The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients
| dc.contributor.advisor | Peter, Jonathan | |
| dc.contributor.author | Chimbetete, Tafadzwa | |
| dc.date.accessioned | 2026-04-23T11:29:27Z | |
| dc.date.available | 2026-04-23T11:29:27Z | |
| dc.date.issued | 2023 | |
| dc.date.updated | 2026-04-23T10:58:52Z | |
| dc.description.abstract | Introduction: A greater incidence of severe cutaneous adverse drug reaction (SCAR) such as Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) occur among HIV-infected patients. We sought to characterize the immunohistological phenotype of the skin in these reactions to first-line TB drugs in HIV-infected cases, with a hypothesis that a possible depletion of T-regulatory cells (Tregs) and increased infiltration of effector cells may contribute to SCAR in the context of HIV. Participants and Methods: HIV cases with validated SCAR phenotypes (probable or definite) and confirmed reactions to either one or multiple first-line anti-TB (FLTB) drugs were chosen (n=20). These cases were matched against controls of HIV-uninfected patients who develop SCAR (n=6). Immunohistochemistry assays were carried out with the following antibodies: CD3, CD4, CD8, CD45RO and FOXP3. Positive cells were normalized to the number of CD3+ cells present. Results: Infiltrated immunoreactive T cells in SCAR were mainly found in the dermis. Dermal and epidermal CD4+ T-cells (and CD4+/CD8+ ratios) were lower in HIV-infected versus uninfected DRESS; p < 0.001 and p = 0.004, respectively. In contrast, no difference in dermal CD4+FOXP3+ Tregs were found in HIV-infected versus uninfected DRESS; median (IQR) CD4+FOXP3+ Tregs: [10 (0 - 30) cells/mm2 versus 4 (3 - 8) cells/mm2, p = 0.325]. HIV-infected SCAR patients clinically reacting to more than one FLTB drug (n=4) showed increased dermal CD4+ T-cells compared to single drug reactors (n=12), [32 (23 - 41) versus 15 (11 - 20) cells/high-powered field, p = 0.03]. This was associated with increased dermal CD4+FOXP3+ Tregs in multiple drug reactors, [39 (36- 48) versus 10 (1-22), p = 0.02] Conclusion: HIV-infected and uninfected SCAR was associated with an increased infiltration of cytotoxic CD8+ T-cells compared to normal skin, displaying their role as key mediators of tissue damage. CD4+ T-cells were decreased in HIV-infected SCAR, in line with known HIV pathology and higher dermal infiltrates were associated with risk for reactivity to multiple unrelated medications. While inter-individual variation was high, dermal Tregs were in fact increased in HIV-infected DRESS, and this requires further research to understand their role and any possible impact on lower SCAR mortality amongst HIV-infected patients. | |
| dc.identifier.apacitation | Chimbetete, T. (2023). <i>The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients</i>. (). University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/43128 | en_ZA |
| dc.identifier.chicagocitation | Chimbetete, Tafadzwa. <i>"The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients."</i> ., University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2023. http://hdl.handle.net/11427/43128 | en_ZA |
| dc.identifier.citation | Chimbetete, T. 2023. The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients. . University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. http://hdl.handle.net/11427/43128 | en_ZA |
| dc.identifier.ris | TY - Thesis / Dissertation AU - Chimbetete, Tafadzwa AB - Introduction: A greater incidence of severe cutaneous adverse drug reaction (SCAR) such as Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) occur among HIV-infected patients. We sought to characterize the immunohistological phenotype of the skin in these reactions to first-line TB drugs in HIV-infected cases, with a hypothesis that a possible depletion of T-regulatory cells (Tregs) and increased infiltration of effector cells may contribute to SCAR in the context of HIV. Participants and Methods: HIV cases with validated SCAR phenotypes (probable or definite) and confirmed reactions to either one or multiple first-line anti-TB (FLTB) drugs were chosen (n=20). These cases were matched against controls of HIV-uninfected patients who develop SCAR (n=6). Immunohistochemistry assays were carried out with the following antibodies: CD3, CD4, CD8, CD45RO and FOXP3. Positive cells were normalized to the number of CD3+ cells present. Results: Infiltrated immunoreactive T cells in SCAR were mainly found in the dermis. Dermal and epidermal CD4+ T-cells (and CD4+/CD8+ ratios) were lower in HIV-infected versus uninfected DRESS; p < 0.001 and p = 0.004, respectively. In contrast, no difference in dermal CD4+FOXP3+ Tregs were found in HIV-infected versus uninfected DRESS; median (IQR) CD4+FOXP3+ Tregs: [10 (0 - 30) cells/mm2 versus 4 (3 - 8) cells/mm2, p = 0.325]. HIV-infected SCAR patients clinically reacting to more than one FLTB drug (n=4) showed increased dermal CD4+ T-cells compared to single drug reactors (n=12), [32 (23 - 41) versus 15 (11 - 20) cells/high-powered field, p = 0.03]. This was associated with increased dermal CD4+FOXP3+ Tregs in multiple drug reactors, [39 (36- 48) versus 10 (1-22), p = 0.02] Conclusion: HIV-infected and uninfected SCAR was associated with an increased infiltration of cytotoxic CD8+ T-cells compared to normal skin, displaying their role as key mediators of tissue damage. CD4+ T-cells were decreased in HIV-infected SCAR, in line with known HIV pathology and higher dermal infiltrates were associated with risk for reactivity to multiple unrelated medications. While inter-individual variation was high, dermal Tregs were in fact increased in HIV-infected DRESS, and this requires further research to understand their role and any possible impact on lower SCAR mortality amongst HIV-infected patients. DA - 2023 DB - OpenUCT DP - University of Cape Town KW - Eosinophilia Systemic Symptoms KW - HIV LK - https://open.uct.ac.za PB - University of Cape Town PY - 2023 T1 - The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients TI - The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients UR - http://hdl.handle.net/11427/43128 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/43128 | |
| dc.identifier.vancouvercitation | Chimbetete T. The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients. []. University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2023 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/43128 | en_ZA |
| dc.language.iso | en | |
| dc.language.rfc3066 | eng | |
| dc.publisher.department | Department of Medicine | |
| dc.publisher.faculty | Faculty of Health Sciences | |
| dc.publisher.institution | University of Cape Town | |
| dc.subject | Eosinophilia Systemic Symptoms | |
| dc.subject | HIV | |
| dc.title | The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients | |
| dc.type | Thesis / Dissertation | |
| dc.type.qualificationlevel | Masters | |
| dc.type.qualificationlevel | Masters |