A newsletter that delivers the latest in dermatology research directly to you.
One-Hundredth issue
December 10th, 2025
JAK2 fusions in adult patients with mycosis fungoides and CD30 lymphoproliferative disorders
JAMA Dermatology
JAMA Dermatology
Trying to explain that JAK2 fusions are in both aggressive and indolent CTCL without freaking out the whole tumor board
Cutaneous T-cell lymphoma (CTCL) encompasses a spectrum of diseases ranging from indolent mycosis fungoides (MF) to rare, highly aggressive cytotoxic variants such as primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (pcAETCL). JAK2 gene fusions, long associated with aggressive cytotoxic lymphomas, have historically been considered markers of poor prognosis. However, robust data describing their presence in early or indolent CTCL have been limited to isolated case reports. This retrospective case series from a single cancer center examined 43 adults with CTCL harboring JAK2 fusions, aiming to clarify the diagnostic, prognostic, and therapeutic significance of these alterations across the disease spectrum.
What did they find?
Main Takeaway: Although JAK2 fusions have historically been linked to aggressive cytotoxic CTCL, this study shows they may be more common in early-stage, indolent disease, including MF and CD30-positive LPD. The presence of a JAK2 fusion may represent precursor alterations that acquire aggressive behavior in the context of additional triggers. These findings raise the possibility that targeted inhibition of the JAK/STAT pathway could play a future therapeutic role in early-stage MF and CD30-positive LPD.
Cutaneous T-cell lymphoma (CTCL) encompasses a spectrum of diseases ranging from indolent mycosis fungoides (MF) to rare, highly aggressive cytotoxic variants such as primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (pcAETCL). JAK2 gene fusions, long associated with aggressive cytotoxic lymphomas, have historically been considered markers of poor prognosis. However, robust data describing their presence in early or indolent CTCL have been limited to isolated case reports. This retrospective case series from a single cancer center examined 43 adults with CTCL harboring JAK2 fusions, aiming to clarify the diagnostic, prognostic, and therapeutic significance of these alterations across the disease spectrum.
What did they find?
- 88% (n = 38) had indolent presentations, including MF, CD30-positive lymphoproliferative disorders (LPD), or overlap features. Only 5 patients (11.6%) had aggressive CTCL, including pcAETCL or PTCL-NOS.
- Fusion partner, mutational burden, and mutational type did not distinguish indolent from aggressive disease.
- Recurrent fusion partners included PCM1 and ATXN2L (each 23%), CAPRIN1 (14%), and STAT3 (9%), among others.
- Most patients had skin-limited disease, often presenting with patches or plaques, and required only skin-directed therapy.
- Systemic involvement and need for chemotherapy or stem-cell transplant were rare and limited to the aggressive subtypes.
- Large-cell features, CD8 positivity, and ulceration were more common in cases with aggressive histology, but these features were not restricted to any specific fusion partner.
Main Takeaway: Although JAK2 fusions have historically been linked to aggressive cytotoxic CTCL, this study shows they may be more common in early-stage, indolent disease, including MF and CD30-positive LPD. The presence of a JAK2 fusion may represent precursor alterations that acquire aggressive behavior in the context of additional triggers. These findings raise the possibility that targeted inhibition of the JAK/STAT pathway could play a future therapeutic role in early-stage MF and CD30-positive LPD.
Isotretinoin may slow the sprint, but the finish line stays the same.
Isotretinoin is considered a first-line treatment for severe acne vulgaris. However, premature epiphyseal closure is a listed adverse effect of isotretinoin, and concerns about its impact on adolescent growth may influence treatment decisions. With existing evidence limited to case reports and postmarketing FDA surveillance, this retrospective population-based study examined whether starting isotretinoin before age 15 affects final adult height or height velocity compared with a control group of adolescents treated with oral antibiotics.
What did they find?
Main Takeaway: Isotretinoin may temporarily reduce growth velocity during treatment, but does not impact final adult height.
Isotretinoin is considered a first-line treatment for severe acne vulgaris. However, premature epiphyseal closure is a listed adverse effect of isotretinoin, and concerns about its impact on adolescent growth may influence treatment decisions. With existing evidence limited to case reports and postmarketing FDA surveillance, this retrospective population-based study examined whether starting isotretinoin before age 15 affects final adult height or height velocity compared with a control group of adolescents treated with oral antibiotics.
What did they find?
- 227 patients who received isotretinoin and 1,179 age- and sex-matched acne controls treated with oral antibiotics were included.
- There was no difference in the final adult height (i.e., height at age 18) among 179 adolescents treated with isotretinoin compared to controls (mean difference −0.67 cm, 95% CI: − 2.21 to 0.87; P = 0.392).
- After starting treatment, the isotretinoin group experienced a slower height velocity (0.23 cm/month) compared with the control group (0.34 cm/month) (difference adjusted for age and sex: −0.12 cm/mo, 95% CI: −0.21 to −0.04; P = 0.005).
- Across a range of isotretinoin doses (<120 mg/kg (n = 24), 120 to 220 mg/kg (n = 155), and >220 mg/kg (n = 48)), no dose-related differences in final height were observed in the <120 mg/kg group (P = 0.218) or > 220 mg/kg group (P = 0.370) compared to the 120-220 mg/kg group.
- Rates of short stature (final height <2 SD below the mean) were similarly low in both groups, occurring in 2.34% of isotretinoin patients (n=3) and 1.28% of controls (n=6) (P = 0.383).
Main Takeaway: Isotretinoin may temporarily reduce growth velocity during treatment, but does not impact final adult height.
Comparing two topical therapies for localized vitiligo: similar efficacy, different speed
Vitiligo affects ~1 in 100 people and often causes profound psychosocial distress. While topical tacrolimus is an established treatment for localized vitiligo, evidence directly comparing it with newer Janus kinase (JAK) inhibitors is limited. This single-centre, investigator-blinded intra-individual trial randomized 30 patients (60 symmetrical patches) to receive 2% tofacitinib vs 0.1% tacrolimus ointment twice daily for 16 weeks.
What did they find?
Main Takeaway: Topical tofacitinib achieved efficacy comparable to tacrolimus but tended to work faster and cause fewer irritant effects. Its favorable tolerability and earlier patient-reported improvement suggest a promising alternative for localized vitiligo, pending confirmation in larger trials.
Vitiligo affects ~1 in 100 people and often causes profound psychosocial distress. While topical tacrolimus is an established treatment for localized vitiligo, evidence directly comparing it with newer Janus kinase (JAK) inhibitors is limited. This single-centre, investigator-blinded intra-individual trial randomized 30 patients (60 symmetrical patches) to receive 2% tofacitinib vs 0.1% tacrolimus ointment twice daily for 16 weeks.
What did they find?
- Tofacitinib achieved higher patient-reported success than tacrolimus (47% vs 37%) and did so four weeks sooner (median 8 vs 12 weeks).
- A greater proportion of patches treated with tofacitinib reached >80% repigmentation (33% vs 20%).
- Facial lesions showed the best response overall (63%) with both treatments, while acral areas remained the most treatment-resistant (18%).
- Tofacitinib was also better tolerated, with only two local reactions compared with seven on tacrolimus.
Main Takeaway: Topical tofacitinib achieved efficacy comparable to tacrolimus but tended to work faster and cause fewer irritant effects. Its favorable tolerability and earlier patient-reported improvement suggest a promising alternative for localized vitiligo, pending confirmation in larger trials.
TKI Triggered Troubles
Dermatologic adverse events (dAEs) are common with BCR-ABL tyrosine kinase inhibitors (TKIs), yet the mechanisms driving their cutaneous toxicities remain poorly understood. Differences in dAEs among first-generation (imatinib), second-generation (bosutinib, dadatinib, and nilotinib), and third-generation (ponatinib) TKIs have not been well-characterized. In this retrospective study, researchers analyzed clinical and histopathologic characteristics of 32 biopsy-confirmed TKI-related dAEs from 28 patients to identify patterns that may clarify underlying mechanisms.
What did they find?
Main Takeaway: The pathogenesis of TKI-related dAEs varies by TKI generation, with each class revealing distinct inflammatory patterns. Recognizing mechanistic differences by drug class may inform and improve management strategies.
Dermatologic adverse events (dAEs) are common with BCR-ABL tyrosine kinase inhibitors (TKIs), yet the mechanisms driving their cutaneous toxicities remain poorly understood. Differences in dAEs among first-generation (imatinib), second-generation (bosutinib, dadatinib, and nilotinib), and third-generation (ponatinib) TKIs have not been well-characterized. In this retrospective study, researchers analyzed clinical and histopathologic characteristics of 32 biopsy-confirmed TKI-related dAEs from 28 patients to identify patterns that may clarify underlying mechanisms.
What did they find?
- Imatinib was implicated in 32.1% of cases, second-generation TKIs in 57.1%, and ponatinib in 10.7%.
- Imatinib-associated dAEs showed significantly higher rates of papular/plaque morphology (90%, P = 0.002), along with acanthosis (80%, P = 0.001) and eosinophilic infiltrates (80%, P = 0.002).
- Second-generation TKIs were often associated with folliculocentric eruptions with adnexal involvement, including periadnexal infiltrates, perifollicular fibrosis, and decreased follicle density.
- Ponatinib-induced dAEs demonstrated higher rates of ichthyosiform (60%, P = 0.002) and pityriasiform (40%, P = 0.02) morphologies.
Main Takeaway: The pathogenesis of TKI-related dAEs varies by TKI generation, with each class revealing distinct inflammatory patterns. Recognizing mechanistic differences by drug class may inform and improve management strategies.
With an abscess in the right spot, HS might enter the plot
Hidradenitis suppurativa (HS) is frequently diagnosed years after initial symptoms, leading to scarring and reduced quality of life. This retrospective study (2012-2023) reviewed 471 patients with recurrent cutaneous abscesses to determine how often they later developed HS and which early features predicted a future HS diagnosis.
What did they find?
Hidradenitis suppurativa (HS) is frequently diagnosed years after initial symptoms, leading to scarring and reduced quality of life. This retrospective study (2012-2023) reviewed 471 patients with recurrent cutaneous abscesses to determine how often they later developed HS and which early features predicted a future HS diagnosis.
What did they find?
- 15% (n = 71) of patients with recurrent abscesses were later diagnosed with HS, and 80.3% were female.
- HS patients had abscesses in typical HS sites more often, including the axillae (37.5%, P < 0.0001), inframammary region (11.7%, P < 0.0001), and inguinal folds (21.9%, P = 0.005).
- An abscess in a typical HS location increased future HS risk from 5.4% to 35.6% (P < 0.00001).
- The average diagnostic delay was 30.7 months, with some delays up to 12 years, missing the early treatment “window of opportunity.”
Aesthetic medicine management and the role of dermocosmetics for acne-prone skin
Journal of Cosmetic Dermatology
Journal of Cosmetic Dermatology
The moment you realize acne care is a team sport.
Acne therapies target sebum, inflammation, and follicular hyperkeratinization, but many pharmacologic treatments cause irritation and barrier disruption. Dermocosmetics provide a lower-irritation approach to restoring hydration, supporting the microbiome, and limiting microcomedone formation. This review evaluates the role of dermocosmetics as monotherapy, adjunctive therapy, and post-procedure care within an esthetic-medicine framework for acne-prone skin.
What did they find?
Acne therapies target sebum, inflammation, and follicular hyperkeratinization, but many pharmacologic treatments cause irritation and barrier disruption. Dermocosmetics provide a lower-irritation approach to restoring hydration, supporting the microbiome, and limiting microcomedone formation. This review evaluates the role of dermocosmetics as monotherapy, adjunctive therapy, and post-procedure care within an esthetic-medicine framework for acne-prone skin.
What did they find?
- Dermocosmetics used daily can improve sebum regulation, barrier integrity, hydration, and microcomedone prevention by incorporating ingredients such as niacinamide, keratolytics, antimicrobials, and botanicals.
- Dermocosmetics can be used as adjunctive therapy to mitigate irritation from topical retinoids and fixed-combination treatments, improving comfort and adherence. Additionally, they can enhance recovery and outcomes after lasers and aesthetic treatments for acne scars and sequelae.
- Dermocosmetics showed excellent tolerability across studies, with minimal adverse effects.
Disparities in hidradenitis suppuritiva clinical trials from 2020-2024
Journal of Drugs in Dermatology
Journal of Drugs in Dermatology
Geographic equity in HS research? Couldn’t be us.
Hidradenitis suppurativa (HS) is a chronic inflammatory condition with disproportionate prevalence among Black patients. This review analyzed five U.S. interventional trials registered between 2020 and 2024 to evaluate changes in racial and ethnic representation.
What did they find?
Main Takeaway: Black patient enrollment in HS clinical trials has improved in recent years but remains lower than expected based on disease burden. More inclusive trial design, greater geographic diversity, and reporting of skin type data may help advance equity in HS research.
Hidradenitis suppurativa (HS) is a chronic inflammatory condition with disproportionate prevalence among Black patients. This review analyzed five U.S. interventional trials registered between 2020 and 2024 to evaluate changes in racial and ethnic representation.
What did they find?
- Among 411 participants, 22.6% were Black, up from 14.9% in 2008–2020 (P < 0.001), but still below the estimated 32.6% HS prevalence in Black individuals.
- White participants (68.4%) were enrolled three times more often than Black participants, despite HS being twice as prevalent in Black individuals.
- 59.3% of trial sites were located in cities with moderate to high Black populations.
Main Takeaway: Black patient enrollment in HS clinical trials has improved in recent years but remains lower than expected based on disease burden. More inclusive trial design, greater geographic diversity, and reporting of skin type data may help advance equity in HS research.
Acral Lentiginous Melanoma (ALM) is an uncommon yet aggressive melanoma subtype that predominantly affects people of color. Unlike other common skin cancers, ALM is not strongly associated with UV light exposure. This literature review explores the current state of ALM awareness, diagnosis, management, and education campaigns to identify cultural, educational, and systemic barriers that contribute to delayed detection and poorer outcomes.
What did they find?
Main Takeaways: By integrating community-based education, representative imagery, and provider training, this project seeks to shift the paradigm of melanoma awareness toward inclusion. With recognition of the pitfalls in ALM prevention and detection, clinical focus may shift toward ALM detection in skin of color patients and toward increased data collection to revolutionize melanoma awareness among patients with skin of color.
What did they find?
- With skin of color-specific data collection on ALM detection, it will be possible to quantify and adequately address discrepancies in ALM detection.
- Current melanoma education campaigns overwhelmingly feature lighter skin tones, perpetuating misinformation among both patients and providers.
- Early recognition can be improved through culturally inclusive education and the use of visual references that represent all skin types.
Main Takeaways: By integrating community-based education, representative imagery, and provider training, this project seeks to shift the paradigm of melanoma awareness toward inclusion. With recognition of the pitfalls in ALM prevention and detection, clinical focus may shift toward ALM detection in skin of color patients and toward increased data collection to revolutionize melanoma awareness among patients with skin of color.
DERMLITE Dermoscopy QUESTION OF THE WEEK
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Copyright © 2025 - All Rights Reserved.