An Update on Adverse Cutaneous Drug Reactions in HIV/AIDS

Abstract

Background: The global mortality from HIV and the cutaneous burden of infective, inflammatory and malignant diseases in the setting of AIDS have significantly declined following the advent of highly active antiretroviral therapy. Regrettably, there has been a contemporaneous escalation in the incidence of adverse cutaneous drug reactions (ACDR), with studies attesting that HIV-positive individuals are a hundred times more susceptible to drug reactions than the general population, and advanced immunodeficiency portending an even greater risk. Several variables are accountable for this amplified risk in HIV. Summary: Adverse reactions to trimethoprim-sulfamethoxazole are the most common, increasing from approximately 2–8% in the general population over to 43% amongst HIV-positive individuals to approximately 69% in subjects with AIDS. Antituberculosis drugs and antiretrovirals are also well-known instigators of ACDR. Cutaneous reactions range from mild morbilliform eruptions to severe, life-threatening manifestations in the form of Stevens-Johnson syndrome/toxic epidermal necrolysis. Histological features vary from vacuolar interface changes to full-thickness epidermal necrosis with subepidermal blister formation. A precipitous diagnosis of the ACDR, clinically and histologically if necessary, together with the isolation of the causative drug is critical. The identification process, however, is often complex and multifaceted due to polypharmacy and inconclusive data on which drugs are the most likely offending agents, especially against the background of tuberculosis co-infection. Key Messages: Whilst milder cutaneous reactions are treated symptomatically, severe reactions mandate immediate treatment discontinuation without rechallenge. Further studies are required to establish safe rechallenge guidelines in resource-limited settings with a high HIV and tuberculosis prevalence.

Viral Infections and Cutaneous Drug-Related Eruptions

“…The pathogenesis and the reason for the greater propensity for HIV-infected patients to develop DHR to a great variety of drugs that can be particularly severe, remain unknown. It may be related to their greater exposition to medication compared to general population and/or to a higher incidence of co-infection with EBV and CMV (Cytomegalovirus) ( Smith et al, 1997 ; Todd, 2006 ; Hoosen and et al, 2019 ). Since many different drugs are involved, the viral infection appears to enhance drug reactivity in general, not only for specific drugs.…”

Mass migration and climate change: Dermatologic manifestations

“…Presentations are typically mild. Morbilliform eruptions make up 95% of all cases and other milder conditions, such as urticarial rash, erythema multiforme, fixed drug eruption, and lichenoid drug eruptions, can occur ( Hoosen et al, 2019 ). Although the incidence of severe drug reactions, such as Steven-Johnson syndrome and toxic epidermal necrolysis, are higher among patients with HIV, they are still rare and make up only 0.5% of all ACDR cases ( Yunihastuti et al, 2014 ).…”

“…A history of ACDR should be explored prior to reintroducing ART or other therapies in HIV-positive migrants and refugees because ACDR has been reported in numerous antimicrobial agents, prophylactic agents, antituberculous therapy, and ART agents ( Yunihastuti et al, 2014 ). Hoosen et al (2019) described various ACDRs in HIV/AIDS in detail.…”

Latest Evidence Regarding the Effects of Photosensitive Drugs on the Skin: Pathogenetic Mechanisms and Clinical Manifestations

“…Among antiretrovirals, a photosensitive potential has been reported for efavirenz, tenofovir, and tipranavir. However, in the context of HIV infections, it is not always simple to distinguish cutaneous manifestations related to the disease itself from those induced by the drug [ 3 , 53 , 54 , 55 ]. Indeed, nearly 5% of patients with HIV suffer from some form of photosensitive dermatitis, including PSDs-induced reactions, actinic prurigo, chronic actinic dermatitis, lichenoid photoeruptions, porphyria cutanea tarda, pseudoporphyria, photoaggravated granuloma annulare, and actinic lichenoid leukomelanoderma [ 56 ].…”

“…Indeed, nearly 5% of patients with HIV suffer from some form of photosensitive dermatitis, including PSDs-induced reactions, actinic prurigo, chronic actinic dermatitis, lichenoid photoeruptions, porphyria cutanea tarda, pseudoporphyria, photoaggravated granuloma annulare, and actinic lichenoid leukomelanoderma [ 56 ]. Moreover, HIV patients are overall more susceptible to drug reactions than the general population, due to multiple factors among which there are polypharmacy, slow acetylator status, relative glutathione deficiency, and latent Herpesviridae infections [ 55 ].…”