and cause myelitis, motor function deficits, and postherpetic neuralgia (PHN). 21,22 CLINICAL MANIFESTATION Starting with prodromal symptoms such as fever, malaise, headache, and pain abdomen, which directly 24-48 hours before skin lesions appear. Systemic symptoms such as fever, fatigue, and anorexia may arise along with skin lesions. symptoms in respiratory and vomiting rarely happen. 5.6 Early skin lesions on the skin head, face, body, usually very itchy, macula in the form of redness, later changed be small lesions and fluid-filled vesicles in it, like to see a teardrop. 1 Healing is the formation of epithelial cells The new skin that emerged from the base of the lesion. hypopigmentation could happen result healing lesions. Scar or scars rare due to varicella infection. Breakthrough Varicella When infection occurs 2 weeks post-infection primary or immunization with marked reappearance of skin rashes (form maculopapular) without be accompanied fever, thought to be caused by the type VZV virulent. 5.6 progressive Varicella Progressive varicella is a state characterized by coagulopathy, bleeding terrific, and the continuing emergence of new lesions. Extreme pain arises in the area accompanied by abdominal bleeding vesicles. This situation is a risk factor patients with congenital imundefisiensi, malignancy, chemotherapy, and the number of lymphocytes