Cryptococcus neoformans is an encapsulated opportunistic yeast widely distributed in the environment and classified as critical-priority fungal pathogen by the World Health Organisation due to its high mortality and limited access to timely diagnosis and effective treatment. Infection is typically acquired via inhalation, with the primary pulmonary focus often remaining asymptomatic. Particularly in individuals with impaired cell-mediated immunity, it may disseminate hematogenously to central nervous system (CNS), skin and other organs. Cutaneous cryptococcosis is a rare clinical manifestation and in most cases, represents secondary involvement of disseminated disease. Its clinical presentation is highly variable and may mimic cellulitis, abscesses, ulcers or necrotizing soft-tissue infections, posing significant diagnostic challenges. Ruxolitinib is a Janus-kinase inhibitor used to treat myelofibrosis and polycythemia vera. By suppressing interferon-γ and interleukin-12-mediated immune responses, it impairs macrophage activation, reduces T-helper-1 cell responses, suppresses natural-killer cell function, and regulates hematopoietic activity. However, these immunomodulatory effects predispose patients to invasive opportunistic infections, particularly fungal infections. In the literature, cryptococcal infections associated with ruxolitinib have been reported in a limited number of case reports, most commonly involving the pulmonary and/or central nervous system. Cutaneous involvement is exceedingly rare, and to date, no cases from Türkiye have been reported. In this case report, a 67-year-old woman with myelofibrosis who had been receiving ruxolitinib therapy for three-years and developed cutaneous cryptococcosis infection mimicking necrotizing fasciitis, accompanied by asymptomatic pulmonary involvement was presented. Despite broad-spectrum antibacterials, a small papule on the medial thigh rapidly progressed over 25 days, with severe disproportionate pain raising suspicion of necrotizing fasciitis. On admission, physical examination revealed an 8×8 cm ulcerative tissue defect on the left thigh, with surrounding erythema, ecchymosis, desquamation and hemopurulent discharge. Magnetic resonance imaging demonstrated findings suggestive of necrotising soft-tissue infection, prompting urgent surgical intervention. Intraoperatively, diffuse inflammation and patchy necrotic areas were observed and surgical debridement followed by vacuum-assisted wound closure was performed. Microbiological cultures of deep-tissue specimens yielded C.neoformans and the pathogen was confirmed by matrix-assisted laser desorption/ ionisation-time-of-flight-mass spectrometry (MALDI-TOF-MS). Antifungal susceptibility testing showed minimum inhibitory concentrations of 0.5 µg/mL for amphotericin B and 4 µg/mL for fluconazole. Histopathological examination demonstrated yeast cells within a background of suppurative inflammation and focal necrosis. Although the patient had no respiratory symptoms, chest computed tomography revealed a cavitary pulmonary nodule consistent with fungal infection. Bronchoalveolar lavage cultures showed no microbial growth. Evaluation for central nervous system involvement resulted negative for India-ink staining and cerebrospinal fluid multiplex polymerase chain reaction (PCR) test. These findings were considered consistent with systemic cryptococcosis involving the skin and lungs. Antibacterials were discontinued and intravenous liposomal amphotericin-B plus fluconazole was initiated. After central netvous system involvement was excluded, sequential therapy with fluconazole was planned. Ruxolitinib dose was adjusted by haematology. Significant clinical improvement was observed in the early phase of treatment and pain however, the patient died due to acute pulmonary embolism. This case highlights a rare cutaneous presentation of ruxolitinib-associated cryptococcosis and emphasizes the importance of clinical awareness for opportunistic fungal infections in immunosuppressed patients.

Toxic epidermal necrolysis (TEN) is a rare, life-threatening dermatological emergency characterised by blistering and desquamation, often triggered by medications. Early identification and discontinuation of offending agents are critical for improving outcomes.Here, we describe a woman in her 30s with a complex medical history, including systemic lupus erythematosus and common variable immunodeficiency, who developed TEN following antifungal and antibacterial therapy. She initially presented with respiratory distress and was treated for pneumonia. Over the ensuing days, her clinical course rapidly deteriorated as she developed skin desquamation, tachycardia, hyperkalaemia and acute renal failure, and she was diagnosed with TEN. Suspected offending agents were discontinued, and treatment was initiated with intravenous immunoglobulin, corticosteroids and tumour necrosis factor-alpha blockade.This case illustrates the complexity of managing TEN in a patient with multiple comorbidities and ongoing immunosuppression, emphasising the importance of prompt recognition and treatment given the high mortality and morbidity of TEN.

Background/Objectives: FLASH radiotherapy (RT) has shown potential to reduce normal tissue toxicity compared with conventional (CONV) RT while maintaining tumor control. FLASH RT is characterized by ultra-high dose rate delivery, commonly using mean dose rates ≥ 40 Gy/s and sub-second delivery times. Most preclinical studies have used single-fraction regimens, leaving the feasibility and normal tissue impact of clinically relevant fractionation largely unexplored. We evaluated electron FLASH RT given in a standard five-fraction regimen to a porcine skin model, simulating adjuvant treatment workflow for high-risk cutaneous melanoma. Method: Three Yorkshire-Landrace swine received paired five-fraction electron irradiations to dorsolateral skin using either FLASH RT (mean dose rates 175-246 Gy/s) or CONV RT (8 Gy/min). Radiation was delivered with a 9-MeV electron beam; field diameters of 4, 7, or 10 cm; and doses of 5 × 6, 5 × 7, or 5 × 8 Gy. Dosimetry was validated with several dosimeters and real-time beam monitoring, confirming dose accuracy within 3%. Skin toxicity was assessed over 22-24 weeks using clinical grading, erythema spectrophotometry, and histopathologic evaluation. Results: FLASH RT was well tolerated at 5 × 6 Gy and 5 × 7 Gy, with no significant differences in peak radiation dermatitis, erythema index, or histologic damage compared with CONV RT. At 5 × 8 Gy, both modalities caused unacceptable toxicity, including moist desquamation and necrosis. No volume-dependent effects were observed. Conclusions: Although a FLASH-specific normal tissue sparing effect was not observed, this study demonstrates the technical feasibility and safety of delivering fractionated electron FLASH RT in a large animal model using a clinically relevant workflow. These findings support further investigation of physical beam parameters and biological modifiers, such as tissue oxygenation, and inform the clinical translation of fractionated FLASH RT for cutaneous malignancies.

Frankincense, a traditional Chinese medicinal resin with well-documented skin barrier-protective and anti-inflammatory properties, has elusive underlying mechanisms in psoriasis-like dermatitis. This study aimed to elucidate its therapeutic potential and molecular targets by investigating frankincense oil extract (FOE) and three key constituents (linalool, α-pinene and 1-octanol) in a classic imiquimod-induced murine psoriasis model, with clinical first-line topical drugs (calcipotriol, tapinarof and dithranol) used as positive controls. Phenotypically, FOE and its constituents significantly ameliorated core psoriasis symptoms (desquamation, erythema, epidermal thickening and splenomegaly) at an efficacy comparable to that of positive controls. FOE suppressed epidermal hyperproliferation and dermal inflammatory infiltration, attenuated the abnormally elevated epidermal expression of TRPV3, β-catenin and COX-2, and increased the expression of the barrier protein K10. Taken together, these findings suggest that FOE restores impaired epidermal barrier function by regulating TRPV3, β-catenin, COX-2 and K10 expression, providing a novel mechanistic basis for the clinical application of traditional frankincense in psoriasis and identifying promising targets for antipsoriatic-drug development.

The composite index lesion severity (CAILS) score is used to monitor disease and therapeutic response in mycosis fungoides (MF), but is limited by interobserver variability and low sensitivity. Emerging imaging techniques, such as multispectral imaging (MSI), colourimetry and laser speckle contrast imaging (LSCI), offer objective alternatives for quantifying CAILS parameters. The aim of this study was to evaluate non-invasive imaging modalities for objective and reliable quantification of disease extent in MF. Sixty-six participants were enrolled in two prospective studies: a cross-sectional discovery cohort to assess baseline characteristics of 35 MF patients (IA-IVB) and 10 healthy controls using CAILS and MSI, and a longitudinal confirmation cohort including 21 early-stage MF patients (IA-IIA) treated with chlormethine gel 0.016% for 16 weeks, in whom lesional and non-lesional skin were assessed using CAILS, MSI, colourimetry and LSCI at multiple time points. Candidate biomarkers were required to meet five clinical validation criteria: disease discrimination, repeatability, treatment responsiveness, correlation with CAILS and patient acceptability. In the discovery cohort, MSI detected significant differences in erythema, pigmentation, elevation and desquamation between healthy, non-lesional and lesional skin. In the confirmation cohort, four candidate biomarkers met all validation criteria: MSI CIELAB a*, MSI average haemoglobin, and colourimetry CIELAB a* (DSMIII) for quantifying erythema, and MSI individual typology angle (ITA) for pigmentation. These biomarkers reliably discriminated lesional from non-lesional skin (p ≤ 0.001), showed strong test-retest reliability (CV < 10%, ICC > 0.84), detected treatment effects, showed moderate concordance with CAILS, and were associated with low patient burden (mean 3.4/100). These findings show that MSI- and colourimetry-derived biomarkers can objectively monitor disease extent in MF and complement existing clinical assessments.

Toxic epidermal necrolysis (TEN) is a rare and life-threatening cutaneous adverse reaction characterized by > 30% total body surface area desquamation and mucosal involvement. Although ocular, oral, and urogenital mucosal involvements are well described, pulmonary mucosal injury is uncommon and associated with high mortality. We report a case of a 33-year-old woman with rapidly progressive TEN complicated by respiratory failure. Despite early multidisciplinary management including local wound care, immunomodulatory therapy, systemic corticosteroids, and lung-protective mechanical ventilation, she developed worsening hypoxemia and hypercarbia with radiographic findings consistent with acute respiratory distress syndrome. As respiratory failure progressed despite maximal conventional therapy, she was cannulated for venovenous extracorporeal membrane oxygenation (ECMO). Following ECMO therapy, her pulmonary infiltrates gradually resolved in parallel with cutaneous re-epithelialization. She underwent tracheostomy for prolonged ventilatory support, was successfully decannulated after 9 days of ECMO support, and survived to discharge. This case adds to the limited data supporting the feasibility of ECMO as a rescue therapy for TEN-associated severe respiratory failure. In carefully selected patients with TEN having refractory respiratory failure, ECMO may serve as an effective bridge to pulmonary recovery. Further studies are needed to better define patient selection, timing, and outcomes in this population.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease characterized by hyperkeratotic follicular papules, palmoplantar hyperkeratosis, and associated normal "islands of unaffected skin". Its pathogenesis has not been fully elucidated, and treatment poses significant challenges. Conventional therapies include oral retinoids and topical emollients. In recent years, although biological agents have been used in treatment, they are associated with side effects such as an increased risk of infection, and some patients show no response to treatment, thus necessitating the exploration of new therapeutic approaches.This case represents the first reported use of a TYK2 inhibitor (deucravacitinib) for the treatment of PRP. The patient was a 39-year-old male who developed extensive erythema in December 2024. The erythema gradually increased and progressed to red punctate eruptions accompanied by mild desquamation, slight pruritus with a stinging sensation, and "islands of unaffected skin". Initial treatment with topical dinoprostone and mometasone furoate cream was ineffective. In March 2025, the patient received deucravacitinib (6 mg daily) in combination with topical halometasone cream. At the 1-month follow-up, significant improvements were observed in erythema, desquamation, and pruritus. At the final 6-month follow-up, the skin lesions almost resolved, leaving only mild erythema and a small amount of desquamation. Both the disease severity and the patient's quality of life were significantly improved. This case suggests that deucravacitinib exhibits favorable efficacy and safety in the treatment of PRP. However, due to the low incidence of PRP, which makes large-scale controlled trials difficult, and the lack of recognized treatment guidelines, more clinical studies are needed in the future to further verify the potential of deucravacitinib in the treatment of PRP.

Radiation-induced skin injury is the most common side effect of radiotherapy (RT), affecting up to 95% of patients. Severe skin reactions may restrict radiation delivery or limit further treatment. Acute radiation dermatitis (ARD) arises within three months of the initiation of RT and is characterized by erythema, desquamation, ulceration, and even necrosis. To prevent or manage ARD, multiple systemic and topical medications have been employed, including topical vitamins, metallic ointments, and dressings. Among them, dressings are widely used and competitive, as they provide an intact, moist environment to facilitate the re-epithelialization of impaired skin. Polyurethane film dressings (such as Mepitel film and Hydrofilm dressings) are guaranteed in preventing ARD, whereas foam dressings (such as Mepilex® Lite dressings) can effectively manage ARD. Hydrogels are the most promising material for radiation-induced wound dressings due to their biodegradability, porous structure, and delivery features. However, due to the complexity of the skin repair process and the uncertainty surrounding its underlying mechanisms, the wide clinical application of hydrogels in ARD still requires further investigation. This review discusses the classification and pathological processes of ARD, the types of dressings available for clinical use, and modern dressings used to prevent and treat ARD. The aim is to provide valuable insights for optimizing ARD prevention and management.

Photoaging, driven by chronic UVR, disrupts skin structure and function. Traditional retinoids enhance extracellular matrix regeneration but cause irritation. Hydroxypinacolone 9-cis retinoate (9-cis HPR), a derivative of 9-cis retinoic acid, selectively activates retinoic acid receptor α and retinoid X receptor α, improving efficacy and tolerability. In a UVR-induced SKH-1 mouse photoaging model, 9-cis HPR reduced erythema, desquamation, and loss of elasticity while promoting collagen and elastin production. Single-cell RNA sequencing and spatial transcriptomics revealed restoration of fibroblast, basal cell, and melanocyte proportions; suppression of myofibroblast differentiation; and upregulation of extracellular matrix-related genes (eg, Col1a2, Col3a1, Elastin). In addition, 9-cis HPR inhibited melanogenesis by downregulating melanogenesis-related genes (Tyr, Dct, Tyrp1), melanosome biogenesis genes (Mlana, Pmel), and the melanocyte proliferation gene Kit, likely through ROS suppression. Cell-cell interaction analysis showed that 9-cis HPR promoted fibroblast-driven repair through neuropeptide Y-NPY1R, PTN-SDC2, and POSTN-ITGA/BV signaling, while inhibiting KITL-KIT-mediated melanocyte proliferation. In a single-blind, split-face clinical trial involving 31 Chinese women, 0.03% 9-cis HPR applied daily for 4 weeks demonstrated comparable or superior improvements in wrinkles, elasticity, hydration, dermal density, and radiance versus 0.3% retinol, without observed irritation. These findings support 9-cis HPR as a safe and effective retinoid that mitigates photoaging through extracellular matrix restoration, inflammation modulation, and pigmentation control.

Keratosis pilaris (KP) is a highly prevalent, benign disorder of follicular keratinization characterized by rough keratotic papules and variable perifollicular erythema, most commonly affecting the extensor upper arms, thighs, and buttocks. Although medically harmless, KP is frequently associated with cosmetic distress, reduced self-confidence, and persistent dissatisfaction with skin texture and appearance. The fundamental pathological process involves follicular hyperkeratosis with retention keratosis and abnormal desquamation, often occurring in the context of xerosis and epidermal barrier dysfunction, including associations with atopic dermatitis, ichthyosis vulgaris, and filaggrin-related barrier impairment. These mechanisms provide a strong rationale for topical keratolytic therapy, which aims to reduce corneocyte cohesion, facilitate desquamation, soften keratin plugs, and improve hydration of the stratum corneum. Topical keratolytics remain reasonable first-line, symptom-directed options for KP, with AHAs, BHAs, and urea all demonstrating potential benefit. However, the overall evidence base is constrained by small sample sizes, heterogeneous outcome measures, limited blinding, and short follow-up, with sparse long-term maintenance data and limited differentiation between texture-dominant and erythematous KP phenotypes.