CRUSE® -An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user-friendly platform to complete patient-reported outcome measures (PROMs) on their mobile devices. CRUSE® , the Chronic Urticaria Self Evaluation app, aims to address this unmet need. METHODS: CRUSE® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real-time insights. Additionally, CRUSE® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations. RESULTS: CRUSE® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country-specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second-generation antihistamines were used in 74.0% of days. CONCLUSIONS: The initial data from CRUSE® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management.

Influence of Storage and Preservation Techniques on Egg-Derived Carotenoids: A Substantial Source for Cutaneous Antioxidants.

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.

Inactivation of RUNX3/p46 Promotes Cutaneous T-Cell Lymphoma.

The key role of RUNX3 in physiological T-cell differentiation has been extensively documented. However, information on its relevance for the development of human T-cell lymphomas or leukemias is scarce. Here, we show that alterations of RUNX3 by either heterozygous deletion or methylation of its distal promoter can be observed in the tumor cells of 15 of 21 (71%) patients suffering from Sézary syndrome, an aggressive variant of cutaneous T-cell lymphoma. As a consequence, mRNA levels of RUNX3/p46, the isoform controlled by the distal promoter, are significantly lower in Sézary syndrome tumor cells. Re-expression of RUNX3/p46 reduces cell viability and promotes apoptosis in a RUNX3/p46low cell line of cutaneous T-cell lymphoma. Based on this, we present evidence that RUNX3 can act as a tumor suppressor in a human T-cell malignancy and suggest that this effect is predominantly mediated through transcripts from its distal promoter, in particular RUNX3/p46.

The Effects of Arsenic Trioxide in Combination with Retinoic Acids on Cutaneous T-Cell Lymphoma Cell Lines.

Cutaneous T-cell lymphomas (CTCL) are characterized by an infiltration of the skin with malignant T cells. Curative treatments for aggressive entities such as Sézary syndrome have not been identified yet. Arsenic trioxide (AsO3) is used for the treatment of acute promyelocytic leukemia in combination with retinoids. As the latter are established treatment options in CTCL, we sought to evaluate the efficacy of AsO3 for mono- and combination therapy in vitro. Analyses for apoptosis, cell cycle inhibition, cytotoxicity and cell viability were made after incubation of CTCL cells with AsO3 alone or in combination with the retinoids all-trans-retinoic acid or bexarotene. While AsO3 induced apoptosis, retinoids did not at the time point of analysis. However, retinoids strongly reduced cell viability. Due to the efficient apoptosis induction, AsO3 might be a potentially suitable agent for CTCL treatment, although this effect was not increased by retinoids.

Significance of the follicular pathway for dermal substance penetration quantified by laser Doppler flowmetry.

The understanding of transdermal substance penetration pathways remains an important field for the development of future topical drugs and cosmetics. Laser Doppler flowmetry is a well-established method for evaluating cutaneous perfusion. In a study on 6 healthy male volunteers, we topically applied the vasoactive substance benzyl nicotinate on two test areas with open and obturated hair follicles and measured changes in the blood flow by Doppler flowmetry. Contrary to occluded follicles, the application onto the test area with open follicles led to a statistically significant perfusion increase within the first 5 minutes, emphasizing the importance of the follicular pathway for epidermal penetration.

Treatment of localized mycosis fungoides with digital UV photochemotherapy.

BACKGROUND/PURPOSE: Photochemochemotherapy with 8-methoxypsoralen and UV-A light (PUVA) is a well-established treatment for mycosis fungoides (MF), although evidence for this therapy by means of prospective studies is scarce. However, long-term risks of PUVA are premature skin aging and development of nonmelanoma skin cancer. We therefore evaluated a device for targeted UV therapy, which reduces irradiation of unaffected skin in MF patients. METHODS: Ten patients with patch- or plaque-type MF affecting less than 10% body surface area were included in a prospective study. A total of 14 lesions were treated with cream PUVA using the digital phototherapy device skintrek(®) PT3. RESULTS: Seven of ten patients showed response to treatment. Complete clinical remission was achieved in four of ten patients (complete remission of seven of fourteen treated lesions) after an average of 13.4 weeks and an average cumulative UV dose of 42.6 J/cm(2) in a mean of 31.2 treatment sessions. Adverse events were rare and of mild severity. CONCLUSIONS: This study is the first prospective trial demonstrating efficacy and safety of cream PUVA in MF patients. As healthy adjacent skin remains unaffected, the potential to reduce the carcinogenic risk of PUVA treatment makes this new method a promising therapeutic option for localized MF.

Complete remission of critical neurohistiocytosis by vemurafenib.

OBJECTIVE: To describe a patient with life-threatening brainstem neurohistiocytosis who recovered completely upon targeted treatment with the V600E mutation-specific BRAF inhibitor vemurafenib. METHODS: We report clinical, histiologic, genetic, and sequential imaging findings, including fluorodeoxyglucose (FDG)-PET, over a follow-up period of 11 months. RESULTS: The patient presented with central hyperventilation, skeletal and perirenal Erdheim-Chester disease, and cutaneous Langerhans cell histiocytosis. A BRAF V600E hotspot mutation was detected in all afflicted tissues. Therapy with vemurafenib led to complete and stable clinical remission of CNS lesions and systemic disease that could be demonstrated by brain MRI and whole-body FDG-PET. CONCLUSIONS: Neurologic involvement in Erdheim-Chester disease usually confers a poor prognosis. In this patient, vemurafenib was well-tolerated and highly efficacious for severe brainstem involvement in Erdheim-Chester disease with overlapping Langerhans cell histiocytosis. This case illustrates the heterogeneous phenotypic spectrum of neurohistiocytosis and underscores the importance of genetic testing. CLASSIFICATION OF EVIDENCE: This article provides Class IV evidence. This is a single observational study without controls.

Blue-violet light irradiation dose dependently decreases carotenoids in human skin, which indicates the generation of free radicals.

In contrast to ultraviolet and infrared irradiation, which are known to facilitate cutaneous photoaging, immunosuppression, or tumour emergence due to formation of free radicals and reactive oxygen species, potentially similar effects of visible light on the human skin are still poorly characterized. Using a blue-violet light irradiation source and aiming to characterize its potential influence on the antioxidant status of the human skin, the cutaneous carotenoid concentration was measured noninvasively in nine healthy volunteers using resonance Raman spectroscopy following irradiation. The dose-dependent significant degradation of carotenoids was measured to be 13.5% and 21.2% directly after irradiation at 50 J/cm² and 100 J/cm² (P < 0.05). The irradiation intensity was 100 mW/cm². This is above natural conditions; the achieved doses, though, are acquirable under natural conditions. The corresponding restoration lasted 2 and 24 hours, respectively. The degradation of cutaneous carotenoids indirectly shows the amount of generated free radicals and especially reactive oxygen species in human skin. In all volunteers the cutaneous carotenoid concentration dropped down in a manner similar to that caused by the infrared or ultraviolet irradiations, leading to the conclusion that also blue-violet light at high doses could represent a comparably adverse factor for human skin.

Evaluation of blood parameters for the monitoring of erythrodermic cutaneous T-cell lymphoma.

BACKGROUND AND OBJECTIVES: Erythrodermic cutaneous T-cell lymphomas are aggressive diseases posing diagnostic and therapeutic challenges. Numerous indicators for confirming diagnosis and disease-monitoring have been proposed. CD26-negativity of peripheral CD4+ T-cells has been reported to have these properties. Our aim was to test, if the CD4(+) T-cell count, fraction of CD26- or CD7-negative CD4+ T-cells during the course of disease are valuable markers to predict therapeutic efficacy or disease progression in relation to changes in skin status. PATIENTS AND METHODS: Retrospective cohort analysis of eleven patients treated at a tertiary referral centre. Statistics were done by linear regression analysis and logrank test. RESULTS: Five patients displayed response to therapy in the skin, nine in the blood. Patients with cutaneous response showed a decrease of CD4+ T-cells, preceding the clinical response in most patients, whereas the percentage of CD26-negative T-cells changed first during clinical improvement. The calculated positive predictive values for response or progression were low for both CD4-count and CD26-expression. CONCLUSIONS: CD26 is not a reliable marker of either response or progression. As cutaneous response was always associated with a response in blood and not vice versa, we conclude, that the clinical status represents the most important parameter for guiding therapeutic decisions.

Analysis of the IL-31 pathway in Mycosis fungoides and Sézary syndrome.

IL-31, predominantly produced by CD45RO + CLA + Th2 cells, plays an important pathogenetic role in pruritic skin diseases like atopic dermatitis. As tumor cells in Sézary syndrome (SS) and Mycosis fungoides (MF) possess similar immunophenotypes and the conditions mentioned are often associated with pruritus, the analysis of the IL-31 pathway in MF/SS patients is of interest. Serum samples from the peripheral blood of 23 patients and 17 controls were analyzed for IL-31 abundance and correlated with disease stage and pruritus. Furthermore IL-31-, IL-31 receptor alpha (IL-31Rα)- and Oncostatin M receptor beta (OSMRß)-mRNA expression was measured in blood tumor cells from SS patients, memory T-cells from controls and lymphoma cell lines. Serum IL-31 levels were low but differed between groups with no or strong pruritus. Expression of IL-31 was detectable at low levels in cell lines, but not in the tumor cells of SS patients. Stimulation with PMA/ionomycin led to indiscriminate expression in peripheral blood tumor cells and control T-cells. IL-2-stimulation resulted in expression only in 9/11 patient samples. IL-31Rα-expression was detectable in 10/10 cell lines, 8/15 peripheral blood samples from SS patients, and 4/10 controls; whereas, OSMRß mRNA was detectable in 4/10 cell lines, but only one patient and control sample. The results of our analyses regarding serum levels and receptor expression do not suggest a central role of IL-31 in MF/SS pathogenesis. However, the results of IL-2 stimulation as well as the increased IL-31 levels in patients with strong pruritus offer a rationale for therapeutic approach in this subset of patients.

Combined antibacterial effects of tissue-tolerable plasma and a modern conventional liquid antiseptic on chronic wound treatment.

Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds.

Systematic review of combination therapies for mycosis fungoides.

BACKGROUND: A variety of therapeutic options are available for mycosis fungoides, the most prevalent subtype of cutaneous T cell lymphomas, but thus far, no regimen has been proven to be curative. A combination of treatments is a well-established strategy to increase the therapeutic efficacy. However, data from clinical trials analyzing such combinations for the treatment of mycosis fungoides are scarce. OBJECTIVE: To analyze the available evidence on combination therapies with emphasis on the combination of psoralen with UVA phototherapy (PUVA), interferon-alpha and bexarotene with another treatment. METHODS: Systematic literature review of the databases Embase, Cochrane, Medline, and Medline in Process. RESULTS: Combination of PUVA with interferon-alpha or retinoids did not result in an increased overall response rate. Addition of methotrexate but not retinoids to interferon-alpha may increase the overall response rate. Bexarotene was investigated in one trial each with vorinostat, methotrexate or gemcitabine, whereby only methotrexate possibly enhanced the effect of bexarotene. CONCLUSION: For mycosis fungoides, no combination treatment has been demonstrated to be superior to monotherapy. Based on our analysis, we conclude that in certain clinical situations, patients may benefit from a combination of PUVA with interferon-alpha or a retinoid or a combination of the latter two. Furthermore, patients in advanced stages may benefit from the combination of methotrexate and interferon-alpha or bexarotene. Finally, the combination of bexarotene with either vorinostat or gemcitabine did not increase the overall response rate but resulted in more pronounced side effects and cannot be recommended.

T-cell receptor gene rearrangement analysis of sequential biopsies in cutaneous T-cell lymphomas with the Biomed-2 PCR reveals transient T-cell clones in addition to the tumor clone.

Detection of a dominant T-cell clone by T-cell receptor (TCR) gene rearrangement analysis is often essential for the diagnosis of cutaneous T-cell lymphomas (CTCL). The occurrence of T-cell clones in addition to the diagnostic T-cell clone during the course of CTCL has been reported, but the data of these studies have been contradictory. We retrospectively evaluated the data of 114 lesional skin biopsies from 26 patients with Mycosis fungoides and two patients with primary cutaneous anaplastic large cell lymphoma, which were analysed with the standardized Biomed-2 PCR for the TCRγ and TCRß locus. A dominant T-cell clone was repetitively detected in 93% (26/28) of patients. Additional T-cell clones appeared temporarily in 39% (11/28) of patients. Correlation with the clinical data did not show an association of the presence of additional T-cell clones with age, number of treatments, progression of disease or survival. Our findings demonstrate that a persistent T-cell clone, most likely the disease causing tumor clone, is detectable in almost all CTCL patients. In addition, transiently appearing T-cell clones frequently occur during the course of disease. The biological relevance of these additional clones has still to be determined. However, it is important to take the possibility of additional T-cell clones into account for diagnostic analyses.

Treatment of indolent primary cutaneous B-cell lymphomas with subcutaneous interferon-alfa.

BACKGROUND: Interferon-alfa is used in the treatment of primary cutaneous B-cell lymphoma (PCBCL). Therapy with interferon-alfa has thus far been reported solely in case reports and small case series, mostly describing intralesional use. OBJECTIVE: We sought to evaluate efficacy, response rate, time to response, duration of response, and safety of subcutaneously administered interferon-alfa for the treatment of cutaneous B-cell lymphoma. METHODS: We conducted a retrospective chart analysis of patients given the diagnosis of PCBCL and treated with interferon-alfa subcutaneously at a tertiary referral center. RESULTS: Fifteen patients with indolent subtypes of PCBCL were identified. The overall response rate was 66.7%; all responding patients went into complete remission. Response was not significantly associated with the maximum tolerated dose. Within the median follow-up time of 40 months, 90% of the responders experienced a relapse; median duration of response was 15.5 months. Adverse events were predominantly mild and in no case led to cessation of therapy. LIMITATIONS: Retrospective nature of the analysis and small number of patients because of scarcity of the disease are limitations. CONCLUSION: Treatment of indolent PCBCL with subcutaneously injected interferon-alfa demonstrated good response rates and tolerability. Response was not dose dependent. Relapses were observed in nearly all responding patients raising the question of interferon-alfa maintenance therapy in PCBCL.