The Assessment of the Long-Term Impact of Radiotherapy on Biophysical Skin Properties in Patients after Head and Neck Cancer.

Background and Objectives: Chronic radiotherapy-induced skin injury (cRISI) is an irreversible and progressive condition that can significantly impact a patient's quality of life. Despite the limited literature available on the assessment of the epidermal barrier in cRISI, there is a consensus that appropriate skincare, including the use of emollients, is the primary therapeutic approach for this group of patients. The aim of this study was to evaluate the biophysical properties of the skin during the late period (at least 90 days) following radiation therapy (RT) for head and neck cancer. Materials and Methods: This was a single-center prospective non-randomized study. It involved the analysis of 16 adult patients with head and neck cancer who underwent RT at the Greater Poland Cancer Center, along with 15 healthy volunteers. The study and control groups were matched for gender and age (p = 0.51). Clinical assessment, based on the LENT-SOMA scale, was conducted for all patients. Evaluation of the skin's biophysical properties included: an analysis of transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin visualization using high-frequency ultrasonography (HF-USG). Results: A significantly higher TEWL was observed in the irradiated area compared to the control area in the study group (p = 0.004). However, there was no statistically significant difference in SCH (p = 0.073). Additionally, no significant difference was observed in the values of TEWL and SCH in the irradiated area between the group of patients with and without clinically obvious RISI (p = 0.192 and p = 0.415, respectively). The skin thickness of the irradiated area, assessed by HF-USG, did not differ significantly from the skin thickness of the control area (p = 0.638). Furthermore, no difference in skin thickness was observed in patients with clinical features of cRISI in the irradiated and control areas (p = 0.345). The mean time after RT was 6.1 years. Conclusions: This study marks the first demonstration of epidermal barrier damage in patients in the long term following RT for head and neck cancer. The impairment of the epidermal barrier was observed independently of evident cRISI features. This observation underscores the necessity to recommend appropriate skin care, including the use of emollients, for all patients following RT. We also suggest that HF-USG examination is generally inconclusive in determining the degree of skin damage in the late period after RT.

Afamelanotide in protoporphyria and other skin diseases: a review.

Afamelanotide is a synthetic alpha melanocyte stimulating hormone presenting a higher activity than natural hormones. Its main properties are related to the enhanced production of eumelanin by agonistically binding to the melanocortin-1 receptor. Since 2016 afamelanotide has been especially applied to treat cases of erythropoietic porphyria (EPP), where painful photosensitivity has been observed since early childhood. The positive effect of afamelanotide in EPP administered subcutaneously improved tolerance to artificial white light and increased pain-free time spent in direct sunlight. In this review we summarize the possible use of afamelanotide in dermatology, with special emphasis on EPP and encourage including afamelanotide as a treatment option in patient care.

Non-invasive detection of early microvascular changes in juveniles with type 1 diabetes.

AIMS/HYPOTHESIS: The study aimed to assess the usefulness of capillaroscopy and photoplethysmography in the search for early vascular anomalies in children with type 1 diabetes. METHODS: One hundred sixty children and adolescents aged 6-18, 125 patients with type 1 diabetes, and 35 healthy volunteers were enrolled in the study. We performed a detailed clinical evaluation, anthropometric measurements, nailfold capillaroscopy, and photoplethysmography. RESULTS: Patients with diabetes had more often abnormal morphology in capillaroscopy (68.60%, p = 0.019), enlarged capillaries (32.6%, p = 0.006), and more often more over five meandering capillaries (20.90%, p = 0.026) compared to healthy controls. Meandering capillaries correlated with higher parameters of nutritional status. In a photoplethysmography, patients with diagnosed neuropathy had a higher percentage of flow disturbance curves (p < 0.001) with a reduced frequency of normal curves (p = 0.050). CONCLUSIONS: Capillaroscopic and photoplethysmographic examinations are non-invasive, painless, fast, and inexpensive. They are devoid of side effects, and there are no limitations in the frequency of their use and repetition. The usefulness of capillaroscopy and photoplethysmography in the study of microcirculation in diabetic patients indicates the vast application possibilities of these methods in clinical practice.

Disturbances of the stomatognathic system and possibilities of its correction in patients with craniofacial morphea.

Morphea en coup de sabre and progressive hemifacial atrophy are extremely rare connective tissue disorders causing facial deformity. In extreme cases, morphological disorders are accompanied by symptoms of a clear impairment of the stomatognathic system. The aetiology of the above-mentioned diseases is still unknown. Properly planned therapy in the field of maxillofacial orthopaedics makes it possible to correct the asymmetric pattern of hard tissue growth and thus enable rehabilitation. The task of augmentation techniques is the volumetric supplementation of tissue defects resulting from atrophic processes. The degree of destruction and the extent of changes determine the method of correction. Mild and moderate defects are treated mainly with biomaterials and autologous adipose tissue. The severe course of hemifacial atrophy and morphea en coup de sabre and the associated significant tissue atrophy necessitate the search for more complex methods of treatment. In this paper, we summarize the disturbances of the stomatognathic system in patients with craniofacial morphea, together with an analysis of current treatment options.

Usefulness of high-frequency ultrasonography in the assessment of alopecia areata - comparison of ultrasound images with trichoscopic images.

Introduction: Trichoscopy allows us to distinguish between different types of alopecia and to determine the stage of the disease. High-frequency ultrasonography (HF-USG) enables the evaluation of structures that are not available for clinical and trichoscopic examination, but it has not been widely used to date in the evaluation of patients with alopecia areata (AA) and other scalp disorders. Aim: To characterise the ultrasound images of patients with AA, including different stages of the disease, and to compare them with trichoscopic images and other scalp diseases. Material and methods: Twenty-five patients with AA, on the basis of trichoscopic examination, were qualified to three groups: with active, inactive, and regrowth phase. Next, HF-USG (20 MHz) with qualitative and quantitative evaluation of various elements of the images was performed: entrance echo (EE), dermis (dermal background; DB), follicular structures (FS), dermal/ subdermal border (D/SB). The results were compared with 10 healthy volunteers, 10 patients with androgenic alopecia (AGA), and 12 with seborrhoeic dermatitis (SebD). Results: Active AA was characterised by FS with distinct borders, drop-like shaped, with a widened distal end located in the lower layers of DB. Inactive AA was characterised by a smaller number of FS without distinct borders. In the regrowth phase, FS of different widths, elongated, and with widened distal parts located at different DB depths were observed. Conclusions: HF-USG (20 MHz) may be a valuable diagnostic method in patients with AA. Ultrasound images of AA vary according to the stage of the disease and in comparison with AGA, SebD, and healthy individuals.

Epidermal barrier function in patients after allogeneic hematopoietic stem cell transplantation - a pilot study.

Introduction: The skin is the typically and predominantly affected organ in patients after allogeneic hematopoietic stem cell transplantation (alloHSCT). The supportive therapy in patients after alloHSCT includes especially ultraviolet protection and the use of emollients. Aim: Due to the lack of studies regarding epidermal barrier function in patients with alloHSCT, our aims were to monitor dermatologically patients 1 year after the procedure with special emphasis on epidermal barrier function and to evaluate the properties of epidermal barrier function in patients with confirmed chronic GvHD (cGvHD). Material and methods: Our pilot study included 30 patients after alloHSCT and 20 healthy controls. In the group of patients after alloHSCT there were 10 individuals who were monitored dermatologically (including evaluation of skin, mucosae, nails and hair) within 1 year after the procedure (subgroup 1) and 20 patients with previously confirmed cGvHD (subgroup 2). We evaluated transepidermal water loss (TEWL), skin hydration and skin color. The clinical assessment and all noninvasive evaluations in patients included in subgroup 1 were performed before (at baseline) and 3, 6, 9 and 12 months after the procedure, while in subgroup 2 they were performed once. Results: In subgroup 1 we did not observe significant differences between baseline results and periods of assessments in TEWL values or corneometry, erythema and melanin measurements. In subgroup 2 the highest TEWL values and the lowest corneometry results were observed in patients with sclerodermoid chronic cutaneous GvHD in comparison to patients with lichenoid chronic cutaneous GvHD and patients with cGvHD but without skin lesions. TEWL values and melanin level were significantly higher in patients with cGvHD than in controls. Conclusions: Our pioneer observations proved the disturbed epidermal barrier function among patients after alloHSCT. Therefore it seems that proper skin care, including photoprotection, should be recognized as a crucial component in long-term management of these patients.

Clinical characteristics of itch in cutaneous lupus erythematosus: A prospective, multicenter, multinational, cross-sectional study.

OBJECTIVE: Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE. METHODS: A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life. RESULTS: Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as "pure itch". More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index. CONCLUSIONS: Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.

Suitability of high-frequency ultrasonography (20 MHz) in evaluation of various forms of primary cicatricial alopecia in relation to trichoscopy - pilot study.

BACKGROUND: Primary cicatricial alopecia is a potentially irreversible process of hair loss, in which for proper diagnosis a skin biopsy is necessary. Searching for new, non-invasive diagnostic methods may shorten the time for final diagnosis, initiating appropriate treatment and reduce the need for biopsy. The aim of this study was to evaluate the usefulness of high-frequency ultrasonography (HF-USG) as a diagnostic method in patients with primary scarring alopecia and to compare it with trichoscopy. MATERIALS AND METHODS: The study covered a total of 44 adults: 8 with classic lichen planopilaris (LPP), 11 with discoid lupus erythematosus (DLE), 14 with frontal fibrosing alopecia (FFA), and 11 healthy volunteers. Each patient underwent physical and trichoscopic examination which was the base for qualification for active/inactive stage of the disease. Then, HF-USG was performed using a probe with a frequency of 20 MHz. In HF-USG images, the following elements were evaluated and measured: entrance echo (EE), follicular structures (FS), dermal background (DB), and dermal/subdermal border (D/SB). RESULTS: Inactive phase was characterized by significantly lower number/lack of FS compared to the active phase of scarring alopecia. HF-USG of active LPP/FFA presented cigar-like shaped FS, while inactive stage pronounced D/SB forming saw-like pattern. Active DLE in HF-USG were associated with focal, doubled EE and widened FS with a tendency to create hypoechogenic wide, structureless bands within the skin. In inactive DLE, there was no specific pattern of D/SB or rarely puzzle-like pattern. CONCLUSION: HF-USG images differ depending on the phase of the disease and the type of scarring alopecia, similarly to trichoscopic examination.

High-frequency ultrasonography of the scalp - Comparison of ultrasound and trichoscopic images in healthy individuals.

BACKGROUND: Hair loss is a common problem in dermatological patients. Its diagnosis is based on selected non-invasive and invasive tests. Searching for new diagnostic methods, especially non-invasive ones, aims to accelerate the correct diagnosis in the least invasive way possible. The aim of our study was to establish the characteristics of ultrasound images in healthy individuals and to compare them to selected trichoscopic parameters. MATERIALS AND METHODS: Eighteen healthy adults (10 women and 8 men) underwent trichoscopy and high-frequency ultrasound (HF-USG) with 20 MHz DermaScan transducer on the parietal region of the scalp. Selected parameters were compared in relation to sex and the research method used. RESULTS: HF-USG of the parietal area in all examined patients revealed hyperechogenic entrance echo and less echogenic layer corresponding to the dermis with well-defined hypoechoic follicular structures (FS). The number of hair units in trichoscopy and the number of FS in HF-USG did not differ significantly, while the differences in the studied distances between structures were statistically significant. The width of FS in HF-USG was significantly higher than hair shafts thickness in trichoscopy. CONCLUSIONS: HF-USG (20MHz) due to the possibility of visualization of FS can be a valuable complement to the range of non-invasive diagnostic procedures used in evaluation of the scalp.

Controversy around the morphea.

Morphea, also known as localized scleroderma, is a chronic, autoimmune disease of connective tissue. It is characterized by a typical clinical feature. In morphea, there is no Raynaud's phenomenon, no sclerodactyly or no ulcerations on the fingertips. Although morphea and systemic sclerosis have been perceived as separate disease entities for years, they are still confused both by patients (which is a source of unnecessary stress) and doctors. This may be due to, in part, misunderstood terminology. The controversy around morphea also concerns the division of this disease entity, including its less common subtypes, such as eosinophilic fasciitis. Discussions also revolve around the diagnostic aspects and possible treatment options. The paper attempts to present the debatable aspects regarding nomenclature, classification, diagnosis and treatment of morphea.

High-frequency ultrasonography a new quantitative method in evaluation of skin lymphomas-First comparative study in relation to histopathology.

INTRODUCTION: High-frequency ultrasonography (HF-USG) is a noninvasive method used in evaluation of depth and width of skin neoplasms. Recent data suggest that this method may also supplement objective clinical assessment in skin lymphomas, especially in mycosis fungoides, where subepidermal low echogenic band (SLEB) can be observed. The aim of the study was to present characteristic ultrasonic picture of MF in relation to histopathologic findings. MATERIALS AND METHODS: Ten patients diagnosed as MF were included in the study. The USG examination was performed with the use of 20 MHz transducer within representative plaque. From the scanning lesion, the skin biopsy was taken. The relationship between histopathologic infiltrate with clonal T cells and USG image was investigated. RESULTS: In all analyzed sonograms obtained from lesional skin of early-stage MF, we could detect the presence of subepidermal low echogenic band (SLEB). We detected strong correlations between SLEB thickness and the thickness of subepidermal infiltration (0.994, P < 0.05). CONCLUSIONS: Subepidermal low echogenic band is a typical sign of infiltrative stage of MF, and its thickness may depend on the type of skin lesion. HF-USG may be a reliable noninvasive method of quantitive assessments in MF, which corresponds to the thickness on T-cell infiltration in histopathology.

An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers.

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi-quantitative clinical scores, which are not validated and may be subject to inter-observer variability. A few previous studies suggested that high-frequency ultrasonography (HF-USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF-USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF-USG as well as dermatological assessment (target lesion score-TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non-irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1-4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1-4; P = .0002). There was no significant difference between non-irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF-USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.

Outdoor work as a risk factor for high-grade cutaneous squamous cell carcinoma of the head and neck.

INTRODUCTION: While it is clear that individuals with outdoor occupations are at a significantly greater risk of developing cutaneous squamous cell carcinoma (cSCC), no previous studies have investigated the potential association between the tumour grade and occupation in this patient population. AIM: To assess occupation as a risk factor for the development of high-grade cSCC. Secondarily, to determine the association between the tumour grade and other clinical characteristics. MATERIAL AND METHODS: Retrospective analysis of 256 patients treated for head and neck cSCC at our institution in 2007-2016. The following patient characteristics and variables were assessed: age; sex; tumour location and grade; profession; and education level. A univariate analysis was performed to assess the association between each study variable and grade 3 tumour differentiation. RESULTS: The following variables were significantly associated (p < 0.05) with grade 3 (G3) cSCC tumours: outdoor work vs. indoor work; primary school vs. high school education; and age. Additionally, patients with low-grade (G1) tumours were significantly younger (mean age: 72) than patients with high-grade (G3) tumours (mean age: 79) (p = 0.046). CONCLUSIONS: To our knowledge, this is the first study to assess the variables associated with the tumour grade among outdoor workers. These findings suggest that outdoor workers who develop cSCC are at a greater risk of developing more aggressive cancers. These findings provide additional support for classifying cSCC as an occupational disease. Early education about the dangers of sun exposure during the first years of school is essential to minimize the risks of developing high-grade skin cancer.

Morphea and antithyroid antibodies.

INTRODUCTION: Morphea, also known as localized scleroderma, is an autoimmune skin disease which is characterized by excessive accumulation of collagen that leads to the thickening of the dermis and subcutaneous tissue. There is an unclear relationship between morphea and other autoimmune diseases, especially related to the thyroid gland. AIM: To determine the occurrence of increased antithyroid antibodies in patients with morphea in relation to the clinical manifestations of the disease. MATERIAL AND METHODS: Forty-two Caucasian patients with different forms of morphea were included into the study. To determine the thyroid status, thyrotropin (TSH), anti-peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab) were evaluated with the use of the electrochemiluminescence method and TSH receptor autoantibodies (TRAb) - with the use of the radioimmunoassay method. RESULTS: Increased levels of antithyroid antibodies were observed in 6 cases in relation to TPO-Ab (14.3%), in 4 cases in relation to of Tg-Ab (9.5%) and in 1 patient in relation to TRAb (2.3%). There was no difference in the level of antithyroid antibodies between circumscribed and generalized forms of morphea. CONCLUSIONS: Although morphea is an autoimmune disease, it does not seem to be associated with increased prevalence of positive antithyroid antibodies. We conclude that there is no need to perform routine laboratory tests for thyroid disorders in patients with morphea.

Effects of UVA1 Phototherapy on Expression of Human Endogenous Retroviral Sequence (HERV)-K10 gag in Morphea: A Preliminary Study.

BACKGROUND Morphea, also known as localized scleroderma, is a rare autoimmune connective tissue disease characterized by skin fibrosis. UVA1 phototherapy is an important asset in the reduction of clinical manifestations in morphea. There are studies claiming that UV light modulates the expression of some human endogenous retroviral sequences. The aim of this study was to determine if the expression of HERV-K10 gag element is lowered by UVA1 phototherapy in morphea, a disease in which such irradiation has a soothing effect. MATERIAL AND METHODS The expression levels of the HERV-K10 gag were assessed by real-time PCR (polymerase chain reaction) in peripheral blood mononuclear cells (PBMC) and skin-punch biopsies of healthy volunteers and 9 morphea patients before and after phototherapy. Additionally, correlations between the HERV-K10 gag expression and age, disease duration, the Localized Scleroderma Skin Severity Index (LoSSI), and antinuclear antibody (ANA) titers were assessed. RESULTS In PBMC, HERV-K10 gag mRNA was significantly elevated after UVA1 phototherapy compared to healthy controls. Most of the patients responded with an increased expression level of this sequence. However, we found no statistical evidence at this point that phototherapy indeed has an effect on the HERV-K10 gag expression (there were no statistical differences in PBMC of morphea patients before and after phototherapy). Similarly, there was no statistically relevant effect of the UVA1 on the expression of HERV-K10 gag in skin. CONCLUSIONS At this point, the effect of UVA1 phototherapy on the expression of HERV-K10 gag cannot be statistically confirmed.

Current applications of high-frequency ultrasonography in dermatology.

The era of ultrasounds in dermatology started in 1979, when pioneering use of 15 MHz by Alexander and Miller in measuring the skin thickness was introduced. Since then, some new applications of high-frequency ultrasonography (HF-USG) have emerged providing the clinicians with an extra hand in their everyday practice. The main advantages of HF-USG include the possibility of real-time imaging, measurements of morphological and physiological aspects of the skin, safety associated with the use of non-ionizing media as well as the lack of contraindications to its performance. Currently the main clinical use of HF-USG in dermatology regards preoperative assessment of the depth of invasion in melanomas and basal cell carcinomas. The ultrasound image analysis allows noninvasive follow-up of inflammatory skin diseases, like atopic dermatitis, psoriasis and may be used for monitoring effectiveness of therapy in skin lymphomas and sclerotic skin diseases.

Human endogenous retroviruses and chosen disease parameters in morphea.

INTRODUCTION: Morphea (localized scleroderma) is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV) are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. AIM: In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index). MATERIAL AND METHODS: Real-time polymerase chain reaction (PCR) targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC) and skin biopsies. RESULTS: In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01). Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. CONCLUSIONS: Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing.

Microbiological analysis of acute infections of the nail fold on the basis of bait thread test.

INTRODUCTION: An acute infection of the nail fold, called paronychia, is a common clinical problem. The basis for the implementation of the treatment is the result of microbiological examination. Due to the rapid and painful course of infection, usually an empirical antimicrobial treatment prior to obtaining microbiological test results is introduced. AIM: The microbial analysis of acute infections of the nail fold. MATERIAL AND METHODS: The study included 32 tests conducted on 31 patients of the Department of Dermatology. Microbiological analysis was performed with the use of the so-called bait thread test. RESULTS: In 73% of analyzed cases microbiological examination revealed mixed microbiological flora. Most cultured microorganisms were: Enterococcus faecalis (14%), Staphylococcus aureus (12%), Candida albicans (9%), Enterobacter cloacae (8%), and Klebsiella pneumoniae (7%). Most cultured bacteria belonged to the families or genera of Enterobacteriaceae (36%), other cultured bacteria were staphylococci (26%), enterococci (16%), Candida species (14%), and Gram-negative non-fermenting bacilli (8%). CONCLUSIONS: The acute infection of the nail fold in the vast majority of cases is caused by mixed bacterial flora. A profile of isolated microorganisms suggests that the cause of the infection can be associated with neglect of hygiene. Fluoroquinolone and fusidic acid are recommended as the empirical therapy. Microbiological examination is the basis for the appropriate final treatment.