Search

OBJECTIVE: The first report concerning methotrexate (MTX) in the treatment of Mycosis fungoides (MF) was published in 1964 by Wright. The mechanism of MTX action in the treatment of primary cutaneous T-cell lymphoma (CTCL) has been not explained in detail yet (the anti-inflammatory, immunomodulating, immunosuppressive, and cytostatic actions have been under discussion). PATIENTS AND METHODS: This is a retrospective analysis of 79 MF patients in 4 dermatology clinical centers in Poland. Data are presented in terms of the duration, use of MTX, the effectiveness of treatment with MTX in terms of time required to achieve remission, the disease stage, route of administration, age at diagnosis and the dosage. Moreover, the occurrence of side effects depending on the route of administration and duration of therapy with MTX was analyzed. RESULTS: The analysis has revealed that 56 patients (70,9%) had achieved remission on the MTX. The remission began in the 1st month of therapy in 20% of patients, lasted 4 to 6 months in 50% of cases. At least 12 months' remission was confirmed in 25% of patients (2-year-long only in 10% and 3-year-long in 5% of patients). The time to remission was related to the stage of disease at diagnosis as well as to minimal and maximal dose of MTX. The total therapeutic dose of MTX was found important for the course of the disease: higher total dose had prolonged the remission. CONCLUSIONS: Despite the common use of MTX in MF patients, relatively few clinical studies have been published. The response of MF subjects to MTX seems to depend on the stage and, more importantly, the dose of MTX treatment. Methotrexate appears to be an effective treatment at every stage of MF; however, it is not devoided of side effects such as infections and elevated level of aminotransferases, which are most common. [ABSTRACT FROM AUTHOR]

Pruritus is a natural defence mechanism of the body and creates the scratch reflex as a defensive reaction to potentially dangerous environmental factors. Together with pain, pruritus is a type of superficial sensory experience. Pruritus is a symptom often experienced both in healthy subjects and in those who have symptoms of a disease. In dermatology, pruritus is a frequent symptom associated with a number of dermatoses and is sometimes an auxiliary factor in the diagnostic process. Apart from histamine, the most popular pruritus mediators include tryptase, endothelins, substance P, bradykinin, prostaglandins and acetylcholine. The group of atopic diseases is characterized by the presence of very persistent pruritus. It is found in almost all patients with atopic dermatitis or urticaria. Cutaneous T-cell lymphoma is another group of pruritic diseases where the symptom of pruritus develops at an early stage and becomes intensified as the disease progresses. Other dermatoses include psoriasis, parasitic diseases and also systemic diseases in which pruritus is often the first and the only symptom suggesting an internal health problem. Cases of pruritus in healthy subjects, possibly associated with skin dryness or pregnancy in women, have also been reported. This paper presents mechanisms responsible for pruritus and the most important dermatoses in which this symptom is found. Treatment of pruritic dermatoses is difficult and always requires an interdisciplinary approach. Not all dermatoses can be successfully treated with antihistamine drugs, particularly if patients suffer from cutaneous T-cell lymphoma, liver or kidney diseases. For this reason, the problem of pruritus is the focus of attention of many scientists, and the subject of interdisciplinary studies. [ABSTRACT FROM AUTHOR]

Introduction: ESMO guidelines recommend interferon (IFN) and methotrexate (MTX) as first-line systemic therapies in mycosis fungoides (MF) and Sezary syndrome (SS)., Aim: A prospective, head-to-head trial comparing the efficacy and safety of INF-α and MTX as first-line treatment in MF/SS patients., Material and Methods: Forty-three patients were enrolled in the trial. The response to treatment and side effects were assessed. Study variables included mSWAT, DLQI, and VAS scores., Results: The response rate in stage IV including SS was significantly higher in the IFN-α group than in the MTX group (100% vs. 40%; p = 0.03, respectively). No significant differences were found in response rate in stage IIB and III between treatment groups. Patients treated with IFN-α had significantly shorter time to achieve response (TTR). Significantly fewer in the IFN-α group experienced adverse events (AE) in comparison to patients treated with MTX (81% vs. 45%; p = 0.02). There was no statistically significant difference between both groups in terms of time to progression (TTP), progression-free survival (PFS), time on treatment (ToT), and time to next treatment (TTNT). The improvement in quality of life and reduction of pruritus was comparable in both treatment groups., Conclusions: The obtained data suggest that the efficacy of IFN-α as first-line treatment in advanced stage (IV) MF and SS is significantly better than MTX. IFN-α presented significantly better safety and tolerability and shorter TTR than MTX. However, the results should be interpreted with caution due to scarce study groups., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) characterized by the presence of circulating malignant CD4+ T cells (Sézary cells) with many complex changes in the genome, transcriptome and epigenome. Epigenetic dysregulation seems to have an important role in the development and progression of SS as it was shown that SS cells are characterized by widespread changes in DNA methylation. In this study, we show that the transmembrane protein coding gene TMEM244 is ectopically expressed in all SS patients and SS-derived cell lines and, to a lower extent, in mycosis fungoides and in a fraction of T-cell lymphomas, but not in B-cell malignancies and mononuclear cells of healthy individuals. We show that in patient samples and in the T-cell lines TMEM244 expression is negatively correlated with the methylation level of its promoter. Furthermore, we demonstrate that TMEM244 expression can be activated in vitro by the CRISPR-dCas9-induced specific demethylation of TMEM244 promoter region. Since both, TMEM244 expression and its promoter demethylation, are not detected in normal lymphoid cells, they can be potentially used as markers in Sézary syndrome and some other T-cell lymphomas., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: A wide range of treatments are available for psoriasis, including pharmaceuticals and phototherapy. Calcipotriol/betamethasone dipropionate and narrow-band ultraviolet phototherapy (NB-UVB) are both effective monotherapies for psoriasis; however, these two therapies have never been directly compared in a prospective clinical study. In this study, we compared the efficacy of combined calcipotriol/betamethasone dipropionate to NB-UVB in psoriatic patients with Psoriasis Area Severity Index (PASI) 9-10 treated in a routine clinical practice., Patients and Methods: This prospective, observational study included 58 consecutive patients (age range, 19-65 years) diagnosed with recurrent chronic small plaque psoriasis. Patients were offered either topical therapy with a two-compound ointment containing calcipotriol (50 μm/g) and betamethasone dipropionate (0.5 mg/g) or NB-UVB (311 nm). Disease severity was assessed at baseline and posttreatment according to PASI and target lesion score (TLS) and by high-frequency (20 MHz) ultrasonography (HF-USG)., Results: No statistically significant difference between the groups was observed in baseline or posttreatment PASI scores. Both treatments resulted in substantial reductions in PASI: 85% and 82%, respectively, for the calcipotriol/betamethasone group and the NB-UVB group. Both treatments significantly decreased the subepidermal low echogenic band (SLEB) thickness, with no significant differences between the two groups in terms of the percentage reduction in SLEB., Conclusions: This study demonstrates, for the first time, that NB-UVB phototherapy and fixed combination calcipotriol/betamethasone ointment are equally effective in treating plaque psoriasis in patients with PASI 9-10 in routine clinical practice. In addition, measurement of SLEB thickness with HF-USG may be a useful objective parameter to assess skin lesions., (© 2018 The International Society of Dermatology.)

The aim of the present study was to assess the effectiveness of UVA1 and PUVA therapy in treating patients with mycosis fungoides (MF) and to evaluate high-frequency ultrasonography (HF-USG) to monitor the clinical response of these patients. A total of 18 patients diagnosed with MF (stages I-IIA) underwent phototherapy, either UVA1 (6 cases) or PUVA (12 cases). Clinical response was evaluated according to modified Severity Weighted Assessment Tool (mSWAT) criteria and HF-USG (20 MHz). In the PUVA group, 50% of patients (6/12) achieved complete remission (CR) versus 33% (2/6) of patients in the UVA1 group. Before treatment, all subjects (100%) presented a subepidermal low echogenic band (SLEB) on HF-USG in the lesional skin. After phototherapy, the SLEB decreased significantly in all cases, with complete disappearance in 66% of cases. SLEB thickness was associated with disease severity and was wider in stage IIA patients than in stage IA and IB. These findings demonstrate that skin ultrasonography can be used to monitor treatment response in these patients. Moreover, HF-USG can quantify response, thus providing an objective measure of response that closely corresponds to scoring systems such as mSWAT used in routine clinical practice.

Sézary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma variant. Molecular pathogenesis of SS is still unclear despite many studies on genetic alterations, gene expression and epigenetic regulations. Through whole genome and transcriptome next generation sequencing nine Sézary syndrome patients were analyzed in terms of copy number variations and rearrangements affecting gene expression. Recurrent copy number variations were detected within 8q (MYC, TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1), but no recurrent rearrangements were identified. However, expression of five genes involved in rearrangements (TMEM244, EHD1, MTMR2, RNF123 and TOX) was altered in all patients. Fifteen rearrangements detected in Sézary syndrome patients and SeAx resulted in an expression of new fusion transcripts, nine of them were in frame (EHD1-CAPN12, TMEM66-BAIAP2, MBD4-PTPRC, PTPRC-CPN2, MYB-MBNL1, TFG-GPR128, MAP4K3-FIGLA, DCP1A-CCL27, MBNL1-KIAA2018) and five resulted in ectopic expression of fragments of genes not expressed in normal T-cells (BAIAP2, CPN2, GPR128, CAPN12, FIGLA). Our results not only underscored the genomic complexity of the Sézary cancer cell genome but also showed an unpreceded large variety of novel gene rearrangements resulting in fusions transcripts and ectopically expressed genes.

Over the last decade the availability of biological drugs for the treatment of psoriasis vulgaris, psoriatic arthritis and many other inflammatory diseases has revolutionized the treatment of these diseases around the world. Due to the high cost of therapy, the search has started for biosimilars. In dermatology the greatest interest in biosimilar medicines concerns inhibitors of tumor necrosis factor a (TNF-α), for use in the treatment of psoriasis vulgaris and psoriatic arthritis (infliximab, etanercept, adalimumab). The most important element of the safety of biologicals is their immunogenicity. Therefore, when discussing biosimilars, attention needs to be paid to the dangers of their immune activity. In view of the fact that the drugs contain and aggregates, produced by living organisms or cultures of living cells, they cannot be compared in any way to low molecular weight synthetic generics (called generics). Biosimilars are authorized for use in patients and treated as equivalent to the reference medicine only after passing a number of studies and assessments. As it is well known, the development of medicine and pharmacology is extremely intense, and the market in biological medicine is developing much faster than that of all other drugs, which underlines their important role in modern medicine. Currently, the subject of biosimilars is one of the most important challenges and topics of discussion around the world, including pharmacovigilance and legal and economic regulatory standards. It seems inevitable that biosimilar products will be introduced for the treatment of diseases with indications corresponding to the original product on which they are based.

Primary cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative neoplasms, with lymphatic proliferation limited to the skin with no involvement of lymph nodes, bone marrow or viscera at the diagnosis. Cutaneous lymphomas originate from mature T-lymphocytes (65% of all cases), mature B-lymphocytes (25%) or NK cells. Histopathological evaluation including immunophenotyping of the skin biopsy specimen is the basis of the diagnosis, which must be complemented with a precise staging of the disease and identification of prognostic factors, to allow for the choice of the best treatment method as well as for the evaluation of the treatment results.

Introduction: Radiotherapy (RT) in combination with chemotherapy is a standard of care for patients with head and neck squamous cell carcinoma (HNSCC). The RT is associated with side effects, which impact on quality of life (QoL). Thus, the aim of this prospective longitudinal study was to investigate the impact of RT on the QoL of patients with HNSCC during RT., Material and Methods: From September 2008 to February 2010, 205 patients with locally advanced HNSCC were enrolled. The data pertaining to their QoL were collected using the EORTC QLQ-C30 and the EORTC Head and Neck Module (QLQ-H&N35) and then all items were transformed to a 0-100 scale according to the guidelines of the EORTC. The following clinical factors were chosen to study their potential influence on the QoL; site of primary, clinical stage, and methods of therapy: RT vs. chemoradiotherapy (CRT). Additionally, the sociodemographic factors (age, gender, education, habit of smoking) were studied., Results: Deterioration of almost all scales and items in the QLQ-C30 and QLQ-H&N35 questionnaire were noted at the end of RT. The following factors negatively influenced the QoL: age < 60 years (p < 0.05), female gender (p < 0.05), habit of smoking (p < 0.01), advanced clinical stage (III and IV) (p < 0.05), site of primary (larynx, hypopharynx) (p < 0.01), and CRT (p < 0.01)., Conclusions: Our study showed that RT significantly negatively influenced QoL at the end of the RT course. Additionally, this study demonstrated that age, gender, smoking habit, tumor site, and clinical stage of disease showed a significant effect on the QoL of HNSCC patients during RT.

Aim: The aim of this paper was to present diagnostic methods helping in the recognition of mycosis fungoides (MF) and Sezary syndrome (SS)., Background: Mycosis fungoides is the most common form of primary cutaneous T-cell lymphomas. It is characterized by a distinctive long-term course and malignant T-cell proliferation. MF diagnosis is not easy, mainly due to the atypical clinical presentation of the disease at an early stage., Materials and Methods: Low specific changes, which can be observed at the histopathological examination. Initially, the skin lesions may resemble psoriasis, atopic dermatitis or chronic eczema. Patients are qualified according to the available, and generally accepted WHO-EORTC classification, based on a combination of clinical and histopathological markers. From a clinical point of view, it is also important to carry out the qualification according to the TNMB assessment, which allows to specify the stage of the disease, and is helpful in the monitoring of the course of disease and therapeutic effects., Results: In this paper we try to present currently available diagnostic methods., Conclusion: Diagnosis of MF and SS still causes many problems due to less characteristic changes in the early stage of disease and requires wide interdisciplinary knowledge.

Numerous cutaneous lesions are located in the region of the female genital organs, occasionally presenting a diagnostic and therapeutic challenge. The most common cases include: eczema vulvae, lichen simplex chronius, lichen sclerosus et atrophicus or lichen planus. Clinical presentation of these lesions is not always characteristic for certain dermatoses. Thus, it is important to conduct proper tests, including histopathological or contact allergy examination. Only thorough diagnostics allows to implement correct therapy. This paper shows a detailed description of dermal lesions located in the region of the female genital organs of the allergic and lichenoid origin, together with the literature review on diagnosis and treatment.

Introduction: Atopic dermatitis (AD) is a chronic and relapsing skin disorder, which is characterized by abnormal skin barrier function within the entire skin surface. Several noninvasive bioengineering methods have been commonly used to quantify disease severity. High-frequency ultrasonography (HF-USG) is an important contribution to this field., Aim: To evaluate noninvolved skin during the external treatment in relation to involved regions in patients with AD skin using noninvasive methods., Material and Methods: Transepidermal water loss (TEWL), capacitance and erythema assessment and HF-USG were performed in 55 AD patients within 2 regions (involved and uninvolved skin) before and after therapy. The clinical severity of the disease process was based on the eczema area and severity index (EASI) score. A control group consisting of 15 subjects was also included., Results: On the basis of 4 bioengineering methods our study revealed that uninvolved skin in AD presents subclinical disturbances and significantly changes during therapy. The HF-USG detects inflammation in the upper dermis in AD patients in the form of a hypoechoic band, which may also be observed to a lesser extent within normal-appearing skin., Conclusions: Nonlesional skin differs significantly from lesional skin in AD and from skin of healthy subjects. Noninvasive methods are able to measure subclinical skin disturbances within normal-appearing skin, which are not evaluated using standard clinical scores. They are objective and may facilitate communication between different research groups.

Background: Radical nephrectomy is the gold standard for treatment of renal cell carcinoma (RCC), but even for localized disease the survival rates are still unsatisfactory. Identification of prognostic factorsl is the basis for future treatment strategies for an individual patient., Aim: The aim of our study was to assess the usefulness of the concentration of IL-6 and CRP as prognostic factors in patients after nephrectomy due to localized RCC., Materials and Methods: Our prospective study included 89 patients (55 men and 34 women) who had been surgically treated for RCC. The examined group included patients with localized advanced disease (from T1 to T3) with no metastases in lymph nodes (N0), and with no distant metastases (M0). All patients had blood samples drawn three times during the study (one day before surgery, six days after surgery and 6 months after surgery) to evaluate the concentration of CRP and IL-6. In each patient RCC of the kidney was removed during radical nephrectomy. Statistical analysis was conducted using statistica v.7.0., Results: Statistically significant relationships were found between the concentration of CRP before the operation and OS (p = 0.0001). CRP concentration at baseline was statistically significantly correlated with CSS (p = 0.0004). The level of IL-6 assessed before the surgery was significantly correlated with survival times such as OS (p = 0.0096) and CSS (p = 0.0002). The concentration of IL-6 and CRP measured 6 days after surgery and 6 months after surgery were not statistically significantly correlated with survival times., Conclusions: Results of our study showed that elevated levels of IL-6 and CRP in peripheral blood before surgery of RCC were correlated with worse OS and CSS.

The development of an adverse graft-versus-host disease (GvHD) is a major complication of stem cell transplantations, which are widely used to cure increasing number of hematologic malignancies. Patients with chronic GvHD are at risk of joint contractures secondary to sclerodermatous skin changes. Several clinical scores or serologic markers have been used to assess skin sclerosis in scleroderma patients. Evaluation of sclerotic skin changes using biometric tools remains to be challenging. The purpose of this study was to illustrate and exemplify ultrasound measurement and measurement of skin elasticity of five chronic sclerodermoid GvHD patients. There is still a substantial lack of studies using objective and non-invasive methods helpful in assessment of patients with skin involvement of GvHD. Although ultrasound is not the ideal method, it is worth emphasizing that it is still useful, non-invasive, and repeatable device in monitoring patients suffering from GvHD. It should also be added, that it seems to be advisable to repeat USG examination at an interval of 3 months after the treatment. In addition, skin echogenicity may be a more sensitive parameter than skin thickness in assessment of cGvHD patients., (© 2012 John Wiley & Sons A/S.)

Lichen sclerosus is a chronic inflammatory skin disorder that belongs to a group of autoimmune connective tissue diseases, localized within the skin and mucous membrane of the anogenital area. In the latter location, the focal atrophy of the mucosa is the most visible sign. Lesions may be accompanied by symptoms such as itching, pain, burning. The disease occurs more often in females. The etiology is not fully understood. Genetic, infectious, hormonal factors and autoimmune mechanisms are taken into consideration. Early diagnosis and appropriate treatment is important to avoid further complications. This review aims to analyze available literature on the treatment of this disease entity

Penile cancer occurs quite seldom, mostly in men around 60 years of age. However penile squamous cell carcinoma is also observed in younger men. Etiology remains unclear but we can recognize some risk factors such as poor hygiene for example. The authors report a case of a patient who refused treatment in early stages of the disease and was treated only after disease progression. Applied surgical treatment, unfortunately proved to be insufficient and the patient was transferred to complete therapy at the oncology department. This case inspired us to recall the basic diagnostic and therapeutic methods used at the time of diagnosis of the penile tumor

An objective of this article is a review of contemporary knowledge on various environmental factors, that influence prevalence and course of allergic diseases, like asthma, allergic rhinitis, atopic dermatitis and also contact dermatitis. Surrounding climate may directly influence each patient, but also determines type of flora and fauna within particular geographical regions and thus affects sources of airborne and food allergens. Epidemiological studies suggest that there is a strong relationship between air pollution and development and exacerbation of asthma and other allergic diseases--main attention has been concentrated on gaseous materials such as ozone (O(3)) and nitrogen dioxide (NO(2)), as well as particulate matter (PM), generated by car traffic and industry. Diesel exhaust particulate (DEP) has the ability to bind proteins and may serve as a potential carrier of allergens, penetrating deep into respiratory tract. Among the most extensively studied environmental factors influencing allergy are airborne allergens: dust mites, pollens, fungi and animal dander. Foods may elicit both true IgE-mediated allergy and also various non-immunological reactions, associated with direct release of mediators or toxic activity. It has been estimated, that over 85,000 chemicals are recognized in the human environment and they may act as contact allergens or irritants, causing allergic or non-allergic contact dermatitis. Among them metals, fragrances, preservatives, botanicals and paraphenylenediamine are considered as the most significant. Infections have always been associated with etiopathogenesis of allergic diseases and they may contribute to exacerbation of their course.

Transdermal therapeutic systems (TTS) belong to the widely used methods of drug administration, which allow rate-controlled drug delivery and avoidance of first-pass metabolism in the liver Beside scopolamine, nitroglycerin (glyceryl trinitrate), nicotine, clonidine and fentanyl, also transdermal delivery of sex steroids for hormone replacement therapy and contraception is a well-known and popular method in daily clinical practice. It is estimated that approximately 20% of patients using transdermal estradiol may complain of adverse cutaneous side effects. Most of those reactions are mild or moderate, usually limited to the area of drug application. However, prolonged use may increase the chance of developing sensitization. The purpose of this review is to provide up-to date information on the spectrum of cutaneous reactions caused by TTS and the characteristics of potential contact allergens, including sex hormones. Proper management and prophylactic measures were also included.

Introduction and Objective: Sunlight is the major source of the energy on Earth. Visible light, ultraviolet and infrared radiation are necessary to sustain life on our planet. However, besides the range of positive effects, such as photosynthesis in plants, warmth, vision, and synthesis of vitamin D, sunlight may also be responsible for negative biologic effects - sunburn, induction of photodermatoses or carcinogenesis. Ultraviolet is regarded as the major environmental, physical hazard to the human skin., Abbreviated Description of the State of Knowledge: The acute clinical effect of ultraviolet involves melanogenesis, i.e. tanning, which protects from sunburn if exposure is overdosed. A single exposure, as well as acute suberythemal irradiation, suppresses sensitization of the contact hypersensitivity. The chronic biological effects are photoageing and skin cancer, especially squamous cell carcinoma (SCC). Vitamin D synthesis is regarded as a benefit of natural acute and chronic exposure to ultraviolet. Ultraviolet also plays an important role in aetiology of the group of disorders characterized by photosensitivity. On the other hand ultraviolet is a known inducer of immunosuppression in the skin; therefore, phototherapy is a therapeutic option for patients with activation of dermal immunity., Summary: Without sunlight, the existence of life on Earth is not possible. On the other hand, UVR radiation is regarded as representing one of the most important environmental hazards for human skin. For a better understanding of the mechanisms related to the influence of UVR on human skin, and the most dangerous chronic effects of carcinogenesis, it is necessary to undertake some protective activities. Moreover, UVR may become our ally in the treatment of selected skin disorders.