Pr Christian ChidiacDepartment of Infectious and Tropical DiseasesHôpital de la Croix Rousse F69317 Lyonchristian.chidiac@chu-lyon.fr

Pr Christian ChidiacDepartment of Infectious and Tropical DiseasesHôpital de la Croix Rousse F69317 Lyonchristian.chidiac@chu-lyon.fr

Management of VZV infections :Current guidelines

Management of VZV infections :Current guidelines

ECC RICAIParis December 1-3, 2004

Aim of the presentationAim of the presentation

To present and discuss guidelines

For treatment and prophylaxis of Varicella and herpes zoster

• For immunocompetent pts

• For immunocompromised pts

Neonates management and vaccine are

excluded from this presentation

To present and discuss guidelines

For treatment and prophylaxis of Varicella and herpes zoster

• For immunocompetent pts

• For immunocompromised pts

Neonates management and vaccine are

excluded from this presentation

IHMF : International Herpes Manag²ement Forum

www.ihmf.org

SPILF (French Society for Infectious Diseases) Med mal inf 1998;28:692-712

British Society for the Study of Infection J infect 1998 36(suppl1):31-38

German Dermatology Society J Clin Vir 2003;26:277-289

IHMF : International Herpes Manag²ement Forum

www.ihmf.org

SPILF (French Society for Infectious Diseases) Med mal inf 1998;28:692-712

British Society for the Study of Infection J infect 1998 36(suppl1):31-38

German Dermatology Society J Clin Vir 2003;26:277-289

Main referencesMain references

IntroductionIntroduction

VZV causes 2 distinct clinical diseases Varicella or chickenpox

• Occurs in 90% children < 13 years

Herpes zoster or shingles• Recurrent localized infection• Occurs likely in elderly

Complications : More severe : Immunocompromised host +++ Elderly : PHN after herpes zoster

VZV causes 2 distinct clinical diseases Varicella or chickenpox

• Occurs in 90% children < 13 years

Herpes zoster or shingles• Recurrent localized infection• Occurs likely in elderly

Complications : More severe : Immunocompromised host +++ Elderly : PHN after herpes zoster

Management of varicella in the immunocompetent host

Management of varicella in the immunocompetent host

VaricellaAntiviral treatment for healthy children VaricellaAntiviral treatment for healthy children

Oral aciclovir (ACV) Recommended by IHMF

20 mg/kg up to 800 mg/d for 5 d

Not recommended in French guidelines (SPILF) Not a severe disease Risk of viral resistance related to antiviral use No evidence that ACV may prevent complication Cost/effectiveness not established in France

Oral aciclovir (ACV) Recommended by IHMF

20 mg/kg up to 800 mg/d for 5 d

Not recommended in French guidelines (SPILF) Not a severe disease Risk of viral resistance related to antiviral use No evidence that ACV may prevent complication Cost/effectiveness not established in France

VaricellaAntiviral for adults and adolescents (1)VaricellaAntiviral for adults and adolescents (1)

Recommended by IHMF Complications more likely and frequently more serious

than in children

Secondary cases more severe in households

Oral ACV 800 mg four to five times daily 5-7 d

V-ACV and FCV likely to be as effective as ACV• But no controlled trials

Not recommended by SPILF as routine

Recommended by IHMF Complications more likely and frequently more serious

than in children

Secondary cases more severe in households

Oral ACV 800 mg four to five times daily 5-7 d

V-ACV and FCV likely to be as effective as ACV• But no controlled trials

Not recommended by SPILF as routine

VaricellaAntiviral for adults and adolescents (2)VaricellaAntiviral for adults and adolescents (2)

Varicella-associated pneumonia :

Recommended by IHMF and SPILF

• Whether pregnant or not (IHMF)

• IV ACV 10 mg/kg/8h

More severe cases in adults and adolescents and

other at-risk individuals

Antiviral treatment recommended by IHMF as a priority

Varicella-associated pneumonia :

Recommended by IHMF and SPILF

• Whether pregnant or not (IHMF)

• IV ACV 10 mg/kg/8h

More severe cases in adults and adolescents and

other at-risk individuals

Antiviral treatment recommended by IHMF as a priority

VaricellaAntiviral for pregnant womenVaricellaAntiviral for pregnant women Recommended by IHMF

Oral ACV, V-ACV or FCV When varicella occurs in their second or third trimester BUT

• Recommendation based on anecdotal evidence• Drugs no licensed for use during pregnancy

SPILF Not recommended as routine But in case of risk of delivery in days following the rash

Severe and/or complicated varicella Recommended by IHMF and SPILF

Recommended by IHMF Oral ACV, V-ACV or FCV When varicella occurs in their second or third trimester BUT

• Recommendation based on anecdotal evidence• Drugs no licensed for use during pregnancy

SPILF Not recommended as routine But in case of risk of delivery in days following the rash

Severe and/or complicated varicella Recommended by IHMF and SPILF

VaricellaAntiviral for pts with serious complicationsVaricellaAntiviral for pts with serious complications

Cerebral ataxia, varicella-associated pneumonia, VZV encephalitis and cutaneous bacterial complications

Recommended by IHMF IV ACV 10 mg/kg Based on anecdotal evidence

Recommended by SPILF ACV licensed for severe manifestations of VZV

infections

Cerebral ataxia, varicella-associated pneumonia, VZV encephalitis and cutaneous bacterial complications

Recommended by IHMF IV ACV 10 mg/kg Based on anecdotal evidence

Recommended by SPILF ACV licensed for severe manifestations of VZV

infections

Management of herpes zoster in immunocompetent host

Management of herpes zoster in immunocompetent host

Herpes zosterMain problem is PainHerpes zosterMain problem is Pain

Definition Zoster Associated Pain (ZAP) :

• a continuum of pain from prodrome to PHN and as long as pain persists

Postherpetic Neuralgia (PHN) :• Established persisting pain and/or

dysaesthesia

Definition Zoster Associated Pain (ZAP) :

• a continuum of pain from prodrome to PHN and as long as pain persists

Postherpetic Neuralgia (PHN) :• Established persisting pain and/or

dysaesthesia

Herpes zosterAntiviral therapyHerpes zosterAntiviral therapy

Recommended by IHMF, SPILF, German guidelines For immunocompetent adults > 50 years Within 72 hours of lesion onset Oral route

• V-ACV 1000 mg three times a days, 7 d• FCV 250 or 500 mg three times a day• ACV 800 mg five time a day not preferred • Brivudin 125 mg once a day (Germany)

Recommended by IHMF, SPILF, German guidelines For immunocompetent adults > 50 years Within 72 hours of lesion onset Oral route

• V-ACV 1000 mg three times a days, 7 d• FCV 250 or 500 mg three times a day• ACV 800 mg five time a day not preferred • Brivudin 125 mg once a day (Germany)

Herpes zosterSteroidsHerpes zosterSteroids

Recommended by IHMF and German guidelines To reduce the inflammation that may contribute

to acute pain Provided there are no contra-indications Reduce acute symptoms and may facilitate

return to normal quality of life But do not prevent PHN

Recommended by IHMF and German guidelines To reduce the inflammation that may contribute

to acute pain Provided there are no contra-indications Reduce acute symptoms and may facilitate

return to normal quality of life But do not prevent PHN

Herpes zosterAcute pain (1)Herpes zosterAcute pain (1) Main cases

1st step : non steroidal analgesics (e.g. paracetamol) 2nd step : additional low potency opioid analgesic

(tramadol, codein) in combined preparations if needed 3rd step : in addition to a peripheral analgesic,

administration of high-potency central opioid (e.g. buprenorphine, oral morphine)

Severe neuralgic pain Anti-convulsivants (carbamazepine) Gabapentine Antidepressants amitryptillin and neuroleptics

(levomepromazin)

Main cases 1st step : non steroidal analgesics (e.g. paracetamol) 2nd step : additional low potency opioid analgesic

(tramadol, codein) in combined preparations if needed 3rd step : in addition to a peripheral analgesic,

administration of high-potency central opioid (e.g. buprenorphine, oral morphine)

Severe neuralgic pain Anti-convulsivants (carbamazepine) Gabapentine Antidepressants amitryptillin and neuroleptics

(levomepromazin)

Herpes zosterAcute pain (2)Herpes zosterAcute pain (2)

German guidelines

Early presentation to pain therapist or pain outpatient

clinic is suggested

IHMF, SPILF

Presence of risk factors for the development of PHN

should be assessed and documented for each patient

German guidelines

Early presentation to pain therapist or pain outpatient

clinic is suggested

IHMF, SPILF

Presence of risk factors for the development of PHN

should be assessed and documented for each patient

Management of VZV infections in immunocompromised host

Management of VZV infections in immunocompromised host

VZV infections in immunocompromised pts Antiviral treatment (1)VZV infections in immunocompromised pts Antiviral treatment (1)

IHMF, SPILF, German guidelines, UK* : IV ACV therapy is the standard of care

for imunocompromised patients with disseminated VZV disease, including those with complications such as

varicella pneumonia Recommended dose

Adults : 10 mg/kg every 8 h Children

• UK, France : 500 mg/m2 body surface area every 8 h• USA : 20 mg/kg every 8 h

IHMF, SPILF, German guidelines, UK* : IV ACV therapy is the standard of care

for imunocompromised patients with disseminated VZV disease, including those with complications such as

varicella pneumonia Recommended dose

Adults : 10 mg/kg every 8 h Children

• UK, France : 500 mg/m2 body surface area every 8 h• USA : 20 mg/kg every 8 h

* varicella

VZV infections in immunocompromised pts Antiviral treatment (2)VZV infections in immunocompromised pts Antiviral treatment (2)

IHMF, SPILF : Oral antiviral therapy Anecdotal evidence suggests that oral antiviral

therapy may be appropriate for the treatment of VZV disease in some immunocompromised individuals Varicella (IHMF) Herpes zoster (IHMF, SPILF), specially for segmented

herpes zoster without any dissemination, and with moderate immunosuppression (e.g HIV pts with CD4 > 200/mm3)

IHMF, SPILF : Oral antiviral therapy Anecdotal evidence suggests that oral antiviral

therapy may be appropriate for the treatment of VZV disease in some immunocompromised individuals Varicella (IHMF) Herpes zoster (IHMF, SPILF), specially for segmented

herpes zoster without any dissemination, and with moderate immunosuppression (e.g HIV pts with CD4 > 200/mm3)

ProphylaxisProphylaxis

Post exposure prophylaxisPost exposure prophylaxis

VZV immune globulin should be considered as soon as possible after exposure to varicella (< 72 h) for Immunocompromised individuals (IHMF, UK) Pregnant woman (IHMF, SPILF, UK)

Oral ACV recommended for pregnant woman (IHMF) Suppressive antiviral therapy (IV ACV) should be

considered for : Transplant pts (BMT) : (IHMF) Pts with immunosuppression for GVHD : (IHMF) Stem cell transplant recipient : (SPILF)

VZV immune globulin should be considered as soon as possible after exposure to varicella (< 72 h) for Immunocompromised individuals (IHMF, UK) Pregnant woman (IHMF, SPILF, UK)

Oral ACV recommended for pregnant woman (IHMF) Suppressive antiviral therapy (IV ACV) should be

considered for : Transplant pts (BMT) : (IHMF) Pts with immunosuppression for GVHD : (IHMF) Stem cell transplant recipient : (SPILF)

ConclusionConclusion

Conclusion Conclusion

Guidelines may differ among countries IV ACV is the standard of care for severe

VZV infections Oral antiviral therapy :

Recommended for pts > 50 years with herpes zoster to prevent PHN

Discussed for varicella in non compromised host and for prophylaxis

Guidelines may differ among countries IV ACV is the standard of care for severe

VZV infections Oral antiviral therapy :

Recommended for pts > 50 years with herpes zoster to prevent PHN

Discussed for varicella in non compromised host and for prophylaxis