Updated March 2004
Primary care clinicians should refer HIV-infected children to a dermatologist when they cannot determine the etiology of a skin lesion based on clinical evaluation.
Primary care clinicians should be familiar with the wide variety of mucocutaneous manifestations in HIV-infected children.1-3 Skin manifestations tend to occur more frequently in children with advanced HIV disease and often resolve with the initiation of HAART. Cutaneous manifestations in HIV-infected children can often be symptomatic of systemic or more extensive illness. Viral, bacterial, and fungal infections are most common. Other skin diseases are caused by exacerbation of childhood dermatoses (atopic or seborrheic dermatitis) or are reactions to medications. Cutaneous Kaposi’s sarcoma is extremely uncommon in children.4
II. BACTERIAL INFECTIONS
Cellulitis, impetigo, ecthyma, and abscesses may occur in children with HIV infection.
Cellulitis, impetigo, and ecthyma present as local inflammation characterized by redness, warmth, and swelling of the area. Purulent drainage may be present. Systemic signs, such as fever or leukocytosis, may or may not be present. Skin abscesses may present as purulent nodules.
The clinician should attempt to identify bacterial pathogens by culture of purulent fluids.
The clinician should perform a blood culture in patients with cellulitis.
In patients with cellulitis, impetigo, and abscesses, the clinician should immediately initiate empiric antibiotic therapy (e.g., first-generation cephalosporins, anti-staph penicillins, clindamycin) that covers Staphylococcus aureus and beta hemolytic streptococci. Antibiotics should be adjusted based on culture result.
In an immunocompetent patient, the clinician should treat mild, localized impetigo with topical antibiotics that are effective against both staphylococci and streptococci. A child who has more severe impetigo or who is more severely immunocompromised will require systemic treatment.
Incision and drainage of lesions caused by bacterial infection may improve the therapeutic outcome. Most HIV-infected children with cellulitis require hospitalization and intravenous antibiotics.
If empiric treatment of bacterial infection fails, a skin biopsy may be warranted.
III. FUNGAL INFECTIONS
Candidiasis may be an initial presentation of HIV disease. Oral thrush and recalcitrant monilial diaper dermatitis are the most common mucocutaneous manifestations of HIV infection in children.
Pseudomembranous candidiasis (thrush) is generally diagnosed by its characteristic clinical appearance: white, curd-like material that can be wiped off and, when removed, reveals an erythematous mucosa. For more information on pseudomembranous candidiasis, refer to Chapter 12: Oral Health Care.
Cutaneous candidal infection may involve any area where there is breakdown of the skin, including intertriginous areas (e.g., diaper area, axilla, neck folds) and proximal nail folds (e.g., paronychia). Candidal diaper rash is a pink rash, sometimes slightly raised, that can involve the skin folds and often contains small satellite lesions outside of the affected area.
Diagnosis of candidiasis should be made by the identification of clinically distinctive lesions.
The clinician should treat oral candidiasis with fluconazole (3 to 6 mg/kg/day) or mycostatin (lozenges or oral suspension).
The clinician should advise the caregiver to regularly wash the mouth of younger children and sterilize all bottles, bottle nipples, and pacifiers to prevent recurrence of oral candidiasis.
Mycostatin or imidazole topical cream should be used to treat candidal infection of the skin.
Newer alternatives such as ciclopirox and terbinafine have additional anti-inflammatory properties that may expedite improvement.
Although mild oral disease is occasionally treated with mycostatin, in immunodeficient children, there is a high failure rate. These children usually respond to 3 to 6 mg/kg/day of fluconazole. Itraconazole in liquid form has also been used successfully to treat refractory thrush, although no safety data exist in children. Mechanical débridement by aggressively rubbing the mucosa with a slightly abrasive cloth may hasten improvement.
Development of feeding difficulty or dysphagia in a child with oral thrush may signal the presence of candidal esophagitis.
Cutaneous candidal infection can usually be treated with mycostatin or imidazole creams. Therapeutic regimens for candidal diaper rashes sometimes include oral therapy to eliminate a gastrointestinal source of the fungus. Ciclopirox and terbinafine may also be used for cutaneous candidal infections. Additional measures for improving candidal diaper rashes include frequent diaper changes with larger sized diapers and keeping the affected area open to air as much as possible.
B. Dermatophyte Infection
HIV-infected children may develop severe or widespread tinea corporis or tinea capitis. They are also more likely to have onychomycosis or fungal infections of the nails.
Tinea corporis presents as a single or several scaly oval patches that are often hyperpigmented with a raised outer rim. If treated with a topical corticosteroid, the characteristic features may not be present.
Tinea capitis can present as an area of flaking within the scalp, with or without hair loss, or a weeping or crusting kerion. It can also present as a diffuse flaking throughout the scalp.
Tinea versicolor presents as many small hypopigmented lesions often on the shoulders, neck, and face.
Onychomycosis is a dermatophytic infection of the nails. It usually presents as yellowed, darkened, thickened, or pitted nails.
Diagnosis of dermatophyte infections should be made on a clinical basis and can be verified by the presence of fungal organisms on potassium hydroxide preparation or fungal culture.
The clinician should treat tinea corporis with application of an imidazole cream twice a day. Topical ciclopirox or terbinafine creams are alternative treatment options.
Tinea capitis should be treated with a 4- to 6-week course of oral griseofulvin (15 to 20 mg/kg/day). Possible alternatives include fluconazole (3 to 6 mg/kg/day) and itraconazole (5 mg/kg/day).
The clinician should treat tinea versicolor with selenium sulfide shampoos, topical imidazole gel and lotions, or single-dose itraconazole. Topical ciclopirox and terbinafine and oral itraconazole and fluconazole are alternative treatment options.
Tinea capitis does not respond to topical antifungal medications and often requires an increased dose of 20 to 25 mg/kg/day of griseofulvin for 6 weeks to achieve significant improvement. Some experts have suggested the addition of a short course (e.g., 5-day) of oral steroids for severe disease. Although fluconazole and itraconazole are effective, the duration of therapy for these agents has not been determined. Aggressive and prompt treatment is essential to prevent permanent hair loss.
Treatment of onychomycosis is most effective with terbinafine or itraconazole for at least 6 weeks and often 3 months; however, neither drug has dosing recommendations for children. The dose of terbinafine in adults is 250 mg once daily, and a variety of dosing schedules have been used for itraconazole. Fluconazole and griseofulvin have also been used.
IV. VIRAL INFECTIONS
A. Herpes Simplex
Severe, chronic, or recurrent infection with herpes simplex virus (HSV) can be a complication of HIV infection in children.
The most common presentation of herpes simplex is development of severe and persistent and/or crusting erosions of the lips, gums, and tongue. However, vesicular and ulcerative lesions of the fingers and other cutaneous surfaces are sometimes seen.
The clinician should perform culture or immunofluorescent antibody testing for the presence of HSV for any chronic ulcer of the mouth or skin.
The clinician should treat children with mild HSV infection and good immune function with oral acyclovir (see above for dosages).
The clinician should treat children with severe mucocutaneous HSV infection or severe immune deficiency with intravenously administered acyclovir (see above for dosages).
Because absorption of orally administered acyclovir may be erratic, intravenous administration is preferable. In cases of recurrent lesions, chronic suppressive therapy with orally administered acyclovir may be necessary (200 mg, 2-4 times a day). This should be administered in consultation with a pediatric HIV Specialist.
For children who can swallow pills, valacyclovir and famcyclovir provide higher levels of active drug than oral acyclovir and may decrease the need for intravenous therapy. Safety data and dosing recommendations have not been established for children. In adults, famcyclovir dosages are 500 mg bid for initial episodes of HSV, then 250 mg bid for recurrences or suppression. Dosages of valacyclovir are 1 gram bid for an initial episode of HSV, then 500 mg bid or 1 gram qd for recurrences or suppression.
Treatment failure may be caused by either erratic absorption or development of acyclovir resistance. In these cases, further evaluation of the lesion, perhaps assessing its drug susceptibility, may be necessary. Foscarnet (40 mg/kg IV q8h for 10-14 days) has been used successfully to treat acyclovir-resistant HSV. If foscarnet is used, the clinician should ensure that the patient is adequately hydrated.
B. Herpes Zoster (Varicella-Zoster Virus)
|Herpes Zoster (Varicella-Zoster Virus)|
|* Occasionally, in children with immune deficiency, shingles can affect multiple dermatomes and/or both sides of the body.|
Varicella zoster, or chickenpox, usually presents similarly in both HIV-infected and non-infected children. It presents as vesicular and ulcerative lesions all over the child’s body in multiple different stages. In severely immunocompromised children, it can be more severe and is more likely to have manifestations beyond the dermatologic features, such as pulmonary, central nervous system, or systemic manifestations.
Herpes zoster, or shingles, presents as blistering lesions, usually in a single dermatome on one side of the body. Occasionally, in children with immune deficiency, multiple dermatomes on both sides of the body can be affected. Herpes zoster can be painful or pruritic and may cause scarring. Because of delays in presentation, the typical blistering stage may be missed, and it may look more ulcerative at the time of presentation.
Chronic varicella is unique to patients with HIV infection. It usually follows an episode of chickenpox or shingles and is characterized by vesicular and ulcerative lesions, often expanding in diameter, each with a dry central core and a wet, active outer ring. Mixed infections with other viral or bacterial pathogens may occur.
Diagnosis of chickenpox, shingles, or chronic chickenpox should be based on the appearance of classical lesions noted on physical examination. If the diagnosis is unclear after physical examination, diagnosis should be made by culture or fluorescent antibody of the lesions.
Treatment of all forms of varicella zoster should be dependent on the extent and severity of the varicella and the severity of immune deficiency of the child. Most HIV-infected children with normal immune function will not need treatment for chickenpox.
Clinicians should treat children with mild immune deficiency with oral acyclovir and those with severe immune deficiency with intravenous acyclovir.
Clinicians should treat HIV-infected children with shingles with oral or intravenous acyclovir, depending on the severity of immune deficiency and number of lesions. Multidermatomal lesions or recurrent lesions should be treated with intravenous medication.
Chronic varicella is indicative of severe immune deficiency and should be treated with intravenous acyclovir.
Famcyclovir or valacyclovir may be used to treat herpes zoster in older children who can swallow pills. Because dosing recommendations of these drugs in children do not exist, the doses should be determined by using a percentage of the adult doses of valacyclovir 1 gram tid or famcyclovir 500 mg tid for 7 days.
Development of acyclovir-resistant strains has been reported.5,6 Lesions that do not improve despite treatment with acyclovir should be cultured and analyzed for resistance. Resistant strains have been treated with foscarnet or cidofovir.
The infectious period (via respiratory spread) for people with chickenpox begins 2 days prior to developing symptoms and ends when the pox lesions are dry. HIV-infected persons with no previous history of varicella who are exposed to chickenpox should be given varicella-zoster immune globulin (VZIG) as soon as possible and within 96 hours of exposure. People with shingles are usually only contagious if the actual lesion is touched.
C. Molluscum Contagiosum
Widespread molluscum contagiosum can occur in HIV-infected children but has been rarely noted since the introduction of HAART.
Molluscum contagiosum is a common viral condition in children. The lesions are pearly, flesh-colored, umbilicated papules containing caseous material. Lesions of molluscum contagiosum can appear anywhere on the body, but most commonly on the face, neck, genitals, and creases and folds or sites of friction, such as the axilla or flank. Persistent, recalcitrant molluscum is common among immunocompromised adults and children.7
Molluscum contagiosum should be diagnosed by its characteristic appearance.
If the diagnosis cannot be made on clinical appearance alone, the contents of the papules should be stained with potassium hydroxide, which will show clusters of large clear cells, or with other stains that will show intracytoplasmic inclusion bodies.
Clinicians should treat patients with widespread molluscum contagiosum lesions with standard regimens of ARV medications.
Optimal therapy for widespread molluscum contagiosum lesions has not been determined; however, treatment of the patient’s HIV disease with HAART usually results in improvement of the molluscum.
If the lesions are not too numerous, removal by gentle curettage is usually performed. EMLA or ElaMax cream may be applied for anesthesia 30 minutes to 1 hour before the procedure. When lesions are numerous, some dermatologists use liquid nitrogen or an exfoliant, such as topical tretinoin cream 0.1%, benzoyl peroxide, imiquimod, or cantharidin.
Additional treatment options include salicylic acid preparations, podophyllotoxin gel/solution or oral cimetidine at 40 mg/kg/day divided twice a day. Topical cidofovir has also been used to treat extremely widespread molluscum in immunocompromised patients.8
D. Human Papillomavirus Infection
When prepubescent children beyond infancy present with anogenital warts, clinicians should consider the possibility of sexual abuse.9
|Human Papillomavirus Infection|
Children with human papillomavirus (HPV) infection may develop verruca vulgaris, widespread flat warts, and condylomata acuminata. Verrucae are thickened keratotic papules, whereas flat warts are thin discrete papules. Condylomata present as filiform or hyperkeratotic papules on the mucous membranes.
Diagnosis of anogenital warts should usually be made by clinical presentation and, in mucosal cases, can be confirmed by whitening of the mucosa when acetic acid is applied.
If ordinary warts persist for an extended amount of time, the clinician should treat with daily application of salicylic acid or cryotherapy (see text for additional options).
Small condylomata acuminata should be treated with 20% podophyllum resin, which should be washed off thoroughly after 2 hours.
A multidisciplinary approach, including consultation with a gynecologist, should be used to treat female patients with large lesions of condylomata acuminata.
Ordinary warts sometimes resolve spontaneously; however, if they persist for an extended period of time, the following treatment options are available:
- daily application of salicylic acid or cryotherapy
- imiquimod cream
- podophyllotoxin gel or solution
- tretinoin or fluorouracil cream
Extensive lesions that are not responsive to topical therapy may respond to a course of oral cimetidine at 40 mg/kg/day divided twice a day.10
Large lesions of condylomata acuminata may be treated with cryosurgery or surgical excision. Imiquimod applied qid may also be effective. Treatment with alpha interferon has been attempted with variable success,11,12 and some patients have benefited from topical cidofovir.
V. PARASITIC INFECTIONS
HIV-infected children with scabies may also develop crusted, or “Norwegian,” scabies. Children with crusted scabies harbor hundreds of mites and are extremely contagious to family members and healthcare workers.
Scabies presents as punctate papules on the hands, feet, arms, legs, periumbical area, face, or scalp. The lesions may be extremely itchy and therefore somewhat disguised by the self-inflicted scratch marks.
Crusted, or “Norwegian,” scabies has the appearance of widespread eczematous eruption, lacks the characteristic papules and burrows, and may easily go undiagnosed.13,14
Diagnosis of scabies should be made by scraping burrows and looking for mites or feces.
Clinicians should treat children with scabies with a single application of 5% permethrin cream. In infants, the head should also be treated.
The clinician should advise the caregiver to launder, in hot water, all bedding and clothing that was worn next to the skin during the 4 days prior to treatment initiation.
The clinician should provide prophylactic treatment for household members. All household members should be treated at the same time to prevent reinfestation.
Systemic ivermectin has been used with some success in children with severe scabies or failed permethrin treatment; however, it has not been approved for use in children.
VI. INFLAMMATORY DERMATOSES
A. Seborrheic Dermatitis
Severe seborrheic dermatitis has been noted in children with HIV infection. Although manifestations may be worse in HIV-infected children, the treatment is the same as in healthy children.
Seborrheic dermatitis presents in areas with maximal numbers of sebaceous glands, including the scalp, ears, T zone of the face, chest, and genital areas. Erythema and scaling of the scalp, skin behind the ears, and nasolabial folds are particularly characteristic.
Seborrheic dermatitis should be diagnosed by clinical presentation.
The clinician should treat seborrheic dermatitis with 1% or 2.5% hydrocortisone cream and/or ketoconazole cream or shampoo.
B. Atopic Dermatitis
Atopic dermatitis may be exacerbated by the presence of HIV infection.
In infants, atopic dermatitis involves the face and extensor surfaces and often spares the diaper area. As children get older, it tends to involve the flexural surfaces.
Atopic dermatitis should be diagnosed by clinical presentation.
The clinician should ask for a family history of atopy (i.e., asthma, urticaria, hay fever).
The clinician should treat atopic dermatitis with emollients, antihistamines, non-fluorinated topical steroid ointments, or immodulatory topical treatments (tacrolimus and pimecrolimus).
The clinician should advise the caregiver to avoid provocative factors, such as using harsh soaps and detergents, dressing children in wool clothing, and bathing children too frequently.
The clinician should consult with a dermatologist in severe cases.
Progression of rashes since childhood from flexural intertriginous to extensor parts of the body is also indicative of atopic dermatitis.
VII. CUTANEOUS MANIFESTATIONS OF DRUG REACTIONS
Pharmacologic drug reactions are more common in HIV-infected children than in the general population, with the incidence of reaction to drugs increasing in proportion to the degree of the host’s level of immune dysfunction.2 The most common cause of drug-induced rashes is from antibiotics and ARV therapy. Among antibiotics, drug reactions resulting from trimethoprim/sulfamethoxazole (TMP/SMZ) are relatively common, although they are much less common in HIV-infected children than adults. Penicillins and cephalosporins are also common antibiotics resulting in exanthems. Although skin rashes are fairly common side effects of many ARV drugs, the most serious drug reactions that are associated with life-threatening situations have been ascribed to nevirapine, abacavir, and amprenavir.
|Cutaneous Manifestations of Drug Reactions|
The most frequent form of drug reaction is a simple, morbilliform rash. Rashes may present as diffuse redness, papules, or targetoid lesions. In more severe cases, blisters or skin desquamation may ensue. The most serious cutaneous drug reactions are erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the unique hypersensitivity reaction associated with abacavir. Rarely, photosensitivity drug reactions and pigmentary alteration secondary to drugs can occur.
Clinicians should suspect drug reactions as the cause of a rash in any patient who develops a rash while he/she is on medication. Antibiotics should be suspected first when drug reaction is being considered.
Reactions due to ARV drugs typically occur early after onset of the particular drug, except for in situations associated with pigmentary alteration and photosensitivity drug reactions.
Among ARV drugs, the nevirapine-associated rash usually occurs within the first 18 weeks of therapy and often within the first 2 weeks. The rash consists of a truncal, maculopapular, erythematous eruption. In some instances, it can progress into mucosal surfaces and evolve into Stevens-Johnson syndrome, often with accompanying fever and severe hepatitis. Serum liver enzymes should be obtained in patients who develop a rash during nevirapine therapy, particularly during the first 18 weeks of therapy. Deaths associated with these reactions have been reported. Patients who develop mild rashes without systemic toxicity may be managed with antihistamines and close monitoring. However, those with severe cutaneous toxicity or with suspected hepatic toxicity should discontinue nevirapine promptly and should not be re-challenged with this drug.
The other NNRTIs that can lead to skin rashes are delavirdine, which is rarely used in pediatrics, and efavirenz, which can lead to a mild morbilliform rash early in the treatment but usually resolves while the patient is receiving therapy.
Abacavir can lead to a typical morbilliform drug rash, sometimes accompanied by constitutional symptoms early in the course of therapy. Abacavir can also lead to a serious hypersensitivity reaction with a maculopapular or urticarial rash, which usually occurs when a patient is re-challenged with the drug after having stopped it previously. Hypersensitivity reactions to abacavir are rare and can occur in the absence of cutaneous manifestations. If abacavir is stopped, it should never be restarted. Lamivudine often causes a typical drug rash. Rarely, zidovudine can lead to hyperpigmentation. Zalcitabine has been associated with oral ulcers; however, the use of this drug is infrequent.
Skin rash is a common side effect of the protease inhibitors. Amprenavir, lopinavir/ritonavir (co-formulated as Kaletra), and saquinavir rashes will present 8 to 12 days after initiation of therapy. With nelfinavir, skin rashes are less common. Steven-Johnson’s syndrome has been reported to occur in 1% of adults receiving amprenavir. With indinavir, a form of ectodermal dysplasia, manifesting as excessively dry skin, cheilitis (cracked lips), persistent paronychia, and increased incidence of eczematous patches has been described in adults.
The decision to discontinue drug therapy in a child with a rash should be individualized and based on the severity of cutaneous disease and the availability of treatment alternatives.
When abacavir is stopped, it should NEVER be restarted.
If the degree of involvement is mild, it can usually be treated with hydration and systemic antihistamines. In more severe cases, when the benefits of the drug are thought to outweigh the potential risks, management may involve cautious continuation of therapy. In many instances, constitutional symptoms resolve within several weeks, even with continuation of the drug (e.g., with efavirenz). In other situations, a desensitization procedure may have to be considered.
Nevirapine should always be started at a lower dose and increased in a stepwise fashion, as described in the package insert. This procedure greatly reduces the incidence of skin reactions.
Hypersensitivity reaction to abacavir should be reported to the Abacavir Hypersensitivity Registry (1-800-270-0425), and the drug should be permanently discontinued.
1. Prose NS. HIV infection in children. J Am Acad Dermatol 1990;22:1223-1231.
2. Straka BF, Whitaker DL, Morrison SH, et al. Cutaneous manifestations of the acquired immunodeficiency syndrome in children. J Am Acad Dermatol 1988;18:1089-1102.
3. Prose NS, Mendez H, Menikoff H, et al. Pediatric human immunodeficiency virus infection and its cutaneous manifestations. Pediatr Dermatol 1987;4:67-74.
4. Connor E, Boccon-Gibod L, Joshi V, et al. Cutaneous acquired immunodeficiency syndrome-associated Kaposi’s sarcoma in pediatric patients. Arch Dermatol 1990;126:791-793.
5. Pahwa S, Biron K, Lim W, et al. Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS. JAMA 1988;260:2879-2882.
6. Jacobson MA, Berger TG, Fikrig S, et al. Acyclovir-resistant varicella-zoster infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1990;112:187-191.
7. Chang MW, Orlow SJ. Molluscum contagiosum in children: When and how to treat. Consultant 1998;June:1593-1599.
8. Davies EG, Thrasher A, Lacey, et al. Topical cidofovir for severe molluscum contagiosum. Lancet 1999;353:2042.
9. American Academy of Pediatrics. Papillomaviruses. In: Pickering LK, ed. 2000 Red Book: Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics;2000:413-415.
10. Orlow SJ, Paller A. Cimetidine therapy for multiple viral warts in children. J Am Acad Dermatol 1993;28:794-796.
11. Laraque D. Severe anogenital warts in a child with HIV infection. N Engl J Med 1989;320:1220-1221.
12. Douglas JM Jr, Eron LJ, Judson FN, et al. A randomized trial of combination therapy with intralesional interferon alpha-2b and podophyllin versus podophyllin alone for the therapy of anogenital warts. J Infect Dis 1990;162:52-59.
13. Sadick N, Kaplan MH, Pahwa SG, et al. Unusual features of scabies complicating human T-lymphotropic virus type III infection. J Am Acad Dermatol 1986;15:482-486.
14. Judowics P, Ramon ME, Don PC, et al. Norwegian scabies in an infant with acquired immunodeficiency syndrome. Arch Dermatol 1989;125:1670-1671.
Harper J, Oranje A, Prose N, eds. Textbook of Pediatric Dermatology, vol 1. London: Blackwell Science, 2000.
Shio M, Van Dyke RB. Disorders of the skin in HIV-infected children. Curr Opinion Dermatol 1995;123-128.
Wananukul S, Thisyakorn U. Mucocutaneous manifestations of HIV infection in 91 children born to HIV seropositive women. Pediatr Dermatol 1999;16:359-363.
Whitworth JM, Janniger CK, Oleske JM, et al. Cutaneous manifestations of childhood acquired immunodeficiency syndrome and human immunodeficiency virus infection. Cutis 1995;55:62-68.