History

Fact Explanation
Papulovesicular rash [6] Varicella zoster virus (VZV) is a neurotrophic alpha-herpesvirus. [2,6] Which is acquired through the respiratory secretions or direct contact with the vesicles, then the virus spread to regional lymph nodes, giving rise to primary viremic phase where virus disseminate to the liver or other cells of the mononuclear phagocyte system. This occurs during the incubation period which is usually has a 10-21 days of incubation period. [3] The rash initially appears on the face, chest, and back then spread to the rest of the body, it is itchy and fluid-filled blisters later turn into scabs. Rash also involves the inside of the mouth, eyelids and genital area. After about 1 week, blisters will become scabs.
Fever [6] Prodrome period of chickenpox lasts about 24 to 48 h before the first skin lesions appear and it consists of fever and other constitutional symptoms. [3] They will have high fever due to the associated inflammation. [2] Reactivation might cause mild fever.
Constitutional symptoms: malaise, anorexia, and lethargy [1] They can have constitutional symptoms [1] developing 1-2 days before the onset of the rash.
Earache, reduction of hearing This can occur if the varicella infection is complicated with otitis media. [1]
Features of hepatits [9] : Right upper abdominal pain and vomiting This is due to hepatitis, which is a benign complication of the varicella. [3]
Shortness of breath and cough due to pneumonia [7] This occurs if complicated with varicella pneumonitis, which is an uncommon complication of varicella. [1] Develops 1-6 days after the onset of disease.
Skin infections [1] There can be invasion of the skin lesions by group A β-hemolytic streptococci, leading to cellulitis, which might end up in necrotizing fasciitis on some occasions. Skin infections due to secondary bacterial infections are the most common complication of varicella. [1]
Features of cerebelitis [8] : Vertigo, speech disrurbances If complicated with cerebellitis they can have features related to cerebellar pathology. [1] Usually associated with reactvation. [8]
Headache, drowsiness, behavioural change [1] If complicated with encephalitis. [1]
Chest pain [1] Due to the myocarditis and pericarditis. [1]
Features of arthriti [1] : Joint and bone pain Due to the osteomyelitis there can be bone pain. Monoarticular pyogenic arthritis may also be a complication of varicella. [1]
Other complications [1,8] : Upper abdominal pain radiating directly to the back, testicular pain Upper abdominal pain radiating directly to the back may be due to the pancreatitis. [1] Testicular pain may due to the orchitis. [1]
History of immunocompromization [8] : organ transplant, HIV/AIDS, long-term steroid use, malignancy, chemotherapy Risk of acquiring and dissemination of the infection into the internal organs is higher among these groups of people. [1]
History of vaccination [6] Vaccinated persons can also get disease, which is milder with fewer blisters and low grade or no fever. [6]
Haemorrhagic varicella: erythematous skin rash, haematuria, bleeding from the nose(epistaxis) [5] Though this is a rare complication of varicella infection, it can result in severe haemorrhage that is rapidly fatal. They can have thrombocytopenia due to reduced production and survival of platelets and transient hypersplenism, [5] which may need intravenous immunoglobulin therapy. Hemorrhagic disease can lead to disseminated intravascular coagulopathy. Intracranial haemorrhage can develop in these patients. [4]
References
  1. ZIEBOLD C, VON KRIES R, LANG R, WEIGL J, SCHMITT HJ. Severe complications of varicella in previously healthy children in Germany: a 1-year survey. Pediatrics [online] 2001 Nov, 108(5):E79 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11694663
  2. MUELLER NH, GILDEN DH, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis of Disease, and Latency Neurol Clin [online] 2008 Aug, 26(3):675-viii [viewed 05 July 2014] Available from: doi:10.1016/j.ncl.2008.03.011
  3. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899
  4. LARGE DM, BASU A, O'BRIEN H. Intravenous gammaglobulin therapy in the thrombocytopenia of haemorrhagic varicella. Postgrad Med J [online] 1991 Apr, 67(786):383-384 [viewed 06 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398811
  5. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899
  6. OTSUKA T, GOMI Y, INOUE N, UCHIYAMA M. Transmission of Varicella Vaccine Virus, Japan Emerg Infect Dis [online] 2009 Oct, 15(10):1702-1703 [viewed 09 September 2014] Available from: doi:10.3201/eid1510.090597
  7. Passive immunization against chicken-pox. Br Med J [online] 1969 Oct 11, 4(5675):62 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1629478
  8. GILDEN D, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment Lancet Neurol [online] 2009 Aug, 8(8):731 [viewed 09 September 2014] Available from: doi:10.1016/S1474-4422(09)70134-6
  9. AL-HAMOUDI WK. Severe autoimmune hepatitis triggered by varicella zoster infection World J Gastroenterol [online] 2009 Feb 28, 15(8):1004-1006 [viewed 09 September 2014] Available from: doi:10.3748/wjg.15.1004

Examination

Fact Explanation
Febrile [6] Temperature elevation may be less than 38.68 Celsius (101.58F) in uncomplicated primary infection and may be as high as 41 Celsius (1068F) in reactivation. [3]
Papulovesicular rash [6] Rash begins as macules, later progresses to papules, vesicular stage and crusting of lesions. [2] Initially over the
Ear discharge [11] Due to associated otitis media. [1]
Jaundice, right hypochondrial tenderness [9] May be either due to hepatits [3,10] or autoimmune haemolytic anaemia. [9]
Altered level of consciousness [7] Due to encephalitis. [1]
Cerebellar ataxia [9] , dysarthria, pendular knee jerk, intention tremor, nystagmus [7] Due to cerebellitis. [1]
Sunken eyes, dry mucous membranes, dry skin, low blood pressure Due to dehydration. Sepsis can cause septic shock. [2]
Lymphadenopathy [11] Regional lymphadenitis may or may not be seen. [11]
Reduced chest expansion and chest moments, dull percussion, increased vocal fremitus, coarse crepitations and bronchial breathing over localized consolidation, Bilateral fine crepitations if complicated with interstitial pneumonia [8] There can be pneumonia due to varizella pneumonitis, and on some occcasions interstitial pneumonia. [2]
Focal neurological deficits (stroke) [7] Varicella zoster virus vasculopathy results when the infection involves the large or small cerebral arteries. [2]
Herpes zoster [5,7] This is a latent infection where primary infection causes varicella (chickenpox),and then virus becomes latent in cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia which can later reactivates and causes a wide range of neurologic disease. Herpes zoster appears along a 1-3 dermatomes and gradually maculopapular rash evolves into vesicles. [2,5] Other features of reactivation includes postherpetic neuralgia, vasculopathy, myelopathy, retinal necrosis and cerebellitis. [2]
Skin bruising, petechiae, purpura and haemorrhagic vessicles [4] This is due to hemorrhagic varicella, which is a rare but fatal complication of the disease. [4]
References
  1. ZIEBOLD C, VON KRIES R, LANG R, WEIGL J, SCHMITT HJ. Severe complications of varicella in previously healthy children in Germany: a 1-year survey. Pediatrics [online] 2001 Nov, 108(5):E79 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11694663
  2. MUELLER NH, GILDEN DH, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis of Disease, and Latency Neurol Clin [online] 2008 Aug, 26(3):675-viii [viewed 05 July 2014] Available from: doi:10.1016/j.ncl.2008.03.011
  3. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899
  4. LARGE DM, BASU A, O'BRIEN H. Intravenous gammaglobulin therapy in the thrombocytopenia of haemorrhagic varicella. Postgrad Med J [online] 1991 Apr, 67(786):383-384 [viewed 06 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398811
  5. BREUER J. Vaccination to prevent varicella and shingles J Clin Pathol [online] 2001 Oct, 54(10):743-747 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1731286
  6. OTSUKA T, GOMI Y, INOUE N, UCHIYAMA M. Transmission of Varicella Vaccine Virus, Japan Emerg Infect Dis [online] 2009 Oct, 15(10):1702-1703 [viewed 09 September 2014] Available from: doi:10.3201/eid1510.090597
  7. GILDEN D, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment Lancet Neurol [online] 2009 Aug, 8(8):731 [viewed 09 September 2014] Available from: doi:10.1016/S1474-4422(09)70134-6
  8. Passive immunization against chicken-pox. Br Med J [online] 1969 Oct 11, 4(5675):62 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1629478
  9. KUMAR KJ, KUMAR HC, MANJUNATH VG, ARUN V. Autoimmune Hemolytic Anemia due to Varicella Infection Iran J Pediatr [online] 2013 Aug, 23(4):491-492 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883384
  10. AL-HAMOUDI WK. Severe autoimmune hepatitis triggered by varicella zoster infection World J Gastroenterol [online] 2009 Feb 28, 15(8):1004-1006 [viewed 09 September 2014] Available from: doi:10.3748/wjg.15.1004
  11. CATRON T, HERN HG. Herpes Zoster Ophthalmicus West J Emerg Med [online] 2008 Aug, 9(3):174-176 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672268

Differential Diagnoses

Fact Explanation
Meningoencephalitis [8] Altered level of consciousness, seizures, fever, vasomotor instability may be present. Evaluation requires a lumbar puncture. [1] Most of the time cause would be Herpes simplex encephalitis. Meningeal irritation will result in neck stiffness, positive kernig and Brudzinski sign.
Herpes Simplex infection [5] There are 2 types of this virus: Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) HSV 1 transmits via oral contact and causes oropharyngeal infection. [3] HSV-2 infection is usually transmitted sexually and causes vesicular lesions over the genital area.
Impetigo [7] This is a common condition in children. Localized red rash where skin may appear red or brown with blisters and pus will be evident, there may be associated lymphadenopathy. A bacterial culture of the skin is the investigation to diagnose the condition. Secondary bacterial infections complicating the varicella [2] may look similar to impetigo.
Acute Nerve Injury [6] Focal neurologic deficits such as facial nerve palsy, concomitant hemiplegia, paresis of the arm, radiculitis resulting in paresis of the leg, and abducens nerve palsy can be seen in patients with varicella as well. [4]
References
  1. GRINSCHGL G. Virus meningo-encephalitis in Austria: 2. Clinical features, pathology, and diagnosis Bull World Health Organ [online] 1955, 12(4):535-564 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542296
  2. ZIEBOLD C, VON KRIES R, LANG R, WEIGL J, SCHMITT HJ. Severe complications of varicella in previously healthy children in Germany: a 1-year survey. Pediatrics [online] 2001 Nov, 108(5):E79 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11694663
  3. SMIT C, PFROMMER C, MINDEL A, TAYLOR J, SPAARGAREN J, BERKHOUT B, COUTINHO R, DUKERS NH. Rise in seroprevalence of herpes simplex virus type 1 among highly sexual active homosexual men and an increasing association between herpes simplex virus type 2 and HIV over time (1984-2003) Eur J Epidemiol [online] 2007 Dec, 22(12):937-944 [viewed 05 July 2014] Available from: doi:10.1007/s10654-007-9178-2
  4. ZIEBOLD C, VON KRIES R, LANG R, WEIGL J, SCHMITT HJ. Severe complications of varicella in previously healthy children in Germany: a 1-year survey. Pediatrics [online] 2001 Nov, 108(5):E79 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11694663
  5. ESPY MJ, UHL JR, MITCHELL PS, THORVILSON JN, SVIEN KA, WOLD AD, SMITH TF. Diagnosis of Herpes Simplex Virus Infections in the Clinical Laboratory by LightCycler PCR J Clin Microbiol [online] 2000 Feb, 38(2):795-799 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC86206
  6. MORRISON CM, THOMPSON NW, HERBERT KJ, BRENNEN MD. Missed injuries in the acutely traumatised hand. Ulster Med J [online] 2003 May, 72(1):22-25 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475407
  7. COHEN EL. Local Treatment of Impetigo with Sulphanilamide Br Med J [online] 1942 Mar 14, 1(4236):359 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2160264
  8. KENNEDY P. VIRAL ENCEPHALITIS: CAUSES, DIFFERENTIAL DIAGNOSIS, AND MANAGEMENT J Neurol Neurosurg Psychiatry [online] 2004 Mar, 75(Suppl 1):i10-i15 [viewed 09 September 2014] Available from: doi:10.1136/jnnp.2003.034280

Investigations - for Diagnosis

Fact Explanation
Serology [2] IgG or IgM antibodies to varicella should be checked in acute- and convalescent-phase serum. [6] This lacks a clinical significance as rapid confirmation of infection is necessary for the management. Therefore diagnosis is made primarily on clinical features. IgM antibodies are not used routinely as it lacks the specificity and sensitivity. These tests are valuable in identifying individuals who may benefit from immunization with varicella vaccine. [1]
Immunofluorescence [1] Polyclonal or monoclonal antibodies to VZV antigens can be used to rapid identification using the epithelial cells from suspected varicella lesions. [1]
Hybridization procedures or PCR [2] Southern blot , in situ hybridization procedures or PCR amplification can be a reliable identification method. [1]
References
  1. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899
  2. OTSUKA T, GOMI Y, INOUE N, UCHIYAMA M. Transmission of Varicella Vaccine Virus, Japan Emerg Infect Dis [online] 2009 Oct, 15(10):1702-1703 [viewed 09 September 2014] Available from: doi:10.3201/eid1510.090597

Investigations - Fitness for Management

Fact Explanation
Full blood count [2] These patients may be having thrombocytopenia (<30 000/μl), granulocytopenia (<500/μl), neutropenia as haematologic complications. [1] As they present with fever and have a high risk of superinfections with bacteria, it is important to evaluate for other infections. Elevated lymphocytes may be seen in these patients. White cell count may be elevated in bacterial infections (leucocytosis), platelets may become low in dengue fever.
Haemoglobin [2] They can develop anemia requiring transfusion. [1] Anaemia occurs due to the haemolysis induced by varicella infection.
References
  1. ZIEBOLD C, VON KRIES R, LANG R, WEIGL J, SCHMITT HJ. Severe complications of varicella in previously healthy children in Germany: a 1-year survey. Pediatrics [online] 2001 Nov, 108(5):E79 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11694663
  2. KUMAR KJ, KUMAR HC, MANJUNATH VG, ARUN V. Autoimmune Hemolytic Anemia due to Varicella Infection Iran J Pediatr [online] 2013 Aug, 23(4):491-492 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883384

Investigations - Followup

Fact Explanation
IgG antibody [2] If there are no complications, no investigations are required for the follow up. IgG antibodies to varicella can be checked in convalescent phase serum. [1]
References
  1. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899
  2. GILDEN D, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment Lancet Neurol [online] 2009 Aug, 8(8):731 [viewed 09 September 2014] Available from: doi:10.1016/S1474-4422(09)70134-6

Investigations - Screening/Staging

Fact Explanation
Alanine and aspartate transaminase [1] Even in asymptomatic hepatitis these levels may be elevated. [1]
References
  1. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899

Management - General Measures

Fact Explanation
Isolation VZV is a highly infectious disease. Infected individual transmits the disease by direct contact with skin lesions and by respiratory droplets. [1] They can return to their usual work after about 10 days of onset of the rash.
Supportive management [1] Rest, fever control, fluids and electrolyte balance is important. [1] Cool baths or cool compressive bandages can be prescribed. Regular bathing and cleaning of skin lesions are important.
Controlling the scratching Eg:-Hydroxyzine hydrochloride, Diphenhydramine etc [6] As the rash is itchy, patient tends to scratch the lesions often. Scratching leads to scarring of the skin and high risk of bacterial infections. [1] Wearing gloves on hands, especially at night, trimming fingernails and using medications to reduce itching: Hydroxyzine hydrochloride, Diphenhydramine etc are valuable measures in reducing the itching.
Diet No restrictions, but a soft, blended diet may be needed if sores are there in the mouth. [2]
Analgesics [5] Acetaminophen or ibuprofen used for fever. Aspirin should not be used as, the combination can cause Reye's syndrome. [1]
Vaccination [4] Live Attenuated Varicella vaccines are shown to be safe and effective. [2] Usually 2 doses are required for children aged 12 m–13 yrs and single dose is required for age >13 yrs Two doses, should be given at 4–8-wk interval. Congenital immunodeficiency, blood dyscrasias, leukemia, lymphoma, other malignancies , symptomatic HIV infection, high-dose systemic corticosteroids, pregnancy are main contraindications for vaccination. [3]
References
  1. MUELLER NH, GILDEN DH, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis of Disease, and Latency Neurol Clin [online] 2008 Aug, 26(3):675-viii [viewed 05 July 2014] Available from: doi:10.1016/j.ncl.2008.03.011
  2. DUNKLE LISA M., ARVIN ANN M., WHITLEY RICHARD J., ROTBART HARLEY A., FEDER HENRY M., FELDMAN SANDOR, GERSHON ANNE A., LEVY MOISE L., HAYDEN GREGORY F., MCGUIRT PAUL V., HARRIS JANNA, BALFOUR HENRY H.. A Controlled Trial of Acyclovir for Chickenpox in Normal Children. N Engl J Med [online] 1991 November, 325(22):1539-1544 [viewed 05 July 2014] Available from: doi:10.1056/NEJM199111283252203
  3. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899
  4. OTSUKA T, GOMI Y, INOUE N, UCHIYAMA M. Transmission of Varicella Vaccine Virus, Japan Emerg Infect Dis [online] 2009 Oct, 15(10):1702-1703 [viewed 09 September 2014] Available from: doi:10.3201/eid1510.090597
  5. KU CH, LIU YT, CHRISTIANI DC. Case Report: Occupationally Related Recurrent Varicella (Chickenpox) in a Hospital Nurse Environ Health Perspect [online] 2005 Oct, 113(10):1373-1375 [viewed 09 September 2014] Available from: doi:10.1289/ehp.7766
  6. WANG H, YOSIPOVITCH G. New insights into the pathophysiology and treatment of chronic itch in patients with End-stage renal disease, Chronic liver disease and Lymphoma Int J Dermatol [online] 2010 Jan, 49(1):1-11 [viewed 09 September 2014] Available from: doi:10.1111/j.1365-4632.2009.04249.x

Management - Specific Treatments

Fact Explanation
Antiviral therapy : Acyclovir [3] Treatment with intravenous Acyclovir is required in patients who have the evidence of disseminated disease, in newborns who were exposed to VZV shortly after birth and high risk groups such as malignancy, bone marrow or organ transplantation, high-dose steroid therapy, congenital T-cell immunodeficiencies and HIV infection. Dose would be : children < 1 yr, 10 mg/kg/dose given every 8 h as 1h infusion children > 1 yr, 500 mg/m2/dose given every 8 h as 1-h infusion Adults, 10 mg/kg/dose given every 8 h as 1-h infusion for 7 days. [2] But studies have shown that use of acyclovir within 24 hours of illness , reduces the overall severity of the illness. [1]
Varicella-zoster immune globulin [VZIG] [4] When an immunocompromised person is exposed to an infected patient with chicken pox, they should receive IVIG within 96 hrs of exposure. [1]
Treating complications Eg:- pneumonia, [4], skin infections Skin infections and pneumonia may be treated with antibiotics. Encephalitis patients should receive antiviral drugs. Hospitalization may be required. [1]
References
  1. MUELLER NH, GILDEN DH, COHRS RJ, MAHALINGAM R, NAGEL MA. Varicella Zoster Virus Infection: Clinical Features, Molecular Pathogenesis of Disease, and Latency Neurol Clin [online] 2008 Aug, 26(3):675-viii [viewed 05 July 2014] Available from: doi:10.1016/j.ncl.2008.03.011
  2. ARVIN AM. Varicella-zoster virus. Clin Microbiol Rev [online] 1996 Jul, 9(3):361-381 [viewed 05 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172899
  3. OTSUKA T, GOMI Y, INOUE N, UCHIYAMA M. Transmission of Varicella Vaccine Virus, Japan Emerg Infect Dis [online] 2009 Oct, 15(10):1702-1703 [viewed 09 September 2014] Available from: doi:10.3201/eid1510.090597
  4. Passive immunization against chicken-pox. Br Med J [online] 1969 Oct 11, 4(5675):62 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1629478