Dermatoscopy of Cutaneous Lichen Planus - Attempt to Translate Metaphoric Terminology Into Descriptive Terminology.

INTRODUCTION: Dermatoscopy is gaining appreciation in assisting the diagnosis of inflammatory dermatoses (inflammoscopy). Lichen planus (LP) is a common inflammatory skin disease with characteristic dermatoscopic features. Over the last few years, numerous articles were published on the dermatoscopy of LP and a high number of terms have been used to describe the dermatoscopic features of this disease. OBJECTIVES: The objective of this study was to review the literature on the dermatoscopy of LP and to re-evaluate the published descriptions in the light of the 2019 expert consensus on the terminology of dermatoscopy for non-neoplastic skin diseases. METHODS: We searched the PubMed database using the keywords 'lichen planus and dermatoscopy', 'lichen planus and dermoscopy', 'lichen planus and epiluminescence microscopy', and 'lichen planus and inflammoscopy'. RESULTS: Of 408 articles retrieved, we selected 67 articles for full-text review, and finally included 58 articles, mostly case reports or small case series, comprising 572 patients with LP. We identified 118 different terms or short descriptions that were used to characterize the dermatoscopy of LP and redescribed them according to International Dermoscopy Society consensus paper. Frequently, authors applied various terms or descriptions to variants of the same feature. Although reported under different designations, Wickham striae were the most consistent dermatoscopic feature of LP. Other characteristics of LP, such as vascular patterns, pigmented structures and follicular findings were less consistent or depended on skin type, anatomic site, disease stage and applied treatment. CONCLUSIONS: While Wickham striae are the single most important clue for the diagnosis, other dermatoscopic characteristics of LP are less consistent. Based on the descriptions published in the literature we established a dictionary of useful terms for the description of LP that is consistent with the terminology suggested by the recent consensus conference.

Future Treatment Options in Systemic Sclerosis-Potential Targets and Ongoing Clinical Trials.

Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy and fibrosis of the skin and internal organs. The pathogenesis of systemic sclerosis is very complex. Mediators produced by immune cells are involved in the inflammatory processes occurring in the tissues. The currently available therapeutic options are often insufficient to halt disease progress. This article presents an overview of potential therapeutic targets and the pipeline of possible future therapeutic options. It is based on research of clinical trials involving novel, unestablished methods of treatment. Increasing knowledge of the processes and mediators involved in systemic scleroderma has led to the initiation of drug trials with therapeutic targets of CD28-CD80/86, CD19, CCL24, CD20, CD30, tumor necrosis factor (TNF), transforming growth factor ß (TGF-ß), B-cell activating factor (BAFF), lysophosphatidic acid receptor 1 (LPA1 receptor), soluble guanylate cyclase (sGC), Janus kinases (JAK), interleukin 6 (IL-6), endothelin receptor, and autotaxin. Data from clinical trials on these drugs indicate a significant potential for several new therapeutic options for systemic sclerosis in the upcoming future.

A Six-Year Gynecological Follow-Up of Immunosuppressed Women with a High-Risk Human Papillomavirus Infection.

Immunocompromised women are at an increased risk of developing malignancies, especially those that are viral-induced, such as invasive cervical cancer caused by the human papillomavirus (HPV). The aim of the study was to describe gynecological follow-up of women undergoing chronic immunosuppressive therapy for various reasons (e.g., kidney/liver transplant, systemic lupus erythematosus), diagnosed with a high-risk HPV (hrHPV) infection based on a self-sampling test. Twenty-six hrHPV-positive women were invited to take part in a gynecological follow-up, including a visual assessment of the anogenital region, two-handed gynecological examination, and cervical cytology as well as a colposcopy and cervical biopsy when necessary. Four women declined taking part in the study. Over six years of observation, low-grade squamous intraepithelial lesions (LSIL) were detected at least once in 7/22 women (31.8%), and a cervical intraepithelial lesion 1 (CIN 1) histopathologic result was obtained five times in 3/22 women. No cases of high-grade squamous intraepithelial lesions, CIN 2/3, or invasive cervical cancers were observed. Loop electrosurgical excision procedure (LEEP) was performed in three patients. As immunocompromised women are prone to persistent hrHPV infections, they should be under strict gynecological supervision because only vigilant surveillance enables fast detection and treatment of early dysplasia and, therefore, provides a chance for the reduction of the cervical cancer burden.

Cutaneous T-cell lymphoma in erythrodermic cases may be suspected on the basis of scalp examination with dermoscopy.

Erythrodermic variants of cutaneous T-cell lymphoma (CTLC) are one of the case of erythroderma. The aim of the study was to assess the value of scalp dermoscopy in differentiation between erythrodermic CTCL, psoriasis, and atopic dermatitis. A total of 76 patients were included into the study (16 patients with erythrodermic CTCL, 20 patients with psoriatic erythroderma, 20 with erythrodermic atopic dermatitis, and 20 healthy volunteers). The most common trichoscopic features of erythrodermic CTCL were: numerous pili torti, numerous broken hairs, white thick interfollicular bands, and patchy hyperpigmentation of the background. They were observed in 81% (13/16), 75% (12/16), 56% (9/16), and 37.5% (6/16) of patients with CTCL, respectively (p < 0.001). Other specific features of erythrodermic CTCL were 8-shaped hairs (19%; 3/16) and visible anagen bulbs (12.5%; 2/16) (p < 0.05 and p = 0.052, respectively). The most common vascular pattern of erythrodermic CTCL was perifollicular arrangement of glomerular (50%; 8/16; p < 0.001) or linear vessels (31%; 5/16; p < 0.05). Follicular spicules-like scaling was pathognomonic for erythrodermic CTCL (12%, 2/16) although its presence did not reach statistical significance (p = 0.052). In conclusion, the characteristic trichoscopic findings of erythrodermic CTCL are numerous pili torti, eight-shaped hairs, thick white interfollicular bands, color heterogeneity of the background and perifollicular arrangement of vessels.

Human Papillomavirus (HPV) DNA Detection Using Self-Sampling Devices in Women Undergoing Long Term Immunosuppressive Therapy.

Immunosuppression is a risk factor of persistent human papillomavirus (HPV) infections, which might lead to development of (pre)malignant lesions of the cervix and lower anogenital tract. Results of HPV DNA testing using cervicovaginal self-samples are comparable to those that are clinician-obtained and therefore might be used in cervical screening. The aim of this study was to assess the prevalence of high-risk HPV (hrHPV) infections, their risk factors and the genotypes distribution among women undergoing immunosuppressive therapy. Women undergoing immunosuppressive therapy for at least three months due to solid organ transplantation or autoimmune disorders were asked to self-collect samples for HPV testing using cervicovaginal brushes and complete questionnaires regarding cervical cancer risk factors. HPV DNA detection and genotyping were performed using Genotyping kit HPV GP version 2. hrHPV was detected in 26/90 (28.9%) specimens. Genotyping revealed a broad range of hrHPV, with type 16 being the most common genotype (11/26). The components of bivalent/quadrivalent or nonavalent vaccines cover all genotypes present in 4.4% and 17.8% women, respectively, and occur as a co-infection with other types in 12.2% and 23.3% of women, respectively. The only feature significantly associated with being hrHPV-positive was having at least two lifetime sexual partners. The high prevalence of hrHPV infections among immunosuppressed women emphasizes the need for regular cervical cancer screening with HPV DNA testing, which might be performed on self-collected specimen.

Cardiovascular Drug Use and Risk of Actinic Keratosis: A Case-Control Study.

INTRODUCTION: Actinic keratosis (AK) is a precancerous skin lesion. Currently, many experts treat actinic keratosis as squamous cell carcinoma in situ. It is well established that exposure of the skin to ultraviolet radiation is a major risk factor for the development of actinic keratosis. Some studies suggest an association between keratinocyte cancers and photosensitizing cardiovascular drugs. The aim of this study was to establish an association between cardiovascular drug use and the presence of AK. METHODS: A total of 400 patients were enrolled into the study (200 with AK; 200 healthy persons in the control group). The group of patients with AK consisted of 106 women and 94 men (mean age 71 years). The control group included 102 women and 98 men (mean age 69 years). An analysis of the risk factors for developing actinic keratosis was performed in all patients with AK on the basis of a detailed, standardized interview. RESULTS: The statistical analysis showed that features independently associated with increased risk of AK included: age > 80 years (OR 4.14; 95% CI 2.4-7.3), positive cancer history (OR 1.94; 95% CI 1.0-3.6), positive history of sunburns when < 18 years old (OR 2.18; 95% CI 1.3-3.7) and taking angiotensin-converting enzyme inhibitors (OR 2.28; 95% CI 1.2-4.3), angiotensin receptor AT1 blockers (OR 2.90; 95% CI 1.1-7.9) and calcium channel blockers (OR 2.4; 95% CI 1.0-5.3). CONCLUSION: In conclusion, our study presented an association between cardiovascular drug use and the risk of developing AK.

Adalimumab - Safe and Effective Therapy for an Adolescent Patient with Severe Psoriasis and Immune Thrombocytopenia.

Psoriasis has been linked to several comorbidities, including metabolic syndrome, atopy, and celiac disease. However, the association between immune thrombocytopenia and psoriasis has rarely been described. We report the case of an adolescent with severe psoriasis and concomitant immune thrombocytopenia who obtained remission during treatment with adalimumab. Increased concentration of tumor necrosis factor-α seems to be a pathogenic linkage and therapeutic target for both diseases.

The Use of Naltrexone in Dermatology. Current Evidence and Future Directions.

Naltrexone is a competitive opioid receptor antagonist approved as supportive treatment in alcohol dependence and opioid addiction. At a dose of 50-100 mg daily, naltrexone is used off-label in dermatology for the treatment of trichotillomania and different types of pruritus. At a dose as low as 1- 5 mg per day, naltrexone demonstrates immunomodulatory action i.e. modulates Toll-like receptors signaling, decreases release of proinflammatory cytokines (tumor necrosis factor, interleukin-6, interleukin- 12), inhibits T lymphocyte proliferation, down-regulates the expression of chemokine receptors and adhesion molecules. The efficacy of standard and low doses of naltrexone in a variety of dermatological disorders has been reported. These include diseases such as familial benign chronic pemphigus (Hailey-Hailey disease), dermatomyositis, systemic sclerosis, psoriasis and lichen planopilaris. Optimistic preliminary findings, low cost of therapy and good tolerance make naltrexone a promising alternative therapy or adjunct drug in dermatology.

JAK-inhibitors in dermatology: current evidence and future applications.

The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is a ubiquitous intracellular signaling network. Selective JAK-inhibitors have anti-inflammatory properties and have been approved in many countries for the treatment of rheumatoid arthritis (tofacitinib, baricitinib) and myelofibrosis or polycythemia vera (ruxolitinib). The aim of the publication was to summarize and critically analyze the efficacy and safety of JAK-inhibitors in skin diseases, such as psoriasis, alopecia areata, atopic dermatitis and vitiligo. Databases PubMed, Scopus and EBSCO were searched. After exclusions, 17 articles were analyzed (11 randomized clinical trials, 4 case reports, 1 retrospective study of a case series and 1 nonrandomized pilot study). The strongest evidence of JAK-inhibitor efficacy was established for treatment of psoriasis. Additionally, data are available on the potential efficacy of JAK-inhibitors in alopecia areata, atopic dermatitis and vitiligo. Mostly, JAK-inhibitors are used orally. However, there are studies showing efficacy of topical administration of this group of drugs in psoriasis and vitiligo. Further research is needed, especially the head-to-head comparison studies with JAK-inhibitors and current therapeutic methods to verify the superiority of this new group of drugs in dermatological diseases.

Genetic polymorphisms may influence the vertical growth rate of melanoma.

Background: Identification of new predictive markers in melanoma is of great clinical importance. This study was aimed to analyze association between selected common variants in the cancer susceptibility genes and melanoma progression at the time of diagnosis. Material and Method: The study included 243 consecutive patients with melanoma. Genotyping was performed using real-time PCR. Results: Our data revealed modest association between xeroderma pigmentosum complementation group D (XPD) codon 312 polymorphism and tumor thickness (as defined by Breslow score; XPD D312N CC: 3.00 ± 3.78mm, CT: 1.71 ± 2.48mm, TT: 2,53 ± 3,24mm, P=0.023). The CT genotype in XPD D312N polymorphism was more frequently represented in non-invasive melanomas compared to deeply penetrating tumors. None of the common SNPs in cyclin dependent kinase inhibitor 2A (CDKN2A), vitamin D receptor (VDR), melanocortin 1 receptor (MC1R) were associated with Breslow depth. Conclusion: These findings suggest that genetic alteration in XPD contributes to melanoma progression and may be a potential diagnostic and molecular prognostic marker.

Hypotensive effect of S-adenosyl-L-methionine in hypertensive rats is reduced by autonomic ganglia and KATP channel blockers.

S-adenosyl-L-methionine (SAM) is an amino acid involved in a number of physiological processes in the nervous system. Some evidence suggests a therapeutic potential of SAM in hypertension. In this study we investigated the effect of intracerebroventricular (ICV) infusions of SAM on arterial blood pressure in rats. Mean arterial blood pressure (MABP) and heart rate (HR) were measured at baseline and during ICV infusion of either SAM or vehicle (aCSF; controls) in conscious, male normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR). MABP and HR were not affected by the vehicle. WKY rats infused with SAM (10 µM, 100 µM and 1 mM) showed a biphasic hemodynamic response i.e., mild hypotension and bradycardia followed by a significant increase in MABP and HR. On the contrary, SHR infused with SAM showed a dose-dependent hypotensive response. In separate series of experiments, pretreatment with hexamethonium, a ganglionic blocker as well as pretreatment with glibenclamide, a KATP channel blocker reduced the hemodynamic effects of SAM. SAM may affect the nervous control of arterial blood pressure via the autonomic nervous system and KATP channel-dependent mechanisms.

Exogenous hydrogen sulfide produces hemodynamic effects by triggering central neuroregulatory mechanisms.

Recently, it was found that hydrogen sulfide (H2S) may serve as an important transmitter in peripheral organs as well as in the brain. The aim of the present study was to evaluate the possible function of H2S in the brain regulation of the circulatory system. Experiments were performed on conscious, male, Wistar-Kyoto rats. Mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously under baseline conditions and during infusions into the lateral cerebral ventricle (LCV) of the experimental animals. In control series LCV infusion of vehicle (Krebs-Henseleit bicarbonate-buffer) did not cause significant changes in MABP or HR. LCV infusion of H2S donor (NaHS) at the rate of 400 n/h resulted in an increase in MABP, whereas infusions at the rate of 100 n/h and 200 n/h failed to change MABP. On the other hand LCV infusion of H2S donor at the rate of 200 n/h caused a significant increase in HR while infusion at the rate of 400 n/h produced an increase in HR, which was smaller than this observed during infusion at the rate of 200 n/h. H2S donor administered at the rate of 100 n/h failed to affect HR. In conclusion, the present study demonstrates that exogenous hydrogen sulfide changes hemodynamic parameters by centrally mediated mechanisms. The hemodynamic effect seems to be dependent on H2S concentration in cerebrospinal fluid. It appears that the hypertensive response may occur at a concentration, which does not exceed twice the physiological level.