Rare COVID-19 vaccine side effects got lost in the shuffle. Primary cutaneous lymphomas following COVID-19 vaccination: a systematic review.

Introduction: COVID-19 vaccines are generally safe and effective; however, they are associated with various vaccine-induced cutaneous side effects. Several reported cases of primary cutaneous lymphomas (CLs) following the COVID-19 vaccination have raised concerns about a possible association. This systematic review aims to investigate and elucidate the potential link between CLs and SARS-CoV-2 vaccines. Methods: We performed a systematic literature search on PubMed, EBSCO and Scopus from January 01, 2019, to March 01, 2023, and analyzed studies based on determined eligibility criteria. The systematic review was performed based on the PRISMA protocol. Results: A total of 12 articles (encompassing 24 patients) were included in this analysis. The majority of CLs were indolent cutaneous T-cell lymphomas (CTCLs) (66,7%; 16/24), with Lymphomatoid papulosis (LyP) being the most common type (33,3%; 8/24). Most patients (79,2%; 19/24) developed lesions after receiving the COVID-19 mRNA-based vaccines, and predominantly after the first immunization dose (54,2%; 13/24). The presented CLs cases exhibited a tendency to exacerbate following subsequent COVID-19 vaccinations. Nevertheless, CLs were characterized by a favorable course, leading to remission in most cases. Conclusion: The available literature suggests an association between the occurrence and exacerbation of CLs with immune stimulation following COVID-19 vaccination. We hypothesize that post-vaccine CLs result from an interplay between cytokines and disrupted signaling pathways triggered by vaccine components, concurrently playing a pivotal role in the pathomechanism of CLs. However, establishing a definitive causal relationship between these events is currently challenging, primarily due to the relatively low rate of reported post-vaccine CLs. Nonetheless, these cases should not be disregarded, and patients with a history of lymphoproliferative disorders require post-COVID-19 vaccination monitoring to control the disease's course.Systematic review registrationwww.researchregistry.com, identifier [1723].

Contact Dermatitis to Diabetes Medical Devices.

Skin adverse reactions to diabetes medical devices have been reported frequently over recent years. Adhesives attaching glucose sensors and continuous insulin infusion sets to the skin are proven to cause both allergic contact dermatitis and irritant contact dermatitis in patients with diabetes mellitus. Several allergens contained in adhesives and/or parts of medical devices are documented to cause allergic contact dermatitis, with acrylate chemicals being the most common culprit-especially isobornyl acrylate (IBOA), but also 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate or cyanoacrylates. Epoxy resin, colophonium and nickel were also identified as causative allergens. However, repetitive occlusion, maceration of the skin and resulting disruption of the skin barrier seem to have an impact on the development of skin lesions as well. The purpose of this study is to highlight the burden of contact dermatitis triggered by diabetes medical devices and to show possible mechanisms responsible for the development of contact dermatitis in a group of diabetic patients.

Etiopathogenesis and Emerging Methods for Treatment of Vitiligo.

Vitiligo is an acquired chronic depigmenting disorder of skin. It is mostly asymptomatic and characterized by amelanotic macules and patches that affects 0.5% to 2% of the world's population. The etiology of vitiligo has not been clearly elucidated and multiple theories have been proposed regarding the causes of the disorder. Among the most prevalent theories, the genetic predisposition, oxidative stress theory, promotion of cellular stress and pathologic influence of lymphocytes T have been highlighted. As a result of increases in in-depth knowledge concerning the pathogenetic processes in vitiligo, we review the most recent information concerning its etiopathogenesis and treatment methods including topical and oral Janus kinase inhibitors, prostaglandins and their analogues, namely afamelanotide, Wnt/ß-catenin-signaling agonists and cell-based therapies. Topical ruxolitinib has been registered for vitiligo treatment, whereas other agents as oral ritlecitinib, afamelanotide and latanoprost have been studied in ongoing clinical trials. New highly effective therapeutic strategies may be developed thanks to molecular and genetic studies.

Penile metastasis secondary to urothelial bladder cancer.

Penile metastasis is extremely rare. The most common neoplasms that spread to the external male genital area are bladder and prostate cancer. The diagnosis usually begins with the appearance of penile symptoms. Further examination usually reveals metastasis to other organs, which worsens the patient prognosis. We present a case report of an 80-year-old patient who was accidently diagnosed with metastatic high-grade urothelial cancer during a male circumcision. Further diagnostic process revealed a disseminated neoplastic disease. Whole-body computed tomography (CT) scan often reveals disseminated neoplastic disease, which is the cause of high mortality in secondary penile neoplasms.

Altered mRNA Expression of NFKB1 and NFKB2 Genes in Penile Lichen Sclerosus, Penile Cancer and Zoon Balanitis.

BACKGROUND: The nuclear factor-κB transcription factors 1 and 2 (NFKB1 and NFKB2) are key components of the NF-κB pathway, which responds to inflammatory signals. Since the NFKB1/2 factors are activated via different inflammatory molecules, we aimed to check their expression levels in penile cancer (PC), penile dermatoses: lichen sclerosus (PLS) and zoon balanitis (ZB). METHODS: Skin biopsies from altered and healthy looking foreskin were obtained from 59 (49 LS; early PLS: 13, moderate PLS: 32, severe PLS: 4; 6 PC; 4 ZB) and unchanged foreskin from 13 healthy control adult males undergoing circumcision. NFKB1/2 mRNA levels were quantified by qPCR. RESULTS: The highest levels of NFKB1 and NFKB2 were observed in PC, ca. 22 and 3.5 times higher than in control, respectively. NFKB1 expression was correlated with PLS progression (rs = 0.667) and was ca. 20 times higher in advanced PLS than in controls and early PLS. Occurrence of micro-incontinence was associated with elevated NFKB1 levels in PLS. CONCLUSION: This is the first study regarding gene profiles of NFKB1/2 in PC and penile dermatoses. New drugs targeting modulation of canonical-activated NF-κB pathway should be studied and introduced to the treatment of PLS and PC apart from other treatments.

Seasonal Patterns and Trends in Dermatoses in Poland.

BACKGROUND: The amount of data available online is constantly increasing, including search behavior and tracking trends in domains such as Google. Analyzing the data helps to predict patient needs and epidemiological events more accurately. Our study aimed to identify dermatology-related terms that occur seasonally and any search anomalies during the SARS-CoV-2 pandemic. METHODS: The data were gathered using Google Trends, with 69 entries between January-2010 and December-2020 analyzed. We conducted the Seasonal Mann-Kendal Test to determine the strength of trends. The month with the highest seasonal component (RSV) and the lowest seasonal component (RSV) was indicated for every keyword. Groups of keywords occurring together regularly at specific periods of the year were shown. RESULTS: We found that some topics were seasonally searched in winter (e.g., herpes, scabies, candida) and others in summer (e.g., erythema, warts, urticaria). CONCLUSIONS: Interestingly, downward trends in searches on sexually transmitted diseases in comparison with increased infection rates reported officially show a strong need for improved sexual education in Poland. There were no significant differences in trends for coronavirus-related cutaneous symptoms during 2020. We have shown that the seasonality of dermatologically related terms searched in Poland via Google did not differ significantly during SARS-CoV-2 pandemic.

Interleukin-31 is overexpressed in skin and serum in cutaneous T-cell lymphomas but does not correlate to pruritus.

Introduction: Cutaneous T-cell lymphomas (CTCL) are malignant lymphoproliferative disorders accompanied by persistent pruritus. Pruritogenic role of interleukin-31 (IL-31) has been studied extensively and was proven in atopic dermatitis (AD), while its role in CTCL is still rather vague. Aim: To investigate IL-31 serum level along with IL-31, IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMR) skin expression in CTCL and compare it to controls: AD and healthy volunteers. Material and methods: The level of IL-31 in serum was measured using ELISA, while IL-31 and receptors' expression in the skin were measured using immunohistochemistry and correlated with the stage of disease and pruritus severity. Results: Expression of IL-31 and IL-31 receptor in serum and skin were significantly higher in CTCL and AD in comparison to healthy controls. No significant correlation between the IL-31 serum level and pruritus severity in CTCL patients was found. There was also no correlation between IL-31/IL-31RA/OSMR expression in the skin and CTCL pruritus, while IL-31 and IL-31RA in CTCL skin negatively correlated with the stage of disease. Conclusions: Our data indicate that IL-31 does not play a crucial role in pruritus in CTCL but it is rather involved in the pathogenesis of the disease. It seems that IL-31 plays an essential role in the pruritus pathomechanism that is unique to AD.

Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society.

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

Safety and Danger Considerations of Novel Treatments for Atopic Dermatitis in Context of Primary Cutaneous Lymphomas.

The impact of new and emerging therapies on the microenvironment of primary cutaneous lymphomas (PCLs) has been recently raised in the literature. Concomitantly, novel treatments are already used or registered (dupilumab, upadacitinib) and others seem to be added to the armamentarium against atopic dermatitis. Our aim was to review the literature on interleukins 4, 13, 22, and 31, and JAK/STAT pathways in PCLs to elucidate the safety of using biologics (dupilumab, tralokinumab, fezakinumab, nemolizumab) and small molecule inhibitors (upadacitinib, baricitinib, abrocitinib, ruxolitinib, tofacitinib) in the treatment of atopic dermatitis. We summarized the current state of knowledge on this topic based on the search of the PubMed database and related references published before 21 October 2021. Our analysis suggests that some of the mentioned agents (dupilumab, ruxolitinib) and others may have a direct impact on the progression of cutaneous lymphomas. This issue requires further study and meticulous monitoring of patients receiving these drugs to ensure their safety, especially in light of the FDA warning on tofacitinib. In conclusion, in the case of the rapid progression of atopic dermatitis/eczema, especially in patients older than 40 years old, there is a necessity to perform a biopsy followed by a very careful pathological examination.

Translation, cross-cultural adaptation and validation of the vitiligo-specific health-related quality of life instrument (VitiQoL) into Polish.

INTRODUCTION: Vitiligo is an acquired chronic depigmenting disorder of the skin, predominantly asymptomatic. Although vitiligo does not cause direct physical impairment, it is commonly believed that it can produce an important psychosocial burden. AIM: To translate, cross-culturally adapt and validate the vitiligo-specific health-related quality of life instrument (VitiQoL) into Polish. MATERIAL AND METHODS: The study was conducted online on 97 patients with vitiligo from our private outpatient departments in Gdynia and Gdansk, Poland from May 2018 to December 2019. RESULTS: There was a significant correlation between VitiQoL and DLQI (r = 0.90, p < 0.001) and also between VitiQoL-PL and subjects' assessment of the severity of their disease (r = 0.94, p < 0.001). We also found a good correlation between the total DLQI and subjects' assessment of the severity of their disease (r = 0.87, p < 0.001). CONCLUSIONS: The physicians treating this disease still do not have a specific instrument for assessing patients' QoL in Poland. They have to administer other non-vitiligo specific questionnaires to do so. A Polish version of a specific index for estimating quality of life of patients with vitiligo was validated and implemented through an online survey.

Significance of interleukin-31 (IL-31) gene polymorphisms and IL-31 serum level in psoriasis in correlation with pruritus.

INTRODUCTION: Interleukin-31 (IL-31) impact on the development and clinical presentation of psoriasis as well as pruritus has not been widely investigated so far. AIM: To analyse IL-31 -1066G/A and -2057G/A promoter gene polymorphisms as well as serum IL-31 level and their correlation with severity of psoriasis and pruritus in the population of northern Poland. MATERIAL AND METHODS: The study included 300 psoriasis patients and 186 healthy volunteers. The polymorphisms were analysed using amplified refractory mutation system - polymerase chain reaction (ARMS-PCR) method. Serum levels of IL-31 were measured using the enzyme-linked immunosorbent assay (ELISA) test. RESULTS: The -1066 AA genotype of the IL-31 gene was statistically more frequent in patients and it increased the risk of psoriasis (OR = 1.80; p = 0.04). The GG genotype as well as G allele of the IL-31 -2057 gene polymorphism were rarely observed in psoriasis and were associated with a decreased risk of the disease (OR = 0.6, p = 0.007 and OR = 0.7, p = 0.01, respectively). Serum levels of IL-31 were significantly elevated in psoriasis patients (p < 0.000001), however, they did not correlate with the studied polymorphic variants of the IL-31 gene, severity of psoriasis, disease onset, presence of psoriatic arthritis and pruritus intensity. CONCLUSIONS: Distinct IL-31 promoter gene polymorphisms may be involved in psoriasis development. It seems that serum concentration of IL-31 may not be a reliable marker of psoriatic pruritus.

The incidences of other primary cancers in patients with mycosis fungoides and Sézary syndrome.

INTRODUCTION: Cutaneous T-cell lymphomas (CTCLs) are a diverse group of non-Hodgkin's lymphomas with malignant T lymphocytes infiltrating the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) belong to the group of CTCLs, among others. In previous studies it was suggested that primary cancers more often occur in patients with cutaneous lymphoma. AIM: To analyse the incidence of other malignancies in CTCL patients. MATERIAL AND METHODS: The evaluation of the coexistence of primary malignant neoplasms in CTCL patients was conducted by analysis of the patients' database, with diagnosis of mycosis fungoides and Sézary syndrome, treated in the Dermatological Department of the Medical University of Gdansk between 2010 and 2018. RESULTS: Among CTCL patients, 177 were diagnosed with MF/SS (stage MFIA 37.61%, MFIB 30.77%, MFIIA 0.85%, MFIIB 11.11%, MFIII 8.55% MFIV 4.27%; SS 6.84%). The group was characterized by a male-to-female ratio of 1.21 : 1. 16.94% of MF/SS patients had one co-existing cancer, while 1.13% of patients had 2 co-existing cancers; the most common were basal cell carcinoma, lymphomatoid papulosis, lung cancer, and B-cell lymphoma. The obtained data highlight that MF/SS is associated with increased risk of cancer. CONCLUSIONS: Our study suggests that special attention should be paid to careful examination of CTCL patients - what force to perform solid clinical examination, the X-ray chest examination, abdomen USG, mammography, and others, even in early stages of MF/SS. Clinicians should be aware of the coexistence of other neoplasms such as lung, skin, and breast cancer.

Male Circumcision Due to Phimosis as the Procedure That Is Not Only Relieving Clinical Symptoms of Phimosis But Also Improves the Quality of Sexual Life.

INTRODUCTION: Male circumcision is recognized as the most effective method of phimosis treatment. Analyzing the literature, the information about the influence of male circumcision due to phimosis for patients' subjective symptoms such as itching, burning, penile pain, pain during intercourse, and quality of sexual life is insufficient. AIM: To investigate the effect of male circumcision due to phimosis to patients' subjective symptoms, including erectile function and satisfaction with their genitals. METHODS: The single-center prospective study began in January 2018 and ended in January 2020. Sixty-nine male, adult patients, who were qualified for circumcision due to phimosis, were included in the study. MAIN OUTCOMES MEASURES: The study outcomes were obtained using questionnaires such as visual analog scale 0-10 for itching, burning, penile pain, and penile pain during intercourse; International Index of Erectile Function (IIEF-5) and Male Genital Self Image Scale 7 (MGSIS-7) to assess the changes in patients sexual functioning. RESULTS: Before the circumcision of the 69 patients included in the study, 59 patients (86%) reported some subjective symptoms of phimosis. The most frequent and most severe complaint was pain during intercourse, then itching and burning of the penis. Penile pain at rest was the least frequent. After 3 months from circumcision, subjective symptoms almost completely disappeared. All of 69 patients declared to have a sexual partner. 3 months after circumcision, all patients achieved significant improvement in both obtaining and maintaining an erection based on IIEF-5 score. Their sexual intercourse was more satisfying for them. All patients suffering from phimosis were embarrassed about their genitals before surgery. 3 months after circumcision, satisfaction with genital self-image increased significantly. CONCLUSION: Male circumcision due to phimosis is not only relieving the clinical symptoms of phimosis, but it also improves the quality of sexual life. Czajkowski M, Czajkowska K, Zaranska K, et al. Male Circumcision Due to Phimosis as the Procedure That Is Not Only Relieving Clinical Symptoms of Phimosis But Also Improves the Quality of Sexual Life. Sex Med 2021;9:100315.

Safety and danger of biologic treatments in psoriasis in context of cutaneous T-cell lymphoma (CTCL).

Microenvironment has a significant impact on the pathogenesis of cutaneous T-cell lymphoma (CTCL), especially in the context of new emerging biologic therapies. Our aim was to review the literature on interleukins 12, 17, 23 and tumour necrosis factor-α in mycosis fungoides in order to clarify the safety of using biologics in the treatment of psoriasis. Our analysis suggests that these drugs may have an impact on the progression of CTCL. Concluding, in case of uncertain psoriatic lesions, a biopsy followed by pathologic examination should exclude the possibility of co-existence of a primary cutaneous lymphoma before administration of therapies affecting cytokine profiles.

Efficacy, quality of life, and safety of methotrexate versus interferon in head-to-head treatment in advanced stages of mycosis fungoides and Sezary syndrome. Prospective trial (NCT02323659).

Introduction: ESMO guidelines recommend interferon (IFN) and methotrexate (MTX) as first-line systemic therapies in mycosis fungoides (MF) and Sezary syndrome (SS). Aim: A prospective, head-to-head trial comparing the efficacy and safety of INF-α and MTX as first-line treatment in MF/SS patients. Material and methods: Forty-three patients were enrolled in the trial. The response to treatment and side effects were assessed. Study variables included mSWAT, DLQI, and VAS scores. Results: The response rate in stage IV including SS was significantly higher in the IFN-α group than in the MTX group (100% vs. 40%; p = 0.03, respectively). No significant differences were found in response rate in stage IIB and III between treatment groups. Patients treated with IFN-α had significantly shorter time to achieve response (TTR). Significantly fewer in the IFN-α group experienced adverse events (AE) in comparison to patients treated with MTX (81% vs. 45%; p = 0.02). There was no statistically significant difference between both groups in terms of time to progression (TTP), progression-free survival (PFS), time on treatment (ToT), and time to next treatment (TTNT). The improvement in quality of life and reduction of pruritus was comparable in both treatment groups. Conclusions: The obtained data suggest that the efficacy of IFN-α as first-line treatment in advanced stage (IV) MF and SS is significantly better than MTX. IFN-α presented significantly better safety and tolerability and shorter TTR than MTX. However, the results should be interpreted with caution due to scarce study groups.

The polymorphisms of IL-6/STAT3 signaling pathway may contribute to cutaneous T-cell lymphomas susceptibility.

IL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8, p = 0.04 for IL-6 and OR 2.53, p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.

Lichen Sclerosus and Phimosis - Discrepancies Between Clinical and Pathological Diagnosis and Its Consequences.

OBJECTIVE: To assess the accuracy of clinical diagnoses and the true incidence of lichen sclerosus (LS) in patients with phimosis. MATERIALS AND METHODS: The 92 adult male patients who were qualified for circumcision due to phimosis, were included in the study. The patients were diagnosed clinically by a urologist and dermatologist before the surgical procedure. After the circumcision, the resected foreskins were examined by 2 independent uropathologists. RESULTS: Preoperative clinical diagnosis of LS was established in 54 patients (58.7%); healthy-looking skin in 26 (28.3%) and other penile diseases in 12 (13.1%) patients. After histopathological examination, the diagnosis of LS was established in 62 patients (67.4%), but only in 44 patients with previous LS clinical diagnosis. LS was histopathologically confirmed in 18 other patients with clinically diagnosed healthy skin (n = 17) or lichen planus (n = 1). Healthy skin was histopathologically confirmed in 10 cases in patients diagnosed clinically before as LS. Other 15 histopathological diagnoses were Zoon balanitis (n = 3), nonspecific balanitis (n = 5), lichen planus (n = 1), psoriasis (n = 1), invasive penile cancer (n = 3), Bowen's disease (n = 1), penile intraepithelial neoplasia 2 usual type (n = 1). CONCLUSION: LS has been revealed as the most common histopathological diagnosis in patients undergoing circumcision in our study. Histopathological examination seems to be necessary to exclude this disease.