Management of VZV infections : ECC RICAI Paris December 1-3, 2004 Management of VZV infections : Current guidelines Pr Christian Chidiac Department of Infectious and Tropical Diseases Hôpital de la Croix Rousse F69317 Lyon christian.chidiac@chu-lyon.fr

Aim 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

Main references 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

VZV causes 2 distinct clinical diseases Introduction 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

Varicella Antiviral 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

Varicella Antiviral 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

Varicella Antiviral 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 Antiviral 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

Varicella Antiviral 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

Management of herpes zoster in immunocompetent host

Herpes zoster Main 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

Herpes zoster Antiviral 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)

Herpes zoster Steroids 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 zoster Acute 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)

Herpes zoster Acute 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

Management of VZV infections in immunocompromised host

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 * varicella

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)

Prophylaxis

Post 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)

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