Effectiveness of PUVA vs. UVA1 phototherapy in the treatment of morphea patients.

Introduction: Morphea (localized scleroderma) is an inflammatory connective tissue disease, characterized by immune system dysfunction, vasculopathy and skin fibrosing. Phototherapy has been found to be effective in treating localized scleroderma. Psoralen + ultraviolet A (PUVA) and ultraviolet A1 (UVA1) phototherapy significantly enriched therapeutic possibilities. Aim: To compare the clinical effect of PUVA photochemotherapy and UVA1 phototherapy and to evaluate the treatment response rates. Material and methods: It was a retrospective one-centre research and observational study of all morphea patients treated with PUVA and UVA phototherapy. We reviewed phototherapy notes along with electronic and paper case records for all patients with morphea treated with PUVA and UVA1 phototherapy from January 2010 to December 2019. Results: The study shows that patients in both groups experienced improvement based on clinical measures, resulting in a reduction in the clinical score in all groups. There is positive short- and long-term efficacy of UVA1 and PUVA phototherapy in patients with morphea. There were no statistical differences between the treatment response rates. Limitations: We had a relatively small study sample and it was a retrospective, observational study. Conclusions: Our data suggest that ultraviolet PUVA and UVA1 should be considered for the treatment of morphea with disseminated lesions or not responding to topical treatment. UVA1 is free of side effects linked to oral psoralens such as nausea, vomiting, photokeratosis, but we showed that there was no statistical advantage in the effectiveness of both. UVA1 phototherapy is, however, a less accessible form of treatment, available in the centres of higher quality.

Oral mucosal lesions in psoriatic patients based on disease severity and treatment approach.

BACKGROUND: This observational case-control study was designed to investigate the frequency of oral lesions in psoriatic patients and to identify an association between mucosal involvement, the severity of the disease, and a form of treatment. METHODS: One hundred twenty-seven patients diagnosed with psoriasis were enrolled in this study from November 2018 to September 2019. The oral mucosa evaluation was based on the clinical appearance, location, and morphology of the lesions. All patients completed a general medical history and a Dermatology Life Quality Index (DLQI) questionnaire. The severity of skin involvement was assessed using the Psoriasis Area and Severity Index (PASI) scale. RESULTS: The most common oral lesions in patients with psoriasis were found to be fissured (FT), white coated (CT), and geographic tongue (GT). A significantly lower prevalence of GT was evident in the group managed with a new class of biological drugs and smokers. There appeared to be no association between the oral manifestation and the PASI score. FT appeared significantly more often in patients that experienced an extremely large effect of psoriasis on their quality of life as determined by the DLQI questionnaire and smokers. Only 25% of patients presented normal oral mucosa. CONCLUSIONS: Tongue lesions seem to be associated with skin psoriasis regardless of the treatment. The severity of the disease, according to the PASI scale, does not influence mucosal involvement. The type of treatment may affect the prevalence of oral lesions. Further investigations are required to confirm the influence of biological therapies on mucosal improvement.

Secondary failure of TNF-α inhibitors in clinical practice.

Tumor necrosis factor alpha (TNF-α) is a leading inflammatory cytokine that plays a pivotal role in the pathogenesis of psoriasis. In case of a severe course of psoriasis and moderate-to-severe disease in which traditional systemic treatments are ineffective or contraindicated, TNF-α inhibitors (iTNF-α) are used. This class of drugs includes monoclonal antibodies and a fusion protein (etanercept) and can induce a humoral or cell-mediated immune response, leading to formation of anti-drug antibodies (ADAs). The immunogenicity may affect iTNF-α drug pharmacokinetics, which would lead to hampering the clinical response (secondary drug failure), so a need to increase the drug dose arises. Antibodies against monoclonal antibodies (adalimumab, infliximab) have been associated with diminished clinical response, while against etanercept are non-neutralizing and appear to have no significant effect on clinical response and treatment safety. Switching of biologic agents may be one strategy in ADA-associated secondary failure of iTNF-α. However researches are needed to identify risk factors for ADA development and investigate management strategies for optimized treatment response. The authors reviewed the literature on the effectiveness of iTNF-α and pointed out the prevention of secondary failure in clinical practice.

Genetic polymorphism in psoriasis and its meaning for the treatment efficacy in the future.

The concept of personalized medicine is a new individualized approach which helps application of the targeted therapy. In fact, tailored medicine is mostly present in the field of life-threatening diseases such as oncology. However, skin diseases as such might be regarded as a potential area of implementation of this approach in the future. Stratified medicine in polygenetic and heterogeneous diseases, such as psoriasis, is more complex. Rapid development of science and novel molecular techniques led to better understanding of molecular pathogenetic pathways of many diseases including psoriasis. Identification of the particular immunopathogenetic pathways led to further development of targeted therapies such as biologic drugs. Actually the goal of individualized therapy is to determine the identical homogenous subgroups of patients, according to a biomarker, in which the response to that therapy will be the best and will carry the lowest risk of side effects. This review attempts to analyze the associations between polymorphisms of certain genes and the increased risk of developing psoriasis or psoriatic arthritis. The review of literature has also included the studies investigating the associations between gene polymorphisms and response to biologic therapy in psoriasis and psoriatic arthritis patients.

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.

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.

The role of dendritic cells and regulatory T cells in the pathogenesis of morphea.

Morphea is one of diseases characterised by fibrosis of the skin and subcutaneous tissue. It is a chronic disease that does not shorten the life of the patient, yet significantly affects its quality. The group of factors responsible for its pathogenesis is thought to include disturbed functioning of endothelial cells as well as immune disturbances leading to chronic inflammatory conditions, accompanied by increased production of collagen and of other extracellular matrix components. Dendritic cells (DC) are a type of professional antigen-presenting cells and can be found in almost all body tissues. Individual investigations have demonstrated high numbers of plasmacytoid DC (pDC) in morphoeic skin lesions, within deeper dermal layers, around blood vessels, and around collagen fibres in subcutaneous tissue. It appears that DC has a more pronounced role in the development of inflammation and T cell activation in morphea, as compared to systemic sclerosis (SSc). Regulatory T (Treg) cells represent a subpopulation of T cells with immunosuppressive properties. Recent studies have drawn attention to the important role played by Treg in the process of autoimmunisation. Just a few studies have demonstrated a decrease in the number and activity of Treg in patients with SSc, and only such studies involve morphea. This article reviews recent studies on the role of DC and regulatory T cells in the pathogenesis of morphea. Moreover, mechanisms of phototherapy and potential therapeutic targets in the treatment of morphea are discussed in this context.

The role of selectins in alopecia areata.

INTRODUCTION: One of the main histopathological features of alopecia areata (AA) is a lymphocytic infiltration that surrounds hair follicles. Soluble forms of E, L, P-selectins are known indicators of ongoing inflammation. There are no studies regarding the assessment of their contribution in AA. AIM: To assess serum concentrations of selectins (E-selectin, L-selectin and P-selectin) in patients with AA in relation to selected clinical parameters, including disease severity and activity. MATERIAL AND METHODS: Sixty-four patients with AA were involved in the study. The diagnosis was based on physical examination and photodermoscopy. The control group consisted of 40 healthy subjects. The serum concentrations of soluble E-selectin, L-selectin and P-selectin were detected with ELISA method. RESULTS: Statistically significantly higher levels of E, P, L-selectins were found in AA patients as compared with the healthy group. Serum concentrations of soluble forms of E- and L-selectins correlated with the severity of the disease, while E-selectin with activity of AA. CONCLUSIONS: This study shows that selectins may play an important role in the pathogenesis of AA and may be a target of future therapies in this disease.

"Assessment of chronic sclerodermoid Graft-versus-Host Disease patients, using 20 MHz high-frequency ultrasonography and cutometer methods".

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.

[Selected vulvar dermatoses]. / Wybrane dermatozy sromu.

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.

Scleromyxedema: a rare disorder and its treatment difficulties.

Scleromyxedema is a rare progressive cutaneous mucinosis, usually associated with a systemic involvement and paraproteinemia. Its aetiology remains unknown. The therapeutic options include numerous treatment modalities, however, no standard treatment exists as the rarity of this disease prevents the execution of controlled therapeutic trials. This paper reports a case of a 38-year-old male with progressive scleromyxedema associated with gammopathy. Initially, the patient was treated with prednisolone and later etretinate was added to the therapeutic schedule with quite good clinical improvement. However, after 6 months of treatment, several adverse effects were observed: hypercholesterolemia, hypertriglyceridaemia and cataract of the right eye. The patient was consulted by dermatologists in Warsaw and Gdansk as well as by a haematologist. The patient was excluded from oncological treatment. Melphalan therapy was not recommended as it is associated with very toxic side effects. IVIG treatment (intravenous immunoglobulin) was not initiated because of financial issues. As the disease progressed, treatment with plasmapheresis was introduced. The patient received 4 cycles of the therapy. It was well-tolerated by the patient and gave satisfactory, but temporary results. In order to obtain long-lasting improvement the patient was treated with IVIG (21.0 g/dose for 5 consecutive days). This treatment modality seems to have resulted in a more stable improvement.

Co-occurrence of acanthosis nigricans and bladder adenocarcinoma - case report.

Acanthosis nigricans (AN) is characterized by the occurrence of symmetrical velvety hyperpigmented plaques that can be observed in each location on the skin. However, the lesions are most frequently located in the axillary, inguinal and nuchal areas. Primarily, the lesions appear as hyperpigmented focuses which later transform into papillary lesions. There are two forms of the disease - benign and malignant. Malignant AN is considered to represent paraneoplastic syndrome co-occurring with advanced cancer, but as such it is not malignant. This article presents a case of a patient diagnosed with AN and coexisting bladder cancer and discusses the case in the context of available literature.

Seemingly healthy skin in atopic dermatitis: observations with the use of high-frequency ultrasonography, preliminary study.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disorder which is strictly determined by the epidermal barrier function. In previous studies, there is conclusive evidence that normal-looking, nonlesional skin presents meaningful barrier function defect and a sub-clinical eczematous skin reaction. AIM: The authors intended to visualize nonlesional AD skin with the use of high frequency ultrasonography to show that the normal-looking, nonlesional skin may present significant abnormalities in USG examination. METHODS: We have performed analysis with the use of high-frequency 20 MHz skin sonography in the cases of 15 AD patients of the Department of Dermatology, Medical University, Poznan, Poland. The clinical score has been evaluated on the basis of W-AZS index and EASI. The results were presented in the form of ultrasonographic images. RESULTS: High frequency ultrasonography revealed an echopoor band within nonlesional skin of six (40%) examined AD patients and in all cases within skin lesions. CONCLUSION: Our results indicate the significant role of skin ultrasonography in the complete clinical evaluation of patients with AD, which may serve as an element in selection of the most appropriate topical treatment. An echopoor band beneath the echo entry within nonlesional skin of some AD patients may reflect subclinical eczematous reaction and the readiness for the development of typical skin lesions. For this purpose, we suggest to name an intact skin in AD as seemingly healthy skin.

Treatment of genital lichen sclerosus in women--review.

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

Serological Evidence of Borrelia burgdorferi in Patients with Morphea from West-Central Poland: An Original Paper and Review of Literature.

Morphea (localized scleroderma) is an inflammatory connective tissue disease. Borrelia burgdorferi, as a causative factor, has been discussed controversially. The aim of this original study was to evaluate the frequency of IgM and IgG classes of anti-Borrelia antibodies in groups of morphea and psoriasis patients using the traditional ELISA method. Blood samples of 82 patients with morphea and 112 patients with psoriasis vulgaris were examined for the presence of IgM and IgG classes of anti-Borrelia antibodies (ELISA). IgM and IgG classes of anti-Borrelia antibodies were detected in 4% of blood samples taken from morphea patients, while 4.5% of blood samples from patients with psoriasis vulgaris. There is one major limitation in this study that could be addressed in future research. First, the study focused on the determination of IgM and IgG classes of anti-Borrelia antibodies as a risk factor for morphea, but other infectious agents also require further testing, such as Hepatitis B, Hepatitis C, and other viral or bacterial infections. The results of this study showed no significant relationship between Borrelia infection and morphea. Detection of IgM and IgG classes of anti-Borrelia antibodies is not recommended for routine diagnostics of patients with morphea at this time.

Eosinophilic fascitis: a report of two cases treated with ultraviolet A1 phototherapy.

Eosinophilic fascitis (EF) (synonyms: Shulman's syndrome, diffuse fascitis with eosinophilia) is a disease characterized by a complex set of symptoms with scleroderma-like skin lesions, the absence of Raynaud's phenomenon and other non-mandatory symptoms including eosinophilia, elevated erythrocyte sedimentation rate, hypergammaglobulinemia and high levels of circulating immune complexes. EF is probably not a separate disease entity, but an acute variant of localized scleroderma. This rare disease of unknown etiology is usually seen in middle-aged adults. Sclerodermiform indurations without Raynaud's symptoms develop rapidly usually on the extremities and more rarely on the trunk or the face. The skin becomes hard, tightly bound to the underlying structures, so that contractures can develop in as little as a few weeks. The course of the disease is usually chronic but spontaneous remission is possible. Standard therapy includes high doses of corticosteroids, immunosuppressive drugs such as methotrexate, cyclosporin A, cyclophosphamide or azathioprine and others such as psoralen and ultraviolet A radiation.

Calcipotriol/betamethasone ointment compared to narrow-band UVB in plaque psoriasis: first clinical and ultrasonographic study.

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.

Expression of selected genes of dendritic and Treg cells in blood and skin of morphea patients treated with UVA1 phototherapy.

INTRODUCTION: Morphea is a chronic autoimmune disease characterized by fibrosis of the skin. Dendritic cells (DC) and regulatory T cells (Tregs) play a significant role in development of autoimmune and tolerance mechanisms. The aim of the study was to establish the expression of selected genes of plasmacytoid and myeloid DC, Treg cells, and the microenvironment of cytokines (interleukin-17A (IL-17A), transforming growth factor ß (TGF-ß)) in blood and skin of morphea patients. In addition, the effect of UVA1 phototherapy on expression of the aforementioned genes was evaluated. MATERIAL AND METHODS: The study was performed on 15 blood and 10 skin samples from patients with morphea. The evaluation included expression of CLEC4C (C-type lectin domain family 4, member C receptor), Lymphocyte antigen 75 (LY75), Forkhead box p3 (foxp3) transcription factor, IL-17A and TGF-ß genes in peripheral blood mononuclear cells (PBMC) and in skin samples both before and after UVA1 phototherapy using real-time polymerase chain reaction. RESULTS: The study revealed lower expression of CLEC4C before (p = 0.010) and after (p = 0.009) phototherapy and lower expression of IL-17A before (p = 0.038) phototherapy in PBMC of patients with morphea vs. the control group. Expression of CLEC4C in PBMC correlated negatively (rho = -0.90; p = 0.001) with activity of disease after phototherapy. No significant differences were found between expression of analysed genes before and after UVA1 therapy in PBMC and skin of morphea patients. CONCLUSIONS: The results do not confirm the involvement of analysed subsets of DC and Tregs in UVA1 phototherapy in morphea, but point to CLEC4C as a possible biomarker associated with the disease activity.

High-frequency ultrasonography in objective evaluation of the efficacy of PUVA and UVA 1 phototherapy in mycosis fungoides.

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.