The edition · Dermatology
Two rashes that look alike and are not, and five years of a melanoma vaccine
Single-cell work separates morbilliform drug eruption from SDRIFE at the immune level; defensins turn out to drive psoriatic itch as well as inflammation; and KEYNOTE-942 reaches five years with the recurrence-free survival benefit intact.
The edition in brief
Much of today's dermatology reading is mechanism rather than trial, and it is labelled as such. Single-cell RNA sequencing with spatial transcriptomics separated morbilliform drug eruption from symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): morbilliform lesions were dominated by CD8+ cytotoxic and Th1 CD4+ T cells with high CXCL9-11 and interferon-response genes, while SDRIFE showed little CD8+ infiltrate, CD4+ cells with modest Th2 skewing, and macrophages with an immunomodulatory profile. In a defensin cluster knockout mouse, deleting keratinocyte defensins reduced imiquimod-induced psoriatic inflammation, neutrophil and IL-17+ γδ T cell infiltration, and scratching; human β-defensin 2 directly activated Mrgpra3 pruriceptive neurons. A mouse and zebrafish study found fluoxetine activated melanocyte stem cells through epithelial HTR1A and Wnt signalling, producing more epidermal melanocytes without the oxidative stress or DNA damage seen with narrow-band UVB - preclinical only, with no human vitiligo data. A JAMA Dermatology case report describes progressive slate-grey skin discolouration with darkened urine in a patient with two primary cutaneous melanomas. The edition closes on the five-year update of the phase IIb KEYNOTE-942 trial: in 157 patients with resected stage IIIB-IV melanoma, intismeran autogene (formerly mRNA-4157) plus pembrolizumab continued to prolong recurrence-free survival against pembrolizumab alone (hazard ratio 0.510, 95% CI 0.294-0.887) and distant metastasis-free survival (HR 0.411, 0.200-0.843), with overall survival favourable but not statistically separated (HR 0.471, 0.165-1.345).
Morbilliform drug eruption and SDRIFE are not the same reaction wearing different clothes
Write down which drug eruption you are seeing rather than 'drug rash' - the two patterns have different immune drivers, and the distinction is likely to matter for how each is managed.
Defensins drove psoriatic itch as well as psoriatic inflammation in mice
Score itch separately from plaque severity at psoriasis reviews; it has its own mechanism and it does not reliably track the skin.
Fluoxetine activated melanocyte stem cells in mice and zebrafish
This is research-stage: an epithelial serotonin-Wnt pathway that activates melanocyte stem cells without ultraviolet, not a reason to give anyone fluoxetine for vitiligo.
Slate-grey skin and dark urine in a patient with melanoma
Generalised grey discolouration with dark urine in someone with melanoma is a staging question, not a dermatological one - restage urgently.
In a suspected drug eruption, build the timeline before you name the drug
Write the eight-week drug timeline against the rash onset date before stopping anything, and send the patient home with the culprit drug and its class in writing.
An individualised mRNA neoantigen therapy held its melanoma benefit at five years
The standard after resection is still adjuvant pembrolizumab - but the five-year data mean a patient asking about individualised mRNA therapy deserves a specific answer rather than a dismissal.
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