OVERVIEW: What every practitioner needs to know

Are you sure your patient has pruritic papular eruption of HIV (pruritic papular eruption)? What should you expect to find?

Pruritus is the most common cutaneous complaint in those infected with HIV, and there are a multitude of causes. Early in the HIV epidemic, pruritic papular eruption (PPE) of HIV was identified. Despite its early identification, it remains unclear whether PPE represents a truly distinct condition or an umbrella diagnosis for which to categorize non-specific pruritic conditions in the setting of HIV.

  • Key Symptoms

    Pruritus

    Rash

  • Key Physical Findings

    Symmetrical, multiple, discrete papules (Figure 1); pustules may also be seen.

    Less than 1 cm in size

    Acral predominance (Figure 2) (trunk may also be involved)

    Dorsal hands and extensor forearms/arms most commonly

    Mixed appearance

    New is erythematous

    Older is hyperpigmented with lichenification from manipulation

    Superficial erosion from scratching

Figure 1.

Discrete papules with hyperpigmentation on lower extremities

Figure 2.

Discrete papules with scale and exoriation on lower extremities

How did the patient develop pruritic papular eruption of HIV?

  • PPE is seen in the setting of HIV infected individuals

    Most commonly seen in those with a CD4 less than 100

  • Precise cause is not known; most believe it represents an exaggerated response to arthropod bites.

    More common in tropical regions (i.e., Africa, Haiti, Brazil, Thailand)

    Acral predominance

Which individuals are of greater risk of developing pruritic papular eruption of HIV?

  • HIV+ with CD4 less than 100 (World Health Organization [WHO] Clinical Stage 2 disease)

  • From highly prevalent region (i.e., Africa, Haiti, Brazil, Thailand)

Beware: there are other diseases that can mimic pruritic papular eruption of HIV:

  • Eosinophilic folliculitis

    Edematous, erythematous to pink follicular papules; occasional pustule

    Face, neck, postauricular skin, upper trunk (often superior to nipple line), proximal upper extremities

    Symmetric distribution

    CD4 less than 300

    Histology

    Follicular spongiosis with eosinophil rich infiltrate

    Treatment

    Antiretroviral therapy

    Topical steroids (Face: desonide 0.05% ointment BID; Body: triamcinolone 0.1% ointment BID)

    Antihistamines

    Phototherapy (UVB, PUVA)

    Isotretinoin 0.5-1mg/kg/d

  • Prurigo Nodularis

    Difficult differential to distinguish

    May have fewer lesions

    Erythematous papules uncommon

    May extend onto anterior thighs

  • Papular urticaria (arthropod bite reaction)

    Difficult differential, but may be indistinguishable

    Ask about pets, exposure to biting insects.

    Discrete erythematous, urticarial papules on exposed skin

  • Mite infestation

    Scabies

    Papules, plaques with excoriations, burrows, vesicles, eczematous patches

    Wrists, finger web spaces, axillae, nipples,

    Itchy contacts

    Positive scabies prep: scybala, eggs, mites

    Demodex

    Rosacea-like, erythematous follicular papules/pustules

    Head and neck

    Demodex mite on skin scraping of pustule/papule

  • Folliculitis

    Bacterial

    Follicular pustules predominate over erythematous papules

    Head, neck, trunk, buttocks, axillae, groin

    Staphylococcus aureus most common

    Positive Gram stain, culture

    Pityrosporum ovale

    Follicular pustules predominate over erythematous papules

    Back, chest, shoulders

    Yeast spores on potassium hydroxide staining (KOH) of pustular contents

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

There are no lab studies specific for the diagnosis of PPE. The diagnosis is most often made by clinical findings in the correct clinical setting. Histological evaluation may be helpful if the diagnosis is in question.

  • Elevated serum IgE

  • Peripheral eosinophilia

  • CD4 less than 100

  • Histology of skin biopsy specimen

    Epidermal hyperplasia, spongiosis, parakeratosis

    Predominantly lymphocytic dermal perivascular and interstitial inflammatory infiltrate with variable numbers of eosinophils

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has pruritic papular eruption of HIV, what therapies should you initiate immediately?

Dermatology is most likely helpful in the diagnosis and treatment of PPE.

Key principles of therapy

Treatment is often difficult. There are no randomized controlled studies to inform clinicians regarding the best treatment options for PPE. As the etiology is not definitively known, empiric therapy is directed toward symptoms, predominantly pruritus. Most treatment recommendations are supported by anecdotal evidence only.

Initiation of antiretroviral (ARV) therapy accompanied by successful virological response has been shown to improve PPE in two studies. One study by Castelnuovo and colleagues prospectively followed ARV naive patients. In 86% of individuals, PPE resolved and never returned and only 7% of patients had evidence of PPE at 24 months, of which were significantly improved.

It is important to remember that many patients with HIV can develop xerosis (dry skin), and attending to this may improve their overall sense of pruritus. Some simple techniques to improve xerosis include:

  • Luke-warm showers/baths of less than 10 minutes duration

  • Limited use of mild soaps (soap only areas that are soiled, underarms, groin, and feet)

    If bathing, use soap at the end of the bath so as not to sit in a bath of soapy water.

  • Dab dry with towel (rather than vigorously drying skin)

  • Apply medicated creams/ointments to affected areas

  • Apply moisturizing lotion/cream/ointment to entire body

    Ointments are better than creams, which are better than lotions for moisturizing the skin.

Most clinicians initiate treatment using oral antihistamines combined with topical steroids and antipruritic lotions or creams. A recent retrospective study by Navarini and colleagues suggested that oral promethazine was superior to topical hydrocortisone 1% ointment, one of the least potent topical steroids available.

  • The use of topical corticosteroids should be limited and appropriate for the body site to limit the risk of side effects, including epidermal and dermal atrophy, skin dyspigmentation, telangiectasia, and striae.

  • The site of involvement will not only help determine which topical steroid to use, but also which formulation.

    For example, ointments do not work well in hairy areas, because they are difficult to apply.

Other treatments that have been used include:

  • Phototherapy – ultraviolet radiation

  • Pentoxifylline (in one prospective unblinded study, pentoxifylline was superior to antihistamines plus topical steroids and dapsone)

  • Topical antifungal agents – As there is little to no evidence that PPE is caused by fungus, I do not recommend this treatment.

  • Antiscabetic therapy – As there is little to no evidence that PPE is caused by scabies, I do not recommend this treatment.

Other key therapeutic modalities.

  • Address xerosis in all patients

  • Narrow-band Ultraviolet B (UVB), although not reported in the literature for this particular condition, tends to be as or more effective than broadband UVB and possibly has a safer side effect profile. It is commonly used very effectively in patients with pruritus for other reasons and could be considered as an alternative to broadband UVB if it is available.

What complications could arise as a consequence of pruritic papular eruption of HIV?

Although there are no specific complications related to PPE, patients who are colonized with Staphylococcus aureus may develop pyoderma as a result of a compromised skin barrier from scratching.

What should you tell the family about the patient's prognosis?

  • Although this is a frustrating condition, it is not life threatening.

  • It is commonly a reflection of the level of immunosuppression related to HIV infection and often improves as the CD4 count raises, which can take months.

How frequent is pruritic papular eruption of HIV?

  • The prevalence of PPE is dependent on the geographical location. Although detailed epidemiological studies have not been performed, the prevalence has ranged from 11 to 46%.

  • It has been the presenting sign of HIV in 25-79% of patients, depending on geographic location.

  • It is more common in tropical regions (i.e., Africa, Haiti, Brazil, Thailand).

What are the possible mechanisms of disease in pruritic papular eruption of HIV?

As described, the exact mechanism of PPE is not understood. There are several theories.

  • Arthropod bite reaction

    Hypersensitivity to antigen previously tolerated (similar theory explains increase type IV hypersensitivity to medications in HIV-positive individuals)

    Possibly related to:

    Decreased CD4 accompanied by polyclonal B- and T-cell hyperactivation

    Type 2 helper cell predominance (Th2 > Th1)

  • Adverse drug reaction: No single medication has been implicated epidemiologically.

  • Autoimmunity: One investigator found circulating antibodies to the same antigens as in bullous pemphigoid.

  • Underlying immune dysregulation from HIV infection

    Decreased CD4 accompanied by polyclonal B- and T-cell hyperactivation

    Th2 dominant immune response as disease progresses

How can pruritic papular eruption of HIV be prevented?

There are no studies on prevention; however, because it is seen more commonly in those with lower CD4 counts, it may be prevented by successful ARV therapy.

Table I.
Treatment Modality Specific Drugs Doses Potential Side Effects
Oral antihistamines DiphenhydramineHydroxyzineDoxepinLoratadineFexofenadineCetirizine 25-50 mg PO QHS 25-75 mg PO QHS 10-75 mg PO QHS 10-20 mg PO QD 60-180 mg PO QD-BID 10-20 mg PO QD Drowsiness, confusion, urinary retention in men, dry mouth, constipation, tachycardia
Topical steroids ŠŠŠŠ1. TriamcinoloneŠŠŠŠ1. Clobetasol (not appropriate for long-term use)ŠŠŠŠ1. Desonide (face, intertriginous regions) ŠŠŠŠ1. 0.1% cream, ointment BIDŠŠŠŠ1. 0.05% cream, ointment BIDŠŠŠŠ1. 0.05% cream, ointment BID Epidermal/dermal atrophy, dyspigmentation, striae
Ultraviolet Radiation Broadband UVB Three times per week for 8 weeks, titrate to lowest frequency to control disease Photodamage, potential for skin cancer with long-term use, phototoxic reaction
Antipruritic lotions/creams Camphor-MentholPramoxine 0.5% cream 1%-2.5% lotion TID Irritant dermatitis, hypersensitivity syndrome
Other Pentoxifylline 400 mg PO TID Arrhythmia, dyspepsia, nausea

WHAT'S THE EVIDENCE for specific management and treatment recommendations?

Eisman, S. “Pruritic papular eruption in HIV”. Dermatol Clin. vol. 24. 2006. pp. 449-57. (This is an excellent review of potential etiology, clinical manifestations, histopathology, and treatment of PPE.)

James, WD, Berger, TG, Elston, DM. “Andrews' diseases of the skin”. 2011. pp. 410-11. (This is a review of the salient features of pruritus in the setting of HIV.)

Reiger, A, Chen, TM, Cockerell, CJ, Bolognia, JL, Jorizzo, JL, Rapini, RP. “Cutaneous manifestations of HIV infection and HIV-related disorders”. Dermatology. 2008. pp. 1174(This is a limited review of PPE.)

Castelnuovo, B, Byakawaga, H, Menten, J, Schaefer, P, Kamya, M, Colebunders, R. “Can response of pruritic papular eruption to antiretroviral therapy be used as a clinical parameter to monitor virological outcome”. AIDS. vol. 22. 2008. pp. 269-73. (This is a prospective study of ARV naive patients with PPE to evaluate effect of virologically successful ARV therapy on clinical signs and symptoms of PPE.)

Lakshmi, SJ, Rao, GR, Ramalakshmi, Satyasree, Rao, KA, Prasad, PG, Kumar, YH. “Pruritic papular eruptions of HIV: a clinicopathologic and therapeutic study”. Indian J Dermatol Venereol Leprol. vol. 74. 2008. pp. 501-3. This is a report of a small prospective study of 30 patients with chronic, persistent PPE not yet on ARV therapy.)

Navarini, AA, Stoeckle, M, Navarini, S. “Antihistamines are superior to topical corticosteroids in managing human immunodeficiency virus (HIV)-associated papular pruritic eruption”. Int J Dermatol. vol. 49. 2010. pp. 83-6. (This is a report of a small retrospective study comparing antihistamine (promethazine 50mg daily; n=50) and hydrocortisone 1% ointment daily (n=18).)

Resneck, JS, Van Beek, M, Furmanski, L. “Etiology of pruritic papular eruption with HIV infection in Uganda”. JAMA. vol. 292. 2004. pp. 2614-21. (This is a cross-sectional study of HIV-infected patients with PPE.)

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