Sixty-THIRD issue
June 26, 2024
Cutaneous manifestations of VEXAS Syndrome and associated clinical, genetic, and histopathological features
JAMA Dermatology
JAMA Dermatology
Ignoring skin symptoms in VEXAS? Genius.
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) Syndrome is a newly identified genetic disorder characterized by systemic inflammation, progressive bone marrow failure, and inflammatory skin manifestations predominately affecting men over 50. This observational cohort study of 112 patients (median age 69, 99% male) aimed to identify the spectrum of cutaneous manifestations in VEXAS syndrome and their associations with clinical, genetic, and histological features.
What did they find?
Main Takeaway: Dermatologists must recognize the spectrum of cutaneous and histopathologic features of VEXAS Syndrome to facilitate timely diagnosis and management of this potentially life-threatening systemic disease.
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) Syndrome is a newly identified genetic disorder characterized by systemic inflammation, progressive bone marrow failure, and inflammatory skin manifestations predominately affecting men over 50. This observational cohort study of 112 patients (median age 69, 99% male) aimed to identify the spectrum of cutaneous manifestations in VEXAS syndrome and their associations with clinical, genetic, and histological features.
What did they find?
- Skin involvement was present in 83% of patients.
- Histopathological findings included leukocytoclastic vasculitis (36%), neutrophilic dermatosis (34%), and perivascular dermatitis (30%).
- VEXAS-defining genetic variants in UBA1, which encodes for the ubiquitin-activating enzyme 1, were linked to particular skin manifestations:
- p.Met41Leu variant with neutrophilic dermal infiltrates (82%), mimicking Sweet syndrome.
- p.Met41Val variant with vasculitic lesions (55%) and mixed inflammatory infiltrates (85%).
- Oral prednisone improved skin symptoms in 92% of patients.
Main Takeaway: Dermatologists must recognize the spectrum of cutaneous and histopathologic features of VEXAS Syndrome to facilitate timely diagnosis and management of this potentially life-threatening systemic disease.
Clinical characteristics and symptom progression of dermatomyositis subtypes: A retrospective analysis of a prospective database
Journal of the American Academy of Dermatology
Journal of the American Academy of Dermatology
Dermatomyositis Subtype Shuffling, what does it all mean?
Dermatomyositis (DM) is a chronic, inflammatory skin and skeletal muscle autoimmune disorder with subtypes including classic DM (involvement of skin and skeletal muscle), postmyopathic DM (PmDM) (classic DM with muscle recovery and ongoing skin involvement), and clinically amyopathic DM (CADM) (skin manifestations without clinically evident muscle involvement). This retrospective, monocentric cohort study aimed to characterize and longitudinally track the progression of classic DM and CADM. Skin involvement was recorded using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI).
What did they find?
Main Takeaway: The majority of classic DM patients continued to meet criteria for diagnosis of classic DM, demonstrating muscle disease and skin involvement throughout their disease course. CADM patients demonstrated a low risk of progressing to classic DM, with the severity skin involvement serving as a potential predictive factor.
Dermatomyositis (DM) is a chronic, inflammatory skin and skeletal muscle autoimmune disorder with subtypes including classic DM (involvement of skin and skeletal muscle), postmyopathic DM (PmDM) (classic DM with muscle recovery and ongoing skin involvement), and clinically amyopathic DM (CADM) (skin manifestations without clinically evident muscle involvement). This retrospective, monocentric cohort study aimed to characterize and longitudinally track the progression of classic DM and CADM. Skin involvement was recorded using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI).
What did they find?
- 269 patients were included, 138 with classical DM and 131 with CADM.
- 40% (n = 55) of classic DM progressed to PmDM, with a median time-to-subtype conversion after onset of 3.8 years (IQR = 7.1).
- Patients who converted from classic DM to PmDM had milder skin disease at the time of subtype conversion (median CDASI activity [CDASI-A] 13.0 at conversion vs. 15.5 at baseline; P = 0.02).
- 5% (n = 7) of initially CADM diagnosed patients developed muscle involvement, reclassifying them as classic DM, with a median time-to-subtype conversion after DM onset of 6.3 years (IQR = 8.8).
- CADM patients who converted to classical DM had milder skin disease at the time of subtype conversion compared to CADM patients who did not convert (median CDASI-A 9.0 vs. 16.0, respectively; P = 0.01).
Main Takeaway: The majority of classic DM patients continued to meet criteria for diagnosis of classic DM, demonstrating muscle disease and skin involvement throughout their disease course. CADM patients demonstrated a low risk of progressing to classic DM, with the severity skin involvement serving as a potential predictive factor.
How does chronic UV exposure of the skin affect metabolic homeostasis?
Journal of Investigative Dermatology
Journal of Investigative Dermatology
Eat more, gain less?
Ultraviolet radiation (UVR) has been shown to play a role in the inhibition of lipid synthesis. Similarly, prior studies have shown that UV exposure may prevent weight gain in obese mice. In this study, researchers aimed to investigate the impact of UVR on metabolic homeostasis, specifically examining the variations in leptin and norepinephrine levels.
Female mice were fed either a standard or high-fat diet and received UV or sham UV irradiation three times a week for 12 weeks. Their energy use was measured initially and then at the 6 and 12-week points in the study. Food intake and body weight were measured weekly.
What did they find?
Main Takeaway: Chronic UV exposure demonstrated increased appetite while preventing weight gain in mice, suggesting UVR may serve as a potential therapeutic approach for obesity and associated metabolic disorders.
Ultraviolet radiation (UVR) has been shown to play a role in the inhibition of lipid synthesis. Similarly, prior studies have shown that UV exposure may prevent weight gain in obese mice. In this study, researchers aimed to investigate the impact of UVR on metabolic homeostasis, specifically examining the variations in leptin and norepinephrine levels.
Female mice were fed either a standard or high-fat diet and received UV or sham UV irradiation three times a week for 12 weeks. Their energy use was measured initially and then at the 6 and 12-week points in the study. Food intake and body weight were measured weekly.
What did they find?
- Food intake increased in both standard and high-fat diet mice exposed to UV irradiation compared to those receiving sham irradiation (P<0.05).
- Body weight increased more in mice receiving sham UV irradiation regardless of diet type (P<0.01).
- UV irradiation increased serum norepinephrine levels (P<0.01) and decreased serum leptin levels (P<0.01) compared to sham irradiated mice.
Main Takeaway: Chronic UV exposure demonstrated increased appetite while preventing weight gain in mice, suggesting UVR may serve as a potential therapeutic approach for obesity and associated metabolic disorders.
Apoptosis pathway–associated proteins are frequently expressed in melanoma: A study of 32 cases with a focus on acral lentiginous melanoma
The American Journal of Dermatopathology
The American Journal of Dermatopathology
ALMighty apoptosis proteins rule melanoma!
Acral lentiginous melanoma (ALM) is an aggressive subtype of cutaneous melanoma that arises on the palms, soles, and nails. In vitro and in vivo studies of ALM show that defects in the apoptotic pathway contribute to tumorigenesis and therapeutic resistance. However, the clinical significance of the expression of apoptosis-related proteins is unknown. Researchers assessed the expression of anti-apoptotic proteins, BCL2 and MCL1, and pro-apoptotic protein, BIM, in conjunction with BRAF V600E mutation status in ALM (n=20) and non-ALM (n=12) tumors.
What did they find?
Main Takeaway: Frequent expression of apoptosis-related proteins BCL2, MCL1, and BIM in melanoma, including ALM, was confirmed. As such, patients with both ALM and non-ALM may be candidates for apoptosis-directed therapies.
Acral lentiginous melanoma (ALM) is an aggressive subtype of cutaneous melanoma that arises on the palms, soles, and nails. In vitro and in vivo studies of ALM show that defects in the apoptotic pathway contribute to tumorigenesis and therapeutic resistance. However, the clinical significance of the expression of apoptosis-related proteins is unknown. Researchers assessed the expression of anti-apoptotic proteins, BCL2 and MCL1, and pro-apoptotic protein, BIM, in conjunction with BRAF V600E mutation status in ALM (n=20) and non-ALM (n=12) tumors.
What did they find?
- BCL2, MCL1, and BIM proteins were expressed in ALM (87%) and non-ALM (75%) tumors.
- There was no significant difference in the expression of any apoptosis-related proteins between ALM and non-ALM tumors.
- No significant associations existed between the expression of apoptosis-related proteins and BRAF V600E mutation status.
Main Takeaway: Frequent expression of apoptosis-related proteins BCL2, MCL1, and BIM in melanoma, including ALM, was confirmed. As such, patients with both ALM and non-ALM may be candidates for apoptosis-directed therapies.
Hidradenocarcinoma: Insights from a Scripps Clinic case series with a systematic review
Dermatologic Surgery
Dermatologic Surgery
Never underestimate the little guy!
Hidradenocarcinoma (HAC) is a rare and aggressive form of adnexal carcinoma that poses significant diagnosis and treatment challenges due to its scarcity paired with high recurrence and metastasis rates. This study aims to provide a reference for HAC diagnosis, workup, and management by systematically integrating a case series with the literature. This case series included 9 patients, 165 cases of HAC described in the literature, and 225 non-case-based articles.
What did they find?
Main Takeaway: Early detection and accurate histologic interpretation are vital for managing HAC, with MMS treatment showing promise for improved patient outcomes.
Hidradenocarcinoma (HAC) is a rare and aggressive form of adnexal carcinoma that poses significant diagnosis and treatment challenges due to its scarcity paired with high recurrence and metastasis rates. This study aims to provide a reference for HAC diagnosis, workup, and management by systematically integrating a case series with the literature. This case series included 9 patients, 165 cases of HAC described in the literature, and 225 non-case-based articles.
What did they find?
- The median age of presentation was 61, with a slight male predominance (60%).
- The head and neck regions are most commonly affected, accounting for 39.4% of cases.
- Over 36% of patients experienced metastasis, with better outcomes noted in those treated with Mohs micrographic surgery (MMS).
- Immunohistochemical markers such as CK AE1/AE3, CK 5/6, phosphohistone H3, and p63 showed 100% positivity.
Main Takeaway: Early detection and accurate histologic interpretation are vital for managing HAC, with MMS treatment showing promise for improved patient outcomes.
Disparities in state Medicaid coverage of tretinoin for pigmentary disorders compared to acne vulgaris
Skin of Color
Skin of Color
When Medicaid can't see beyond acne…
Melasma and post-inflammatory hyperpigmentation (PIH) predominantly affects individuals with skin phototypes III-VI, often causing significant psychosocial issues. Tretinoin is a first-line treatment for melasma and PIH, yet its FDA approval is limited to acne vulgaris. This study explores Medicaid coverage for tretinoin across the US for acne vulgaris versus melasma and PIH.
What did they find?
Main Takeaway: Medicaid significantly favors covering tretinoin for acne vulgaris over melasma and PIH. This highlights broader inequalities in dermatologic care, especially for conditions predominantly affecting people of color.
Melasma and post-inflammatory hyperpigmentation (PIH) predominantly affects individuals with skin phototypes III-VI, often causing significant psychosocial issues. Tretinoin is a first-line treatment for melasma and PIH, yet its FDA approval is limited to acne vulgaris. This study explores Medicaid coverage for tretinoin across the US for acne vulgaris versus melasma and PIH.
What did they find?
- Tretinoin is covered for acne vulgaris in 45 states and melasma and PIH in 20 states.
- States that cover tretinoin for melasma and PIH often do so because it is included in the state’s preferred drug list, not based on clinical indication.
- Many states exclude coverage for cosmetic conditions except for acne, despite acne vulgaris and melasma/PIH having similar psychosocial morbidity profiles.
Main Takeaway: Medicaid significantly favors covering tretinoin for acne vulgaris over melasma and PIH. This highlights broader inequalities in dermatologic care, especially for conditions predominantly affecting people of color.
Evaluating Disease-Specific Quality of Life and Chemoprevention Utilization in Patients With More Than One Lifetime Skin Cancer
Keratinocyte carcinomas (KC) are among the most prevalent cancers worldwide. However, limited attention has been afforded to their impact on patients' quality of life (QoL). Additionally, there is a lack of research evaluating chemoprevention use in patients with >1 KC.
This retrospective cohort study compared 49 patients with 2-4 and 75 patients with 5+ lifetime KCs, evaluating demographics and chemoprevention use via survey administration and QoL via the validated Skin Cancer Index Survey.
What did they find?
Main Takeaway: Quality of life and healthcare use differences persist between those with 2-4 KCs and those with 5+. With less than half of patients in both groups utilizing chemoprevention, improving the employment of chemoprevention strategies could help reduce overall patient burden.
This retrospective cohort study compared 49 patients with 2-4 and 75 patients with 5+ lifetime KCs, evaluating demographics and chemoprevention use via survey administration and QoL via the validated Skin Cancer Index Survey.
What did they find?
- There was a significant difference in family history of skin cancer noted in patients with 5+ KCs compared to those with 2-4 (P = 0.0302).
- Patients with 5+ KCs had a more significant emotional burden of disease based on results from the skin cancer index (P = 0.0078).
- Chemoprevention is underutilized in both groups.
Main Takeaway: Quality of life and healthcare use differences persist between those with 2-4 KCs and those with 5+. With less than half of patients in both groups utilizing chemoprevention, improving the employment of chemoprevention strategies could help reduce overall patient burden.