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The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients
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 p...
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| Format: | Thesis |
| Language: | English English |
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Department of Medicine
2026
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| _version_ | 1867613260830736384 |
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| access_status_str | Open Access |
| author | Chimbetete, Tafadzwa |
| author2 | Peter, Jonathan |
| author_browse | Chimbetete, Tafadzwa Peter, Jonathan |
| author_facet | Peter, Jonathan Chimbetete, Tafadzwa |
| author_sort | Chimbetete, Tafadzwa |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/43128 |
| institution | University of Cape Town (South Africa) |
| language | English eng |
| last_indexed | 2026-06-10T12:33:19.547Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | Department of Medicine |
| publisherStr | Department of Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/43128 The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients Chimbetete, Tafadzwa Peter, Jonathan Eosinophilia Systemic Symptoms HIV 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. 2026-04-23T11:29:27Z 2026-04-23T11:29:27Z 2023 2026-04-23T10:58:52Z Thesis / Dissertation Masters Masters http://hdl.handle.net/11427/43128 en eng application/pdf Department of Medicine Faculty of Health Sciences University of Cape Town |
| spellingShingle | Eosinophilia Systemic Symptoms HIV Chimbetete, Tafadzwa The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients |
| thesis_degree_str | Master's |
| title | The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients |
| title_full | The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients |
| title_fullStr | The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients |
| title_full_unstemmed | The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients |
| title_short | The immunological profile of the skin in DRESS and SJS/TEN reactions to first-line tuberculosis drugs in HIV-infected patients |
| title_sort | immunological profile of the skin in dress and sjs ten reactions to first line tuberculosis drugs in hiv infected patients |
| topic | Eosinophilia Systemic Symptoms HIV |
| url | http://hdl.handle.net/11427/43128 |
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