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Discussion

Background and Epidemiology

Pruritic papular eruption of HIV (PPE-HIV) is the one of the most common dermatologic disorder in untreated HIV-infected adults, with between 11% and 46% of patients affected, depending on the geographic location[1]. The disease manifests as chronic, waxing and waning, intensely pruritic papules, located predominantly on the extremities and trunk, though facial involvement can also occur[2]. The resulting excoriations and pigment changes can be disfiguring and stigmatizing for patients, and the chronic pruritus further compromises the quality of life for those with PPE-HIV[3].  In some regions, particularly in the tropic zones, PPE-HIV is often the presenting symptom of HIV infection and therefore may play a role in the diagnosis of HIV infection, especially when serologic testing is not available or affordable[4]. Most patients with PPE-HIV have advanced HIV disease and low CD4 counts, and the severity of PPE increases as CD4 counts decrease[3,5,6]. In many patients, other skin disorders, such as seborrheic dermatitis or atopic-like dermatitis, are already present at the time of diagnosis of PPE-HIV[5].

Pathogenesis

The pathogenesis of PPE-HIV remains unclear, although several etiologies have been proposed. An altered and exaggerated response to arthropod bites has been implicated, as suggested by the increased involvement of exposed or uncovered skin, histologic findings consistent with arthropod bites[3] in the setting of immune dysregulation associated with chronic HIV infection[1]. A drug reaction is less likely given that inciting medications that predate the onset of PPE-HIV have not been consistently identified in patients with PPE-HIV[7]. Similarly, an infectious etiology is unlikely given that histologic examination of skin lesions biopsies have not revealed infectious agents such as scabies or other ectoparasites[6].

Clinical Findings

Patients with PPE-HIV typically present with multiple, discrete, skin colored papules that are often eroded from scratching.  Lesions are commonly distributed on the extensor surfaces of the arms and legs, the dorsum of the hands, the trunk, and the face[2]; the mucous membranes, palms and soles are spared[1]. The papules may be erythematous, and do not form confluent plaques. Pustules are infrequently present. Many patients will scratch to the point of extensive excoriation with subsequent scarring. In patients with darker skin tones, post-inflammatory hyperpigmentation is often the most visible manifestation. 

Histologic Findings

Skin biopsy may be useful in distinguishing PPE-HIV from other potential causes of pruritus in HIV-infected patients, as the clinical findings can overlap. Histologic findings include a perivascular dermal lymphocytic inflammatory infiltrate with increased eosinophils and CD8+ lymphocytes[6].  Follicular involvement is not a prominent feature, which helps to distinguish PPE-HIV from eosinophilic folliculitis or infective folliculitis, since both of these disorders also commonly cause discrete itchy papules.

Diagnosis

Evaluation of an HIV-infected patient with a pruritic and papular eruption should begin by determining if pustules or papules are dominant. The primary presence of pustules warrants swabbing a pustule and testing the sample of pus for Gram’s stain and culture, in order to distinguish between infectious (bacterial or fungal) folliculitis versus non-infectious causes, such as steroid-induced acne or acneiform drug eruption.  If pustules are not predominant, eosinophilic folliculitis, scabies, and arthropod bites should be excluded. Scabies can present atypically in HIV-infected patients, so one should have a low threshold to scrape papules to look for mites or their ova microscopically.  The clinical presentation of eosinophilic folliculitis is similar to PPE-HIV, though eosinophilic folliculitis typically presents on the head, neck, and upper trunk (Figure 1 and Figure 2), whereas the lesions of PPE-HIV are more commonly found on the extremities.  Histology can be used to differentiate between the two conditions: eosinophilic folliculitis is characterized by a folliculocentric collection of eosinophils, though there is overlap in this feature with PPE-HIV, and it has been suggested that the two conditions are part of the same disease spectrum[8]. Scabies can be often excluded by a scraping or response to antiscabietic treatment. Drug eruption, papular syphilis, psoriasis, and seborrheic dermatitis should also be considered before making the diagnosis of pruritic papular eruption[1].

Management of PPE-HIV

Unfortunately, PPE-HIV often responds poorly to conventional antipruritic treatment. One study documented superiority of oral antihistamines over topical steroids in relieving itching[9]. Ultraviolet B (UVB) light therapy, given three times weekly, has also been shown to reduce itching and improve cosmetic appearance[10]. Although concerns have arisen regarding UVB radiation potentially activating HIV gene expression, significant changes in HIV RNA levels, CD4 lymphocyte count, or opportunistic infections have not been seen in patients receiving UVB light therapy[11]. Pentoxifylline, dosed at 400 mg three times daily, improved pruritus in an 8-week trial of patients with PPE-HIV[12], but this medication is not available in many resource-limited areas. Due to the possible association of PPE-HIV with an exaggerated response to arthropod bites, bed nets and insecticides may play an important role in prevention. In addition, initiation of potent antiretroviral therapy has been shown to dramatically decrease the severity of PPE-HIV, often with lesions disappearing and not returning[13]. We recommend initiating therapy with potent antiretroviral therapy, and using both mid- to high potency topical steroids with oral antihistamines to relieve itching in the interim period before PPE-HIV improves from antiretroviral therapy. If PPE-HIV fails to improve after initiation of antiretroviral therapy, then virologic failure should be considered.  Where available, metered dosing of UV-B phototherapy can be used if symptomatic relief is not achieved with the measures suggested above.  Published studies using ambient UV light for treatment of PPE are lacking, but in many resource-limited areas, this approach is widely used.  Care should be taken to avoid burning the skin or inciting a photosensitive eruption, especially when patients are also using potentially photosensitizing medications, such as cotrimoxazole.

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    Figure 1. HIV-Associated Eosinophilic Folliculitis.

    The upper trunk involvement and lack of pustules are typical of eosinophilic folliculitis, and less consistent with PPE-HIV.


    Figure 1
  • The following link will open in a new window.
    Figure 2. HIV-Associated Eosinophilic Folliculitis.

    Edematous, erythematous and hyperpigmented papules on the forehead, lesions that are more commonly seen with EF than PPE-HIV.


    Figure 2