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Guidelines on the Treatment of Skin and Oral HIV-Associated Conditions in Children and Adults. Geneva: World Health Organization; 2014.

Cover of Guidelines on the Treatment of Skin and Oral HIV-Associated Conditions in Children and Adults

Guidelines on the Treatment of Skin and Oral HIV-Associated Conditions in Children and Adults.

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6Evidence and recommendations on papular pruritic eruption

6.1. Background

6.1.1. Epidemiology

Papular pruritic eruption is one of the most common skin conditions associated with HIV disease in tropical and subtropical regions, with reported prevalence of 11% to 46% (Bason et al., 1993; Boonchai et al., 1999; Rosatelli et al., 1997; Sivayathorn et al., 1995; Smith et al., 1991). The prevalence in HIV-infected children ranges from 38% to 42% (Panya et al., 2009; Lowe et al., 2010). It is more common with lower CD4 counts (Resneck et al., 2004; Wiwanitkit, 2004) and advanced HIV disease (WHO clinical stages 3 and 4) (Castelnuovo et al., 2008). More than half of HIV-infected patients in some countries report the eruption as the initial manifestation of their disease (Colebunders et al., 1987).

6.1.2. Etiology

The pathophysiology of papular pruritic eruption is not completely understood. Hypersensitivity to arthropod bites and a form of chronic recall reaction to arthropod antigens in the setting of HIV-associated immune dysregulation has been suggested (Penneys et al., 1989).

6.1.3. Clinical features

Papular pruritic eruption is characterized by symmetrically distributed itchy papular eruptions on the extremities, face and trunk with sparing of the mucous membranes, palms, soles and digital web spaces. On the arms, lesions are specifically localized on the extensor surface and on the dorsum of the hands. Postinflammatory pigmentation and even prurigo-like nodules and scarring may develop secondary to extensive excoriations because of severe pruritus. Scabies, eosinophilic folliculitis and drug eruptions should always be considered in the differential diagnosis.

Papular pruritic eruption can adversely impact health-related quality of life (Yosipovitch et al., 2000; Zachariae et al., 2004 & 2008). Depression, distress and sleep impairment have been reported as a consequence of chronic pruritus in this condition (Zachariae et al., 2008).

6.2. Recommendations

  • In HIV-infected children, adolescents, pregnant women and adults with papular pruritic eruption, ART should be considered as the primary treatment (see SECTION 3).
    (Strong recommendation, low quality evidence)
  • Additional symptomatic therapy with antihistamines and topical corticosteroids (class 3, 4, 5 or 6, e.g. betamethasone valearate) is also recommended for the duration of persistent symptoms.
    (Conditional recommendation, very low quality evidence)

Remarks

  • Drugs: If betamethasone is not available other potent topical steroids, class III or above, may be used instead.
  • If there is no response or a failure in response, evaluate for other causes of papular eruptions of HIV.
  • Caution should be exercised in the use of oral antihistamines in infants under one year of age. Dosage needs to be adjusted in children by weight. Caution should also be exercised in the use of sedating antihistamines in children attending school.
  • Relevant drug interactions are described in ANNEX 2.

6.3. Review question and summary of evidence

The systematic review (Chua et al., in preparation) was based on the PICO question: in children and adults living with HIV infection (receiving and not receiving ART) (P) does ART alone or ART with pentoxifylline, or antihistamines plus topical cortisteroids, or pentoxifylline alone, or dapsone (I) compared to no treatment (C) result in resolution of skin lesions or resolution of pruritus (O).

Participants in all included studies were adults. There were no studies of interventions for papular pruritic eruption in children, and no RCTs were identified in this review. However, two relevant prospective studies that compared at least two interventions were identified. Other relevant publications identified included three prospective studies investigating one intervention without comparison group(s), one case series and four case reports.

Use of ART

Resolution of papular pruritic eruption has been reported with ART initiation. Colebunders and colleagues (2006) found that mean papular pruritic eruption score declined from 3.9 at enrollment to 0.1 at 24 months. The condition disappeared and never returned in 37 (86%) of the 43 patients with at least six months of follow-up data. However, ART initiation was associated with an exacerbation of the skin condition as a result of IRIS in 13% of patients (seven out of 53). Despite limitations of this study, including 19% loss to follow-up (10 out of 53 participants), lack of blinding at outcomes assessment and lack of ascertainment of diagnosis by biopsy, it provides evidence for the positive impact of ART on papular pruritic eruption.

Other treatments not considered in recommendations due to lack of RCTs and very low quality evidence

Two prospective non-randomized studies that compared at least two interventions were identified. Oral dapsone versus oral pentoxifylline versus oral antihistamines and topical clobetasol were examined in 30 participants (10 per group) in the first study. Participants treated with pentoxifylline had a faster clinical response and longer remission (Lakshmi et al., 2008). The other study investigated oral promethazine (n=50) versus topical 1% hydrocortisone (n=18).

Reduction in mean pruritus scores was greater in the group receiving oral promethazine (Navarini et al., 2010). Hydrocortisone reduced itch by 16% whereas promethazine reduced itch by 50%.

In a study by Berman and colleagues (1998), among participants who received pentoxifylline 400 mg three times daily for eight weeks the average degree of pruritus was significantly reduced (p = 0.0009) from 6.5 at baseline examination to 3.6 at the end of the study. However, due to lack of randomization and small sample size, the study provided very low quality evidence.

6.4. Considerations for development of recommendations

There is a lack of RCTs investigating interventions for papular pruritic eruption. Although the regression of the condition with initiation of ART is recognized (Colebunders et al., 2006), there are few studies systematically documenting the response of papular pruritic eruption to ART. The available evidence on other possible interventions is very limited, and the quality of evidence is very low.

The expert panel considered that there is benefit from using symptomatic therapy in the form of oral antihistamines and topical corticosteroids for treatment of papular pruritic eruption in HIV-infected individuals. It is common practice to use these medications for this condition. Although this treatment provides symptom relief, the papular pruritic eruption does recur. Due to lack of RCTs and even non-RCTs this recommendation is based on expert panel opinion, and therefore graded as conditional with very low quality evidence.

The panel also considered ART initiation, with or without symptomatic therapy, as the best option in HIV-infected children and adults. The present WHO recommendation (WHO, 2013) is ART initiation for all symptomatic patients. ART would be acceptable to most patients who are eligible for treatment, and the incremental cost is probably small. Therefore, the recommendation for ART for papular pruritic eruption in HIV-infected children and adults is graded as strong. However, because of lack of RCTs, and very limited evidence from other studies, the quality of evidence is very low.

For all other treatments studied, such as pentoxifylline, ultraviolet light – B (UVB) phototherapy, and psoralen combined with ultraviolet A (PUVA) therapy, not only is the evidence of very low quality, but the treatments are expensive and neither easily accessible nor feasible to implement in control programmes.

Adverse effects, costs, availability and other implementation considerations

As stated above, the present WHO recommendation is ART initiation for all symptomatic patients. ART would be acceptable to most patients who are eligible for treatment and the incremental cost is probably small. There is free access to ART in most settings.

Topical corticosteroids are easily available at low cost. However, though effective, they do have the potential for side effects, such as striae and telangiectasia, especially with long-term use. Potent topical steroids should not be used for more than three weeks continuously. If a longer duration is needed, the steroid should be gradually tapered to avoid rebound symptoms, and treatment should be resumed after a steroid-free period of at least one week. This intermittent schedule can be repeated chronically or until the condition resolves. Side effects are rare when topical steroids are used for three months or less.

Antihistamines are also easily available at low cost. Antihistamines have been in clinical use for six decades and are relatively free of adverse effects, although no long-term safety studies have been published.

6.5. Research gaps

Research gaps identified included:

  • Well-designed, prospective, blinded RCTs in HIV-infected adults and children to provide high quality evidence upon which to base clinical decision-making;
  • Establishment of a standardized outcome measure (e.g. time to resolution of the lesions or resolution after three months) to ensure studies are easier to compare.
  • Improvement of assessment of other clinical conditions/manifestations, CD4 and viral load associated with these conditions.
Copyright © World Health Organization 2014.

All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: tni.ohw@sredrokoob). Requests for permission to reproduce or translate WHO publications – whether for sale or for non-commercial distribution – should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html).

Bookshelf ID: NBK305405

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