May 2026. Volume 38.
Dermatology Snapshots
Highlights:
Does Senital Node Biopsy improve survival in melanoma patients?
Co-treating Ixekizumab With Tirzepatide - does it enhance response?
Adjuvant cemiplimab in high-risk SCC, does it help?
Do we need to do CXR before starting methotrexate?
How effective are systemics at controlling generalised pustular psoriasis?
Stage IIC vs IIIA melanoma survival analysis
Assessment of survival benefit from sentinel node biopsy for melanoma: a systematic review and meta-analysis
Varey AHR et al. Lancet Oncol 2026; 27: 452–60.
Why we chose this paper?
Whether sentinel node biopsy (SNB) improves survival remains highly controversial in clinical practice. Previous benchmark trials like MSLT-I were underpowered to show a definitive survival advantage , and older meta-analyses relied too heavily on single cohorts. This extensive global study provides dermatologists with the most robust, high-certainty evidence to date.
Study aim and design
This systematic review and meta-analysis analysed medical databases up to January 2025 to determine if SNB reduces melanoma-specific mortality and recurrence in adults. To eliminate confounding, researchers pooled 13 well-adjusted studies—encompassing randomised controlled trials, multivariable analyses, and propensity-score matching—which evaluated 40,287 unique patients.
What were the main findings?
SNB was associated with a statistically significant 14% reduction in the overall risk of melanoma-specific death (HR 0.86, 95% CI 0.81–0.92, p<0.0001).
The 5-year melanoma-specific mortality risk was similarly reduced by 16% in patients undergoing the procedure (HR 0.84, 95% CI 0.78–0.90, p<0.0001).
The risk of any melanoma recurrence dropped significantly by 29% (HR 0.71, 95% CI 0.66–0.76, p<0.0001).
Comprehensive sensitivity analyses confirmed these findings were highly robust, showing consistently low heterogeneity across global centres.
Limitations and applicability
Most included records were retrospective cohorts, presenting inherent risks of residual confounding. Additionally, long-term 10-year mortality data lacked statistical significance due to a smaller available sample size. Nevertheless, the results remain directly applicable to standard clinical staging and management guidelines for adults presenting with localized primary cutaneous melanomas.
What’s the take-home message?
SNB seems to provide true survival and recurrence benefits, reinforcing its role as a therapeutic intervention rather than just a staging tool. It ensures optimal regional disease control and represents a highly cost-effective approach compared to managing recurrences with advanced systemic immunotherapies.
Ixekizumab With Tirzepatide Achieved Greater Disease Control Than Ixekizumab Alone in Adults With Psoriatic Arthritis and Overweight or Obesity: Results From a Randomized Clinical Trial
Merola JF et al. Arthritis Rheumatol. 2026; doi:10.1002/art.70134.
Why we chose this paper?
Obesity significantly worsens psoriatic disease severity and weakens biologic treatment responses. This landmark trial is the first to evaluate a dual-targeting strategy combining an anti-IL-17A biologic with a GIP/GLP-1 receptor agonist, directly addressing the core inflammatory-metabolic intersection dermatologists manage daily.
Study aim and design
The TOGETHER-PSA phase 3b randomiSed clinical trial assigned 271 adults with active psoriatic arthritis (PsA) and obesity or overweight with comorbidities to receive either ixekizumab plus tirzepatide (IXE+TZP) or ixekizumab alone. The primary endpoint was simultaneous achievement of an ACR50 response and ≥10% weight reduction at 36 weeks.
Psoriasis Coexistence: Out of the 271 randomized patients in the modified intent-to-treat (mITT) population, 71.6% presented with coexistent psoriasis at baseline.
Severe Cutaneous Disease Dosing: Within this cohort, 4.4% of the participants had moderate-to-severe plaque psoriasis and were assigned to the approved psoriasis-specific ixekizumab dosing regimen (160-mg starting dose followed by 80 mg every 2 weeks for the first 12 weeks, then every 4 weeks) rather than the standard psoriatic arthritis schedule.
What were the main findings?
The dual primary endpoint was met by 31.7% of the combination group versus 0.8% with monotherapy (P<0.001).
Joint disease control was significantly greater, with 33.5% achieving ACR50 with IXE+TZP compared to 20.4% with ixekizumab alone (P=0.02).
Marked weight loss occurred, with 84.5% in the combination arm reaching ≥10% weight reduction versus 4.5% with monotherapy (P<0.001).
Safety profiles showed no new concerns, though mild-to-moderate gastrointestinal events (nausea, diarrhea) were more frequent with tirzepatide.
Significant Absolute PASI Improvements
Absolute PASI Reduction: Concomitant therapy achieved a statistically significant greater reduction in the absolute Psoriasis Area and Severity Index (PASI) score compared to biologic monotherapy.
Statistical Metrics: The adjusted mean change from baseline (CFB) in absolute PASI was -4.3 in the ixekizumab plus tirzepatide (IXE+TZP) group versus -3.3 in the ixekizumab (IXE) monotherapy group. This represents a clear treatment difference of -0.9 (95% CI -1.6 to -0.2; nominal P=0.008) favoring the combination.
Categorical Skin Clearance Trends (PASI 75 / 90 / 100)
While ixekizumab alone is highly potent, adding tirzepatide led to consistently higher numeric clearance rates across all standard dermatologic thresholds at 36 weeks:
PASI 75 Response: Achieved by 64.4% (95% CI 52.8% to 76.0%) of patients in the combination group compared to 52.5% (95% CI 40.3% to 64.8%) in the monotherapy group (treatment difference: 11.9%, 95% CI -5.5% to 29.2%; nominal P=0.177).
PASI 90 Response (Near-Complete Clearance): Reached borderline nominal significance, with 52.2% (95% CI 40.1% to 64.2%) in the combination cohort vs. 35.6% (95% CI 24.2% to 47.0%) in the monotherapy cohort (treatment difference: 16.6%, 95% CI -0.0% to 33.1%; nominal P=0.050).
PASI 100 Response (Complete Skin Clearance): Showed a notable numeric advantage, with 36.9% (95% CI 25.9% to 47.8%) of combination patients achieving completely clear skin compared to 26.6% (95% CI 16.5% to 36.8%) on ixekizumab alone (treatment difference: 10.2%, 95% CI -4.7% to 25.2%; nominal P=0.179).
Limitations and applicability
The trial's open-label nature (mitigated by blinded assessors) and sole focus on US cohorts limit its generalisability. It also excluded normal-weight patients and prior IL-17 inhibitor failures. However, it remains highly applicable to the substantial subset of psoriatic patients with concurrent metabolic syndrome.
What’s the take-home message?
Concomitant treatment with ixekizumab and tirzepatide delivers superior, multi-domain control of skin, joint, and metabolic disease. Actively treating obesity in psoriatic patients represents a paradigm shift that fundamentally optimises overall disease clearance and systemic health.
Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma
Rischin D, Porceddu S, Day F, et al. N Engl J Med 2025;393:774-85.
Why we chose this paper?
Patients with aggressive cutaneous squamous-cell carcinoma (cSCC) face a high risk of local or distant recurrence despite definitive surgery and radiotherapy. This landmark phase 3 trial addresses a critical clinical gap by establishing high-level evidence for systemic adjuvant immunotherapy where effective treatment standardisations have historically been lacking.
Study aim and design
The international, randomised, double-blind, phase 3 C-POST trial evaluated whether adjuvant cemiplimab prolonged disease-free survival (DFS) compared to placebo. Following macroscopically successful surgical resection and postoperative radiotherapy (≥50 Gy), 415 adults with high-risk local or regional cSCC were randomised 1:1 to receive cemiplimab (350 mg every 3 weeks for 12 weeks, followed by 700 mg every 6 weeks) or placebo for up to 48 weeks. Eligible high-risk features included extensive nodal disease (such as extracapsular extension with a node ≥20 mm) or aggressive nonnodal components like perineural invasion, T4 bone invasion, or in-transit metastases.
What were the main findings?
Adjuvant cemiplimab significantly improved DFS, reducing the relative risk of disease recurrence or death by 68% compared to placebo (HR 0.32; 95% CI, 0.20 to 0.51; P<0.001).
The estimated 24-month DFS rate was 87.1% with cemiplimab versus 64.1% with placebo.
Cemiplimab treatment drastically lowered both locoregional recurrence (HR 0.20; 95% CI, 0.09 to 0.40) and distant recurrence risks (HR 0.35; 95% CI, 0.17 to 0.72).
The therapeutic DFS benefit was consistently maintained regardless of the tumor's baseline PD-L1 expression level.
Grade 3 or higher adverse events occurred in 23.9% of cemiplimab patients versus 14.2% with placebo, causing a 9.8% treatment discontinuation rate.
Limitations and applicability
The trial excluded solid-organ or stem-cell transplant recipients and individuals with active autoimmune disease, who represent populations that frequently develop highly aggressive cSCC in real-world clinical practice. Furthermore, extended follow-up remains necessary to fully confirm long-term overall survival advantages
What’s the take-home message?
Adjuvant cemiplimab following surgical resection and radiation provides outstanding disease-free survival benefits, establishing a definitive new standard of care for patients with high-risk cutaneous squamous-cell carcinoma.
Fibrotic interstitial lung disease in patients with psoriasis using methotrexate: a descriptive cohort study using British Association of Dermatologists Biologics and Immunomodulator registry data
Clarke E, van Bodegraven B, Shipman AR. Clin Exp Dermatol. 2026;51(4):634-637 . doi:10.1093/ced/llaf553.
Why we chose this paper?
Methotrexate (MTX) has historically carried an ominous reputation for inducing fibrotic interstitial lung disease (fILD), driving conventional guidelines to recommend baseline screening chest X-rays and causing lingering clinical anxiety when treating psoriasis. This large-scale, real-world study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) directly challenges this dogma within a dedicated dermatology population, providing reassuring evidence that reshapes routine drug monitoring protocols.
Study aim and design
This retrospective descriptive cohort study utilised pharmacovigilance data from the BADBIR registry across the UK and Republic of Ireland to examine the association between MTX exposure and fILD in patients with psoriasis. Out of 18,441 total registered psoriasis patients on systemic therapies, the study compared 3,009 individuals ever exposed to MTX after entry against 15,432 unexposed individuals. The primary outcome evaluated was the development of fILD, classified via specific MedDRA preferred terms.
What were the main findings?
There was no statistically significant association between methotrexate exposure and the occurrence of lung fibrosis (χ2=3.3, P=0.071).
The incidence of fILD was actually lower in the methotrexate-exposed cohort than in the unexposed cohort, demonstrating a rate of 2.005 versus 4.545 cases per 10,000 person-years.
Psoriasis patients taking methotrexate experienced 2.5 fewer cases of lung fibrosis per 10,000 person-years compared to those who did not take the medication.
Development of fILD was strongly driven by patient-specific factors rather than drug exposure, with older age, smoking history, psoriatic arthritis, and metabolic/cardiovascular comorbidities (hypertension, myocardial infarction, diabetes, and dyslipidemia) being significantly more common in patients who developed fibrosis.
Chronic, progressive fILD must be clearly distinguished from acute MTX-associated interstitial pneumonitis (MTXip), which is an entirely separate acute hypersensitivity reaction that presents within the first year and carries a high untreated mortality rate of ~20%.
Historical clinical literature linking MTX to chronic fILD is largely flawed, low-quality, or heavily confounded by high background rates of subclinical fibrosis inherent to rheumatoid arthritis patients rather than the drug itself.
Limitations and applicability
The study's descriptive and retrospective design limits the ability to establish definitive causality or fully rule out channel bias, such as clinicians systematically avoiding prescribing MTX to patients with pre-existing pulmonary disease. Furthermore, pre-existing lung conditions could not be thoroughly categorised due to registry data collection limitations in free-text fields. Nevertheless, its substantial sample size and reliance on a major nationwide dermatology registry make these findings highly applicable to standard outpatient dermatology clinics.
What’s the take-home message?
Methotrexate does not increase the risk of developing fibrotic interstitial lung disease in patients with psoriasis above their baseline risk. Historical assumptions of pulmonary fibrosis risk are confounded by rheumatology cohorts or a misdiagnosis of acute hypersensitivity pneumonitis. Consequently, performing routine screening or baseline chest radiography is unnecessary in dermatology drug monitoring clinics for psoriasis patients initiating methotrexate.
Contrasting survival outcomes and patient characteristics in 5815 patients with stage II and III melanoma: a nationwide population-based registry study from Sweden
Marjanovic M, Mikiver R, Nielsen K, Isaksson K, Claeson M. Br J Dermatol. 2026;194(4):648-655. doi:10.1093/bjd/ljaf478.
Why we chose this paper?
Accurate prognostic staging determines standard follow-up intensity and modern therapeutic pathways in cutaneous melanoma. This large-scale, nationwide study highlights a stark, counterintuitive paradox in oncology: patients with localised, thicker tumors (Stage IIC) experience substantially worse long-term survival than those whose melanoma has already spread to regional lymph nodes (Stage IIIA). This research challenges current clinical tracking guidelines that historically favour less frequent follow-ups for localised skin disease.
Study aim and design
The retrospective, nationwide, population-based cohort study linked the Swedish Melanoma Register (SweMR) with multi-variable administrative health records to analyse 5,815 adult patients pathologically diagnosed with stage II or III melanoma between 2001 and 2018. To prevent understaging biases, the cohort was restricted to individuals who had verified sentinel lymph node biopsies (SLNB) or clinically detected nodal/in-transit metastases at initial diagnosis. Researchers thoroughly evaluated 10-year melanoma-specific survival (MSS) rates, socioeconomic factors, and specific individual comorbidities across substages.
What were the main findings?
Survival Paradox: Localized stage IIC melanoma is significantly more lethal than lymph node-positive stage IIIA melanoma, with a 10-year MSS rate of 61% for Stage IIC versus 78% for Stage IIIA (P<0.001).
The Full Survival Curve: The 10-year MSS rates across all assessed substages were: IIA (86%), IIB (73%), IIC (61%), IIIA (78%), IIIB (56%), IIIC (43%), and IIID (19%).
Patient Disparities: Patients with stage IIC tumours were drastically older (median age 70.0 years) and predominantly male (59.2%), whereas stage IIIA patients were substantially younger (median age 55.0 years) with a balanced sex distribution (51.5% male).
Comorbidities and Socioeconomics: Stage IIC individuals exhibited higher rates of significant lifestyle comorbidities (e.g., type 2 diabetes, hypertension) and lower socioeconomic metrics (income and education levels) compared to their Stage IIIA peers.
Statistical Independence: Multivariable Cox regression analysis showed that stage IIC carried a crude hazard ratio (HR) of 2.38 for melanoma death compared to IIIA. Even after adjusting for age, sex, and tumor thickness, the survival disadvantage for localized IIC remained statistically significant (adjusted HR 1.79).
Tumor Biologics: Nodular melanoma (NM) was heavily prominent in stages IIB and IIC, while superficial spreading melanoma (SSM) was much more frequent in stage IIIA.
Limitations and applicability
As a retrospective registry analysis, certain clinical updates across the long inclusion window (2001–2018)—such as the wide introduction of modern adjuvant checkpoint inhibitors post-2015—could skew absolute historical survival numbers. However, a dedicated sensitivity analysis checking patients diagnosed before 2015 confirmed that the fundamental survival gap between IIC and IIIA remained completely persistent. Given Sweden's exceptional global melanoma incidence rates and near-total registration coverage (99%), the data is highly valid and representative of Western populations.
What’s the take home message?
Localised Stage IIC melanoma carries an independent, biologically aggressive risk of hematogenous dissemination and a much lower survival rate than regional Stage IIIA disease. Current clinical guidelines must be reevaluated globally to ensure that thick, high-risk localised melanomas receive monitoring and modern therapeutic options at least as intensive as those routinely offered to lymph node-positive cohorts.
A prospective, observational study of the epidemiology, disease characteristics and treatment outcomes of generalized pustular psoriasis in India
Dogra S, Sharma A, Narang T, Handa S. Clin Exp Dermatol. 2026;51(4):571-577. doi:10.1093/ced/llaf507.
Why we chose this paper?
Generalised pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory skin disease characterized by sudden, painful eruptions of sterile pustules over erythematous skin. While modern, high-cost targeted biologics (such as IL-36 inhibitors) have reshaped standard global guidelines, prospective data from low- and middle-income countries (LMICs) remain extremely scarce. This real-world study provides vital insight into how GPP can be successfully and cost-effectively managed in a resource-limited tertiary care setting primarily utilising conventional systemic treatments.
Study aim and design
Conducted from March 2022 to March 2025 at a major tertiary care referral hospital in North India, this prospective, observational registry study evaluated 46 patients diagnosed with GPP (representing 5.3% of 857 newly registered psoriasis patients). Diagnostic categorisation relied on the European Rare and Severe Psoriasis Expert Network (ERASPEN) criteria. Disease severity and quality of life were objectively tracked using the Generalised Pustular Psoriasis Area and Severity Index (GPPASI) and the Dermatology Life Quality Index (DLQI) at admission, throughout their inpatient stay, and up to a 1-year follow-up period.
What were the main findings?
Patient Demographics & Presentation: The cohort presented with a mean age of 36.2 years and showed a strong male predominance (63% male). Paediatric GPP accounted for 4.3% of the cases. Additionally, 52% of the patients experienced GPP arising from chronic plaque psoriasis, while the remainder experienced de novo GPP.
Precipitating Triggers: The study identified clear triggers in 61% of flares, with an average latency of 10.4 days from exposure to flare onset. The most common drivers were commercial pharmacological agents (22%—primarily terbinafine, NSAIDs, and β-lactam/tetracycline antibiotics), intercurrent infections (15%), complementary and alternative medicine (CAM) (11%), COVID-19 infection (7%), and pregnancy (4%).
Systemic Inflammation & Comorbidities: Strong systemic involvement was reflected by elevated mean white blood cell counts (11.3×103μL−1 with neutrophilia in 72% of patients) and highly elevated inflammatory markers, including a mean C-reactive protein (CRP) of 55.4 mg/L and erythrocyte sedimentation rate (ESR) of 47.8 mm/h. Concurrently, metabolic comorbidities were highly prevalent: obesity (30%), dyslipidaemia (26%), hypertension (24%), and diabetes (13%).
Therapeutic Remission Rates: Systemic treatments were highly effective at securing prompt disease control. Early remission (≥50% GPPASI reduction within 5 days) and sustained remission (at 3 months) were comparable across conventional and biologic therapies:
Biologics (9% of patients): 75% early remission; 75% sustained remission at 3 months.
Ciclosporin (13% of patients): 67% early remission; 50% sustained remission at 3 months.
Acitretin (44% of patients): 65% early remission; 55% sustained remission at 3 months.
Methotrexate (26% of patients): 50% early remission; 42% sustained remission at 3 months.
Relapse and Mortality: Demonstrating the severe and unstable nature of the disease, 26% of patients relapsed within 3 months, and 13% had persistent disease. Securing an early treatment response on day 5 was a statistically significant predictor of achieving long-term sustained remission (P=0.032). There were three deaths (6.5% mortality rate): two from progressive respiratory failure and multiorgan dysfunction triggered by COVID-19, and one from severe sepsis resulting from a CAM-precipitated flare.
Limitations and applicability
The study is limited by its single-center design, relatively small overall sample size (46 patients), and the fact that comparisons between de novo and chronic plaque-associated sub-types were not pre-specified. However, because it mirrors real-world clinical operations and drug access constraints in an LMIC tertiary referral ecosystem, the results are highly applicable to dermatology clinics managing severe psoriasis globally under strict financial or institutional restrictions.
What’s the take-home message?
Generalised pustular psoriasis is a severe neutrophilic dermatosis that carries a significant risk of systemic morbidity and mortality if left untreated. While advanced targeted biologics provide rapid clearance, conventional systemic medications—specifically acitretin and ciclosporin—remain highly effective, accessible, and essential alternatives for inducing and sustaining remission in resource-limited settings. Achieving a strong clinical response within the first 5 days of therapy is paramount to securing long-term disease stabilisation.
