TWENTIETH ISSUE
October 19, 2022
Dermatomyositis is an inflammatory disease marked by skin rash and muscle weakness, which is treated with both steroid and steroid-sparing systemic therapies. In certain patients, cutaneous manifestations of dermatomyositis may be resistant to therapy despite improvements in muscular inflammatory symptoms. A phase 2 open label single arm nonrandomized controlled trial investigated response to apremilast in dermatomyositis patients (n=8) with refractory skin disease. Patients took apremilast, a systemic phosphodiesterase inhibitor, 30 mg twice daily for 6 months. Follow-up was performed at 1, 3, 6 and 7 months, during which researchers investigated clinical outcomes, quality of life, genetic changes, and inflammatory outcomes to evaluate efficacy.
Key findings:
- 7 patients had a decrease in CDASI (Cutaneous Disease Activity Severity Index) score of 4 or more at 3 months giving an overall response rate of 87.5%. There was no evidence of change in muscle disease. Of note, one patient discontinued due to adverse effects from treatment.
- Patients’ experienced significant improvements in quality of life index; at baseline, patients scored 15.1 on average, and improved to 6.3 at 3 months and 4.2 at six months.
- Researchers found altered expression of 195 genes (123 downregulated and 72 upregulated) by 2-fold or more over the course of the study.
- STAT1, STAT3, IL-4, IL-6, Il-12, Il-23, IFN alpha, IFN gamma, TNF alpha signals were downregulated. CCL5 levels were not altered.
- Interestingly 2 patients tapered their steroid use; 1 patient tapered their steroid sparing agent.
- No patient improved by using monotherapy within 6 months.
Limitations: Limitations of this study include small sample size, lack of control group, use of other concomitant treatments and homogeneity of patient population
Main Takeaway: Apremilast may be used as adjuvant treatment for refractory skin disease in dermatomyositis as it has improved quality of life and clinical outcomes.
Tetracycline-associated hyperpigmentation for treatment of acne vulgaris is more likely in patients with skin of color
Journal of the American Academy of Dermatology
Journal of the American Academy of Dermatology
To give or not give antibiotics?
Systemic tetracycline (TCN) therapy is a mainstay in the treatment of acne vulgaris due to its anti-inflammatory properties, but hyperpigmentation is a known side-effect of this treatment. In this retrospective study, researchers sought to analyze relationships between TCN-associated hyperpigmentation and ethnic background.
Using the Mass General Brigham (1992-2022) and TriNetX (2001-2022) databases, 186,158 patients diagnosed with acne vulgaris were identified. Cohorts were subsequently identified of patients who were prescribed TCN monotherapy and later developed new-onset hyperpigmentation after ≥2 weeks of treatment. Prior history of hyperpigmentation or isotretinoin use were criteria for exclusion. Researchers compared rates of new-onset hyperpigmentation between ethnic groups, using patients treated with cephalexin as a control (an antibiotic not associated with hyperpigmentation). Results showed that patients who were prescribed doxycycline had an increased risk of developing new hyperpigmentation compared to the cephalexin group (OR=1.13, p=0.004). Black (OR=1.74, p<0.0001) and Hispanic (OR=1.56, p=0.001) patients had the highest risk compared to white patients. Researchers also compared the effects of minocycline, a TCN alternative. They found that minocycline was associated with a lower risk of hyperpigmentation overall (OR=0.88, p=0.013). Black patients had increased risk of hyperpigmentation with minocycline (OR=1.37, p=0.013), but this risk was lower than in Black patients prescribed doxycycline.
Limitations: Reliance on prescription coding data which may not accurately reflect medication usage.
Main Takeaway: Tetracycline therapy for the treatment of acne vulgaris is associated with higher risk of treatment-associated hyperpigmentation, particularly in Black and Hispanic patients.
Characterizing the risk of nonkeratinocyte skin cancers in patients with HIV in the era of antiretroviral therapies
Journal of Investigative Dermatology
Journal of Investigative Dermatology
What is earth without “ART” in it? “Eh”
There are multiple contributors to the development of nonkeratinocyte skin cancers ( NKSC, e.g. melanoma and merkel cell), including UV exposure, oncogenic viruses, and immunosuppression. As long-term immunosuppression is a major risk factor, a potentially affected population includes patients with HIV, or human immunodeficiency virus. Antiretroviral therapy (ART) has been instrumental in improving immunosuppression in this patient population. Thus, the authors asked whether this improvement in immune function with ART could affect the risk of developing nonkeratinocyte skin cancers in patients with HIV. They examined the risk for 27 different skin cancers in patients with HIV during the ART era (1996-2018) using population-based data from cancer registries. They found that:
Main Takeaway: In the era of antiretroviral therapy, apart from Kaposi sarcoma, risk for developing most non-keratinocyte skin cancer was similar between the HIV patient population and the general population. As such, intensive skin surveillance for NKSC may not be as necessary in this patient population, in the absence of additional risk factors.
There are multiple contributors to the development of nonkeratinocyte skin cancers ( NKSC, e.g. melanoma and merkel cell), including UV exposure, oncogenic viruses, and immunosuppression. As long-term immunosuppression is a major risk factor, a potentially affected population includes patients with HIV, or human immunodeficiency virus. Antiretroviral therapy (ART) has been instrumental in improving immunosuppression in this patient population. Thus, the authors asked whether this improvement in immune function with ART could affect the risk of developing nonkeratinocyte skin cancers in patients with HIV. They examined the risk for 27 different skin cancers in patients with HIV during the ART era (1996-2018) using population-based data from cancer registries. They found that:
- 0.5% of patients with HIV developed a nonkeratinocyte skin cancer in the follow-up period
- In this patient population, Kaposi sarcoma was the most common nonkeratinocyte skin cancer (82%), followed by melanoma (12%) and cutaneous lymphoma (2.6%)
- Virus-related nonkeratinocyte cancers, such as Kaposi sarcoma, diffuse large B-cell lymphoma, and Merkel cell carcinoma, had the highest incidence rates
- No increase in incidence was observed for melanoma, adnexal carcinomas, or sarcomas
- There was a disproportionate increase in melanoma and merkel cell carcinoma on sun-exposed skin
Main Takeaway: In the era of antiretroviral therapy, apart from Kaposi sarcoma, risk for developing most non-keratinocyte skin cancer was similar between the HIV patient population and the general population. As such, intensive skin surveillance for NKSC may not be as necessary in this patient population, in the absence of additional risk factors.
The road to biologics in patients with hidradenitis suppurativa: a nationwide drug utilization study
British Journal of Dermatology
British Journal of Dermatology
Are we there yet?! Are we there yet?!
Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle characterized by recurrent, painful nodules that lead to sinus tracts and scarring in body folds. Treatment is challenging, and there is often a delay in diagnosis (mean disease duration prior to diagnosis of 7.2 years). Patients are often treated with prolonged courses of antibiotics before biologics are initiated, even though TNF-alpha inhibitors have been approved for the treatment of HS and many others are showing promising results in initial trials. The authors conducted a retrospective review of all patients with HS being treated with biologics in the Danish National Patient Registry over an 8-year period (2010-2018) to determine treatment pathways leading to the prescription of biologics.
The authors identified 225 patients with HS being treated with biologics. Prior to biologic therapy, patients were most commonly prescribed penicillin (n=214, 95.1%), dicloxacillin (n=194, 86.2%), tetracycline (n=145, 64.4%), and rifampin/clindamycin (n=111, 49.3%). Patients underwent a mean of 4.0 different treatments, and 16.9 different treatment series (sequences of continuous treatment with the same drug), prior to biologic prescription. The mean time from first systemic therapy until initiation of a biologic was 15.3 +5.1 years.
Limitations: This study is limited by its retrospective nature and lack of access to Hurley staging (which is used as a surrogate for disease severity). As HS patients are known to have other comorbid dermatologic diseases, some of these systemic therapies may have been prescribed for indications other than HS.
Main Takeaway: The extended duration of time between systemic and biologic therapies may represent a missed opportunity for preventing disease progression in HS patients and emphasizes the need to develop evidence-based guidelines to streamline HS treatment schemas.
Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle characterized by recurrent, painful nodules that lead to sinus tracts and scarring in body folds. Treatment is challenging, and there is often a delay in diagnosis (mean disease duration prior to diagnosis of 7.2 years). Patients are often treated with prolonged courses of antibiotics before biologics are initiated, even though TNF-alpha inhibitors have been approved for the treatment of HS and many others are showing promising results in initial trials. The authors conducted a retrospective review of all patients with HS being treated with biologics in the Danish National Patient Registry over an 8-year period (2010-2018) to determine treatment pathways leading to the prescription of biologics.
The authors identified 225 patients with HS being treated with biologics. Prior to biologic therapy, patients were most commonly prescribed penicillin (n=214, 95.1%), dicloxacillin (n=194, 86.2%), tetracycline (n=145, 64.4%), and rifampin/clindamycin (n=111, 49.3%). Patients underwent a mean of 4.0 different treatments, and 16.9 different treatment series (sequences of continuous treatment with the same drug), prior to biologic prescription. The mean time from first systemic therapy until initiation of a biologic was 15.3 +5.1 years.
Limitations: This study is limited by its retrospective nature and lack of access to Hurley staging (which is used as a surrogate for disease severity). As HS patients are known to have other comorbid dermatologic diseases, some of these systemic therapies may have been prescribed for indications other than HS.
Main Takeaway: The extended duration of time between systemic and biologic therapies may represent a missed opportunity for preventing disease progression in HS patients and emphasizes the need to develop evidence-based guidelines to streamline HS treatment schemas.
Clinical Features and Prognosis of Young and Middle Aged Adults with Skin Sebaceous Adenocarcinoma
Dermatologic Surgery
Dermatologic Surgery
Pretty rare – but be aware.
Cutaneous sebaceous adenocarcinoma is a rare skin cancer with low incidence and is typically seen in elderly patients. While this cancer can be clinically aggressive, it is thought to be particularly aggressive in patients with a genetic condition named Muir-Torre syndrome, a syndrome caused by mismatch repair gene defects leading to microsatellite instability. It couples the propensity for visceral malignancy (think gastrointestinal and genitourinary) seen in Lynch Syndrome/Hereditary Non-Polyposis Colorectal Carcinoma with sebaceous neoplasms (particularly around the eye) and keratoacanthomas.
Due to the low incidence of cutaneous sebaceous adenocarcinoma, little is known about how this condition behaves in middle-aged patient populations. This study evaluated 739 patient cases over 41 years and identified characteristic features and prognostic indicators for young and middle-aged patients with sebaceous adenocarcinoma.
What did they find?
Main Takeaway: Although rare, it is important to identify sebaceous adenocarcinomas with poor prognostic factors in young and middle-aged patients, especially those with Muir-Torrre syndrome.
Takeaway suggestion: Although cutaneous sebaceous adenocarcinomas are rare, it is important to identify these cancers, especially in patients with Muir-Torre Syndrome.
Cutaneous sebaceous adenocarcinoma is a rare skin cancer with low incidence and is typically seen in elderly patients. While this cancer can be clinically aggressive, it is thought to be particularly aggressive in patients with a genetic condition named Muir-Torre syndrome, a syndrome caused by mismatch repair gene defects leading to microsatellite instability. It couples the propensity for visceral malignancy (think gastrointestinal and genitourinary) seen in Lynch Syndrome/Hereditary Non-Polyposis Colorectal Carcinoma with sebaceous neoplasms (particularly around the eye) and keratoacanthomas.
Due to the low incidence of cutaneous sebaceous adenocarcinoma, little is known about how this condition behaves in middle-aged patient populations. This study evaluated 739 patient cases over 41 years and identified characteristic features and prognostic indicators for young and middle-aged patients with sebaceous adenocarcinoma.
What did they find?
- Younger patients had an overall better prognosis than middle-aged patients
- Female predominance was seen in Asian populations with female sex overall leading to a better prognosis
- Patients with Muir-Torre Syndrome had a worse prognosis compared to patients with sebaceous adenocarcinoma not in the setting of Muir-Torre Syndrome
- Proportion of extra-ocular sebaceous adenocarcinoma in the non-elderly has been increasing overtime
Main Takeaway: Although rare, it is important to identify sebaceous adenocarcinomas with poor prognostic factors in young and middle-aged patients, especially those with Muir-Torrre syndrome.
Takeaway suggestion: Although cutaneous sebaceous adenocarcinomas are rare, it is important to identify these cancers, especially in patients with Muir-Torre Syndrome.
