Hyperdiluted Botulinum Toxin and Intense Pulsed Light Treatment: A Case Series to Illustrate a Novel Protocol for Hypertrophic Scar Reduction.

Hypertrophic scars can have significant and far-reaching effects on patients that range from itching to creating difficulty with mobility, all of which can negatively impact the individual's quality of life. A recent study showed that many patients with recent scars report pain, burning, pruritus, erythema, in combination with psychological difficulties that impact bodily movement, choice of clothing, and participation in leisure activities. Botulinum toxin Type A (BoNTA) and intense pulsed light (IPL) have shown promise in treating such scars. We propose a novel treatment protocol involving a 4-week intervention with hyperdiluted BoNTA injections and supplemental treatment with IPL for erythema, and a 6-month scar scale assessment and photographic documentation that occurs before and 6 months after treatment. We report four cases where using hyperdiluted BoNTA, either alone or in conjunction with IPL, substantially reduced scar size, improved overall scar appearance, and diminished erythema in areas on the face and the breasts. Although this report suggests that a schedule of alternating treatments with BoNTA and IPL may be beneficial in reducing scar size and enhancing appearance, further research is necessary to better understand the most effective dosages, the relationship between BoNTA and IPL, and the optimal management of scarring.

A comparative perspective on brucellar, pyogenic, and tuberculous spondylodiscitis.

OBJECTIVE: Non-specific features of spondylodiscitis lead to a delay and challenge in the diagnosis/differential diagnosis/treatment processes, and thus, serious complications may arise. This study aims to compare brucellar, pyogenic, and tuberculous types of spondylodiscitis, considering their demographic, clinical, and laboratory differences. This may provide more rapid management and good outcomes. PATIENTS AND METHODS: A total of 131 patients with infectious spondylodiscitis were included in the study. The patients were divided into brucellar (n=63), pyogenic (n=53), and tuberculous (n=15) types of spondylodiscitis and compared for demographic, clinical, laboratory, and imaging features. RESULTS: Tuberculous spondylodiscitis had higher scores for weight loss, painless palpation, thoracic spine involvement, and psoas abscess formation than other spondylodiscitis. Also, tuberculous spondylodiscitis had higher rates of neurologic deficit and lower rates of lumbar involvement than brucellar spondylodiscitis. Pyogenic spondylodiscitis is more likely to occur in patients who have a history of spine surgery compared to other forms of spondylodiscitis. Also, pyogenic spondylodiscitis had higher rates of fever, erythema, paraspinal abscess, white blood cell (WBC), and erythrocyte sedimentation rate (ESR) than brucellar spondylodiscitis. On the other hand, brucellar spondylodiscitis had higher rates of rural living and sweating than pyogenic spondylodiscitis. CONCLUSIONS: Weight loss, painless palpation, involved thoracic spine, psoas abscess, and neurologic deficit are symptoms favoring tuberculous spondylodiscitis. History of spine surgery, high fever, skin erythema, and paraspinal abscess are findings in favor of pyogenic spondylodiscitis. Rural living, sweating, and involved lumbar spine are symptoms that indicate brucellar spondylodiscitis. These symptoms can be used to distinguish the types of spondylodiscitis.

Eradication of skin microbiota restores cytokine production and release in polymorphic light eruption.

Polymorphic light eruption (PLE) has been mechanistically linked to cytokine abnormalities. Emerging preclinical evidence posits the skin microbiome as a critical modulator of ultraviolet (UV)-induced cytokine expression, thereby influencing subsequent immune responses. This intricate relationship remains underexplored in the context of PLE. Hence, we investigated the differential responses between disinfected and non-disinfected skin following both single and repetitive exposures to solar-simulated UV radiation in patients with PLE. An experimental, half-body pilot study was conducted involving six PLE patients and 15 healthy controls. Participants' skin was exposed to single and multiple doses of solar-simulated UV radiation, both in disinfected and in non-disinfected skin areas. The co-primary outcomes were PLE score and cytokine expression in blister fluid analysed through OLINK proteomic profiling. Secondary outcomes were erythema, pigmentation, induction of apoptotic cells in vacuum-generated suction blisters, and density of infiltrate in skin biopsies of PLE patients. Among the 71 cytokines analysed, baseline expression levels of 20 specific cytokines-integral to processes such as apoptosis, inflammation, immune cell recruitment, cellular growth, and differentiation-were significantly impaired in PLE patients compared with healthy controls. Notably, skin disinfection reversed the observed cytokine imbalances following a single UV exposure at the minimal erythema dose (MED) level and exhibited even more pronounced effects after multiple UV exposures. However, no significant differences were evident in PLE score, erythema, pigmentation, or rates of apoptotic cell induction upon UV radiation. These findings provide evidence for UV-driven cytokine regulation by the skin microbiota and imply microbiome involvement in the PLE immune response.

Evaluation of combining ultrapulse CO2 with fractional CO2 laser for the treatment of atrophic scars in Asians.

Various treatment modalities have been applied to atrophic scars. Fractional CO2 laser treatment has attracted increasingly more attention because of its quicker recovery time and fewer side effects. However, its limitation of sculpting the edge is an urgent shortcoming. In order to achieve a more effective result with fewer complications, we have integrated ultrapulse CO2 and fractional CO2 lasers to for the treatment of facial atrophic scars. The study included 25 patients (10 males and 15 females) diagnosed with moderate to severe atrophic scars between August 2020 and July 2022. All subjects underwent the same surgical treatment. The effects were assessed at baseline, 1 week, 1 month, and 3 months using photographic evidence. Objective evaluation of the results was conducted using a quartile grading scale, while the subjects' satisfaction and any adverse events were also recorded. The patients in the study underwent more than two laser sessions (2-5), resulting in substantial improvement in their appearance. The time interval between each session was 3-6 months. The majority of the patients (19/25, 76%) had a significant or even excellent improvement. Any adverse events observed, such as erythema, superficial crusting, and PIH, were of a mild nature and temporary in duration. This treatment combined two CO2 lasers is an effective and safe choice for atrophic scars in Asians.

The oral IRAK4 inhibitors zabedosertib and BAY1830839 suppress local and systemic immune responses in a randomized trial in healthy male volunteers.

This study evaluated and characterized the pharmacological activity of the orally administered interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors BAY1834845 (zabedosertib) and BAY1830839 in healthy male volunteers. Participants received one of either IRAK4 inhibitors or a control treatment (prednisolone 20 mg or placebo) twice daily for 7 days. Localized skin inflammation was induced by topical application of imiquimod (IMQ) cream for 3 days, starting at Day 3 of treatment. The inflammatory response was evaluated by laser speckle contrast imaging (skin perfusion) and multispectral imaging (erythema). At Day 7, participants received 1 ng/kg intravenous lipopolysaccharide (LPS). Circulating inflammatory proteins, leukocyte differentiation, acute phase proteins, and clinical parameters were evaluated before and after the systemic LPS challenge. Treatment with BAY1834845 significantly reduced the mean IMQ-induced skin perfusion response (geometric mean ratio [GMR] vs. placebo: 0.69 for BAY1834845, 0.70 for prednisolone; both p < 0.05). Treatment with BAY1834845 and BAY1830839 significantly reduced IMQ-induced erythema (GMR vs. placebo: 0.75 and 0.83, respectively, both p < 0.05; 0.86 for prednisolone, not significant). Both IRAK4 inhibitors significantly suppressed the serum TNF-α and IL-6 responses (≥80% suppression vs. placebo, p < 0.05) and inhibited C-reactive protein, procalcitonin, and IL-8 responses to intravenous LPS. This study demonstrated the pharmacological effectiveness of BAY1834845 and BAY1830839 in suppressing systemically and locally induced inflammatory responses in the same range as prednisolone, underlining the potential value of these IRAK4 inhibitors as future therapies for dermatological or other immune-mediated inflammatory diseases.

Combined microfocused ultrasound and delicate pulsed light for facial rejuvenation: A prospective, randomized, and split-face study.

OBJECTIVES: Public's interest in noninvasive skin rejuvenation treatments continues to grow. The advantage of combination therapy lies in that it can target different aspects of skin rejuvenation. This study aimed to assess the efficacy and safety of microfocused ultrasound (MFU) combined with delicate pulsed light (DPL) for facial rejuvenation. METHODS: Twenty-one patients with facial relaxation were enrolled. All patients received whole-face MFU treatment, and one side of the face was randomly assigned to receive DPL. MFU treatment was performed at Months 0 and 3, while DPL treatment was performed at Months 1, 2, 4, and 5. The length and angle of the nasolabial fold and perioral wrinkles, melanin index (MI), erythema index (EI), transepidermal water loss (TEWL), and follow-up time were recorded at Months 0, 3, and 6. Side effects were recorded during treatment and each follow-up visit. RESULTS: Twenty patients successfully completed the study. At the sixth month, the average length of perioral wrinkles and nasolabial folds on the combined side decreased by 11.5% (pwithin < 0.001) and 6.5% (pwithin = 0.011), while 8.3% (pwithin = 0.012) and 3.8% (pwithin = 0.02) on the MFU side. Compared with MFU treatment alone, the combined treatment also showed significant improvements in nasolabial fold angle (from 28.8 ± 3.4° to 32.7 ± 5.0°) and perioral wrinkle angle (from 39.3 ± 5.0° to 43.7 ± 5.1°). In addition, the combined side had greater benefits than the MFU side in improving MI, EI, TEWL, and skin elasticity (pbetween < 0.05). Except for one patient who withdrew due to increased skin sensitivity after MFU treatment, other subjects did not experience permanent or serious side effects. CONCLUSIONS: The combination of MFU and DPL for facial rejuvenation treatment is safe and effective. The combined treatment has better efficacy in skin firmness, and improving skin tone.

A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study.

INTRODUCTION: Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. METHODS: Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. RESULTS: This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre-existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620-18,282) mg, and the mean number of doses was 14 (4-63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. CONCLUSION: Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Assessing the Effect of Enzymatic Debridement on the Scar Quality in Partial-Thickness Burns to Deep Dermal Burns of the Hand: A Long-Term Evaluation.

Background and Objectives: Burn surgery on the hands is a difficult procedure due to the complex anatomy and fragility of the area. Enzymatic debridement has been shown to effectively remove burn eschar while minimizing damage to the surrounding tissue and has therefore become a standard procedure in many burn centers worldwide over the past decade. However, surprisingly, our recent literature review showed limited valid data on the long-term scarring after the enzymatic debridement of the hands. Therefore, we decided to present our study on this topic to fill this gap. Materials and Methods: This study analyzed partial-thickness to deep dermal burns on the hands that had undergone enzymatic debridement at least 12 months prior. Objective measures, like flexibility, trans-epidermal water loss, erythema, pigmentation, and microcirculation, were recorded and compared intraindividually to the uninjured skin in the same area of the other hand to assess the regenerative potential of the skin after EDNX. The subjective scar quality was evaluated using the patient and observer scar assessment scale (POSAS), the Vancouver Scar Scale (VSS), and the "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire and compared interindividually to a control group of 15 patients who had received traditional surgical debridement for hand burns of the same depth. Results: Between January 2014 and December 2015, 31 hand burns in 28 male and 3 female patients were treated with enzymatic debridement. After 12 months, the treated wounds showed no significant differences compared to the untreated skin in terms of flexibility, trans-epidermal water loss, pigmentation, and skin surface. However, the treated wounds still exhibited significantly increased blood circulation and erythema compared to the untreated areas. In comparison to the control group who received traditional surgical debridement, scarring was rated as significantly superior. Conclusions: In summary, it can be concluded that the objective skin quality following enzymatic debridement is comparable to that of healthy skin after 12 months and subjectively fares better than that after tangential excision. This confirms the superiority of enzymatic debridement in the treatment of deep dermal burns of the hand and solidifies its position as the gold standard.

Narrow-band UVB radiation triggers diverse changes in the gene expression and induces the accumulation of M1 macrophages in human skin.

BACKGROUND: The underlying molecular mechanisms that determine the biological effects of UVB radiation exposure on human skin are still only partially comprehended. OBJECTIVES: Our goal is to examine the human skin transcriptome and related molecular mechanisms following a single exposure to UVB in the morning versus evening. METHODS: We exposed 20 volunteer females to four-fold standard erythema doses (SED4) of narrow-band UVB (309-313 nm) in the morning or evening and studied skin transcriptome 24 h after the exposure. We performed enrichment analyses of gene pathways, predicted changes in skin cell composition using cellular deconvolution, and correlated cell proportions with gene expression. RESULTS: In the skin transcriptome, UVB exposure yielded 1384 differentially expressed genes (DEGs) in the morning and 1295 DEGs in the evening, of which the most statistically significant DEGs enhanced proteasome and spliceosome pathways. Unexposed control samples showed difference by 321 DEGs in the morning vs evening, which was related to differences in genes associated with the circadian rhythm. After the UVB exposure, the fraction of proinflammatory M1 macrophages was significantly increased at both timepoints, and this increase was positively correlated with pathways on Myc targets and mTORC1 signaling. In the evening, the skin clinical erythema was more severe and had stronger positive correlation with the number of M1 macrophages than in the morning after UVB exposure. The fractions of myeloid and plasmacytoid dendritic cells and CD8 T cells were significantly decreased in the morning but not in the evening. CONCLUSIONS: NB-UVB-exposure causes changes in skin transcriptome, inhibiting cell division, and promoting proteasome activity and repair responses, both in the morning and in the evening. Inflammatory M1 macrophages may drive the UV-induced skin responses by exacerbating inflammation and erythema. These findings highlight how the same UVB exposure influences skin responses differently in morning versus evening and presents a possible explanation to the differences in gene expression in the skin after UVB irradiation at these two timepoints.

XdemvyTM (Lotilaner Ophthalmic Solution) 0.25% Topical Solution for the Treatment of Demodex Blepharitis.

XdemvyTM (lotilaner ophthalmic solution) 0.25% topical solution was recently approved for the treatment of Demodex blepharitis in adults aged ≥18 years. As an antiparasitic agent, lotilaner selectively inhibits gamma-aminobutyric acid chloride channels specific to the parasite and induces spastic paralysis, leading to death of Demodex blepharitis mites. In two randomized, double-masked, vehicle-controlled, multi-center, phase-3 clinical trials (Saturn-1 and Satuirn-2), lotilaner 0.25% topical solution was investigated for the treatment of Demodex blepharitis. Patients were assigned to receive either lotilaner 0.25% topical solution or vehicle (solution that did not contain lotilaner as an active ingredient) twice daily for 6 weeks. On day 43, lotilaner group demonstrated primary efficacy in achieving collarette cure ([collarette grade 0], Saturn-1: study group 44% [92/209], vehicle 7.4% [15/204]; Saturn-2: study group 56% [108/193], vehicle 12.5% [25/200]). Secondary efficacy was achieved by eradication of mite ([0 mite/lash], Saturn-1: study group 67.9% [142/209], vehicle 17.6% [36/304]; Saturn-2: study group 51.8% [99/193], vehicle 14.6% [29/200]), composite cure ([grade 0 collarette as well as grade 0 erythema], Saturn-1: study group 13.9% [29/209], vehicle 1.0% [2/204]; Saturn-2: study group 19.2% [37/193], vehicle 4% [8/200]), and erythema cure ([grade 0 erythema], study group 19.1% [40/209], vehicle 6.9% [14/204]; Saturn-2: study group 31.1% [60/193], vehicle 9.0% [18/199]). The adverse events were mild, with the most common being pain at instillation site. The recommended regimen for lotilaner 0.25% solution is one drop in each eye twice daily for 6 weeks.

Measuring Psoriasis Severity at Home.

Psoriasis plaque severity metrics, such as induration (thickness), erythema (redness), and desquamation (scaliness), are associated with the subsequent development of psoriatic arthritis (PsA) among cutaneous-only psoriasis patients (patients with skin or nail psoriasis but no psoriatic arthritis). These metrics can be used for PsA screening. However, a key challenge in PsA screening is to optimize accessibility and minimize costs for patients, while also reducing the burden on healthcare systems. Therefore, an ideal screening tool consists of questions that patients can answer without a physician's assistance. Although reference images can be used to help a patient self-assess erythema and desquamation severity, a patient would need a tactile induration reference card to self-assess induration severity. This protocol describes how to create an induration reference card, the Psoriasis Thickness Reference Card, as well as how to use it to assess lesion induration severity. Administration of reference images for erythema and desquamation and a Psoriasis Thickness Reference Card for induration to 27 psoriasis patients showed that patients were moderately successful at self-assessing the severity of these three metrics. These findings support the feasibility of a future PsA screening test that patients can complete without the need for physician assistance.

Skin erythematous migrant lesions consistent with histologically confirmed dermal arteriolar thrombosis connected to APS.

Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder related to the presence of antiphospholipid antibodies (LAC, anticardiolipin, anti Beta2-glycoprotein) known to cause venous and arterial thrombosis and recurrent pregnancy loss. Skin disorder is a frequent finding usually due to vascular thrombosis involving the dermal layer and can be either localized or widespread causing necrosis and ulceration of the skin, without histological evidence of vasculitis. We present a case of a woman with APS with both arterial and venous thrombotic involvement associated with an atypical dermatological manifestation histologically consistent with a pauci-inflammatory intermediate-deep dermal arteriolar platelet-mediated thrombosis that appeared despite anticoagulation with warfarin and responding to the addition of antiplatelet therapy.

Acquired diffuse palmoplantar erythema with keratoderma in Chinese patients with pustular psoriasis: A predictor for IL36 receptor antagonist c.115+6T>C mutation?

Several studies have suggested that mutation of the interleukin 36 receptor antagonist gene (IL36RN) is related to generalized pustular psoriasis (GPP), and the presence of IL36RN mutation may affect the clinical manifestations and treatment responses. However, genetic testing is not routinely available in clinical practice for the diagnosis of GPP. Previously, GPP patients with acrodermatitis continua of Hallopeau (ACH) were found to have a high percentage of carrying IL36RN mutation. In this study, we reported six patients with pustular psoriasis presenting as diffuse palmoplantar erythema with keratoderma among 60 patients who carried IL36RN mutation. ACH was present in five patients and five patients had acute flare of GPP. This unique presentation may serve as a predictor for IL36RN mutation in patients with pustular psoriasis, similar to ACH.