Randomized clinical trial testing the efficacy and safety of 0.5% colchicine cream versus photodynamic therapy with methyl aminolevulinate in the treatment of skin field cancerization: study protocol.

BACKGROUND: The primary clinical manifestation of skin field cancerization is the presence of actinic keratoses (AKs). Current treatments for AKs related to skin field cancerization include photodynamic therapy (PDT) and colchicine. The objective of this study is to evaluate the efficacy and safety of 0.5% colchicine cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin field cancerization. METHODS: In a randomized controlled and open clinical trial with a blind histopathological and immunohistochemical analysis, 36 patients with up to 10 AKs on their forearms will be included from the outpatient clinic. The forearms will be randomized into two groups, clinically evaluated and biopsied for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be treated with 0.5% colchicine cream for 10 days, and the other forearm will receive one session of MAL-PDT; the forearms will subsequently be reassessed clinically and histologically after 60 days (T60) of treatment. The primary endpoint will be the point of complete clearance of AKs in T60. The sample size will enable a detection in the reduction of over 10% in AK counts between the groups with power of 0.9 and an alpha of 0.05, accounting for an estimated dropout rate of 10%, resulting in 36 patients (72 forearms). All participants included in the randomized study will be part of the analysis, and the final outcomes of any dropouts will be the value of their last visit (LOCF). The statistical analysis will be performed using SPSS 22.0, and a p value < 5% will be considered to be significant. DISCUSSION: It is expected that colchicine will be superior to MAL-PDT in reducing AKs and in the skin field cancerization, and there will be good tolerability in both groups. Colchicine intervention is novel in that it provides a new alternative to MAL-PDT. Moreover, this drug is inexpensive that may be a potential treatment of skin field cancerization that can be prescribed in public health systems with good results. TRIAL REGISTRATION: The trial is registered in Brazilian Registry for Clinical Trials (Registration number: RBR-8y3sj9 , date assigned May 4, 2016, retrospectively registered).

Efficacy and safety of 0.5% colchicine cream versus 5% 5-fluorouracil cream in the treatment of cutaneous field cancerization: a randomized clinical trial.

BACKGROUND: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). OBJECTIVE: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. METHOD: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. RESULTS: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). STUDY LIMITATIONS: Single-center study. CONCLUSIONS: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.

Cardiovascular events associated with thalidomide and prednisone in leprosy type 2 reaction.

BACKGROUND: Thalidomide is the drug of choice for the treatment of type 2 leprosy reactions and is often associated with corticosteroids. The use of these drugs in multiple myeloma is associated with the risk of cardiovascular events, but there have been few studies assessing this risk in leprosy patients. OBJECTIVE: To evaluate the occurrence of cardiovascular events in patients with multibacillary leprosy and their correlation with the use of thalidomide and prednisone. METHODS: Analytical cross-sectional study of all patients diagnosed with multibacillary leprosy treated at the Dermatology Service between 2012 and 2022, using electronic medical records. Thromboembolic vascular events, both arterial and venous, including acute myocardial infarction, were considered. The main independent variable was the concomitant use of thalidomide and prednisone during follow-up. RESULTS: A total of 89 patients were included, of which 19 used thalidomide and prednisone concomitantly. There were five cardiovascular events (26.3%), three of which of deep venous thrombosis. The combined use of medications was associated with the events (PR=6.46 [3.92 to 10.65]; p<0.01). STUDY LIMITATIONS: Small number of events, single-center retrospective study. CONCLUSION: The hypothesis of an association between cardiovascular events and the concomitant use of thalidomide and prednisone is supported, but more robust prospective studies are required for a better assessment.

Association between calcium channel blockers and the severity of actinic keratosis on face and scalp: a cross-sectional study.

BACKGROUND: Actinic keratosis (AK) is a skin condition associated with age, sun exposure, and immunosuppression. Certain drugs, such as photosensitizing medications and calcium channel blockers (CCBs), have been linked to AK. This study explores the impact of individual, behavioral, and exposure factors on the severity of AKs on the face and scalp. METHODS: A multicenter cross-sectional study was conducted on immunocompetent individuals with at least one AK on their face or scalp and assessed demographic factors, sun exposure and protection, history of skin cancer, and medication use within the last 6 months. The primary outcome was the Actinic Keratosis Area and Severity Index (AKASI) score, and a hierarchical generalized linear model was used to evaluate the variation in AKASI scores, adjusting for gender, age, and skin phototype. RESULTS: Two hundred seventy subjects between 39 and 92 years were evaluated. The majority had phototype I or II (77%), male gender (51%), personal history of skin cancer (55%), and low adherence to sunscreen use (29%). The use of photosensitizing medications was reported by 61%. Through multivariate analysis, older age (ßSE = 0.14; P < 0.01), lighter skin phototype (ßSE = 0.15; P = 0.01), history of skin cancer (ßSE = 0.12; P < 0.01), sunburning (ßSE = 0.12; P < 0.01), and use of CCBs (ßSE = 0.11; P = 0.02) were identified as independent risk factors for AK severity. Photosensitizing drugs were not identified as risk factors. CONCLUSION: Older age, lower skin phototype classifications, and a personal history of skin cancer were confirmed as severity risk factors for AK, while the use of CCBs was associated with more severe AK.

Efficacy of sunscreen with photolyase or regular sunscreen associated with topical antioxidants in treating advanced photodamage and cutaneous field cancerization: a randomized clinical trial.

BACKGROUND: Several treatments are available for skin with advanced photodamage, which is characterized by the presence of actinic keratoses (AK). OBJECTIVES: Evaluate the efficacy of using sunscreen with photolyase compared to regular sunscreen, as well as to compare the combination of a topical formulation of antioxidants versus placebo in the treatment of advanced photodamage. METHODS: This was a randomized, double-blind, factorial clinical trial. Participants with AKs on their forearms were randomized to apply regular sunscreen (SC) or sunscreen with photolyase (SC+P) on both forearms during the day. One of the forearms in each group was randomized again to receive topical antioxidants (AOx), and the other forearm received a placebo cream (both for night application). The four groups were SC/AOx, SC/placebo, SC+P/AOx, and SC+P/placebo. The duration of treatment was 8 weeks. Primary outcomes were total AK clearance, decrease in Forearm Photoaging Scale (FPS), and AK severity scores. Secondary outcomes were reduction in AK count, partial clearance rate, and safety. RESULTS: Forty participants (80 forearms) were included. All groups showed significant improvement in outcomes at week eight. There were no significant differences between SC and SC+P for either outcome. AOx led to a significant reduction in AK count (22%; p < 0.05). Partial clearance was obtained in 18 (47.4%) forearms treated with AOx and in 9 (23.7%) treated with placebo (p < 0.05). All groups reduced the FPS score, without significant differences among them. CONCLUSIONS: There is no difference in the treatment of advanced photodamage skin when comparing the use of sunscreen with photolyase and regular sunscreen, and topical antioxidants were more efficient in reducing AK count than placebo. STUDY LIMITATIONS: Short interval of follow-up and absence of re-evaluation in the absence of treatment were limitations of the present study.

Disseminated tuberculosis associated with reactive arthritis of Poncet in an immunocompetent patient.

Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl-Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment.

Efficacy and safety of 0.5% colchicine cream versus 5% 5-fluorouracil cream in the treatment of cutaneous field cancerization: a randomized clinical trial

Abstract Background 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). Objective To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. Method This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. Results After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). Study limitations Single-center study. Conclusions 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.

Contribution to characterization of skin field cancerization activity: morphometric, chromatin texture, proliferation, and apoptosis aspects.

BACKGROUND: A skin field cancerization is a cutaneous area with subclinical changes resultant from chronic sun exposure, with a higher predisposition to development of pre-neoplastic and neoplastic lesions. So far, there are no well-defined objective parameters that can indicate their degree of activity. OBJECTIVES: To describe and compare morphometric aspects and expression of factors related to apoptosis and cell proliferation in actinic keratosis (AK), in both photoexposed and photoprotected epidermis. METHODS: A cross-sectional study of patients with actinic keratosis in the forearms, biopsied at two points: the actinic keratosis and the axillary region. The biopsies of the actinic keratosis, perilesional area, and axilla were evaluated through keratinocyte intraepithelial neoplasia (KIN), and immunohistochemistry of p53, survivin, and Ki67. Nuclear morphometry of basal layer cells was performed through digital image analysis: entropy, area, perimeter, Ra, fractal dimension, circularity, color intensity, and largest diameter. RESULTS: There were 13 patients included and 38 actinic keratosis biopsied. In morphometry, 1039 nuclei were analyzed, of which 228 represented axillary skin, 396 demonstrated actinic keratosis, and 415 represented the perilesional area to the actinic keratosis. There was a significant difference (p<0.05) in all variables tested for the topographies evaluated. A significant correlation was identified between nucellar morphometric elements, KIN, proliferation markers, and apoptosis. Joint patterns of p53, Ki67, and KIN discriminated the topographies sampled. STUDY LIMITATIONS: This was a cross-sectional study with a small number of patients. CONCLUSIONS: There are patterns of proliferation, resistance to apoptosis, and different cellular morphometrics between photoprotected skin and photoexposed skin. The joint expression of p53, Ki67, and KIN can characterize skin field cancerization activity.

Cardiovascular events associated with thalidomide and prednisone in leprosy type 2 reaction

Abstract Background: Thalidomide is the drug of choice for the treatment of type 2 leprosy reactions and is often associated with corticosteroids. The use of these drugs in multiple myeloma is associated with the risk of cardiovascular events, but there have been few studies assessing this risk in leprosy patients. Objective: To evaluate the occurrence of cardiovascular events in patients with multibacillary leprosy and their correlation with the use of thalidomide and prednisone. Methods: Analytical cross-sectional study of all patients diagnosed with multibacillary leprosy treated at the Dermatology Service between 2012 and 2022, using electronic medical records. Thromboembolic vascular events, both arterial and venous, including acute myocardial infarction, were considered. The main independent variable was the concomitant use of thalidomide and prednisone during follow-up. Results: A total of 89 patients were included, of which 19 used thalidomide and prednisone concomitantly. There were five cardiovascular events (26.3%), three of which of deep venous thrombosis. The combined use of medications was associated with the events (PR = 6.46 [3.92 to 10.65]; p<0.01). Study limitations: Small number of events, single-center retrospective study. Conclusion: The hypothesis of an association between cardiovascular events and the concomitant use of thalidomide and prednisone is supported, but more robust prospective studies are required for a better assessment.