Hard-to-heal wounds, such as diabetic foot ulcers and pressure injuries, pose major clinical challenges due to chronic inflammation and cellular senescence. Cellular senescence-associated mechanisms, including stress-responsive p53/p21 signaling and senescence-associated secretory phenotype-related inflammation, contribute to impaired wound repair. We investigated whether local low-frequency vibration modulates wound healing and senescence-associated markers in tissues and exudates in a hyperglycemic rat full-thickness wound model, and whether treatment frequency affects its efficacy. A full-thickness wound model was established in hyperglycemic rats and local low-frequency vibration at 52 Hz was applied once or twice daily for 40 min (n = 5). The relative wound area was monitored, and molecular and histological analyses were performed on tissue samples and exudates to evaluate cellular senescence and the senescence-associated secretory phenotype. Local low-frequency vibration application twice daily significantly accelerated wound closure compared with that observed in the control group. Molecular and histological analyses revealed a reduction in the number of PTX3-positive cells and p53 expression in the twice-daily treatment group. Senescence-associated genes related to p53/p21 signaling, including Cdkn1a and Rb1, were downregulated in tissues and exudates. The number of p53-positive cells in exudate was lower in the twice-daily treatment group. In conclusion, local low-frequency vibrations enhanced wound healing and reduced the expression of senescence-associated markers and inflammatory mediators in tissues and exudates. These findings suggest that local low-frequency vibrations may act as a noninvasive, senomorphic physical therapy that modulates senescence-related pathways and inflammation, although future studies should determine whether local low-frequency vibrations further modulate senescence pathways.
Pustular psoriasis (IL-36/Th17) and atopic dermatitis (Th2) are associated with different but partially overlapping inflammatory pathways. Sequential expression of these phenotypes in the same patient is uncommon. We describe a 64-year-old woman with longstanding psoriasis vulgaris, asthma, allergic rhinitis, and a family history of atopy who developed generalized pustular psoriasis after biologic treatments. Genetic testing identified a novel, previously unreported heterozygous IL36RN frameshift variant, c.319del (p.Leu107Serfs65). Over subsequent months, the pustular phenotype was replaced by chronic, intensely pruritic, xerotic, eczematous dermatitis fulfilling the Hanifin-Rajka criteria. Serial biopsies demonstrated mild spongiosis and an eosinophil-rich superficial perivascular infiltrate. Risankizumab and adalimumab were temporally associated with pustular exacerbations, whereas dupilumab was followed by worsening of the eczematous phenotype without recurrent pustulation. Methotrexate 15 mg weekly, which restrains both axes, together with topical treatment was associated with sustained near-complete clearance through Month 12. To our knowledge, this is the first report of a three-class biologic paradox in a single patient. Sequential single-pathway blockade in a genetically destabilized immune network may disinhibit alternative effector arms with cytokine shunting. Inborn errors of immunity should be considered in refractory inflammatory dermatoses-even in geriatric patients-and pathway-specific biologics used cautiously when the underlying immune architecture is monogenically perturbed.
Patient-initiated therapy (PIT) is a treatment approach in which patients with recurrent herpes simplex self-administer medication at the onset of prodromal symptoms. PIT, which allows patients to receive medication in advance and initiate treatment at any time, is a therapeutic approach that alleviates the burden of urgent clinic visits for acute diseases like herpes simplex and benefits many people. Furthermore, its utility is particularly high for breastfeeding women for whom clinic visits can sometimes be difficult. When PIT is used in breastfeeding patients, potential drug transfer into breast milk and infant exposure must be considered. However, no studies have evaluated the extent of amenamevir transfer into human breast milk or its safety in infants. In this study, the relative infant dose (RID) was estimated from breast milk concentrations after a single oral dose of amenamevir. In the two cases evaluated, the estimated RID values were below 1%. This preliminary data suggest low estimated transfer of amenamevir into human milk after PIT. However, because breastfeeding was interrupted and infant exposure was not evaluated, clinical safety in breastfed infants remains undetermined. Trial Registration: Japan Registry of Clinical Trials identifier: jRCTs031230591.
Erythroderma is most often secondary to psoriasis, atopic dermatitis (AD), or drug eruption. These three subtypes have different immune mechanisms, but most biomarker studies treat erythroderma as one condition. We examined whether routine complete blood count (CBC) indices behave differently across the three subtypes. This was a single-center retrospective study of inpatients admitted between April 2015 and March 2026. We compared eosinophil-to-lymphocyte ratio (ELR), absolute eosinophil count (AEC), and neutrophil-to-lymphocyte ratio (NLR) between erythroderma cases and non-erythrodermic controls within each subtype, with Benjamini-Hochberg correction. We assessed ROC discrimination using a 5 000-iteration bootstrap and Harrell's optimism correction. Of 375 inpatients (18, 19, and 19 erythroderma cases in psoriasis-type, AD-type, and drug eruption-type), ELR was higher in cases than controls in all three subtypes (all q ≤ 0.007), with corrected AUCs of 0.84, 0.69, and 0.80. NLR was higher in cases for psoriasis-type (AUC 0.71) and AD-type (AUC 0.75) but not for drug eruption-type (AUC 0.56). In AD-type, a combined model with ELR and NLR gave a corrected AUC of 0.76; no gain was seen in the other two subtypes. In this small exploratory cohort, ELR appears higher in erythroderma across the three subtypes, while NLR carries information only in psoriasis-type and AD-type. The pattern is consistent with eosinophil-compartment activity being a shared feature and neutrophil-compartment activity being subtype-restricted. The findings are hypothesis-generating and need confirmation in prospective multicenter cohorts that can also control for pre-admission medication.
This study aimed to compare depressive symptoms, anxiety symptoms, and health-related quality of life between children with molluscum contagiosum and healthy controls and to examine whether lesion number and anatomical localization were associated with these outcomes. This prospectively conducted cross-sectional study included 72 children with molluscum contagiosum and 80 age- and sex-matched healthy controls aged 6-12 years. Depressive symptoms, anxiety symptoms, and health-related quality of life were assessed using validated pediatric instruments. Psychological outcomes were also compared according to lesion number and anatomical localization. Children with molluscum contagiosum had significantly higher depression and anxiety scores and significantly lower total quality-of-life scores than healthy controls. Depression and anxiety scores differed significantly according to lesion localization. Children with lesions involving highly visible areas, including the face, periocular region, lips, and hands, had higher depression and anxiety scores than those with lesions on the trunk and legs. Lesion number was not significantly associated with depression, anxiety, or quality-of-life scores. Female sex was independently associated with approximately twofold higher odds of an elevated anxiety score. Children with molluscum contagiosum may experience greater depressive and anxiety symptoms and poorer health-related quality of life than healthy peers. Psychological burden appears to be more closely related to lesion visibility and anatomical localization than to lesion number alone. These findings support consideration of psychological screening, particularly in children with highly visible lesions, and highlight the relevance of a broader psychodermatological approach.
Eccrine angiomatous hamartoma is an uncommon benign cutaneous hamartoma characterized by proliferation of eccrine and vascular components. It usually presents at birth or in childhood as a solitary extremity lesion and may be associated with pain, tenderness, hypertrichosis, or hyperhidrosis. We report a 6-year-old boy with a recurrent warm, hyperhidrotic subcutaneous tumor on the lateral aspect of the right ankle. The lesion had previously been excised under the clinical impression of hemangioma and was reported as angiolipoma, but later recurred and enlarged. Clinical examination showed a flesh-colored 5 × 4.5 cm tumor with clear surface secretion. Qualitative infrared thermography demonstrated focal surface warmth over the lesion. Histopathology showed well-circumscribed unencapsulated dermal and subcutaneous nodules composed of proliferating eccrine glands, vascular channels, mucinous stroma, mature fat, dilated sweat ducts, and large vessels with organizing thrombus, confirming eccrine angiomatous hamartoma. In this case, infrared thermography converted clinically perceived warmth into a visible, non-contact surface map that may help localize symptomatic surface involvement when planning conservative excision. Histopathology remains essential for diagnosis.
The optimal surgical margin for cutaneous melanoma remains controversial, particularly in anatomically constrained areas such as the acral regions. We conducted a retrospective cohort study of 79 patients with invasive cutaneous melanoma treated at National Cheng Kung University Hospital between 2012 and 2024, including 51 cases of acral lentiginous melanoma (ALM). Patients were categorized as having adequate surgical margins (per NCCN guidelines) or inadequate but histologically tumor-free margins. Survival outcomes, including overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and melanoma-specific survival (MSS), were analyzed using Kaplan-Meier estimates and Cox proportional hazards models after a median follow-up of 60 months. No significant differences were observed in OS, LRFS, or MSS between the two groups. Although univariate analysis suggested a difference in PFS, the association did not persist in multivariate analysis, where margin inadequacy was not independently associated with poorer outcomes (OS: HR 1.81, 95% CI 0.84-3.90, p = 0.13; PFS: HR 1.87, 95% CI 0.90-3.87, p = 0.093). Subgroup analyses of ALM and high-risk tumors (Breslow thickness > 2 mm) yielded consistent results, showing no significant differences in oncologic outcomes. In conclusion, our study showed that inadequate but histologically tumor-free excision margins may not independently compromise survival outcomes in cutaneous melanoma. A narrower margin may be acceptable in selected patients when wider excision is precluded by anatomic or functional constraints.
Sarcoidosis affects various organs, with cardiac involvement being clinically crucial due to its impact on prognosis. To date, there have been few reports on the association between cutaneous manifestations and cardiac sarcoidosis. We retrospectively examined 111 patients with cutaneous sarcoidosis and identified cardiac sarcoidosis in 16 patients (14.4%, 4 males and 12 females). The skin lesions were plaque (n = 7), nodular (n = 4), subcutaneous (n = 3), scar (n = 3), and lupus pernio (n = 1) types. A statistically significant correlation was observed between facial plaque-type cutaneous sarcoidosis and cardiac sarcoidosis. Although the examined number is small, our results suggest that plaque-type sarcoidosis in the face may be a useful sign for considering cardiac involvement. Further studies are necessary to elucidate the association of cutaneous and cardiac sarcoidosis.
Systemic treatments for moderate-to-severe plaque psoriasis have been advanced from broad immunosuppressants up to agents more selectively targeting cytokines, cytokine receptors, or intracellular signaling. The current systemic treatments mainly consist of conventional systemic agents, biologics targeting tumor necrosis factor (TNF)-α, interleukin (IL)-12/23p40, IL-17, or IL-23p19, and targeted oral agents. This review summarizes current evidence on efficacy, long-term disease control, safety, head-to-head comparisons, and practical selection of systemic treatments for adults with moderate-to-severe plaque psoriasis. Older conventional systemic agents, such as cyclosporin, acitretin, or methotrexate, remain useful in selected settings, especially when treatment options are limited by cost or availability, when short-term disease control is needed, or when the patient prefers these treatments. However, these conventional agents require careful monitoring and generally achieve lower rates of complete skin clearance compared to high-efficacy biologics. Biologics targeting TNF-α or anti-IL-12/23p40 ustekinumab have established the biologic treatment era, and remain clinically relevant, especially for patients having psoriatic arthritis or prioritizing long-term safety. Biologics targeting IL-17 can provide rapid and complete or almost complete skin clearance; however, require attention to mucocutaneous candidiasis and inflammatory bowel diseases. Biologics targeting IL-23p19 offer durable treatment responses and longer dosing intervals. Targeted oral therapies increase options for patients who prefer non-injectable treatment; established or emerging agents include apremilast, deucravacitinib, icotrokinra, zasocitinib, envudeucitinib, and orismilast. Emerging IL-17-directed agents, including sonelokimab and izokibep, may further refine pathway targeting. Selection of treatment should be decided dependently on the completeness of skin clearance achieved, speed and duration of responses, effectiveness on high-impact sites, safety, route of administration, monitoring requirements, patients' comorbidities, and the treatment goals aimed.
Lichen sclerosus (LS) is a chronic inflammatory dermatosis of the anogenital region with limited therapeutic options. Emerging evidence implicates dysregulation of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in LS pathogenesis, supporting investigation of targeted therapies. We report a series of 6 patients treated with topical ruxolitinib for vulvar LS, applied twice daily. Clinical outcomes were assessed using the Clinical Scoring System (CSS) and Patient Global Assessment (PtGA) over a mean follow-up of 7.5 months. All patients reported early symptomatic improvement in pruritus and burning. In parallel, PtGA scores showed significant improvement (p < 0.05). No local or systemic adverse events were observed. These findings suggest that topical JAK-STAT inhibition may represent a steroid-sparing option for achieving symptomatic improvement in LS, particularly in patients with concomitant autoimmune conditions. Larger controlled studies are warranted to confirm these preliminary observations.
