Skin and Mucosal Lesions in HIV-Infected Children

1. Skin and Mucosal Lesions in HIV-Infected Children HAIVN Harvard Medical School AIDS Initiative in Vietnam

2. www.hivguidelines.org

3. Learning Objectives By the end of this session, participants should be able to: • Diagnose common skin diseases/conditions in HIV-infected children • Understand the treatment of common skin diseases in HIV-infected children

4. Overview • Diseases affecting skin and mucosal flora are extremely common in HIV patients: • Prevalence is approximately 36-84% • Certain skin conditions are the first indicators of HIV infection • HIV patients are affected by the same skin conditions in the general population, but they tend to be more severe, more extensive, and prone to relapse and present atypically

5. Manifestations of Local Infections • Acne • Vesicles / blisters • Impetigo • Ulcers • Abscesses • Myositis, osteomyelitis • Fever

6. Common Dermatologic Conditions Seen in HIV-infected Children (1) • Oral mucocutaneous conditions: • Oral candidiasis • Herpes simplex infection • Oral hairy leukoplakia • Aphthous ulcer • Dental problems: linear gingival erythema, poor dentition • Parotid enlargement

7. Common Dermatologic Conditions Seen in HIV-infected Children (2) • Infectious etiologies: • Bacteria: • Staphylococcus • streptococcus • Fungi: cutaneous or systemic • Candida • Penicillium marneffei • Viruses: • Herpes Simplex (HSV) • Herpes Zoster (VZV) • Human Papilloma Virus (HPV) • Molluscumcontagiosum • Other: • Scabies

8. Common Dermatologic Conditions Seen in HIV-infected Children (3) • Non-infectious etiologies • Papular pruritic eruption (PPE) • Eczema • Psoriasis • Seborrheic dermatitis • Cutaneous hypersensitivity reaction to drugs or insect bites • Tumors: • Non-Hodgkin lymphoma • Kaposi Sarcoma

9. Candidiasis

10. Oral Mucosal Infection • Oral candidiasis: • Most common mucocutaneous disease seen in HIV children • Common types: • Pseudomembranous (most common) • Atrophic/erythematous • Hypertrophic • Angular cheilitis • Esophageal candidiasis: • secondary to extension of oral candida infection • probably present If the child has difficulty feeding or swallowing, or complains of pain on swallowing

12. Skin Infection • Ill-defined erythematous plaques with satellite lesions • Diaper or intertriginous areas • Nail fold infection (paronychia) with secondary nail dystrophy

13. Nail Infections

14. Note redness around nails, and secondary nail atrophy

15. Diagnosis • Mainly clinical • Empirically treat and if no relief: • Further diagnostic such as esophageal endoscopy, vaginal exam • Culture if atypical presentation

16. Treatment • Oral candidiasis: • Miconazole 2% (daktarin), clotrimazole 2%, nystatin, oral • apply on palate and tongue twice daily for oral or cutaneous candida • Esophageal candidiasis : • Fluconazole 6mg/kg/day on first day then 3-6mg/kg/day for 2-3 weeks • Invasive infection: • Amphotericin B 0.5-1.0mg/ kg/ day for 2-3 weeks • Nail infection: • Treat as above for invasive infection

17. Nodular Papules

18. Nodular Papules • Systemic symptoms may include: high fever, signs of anemia, hepatosplenomegaly, lymphadenopathy, weight loss • Associated with severe immunodeficiency • Diagnosis is mainly clinical

19. Common Etiologies: Fungi • Penicillium marneffei: • Most common (up to 70% of fungal diseases) • Systemic symptoms • Lesions: Papules with central necrotic umbilication mainly on the head, face, upper trunk • CD4% typically <15% • Can occur as immune system reconstitutes (IRIS)

21. Lesions similar to molluscum, older lesions have central necrosis, 1-5mm, distribution most concentrated on face, scattered on neck, back, arms, and legs

22. Less Common Fungi • Cryptococcus neoformans: • Less frequent (~10% of fungal diseases) but more common in children> 6 years of age • Systemic symptoms • Lesions: Whole body nodular papules, may ulcerate and may have central necrosis • Often seen with meningitis or pneumonia, diarrhea • CD4 cells typically <100/mm3. • Histoplasmosis: • Least common (~5-10% of fungal diseases) • Systemic symptoms • Can occur with lung process, meningitis, diarrhea. • Lesions: nodular papules and purpura

23. Common Etiologies: Viruses (1) • Molluscumcontagiosum: • Common in children with HIV • No systemic symptoms • Caused by a poxvirus • Occurs by direct contact with lesion, or contaminated towels, clothings, toys • Lesions: Shiny surface, dome shaped papules and central umbilication, often granulomatous containing, no necrosis, usually in the face or genitals, chest, abdomen, arms, buttocks, thighs

24. Common Etiologies: Viruses (2) • Human papillomavirus (HPV)(genital warts): • Localized in anal, genital areas • No systemic symptoms • Lesions: Cauliflower-like warts, pink, soft, no pain, easily bleeds; another type is wide flat like grains of rice with thickened horny papules

25. Disseminated Fungal Infection • Penicillium marneffei : • Endemic to Southeast Asia • Transmission: inhalation into lungs, then hematogenously spread • Clinical manifestations: • Usually occurs in older children (≥5) • Always with systemic symptoms: prolonged fevers, anemia, +/- hepatosplenomegaly • Skin lesions seen in 70-80% of penicillium cases • Diagnosis: giemsa stain/culture of skin scraping, blood culture (specify fungal) • Treatment: amphotericin or itraconazole, ART

26. Diagnosis • Fungi - Wet mount preparation or culture • Skin lesions • Lymph nodes • Bone marrow • Cerebrospinal fluid (CSF) • Blood • If suspect Cryptococcus neoformans meningitis: • check for antigen in serum and CSF

27. 8 year old boy, history of fevers, anemia weight loss, skin lesions > 1 month Abundant penicillium conidia seen on Giemsa stain of skin scraping

28. Treatment: Fungi • Amphotericin B 0.5-1.0mg/kg/day: • Penicillium marneffei: 2 months (or itraconazole 200mg twice daily x 2 months) • Cryptococcus neoformans: 2 weeks induction then fluconazole 400-800mg / day x 8 weeks maintenance (can also use itraconazole 400mg / day for maintenance) • Histoplasma: if severe (CNS disease, hemodynamic instability), treat until symptoms resolve then itraconazole 400mg/day for 6 months

29. Treatment: Viruses • Molluscumcontagiosum • Cryotherapy or curettage, surgery • If not effective, use topical Imiquimod or cidofovir • ARV therapy is effective to prevent and treat • HPV (warts): • Apply Podophyllin 10-25% / time / day or 3 times/week or trichloroacetic acid 30% / time / day • If lesions in mouth and throat, just use cryotherapy, electrocautery, laser • When using Podophyllin, apply only to lesions, instruct patient to rinse after 1-4 hours and if no improvement after 4-6 weeks, change to electrocautery

30. Healed and active lesions

31. Vesicular Lesions

32. -Vesicular lesions on erythematous base -At different stages of healing -Some are pustular

33. Disseminated Infection Herpes Zoster

34. Etiologies: Viruses (1) • Herpes Varicella Zoster Virus (VZV) • Chickenpox - primary: • Vesicular lesions throughout the body which rupture then scab • Varying stages of healing • Highly infectious • Zoster / Shingles - reactivation: • Vesicular lesions often preceded by or occurring with burning pain • Along dermatome, unilateral, commonly on the ribs, chest, back and face • Only infectious to those without history of primary infection / vaccination

35. Etiologies: Viruses (2) • Herpes simplex (HSV): • Cluster of vesicles which rupture then scab, typically around mouth, anus, genitals • If spread to esophagus, can cause difficulty or pain in swallowing • Possible complications of encephalitis

36. Herpes Zoster

37. Diagnosis • Mainly clinical • VZV: • Tzanck smear: giant cells • Viral culture • Immunofluorescent antibody • PCR if available

38. Photo quiz What is the diagnosis? How do you manage/ treat?

40. Chronic, present >1 month

43. Treatment • Apply methylene, milian on lesions to prevent superinfections • Topical antivirals often less effective and can irritate lesions • Systemic therapy ideally within 72 hours of appearance of first vesicles • Mild: Oral Acyclovir 40-80mg/kg/day divided into 3 times/day for 7 days • Severe, invasive Shingles: IV Acyclovir 15-30mg/kg/day divided into 3 times/day for 7-14 days • Prevention of relapse (≥ 1 time/month): Acyclovir 400 mg 2 times/day

44. Maculopapular Lesions - Erythema

45. Drug Related • Measles-like, morbiliform, erythematous • Severe cases – Stevens-Johnson syndrome (antibiotics, ARVs) • Nevirapine-associated rash • Typically presents in first 2 weeks • Can occur with hypersensitivity syndrome of fever, hepatitis, transaminitis; can be fatal

47. Disease Related • HIV-associated: Pruritic papular eruption (PPE) • Hyperpigmented, palpable • Often occurs on extremities • Typically in patients with severe immunosuppression • Syphilis • Lesions found on palms and soles as well as trunk • Can manifest with severe systemic signs (fever, hepatosplenomegaly, lymphadenopathy, jaundice, anemia) • Serum RPR, VDRL usually positive • Histoplasmosis (discussed previously)

48. Treatment • Steroids • Antihistamines • Apply UVB therapy if rash is associated with HIV • If drug allergy suspected: • Stop drug • If rash is related to NVP, change to non-NNRTI ARV

49. Treatment: Syphilis • Congenital syphilis in children <2 years of age and: • Normal CSF: IM benzathine penicillin 50,000 U/kg x single dose • Abnormal CSF: IV or IM benzyl penicillin 50,000 U/kg/ day divided twice per day x 10 days, or procaine penicillin G 50.000 U/kg/day x 10 days • Congenital syphilis in children> 2 years of age and: • Normal CSF: IM benzyl penicillin 30,000 U/kg x single dose • Abnormal CSF: IV benzyl penicillin 20,000-30,000 U/kg/day divided twice per day x 14 days • Penicillin allergy: replace with erythromycin 30-50mg/kg/day orally divided 4 times a day x 30 days • If the mother was not treated with penicillin, children should be treated even if asymptomatic and serum (-)

50. Key points • Oral candidiasis and PPE are the most common skin/oral conditions associated with HIV in children • Shallow non-healing ulcers on face may be due to HSV • Invasive fungal diseases such as Penicilliosis are life-threatening and need immediate treatment with antifungal and initiation of ART shortly after • Drug hypersensitivity may occur with NVP or other ARVs or antibiotics