Significance of the angiotensin I/angiotensin II/angiotensin-(1-7) axis in the pathogenesis of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a multisystemic disease with an extensive microvasculopathy. Previously, disturbances in plasma levels of angiotensin II (Ang II) and its antagonistic angiotensin-(1-7) (Ang-(1-7)) were found in patients with SSc. Their significance in a pathogenesis of SSc stays unclear due to discrepancies of earlier studies. OBJECTIVES: To evaluate a significance of disturbances in production pathway of angiotensins in a development of SSc. METHODS: There were enrolled 27 patients with established SSc, 23 subjects with very early SSc and 23 healthy controls. The diagnosis of SSc was established in patients who met EULAR/ACR 2013 classification criteria. Very early SSc described patients with Raynaud's phenomenon having SSc-specific antinuclear antibodies and SSc-like abnormalities in nailfold videocapillaroscopy. Patients were submitted to evaluation of internal organ involvement and blood sampling to assay plasma levels of angiotensin I, angiotensin II and angiotensin-(1-7) with ELISA technique. RESULTS: Plasma level of angiotensin-(1-7) was significantly reduced in both SSc group (median = 47.2 pg/mL; P < 0.001) and ones with very early SSc (median = 102.7 pg/mL; P = 0.002) when compared to healthy controls (median = 176.1 pg/mL). A tendency to higher than in control group (median = 214 pg/mL) plasma level of angiotensin I was seen in SSc group (median = 392 pg/mL; P = 0.059). Differences in plasma level of angiotensin II were insignificant between all study groups. Those disturbances produced unfavourable angiotensin-(1-7)/angiotensin II (%) ratio in both groups of patients, which achieved statistical significance in subjects with established SSc (P < 0.001). Production pathway of angiotensins showed a dependence on a subtype of SSc, immune profile and a presence of interstitial lung disease. CONCLUSIONS: Production of angiotensin-(1-7) was significantly reduced in both SSc patients and those ones with very early SSc, although a significant imbalance between angiotensin II and angiotensin-(1-7) occurred only in subjects with established disease.

Detecting and quantifying activity/inflammation in localized scleroderma with thermal imaging.

BACKGROUND: The disease phase in localized scleroderma (LoS) is commonly assessed by clinical investigation using the LoS cutaneous assessment tool (LoSCAT). There is a need for more objective methods for assessing the degree of activity/inflammation in LoS. The aim of our work was to evaluate the correlation between severity of the LoS lesions scored using LoSCAT and the degree of hyperthermia observed with infrared thermography (IRT). MATERIALS AND METHODS: The LoS lesions were examined using the LoSCAT and IRT independently by two examiners. The average temperature (Tavg) of the LoS lesional dermis were measured in the area of each lesion with the highest score for erythema (ER), skin thickness (ST), dermal atrophy (DAT) and subcutaneous atrophy (SAT). Measurements were compared to the contralateral healthy skin. The difference of the Tavg (ΔTavg) was calculated between each lesion and its normal control. RESULTS: One hundred and four LoS lesions were examined in 40 adults. Thirty-one lesions were erythematous, 26 were sclerotic, 35 presented as atrophy of the dermis and 11 as atrophy of the subcutaneous tissue. The sensitivity and specificity of IRT for detecting activity/inflammation were 80.7% and 86.3%, respectively. The positive predictive value was 71%, negative predictive value 91%. Statistically significant positive correlation was found between the ΔTavg and the clinical ER and DAT scores. CONCLUSION: IRT may be a useful method for assessing erythematous LoS lesions and quantifying the degree of activity/inflammation. Knowing the patient, false positive results attributable to more severe degree of skin and subcutaneous fat atrophy can be easily recognized.

Overweight and obesity may play a role in the pathogenesis of chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is one of the commonest diseases in allergological and dermatological practice. It constitutes an interdisciplinary problem, and its pathogenesis is not always easily determined. It has been suggested that metabolic syndrome and hyperlipidaemia are more frequent in patients with CSU, but the influence of overweight and obesity on the development of CSU has not been thoroughly investigated. AIM: To assess the association between body parameters and the development of CSU. METHODS: The study enrolled 85 patients with CSU, who were divided into three subgroups: patients whose only symptoms were weals, patients whose only symptom was angio-oedema, and patients with urticaria and accompanying angio-oedema. Mean weight, height, body mass index (BMI), body surface area, disease duration and age of disease onset were recorded RESULTS: There was a statistically significant association between CSU and heavier weight, higher BMI, greater affected body surface area and older age at disease onset. Subjects with higher BMI values had a tendency towards longer disease duration. There were no statistically significant differences between the three subgroups. CONCLUSIONS: Our results suggest that CSU, especially if of long duration, may be associated with overweight and obesity, while increased body mass can result in later onset of urticaria symptoms. Further analyses to confirm the presented results and possible association between obesity and CSU occurrence are needed.

Serum androgens and prostate-specific antigen levels in androgenetic alopecia: is there a difference between frontal and vertex baldness?

BACKGROUND: Androgenetic alopecia (AGA) seems to be a marker of increased risk of prostate cancer (PCa). OBJECTIVE: We sought to investigate potential pathophysiological differences between frontal and vertex balding that might have the impact on the incidence of PCa. METHODS: Serum concentrations of testosterone (T), dihydrotestosterone (DHT) and prostate-specific antigen (PSA) were measured in 88 subjects with AGA. RESULTS: We have examined sixty patients with frontal baldness and 28 patients with vertex baldness. The subgroups did not differ significantly in age, BMI and as regards age of AGA onset, duration of AGA and comorbidities. The mean value of DHT in serum of the men with vertex baldness was higher than those in the men with frontal baldness with statistical significance (P < 0.05). The groups did not show significant differences in mean value of serum T and PSA levels, and DHT/T ratio. No correlation was found between the serum PSA level and serum androgen levels as well as DHT/T ratio. CONCLUSIONS: Vertex baldness may signal higher exposures to circulating DHT. Serum PSA level cannot serve as surrogate diagnostic marker of increased androgenic activity in men with AGA.

Alopecia areata - hyperactivity of the hypothalamic-pituitary-adrenal axis is a myth?

INTRODUCTION: Psychological stress is known to cause exacerbation of different skin pathologies including alopecia areata (AA). A hyperactivity of the hypothalamic-pituitary-adrenal axis (the HPA axis) in patients affected by AA (AA patients) was proposed to be a neuroendocrine response to stress. Still little is known about melanocyte-stimulating hormone (MSH) and cortisol production in AA settings. AIM: The aim of the study was to compare trends in a production of MSH and cortisol in patients with AA patients and healthy controls. MATERIAL AND METHODS: Plasma concentrations of free cortisol and MSH were measured in 43 AA patients (35.5 ± 10.6 years) and 37 healthy subjects (35.9 ± 10.5 years) selected from the Dermatology Outpatient Clinic at Medical University of Silesia in Katowice, Poland. Results were submitted to statistical analysis with Shapiro-Wilk W-test and subsequently nonparametric (Mann-Whitney U-test) or parametric (Student's t-test) statistics were performed. RESULTS: Mean plasma level of MSH was 5.39 ng/mL in AA patients and 5.71 ng/mL in healthy controls. The difference between groups was non-significant (P = 0.435), but the control group manifested higher values of MSH (Q75 = 13.6 ng/mL vs Q75 = 5.98 ng/mL) and this tendency was especially stronger in females. AA patients had greater mean plasma level of cortisol (157.63 ± 91.16 µg/L) than healthy controls (123.32 ± 71.28 µg/L); however, the difference between them was also non-significant (P = 0.063). No sex-dependent tendency to a greater production of cortisol was found. CONCLUSIONS: Expectations of disturbances in production of MSH and cortisol were not fulfilled. Neither MSH nor cortisol plasma levels appear to be clearly changed in AA patients.

Localized scleroderma: clinical and epidemiological features with emphasis on adulthood- versus childhood-onset disease differences.

BACKGROUND: Localized scleroderma is a rare inflammatory skin disorder that affects the skin and sometimes underlying subcutaneous tissue, muscles or bones. The disease has two modes of onset: juvenile- (JLS) and adult-onset (aLoS). Clinical features have impact on diagnostic and treatment recommendations, but no consensus on the disease management depending on the age at diagnosis was given. OBJECTIVE: To identify these features which differentiate aLoS from JLS. METHODS: A review of the literature was carried out using the MEDLINE to identify studies assessing demographics, subtype distribution, extracutaneous manifestations, comorbidities, delay at diagnosis and outcome in JLS and aLoS. Non-English articles, reviews, case reports, treatment trials that did not investigate long-term outcomes and studies with the fused data for children and adults were excluded. The analysed papers were published between June 1986 and December 2016. RESULTS: Fifty-five studies describing JLS or/and aLoS were included for analysis. Female: male ratio in aLoS was higher than in JLS. Adults presented with plaque and generalized subtype more often than paediatric patients. Linear subtype, musculoskeletal, neurologic and ophthalmologic involvement were more frequent, among children. aLoS was likely to be associated with increased prevalence of lichen sclerosus. There was significant delay in diagnosis in both groups of patients. Recurrences of disease were independent of its onset mode. aLoS patients had more poor quality of life scores than did JLS patients. As only a few studies or no studies assessing specified disease subtypes were identified, this limited the ability to compare the adult and paediatric patients with these subtypes. CONCLUSION: Despite more favourable course of aLoS, a thorough understanding of the broad spectrum of domains related to physical, mental, emotional and social functioning of patients seems to be important to the proper management of disease. LoS heterogeneity makes it important to develop universal classification criteria.

A systematic review of tools for determining activity of localized scleroderma in paediatric and adult patients.

Localized scleroderma (LoS) is a rare inflammatory skin disorder that affects the dermis and sometimes subcutaneous tissues. LoS can have very long periods of quiescence followed by reactivation, but the progression or activity of the disease is difficult to measure. To review the measuring tools used for the evaluation of LoS activity, to choose the most appropriate technique to facilitate progress towards properly assessing the disease, a systematic review of the literature was carried out using the PubMed MEDLINE. Sixty-three studies describing groups of children, adults or both were reviewed and included in the analysis. Case reports were excluded. The analysed papers were published between June 1986 and February 2016. Data were extracted with a focus on instruments measuring the clinical signs of LoS, health-related quality of life (HRQoL), laboratory tests and imaging techniques. Perusal of the literature confirmed that clinical characteristics of the lesions were used to identify activity and scoring systems that focused on a series of signs, and were initially validated in cases of childhood-onset disease; however, there were no data concerning the adult-onset form of the disease. Adult patients with LoS scored lower on HDLQI than those with paediatric-onset LoS. No validated biological markers were available as correlative laboratory parameters of LoS activity. For infrared thermography, ultrasound and other imaging techniques, the features of active lesions were described, but were only useful with appropriate clinical correlation. Measuring tools have not been prospectively validated yet. Summarizing, scoring methods seem to provide the most adequate assessment of LoS and deserve to be further investigated. Combined imaging techniques create optimal conditions for the proper interpretation of the temperature at the skin surface, as well as the structure and vascularity of LoS lesions. Additional scores, musculoskeletal or neuroimaging techniques and laboratory parameters are needed for the specific disease subtypes to monitor extracutaneous manifestations.

Von recklinghausen disease: one patient - various problems.

von Recklinghausen disease (vRD), more widely known as neurofibromatosis type 1, belongs to a group of genetic disorders and it is considered to be the most common genodermatosis. The disease has an autosomal dominant pattern of inheritance that involves mutations within the NF1 gene located on chromosome 17 in locus q11.2. The product of the NF1 gene is neurofibromin and the protein is well known to be a tumor suppressor factor. This counteracts possible overactivity of RAS (protein)/MAPK (mitogen-activated protein kinase) and RAS/PI3K/AKT/mTOR (phoshatydyloinositol-3-kinase/V-akt murine thy-moma viral oncogene homologue/mammalian target of rapamycin) signaling transduction pathways, preventing from uncontrolled cell proliferation and subsequent tumor formation. A loss of proper functioning of this protein leads to a development of vRD; however, a large variability in a phenotype of the disease and the onset of cutaneous findings, not necessarily in childhood, may provide a clinical diagnosis of the disease late in adulthood. We present a 52-year-old male in whom the diagnosis of vRD was proposed in the sixth decade of life, despite of multiple nodular lesions disseminated over the skin of the whole body and different neurological disturbances, not considered for a long time as manifestations of genodermatosis.

Nanoscale domains with nematic order in supercooled vitamin-A acetate: molecular dynamics studies.

Vitamin-A acetate is one of the most versatile vitamins. It is applied in medicine because of its antioxidative properties, in tumor therapy because of its cytostatic activity, and in cosmetics because of its nutritional additives. Herein, using broadband dielectric spectroscopy, the molecular dynamics of supercooled and glassy vitamin-A acetate was investigated. It was shown that dielectric measurements carried out at ambient and elevated pressures reveal a number of relaxation processes associated with different types of molecular motions: α, δ, and ν processes-observed above the glass transition temperature and the next two modes: ß and γ identified in the glassy state. The occurrence of the δ mode in the dielectric spectrum may imply the existence of nanoscale domains with nematic order. This hypothesis is further checked by atomic force microscopy measurements. Finally, we have determined the value of the glass transition temperature (T(g)) as well as the steepness index (m(P)) at various T-P conditions.

Early and long-term results of physical methods in the treatment of venous leg ulcers: randomized controlled trial.

OBJECTIVE: To estimate early and long-term results of physical methods in the treatment of venous leg ulcers. METHOD: In group A after surgical operation, 40 patients were treated with the high-voltage stimulation (HVS) (100 µs, 100 Hz, 100 V) and drug therapy. In group B after operation, 37 patients were treated with ultrasound (0.5 W/cm(2), 1 MHz) and drug therapy. In group C after operation, 33 patients were treated with low-level laser therapy (LLLT) (810 nm, 65 mW) and drug therapy. In group D after operation, 35 patients were treated with the compression stockings (25-31 mmHg) and drug therapy. In group E after operation, 37 patients were only treated with drug therapy. Group F consisted of 32 patients, conservatively treated with the HVS and drug therapy. Group G consisted of 20 patients, conservatively treated with ultrasound and drug therapy. Group H consisted of 21 patients, conservatively treated with LLLT and drug therapy. Group I consisted of 30 patients, conservatively treated with compression and drug therapy. Group J consisted of 27 patients only treated with drug therapy. RESULTS: Both short and long term parameters showed that compression therapy is the most efficient in ulcer healing. The electrical and ultrasound methods are less effective. The laser therapy ared useless. CONCLUSION: Superficial venous surgery in addition to compression therapy is the most efficient treatment of venous leg ulcers. The compression therapy should be continued both surgically and conservatively treated patients with healed ulcers. In special cases after superficial venous surgery (isolated superficial reflux) compression therapy could be applied only to the time of ulcer closure without continuing it longer. HVS and ultrasound therapy are useful methods in conservative treatment of venous leg ulcers. For surgically-treated patients these physical therapies are efficient only in superficial plus deep reflux cases. HVS and ultrasound can be alternative methods, but are less effective in recurrence risk. LLLT is not an efficient physical method in treatment of venous leg ulcers.

The use of therapeutic ultrasound in venous leg ulcers: a randomized, controlled clinical trial.

OBJECTIVES: To estimate the usefulness of therapeutic ultrasound for healing of venous leg ulcers. METHODS: Eighty-one patients were included in this study. Patients in groups 1 and 2 were treated surgically. Patients in groups 3 and 4 were treated conservatively. Patients in groups 1 and 3 were additionally treated with the ultrasound (1 MHz, 0.5 W/cm(2)) once daily, six times a week for seven weeks. RESULTS: Comparison of the number of complete healed wounds indicated statistically significant differences between groups 1 and 4 (P = 0.03), 2 and 4 (P = 0.03), 3 and 4 (P = 0.03) in favour of groups 1, 2 and 3. Comparison of the other parameters also demonstrated more efficient therapy effects in groups 1, 2 and 3 than in group 4. There were no statistical differences in all examined parameters between groups 1, 2 and 3 (P > 0.05). CONCLUSIONS: The ultrasound is an efficient and useful method only in conservatively treated venous leg ulcers. There are no special reasons for application of the ultrasound in surgically treated patients. A well-conducted surgical operation is much more effective for a healing process than conservative pharmacological procedures.

Multifocal type of pilomatrixoma.

Pilomatrixoma is a benign skin neoplasm that arises from hair follicle matrix cells. The skin lesion occurs usually as a solitary tumor and the multifocal types are very rare. Skin changes can be described as a firm to hard, non-painful, oval-shaped tumor that is covered by normal skin. It commonly occurs on a scalp, face, neck and rarely back and extremities. Complete surgical excision with the proper margin is the treatment of choice, what guaranteed the radical therapy of pilomatrixoma. In this paper case of 16-years-old male patient with many solid tumors in subcutaneous tissue on both arms will be reported. The first skin lesion appeared on the left arm 6 years ago. Clinically the disturbance was diagnosed as an atheroma, and it was excised. One year after surgical procedure the patient observed the appearance of new nodules on both arms. In the therapy surgical excision was performed with histopathological examination of the tissues. Histopathological test has proved the clinical diagnosis of pilomatrixoma. The case of multifocal pilomatrixoma, which is rarely diagnosed and described in professional literature, will be presented.

Paraneoplastic type of acanthosis nigricans in patient with hepatocellular carcinoma.

UNLABELLED: Paraneoplastic acanthosis nigricans is connected with malignancies in adults in almost 100% of cases. The typical skin changes include: thickening and hyperpigmentation in typical localization with mucocutaneous involvement. PURPOSE: The authors report a case of a malignant type of acanthosis nigricans in 42-year-old female patient with hepatocellular carcinoma. CASE REPORT: First skin lesions appeared in 2000. The patient died within 22 months (of the first appearance of skin symptoms), because of hepatocellular carcinoma. Herein we report the clinical picture, skin involvement and diagnostic procedures in acanthosis nigricans. CONCLUSIONS: Paraneoplastic type of acanthosis nigricans--in patient with hepatocellular carcinoma is not frequently reported in the literature. In the aspect of clinical occurrence of skin lesions suggesting acanthosis nigricans the diagnostics should be focused on internal malignancies.