Guidelines on skin and oral HIV-associated conditions in children

and adults

WHO Department of Maternal, Newborn, Child and Adolescent

Health

Department of HIV/AIDS

Mucocutaneous manifestations in HIV

Common

High morbidity & mortality

Could be an indicator disease

Objectives

…to provide a summary of key evidence and practice

recommendations on

treatment of the main skin and oral conditions

in HIV-infected adults and children

What are these guidelines about?

Criteria for selectionBurden of diseaseSeverityImpact on prognosis of HIV

Marker of low CD4 initiation of ART

Applicability for primary health care levels in resource-poor settings

What are these guidelines about?

Who is the target audience?

Health proffesionals Policy makers Managers of HIV/AIDS control programmes

in settings with HIV infection, primarily where resources are limited.

Kaposi SarcomaSelection of patients for chemotherapy

No standardized criteria presently

Extent of tumour alone may be insufficient

Categorization of KS into mild/moderate & severe symptomatic based on the original ACTG tumour extent criteria

* Pending approval by the WHO guideline Review Committee

Kaposi Sarcoma

Recommended Regimens*

Rationale

Vincristine with Bleomycin and Doxorubicin (ABV)

Bleomycin with Vincristine (BV)

(When available or feasible)Liposomal anthracyclines (doxorubicin or daunorubicin)

Though  Liposomal anthracycline treatment is the standard of care, they are:

• Expensive• not widely available• remain under patent• require cold storage

Kaposi Sarcoma

* Pending approval by the WHO guideline Review Committee

Recommended Regimens

Disease Pending Recommendation*

Rationale

Mild SD Topical ketoconazol

2%

2-3 times / week for four weeksmaintenance treatment once / week as needed

• Evidence for treatment of SD in HIV very limited

• Evidence is strongest for Ketoconazole

• General concensus that combination of antifungals and corticosteroids is effective

• Potential side effects with topical corticosteroids

• Quality of evidence for ART alone is limited & of very low quality

Severe SDTopical antifungals (e.g. ketoconazole 2%) and topical corticosteroids

* Pending approval by the WHO guideline Review Committee

Seborrheic dermatitis

Pending Recommendati

on*

Rationale

ART should be considered as the primary treatment

Evidence for treatment of PPE in HIV very limitedSome evidence is available for resolution of PPE with ART

General concensus: ART initiation, with or without symptomatic therapy, as the best option

Additional symptomatic therapy

Antihistamines Topical corticosteroids

* Pending approval by the WHO guideline Review Committee

Pruritic papular eruption

Pending Recommendation* Rationale

ART should be considered as the primary treatment

Evidence base for all of the interventions was of very low quality

Expert opinion and general concensus: ART as the primary treatment

Should not discontinue the ART

Additional symptomatic therapyoral antihistamine if no adequate response, add:topical corticosteroids / oral itraconazole /permethrin 5% cream

* Pending approval by the WHO guideline Review Committee

Eosinophilic folluculitis

Disease type

Pending Recommendatio

n*

Rationale

TineaNot extensive

Topical terbinafine 1% Topical miconazole 2%

No evidence to determine if one class of antifungal is superior

Terbinafine, Miconazole • In“WHO essential medicine list” • widely available• Terbinafine offers shorter

duration of therapy

For extensive tinea:Expert panel favoured griseofulvin rather than terbinafine because of the latter’s higher cost

TineaExtensive, hair/nail involvement

Oral griseofulvin

If there is no response:Oral terbinafine or itraconazole

* Pending approval by the WHO guideline Review Committee

Tinea

PendingRecommendation*

Rationale

Acyclovir(at any time in the course of the disease)

Acyclovir, famciclovir and valaciclovir are all effectiveThe safety profiles of all three drugs similar

Acyclovir • Better availability• Costs less

* Pending approval by the WHO guideline Review Committee

Herpes zoster

Disease Pending Recommenda

tion*

Rationale

Classical scabies

1st line:Permethrin 5% 2nd line:Oral ivermectin

Permethrin appears to be the most effective treatment for scabies

The limited data on crusted scabies in HIV-infected patients suggest a good effect of oral ivermectin

Crusted scabies

1st line:Oral ivermectin *2nd line:Permethrin 5%

*avoid in children <15kg

Scabies

* Pending approval by the WHO guideline Review Committee

* Pending approval by the WHO guideline Review Committee

Molluscum contagiosum

PendingRecommendati

on*

Rationale

Oral fluconazoleWhen fluconazole is not available or contraindicated:nystatin suspension or pastilles, or clotrimazole troches

ketoconazole, fluconazole, itraconazole and clotrimazole are all effective

Oral fluconazole • Highly effective• Single dose• Better bioavailability• Less toxicity• Less drug interaction

* Pending approval by the WHO guideline Review Committee

Oropharyngeal Candidiasis

Pending Recommendati

on*

Rationale

Suspected causative drug should be promptly discontinued and supportive therapies should be offered

Absence of good evidence to support the use of oral steroids, immunoglobulins or cyclosporine-A

Steroids may:• Decrease survival in the

paediatric group• Place the HIV-infected

patient at risk for OI / sepsis

Stevens-Johnson Syndrome

* Pending approval by the WHO guideline Review Committee

Tool to aid in diagnosis of skin conditionsAfter input from dermatologists in the field, the tool was refined to include better diagnostic criteria, additional diagnoses of relevance, additional pictures of children and of skin diseases in diverse subjects.

The research gaps

Common to all conditions…

Research in HIV infected Research in Children Standardized outcome measures Well designed prospective,

randomized double blind studies with adequate power

Effect of ART … does it manifest as an IRIS

Contributors to the GRADE systematic reviews and supporting evidenceEsther Freeman (Harvard Medical School, USA), Toby Maurer (University of California, USA), Oluwatoyin Gbabe (Stellenbosch University, South Africa), Charles L. Okwundu (Stellenbosch University, South Africa), Miriam Laker (University of California, USA), Philippa J. Easterbrook (World Health Organization, Switzerland), Jeffrey Martin (University of California, USA), Martin Dedicoat (Birmingham Heartlands Hospital, United Kingdom).Andrew Anglemyer (University of California, USA), Anurag K. Agarwal (Baylor College of Medicine, USA), George W. Rutherford (University of California, USA).John Stephen (St. John's Medical College, India) Tony Raj (St. John's Medical College, India), Kedar Radhakrishna (St. John's Medical College, India), Tinku Thomas (St. John's Medical College, India).Ser Ling Chua (University Hospital Birmingham, United Kingdom), Kedar Radhakrishna (St. John's Medical College, India), John Stephen (St. John's Medical College, India), Mike Zangenberg (World Health Organization, Switzerland).Mamaduo O. Diallo (Centers for Disease Control and Prevention, USA), Magdy El-Gohary (University of Southampton, United Kingdom), Esther J. van Zuuren (Leiden University, Netherlands), Hana Burges (University of Southampton, United Kingdom), Liz Doney (University of Nottingham, United Kingdom), Zbys Fedorowicz (Cochrane Collaboration Awali, Bahrain), Michael Moore (University of Southampton, United Kingdom), Paul Litle (University of Southampton, United Kingdom).Dunja Vekic (St. Vincent’s Hospital, Australia), Lisa Abbot (St. Vincent’s Hospital, Australia), Emily Asher (University of California, USA), Margot Whitfeld (Skin and Cancer Foundation, Australia). Elissa M. McDonald (University of Auckland, New Zealand), Johannes de Kock (Wanganui Hospital, New Zealand), Feliz S.F. Ram (Massey University, New Zealand), Cristina C. Chang (Monash University, Australia), Vivek Naranbhai (Doris Duke Medical Research Institute, South Africa), Allen C. Cheng (Monash University, Australia), Monica Slavin (Peter MacCallum Institute, Australia), Abijeet Waghmare (St. John's Medical College, India).Paul Harris (London School of Hygiene & Tropical Medicine, United Kingdom)Elizabeth D. Pienaar (Medical Research Council, South Africa), Taryn Young (Medical Research Council, South Africa), Haly Holmes (University of Western Cape, South Africa). WHO Staff and Consultants Lulu Muhe, Philippa Easterbrook, Mike Zangenberg, Elizabeth, Frank Lule, Kasonde Mwinga, Meg Doherty, Rajiv Bahl, Wilson Were, Peggy Henderson,

Thank you!