Disseminated VZV infection and asymptomatic VZV vasculopathy after steroid abuse

doi:10.1016/j.jcv.2015.03.016

Journal of Clinical Virology

Volume 66, May 2015, Pages 72-75

https://doi.org/10.1016/j.jcv.2015.03.016 Get rights and content

Highlights

•
Long-term corticosteroid use can potentiate VZV infection and dissemination.
•
VZV has a predilection for arteries.
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Early VZV vasculopathy can occur without clinical features.

Abstract

A 60-year-old man who abused corticosteroids developed thoracic-distribution zoster. Varicella zoster virus (VZV) DNA was found in non-healing skin 3 months later. He died suddenly 2 months later. Skin was ulcerated and necrotic. VZV was widespread in organs and arteries, particularly coronary arteries and aorta, with VZV vasculopathy in the posterior cerebral artery.

Section snippets

Why this case is important

Primary infection with VZV usually results in varicella, after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. VZV reactivation in elderly and immunocompromised individuals causes herpes zoster and other neurological diseases, including stroke (VZV vasculopathy). Zoster is also associated with an increased risk of myocardial infarction [1].

Herein is a case of sudden death in a zoster patient who abused steroids. Autopsy

Case description

In August 2013, a 60-year-old man developed right-sided T6-7 distribution zoster. He was treated with valacyclovir and oral prednisone, taken near-continuously for pain relief. Zoster lesions below the right nipple (Fig. 1A) and in the same posterior dermatome (Fig. 1B) became ulcerated and did not heal, and VZV DNA was detected by PCR 3 months later. For 7 years before zoster, he self-administered corticosteroids repeatedly for ill-defined musculoskeletal aches; from 2011–2013, he consumed at

Other similar and contrasting cases in the literature

There have been no previously reported cases of VZV antigen in systemic arteries and cardiovascular structures of subjects with corticosteroid abuse, chronic VZV infection and sudden death.

Discussion

We describe an extraordinary case of sudden death in a 60-year-old man 5 months after thoracic-distribution zoster. Several features are remarkable. First was a 7-year history of frequent corticosteroid use, before and particularly during the interval between zoster and death, which likely potentiated VZV infection [2], as evidenced by amplifiable VZV DNA from skin 3 months after zoster, when rash has usually resolved, as well as by ulceration and necrosis of skin over the site of earlier

Conflict of interest

All authors declare no competing interests.

Funding

This work was supported by the National Institutes of Health (AG032958 to D.G. and M.A.N., AG006127 to D.G., and NS067070 to M.A.N.).

Ethical approval

Not required.

Authors contribution

M.A.N., D.L. and D.G. reviewed the literature, wrote the manuscript, contributed to the conception and design of the study, and acquired, analyzed and interpreted the data. T.W., N.K. and A.H. acquired, analyzed and interpreted data. P.J.B. analyzed and interpreted the data. All authors have approved the final manuscript.

Acknowledgements

The authors thank Marina Hoffman for editorial assistance and Cathy Allen for manuscript preparation.

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Herpes zoster and its cardiovascular complications in the elderly – another look at a dormant virus
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Varicella zoster induced cardiac dysfunction: a case report
Emergency Med. J.
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S. Standing
Gray’s Anatomy
(2008)

There are more references available in the full text version of this article.

Cited by (15)

Herpes Zoster in the Older Adult
2017, Infectious Disease Clinics of North America
Citation Excerpt :
The presence of VZV in the arteries, in conjunction with the increased inflammatory response seen in infected individuals, might result in disruption of atherosclerotic plaques.7,38 In some instances, VZV vasculopathy may result in cardiac dysfunction without any concomitant neurologic manifestation.11 Manifestations of VZV CNS vasculopathy range from transient ischemic attacks, stroke (ischemic or hemorrhagic), aneurysm, subarachnoid and intracerebral hemorrhage, spinal cord infarction, cerebral venous sinus thrombosis, vision loss, giant cell temporal arteritis, or other focal neurologic deficits depending on the location of the infarction.7,13
Clinical Characteristics and Outcomes in a Population With Disseminated Herpes Zoster: A Retrospective Cohort Study
2017, Actas Dermo-Sifiliograficas
El herpes zoster es la expresión cutánea de la reactivación de una infección latente en ganglios sensitivos por el virus varicela zoster que se presenta con vesículas en el dermatoma correspondiente. Cuando compromete más de 2 dermatomas contiguos, presenta más de 20 vesículas por fuera del dermatoma inicial o tiene compromiso sistémico se denomina herpes zoster diseminado (HZD). Esta entidad es infrecuente y se suele presentar en pacientes inmunodeprimidos.
Describir la epidemiología, factores predisponentes, clínica, laboratorio y evolución clínica de pacientes con HZD. Comparar hallazgos entre inmunodeprimidos e inmunocompetentes.
Estudio de una serie de casos retrospectiva, en adultos ingresados entre febrero de 2010 y octubre de 2015.
Se incluyeron 41 pacientes con cuadro clínico de HZD y confirmación virológica. Se detectaron factores de estrés desencadenantes en el 39% y de inmunodepresión en el 58,5%. Los inmunodeprimidos fueron más jóvenes que los inmunocompetentes (60,5 vs 82 años, p < 0,01). En 8 casos sin inmunodepresión ni desencadenantes se halló mayor edad (85 años). En el 95% de los casos el HZD comenzó en dermatomas definidos, y luego se extendió a otros o se generalizó. El 56% de los casos presentó trombocitopenia asociada. Las complicaciones afectaron por igual a inmunodeprimidos e inmunocompetentes (54% vs 59%, p > 0,01). Fallecieron 6 pacientes, sin diferencias de mortalidad entre ambos grupos.
Este estudio aporta evidencia sobre la relación entre el HZD, la presencia de inmunosupresión subyacente y las posibles complicaciones. En pacientes inmunocompetentes, por inmunosenescencia, la edad podría desempeñar un papel importante en la aparición de esta enfermedad.
Shingles is the cutaneous expression of the reactivation of latent varicella zoster virus infection in sensory ganglia. It presents as vesicles in the corresponding dermatome. The condition is called disseminated herpes zoster (DHZ) when more than 2 contiguous dermatomes are affected, more than 20 vesicles are observed outside the initial dermatome, or involvement is systemic. DHZ is rare and most frequently occurs in immunocompromised patients.
To describe the epidemiology, predisposing factors, clinical presentation, laboratory findings, and clinical course of patients with DHZ, and to compare the findings in immunocompromised and immunocompetent patients.
We analyzed a retrospective case series of adults hospitalized between February 2010 and October 2015.
Forty-one patients with virologically confirmed manifestations of DHZ were included. Stress as a trigger factor was detected in 39% and immunodepression in 58.5%. Immunocompromised patients were younger than the immunocompetent patients (mean ages, 60.5 vs 82 years, P < .01). The 8 immunocompetent patients with no detectable trigger factors were older (mean age, 85 years). In 95% of cases, DHZ was initially limited to a single dermatome and then spread to other dermatomes or became disseminated. Thrombocytopenia was detected in 56% of cases. Complication rates were similar in immunocompromised and immunocompetent patients (54% vs 59%, P > .01). Six patients died; there was no difference in mortality between the 2 groups.
This study provides evidence on the relationship between DHZ, the presence of underlying immunodepression, and complications. Immunosenescence may play an important role in the onset of this disease in older immunocompetent patients.
Clinical Characteristics and Outcomes in a Population With Disseminated Herpes Zoster: A Retrospective Cohort Study
2017, Actas Dermo-Sifiliograficas
El herpes zoster es la expresión cutánea de la reactivación de una infección latente en ganglios sensitivos por el virus varicela zoster que se presenta con vesículas en el dermatoma correspondiente. Cuando compromete más de 2 dermatomas contiguos, presenta más de 20 vesículas por fuera del dermatoma inicial o tiene compromiso sistémico se denomina herpes zoster diseminado (HZD). Esta entidad es infrecuente y se suele presentar en pacientes inmunodeprimidos.
Describir la epidemiología, factores predisponentes, clínica, laboratorio y evolución clínica de pacientes con HZD. Comparar hallazgos entre inmunodeprimidos e inmunocompetentes.
Estudio de una serie de casos retrospectiva, en adultos ingresados entre febrero de 2010 y octubre de 2015.
Se incluyeron 41 pacientes con cuadro clínico de HZD y confirmación virológica. Se detectaron factores de estrés desencadenantes en el 39% y de inmunodepresión en el 58,5%. Los inmunodeprimidos fueron más jóvenes que los inmunocompetentes (60,5 vs 82 años, p < 0,01). En 8 casos sin inmunodepresión ni desencadenantes se halló mayor edad (85 años). En el 95% de los casos el HZD comenzó en dermatomas definidos, y luego se extendió a otros o se generalizó. El 56% de los casos presentó trombocitopenia asociada. Las complicaciones afectaron por igual a inmunodeprimidos e inmunocompetentes (54% vs 59%, p > 0,01). Fallecieron 6 pacientes, sin diferencias de mortalidad entre ambos grupos.
Este estudio aporta evidencia sobre la relación entre el HZD, la presencia de inmunosupresión subyacente y las posibles complicaciones. En pacientes inmunocompetentes, por inmunosenescencia, la edad podría desempeñar un papel importante en la aparición de esta enfermedad.
Shingles is the cutaneous expression of the reactivation of latent varicella zoster virus infection in sensory ganglia. It presents as vesicles in the corresponding dermatome. The condition is called disseminated herpes zoster (DHZ) when more than 2 contiguous dermatomes are affected, more than 20 vesicles are observed outside the initial dermatome, or involvement is systemic. DHZ is rare and most frequently occurs in immunocompromised patients.
To describe the epidemiology, predisposing factors, clinical presentation, laboratory findings, and clinical course of patients with DHZ, and to compare the findings in immunocompromised and immunocompetent patients.
We analyzed a retrospective case series of adults hospitalized between February 2010 and October 2015.
Forty-one patients with virologically confirmed manifestations of DHZ were included. Stress as a trigger factor was detected in 39% and immunodepression in 58.5%. Immunocompromised patients were younger than the immunocompetent patients (mean ages, 60.5 vs 82 years, P < .01). The 8 immunocompetent patients with no detectable trigger factors were older (mean age, 85 years). In 95% of cases, DHZ was initially limited to a single dermatome and then spread to other dermatomes or became disseminated. Thrombocytopenia was detected in 56% of cases. Complication rates were similar in immunocompromised and immunocompetent patients (54% vs 59%, P > .01). Six patients died; there was no difference in mortality between the 2 groups.
This study provides evidence on the relationship between DHZ, the presence of underlying immunodepression, and complications. Immunosenescence may play an important role in the onset of this disease in older immunocompetent patients.
Varicella Zoster Virus: A Common Cause of Stroke in Children and Adults
2016, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
As for treatment of GCA, no trials have yet been conducted to determine whether antivirals and steroids confer additional benefit to steroids alone. Although many GCA patients improve with steroids, reports are legion of GCA patients who relapse with corticosteroid withdrawal and may also develop more disseminated VZV vasculopathy and die.60,61 Because VZV triggers the immunopathology of GCA, antiviral treatment is likely to confer additional benefit to corticosteroids.
Varicella zoster virus (VZV) is a neurotropic, exclusively human herpesvirus. Primary infection causes varicella (chickenpox), after which the virus becomes latent in ganglionic neurons along the entire neuraxis. As cell-mediated immunity to VZV declines with advancing age and immunosuppression, VZV reactivates to produce zoster (shingles). One of the most serious complications of zoster is VZV vasculopathy.
We reviewed recent studies of stroke associated with varicella and zoster, how VZV vasculopathy is verified virologically, vaccination to prevent varicella and immunization to prevent zoster, and VZV in giant cell arteritis (GCA).
We report recent epidemiological studies revealing an increased risk of stroke after zoster; the clinical, laboratory, and imaging features of VZV vasculopathy; that VZV vasculopathy is confirmed by the presence of either VZV DNA or anti-VZV IgG antibody in cerebrospinal fluid; special features of VZV vasculopathy in children; vaccination to prevent varicella and immunization to prevent zoster; and the latest evidence linking VZV to GCA.
In children and adults, VZV is a common cause of stroke.
Risk of Stroke and Myocardial Infarction after Herpes Zoster in Older Adults in a US Community Population
2016, Mayo Clinic Proceedings
Citation Excerpt :
Any increased risk of MI within 3 months of zoster may similarly be caused by virus infection of coronary arteries after transaxonal spread of VZV that reactivated from autonomic and dorsal root ganglia. A recent report described a patient taking long-term corticosteroids who developed thoracic herpes zoster and died suddenly 5 months later; postmortem examination revealed VZV in multiple coronary arteries and in the posterior cerebral artery.39 Inflammatory cells that secrete soluble factors that contribute to vascular remodeling and can potentially disrupt preexisting atherosclerotic plaques have also been detected in VZV-infected arteries40 and are noted as potentially important in the increased risk of MI after respiratory and urinary tract infections and sepsis.41,42
To assess the risk of stroke and myocardial infarction (MI) after herpes zoster in a US community population of older adults.
We performed a community cohort study (January 1, 1986, to October 1, 2011) comparing the risk of stroke and MI in 4862 adult residents of Olmsted County, Minnesota, 50 years and older with and without herpes zoster and 19,433 sex- and age-matched individuals with no history of herpes zoster. Odds ratios are presented for MI and stroke at 3, 6, 12, and 36 months after index herpes zoster plus hazard ratios for long-term risk (up to 28.6 years).
Individuals with herpes zoster had more risk or confounding factors for MI and stroke, suggesting that they had worse health status overall. When controlling for the multiple risk factors, those with herpes zoster were at increased risk for stroke at 3 months after herpes zoster compared with those without a history of herpes zoster (odds ratio, 1.53; 95% CI, 1.10-2.33; P=.04). The association between herpes zoster and MI at 3 months was not robust across analytic methods. Herpes zoster was not associated with an increased risk of stroke or MI at any point beyond 3 months.
Herpes zoster was associated with only a short-term increased risk of stroke, which may be preventable with the prevention of herpes zoster.
Targeted RNA Sequencing of Formalin-Fixed, Paraffin-Embedded Temporal Arteries from Giant Cell Arteritis Cases Reveals Viral Signatures
2021, Neurology: Neuroimmunology and NeuroInflammation

View all citing articles on Scopus

¹: M.A.N. and D.L. contributed equally to this work.

View full text

Case reportDisseminated VZV infection and asymptomatic VZV vasculopathy after steroid abuse

Highlights

Abstract

Section snippets

Why this case is important

Case description

Other similar and contrasting cases in the literature

Discussion

Conflict of interest

Funding

Ethical approval

Authors contribution

Acknowledgements

Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study int he UK

Neurology

The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom

Arthritis Rheum

Herpes zoster and its cardiovascular complications in the elderly – another look at a dormant virus

Cardiology

Varicella zoster induced cardiac dysfunction: a case report

Emergency Med. J.

Gray’s Anatomy

Case report
Disseminated VZV infection and asymptomatic VZV vasculopathy after steroid abuse