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Year : 2016  |  Volume : 59  |  Issue : 3  |  Page : 422-424
Maculopapular rash presentation of febrile illness in an adult with Varicella zoster virus infection

1 Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India
2 Department of Medicine, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India

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Date of Web Publication10-Aug-2016


Varicella zoster usually manifests as maculopapular rash (MPR), which later progresses to vesicle. It can also manifest as MPR without progression to the vesicle stage. This atypical manifestation is more common in adults and immunocompromised patients. A 30-year-old female presented with high-grade fever and rash over face and body for 5 days. She was diagnosed to have Varicella zoster virus (VZV) infection by positive VZV immunoglobulin M enzyme-linked immunosorbent assay and polymerase chain reaction. We present this case to increase awareness among clinicians on the atypical manifestations of VZV and prevent complications by early diagnosis.

Keywords: Clinical awareness, maculopapular rash, molecular diagnosis, Varicella zoster virus

How to cite this article:
Ojah S, Barani R, Sudhakar M K, Ramakrishnan S R, Srikanth P. Maculopapular rash presentation of febrile illness in an adult with Varicella zoster virus infection. Indian J Pathol Microbiol 2016;59:422-4

How to cite this URL:
Ojah S, Barani R, Sudhakar M K, Ramakrishnan S R, Srikanth P. Maculopapular rash presentation of febrile illness in an adult with Varicella zoster virus infection. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Aug 16];59:422-4. Available from: https://www.ijpmonline.org/text.asp?2016/59/3/422/188127

   Introduction Top

Varicella zoster virus (VZV) is a double-stranded DNA virus, which belongs to Herpesviridae family. VZV is also known to present as fever with maculopapular rash (MPR) with nonprogression to vesicle.[1] Atypical clinical presentation may occur in immunocompromised patients.[2] VZV infection in older children and adult may lead to lethal complications.[3] There are reports of reactivation of the virus even among immunocompetent patients.[4]

Fever with generalized MPR in an adult usually occurs in viral infections, drug reaction, and immune complex-mediated syndromes. In tropical countries like India, seasonal occurrence of MPR in an adult during monsoon is usually attributed to dengue or leptospira infection.

Here, we present a case of fever with generalized rash in a 30-year-old female who tested negative for dengue and leptospirosis but was diagnosed as VZV by serology and conventional polymerase chain reaction (PCR).

   Case Report Top

A 30-year-old female was admitted following complaints of high grade, intermittent fever associated with headache, chills, rigor, and MPR over face and body with no joint pain for 5 days. Patient also had vomiting, loose stools but not a diabetic or hypertensive or other comorbid conditions. Patient gave no history of receiving VZV vaccine. On examination, patient was febrile (104.6°F) with pulse rate 154/min, blood pressure 90/60 mmHg, and conjunctival congestion in both eyes. Respiratory, abdominal, cardiovascular, and neurological examinations were unremarkable. Hematological examination revealed a white blood cell count of 16,600/cu mm, platelet count of 2.33 lakh/cu mm, and 85% peripheral smear with neutrophils. Among the liver function tests, serum glutamic oxaloacetic transaminase was 35 U/L, serum glutamic pyruvic transaminase 48 U/L, and alkaline phosphatase was 46 U/L. The bilirubin, total protein, albumin, and globulin levels were normal. Routine microscopic examination of urine showed ketones of 1+, 2–3 pus cells/HPF, 1–2 red blood cell/HPF, and 3–4 epithelial cells/HPF. Urine culture showed  Escherichia More Details coli with colony of 105 CFU/ml. Creatine phosphokinase (CPK) was found to be 1364 U/L, creatinine was 1.3 mg/dl, and random blood sugar was 147 mg/dL. Blood culture and stool culture showed no growth and stool wet mount showed no ova and cyst. Serology for leptospira immunoglobulin M (IgM), dengue IgM, IgG antibody, and NS1 antigen was found to be negative. Chest X-ray and abdominal ultrasound were normal. Patient was treated with injection ceftriaxone, tablet nitrofurantoin, and capsule doxycycline.

VZV infection was confirmed by positive VZV IgM quantitative enzyme-linked immunosorbent assay (ELISA) (IBL International, Germany) and positive by conventional PCR with “ORF 8” as the target site for VZV as previously described.[5] The patient serum sample showed an IgM titer of 17 U/mL.

For VZV PCR, serum sample was collected on day 5 of hospital admission. DNA was extracted using QIAamp DNA Blood Mini Kit and used for the PCR. Live attenuated vaccines (Oka strain, Lot No.: 304064, Expiry Date: 03/15, VHB, India) and sterile double-distilled water were used as positive and negative control, respectively. PCR was performed using 50 µL reaction mixture contain 45 µL of 2 U of hot start Taq polymerase, 200 µM dNTP's, 10 pM of VZV ORF8 specific forward and reverse primers includes VP22-CACACGATAATGCCTGATCGG, VM20-TGCTGATATTTCCACGGTACAGC with the addition of 5 µL of extracted DNA, negative control, and positive control. Amplification was performed using cycling conditions described previously.[6] The DNA was amplified using thermal cycler (Veriti 96 well thermal cycler, Applied Biosystems, Foster city, CA, USA). The amplified products were analyzed by 2% agarose gel and documented using gel documentation system (GEL DOC, BIO-RAD, HERCULES, CA, USA). The amplified product of 275bp in the sample was considered positive [Figure 1]. The sample was retested by PCR by another investigator and was found to be repeatedly positive.
Figure 1: Agarose gel electrophoresis of polymerase chain reaction products

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E. coli in urine with a colony count of 105 in the patient may have contributed to the increased total count with neutrophils. Patient also had 1+ ketone probably secondary to the bacterial infection. The raised CPK level may be attributed to rhabdomyolysis associated with the dual infection of E. coli and VZV. Patient recovered well following the treatment for UTI. All the hematological parameters were retested and were found within normal range. Patient was discharged with the advice to continue tablet nitrofurantoin 100 mg for 1 week and capsule doxycycline 100 mg for 4 days. Since the samples were batch tested for IgM and PCR for VZV, the report was available only after the patient was discharged. Therefore, the patient did not receive any antiviral therapy.

   Discussion Top

Chicken pox rash usually manifests as maculopapules, vesicles, and scabs in various stages of evolution. The lesions initially contain clear vesicular fluid, but in a short period of time pustulate and scab. Rash first appears on the trunk and face and then spreads rapidly to involve other areas of the body.[7] Natural immunity is protective against chickenpox; however, it does not always provide immunity against clinical reinfection. Clinical reinfection is more common in immunocompromised than in immunocompetent patients.[8] A routine two-dose Varicella vaccine is highly effective in preventing Varicella; however, it produces robust immunity in children than in adults.[9] Some cases of VZV may present with atypical symptoms in which MPR do not progress to vesicle stage. Such atypical viral exanthems are very difficult to distinguish from drug-induced exanthemas. We suggest that VZV be considered as a possible etiologic agent in such situations, and investigations such as ELISA for IgM and PCR be done to arrive at a diagnosis and prevent the progression to life-threatening complications. The IgM positivity in the presence of clinical evidence of fever with rash is indicative of acute infection and in conjunction with PCR positivity confirms acute VZV infection. Atypical manifestations are sometimes associated with severe life-threatening complications such as pneumonitis, encephalitis, cerebellar ataxia, bacterial superinfection of skin lesions, and maternal and fetal Varicella syndrome. Complications are more common in the immunocompromised host. However, complications such as meningitis have been reported in the immunocompetent patients.[2]

In the present case, patient recovered well even after having secondary bacterial infection because she was not a diabetic, and she was not on any immunosuppressive medication.

This case is being reported to increase awareness among clinicians on the atypical manifestations of VZV. In such circumstances, clinician should perform appropriate diagnostic tests. This needs further investigation, and more studies need to be carried out on patients with fever and rash, especially in the older age group.

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Conflicts of interest

There are no conflicts of interest.

   References Top

LaGuardia JJ, Gilden DH. Varicella-zoster virus: A re-emerging infection. J Investig Dermatol Symp Proc 2001;6:183-7.  Back to cited text no. 1
Gnann JW Jr. Varicella-zoster virus: Atypical presentations and unusual complications. J Infect Dis 2002;186 Suppl 1:S91-8.  Back to cited text no. 2
Balkis MM, Ghosn S, Sharara AI, Atweh SF, Kanj SS. Disseminated Varicella presenting as acute abdominal pain nine days before the appearance of the rash. Int J Infect Dis 2009;13:e93-5.  Back to cited text no. 3
Esposito S, Bosis S, Pinzani R, Morlacchi L, Senatore L, Principi N. A case of meningitis due to varicella zoster virus reactivation in an immunocompetent child. Ital J Pediatr 2013;39:72.  Back to cited text no. 4
Markoulatos P, Georgopoulou A, Siafakas N, Plakokefalos E, Tzanakaki G, Kourea-Kremastinou J. Laboratory diagnosis of common herpesvirus infections of the central nervous system by a multiplex PCR assay. J Clin Microbiol 2001;39:4426-32.  Back to cited text no. 5
Sachithanandham J, Ramamurthy M, Kannangai R, Daniel HD, Abraham OC, Rupali P, et al. Detection of opportunistic DNA viral infections by multiplex PCR among HIV infected individuals receiving care at a tertiary care hospital in South India. Indian J Med Microbiol 2009;27:210-6.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
Arvin AM. Varicella-zoster virus. Clin Microbiol Rev 1996;9:361-81.  Back to cited text no. 7
Hall S, Maupin T, Seward J, Jumaan AO, Peterson C, Goldman G, et al. Second varicella infections: Are they more common than previously thought? Pediatrics 2002;109:1068-73.  Back to cited text no. 8
Gershon AA, Steinberg SP, Gelb L. Clinical reinfection with varicella-zoster virus. J Infect Dis 1984;149:137-42.  Back to cited text no. 9

Correspondence Address:
Dr. Padma Srikanth
Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, #1, Ramachandra Nagar, Porur, Chennai - 600 116, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.188127

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