Pruritic papular eruption of HIV disease

Pruritic papular eruption of HIV disease is a chronic itchy papular and pustular dermatosis that occurs in people living with HIV and is defined by symmetric lesions on the extensor surfaces of the arms, the dorsum of the hands, the trunk and the face with sparing of the palms and soles

The diagnosis requires the absence of another definable cause of itching, so scabies, drug eruption, eczema, psoriasis and eosinophilic folliculitis must be excluded before the eruption is attributed to HIV itself

It is most common in resource-limited settings and in people with advanced immunosuppression, and although it is not life-threatening the intense itch, disfigurement and sleep loss substantially reduce quality of life

Terminology and classification

• The eruption is also called pruritic papular eruption of HIV, HIV-associated pruritic papular eruption or prurigo of HIV, and the abbreviation PPE is used in the dermatology and HIV literature
• It is classified among the HIV-associated inflammatory dermatoses rather than among infectious dermatoses, because no single pathogen is consistently identified and the lesions respond to immune restoration and anti-inflammatory therapy
• The boundary with eosinophilic folliculitis of HIV is contested, because both show eosinophil-rich perifollicular inflammation and itching, and many authors regard PPE as part of the same clinicopathological spectrum
• ICD-11 indexes the entity under a foundation identifier 376749824, UMLS assigns CL936527 and CL1410786, and Wikidata uses Q7253117, while ICD-10 has no dedicated code and cases are usually coded under L73.8 or B23.8
• The main named differentials are scabies, eosinophilic folliculitis, drug eruption, papular pruritic eruption of pregnancy, prurigo nodularis, psoriasis and seborrhoeic dermatitis, each separated by history, distribution and histology
• It is distinct from HIV-associated xerosis and from immune reconstitution inflammatory syndrome, although both can coexist and both can worsen itching after antiretroviral therapy is started

History

• Pruritic papular eruptions were recognised in the first decade of the HIV epidemic, when dermatologists in Africa and the Americas described intensely itchy papules in patients with advanced immunosuppression
• Hevia and colleagues reported in 1991 a series of HIV-infected patients with pruritic papules and eosinophilic folliculitis, helping to separate the eruption from scabies and drug reactions
• Pardo and colleagues reported in 1992 that ultraviolet B phototherapy produced clearance in seven of eight treated patients, one of the earliest controlled observations of an effective therapy
• Boonchai and colleagues showed in 1999 that the eruption correlated with low CD4 counts, supporting the view that it is a marker of advanced HIV disease rather than an independent infection
• Resneck and colleagues described the burden of the eruption in Uganda in 2004, documenting its high frequency in clinics and its association with pruritus-related sleep loss and secondary infection
• The rollout of antiretroviral therapy after 2004 reduced the incidence of the eruption in programmes with broad coverage, but immune reconstitution inflammatory syndrome produced a new group of patients whose itching worsened shortly after treatment began
• The 2021 World Health Organization consolidated HIV guidelines and the 2023 United States HIV treatment guidelines now frame the eruption as a reason to assess adherence, CD4 recovery and alternative diagnoses rather than as an indication for a specific drug regimen

Epidemiology

• Reported prevalence varies geographically from about 12% to 46% of people living with HIV, with the highest figures in sub-Saharan Africa, Haiti and parts of Brazil and India
• Up to 46% of HIV-infected patients may develop the eruption at some point in their illness, and it is one of the commonest dermatological reasons for clinic attendance in settings with limited antiretroviral coverage
• A CD4 count below 200 cells per microlitre roughly triples the risk, and the eruption is uncommon in people with preserved CD4 counts and suppressed viral load on effective therapy
• Children with HIV can develop the same eruption, and in paediatric cohorts it is associated with growth faltering, school absence and secondary bacterial infection of excoriated lesions
• The eruption is more frequent in tropical and resource-limited settings, which may reflect environmental arthropod exposure, delayed HIV diagnosis and limited access to antiretroviral therapy rather than a direct climatic effect
• Sex distribution is roughly equal in most cohorts, although some clinics report a female predominance that may reflect differential health-seeking rather than biological susceptibility
• Incidence falls after sustained viral suppression, but the eruption remains a marker of poor immune recovery and is over-represented among people who start therapy late or interrupt treatment
• Because the diagnosis is clinical and no laboratory test is specific, reported rates depend on how aggressively scabies, drug reactions and eczema are excluded, and comparisons between studies should be interpreted with caution

Pathophysiology

• The eruption is thought to reflect HIV-driven immune dysregulation rather than direct viral infection of the skin, because HIV antigens and virions are not consistently found in lesional tissue
• Advanced HIV disease is associated with a shift toward T helper 2 responses, eosinophilia, elevated IgE and altered chemokine expression, all of which favour eosinophil recruitment into perifollicular and perivascular dermis
• Histology typically shows a perivascular and perifollicular infiltrate rich in eosinophils, with CD8-positive T cells and variable follicular epithelial damage, but these findings overlap with eosinophilic folliculitis and are not pathognomonic
• Arthropod bites, Demodex colonisation and impaired skin barrier function have been proposed as triggers, and the improvement sometimes seen with permethrin or ivermectin supports an environmental or mite-related contribution in some patients
• Scratching and excoriation damage the barrier further, promote secondary bacterial infection and can produce lichenification, hyperpigmentation and scarring, so pruritus itself becomes a driver of chronic skin change
• Immune reconstitution inflammatory syndrome can unmask or worsen the eruption after antiretroviral therapy begins, because restored CD4 responses react to skin antigens that were previously tolerated in the setting of profound immunosuppression

Clinical features

• Intense pruritus is the dominant symptom and often precedes the visible rash, and patients describe scratching until bleeding, sleep loss and difficulty concentrating at work or school
• Lesions are small erythematous papules and pustules, sometimes with excoriation or crust, distributed symmetrically on the extensor arms, dorsum of the hands, trunk and face, with relative sparing of the palms and soles
• Chronic scratching produces lichenification, post-inflammatory hyperpigmentation and scarring, and in darker skin the pigmentary change can be more distressing than the original papules
• Secondary bacterial infection presents with impetigo-like crusting, tenderness, lymphadenopathy and occasionally cellulitis, and it is more common in children and in people with poor access to care
• The face and trunk involvement can be disfiguring and is associated with stigma, social withdrawal and reduced adherence to HIV care, so the psychosocial impact should be assessed at every visit
• General examination should look for signs of advanced HIV disease such as oral candidiasis, weight loss, generalized lymphadenopathy and other opportunistic conditions, because the eruption is a marker of immunosuppression

Diagnosis

• The diagnosis is clinical and requires documented HIV infection, a characteristic symmetric papular eruption with intense itch, and exclusion of other causes of pruritus by history, examination and targeted testing
• Skin scraping and microscopy for scabies should be performed when burrows, web-space involvement or household itching are present, and empiric permethrin is reasonable when scrapings are negative but suspicion remains
• A biopsy is not routinely required but is useful when the diagnosis is uncertain, when lesions are atypical or when eosinophilic folliculitis, drug eruption or cutaneous lymphoma must be excluded
• Assessment should include CD4 count, HIV viral load, adherence history and a full medication review, because low CD4, virological failure and drug hypersensitivity all change the differential and the management plan
• The differential includes scabies, eosinophilic folliculitis, drug eruption, prurigo nodularis, psoriasis, seborrhoeic dermatitis, xerosis, insect bites and, in endemic areas, onchocerciasis and other filarial infections
• Response to antiretroviral therapy is itself diagnostically informative, because improvement in CD4 count and viral suppression with fading of the eruption supports the HIV-associated nature of the condition

Management

• Optimising antiretroviral therapy is the foundation of treatment, because durable viral suppression and CD4 recovery reduce the frequency and severity of the eruption more than any skin-directed therapy
• Topical corticosteroids such as betamethasone valerate or mometasone furoate reduce inflammation and itch, and they should be used for limited periods with attention to skin atrophy, especially on the face
• Oral antihistamines such as cetirizine or loratadine are used for symptomatic relief, and sedating antihistamines may help sleep but should be avoided during the day in people who need to work or drive
• Emollients and barrier repair reduce xerosis and scratching, and patients should be advised to keep nails short, avoid hot showers and use gentle cleansers to limit barrier damage
• Ultraviolet B phototherapy is effective in some patients and was reported to clear lesions in seven of eight treated patients in 1992, but access, cost and skin-cancer risk with cumulative exposure limit its use
• When arthropod bites or Demodex are suspected, permethrin or ivermectin may be tried, and household contacts should be treated if scabies is confirmed to prevent reinfestation
• Secondary bacterial infection requires topical or oral antibiotics guided by severity and local resistance patterns, and extensive cellulitis or systemic symptoms warrant urgent medical assessment
• Immune reconstitution inflammatory syndrome should be managed by continuing antiretroviral therapy, treating the underlying trigger and using anti-inflammatory therapy, with specialist input when the reaction is severe or prolonged

Research and controversies

• Whether PPE and eosinophilic folliculitis of HIV are one disease or two remains unresolved, and the answer affects trial design because studies may be enrolling overlapping populations under different names
• The role of Demodex, arthropod bites and environmental exposure is supported by partial responses to antiparasitic therapy but not by consistent microbiological evidence, and no pathogen has been shown to cause the eruption in controlled studies
• Biomarkers that distinguish PPE from eczema, drug eruption and scabies are lacking, and a validated severity score would improve both clinical trials and routine monitoring in resource-limited clinics
• The optimal timing and duration of phototherapy, the role of topical calcineurin inhibitors and the benefit of early antiretroviral therapy initiation for preventing the eruption are all uncertain and require prospective study
• Patient-reported outcome measures for HIV-related pruritus are underdeveloped, and including itch, sleep, stigma and adherence in future trials would capture the outcomes that matter most to people living with the eruption