zoster immunocompromised.ppt

Zoster Immunocompromised

Ri 楊鎰聰

Herpes Zoster N England J Med 2002; 347(5):340-346

Clinical manifestation of Varicella-Zoster virus infection Dermatologic clinics Volume 20,Number 2,April 2002

Visceral zoster as the presenting feature of disseminated herpes zoster Journal of the American Academy of Dermatology Volume 46,Number 5,May 2002

Management of herpes virus infections following transplantation Journal of Antimicrobial chemothearpy(2000) 45,729-748

References

What in a name?

Herpes: from the Greek word that translate as to creep

Zoster: Greek word for belt

Shingles: Latin word also meaning belt or gridle

Incidence of zoster

90% adult have serologic evidence of VZV infection in America

1.5~3/1000 annually in America

Age 60~80: 5~10/1000

Increasing age , older than 75: 10/1000

The life time risk of Herpes zoster is 10~20%

Incidence of zoster

Immunocompromised patients are at an approximately 20

fold increased risk for zoster than age matched controled

Host immune status Host immune status

NormalNormal ImmunocompromisedImmunocompromised

Number studiedNumber studied 8080 2424Cutaneous eventsCutaneous events

Median days from onset to:Median days from onset to:

Lesions free of VZVLesions free of VZV 5.35.3 7.07.0No new lesionsNo new lesions 4.94.9 5.05.050 % healing50 % healing 11.911.9 12.012.0Number withNumber with

Cutaneous Cutaneous disseminationdissemination

4(5)4(5) 5(21)5(21)

Visceral disseminationVisceral dissemination 00 2(8)2(8)

Post-herpetic neurogiaPost-herpetic neurogia 13(17)13(17) 4(17)4(17)

Acyclovir therapy for acute herpes zoster Lancet 1982;11:118-121

Who is at risk

Patient with underlying disease that are associated with immunocompromised status

1.Cancer: leukemia (lymphoblastic leukemia)

2.Patients taking cytotoxic drugs

3.Patients under chemotheray or raiotherapy

(Previous irradiation dermatomes are observed to have nearly twice the frequency for zoster than other dermatomes)

4. .Patients receiving steroids for condition such as asthma or eczema are at minimal risk

Who is at risk

5. SLE

6.all organ transplant recipient

7.AIDS (especially seropositive for herpes zoster)

Manifestation of VZV infection in immunocompromised patient

Varicella(chicken pox):primary infection

Zoster reactivation:1. localized dermatomal herpes zoster

2. diffuse cutaneous dissemination

(varicelliform zoster)

3. visceral zoster with skin lesions

4. visceral zoster without skin lesions

Host immune status Host immune status

NormalNormal ImmunocompromisedImmunocompromised

Number studiedNumber studied 8080 2424Cutaneous eventsCutaneous events

Median days from onset to:Median days from onset to:

Lesions free of VZVLesions free of VZV 5.35.3 7.07.0No new lesionsNo new lesions 4.94.9 5.05.050 % healing50 % healing 11.911.9 12.012.0Number withNumber with

Cutaneous Cutaneous disseminationdissemination

4(5)4(5) 5(21)5(21)

Visceral disseminationVisceral dissemination 00 2(8)2(8)

Post-herpetic neurogiaPost-herpetic neurogia 13(17)13(17) 4(17)4(17)

Visceral zoster

Visceral zoster has been classically defined as histologic or culture evidence of VZV or clinical evidence of internal organ involvement without other causes in the setting of cutaneous zoster

It has not been reported in immunocompetent patients

Visceral zosterIt occurs in 3~15% of immunocompromised patients

10% of those with cutaneous dissemination

The lungs are the most frequent noncutaneous organ involved in VZV infections

The liver is the most frequent abdominal organ involved

Mortality rate are high,even with intravenous acyclovir therapy,still 5~15%,most deaths by pneumonitis

Zoster in immunocompromised patients

May develop several episodes

Atypical manifestations (varicelliform zoster,chronic hyperkeratotic skin lesions, ACV resistance,bullous erythematous zoster, lichenoid reactions, follicular herpes zosterer

Increased severity of herpes zoster

ComplicationsMost healthy patients recover without sequelae from an attack of herpes zoster

In general,complications are more common among elderly or immunsuppressed patients

Postherpetic neuragia is the most common complications

Others like neurologic,dermatologic,and ocular complications can occur

Complications

Postherpetic neuragia is defined as pain that persists in an affected area for more than 1 month after the lesions have healed

Other neurologic complications like muscle weakness and motor nerve palsy are transient because of direct extension of the inflammatory response from the sensory ganglion to adjacent anterior horn cells in the spinal cord

Complications

Ocular complications like corneal damage accompanied by visual impairment is the most feared .Ocular palsy,lid ptosis, conjunctivitis,panophthalmitis, retinal vasculitis, retinal artery occlusion,optic neuritis,choroid detachment all have been reported

Secondary infection especially impetigo and cellulitis is the most dermatologic complications

Mortality

The most frequent causes of death are related to visceral complications of zoster: pneumonitis,hepatitis,encephalomyelitis,disseminated intravascular coagulopathy

Diagnosis

Clinical diagnosis sometimes is sufficiently distinctive

Typical: unilateral, does not cross the midline

Atypical cutaneous lesions may present especially in immunocompromised patients, it may require laboratory comfirmation

Diagnosis

Viral culture: possible but VZV virus is labile and difficult to recover from swabs of cutaneous lesions

A direct immunofluorescence assay is more sensitive

cells are stains with fluorescein-conjugated monoclonal antibodies against VZV virus, green fluorescence indicates the presence of VZV antigens

Wright stain of Tzanck smear revealed multinucleated giant cells

PCR: detect VZV virus DNA

Type of infectionType of infection Recommended therapyRecommended therapy

VaricellaVaricella Intravenous acyclovirIntravenous acyclovir

Localized dermatomal Localized dermatomal herpes zosterherpes zoster

Intravenous acyclovirIntravenous acyclovir

Oral acyclovir under Oral acyclovir under studystudy

Cutaneous disseminated Cutaneous disseminated herpes zosterherpes zoster


Visceral disseminated Visceral disseminated herpes zosterherpes zoster


Treatment of VZV infections in immunocompromised P’ts

The American Journal of Medicine volume 85(2A) 1988 68-73

Treatment of VZV infections in immunocompromised P’ts

Inmmunocompromised children:

Acyclovir 1500mg/m2/d iv divided into 3 doses for 5~10 days or 10 mg/kg iv q8h for 5~10 days

Immunocompromised adults:

Acyclovir 10 mg/kg dose iv q8h 7~10 days(including disseminated zoster)

For renal failure , substituting 7.5~5mg/kg/dose

Treatment of VZV infections in thoracic transplantation

Intravenous acyclovir is recommended for varicella in solid

organ transplant recipients of all ages (Category 2). For herpes zoster either iv or oral acyclovir, iv penciclovir, oral famciclovir or oral valaciclovir may be used (Category 3).


Prophylaxis of VZV infections in thoracic transplantation

No antiviral prophylaxis specifically directed at VZV infection is recommended (Category 3). Vaccination of seronegative children before transplant with live attenuated vaccine can reduce the risk of post-transplant primary VZV infection (Category 3).


About our patient

This 56 y/o male

A case of pulmonary alveolar proteinosis diagnosed via open lung biopsy in 86/3 with the initial presentation of progressive dyspnea for half a year.

He had undergone whole lung lavage for several times since 86/5. Progressive dyspnea despite home O2 supply since 92/9 happened. He was admitted since 9/10.

After admission, IV steroid was given for PAP but it seemed no effect. His O2 saturation was down to 83-84% while at room air. Chest surgeon was consulted for evaluation of lung trasnplantation

About our patient

He received bilatearl sequential lung transplantation on 12/31 under ECMO support.After that, He was transferred to ICU for post-op care

He began to use cyclosporin to prevent allograft rejection since 93.1.6

50mg/50c.c(1/6)…150mg/50c.c(1/17)……100mg/50mg(1/23)…..300mg/300mg(1/26)…..250mg/250mg(1/28)…..250mg/250mg(2/3)…..100mg(2/12)…..

He began to suffer from cutaneous lesions since 1/25

Dermatologist consulted on 1/27 confirmed the diagnosis of herpes zoster

About our patient

He began to use acyclovir since 1/27

1amp/500c.c N/S ivd (1/27)…..1amp/200c.c(2/1)…..2/5 DC acyclovir

After that, he complained about right ear pain for several months. The impression was post herpetic neuragia V3,C2,C3

Tofranil, Tramadol, Demerol

He suffered from herpes zoster infection again on late June. He began to use acyclovir since 6/30

Summary to his clinical pictureHe suffered from VZV infection at post transplantation 1 month

Risk factors for him are increasing age, immunocompromised

His clinical manifestations are atypical

Post herpetic neuragia happened on him

He suffered second episode of VZV infection on late June

At particular high risk of VZV infection

30% suffer post transplant VZV infection within 1 year (50% of these within 9 months)

45% involved have cutaneous or visceral dissemination

Mortality rate is 10% in above situation

Post herpetic neuragia or bacteria superinfection occurs often within 9 months of transplantation

Bone marrow transplant patient

Infection with VZV after marrow transplantation

J Infect Dis 152:1172,1985

The vaccine provide active immunization by way of the live attenuated virus,known as the Oka strain

Increases cytotoxic lymphocyte responses specific for VZV in seropositive elderly persons

They have not been FDA approved

Whether vaccine induced immune enhancement will reduce the incidence or severity of VZV infection is still in a clinical trials

Present we can do is that proper treatment should be initiated when VZV infection does occur

What can we do better?

Thanks your attentionThanks your attention

zoster immunocompromised.ppt

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