Ninth issue
MAY 4TH, 2022
How much do those pesky little actinic keratoses really matter?
JAMA Dermatology
Severe actinic keratoses (AKs) actually are clinically relevant and may require closer follow-up
We commonly tell people that they have several little “precancerous spots,” but the actual risk may not be known to many. Actinic keratoses (AKs) are common in dermatology and most often treated to prevent squamous cell carcinoma (SCC). This was a secondary analysis of a single-blinded, multicenter randomized clinical trial. Patients with a minimum of 5 AK lesions were eligible for the study. A total of 624 patients were randomized to treatment with 5% fluorouracil cream (155 patients), 5% imiquimod cream (156 patients), methylaminolevulinate PDT (156 patients), or 0.015% ingenol mebutate gel (157 patients). The probability of an indication for additional treatment within 4 years after the end of the first treatment was lowest after treatment with fluorouracil (23.3%) and significantly increased to 34.5% in the imiquimod group (P = .04), 42.7% in the methylaminolevulinate PDT group (P < .001), and 53.1% in the ingenol mebutate group (P < .001). A histologically proven invasive cSCC in the target area was diagnosed in 26 patients. The total 4-year risk of developing cSCC in a previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%), varying from 2.2% (95% CI, 0.7%-6.6%) in patients treated with fluorouracil to 5.8% (95% CI, 2.9%-11.3%) in patients treated with imiquimod. In patients with severe AK, the risk of cSCC was 20.9%, and the risk was especially high (33.5%) in patients with severe AK who needed additional treatment. This study suggests that patients with severe AKs that have required additional treatment may need close follow-up and different treatments can be considered.
What are predictors of successful basal cell treatment in older individuals?
Journal of the American Academy of Dermatology
Age is only a number! Researchers sought to determine which factors (including age) matter most when determining treatment burden, outcomes and overall survival of basal cell carcinoma treatment in older individuals.
Age is only a number! Basal cell carcinoma (BCC) is the most common skin cancer, and it is most frequently seen in older individuals. While BCCs very infrequently metastasize, their growth over time can cause significant morbidity, and therefore, proper treatment can be critical.
However, how do we determine if the treatment burden (e.g. post op surgical recovery) outweighs the risk of potential BCC morbidity?
In this prospective, multicenter observational cohort study, 539 older patients (70+ years old) who underwent surgical intervention for head/neck BCCs were evaluated for predictors of treatment burden, outcomes and overall survival.
What did they find?
Why does this matter? Age alone should not be the only determining factor when deciding BCC management. Patient-specific factors related to frailty such as multiple comorbidities, iADL dependency and polypharmacy should help inform BCC management plans.
Treating dermatomyositis with lenabasum, a CB2 receptor agonist
Journal of Investigative Dermatology
Lenabasum shows promise for treating dermatomyositis by reducing the inflammatory response.
Who would have thought that cannabinoid receptors may have some major health benefits for those suffering inflammatory conditions?? In particular, dermatomyositis is an inflammatory disease which causes muscle weakness and manifests as a painful/pruritic rash in sun-exposed areas with a distinctive heliotrope rash. Lenabasum is a novel type 2 cannabinoid receptor agonist that targets CB2 receptors on activated immune cells, modulating a reduction in inflammatory pathways. Researchers wanted to investigate the use of lenabasum for patients with dermatomyositis. A double-blind, placebo-controlled, Phase 2 clinical trial was performed, during which 22 subjects were randomly assigned to receive lenabasum or placebo treatment. All patients enrolled in the study were taking immunosuppressant medications, and the mean baseline Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was 33.3 ± 9.7 in the lenabasum arm, and 35.8 ± 7.8 in the placebo arm. At the end of the study, 18.2% of participants in the lenabasum arm had CDASI activity scores <14, 27.3% had scores between 14-19, and 54.5% had scores ≥ 20. Those in the treatment arm also expressed significant reductions in IFN-β and IFN-γ levels compared to baseline (p ≤ 0.05). This study was limited by its small sample size and lack of comparison in efficacy to other treatments for dermatomyositis. Overall, lenabasum shows promise for treating dermatomyositis by reducing the inflammatory response, and may be available for clinical use in the near future!
JAMA Dermatology
Severe actinic keratoses (AKs) actually are clinically relevant and may require closer follow-up
- Secondary analysis of a single-blinded, multicenter randomized clinical trial.
- Found that after 4 years of treatment, patients on fluorouracil required the least amount of additional treatment vs those on imiquimod group required the most additional treatment (P = .04).
- 4-year risk of developing cSCC in a previously treated area of AK is 3.7%, but the risk was especially high (33.5%) in patients with severe AK who needed additional treatment.
We commonly tell people that they have several little “precancerous spots,” but the actual risk may not be known to many. Actinic keratoses (AKs) are common in dermatology and most often treated to prevent squamous cell carcinoma (SCC). This was a secondary analysis of a single-blinded, multicenter randomized clinical trial. Patients with a minimum of 5 AK lesions were eligible for the study. A total of 624 patients were randomized to treatment with 5% fluorouracil cream (155 patients), 5% imiquimod cream (156 patients), methylaminolevulinate PDT (156 patients), or 0.015% ingenol mebutate gel (157 patients). The probability of an indication for additional treatment within 4 years after the end of the first treatment was lowest after treatment with fluorouracil (23.3%) and significantly increased to 34.5% in the imiquimod group (P = .04), 42.7% in the methylaminolevulinate PDT group (P < .001), and 53.1% in the ingenol mebutate group (P < .001). A histologically proven invasive cSCC in the target area was diagnosed in 26 patients. The total 4-year risk of developing cSCC in a previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%), varying from 2.2% (95% CI, 0.7%-6.6%) in patients treated with fluorouracil to 5.8% (95% CI, 2.9%-11.3%) in patients treated with imiquimod. In patients with severe AK, the risk of cSCC was 20.9%, and the risk was especially high (33.5%) in patients with severe AK who needed additional treatment. This study suggests that patients with severe AKs that have required additional treatment may need close follow-up and different treatments can be considered.
What are predictors of successful basal cell treatment in older individuals?
Journal of the American Academy of Dermatology
Age is only a number! Researchers sought to determine which factors (including age) matter most when determining treatment burden, outcomes and overall survival of basal cell carcinoma treatment in older individuals.
- Prospective, multicenter observational cohort study evaluating 539 older patients (70+ years old) who underwent surgical intervention for head/neck BCCs
- Spoiler alert- age was not the major predictor for treatment burden and outcomes! In fact, older patients experienced a low overall treatment burden (median VAS score of 8.6)
- Predictors that mattered more for higher treatment burden included female sex, larger tumor diameter, frailty-related patient characteristics (iADL dependency and polypharmacy) and overall mortality (comorbidities and iADL dependency).
Age is only a number! Basal cell carcinoma (BCC) is the most common skin cancer, and it is most frequently seen in older individuals. While BCCs very infrequently metastasize, their growth over time can cause significant morbidity, and therefore, proper treatment can be critical.
However, how do we determine if the treatment burden (e.g. post op surgical recovery) outweighs the risk of potential BCC morbidity?
In this prospective, multicenter observational cohort study, 539 older patients (70+ years old) who underwent surgical intervention for head/neck BCCs were evaluated for predictors of treatment burden, outcomes and overall survival.
What did they find?
- Spoiler alert- age was not the major predictor! In fact, older patients experienced a low overall treatment burden (median VAS score of 8.6).
- Predictors that mattered more for higher treatment burden included female sex, larger tumor diameter, frailty-related patient characteristics (iADL dependency and polypharmacy) and overall mortality (comorbidities and iADL dependency).
Why does this matter? Age alone should not be the only determining factor when deciding BCC management. Patient-specific factors related to frailty such as multiple comorbidities, iADL dependency and polypharmacy should help inform BCC management plans.
Treating dermatomyositis with lenabasum, a CB2 receptor agonist
Journal of Investigative Dermatology
Lenabasum shows promise for treating dermatomyositis by reducing the inflammatory response.
- A double-blind, placebo-controlled, Phase 2 clinical trial was performed, during which 22 subjects were randomly assigned to receive lenabasum or placebo treatment.
- After treatment, 18.2% of participants in the lenabasum arm had CDASI activity scores <14, 27.3% had scores between 14-19, and 54.5% had scores ≥ 20 (CDASI 33.3 ± 9.7 pre-tx).
- Significant reductions in IFN-β and IFN-γ levels were seen compared to baseline (p ≤ 0.05).
Who would have thought that cannabinoid receptors may have some major health benefits for those suffering inflammatory conditions?? In particular, dermatomyositis is an inflammatory disease which causes muscle weakness and manifests as a painful/pruritic rash in sun-exposed areas with a distinctive heliotrope rash. Lenabasum is a novel type 2 cannabinoid receptor agonist that targets CB2 receptors on activated immune cells, modulating a reduction in inflammatory pathways. Researchers wanted to investigate the use of lenabasum for patients with dermatomyositis. A double-blind, placebo-controlled, Phase 2 clinical trial was performed, during which 22 subjects were randomly assigned to receive lenabasum or placebo treatment. All patients enrolled in the study were taking immunosuppressant medications, and the mean baseline Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was 33.3 ± 9.7 in the lenabasum arm, and 35.8 ± 7.8 in the placebo arm. At the end of the study, 18.2% of participants in the lenabasum arm had CDASI activity scores <14, 27.3% had scores between 14-19, and 54.5% had scores ≥ 20. Those in the treatment arm also expressed significant reductions in IFN-β and IFN-γ levels compared to baseline (p ≤ 0.05). This study was limited by its small sample size and lack of comparison in efficacy to other treatments for dermatomyositis. Overall, lenabasum shows promise for treating dermatomyositis by reducing the inflammatory response, and may be available for clinical use in the near future!
QUESTION OF THE WEEK
NEJM CHALLENGE QUESTION
A 53-year-old landscaper presented to the dermatology clinic with a 4-month history of red, raised, itchy skin lesions on his left lower back and buttock. Physical examination showed numerous verrucous nodules and plaques with overlying crusting and surrounding erythema on the left lower back and buttock. Grocott-Gomori methenamine silver staining showed broad-based budding organisms. Chest imaging showed no abnormalities. Which of the following is the best treatment?
1. Clarithromycin and amikacin
2. Itraconazole
3. Penicillin
4. Rifampicin, isoniazid, pyrazinamide, and ethambutol
5. Trimethoprim-sulfamethoxazole
1. Clarithromycin and amikacin
2. Itraconazole
3. Penicillin
4. Rifampicin, isoniazid, pyrazinamide, and ethambutol
5. Trimethoprim-sulfamethoxazole
Answer: Itraconazole
The patient had blastomycosis. The urine antigen test was positive for blastomyces. Primary cutaneous blastomycosis is caused by blastomyces species which is a dimorphic fungi found in eastern half of the US. It grows in soil and wooded areas. The cutaneous presentation usually occurs in disseminated disease, but in this case, it was through primary inoculation. Treatment is itraconazole, and in this case it took 6 months for resolution.
Other answers:
1. Clarithromycin and amikacin- this combination is not used to treat blastomycosis
3. Penicillin- used to treat actinomycosis, which generally presents as red-brown nodules with fistulous abscesses draining characteristic yellow sulfur granules
4. Rifampicin, isoniazid, pyrazinamide, and ethambutol- treatment of mycobacterium tuberculosis
5. Trimethoprim-sulfamethoxazole - treatment for various infections, including nocardia gram positive cocci (e.g., MRSA, E. faecalis, and S. pyogenes), H. influenzae, P. jirovecii, Chlamydia, and various gram negative organisms
The patient had blastomycosis. The urine antigen test was positive for blastomyces. Primary cutaneous blastomycosis is caused by blastomyces species which is a dimorphic fungi found in eastern half of the US. It grows in soil and wooded areas. The cutaneous presentation usually occurs in disseminated disease, but in this case, it was through primary inoculation. Treatment is itraconazole, and in this case it took 6 months for resolution.
Other answers:
1. Clarithromycin and amikacin- this combination is not used to treat blastomycosis
3. Penicillin- used to treat actinomycosis, which generally presents as red-brown nodules with fistulous abscesses draining characteristic yellow sulfur granules
4. Rifampicin, isoniazid, pyrazinamide, and ethambutol- treatment of mycobacterium tuberculosis
5. Trimethoprim-sulfamethoxazole - treatment for various infections, including nocardia gram positive cocci (e.g., MRSA, E. faecalis, and S. pyogenes), H. influenzae, P. jirovecii, Chlamydia, and various gram negative organisms
SK(IN DEPTH) RECAP
What were some conclusions of the IXORA-PEDS trial studying long-term effects of ixekizumab in children? There was an increased risk of candida infections in weeks 48-108.
A. There was an increased risk of anaphylaxis episodes in weeks 48-108.
B. There was increased clearance of nail psoriasis at week 108 compared to week 12.
C. There was increased clearance of palmoplantar psoriasis at week 108 compared to week 12.
D. There was increased clearance of scalp psoriasis at week 108 compared to week 12.
Changes in lentigo maligna scores using reflectance confocal microscopy were observed after 1-month treatment with ___ in Soenen at al.
A. Mohs
B. Imiquimod
C. 5-Fluorouracil
D. Calcineurin Inhibitors
E. Retinol
What were differences reported by Voigt et al. in the microbiomes of cutaneous squamous cell carcinomas?
A. Increased Staph aureus: Cutibacterium acnes
B. Decreased Staph aureus: Cutibacterium acnes
C. No change
A. There was an increased risk of anaphylaxis episodes in weeks 48-108.
B. There was increased clearance of nail psoriasis at week 108 compared to week 12.
C. There was increased clearance of palmoplantar psoriasis at week 108 compared to week 12.
D. There was increased clearance of scalp psoriasis at week 108 compared to week 12.
Changes in lentigo maligna scores using reflectance confocal microscopy were observed after 1-month treatment with ___ in Soenen at al.
A. Mohs
B. Imiquimod
C. 5-Fluorouracil
D. Calcineurin Inhibitors
E. Retinol
What were differences reported by Voigt et al. in the microbiomes of cutaneous squamous cell carcinomas?
A. Increased Staph aureus: Cutibacterium acnes
B. Decreased Staph aureus: Cutibacterium acnes
C. No change
ANSWERS
What were some conclusions of the IXORA-PEDS trial studying long-term effects of ixekizumab in children?
A. There was an increased risk of candida infections in weeks 48-108.
B. There was an increased risk of anaphylaxis episodes in weeks 48-108.
C. There was increased clearance of nail psoriasis at week 108 compared to week 12.
D. There was increased clearance of palmoplantar psoriasis at week 108 compared to week 12.
E. There was increased clearance of scalp psoriasis at week 108 compared to week 12.
The IXORA-PEDS trial examined the long-term efficacy and safety of ixekizumab in children. They found increased clearance of nail psoriasis, clearance of palmoplantar psoriasis, and clearance of scalp psoriasis at 108 weeks of treatment. Additionally, they found no new candida infections or anaphylaxis episodes from 48-108 weeks of treatment. This study supports the continued efficacy and safety of long-term ixekizumab therapy in children.
Changes in lentigo maligna scores using reflectance confocal microscopy were observed after 1-month treatment with ___ in Soenen at al.
A. Mohs
B. Imiquimod
C. 5-Fluorouracil
D. Calcineurin Inhibitors
E. Retinol
In Soenen et al., the authors utilized reflectance confocal microscopy (RCM) to assign scores measuring lentigo maligna severity and compared lentigo maligna scores before and after 1 month of imiquimod therapy. They found that RCM could identify differences in tumor features and could potentially be used as an adjunctive tool to assess response of lentigo maligna to various therapies.
What were differences reported by Voigt et al. in the microbiomes of cutaneous squamous cell carcinomas?
A. Increased Staph aureus: Cutibacterium acnes
B. Decreased Staph aureus: Cutibacterium acnes
C. No change
Voigt et al. examined differences in the microbiota in actinic keratosis (AK) and squamous cell carcinoma (SCC) lesions compared with that of healthy skin. They found significantly decreased ratios of cutibacterium acnes:staphylococcus aureus in SCC samples and a similar downtrend in AK samples. The authors thus postulate that shifts in the microbiota may play important roles in cancer progression and could potentially be used as biomarkers for skin cancer detection.