Is There a Link between Thyroid Peroxidase Gene Promoter Polymorphisms and Autoimmune Thyroiditis in the Polish Population?

(1) Autoimmune thyroiditis (AIT) is the most common cause of primary hypothyroidism and one of the most frequent organ-specific autoimmune diseases. Its pathogenesis is polygenic and still requires further research. The aim of the study was to assess, for the first time in the Caucasian population, the role of selected TPO gene promoter polymorphisms (rs2071399 G/A, rs2071400C/T, rs2071402 A/G, and rs2071403 A/G) in the development of AIT. A total of 237 patients diagnosed with AIT and 130 healthy controls were genotyped for four TPO gene polymorphisms, and the results were statistically analyzed to check for the role of these polymorphisms. There were no significant differences in the genotype and allele frequencies of the studied TPO gene promoter polymorphisms between patients and controls (p > 0.05). The haplotype distribution (rs2071400-rs2071402-rs2071403) between the two studied groups was similar for the most common variants (CGA, CAG, TGG). Only a rare haplotype (CGG) occurred more frequently among patients compared to controls (p = 0.04). The studied TPO gene promoter polymorphisms did not show an association with susceptibility to AIT in the Caucasian Polish population, contrary to the results in Japanese patients.

Lipomas: genetic basis of common skin lesions and their occurrence in rare diseases.

Lipomas are usually sporadic, asymptomatic lesions, and their clinical and histologic presentation does not pose diagnostic difficulties. In ambiguous cases, however, knowledge of genetics is necessary. HMGA2 expression in adipose cells enables the differentiation of normal adipose tissue from lipoma and liposarcoma. Moreover, lipomas can be associated with genetic diseases, such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson's disease, or mitochondrial diseases. Lipomas can run in families (familial multiple lipomatosis) or be a part of genetic syndromes such as PTEN hamartoma tumor syndrome, Proteus syndrome, and Pai syndrome. This study aims to present the genetic basis of lipomas and diseases in which these lesions occur in the clinical picture.

Profiling of microRNAs in actinic keratosis and cutaneous squamous cell carcinoma patients.

Actinic keratosis (AK) is a common skin lesion often defined as premalignant with more evidence indicating it as early stage of cutaneous squamous cell carcinoma (cSCC). The AK may remain stable, transform towards incisive cSCC or in some cases revert spontaneously. Several different underlying conditions can increase risk of cSCC, however, advanced age represents major risk of AK and its progression towards cSCC indicating increased risk during chronological aging. Importantly, AK and cSCC are characterized by similar genetic profile, which lead researchers to search for novel biomarkers allowing early detection. As skin sampling is often invasive and causes scaring, in the current study, we investigated a novel approach to establish potential blood circulating genetic markers in patients diagnosed with AK and cSCC. Based on clinical diagnosis and dermoscopy, we recruited 13 patients with AK (divided into two groups: the first included patients with no more than three lesions, the second group included patients with at least ten lesions) and two additional individuals diagnosed with cSCC. Deep sequencing analysis of serum circulating miRNAs detected a total of 68 expressed miRNAs. Further analysis indicated 2 regulated miRNAs for AK cohort and 12 miRNAs for cSCC patients, while there were 26 miRNAs differentially regulated between cSCC and AK patients. There was also one commonly regulated miRNA between AK and cSCC patients and ten miRNAs that were regulated in cSCC when compared with both control and AK patients. We did not observe any differences between the AK groups. In conclusion, our analysis detected in circulation some miRNA that were previously recognized as important in AK, cSCC, and other type of skin cancer supporting this approach as potential non-invasive diagnosis of AK and cSCC.

Epidermal barrier function in patients after allogeneic hematopoietic stem cell transplantation - a pilot study.

Introduction: The skin is the typically and predominantly affected organ in patients after allogeneic hematopoietic stem cell transplantation (alloHSCT). The supportive therapy in patients after alloHSCT includes especially ultraviolet protection and the use of emollients. Aim: Due to the lack of studies regarding epidermal barrier function in patients with alloHSCT, our aims were to monitor dermatologically patients 1 year after the procedure with special emphasis on epidermal barrier function and to evaluate the properties of epidermal barrier function in patients with confirmed chronic GvHD (cGvHD). Material and methods: Our pilot study included 30 patients after alloHSCT and 20 healthy controls. In the group of patients after alloHSCT there were 10 individuals who were monitored dermatologically (including evaluation of skin, mucosae, nails and hair) within 1 year after the procedure (subgroup 1) and 20 patients with previously confirmed cGvHD (subgroup 2). We evaluated transepidermal water loss (TEWL), skin hydration and skin color. The clinical assessment and all noninvasive evaluations in patients included in subgroup 1 were performed before (at baseline) and 3, 6, 9 and 12 months after the procedure, while in subgroup 2 they were performed once. Results: In subgroup 1 we did not observe significant differences between baseline results and periods of assessments in TEWL values or corneometry, erythema and melanin measurements. In subgroup 2 the highest TEWL values and the lowest corneometry results were observed in patients with sclerodermoid chronic cutaneous GvHD in comparison to patients with lichenoid chronic cutaneous GvHD and patients with cGvHD but without skin lesions. TEWL values and melanin level were significantly higher in patients with cGvHD than in controls. Conclusions: Our pioneer observations proved the disturbed epidermal barrier function among patients after alloHSCT. Therefore it seems that proper skin care, including photoprotection, should be recognized as a crucial component in long-term management of these patients.

Suitability of high-frequency ultrasonography (20 MHz) in evaluation of various forms of primary cicatricial alopecia in relation to trichoscopy - pilot study.

BACKGROUND: Primary cicatricial alopecia is a potentially irreversible process of hair loss, in which for proper diagnosis a skin biopsy is necessary. Searching for new, non-invasive diagnostic methods may shorten the time for final diagnosis, initiating appropriate treatment and reduce the need for biopsy. The aim of this study was to evaluate the usefulness of high-frequency ultrasonography (HF-USG) as a diagnostic method in patients with primary scarring alopecia and to compare it with trichoscopy. MATERIALS AND METHODS: The study covered a total of 44 adults: 8 with classic lichen planopilaris (LPP), 11 with discoid lupus erythematosus (DLE), 14 with frontal fibrosing alopecia (FFA), and 11 healthy volunteers. Each patient underwent physical and trichoscopic examination which was the base for qualification for active/inactive stage of the disease. Then, HF-USG was performed using a probe with a frequency of 20 MHz. In HF-USG images, the following elements were evaluated and measured: entrance echo (EE), follicular structures (FS), dermal background (DB), and dermal/subdermal border (D/SB). RESULTS: Inactive phase was characterized by significantly lower number/lack of FS compared to the active phase of scarring alopecia. HF-USG of active LPP/FFA presented cigar-like shaped FS, while inactive stage pronounced D/SB forming saw-like pattern. Active DLE in HF-USG were associated with focal, doubled EE and widened FS with a tendency to create hypoechogenic wide, structureless bands within the skin. In inactive DLE, there was no specific pattern of D/SB or rarely puzzle-like pattern. CONCLUSION: HF-USG images differ depending on the phase of the disease and the type of scarring alopecia, similarly to trichoscopic examination.

High-Frequency Ultrasonography-Possibilities and Perspectives of the Use of 20 MHz in Teledermatology.

High-frequency ultrasonography (HF-USG) is a non-invasive and in vivo method of visualization of the skin and upper part of subcutaneous tissue based on ultrasounds above 20 MHz. Although initially HF-USG was introduced to measure skin thickness, it currently gained widespread acceptance in dermato-oncology, primarily when used to determine skin tumor margins. Moreover, its application in different dermatology fields is known, particularly as a rapidly evolving method in the objective evaluation of the severity of various chronic skin diseases. Among different specialties, teledermatology belongs to leading and continually developing areas of successful telemedicine applications. Various skin conditions are visible to the human eye, which makes them particularly suitable for telemedicine. However, HF-USG enables specialists to look into deeper skin layers, thus extending diagnostic options. On the other hand, teledermatology creates the possibility of sending images for consultation and facilitates the therapeutic decision as HF-USG can be used in an asynchronous store and forward manner. It seems that HF-USG and teledermatology may be regarded as a truly matched pair. The aim of this work is to present current applications of 20-MHz ultrasonography in dermatology, including skin neoplasms and chronic skin diseases. Moreover, the authors aimed to analyze the possibilities of HF-USG use as a valuable tool in teledermatology, especially in diagnosing and monitoring patients suffering from long-lasting skin conditions.

Skin barrier function in patients under radiation therapy due to the head and neck cancers - Preliminary study.

AIM: To present the possibility of non-invasive monitoring of the skin after radiotherapy in regards of epidermal barrier function. BACKGROUND: Radiodermatitis constitutes 95% of all side effects in patients after radiotherapy. The proper assessment of the severity of radiodermatitis can be determined using semi-quantitative clinical scores [Common Terminology Criteria for Adverse Events v 4.0 (CTCAE)].The most accepted way to analyze the epidermal barrier function is to determine Transepidermal Water Loss (TEWL). MATERIAL AND METHODS: In prospective study, we included 16 patients diagnosed with head and neck cancer treated with radiotherapy or concomitant chemoradiation in whom we performed non-invasive assessments of the skin barrier function, including TEWL measurement. The final analysis included 6 patients (4 treated with adjuvant radiotherapy, 2 with radical chemoradiation). Clinical assessment of irradiated skin was based on target lesion score (TLS) and CTCAE v 4.0. RESULTS: The mean TLS score in the middle of irradiation was 1.6 points, after last irradiation it was 2.3 points; 3 months later the mean TLS score was: 0. CTCAE v 4.0 criteria: 2 patients had grade 0, 3 patients - grade 1; 1 patient - grade 2. There were statistically significant differences in TEWL related to irradiated skin in the following time intervals: before vs. in the middle; before vs. day after; in the middle vs. day after; in the middle vs. 3 months after; day after vs. 3 months after. CONCLUSIONS: The study showed that radiotherapy causes skin barrier dysfunction in all patients independently of clinical radiodermatitis. The biophysical features of this dysfunction can precede clinical symptoms and they can be assessed by non-invasive and objective methods.

Vitamin D Receptor Gene Polymorphisms and Autoimmune Thyroiditis: Are They Associated with Disease Occurrence and Its Features?

PURPOSE: Vitamin D, besides its role in calcium-phosphorus metabolism, turned out to play a significant immunomodulating function. Until now four single nucleotide polymorphisms of vitamin D receptor gene (VDR), rs2228570 (FokI), rs1544410 (BsmI), rs7975232 (ApaI), and rs731236 (TaqI), have been studied in autoimmune thyroid disorders, with conflicting results. Another functional polymorphism of the VDR gene, rs11568820 (Cdx2), has been shown to influence the immune system, although it has not been studied for its association with autoimmune thyroiditis to date. Therefore, the study aimed to evaluate the association of these five VDR gene polymorphisms with susceptibility to autoimmune thyroiditis among Caucasian Polish population. A relationship between the studied polymorphisms and selected clinical features of the disease was additionally assessed. METHODS: 223 patients with autoimmune thyroiditis and 130 control subjects were enrolled in the study. VDR polymorphisms were studied by PCR-RFLP or TaqMan real-time PCR. RESULTS: Allele and genotype distributions of any of the studied polymorphisms did not differ significantly between patients and controls. Similarly, frequencies of haplotypes derived from rs1544410-rs7975232-rs731236 (BsmI-ApaI-TaqI) polymorphisms were not significantly different in the two studied groups. However, a weak association between rs1544410 (BsmI) or rs7975232 (ApaI) VDR polymorphisms and thyroid volume was found (p = 0.03 and p = 0.04, resp.). CONCLUSIONS: Our results suggest that VDR gene is not a major susceptibility factor for autoimmune thyroiditis development, at least in Caucasian Polish population.

An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers.

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi-quantitative clinical scores, which are not validated and may be subject to inter-observer variability. A few previous studies suggested that high-frequency ultrasonography (HF-USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF-USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF-USG as well as dermatological assessment (target lesion score-TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non-irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1-4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1-4; P = .0002). There was no significant difference between non-irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF-USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.

High-frequency ultrasonography a new quantitative method in evaluation of skin lymphomas-First comparative study in relation to histopathology.

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.

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.

Cyclooxygenase-2 expression in actinic keratosis.

INTRODUCTION: Actinic keratosis (AK) is a common age-associated dermatosis typical for skin with photo-ageing features. Actinic keratosis lesions transform into invasive squamous cell carcinoma, if left untreated, but inductive factors remain unknown. A role of prostaglandins in the neoplastic process has been postulated. AIM: To evaluate the possible correlation between cyclooxygenase-2 (COX-2) antigen expression in the immunohistochemical reaction and the stage of AK using the keratinocytic intraepidermal neoplasia (KIN) classification, age, sex and skin phenotype. MATERIAL AND METHODS: Skin samples of AK were examined histopathologically using the KIN classification. Immunohistochemical analysis of COX-2 expression was conducted using a commercially available kit and Image Processing and Analysis in Java. The intensity was presented as the percentage of cells with a positive reaction. RESULTS: Out of the 94 subjects with AK (aged 51-93 years; mean: 76.51 ±9.64), 58 were female and 36 male. Phenotype 2 was found in 50 and phenotype 3 in 44 patients. Mean values of positive immunohistochemical reaction for COX-2 were 2.16 ±6.56% for women and 1.96 ±6.59% for men (2.47 ±6.61%), with no statistically significant difference. Mean values of anti-COX-2 antibody reaction were 2.30 ±6.82% in the KIN1 group and 2.48 ±7.01% in the KIN2 group, while no expression was found in all cases with KIN3. No statistically significant differences were found between the percentage of COX-2 positive cells in KIN1/KIN2. CONCLUSIONS: No statistically significant correlations between the intensity of COX-2 reaction and AK stage were found. Cyclooxygenase-2 expression in AK is not affected by age, sex, or skin phenotype.

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.

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.

Current applications of high-frequency ultrasonography in dermatology.

The era of ultrasounds in dermatology started in 1979, when pioneering use of 15 MHz by Alexander and Miller in measuring the skin thickness was introduced. Since then, some new applications of high-frequency ultrasonography (HF-USG) have emerged providing the clinicians with an extra hand in their everyday practice. The main advantages of HF-USG include the possibility of real-time imaging, measurements of morphological and physiological aspects of the skin, safety associated with the use of non-ionizing media as well as the lack of contraindications to its performance. Currently the main clinical use of HF-USG in dermatology regards preoperative assessment of the depth of invasion in melanomas and basal cell carcinomas. The ultrasound image analysis allows noninvasive follow-up of inflammatory skin diseases, like atopic dermatitis, psoriasis and may be used for monitoring effectiveness of therapy in skin lymphomas and sclerotic skin diseases.

The role of altered cutaneous immune responses in the induction and persistence of rosacea.

Rosacea is a chronic inflammatory skin condition that predominantly affects the skin of the face and the eyes. Several factors are associated with the onset and persistence of the condition, including an altered immune response in the skin and elevated levels of Demodex mites. Alterations in the immune response include elevated levels of LL-37 in rosacea skin, increased expression of TLR-2 and increased amounts of vitamin D3 in epidermal tissue. The combined effect of these changes may make the skin more sensitive to external and internal stimuli. External stimuli that may trigger or sustain rosacea inflammation include exposure to ultraviolet light, while internal factors may include the presence of elevated numbers of Demodex mites. These mites may directly stimulate an immune response or release bacteria within the pilosebaceous unit that act as a trigger for inflammation. This review will highlight the changes that occur in the immune response of the skin and describe how Demodex mites and associated bacteria may activate this response and lead to the characteristics of rosacea.

Current views on the etiopathogenesis, clinical manifestation, diagnostics, treatment and correlation with other nosological entities of SIBO.

Small intestinal bacterial overgrowth (SIBO) is a disease of great clinical and socioeconomic importance caused by an excessive amount of bacteria in the upper alimentary tract. Physiological microbiota are replaced by pathogenic bacteria mainly from large intestine, which is called dysbacteriosis. SIBO disturbs digestion and absorption in the alimentary tract, which seems to cause inflammation. SIBO affects the morphology and function of the digestive system and causes systemic complications (e.g. osteoporosis, macrocytic anemia). Inflammation interferes with gene expression responsible for producing and secreting mucus, therefore, a correlation between SIBO and cystic fibrosis, irritable bowel syndrome and chronic abdominal pain are postulated. All conditions leading to bacterial growth such as congenital and anatomical abnormalities in the digestive tract, motility disorder or immunological deficits are risk factors of SIBO. A typical clinical manifestation of SIBO comprises meteorism, enterectasia, abdominal discomfort and diarrhea. Diagnostic procedures such as glucose, lactulose, methane, 13C mixed triglyceride breath tests are being used in diagnosing SIBO.

Inhibitors of phosphodiesterase 4 (PDE 4): A new therapeutic option in the treatment of psoriasis vulgaris and psoriatic arthritis.

Psoriasis vulgaris and psoriatic arthritis are inflammatory diseases in which inflammation and sustained inducing lesions result from immune disorders associated with overactivity of T cells that produce multiple proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin (IL): IL-2, IL-12, IL-17, IL-22 or IL-23. Modern treatment of these diseases is focused on reducing the inflammatory process responsible for the development of the disease. In recent years, the treatment of psoriasis is developing at a dynamic rate. Such therapeutic advances are contributed to the possibility of patient therapy through the use of some registered biologic agents, such as TNF-α inhibitors (infliximab, etanercept and adalimumab), and an inhibitor of the p40 subunit common to IL-12 and IL-23 (ustekinumab). In addition to the already registered medications for the indications mentioned above, there is a large group of preparations that are currently undergoing clinical trials in Europe, Canada and the United States, which provides hopes of therapy efficacy and safety.