Lymphoedema in patients with lentigo maligna treated with imiquimod: a long-term adverse effect

Tio, Darryl; Kirtschig, Gudula; Hoekzema, R.; Montfrans, Catherine van

doi:10.1111/bjd.16267

Cited by 5 publications

(5 citation statements)

References 8 publications

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“…As there are no effective therapeutic strategies available to improve early treatment T. gondii infection, the development of new anti-Toxoplasma drugs should have high priority to tackle toxoplasmosis and reduce infection. Imidazoquinoline compounds such as imiquimod work as immune response modifiers with antiproliferative, antiparasite, antifungal, and antiviral activities that have been examined in several previous studies (van der Fits et al, 2009;de Sousa et al, 2014;Tio et al, 2018;Jabari et al, 2019). The cytotoxic effect of imiquimod against various cancers has been investigated, and it was shown that it induces apoptosis as well as increasing levels of the opioid growth factor receptor (OGFr) (Wybran and Plotnikoff, 1991;Zagon et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Ghaffarifar

Sharifi

Horton

et al. 2020

Front. Cell. Infect. Microbiol.

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Treatment for toxoplasmosis is not completely successful because of their unwanted side effects, and new treatments are needed. Imiquimod has ability to moderate immune response and used to treat a wide variety of infections and tumors. The aim of the present study was to evaluate the effect of imiquimod on the tachyzoites of T. gondii and infected macrophages in vitro and in BALB/c mice. The viability of T. gondii was assessed in the presence of various concentrations of imiquimod by direct counting after 6 and 24 h. The MTT assay was used to identify the viability of uninfected macrophages. The apoptotic effects were determined with flow cytometry on the tachyzoites and infected macrophages. For evaluation of parasite load in pre-treatment or post-treatment of macrophages Quantitative real time PCR (qPCR) was performed. For in vivo experiments, BALB/c mice received imiquimod before and after challenge with parasites. The mortality rate of mice, parasite numbers in spleen, and the INF-γ and IL-4 cytokine levels in spleen lymphocytes were evaluated. Imiquimod demonstrated anti-Toxoplasma effects by reducing the number of tachyzoites. The results of flow cytometry for drug-treated tachyzoites showed that apoptosis did not rise significantly relative to the control group (p < 0.05). Moreover, apoptosis was enhanced in infected macrophages as the concentration of imiquimod was reduced. The parasitic burden in imiquimod pretreated macrophages was significantly lower than those treated after infection (p < 0.01). A marked reduction was observed in survival rate, parasite load and INF-γ level in BALB/c mice that received imiquimod before parasitic challenge relative to those received drug after parasitic challenge (p < 0.01). Overall, imiquimod in the pretreated group had greater anti-Toxoplasma effects than imiquimod in posttreated group in vitro and in vivo. imiquimod may be considered as a candidate for use against Toxoplasmosis both therapeutically and prophylactically.

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Section: Discussionmentioning

confidence: 99%

Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Ghaffarifar

Sharifi

Horton

et al. 2020

Front. Cell. Infect. Microbiol.

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“…[ 34 ] (2018) CR 1 1 69 LM: cheek 1 Partial surgical excision + imiquimod 5% once/d 3 t/w for 3 m (only 15 applications because of inflammation) NR Complete (H) 5 y 0 (C) Tio et al . [ 31 ] (2018) CS 3 3 66–69 μ = 68 LM: cheek H Imiquimod 5% once/d 7 t/w for 8 w If insufficient response: Imiquimod 5% up to 3 t/d 7/w If exaggerated inflammatory response: imiquimod 5% once/d 3 t/w 1–2 Complete (H) NR NR Veraitch et al . [ 100 ] (2018) CR 1 1 75 MIS: vulva H Imiquimod 5% once/d once/w for 8 w then twice/w for 18 m NR Partial (H) NR NR Hamilko de Barros et al .…”

Section: Resultsmentioning

confidence: 99%

“…The most common adverse effects are local erythema, burning, edema, and crusts [ 30 ]. The development of alterations in skin pigmentation, such as post-inflammatory hyper and hypopigmentation, are also possible [ 31 ]. In their study, Di Bartolomeo et al observed the formation of perifollicular blue gray dots after 12 weeks of treatment with imiquimod 5% [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…These authors concluded that conjunctival inflammation can be easily treated without permanent ocular side effects and for that reason the use of imiquimod 5% is safe in the periorbital area. On the other hand, the corneal edema caused by imiquimod 5% could induce fibrosis and lymphohistiocytic infiltrate with a consequent compression of lymphatic vessels and the development of lymphoedema that can potentially persist for years, as reported by Tio et al [ 31 ]. Therefore, in order to limit adverse effects, it is important to adapt the number of weeks of imiquimod application based on the patient’s inflammatory reaction [ 31 ] .…”

Section: Introductionmentioning

confidence: 99%

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Topical Treatment of Melanoma In Situ, Lentigo Maligna, and Lentigo Maligna Melanoma with Imiquimod Cream: A Systematic Review of the Literature

Vaienti,

Calzari,

Nazzaro

2023

Dermatol Ther (Heidelb)

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Introduction The classical management of melanoma is surgery, but this can be challenging because of several factors, such as age, body area, lesion size, among others. Topical imiquimod may be a therapeutic option for the treatment of melanoma in situ and lentigo maligna melanoma due to its efficacy, tolerability, and non-invasiveness. The purpose of this systematic review is to assemble current evidence on the treatment of non-metastatic melanoma with topical imiquimod. Methods The PubMed/MEDLINE and Cochrane Library databases were searched as the primary sources using the main search terms “imiquimod” combined with “lentigo maligna” and “melanoma” with the command “AND.” Articles were identified, screened, and extracted for relevant data, following the PRISMA guidelines. Results A total of 87 studies covering 1803 lesions treated with imiquimod cream were identified and included in this sytematic review. Forty-nine studies were case reports, 16 were retrospective analyses, 3 were open label trials, six were case series; one study was a controlled randomized trial, one was a randomized trial, and one was a single-arm phase III trial. Because of the high number of low-evidence studies, the overall risk of bias resulted high. In 55 studies, imiquimod 5% was used in monotherapy as the primary treatment; only in one study was imiquimod 3.75% introduced. In most cases, the topical treatment was applied once daily, with the exception of nine cases where an increased daily dosage was prescribed. The total duration of the treatment regimen was extremely variable and depended on body area and tolerability, with differences among patients of the same study. In six studies, imiquimod was used as neoadjuvant therapy before the surgical excision, and in 11 studies it was used after surgery as complementary or adjuvant therapy. In total, 1133 of the 1803 (62.8%) lesions were reported to be cleared after the treatment, taking into account that not all of the patients completed the treatment. Of these 1133 lesions, histological clearance was achieved in 645 (56.9%) lesions and clinical clearance only was achieved in 490 (43.2%) lesions; relapse occurred in 107 lesions. Conclusions The heterogeneity of the studies included in this systematic review precludes the drawing of any relevant conclusions regarding the application of imiquimod. Its efficacy in melanoma in situ and lentigo maligna melanoma has been demonstrated, but further evidence from controlled studies concerning the modalities is missing.

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“…This drug may also cause side effects at non-application sites such as flu-like systemic syndrome or distant inflammatory mucosal reactions [ 26 ]. Some long-term adverse effects have been described, such as vitiligo-like depigmentation, associated with the mechanism of the action of imiquimod [ 27 ], and lymphoedema, caused by severe inflammation and dermal fibrosis [ 28 ].…”

Section: Immunotherapy In Melanoma In Situmentioning

confidence: 99%

Topical and Intralesional Immunotherapy for Melanoma In Situ: A Review

Martínez-Fernández,

González-Sixto,

Espasandín-Arias

et al. 2023

Cancers

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The incidence of in situ melanoma (MIS) has increased over the last decades. The mainstay of treatment for MIS, including lentigo maligna (LM), is complete surgical excision with clear margins (0.5 to 1.0 cm). Nevertheless, MIS lesions often affect elderly patients with comorbidities and involve large lesions in cosmetically sensitive areas, which means surgery is not always appropriate. Non-surgical treatments have a role in these cases, and include radiotherapy, cryosurgery, immunotherapy, laser therapy, and other topical medications. This study aims to review the applications of immunotherapy in MIS, either in monotherapy or in combination with other therapeutic alternatives. The main forms of immunotherapy used are imiquimod and, to a lesser extent, intralesional interferon-α (IL-INF-α) and ingenol mebutate (IM). IL-INF-α and IM have not been studied as extensively as imiquimod, whose results in real-life practice are encouraging. The clearance and recurrence rates reported in MIS treated with imiquimod as monotherapy, or as an adjuvant after surgery with affected or narrow margins, make imiquimod a reliable therapeutic alternative in selected cases. Also, its use as a neoadjuvant therapy before surgery was shown to reduce the final surgical defect size required to confirm negative histologic margins. In conclusion, local immunotherapy is frequently used in clinical practice and experience confirms it to be an excellent option for certain patients.

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Lymphoedema in patients with lentigo maligna treated with imiquimod: a long-term adverse effect

Cited by 5 publications

References 8 publications

Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice

Topical Treatment of Melanoma In Situ, Lentigo Maligna, and Lentigo Maligna Melanoma with Imiquimod Cream: A Systematic Review of the Literature

Topical and Intralesional Immunotherapy for Melanoma In Situ: A Review

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