Cellulite: a cosmetic or systemic issue? Contemporary views on the etiopathogenesis of cellulite.

Cellulite (also known as gynoid lipodystrophy or orange peel syndrome) is one of the most common lipodystrophy syndromes, which affects millions of post-adolescent women. Cellulite is manifested by topographic disorders of subcutaneous tissue such as nodules, edema, and abnormal fibrosis. It is located mainly on the pelvic area, especially on the buttocks. Its pathogenesis is complexed and unclear. There are several theories about its pathophysiology. Hormonal disorders, endothelial dysfunction and genetic predispositions are taken under consideration.

Long-term treatment of chronic plaque psoriasis with biological drugs can control platelet activation: targeting the bridge between inflammation and atherothrombosis.

INTRODUCTION: Platelet activation is elevated in moderate to severe psoriasis, and the reduction in platelet activation during short-term treatment has already been demonstrated. Soluble P-selectin is a well-established marker of platelet activation. AIM: To show whether the long-term treatment of psoriasis with biological drugs can reduce elevated platelet activation. MATERIAL AND METHODS: An observational study of 27 patients with chronic plaque psoriasis, treated with infliximab, adalimumab, etanercept, or ustekinumab for up to 12 months was conducted. Psoriasis area and severity index (PASI), serum P-selectin and interleukin (IL)-6 were monitored throughout the treatment. RESULTS: There was no significant correlation between PASI and platelet activation in our patients. After 3 months of treatment, a significant reduction in PASI and IL-6 was found, while P-selectin was not significantly reduced. When a cohort of patients who had shown elevated P-selectin prior to the treatment was evaluated, a significant reduction in P-selectin was observed in all 8 patients following 3 months; a reduction that was sustained after 6 and 12 months of therapy. CONCLUSIONS: We conclude that PASI is not a good predictor of platelet activity in patients with PASI near to 10. Biological drugs reduce platelet activation in patients who have increased platelet activation prior to treatment, and this effect is stable during chronic therapy.

Medium dose ultraviolet A1 phototherapy and mRNA expression of interleukin 8, interferon γ, and chemokine receptor 4 in acute skin lesions in atopic dermatitis.

INTRODUCTION: Mechanisms responsible for UVA1 efficacy in atopic dermatitis (AD) are not fully elucidated. AIM: To investigate IL-8, CCR-4, and IFN-γ mRNA expression in AD before and after UVA1, to identify correlations among them, and to determine whether and to what degree mRNA expression is influenced by UVA1. MATERIAL AND METHODS: Twenty-five patients with AD underwent medium dose UVA1-phototherapy at daily dosages of 10, 20, 30, 45, and then continuing 45 J/cm(2) up to 20 days, from Monday to Friday for 4 weeks. Before and after UVA1, biopsies from acute skin lesions were studied using reverse-transcription and RT-PCR. RESULTS: The levels of CCR-4 mRNA correlated with those of IFN-γ, both before and after UVA1 phototherapy (p < 0.05). A significant correlation was found after UVA1 between mRNA levels of IL-8 and IFN-γ (p < 0.05). After UVA1 an increase in IL-8 mRNA expression in comparison to the baseline assessment (p = 0.02) was found, while no significant difference was revealed in the expression of CCR-4 and IFN-γ mRNA. UVA1 improved both SCORAD and severity of AD (p < 0.001). SCORAD and the severity of AD did not correlate with the degree of expression of measured cytokine mRNA, neither before nor after UVA1. CONCLUSIONS: CCR-4 is expressed in parallel with IFN-γ in acute skin lesions of patients with AD both before and after UVA1 phototherapy. UVA1 significantly improves SCORAD index, lessens the severity of AD and increases the expression of IL-8, with no direct effects on other studied molecules.

[Skin diseases associated with hepatitis C virus]. / Dermatozy wspólistniejace z wirusowymi chorobami watroby.

Chronic hepatic diseases caused by HBV or HCV infection not always demonstrate evident clinical symptoms of liver disease. Non-specific extrahepatic symptoms mainly skin leasions are helpful for establishing the proper diagnosis. This review illustrates the pathogenesis, epidemiology and clinical manifestations of HBV and HCV infections with a special attention to skin signs and symptoms which can associate these infections.

Topical steroid therapy in atopic dermatitis in theory and practice.

INTRODUCTION: Topical glucocorticosteroids (GCSs) are commonly used in treatment of atopic dermatitis (AD). AIM: To assess the patients' compliance with the recommended instructions of the therapy. MATERIAL AND METHODS: The study involved 141 adult AD patients. The clinical course of AD and its treatment with GCSs during the last year were analysed. RESULTS: In the periods of exacerbation the lesions involved 10-50% of the skin surface area. Outpatient treatment in specialised dermatological and/or allergology clinics was given to 93% of the study subjects. Sixty-five out of 141 patients regularly attended medical control examinations. Glucocorticosteroids, mostly very potent ones (70.2%), were applied to all the subjects. 66.7% of patients obtained no information about their medications' anti-inflammatory potential. The substances were applied more frequently than twice daily by 36.4% of the patients. Seventy-two of 141 subjects applied GCSs both temporarily and in the long-term treatment, for 8.3 weeks on average. In the long-term treatment, in which very potent GCSs predominated (70.7%), no one used intermittent therapy. One hundred and thirty patients introduced their own modifications to the instructions concerning GCSs use, among which 37.7% changed the site of application, 58.5% prolonged the duration of application and 49.5% shortened it or occasionally temporarily withdrew the prescribed drug. None of the patients knew the fingertip unit method of dose assessment. Apart from steroid therapy, 56.7% of the patients carried out regular care treatment. CONCLUSIONS: The AD patients need to be thoroughly educated by the medical staff in the topical GCSs therapy in atopic dermatitis.

Disturbed balance between serum levels of receptor tyrosine kinases Tie-1, Tie-2 and angiopoietins in systemic sclerosis.

OBJECTIVE: The aim of this study was to determine the characteristic factors for vascular development and maintenance levels as well as correlation between Tie-1 receptors, Tie-2 receptors and the corresponding ligands--angiopoietins--in systemic sclerosis (SSc) patients. MATERIALS AND METHODS: Serum levels of Tie-1, Tie-2, Ang-1 and Ang-2 were measured in 25 SSc patients and healthy controls. RESULTS: There was a statistically significant difference in serum Tie-1 (p = 0.009) and Ang-2 (p = 0.001) levels in SSc patients compared with healthy controls. Significant correlations between Tie-1 and Tie-2 (ρ = 0.70, p = 0.0001) and between Tie-1 and Ang-2 (ρ = -0.92, p = 0.002) were found in the SSc group. Serum levels of Tie-2 were positively associated with esophagus changes (U = 2.03, p = 0.041) and Ang-1 was negatively correlated with duration of Raynaud's phenomenon (ρ = -0.75, p = 0.00008). CONCLUSION: The increase in serum concentration of Tie-1 and Ang-2 in patients with SSc may confirm a molecular imbalance between receptor tyrosine kinases Tie and their ligands.

Can biologic treatment induce cutaneous focal mucinosis?

Skin mucinosis is a rare skin disease which clinically manifests as firm papules and waxy nodules. We report a case of a 66-year-old female psoriatic patient who developed skin mucinosis during biological therapy. Because of a previous lack of response to the local and conventional systemic treatment of psoriasis, the patient received biological therapy (infliximab from June 2008 to May 2009 - initial clinical improvement and loss of treatment effectiveness in the 36(th) week of the therapy; adalimumab from June 2009 to January 2010 - lack effectiveness; ustekinumab from March 2012 to the present). Throughout 2 months we observed a manifestation of the skin mucinosis as well-demarcated, yellow and brown, papulo-nodular lesions of 5-10 mm in diameter, localized on the back. Histopathological examination with alcian blue staining demonstrated mucin deposits in the dermis. On the basis of clinical and histopathological findings, the diagnosis of cutaneous focal mucinosis was established. We present the case because of the extremely rare occurrence of the disease. Scarce literature and data suggest that there is an association between focal mucinosis and thyroid dysfunction, as well as possible adverse effects of biological therapy with TNF-α antagonists.

Vitamin D effects in atopic dermatitis.

BACKGROUND: Because vitamin D has immunomodulatory properties and immunologic mechanisms play a role in the pathogenesis of atopic dermatitis (AD), it is possible that vitamin D may influence the activity of AD. OBJECTIVE: The aim of the study was to correlate vitamin D concentrations in patients who had AD with clinical, immunologic, constitutional, and environmental factors, and to determine if vitamin D supplementation affects the clinical manifestations of AD. METHODS: Clinical and laboratory parameters of 95 patients with AD and 58 control subjects were measured. Severity of AD was assessed with the SCORAD index. RESULTS: The mean serum concentration of 25(OH)D3 in patients with AD was not statistically different from control subjects. The frequency of bacterial skin infections was higher in patients with AD who had lower 25(OH)D3 levels. No statistical associations between vitamin D levels and other multiple laboratory and clinical parameters were found. After supplementation both mean objective SCORAD and SCORAD index were significantly lower (P < .05). LIMITATIONS: All study patients were Caucasians and only one supplemental vitamin D dose and treatment duration were assessed. CONCLUSION: The results from this study indicate that vitamin D supplementation may help ameliorate clinical signs of the disease and can be considered as a safe and well-tolerated form of therapy.

IL-17 expression in dermatitis herpetiformis and bullous pemphigoid.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP.

Antinuclear antibodies in rosacea patients.

INTRODUCTION: Rosacea is a common inflammatory disorder, characterized by a spectrum of facial manifestations. The clinical similarity to other dermatoses, like lupus erythematosus, might lead to misdiagnosis, particularly in patients with elevated antinuclear antibody titers. AIM: To assess the frequency, titer and specificity of antinuclear antibodies in rosacea patients and correlate these findings with clinical features. MATERIAL AND METHODS: The study included 101 rosacea patients and 26 sex- and age-matched controls. Immunofluorescence antinuclear antibody testing was performed on HEp-2 substrates. Patients' sera with ANA titers of 1 : 160 or higher were evaluated by Euroline analysis. RESULTS: Over a half (53.5%) of rosacea patients had an ANA titer greater than or equal to 1 : 160. Within this group 13.86% had a titer of 1 : 320, 8.91% had a titer of 1 : 640, and 6.93% had a titer of 1 : 1,280 or higher. The specificity of these antibodies could not be identified. Elevated ANA titers were present more often in women (55.8%) than in men (44.15%). Only two of 26 healthy volunteers had elevated ANA titers. One had a titer of 1 : 160 and the other of 1 : 320. During a two-year observation period, after the initial ANA testing, none of the patients with ANA titers above 1 : 640 developed an apparent autoimmune disorder. CONCLUSIONS: Elevated ANA titers are commonly found in rosacea patients, what with simultaneously existing facial erythema and photosensitivity might lead to misdiagnosis of lupus erythematosus. Clinicians should beware of these findings to avoid misdiagnosing lupus erythematosus in rosacea patients with elevated ANA titers.

Expression of selected neuropeptides in pathogenesis of bullous pemphigoid and dermatitis herpetiformis.

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are chronic subepidermal bullous diseases, which progress together with an itch and an inflammatory reaction. These symptoms may be the cause of a phenomenon described in the literature as a neurogenic skin inflammation. Neuropeptides are one of the mediators which take part in this process. The aim of our study was to indicate the expression of selected neuropeptides - CRF (corticotropin releasing factor), CGRP (calcitonin gene-related peptide), NKB (neurokinin B), SP (substance P) and the receptor for endothelin B (ETRB) - in the skin of patients suffering from BP or DH. A significantly increased expression of CRF was found in the specimen collected from the skin lesions of patients with BP and DH as well as a significantly increased expression of receptor for endothelin B in the patients with DH by the immunohistochemical method. The results obtained give evidence of a possible participation of CRF and receptor for endothelin B in the pathogenesis of the itch in the dermatitis herpetiformis as well as CRF in bullous pemphigoid.

[Medical and legal aspects of smoking]. / Medyczne i prawne aspekty palenia tytoniu.

Tobacco is known worldwide for several thousand years. Smoking is the strongest and most common type of addiction. The harmful effect of tobacco on the human body leads to the development of cancer, respiratory, cardiovascular, skin diseases. It was also noted adverse effects of tobacco on inflammatory and immunologic phenomena. Taken numerous legal actions aimed at reducing the negative health effects among smokers as well as measures to reduce exposure to tobacco smoke of people from the surroundings.

An enhanced risk of basal cell carcinoma is associated with particular polymorphisms in the VDR and MTHFR genes.

BACKGROUND: Vitamin D and folate are influenced by ultraviolet radiation (UVR), and both are implicated in skin carcinogenesis. Polymorphisms in the genes involved in the metabolism of these two compounds may alter the risk of basal cell carcinoma (BCC). OBJECTIVE: To assess the frequency of four polymorphisms in the gene encoding the vitamin D receptor (VDR) (FokI, BsmI, TaqI and ApaI) and two in the gene encoding methylenetetrahydrofolate reductase (MTHFR) (677C/T and 1286A/C) in 142 patients of Polish origin with BCC and the same number of controls. The expression of VDR and MTHFR proteins in the skin, and the vitamin D status of a subset of patients and controls were also measured. PATIENTS/METHODS: The polymorphisms were assayed by PCR-RFLP, the VDR and MTHFR proteins by immunoblotting and vitamin D status as 25-hydroxyvitamin D (25(OH)D) level in the serum by RIA. RESULTS: The presence of the TT genotype in the FokI VDR polymorphism resulted in a >10-fold higher risk of BCC development. The CT genotype in 677C/T MTHFR polymorphism and CC genotype in 1286A/C MTHFR polymorphism also significantly increased the risk of BCC development. The expression of the VDR and MTHFR proteins was significantly higher in BCCs of the patients than in the healthy skin of the controls. The median serum level of 25(OH)D was significantly higher in the control group compared with the patients with BCC. CONCLUSIONS: Certain VDR and MTHFR gene polymorphisms increase the risk of BCC development in individuals of Polish origin.

Combined occurrence of filaggrin mutations and IL-10 or IL-13 polymorphisms predisposes to atopic dermatitis.

BACKGROUND: Although filaggrin mutations are presently believed to play a key role in the development of atopic dermatitis (AD), obviously also immunological factors involved in acquired immune response are important for the development of allergic inflammation. OBJECTIVE: To assess the frequency of FLG mutations and the polymorphisms 590 C/T in the IL-4 gene, -1082A/G in the IL-10 gene and -1055C/T in the IL-13 gene in patients with AD and their correlations between severity of AD and asthma. METHODS: R501X and 2282del4 FLG mutations and IL-4, IL-10 and IL-13 polymorphisms were assayed in 163 patients with AD of Polish origin. RESULTS: In the Polish patients with AD, the prevalence of FLG mutations was higher in patients with AD than in the controls and 2282del4 FLG mutation was more frequent than R501X, and it was associated with a 6-fold higher risk for AD development (P < 0.001; OR: 5.76), moderate or severe disease course, early onset of asthma and palmar hyperlinearity. Significant interactions between the 2282del4 FLG mutation and the CT genotype for IL-13 or GG genotype for IL-10 and a higher risk for developing AD were demonstrated. CONCLUSION: FLG mutation, alone and in combination with certain IL-10 or IL-13 polymorphisms, enhances the risk for the development of AD in the Polish population.

Vitamin D serum level changes in psoriatic patients treated with narrowband ultraviolet B phototherapy are related to the season of the irradiation.

BACKGROUND: Vitamin D is produced in the human skin by short wavelength (290-315 nm) ultraviolet (UV) radiation. PURPOSE: The aim of the study was to investigate how outdoor conditions may influence the serum levels of 25(OH) vitamin D in psoriasis patients under narrowband ultraviolet B (UVB) phototherapy. METHODS: The winter and summer groups of patients received almost the same narrowband UV (nUVB) doses during whole-body phototherapy. The 25(OH)D serum concentration was measured before and after two series of 10 exposures. The cabinet doses were compared with potentially available cumulative solar doses. The solar doses (unweighted UVB and vitamin D effective dose) and duration of solar intensity sufficient to produce vitamin D were calculated using a model based on local atmospheric data. RESULTS: After an initial 10 nUVB treatments, 25(OH)D serum concentration increased by 68% for winter patients in relation to the level before therapy, whereas a 20% increase was found for the summer patients. The next 10 treatments caused a much lower increase in 25(OH)D concentration: 5% and 3.5% for the winter and summer patients, respectively. No statistically significant relationship was observed between post-therapy 25(OH)D serum concentration and solar radiation variability. CONCLUSIONS: The different baseline values of 25(OH)D serum levels in winter and summer patients result from seasonal variability in solar irradiance. Thus, outdoor solar radiation affects the patients over a much longer period, and artificial UV light is the main factor responsible for increase in 25(OH)D serum level over a 30-day period of cabinet therapy.

Psychiatric disorders in patients with systemic lupus erythematosus: association of anxiety disorder with shorter disease duration.

Physicians' awareness about neuropsychiatric syndromes in systemic lupus erythematosus (SLE) is not rarely limited to seizures and psychoses included in the American College of Rheumatology (ACR) classification. Involvement of the central nervous system (CNS) with its rich symptomatology still belongs to the faintly recognised and understood aspects of lupus. The objective was to investigate prevalence and clinical correlations of psychiatric disorders in SLE patients. Fifty-two SLE patients were included. Disease duration and current and cumulative corticosteroid doses were calculated. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM). All subjects were examined by a psychiatrist. Psychiatric disorders were classified according to ACR criteria for neuropsychiatric systemic lupus erythematosus (NPSLE). Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) were used to screen for cognitive impairments. Mental disorders were diagnosed in 16 (30.77%), depressive disorder in 6 (11.54%), cognitive dysfunction in 5 (9.62%), anxiety disorder in 4 (7.69%) and psychosis in one patient (1.92%). SLE duration was shorter in patients diagnosed with anxiety disorder (P < 0.05), and cumulative dose of corticosteroids was lower in patients with anxiety disorder (P < 0.01). There was high positive correlation between SLE duration and cumulative dose of corticosteroids (r = 0.684, P < 0.001). Shorter SLE duration in patients with anxiety disorder seems to reflect its adaptative nature.

Psoriasis rupioides: a rare variant of a common disease.

Psoriasis lesions typically are classified by their morphologic appearance and include plaque, guttate, pustular, and erythrodermic forms. Few review articles on psoriasis discuss the rare variant termed psoriasis rupioides. We report a case of psoriasis rupioides and discuss the unique features of this unusual form of psoriasis.

Persistent improvement of previously recalcitrant Hailey-Hailey disease with electron beam radiotherapy.

Hailey-Hailey disease, or familial benign chronic pemphigus, is an autosomal dominant genodermatosis. Disease symptoms may contribute to an adverse impact on quality of life and functional limitation and disability. As Hailey-Hailey disease is chronic and frequently recalcitrant to treatment, multiple therapeutic approaches, including surgical options, have been attempted. We describe here three cases of recalcitrant Hailey-Hailey disease that showed long-term improvement with radiotherapy. Axillary lesions were treated with electron beam at an anti-inflammatory dose (energy 6-8 MeV). Patients received 20 Gy in 10 fractions to 90% isodose, at each axilla. No disease recurrence was observed during a 38 months follow-up of the treated sites. The effect of radiotherapy was thus considered to be locally beneficial, but without any positive influence on the general course of the disease.

[Role of Toll-like receptors in etiology of selected diseases of the skin]. / Udzial receptorów Toll-like w patogenezie wybranych chorób skóry.

Toll-like receptors (TLR) play an important role in anti-infectious defense of organisms. So far in humans 10 receptors have been identified. They were classified into five different subfamilies according to their affinity to characteristic ligands. Every receptor has a similar structure (extracellular part, intramembrane part and cytoplasmic part), irrespective of a type of the ligands with which it reacts. Ligands are present on many cell types, including on those which make up the skin. That is why Toll-like receptors are an important part of the cutaneous, non-specific immunologic response. In the review problems associated with the structure and functions of Toll-like receptors are presented. Moreover, the latest information about the role of TLR in the etiology of some dermatoses (psoriasis, atopic dermatitis, acne vulgaris, rosacea, infections, systemic lupus erythematosus, mycosis fungoides) is discussed. In addition, therapeutic implications are described.

[The role of sonic hedgehog pathway in skin carcinogenesis]. / Rola sciezki przekazywania sygnalu sonic hedgehog w procesie skórnej kancerogenezy.

Non melanoma skin cancers (NMSC) involving basal (BCC)--and squamosus cell carcinomas (SCC) and are the most frequent skin cancers in Caucasians. Ultraviolet radiation is the main environmental risk factor for NMSC development. The aim of this paper is to review the latest opinions concerning the role of sonic hedgehog pathway in non-melanoma skin cancers development. Experimental data indicate that sonic hedgehog pathway might be involved in skin carcinogenesis. Under physiological conditions sonic hedgehog pathway is responsible for normal embryogenesis, regeneration of damaged tissues and for regulation of cell proliferation. It was revealed that UVR caused inactivated mutation in PATCHED gene encoding Ptch1 protein. These events lead to deregulation of sonic hedgehog pathway trough activation of Smo protein and Gli transcriptional factors what stimulates cell proliferation and in consequence NMSC development. Literature data indicate that understanding of molecular background of skin cancers might be a reason for introduction of new therapeutic approaches including sonic hedgehog pathway inhibitors.