Acute skin toxicity of conventional fractionated versus hypofractionated radiotherapy in breast cancer patients receiving regional node irradiation: the real-life prospective multicenter HYPOBREAST cohort.

BACKGROUND: Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data. METHODS: We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity. RESULTS: Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall). CONCLUSION: Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.

Holistic health record for Hidradenitis suppurativa patients.

Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease with a complex etiopathogenesis whose treatment poses a challenge in the clinical practice. Here, we present a novel integrated pipeline produced by the European consortium BATMAN (Biomolecular Analysis for Tailored Medicine in Acne iNversa) aimed at investigating the molecular pathways involved in HS by developing new diagnosis algorithms and building cellular models to pave the way for personalized treatments. The objectives of our european Consortium are the following: (1) identify genetic variants and alterations in biological pathways associated with HS susceptibility, severity and response to treatment; (2) design in vitro two-dimensional epithelial cell and tri-dimensional skin models to unravel the HS molecular mechanisms; and (3) produce holistic health records HHR to complement medical observations by developing a smartphone application to monitor patients remotely. Dermatologists, geneticists, immunologists, molecular cell biologists, and computer science experts constitute the BATMAN consortium. Using a highly integrated approach, the BATMAN international team will identify novel biomarkers for HS diagnosis and generate new biological and technological tools to be used by the clinical community to assess HS severity, choose the most suitable therapy and follow the outcome.

Giant perianal condyloma successfully treated with podophyllin at 25% in solid petrolatum

Purpose: Giant perianal condyloma (GPC) is a rare condition. The effective treatment is a multidisciplinary challenge; topical treatments are usually ineffective, and surgical resection has significant morbidity. Podophyllin at 25% in solid petrolatum (25%PSP) can be an effective treatment option for GPC. The aim of the present study was to assess its response and tolerability. Methods: This retrospective, single-center case series evaluated the clinical response of 14 patients with GPC treated with 25%PSP in a public hospital in Buenos Aires between December 2015 and December 2019. After obtaining a full history and performing a physical exam, the lesions were measured and photographed. Biopsies were performed to exclude malignancy, as well as exams to rule out pregnancy. Podophyllin at 25% in solid petrolatum was administered topically in cases of GPC and washed off by the patients at home after 4 hours. The patients underwent at least 4 weekly visits, which included interval history, photodocumentation of the lesions, and provider-applied 25%PSP. The response rate was assessed by comparingmeasurements and the overall decrease in volume of the GPC based on photos from the first and last sessions. Adverse outcomes were noted. Results: In total, 10 men, 3 women, and 1 transgender woman with GPC unresponsive to prior treatments and a mean age of 34.5 years were included. A total of 12 patients were immunosuppressed. All the perianal lesions were circumferential and measured between 8 cm and 20 cm. Overall, 7 patients had genital condyloma outside of the anus and perianus; the histology showed low-grade squamous intraepithelial lesions in all cases. While on treatment, 7 patients reported dermatitis, and 71% of the patients had 75% reduction in lesion size. Conclusions: Podophyllin at 25% in solid petrolatum is an effective, well-tolerated topical treatment option for GPC. (AU)

Post-Inflammatory Hyperpigmentation: A Review of Treatment Strategies.

Post-inflammatory hyperpigmentation (PIH) is a reactive process resulting from increased melanin or abnormal distribution of melanin secondary to inflammatory skin conditions, dermatologic therapies, and external stimuli. Because PIH is a common condition that has a substantial effect on the quality of life, an understanding of its treatment modalities is essential. Though there are many therapeutic strategies for hyperpigmentary conditions such as melasma that are described in the literature, fewer studies focus on PIH. This article aims to provide a comprehensive literature review of therapies specifically used to treat PIH, such as topical combinations, chemical peels, and lasers. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4887.

A spray containing extracts of oat plantlets and Uncaria tomentosa relieves pain associated with chronic inflammatory skin diseases and dermatological procedures.

BACKGROUND: Inflammation from skin conditions such as psoriasis, eczema-like atopic dermatitis (AD) and hand eczema (HE) and following dermatological procedures (post-acts) can result in intense itching and cutaneous pain. Dermo-cosmetics containing plant extracts have been shown to reduce or alleviate these symptoms. OBJECTIVES: Assessment of the tolerability and efficacy of a spray containing Rhealba\xAE Oat plantlets and Uncaria tomentosa extracts in adults and children with inflammatory skin diseases and after dermatological procedures. METHODS: Data from five open label studies were analysed (Study 1: adults with AD; Study 2: children with AD; Study 3: adults with psoriasis; Study 4: adults with HE; Study 5: adults who had undergone a dermatological procedure: laser, intense pulsed light, glycolic acid peeling, photodynamic therapy or cryotherapy procedure). In all studies, subjects could use the test product up to six times per day for symptom relief. Physical and functional signs of inflammation, treatment-emergent adverse events (TEAEs), soothing effect, changes in quality of life, cutaneous pain and cosmetic acceptability were compared pre- and postapplication. RESULTS: A total of 176 subjects were enrolled across the five studies. Overall, investigators judged the dermatological tolerance of the test product containing Rhealba\xAE Oat plantlets extract and Uncaria tomentosa as good to excellent. All studies showed significant improvements in physical signs, reduction in itching and feeling of pain (P < 0.05). The soothing effect was evident after the first application. TEAEs were mostly mild, transient and occurred within the first few days of treatment. The majority of subjects reported improved QoL across the studies. CONCLUSIONS: The dermo-cosmetic spray containing Rhealba\xAE Oat plantlets extract and U. tomentosa was well tolerated and efficacious in providing relief of symptoms associated with cutaneous pain from inflammatory skin diseases and following dermatological procedures; however, further studies are needed to rule out alternative explanations of symptom reduction such as natural history and response biases.

Therapeutic Insights in Melasma and Hyperpigmentation Management

Melasma and postinflammatory hyperpigmentation (PIH) are the most common forms of dyschromia in patients with skin of color. Both are associated with a high psychological burden of disease. To exacerbate this burden, the need for treatment is chronic, and the results are often suboptimal in the eyes of the patient. Successful treatment is therefore contingent upon a correct diagnosis, patient education, and a carefully considered therapeutic approach. The latter is often multimodal in its design, incorporating sun protection, topical and systemic medications, and in some cases, procedural intervention. Although topical hydroquinone is a mainstay of treatment for melasma and PIH, there are alternatives that have emerged as of late that have shown varying degrees of promise, both in terms of safety and efficacy. In this article, we review the epidemiological, clinical, and histologic features of melasma and postinflammatory hyperpigmentation, and discuss important considerations for both established and emerging treatments for these vexingly common and difficult to treat conditions.

The Impact of Aeroallergens on Military Readiness: A Case Report.

Seasonal aeroallergens commonly cause allergic conjunctivitis, rhinorrhea, sinusitis, and cough in sensitized individuals. These clinical symptoms are the result of IgE-mediated type I hypersensitivity reactions, which trigger the degranulaton of mast cells and basophils. In contrast, aeroallergens are not common precipitants of urticarial dermatitis, which is driven by a cell-mediated type IV hypersensitivity reaction. In this case report, we describe an Active Duty Air Force member stationed in San Antonio, TX, who presented to the dermatology clinic with a three year history of recalcitrant urticarial dermatitis found to be directly related to exposure to the pollen from the Juniperus ashei tree, also referred to as Mountain Cedar. While laboratory findings confirmed a high level of circulating IgE antibody to Mountain Cedar, the patient had no upper respiratory symptoms consistent with a typical allergic reaction. Further, his skin disease rapidly cleared within 24 hours of leaving southern Texas. Because of the recalcitrant nature of his condition upon returning home, he was considered unfit for further military service. This case not only highlights the growing link between IgE and chronic skin disease, but also the impact aeroallergens can have on the medical readiness and world-wide deployability of Airmen, Sailors, Soldiers, and Marines.

Impact of UVA on pruritus during UVA/B phototherapy of inflammatory skin diseases: a randomized double-blind study.

BACKGROUND: Narrowband (TL-01) UVB phototherapy (UVB nb) is effective in treating inflammatory skin disease. The addition of UVA is traditionally advocated to reduce pruritus, but lacks evidence for this recommendation. OBJECTIVES: The aim of this study was to assess the effect of UVB nb and UVA phototherapy in combination compared against UVB nb monotherapy on pruritus, disease activity and quality of life. METHODS: In this double-blind randomized clinical trial, 53 patients suffering from inflammatory skin diseases with pronounced itching (Visual Analogue Scale (VAS) for pruritus ≥5) were randomized into two treatment groups. One group received UVB nb (311 nm) phototherapy alone and another group received a combination of UVB nb and UVA (320-400 nm) phototherapy. UV therapy was performed three times per week over 16 weeks. Pruritus (VAS and 5-D itch score), disease activity and quality of life (Dermatology Life Quality Index, DLQI) were assessed at baseline and weeks 4, 8, 12 and 16. RESULTS: In both treatment groups, there was a reduction in pruritus scores, disease activity and DLQI. No difference in pruritus score, disease activity and quality of life could be detected between the group receiving UVB nb alone and those receiving UVB nb combined with UVA. CONCLUSIONS: Phototherapy with UVB nb alone, and UVB nb combined with UVA are equally effective in treating inflammatory skin disease and indifferent in reducing disease-associated pruritus. Given this non-inferiority for UVB nb monotherapy, the recommendation of adding UVA to UVB nb phototherapy for pruritic inflammatory skin disease should be abandoned.

Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co γ-ray in mice.

OBJECTIVE: To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice. METHODS: Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor ß1 (TGF-ß1) were analyzed by western blot. RESULTS: Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-ß1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-ß1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-ß1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). CONCLUSION: HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

Carotenoid-enriched transgenic corn delivers bioavailable carotenoids to poultry and protects them against coccidiosis.

Carotenoids are health-promoting organic molecules that act as antioxidants and essential nutrients. We show that chickens raised on a diet enriched with an engineered corn variety containing very high levels of four key carotenoids (ß-carotene, lycopene, zeaxanthin and lutein) are healthy and accumulate more bioavailable carotenoids in peripheral tissues, muscle, skin and fat, and more retinol in the liver, than birds fed on standard corn diets (including commercial corn supplemented with colour additives). Birds were challenged with the protozoan parasite Eimeria tenella and those on the high-carotenoid diet grew normally, suffered only mild disease symptoms (diarrhoea, footpad dermatitis and digital ulcers) and had lower faecal oocyst counts than birds on the control diet. Our results demonstrate that carotenoid-rich corn maintains poultry health and increases the nutritional value of poultry products without the use of feed additives.

Reactive oxygen species prevent imiquimod-induced psoriatic dermatitis through enhancing regulatory T cell function.

Psoriasis is a chronic inflammatory skin disease resulting from immune dysregulation. Regulatory T cells (Tregs) are important in the prevention of psoriasis. Traditionally, reactive oxygen species (ROS) are known to be implicated in the progression of inflammatory diseases, including psoriasis, but many recent studies suggested the protective role of ROS in immune-mediated diseases. In particular, severe cases of psoriasis vulgaris have been reported to be successfully treated by hyperbaric oxygen therapy (HBOT), which raises tissue level of ROS. Also it was reported that Treg function was closely associated with ROS level. However, it has been only investigated in lowered levels of ROS so far. Thus, in this study, to clarify the relationship between ROS level and Treg function, as well as their role in the pathogenesis of psoriasis, we investigated imiquimod-induced psoriatic dermatitis (PD) in association with Treg function both in elevated and lowered levels of ROS by using knockout mice, such as glutathione peroxidase-1(-/-) and neutrophil cytosolic factor-1(-/-) mice, as well as by using HBOT or chemicals, such as 2,3-dimethoxy-1,4-naphthoquinone and N-acetylcysteine. The results consistently showed Tregs were hyperfunctional in elevated levels of ROS, whereas hypofunctional in lowered levels of ROS. In addition, imiquimod-induced PD was attenuated in elevated levels of ROS, whereas aggravated in lowered levels of ROS. For the molecular mechanism that may link ROS level and Treg function, we investigated the expression of an immunoregulatory enzyme, indoleamine 2,3-dioxygenase (IDO) which is induced by ROS, in PD lesions. Taken together, it was implied that appropriately elevated levels of ROS might prevent psoriasis through enhancing IDO expression and Treg function.

Retrospective chart review in a cohort of patients with urticarial dermatitis.

Urticarial dermatitis is a poorly understood skin condition while it seems to be much more common than the paucity of reports suggest. It manifests with severely pruritic papules and plaques that resemble eczematous and urticarial lesions morphologically. The key clues to diagnosis are the urticarial appearance and overlap with an eczematous reaction. Here, we present a series of 19 cases (13 women and six men) with urticarial dermatitis clinically and histologically. The patients' average age was 58 and most of the cases were idiopathic. Trunk and proximal extremities were the most common sites involved followed by the distal extremities. Poor response to potent topical corticosteroids and antihistamines was usual and many patients required oral prednisone or other immunosuppressant agents or phototherapy.

Fractalkine signaling in microglia contributes to ectopic orofacial pain following trapezius muscle inflammation.

Fractalkine (FKN) signaling is involved in mechanical allodynia in the facial skin following trapezius muscle inflammation. Complete Freund's adjuvant (CFA) injection into the trapezius muscle produced mechanical allodynia in the ipsilateral facial skin that was not associated with facial skin inflammation and resulted in FKN but not FKN receptor (CX3CR1) expression, and microglial activation was enhanced in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). Intra-cisterna magna anti-CX3CR1 or anti-interleukin (IL)-1ß neutralizing antibody administration decreased the enhanced excitability of Vc and C1-C2 neurons in CFA-injected rats, whereas intra-cisterna magna FKN administration induced microglial activation and mechanical allodynia in the facial skin. IL-1ß expression and p38 mitogen-activated protein kinase phosphorylation were enhanced in activated microglia after CFA injection. The excitability of neurons whose receptive fields was located in the facial skin was significantly enhanced in CFA-injected rats, and the number of cells expressing phosphorylated extracellular signal-regulated kinase (pERK) following noxious mechanical stimulation of the facial skin was significantly increased in Vc and C1-C2. We also observed mechanical allodynia of the trapezius muscle as well as microglial activation and increased pERK expression in C2-C6 after noxious stimulation of the trapezius muscle in facial skin-inflamed rats. These findings suggest that FKN expression was enhanced in Vc and C1-C2 or C2-C6 following trapezius muscle or facial skin inflammation, microglia are activated via FKN signaling, IL-1ß is released from the activated microglia, and the excitability of neurons in Vc and C1-C2 or C2-C6 is enhanced, resulting in the ectopic mechanical allodynia.

GATA3 expression is decreased in psoriasis and during epidermal regeneration; induction by narrow-band UVB and IL-4.

Psoriasis is characterized by hyperproliferation of keratinocytes and by infiltration of activated Th1 and Th17 cells in the (epi)dermis. By expression microarray, we previously found the GATA3 transcription factor significantly downregulated in lesional psoriatic skin. Since GATA3 serves as a key switch in both epidermal and T helper cell differentiation, we investigated its function in psoriasis. Because psoriatic skin inflammation shares many characteristics of epidermal regeneration during wound healing, we also studied GATA3 expression under such conditions.Psoriatic lesional skin showed decreased GATA3 mRNA and protein expression compared to non-lesional skin. GATA3 expression was also markedly decreased in inflamed skin of mice with a psoriasiform dermatitis induced with imiquimod. Tape-stripping of non-lesional skin of patients with psoriasis, a standardized psoriasis-triggering and skin regeneration-inducing technique, reduced the expression of GATA3. In wounded skin of mice, low GATA3 mRNA and protein expression was detected. Taken together, GATA3 expression is downregulated under regenerative and inflammatory hyperproliferative skin conditions. GATA3 expression could be re-induced by successful narrow-band UVB treatment of both human psoriasis and imiquimod-induced psoriasiform dermatitis in mice. The prototypic Th2 cytokine IL-4 was the only cytokine capable of inducing GATA3 in skin explants from healthy donors. Based on these findings we argue that GATA3 serves as a key regulator in psoriatic inflammation, keratinocyte hyperproliferation and skin barrier dysfunction.

[Acne vulgaris. Role of cosmetics]. / Acne vulgaris. Rolle der Kosmetik.

Appropriate cosmetics for skin cleansing are capable of contributing to a reduction of especially inflammatory lesions in acne-prone patients and to support pharmacological intervention in patients with manifest acne. Cleansing of acne-prone skin should employ acidified synthetic cleansers with a pH of 5.5 rather than soap. Furthermore, the ingredients of certain skin care products, i.e. nicotinamide, lactic acid, triethyl acetate/ethyllineolate, and prebiotic plant extracts, affect different mechanisms of acne pathogenesis and therefore may contribute to a decrease in acne lesions. At least some of these ingredients underscore the concept of evidence-based cosmetics. In contrast, the problem of acne lesions caused by comedogenic ingredients in cosmetics today is negligible.

Interstitial granulomatous dermatitis with arthritis.

A 54-year-old woman with a history of arthritis presented for a long-standing history of symmetric, indurated plaques on her thighs and lateral aspects of the trunk. Histopathologic examination of skin biopsy specimens was consistent with interstitial granulomatous dermatitis, and a diagnosis of interstitial granulomatous dermatitis with arthritis was made. Administration of topical potent glucocorticoids, intralesional glucocorticoids, and narrow-band ultraviolet B phototherapy, in addition to continuation of systemic glucocorticoids and methotrexate, resulted in improvement of her cutaneous and musculoskeletal disease.

Glucocorticoid-induced osteoporosis in dermatologic practice: a review.

Systemic glucocorticoids are widely used in dermatologic practice for various conditions including connective tissue and immunobullous diseases, vasculitis, dermatitis, neutrophilic and other dermatoses, and androgen excess syndromes. Long-term use of systemic glucocorticoids has been associated with substantial and rapid bone loss, which places patients at increased risk for bone fractures. Therefore, bone density measurements and the timely initiation of lifestyle modifications and pharmacotherapy are essential for future bone health. The use of several Food and Drug Administration-approved agents to prevent and treat corticosteroid-induced bone loss has been inconsistent among many specialties. In this review, the authors summarize guidelines on the prevention and treatment of corticosteroid-induced bone loss published by the American College of Rheumatology and supplement these guidelines with descriptions of the latest approved pharmacologic therapies and user-friendly flow algorithms. This summary should aid dermatologists in providing education and recommendations regarding bone health for their patients on systemic glucocorticoids.

Oxigenoterapia hiperbárica no tratamento de dermatite periestomal extensa: relato de caso / Hyperbaric oxygen therapy in the treatment of extensive peristomal dermatitis: case story

Os autores apresentam o caso de uma paciente idosa, submetida a colectomia segmentar em regime de urgência, que evoluiu no período pós-operatório com uma dermatite periestomal severa, infecção associada de partes moles e extensa necrose da parede abdominal. O quadro culminou com repercussões sistêmicas, inclusive sepse grave. O quadro só foi satisfatoriamente controlado após a realização da oxigenoterapia hiperbárica (OHB), instrumento terapêutico que se tem mostrado cada vez mais útil no tratamento de feridas de difícil manejo. É feita uma breve discussão das indicações e mecanismos de ação da oxigenoterapia hiperbárica.

[Pruritus in childhood. A diagnostic and therapeutic challenge]. / Pruritus im Kindesalter. Eine diagnostische und therapeutische Herausforderung.

From the clinician's point of view, pruritus in children is quite frequent. It mainly occurs along with dermatoses but rarely with systemic diseases such as renal and liver failure or with genetic disorders. Mostly, it appears in the setting of atopic dermatitis (AD). Other frequent differential diagnoses comprise e.g. scabies, impetigo, varicella, tinea, urticaria, mastocytosis and psoriasis. In children, pruritus is most often associated with severe scratching leading to artefacts. This group of patients requires a therapeutical regimen of its own. The use of topical and systemic treatments depends on the underlying aetiology of pruritus and the stage and status of the skin. The physician has to consider that topically applied drugs may cause intoxication due to the different body volume/body surface proportion, especially in newborns and infants. The dosages of systemic drugs need to be adapted in children and UV phototherapy should be performed with caution due to possible longterm photo damage of the skin. Physicians feel more insecurity treating pruritus in children, especially when systemic treatments are taken into consideration. We want to highlight the major aetiologies of pruritus in children and point out the cornerstones of antipruritic therapy in this challenging group of patients in recognition of our own clinical experiences and the current literature.