Waldemar Placek

Neo-epitope tissue transglutaminase autoantibodies as a biomarker of the gluten sensitive skin disease — Dermatitis herpetiformis

BACKGROUND The deamidated gliadin peptides (DGP) cross linked to human tissue transglutaminase (tTg) comprises a novel neo-epitope structure (Neo-tTg) for serological screening of celiac disease (CD). Our aim is to verify anti-Neo-tTg IgA and IgG in adults with dermatitis herpetiformis (DH). METHODS Multi-centric retrospective evaluation of the IgA/G autoantibodies in sera of DH patients on a regular diet (n=40) and a gluten restricted diet (GRD, n=53) and control adults with autoimmune skin diseases (n=107) by ELISA. RESULTS The sensitivities of Celicheck Neo IgA/G (76%, 95% CI 67-84%) and the Neo tTg-A (85%, 95% CI 70-97%) ELISA were significantly greater than that of tTg-A (56%, 95% CI 46-67%), eTg-A (62%, 95% CI 52-72%), DGP-A (55%, 95% CI 55-65%), DGP-G (61%, 95% CI 51-71%), Glia-A (55%, 95% CI 45-65%) and Glia-G (56%, 95% CI 46-66%) ELISA. The specificities of all 8 ELISA were in the range of 90-100%. The area under the curve (AUC) of receiver operator characteristic curve (ROC) for the two Neo-tTg ELISA (0.863 and 0.949) were higher than the AUCs for ROCs of tTg, DGP and eTG ELISA (range between 0.657 and 0.783). The autoantibody levels of DH patients on a normal diet were significantly higher than those on GRD in the Celicheck Neo IgA/IgG, NeotTg-A; tTg-A and the eTg-A; ELISA (p<0.01) and of no significance in the DGP and Gliadin ELISA. CONCLUSION Neo-epitope IgA autoantibodies represent a new and sensitive serological marker of DH.

Interleukin-17 as a factor linking the pathogenesis of psoriasis with metabolic disorders

Psoriasis is a systemic disease with numerous concomitant metabolic disorders. Apparently, T‐helper 17 lymphocytes and interleukin (IL)‐17 constitute an important element linking those disorders. The role of IL‐17 has been confirmed by numerous studies, although it remains not completely understood, and the study results are controversial. Based on the studies performed so far, it is assumed that IL‐17 contributes to development of atherosclerosis by means of: stimulation of production of proinflammatory compounds; induction of apoptosis of endothelial cells and heart muscle cells; stimulation of von Willebrand factor production; and induction of the matrix metalloproteinase‐9 (atherosclerotic plaque rupture). On the other hand, IL‐17 may exert protective activity due to inhibition of proatherogenic interferon‐γ and vascular cell adhesion molecule‐1, and production of type I collagen by smooth muscle cells. The role of IL‐17 in the pathogenesis of obesity is as important as other proinflammatory cytokines. On the other hand, its deficiency increases diet‐induced obesity and accelerates adipose tissue accumulation. Although the role of IL‐17A in the pathogenesis of metabolic disorders in humans remains controversial, introduction of anti‐IL‐17A treatments brings hope that development of metabolic disorders in patients with psoriasis may be inhibited.

Transplantation of cultured autologous melanocytes: hope or danger?

Cultured human melanocytes are increasingly being used in the treatment of vitiligo. The growth media contain various types of mitogenic factors, both recombinant human (e.g., rhbFGF and rhSCF) and synthetic (e.g., TPA). High concentrations of mitogenic factors accelerate the cell cycle, and consequently may increase the risk of carcinogenesis of transplanted cells. Mutations of genes of the RAS/RAF/MEK/ERK signaling pathway are very often found in the early stages of the development of melanoma. TPA is considered to be an oncogenic factor, but so far there is no evidence to show that it is responsible for damage to the genetic material of cultured melanocytes. The aim of our study was to assess the risk of the development of mutations in selected genes of the RAS/RAF/MEK/ERK signaling pathway during the culturing of melanocytes in various growth media. Based on the results obtained, it can be concluded that TPA and high concentrations of other growth factors intensify the proliferation of melanocytes, without the risk of damage to the HRAS (exon 1 and 2), KRAS (exon 1 and 2), NRAS (exon 1 and 2), and BRAF (exon 11 and 15) genes. In order to assess the total safety of the transplantation of cultured melanocytes, it is necessary to carry out further studies on other signaling pathways as well as carry out biological tests on an animal model.

Influence of ustekinumab on body weight of patients with psoriasis: an initial report

Introduction Many recent epidemiological studies have shown the influence of treatment with anti-TNF-α on body mass of patients with psoriasis but there are no reports in the literature on the influence of ustekinumab on that parameter. Aim To review the effect of ustekinumab therapy on body weight in patients with psoriasis. Material and methods The examined group consisted of 11 patients with psoriasis treated at the Department and Clinic of Dermatology in Olsztyn. Patients’ body mass and body mass index (BMI) were evaluated prior to the first administration of the ustekinumab dose and at week 28 of treatment (the day of the fourth dose). Results Body mass increase was determined in 7 patients (64%), on average by 2.27 kg (p < 0.05), and the BMI increased by 3.35% (p < 0.1). Conclusions Observing a correlation between ustekinumab application and body mass increase, similar to the treatment with anti-TNF-α preparations, an attempt was undertaken at explaining that correlation by analysing the role of IL-12 and IL-23 in psoriasis pathogenesis. IL-12 and IL-23, by influencing the naïve lymphocytes T and stimulating their diversification towards Th1 and Th17, also, indirectly, cause an increase in TNF-α and other cytokines production (IL-2, IFN-γ, IL-17, IL-10, IL-22). Ustekinumab will then have a significant influence on decreasing the production of cytokines, which are important for metabolism and body mass.

Sweet's syndrome with idiopathic thrombocythemia

Diagnosis of paraneoplastic skin syndromes associating neoplastic processes is assumed as the crucial aspect of dermatological practice. Knowledge of clinical findings of dermatoses suggesting coincidence of malignant proliferative processes facilitates diagnostic and therapeutic procedures. We would like to present a case of Sweets syndrome, qualified for comparative paraneoplastic skin syndromes. Sweets syndrome, acute, febrile neutrophilic dermatosis, was first described by Robert Douglas Sweet in 1964 as a disorder characterized by fever, skin lesions of erythematous-infiltrative character, leukocytosis with neutrophilia and dense infiltrations of dermis by mature neutrophils. Sweets syndrome aetiology is not fully understood, although cytokine abnormalities suggest that Th1 lymphocytes play an important role in pathogenesis of the dermatosis. Factors inducing Sweets syndrome include: haematopoietic hyperplasia; neoplasms: genitourinary, breast, gastrointestinal; infections of the respiratory and alimentary system; inflammatory bowel diseases; drugs; pregnancy and vaccinations. Systemic corticosteroids are the “gold standard” of Sweets syndrome treatment; potassium iodide or colchicine may also be used. Indomethacin, clofazimine, cyclosporine A and sulfones are the second-line drugs.

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m2 per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.

The Use of Adipose-Derived Stem Cells in Selected Skin Diseases (Vitiligo, Alopecia, and Nonhealing Wounds)

The promising results derived from the use of adipose-derived stem cells (ADSCs) in many diseases are a subject of observation in preclinical studies. ADSCs seem to be the ideal cell population for the use in regenerative medicine due to their easy isolation, nonimmunogenic properties, multipotential nature, possibilities for differentiation into various cell lines, and potential for angiogenesis. This article reviews the current data on the use of ADSCs in the treatment of vitiligo, various types of hair loss, and the healing of chronic wounds.

Cognitive impairment in patients with severe psoriasis

Introduction Psoriasis is a chronic inflammatory skin disease, in which an important role is played by psychological factors. Aim To evaluate the frontal cognitive functions in patients with psoriasis. Material and methods The study included 188 subjects (97 patients with psoriasis and 91 healthy controls). To assess the dorsolateral prefrontal cortex functions, the Trail Making Test and the Stroop test were applied. Severity of psoriasis was assessed by means of the PASI index. Results Compared to healthy subjects, psoriatics scored lower in neuropsychological tests assessing memory and executive functions. Conclusions Cognitive dysfunction disclosed by neuropsychological assessment of frontal functions was evident in patients with psoriasis.

Frequency of streptococcal upper respiratory tract infections and HLA- Cw*06 allele in 70 patients with guttate psoriasis from northern Poland

Introduction The association of guttate psoriasis with a streptococcal throat infection and HLA-Cw*06 allele is well established in different populations. Nevertheless, only few studies on this form of disease have been performed in the Polish population. Aim To analyze the frequencies of streptococcal-induced guttate psoriasis and HLA-Cw*06 allele in 70 patients with guttate psoriasis originating from northern Poland. Material and methods Seventy patients with guttate psoriasis and 24 healthy volunteers were enrolled into the study. Both groups were sex- and age-matched. The evidence of streptococcal infection was based on the positive throat swabs and/or elevated ASO titers. The modified method, including PCR-SSP and PCR-RFLP, was applied to HLA-Cw*06 genotyping. Results HLA-Cw*06 allele was confirmed in 49 (70%) out of 70 patients, which is significantly higher than in the control population (30%) (p = 0.001). Evidence for streptococcal infection was found in 34 (48.5%) subjects with psoriasis. Twenty-seven of them (79%) carried HLA-Cw*06 allele. In 36 individuals in whom no evidence of streptococcal infection was found, 14 (39%) did not carry HLA-Cw*06 allele. Conclusions Our data confirm that HLA-Cw*06 is a major, but not imperative, genetic determinant for guttate psoriasis.

The most common mistakes on dermatoscopy of melanocytic lesions

Dermatoscopy is a method of in vivo evaluation of the structures within the epidermis and dermis. Currently, it may be the most precise pre-surgical method of diagnosing melanocytic lesions. Diagnostic errors may result in unnecessary removal of benign lesions or what is even worse, they can cause early and very early melanomas to be overlooked. Errors in assessment of dermatoscopy can be divided into those arising from failure to maintain proper test procedures (procedural and technical errors) and knowledge based mistakes related to the lack of sufficient familiarity and experience in dermatoscopy. The article discusses the most common mistakes made by beginner or inexperienced dermatoscopists.