Comment on: Proposal for a new diagnostic classification of photodistributed Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap (SJS/TEN), collectively referred to SJS/TEN, form a spectrum of severe life-threatening adverse drug reactions whose pathomechanism is not fully understood. The article "Photodistributed Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Proposal for a New Diagnostic Classification" by McKinley et. al., discusses a distinct distribution of epidermal necrosis in SJS/TEN, attributable to preceding exposure to ultraviolet radiation (UVR), and relative sparing of photo-protected areas. After reviewing numerous cases within the Immune-mediated Adverse drug Reactions in African HIV endemic setting Register and Biorepository (IMARI-SA) at the University of Cape Town with a similar clinical pattern as those published by McKinley et. al., we propose that the relative sparing of some areas giving an impression of photo-distribution is due to localised increase in skin pressure that reduces the blood supply in that area below a critical threshold. A dip in blood supply below this critical threshold quantitively limited T lymphocytes and cytokines that drive SJS/TEN to reach and damage the skin.

Integrated sun protection advice for the South African population.

Exposure to solar ultraviolet radiation (UVR) is associated with several cutaneous adverse effects. However, to the best of our knowledge, in South Africa there are no formal guidelines on sun protection. A group of South African dermatologists and researchers convened over the course of 1 year to deliberate on integrated advice for sun protection among the multi-ethnic South African population. For people with light skin and those with genetic skin disorders (e.g., oculocutaneous albinism), sun protection was identified as critical to prevent sunburn, skin cancer, and photoaging. The evidence is less clear for people with medium and darker skin types, especially the latter, in whom melanin may confer a degree of protection against some parts of the solar spectrum. Recent studies have demonstrated that visible light can cause pigmentary changes in individuals with darker skin types in particular. Sun protection for people of all skin colors is beneficial to protect against photoaging and ocular damage. Herein sun protection advice is suggested for South Africans of all skin colors to reduce morbidity and mortality from sun exposure, particularly relating to skin cancer. Several knowledge gaps are identified as future research priorities.

HIV-associated photodermatitis in African populations.

Photosensitive dermatoses are seen in 5% of HIV-infected persons. These include drug- and chemical-induced photoallergic and phototoxic reactions, chronic actinic dermatitis of HIV, photo lichenoid drug eruptions, and porphyria. Data on photodermatitis in HIV are limited to case reports and series. The pathogenesis is not completely understood and includes a th2 phenotype in HIV which results in impaired barrier function and resultant allergen sensitisation as well as immune dysregulation. The objective of this manuscript is to review the literature on the clinical phenotype, pathogenesis, role of photo and patch testing, outcomes, and treatment of photodermatitis in HIV in an African population.

Arteriovenous malformation after punch biopsy clinically mimicking a basal cell carcinoma: Case report and review of literature.

Arteriovenous malformations (AVM's) of the skin can be acquired post blunt or penetrating trauma. They may clinically mimic basal cell carcinomas and other lesions with overlying telangiectasia. Specific clinical, dermoscopic, and histological clues differentiate these conditions. AVM's may progress to destructive lesions and early surgical intervention is key.

Genetic diversity of HHV8 subtypes in South Africa: A5 subtype is associated with extensive disease in AIDS-KS.

Human herpes virus 8 (HHV8) is the etiological agent of all forms of Kaposi's sarcoma (KS). Six major subtypes (A-F), based on genetic variability of open reading frame (ORF)-K1, have been identified. Numerous studies point to differing tumorigenic and pathogenic properties of the HHV8 subtypes. The study objectives were to determine the HHV8 subtypes and their prevalence in a cohort of clinical and histologically confirmed KS in Cape Town, South Africa, and analyze associations between the different subtypes and clinical presentation of KS. Clinical records were prospectively reviewed to extract clinical presentation; demographic data were retrospectively collected and tissue biopsies were taken for ORF-K1 subtyping. Eighty six patients were subtyped; 81 AIDS (acquired immune deficiency syndrome)-KS and 5 African endemic-KS. Subtype A5 (42/86) and B2 (16/86) predominated. B1, B3, A1 and A4 subtypes were identified in 10/86, 9/86, 4/86 and 1/86 patients, respectively. A5 and B subtypes were found in African blacks and individuals of mixed ancestry, while subtypes A1 and A4 were found only in whites and individuals of mixed ancestry. Subtype A5 was associated with >10 KS lesions at presentation in the AIDS cohort (adjusted OR: 3.13; CI: 1.02-9.58). Subtypes A1 and A4 combined were less likely to be associated with poor risk tumor extension (P = 0.031) and A1 was associated with lower likelihood of lower limb involvement (P = 0.019). In conclusion, these results indicate that subtype A5 and B predominate in South Africa and A5 may be associated with more extensive disease.

Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy.

A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm (3) in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz). Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

Annular erythema and photosensitivity as manifestations of efavirenz-induced cutaneous reactions: a review of five consecutive cases.

OBJECTIVES: In HIV-infected persons, a rash is the most common manifestation of drug hypersensitivity reactions. Non-nucleotide reverse transcriptase inhibitors are a major cause of cutaneous reactions. While the characteristics of nevirapine-associated cutaneous adverse drug reactions (CADRs) have been well described, there are limited data on efavirenz-associated CADRs. The objective of this study was to characterize the clinical features of consecutive cases of efavirenz-associated CADRs in a single referral centre diagnosed over a 3 year period. METHODS: We retrospectively reviewed the clinical records of 231 patients admitted with CADRs to a tertiary dermatology ward in Cape Town, South Africa. RESULTS: In 42/231(18%) cases, there had been exposure to efavirenz in the preceding 8 weeks. Of these, 5/42 (12%) patients were diagnosed with probable efavirenz-associated CADRs based on the Naranjo score. The median exposure to efavirenz before the onset of the rash was 12 days (range 2-48). All the patients were female, with a median age of 31 years and a median CD4 cell count of 300 cells/mm(3) (range 81-887). Four had a photo-distributed eruption and one had a confluent indurated erythema affecting the face, trunk and limbs. In three out of five cases, there were annular plaques with raised erythematous edges and dusky centres, which were photo-distributed. Two patients had a mild transaminitis and another a mild eosinophilia. Histological features were non-specific, with perivascular lymphocytes the only consistent feature. In all five cases, efavirenz was withdrawn and potent topical steroid was the only CADR-specific intervention. The eruptions resolved on discharge from hospital, with no sequelae except for residual post-inflammatory hyperpigmentation. CONCLUSIONS: Photo-distribution and annular erythema should alert clinicians to the possibility of efavirenz-associated CADRs.