Agnieszka Osmola-Mańkowska

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

Eosinophilic fascitis (EF) (synonyms: Shulmans syndrome, diffuse fascitis with eosinophilia) is a disease characterized by a complex set of symptoms with scleroderma‐like skin lesions, the absence of Raynauds 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 Raynauds 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.

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.

Expression of selected human endogenous retroviral sequences in skin and peripheral blood mononuclear cells in morphea.

Introduction Morphea or localized scleroderma is a relatively rare disease whose main symptom is excessive skin fibrosis. Here we focus on the involvement of human endogenous retroviruses (HERVs) in morphea. The HERVs are a vast and intensely growing field in genomics. HERVs are of special interest as far as autoimmune disorders are concerned, yet little effort has been made until now to assess the possible changes of their expression in morphea. Material and methods Six sequences of particular interest were chosen for this study. Real-time polymerase chain reaction was performed on samples derived from peripheral blood mononuclear cells (PBMCs) and skin biopsies. The results were normalized to the level of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) transcription. Results In PBMCs we found a statistically significant decrease of transcription of HERV-E pol, while HERV-K env, HERV-R pol-env, and HERV-W env were found to be up-regulated. In skin biopsies HERV-K env was strongly up-regulated. On the other hand, we noted a decrease of transcription of HERV-H env 62, HERV-K10 gag, HERV-R pol-env, and HERV-W env. In PBMCs we found a statistically significant decrease of transcription of HERV-E pol (–81.8%, p < 0.001), while HERV-K env (+94.1%, p = 0.010), HERV-R pol-env (+140.0%, p < 0.001), and HERV-W env (+97.7%, p < 0.001) were found to be up-regulated. In skin biopsies HERV-K env was strongly up-regulated (+713.0%, p = 0.003). On the other hand, we noted a decrease of transcription of HERV-H env 62 (–83.5%, p < 0.001, HERV-K10 gag (-33.7%, p = 0.044), HERV-R pol-env (–71.3%, p < 0.001), and HERV-W env (–59.3%, p = 0.029). Conclusions The studied HERV sequences generally show an increase of transcription in PBMCs of morphea patients, while being down-regulated in their skin, with some exceptions for both types of tissue.

“Assessment of chronic sclerodermoid Graft-versus-Host Disease patients, using 20MHz 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.

Nonlesional skin in atopic dermatitis is seemingly healthy skin - observations using noninvasive methods.

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.

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.

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.

High-frequency ultrasonography-New non-invasive method in assessment of skin lymphomas

Mycosis fingoides (MF) is the most common subtype of primary cutaneous T‐cell lymphomas. Current evaluation of disease extent and severity is based on mSWAT scoring system, which seems to be relatively subjective. The aim of this subject was to present the usefulness of 20 MHz in objective 5‐year long monitoring of response to therapy in MF patients.

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.

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.