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].

Non-melanoma skin cancer outcomes in kidney transplant recipients converted from calcineurin inhibitors to mTOR inhibitors: a systematic review.

Renal transplant recipients treated with calcineurin inhibitors (CNIs) are at a high risk of developing a skin cancer. Therefore, new therapeutic options such as inhibitors of the mammalian target of rapamycin (mTORi) have been studied to find treatment regimens decreasing the rate of skin cancers. This systematic review focuses on recent randomized controlled trials studying the impact of conversion from CNI to mTORi in renal transplant recipients on development of non-melanoma skin cancers (NMSC). Outcomes of analysed trials revealed that conversion from CNI to mTORi in post-transplant patients reduces the risk and delays the occurrence of NMSC. However, mTORi protective properties against NMSC are more effective in patients with a history of a single SCC compared with multiple SCCs. At the same time, conversion to mTORi is associated with more common discontinuations secondary to adverse events and also increased mortality. In conclusion, conversion to mTORi is protective against NMSC but given the high AE rates and therapy discontinuation there is a need to determine who would benefit from conversion and search for new treatment regimens including combination strategies with mTORi.

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.

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.

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.

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.

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 ambiguous pruritogenic role of interleukin-31 in cutaneous T-cell lymphomas in comparison to atopic dermatitis: a review.

Cutaneous T-cell lymphomas (CTCLs) comprise a group of chronic heterogeneous diseases of unknown pathogenesis, characterized by non-specific skin lesions such as patches, plaques and tumours. CTCL is accompanied by persistent pruritus poorly responding to antihistamines and therefore significantly reducing quality of life in patients with lymphomas. According to research data, interleukin-31 (IL-31) contributes to initiation and maintenance of the inflammatory process of the skin and pruritus in inflammatory dermatoses such as atopic dermatitis (AD), which is well established. The studies of a similar role of IL-31 in CTCLs are less homogenous. Due to contradictory reports concerning IL-31 and CTCL we have analysed available literature to summarize its role, focusing on CTCL and AD.

Mapping signal transducer and activator of transcription (STAT) activity in different stages of mycosis fungoides and Sezary syndrome.

BACKGROUND: Deregulation of signal transducer and activator of transcription (STAT) signaling is known to participate in the pathogenesis of cutaneous T-cell lymphomas (CTCLs). However, published results regarding STAT expression in different stages of CTCLs are conflicting. The aim of the study was to define the pattern of STAT expression in skin and detect any differences between pruritic and nonpruritic patients but also different stages of disease. METHODS: Thirty-nine skin biopsies from CTCL patients and 24 biopsies from healthy volunteers were taken. Immunohistochemical staining for STAT 3, 5a, 5b, and 6 was performed in formalin-fixed paraffin-embedded sections of mycosis fungoides (MF) and Sezary syndrome (SS) specimens. RESULTS: We found increased expression of STAT proteins in CTCL: MF and SS skin in comparison to the control group. STAT5 but also STAT6 and to a lesser extent STAT3 seems to be constitutively activated in MF and SS. Moreover, also downregulation of STAT5b protein in advanced-stage CTCL appears to contribute to its pathogenesis. There were no significant associations between expression of STATs and pruritus severity. CONCLUSIONS: Our results confirm the possible pathogenetic role of STATs in CTCL. STATs seem to be a promising target for new effective therapeutic agents in CTCL.

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas.

The skin barrier defect in cutaneous T-cell lymphomas (CTCL) was recently confirmed to be similar to the one observed in atopic dermatitis (AD). We have examined the expression level of cornified envelope (CE) proteins in CTCL, AD and healthy skin, to search for the differences and their relation to the courses of both diseases. The levels of FLG, FLG2, RPTN, HRNR, SPRR1A, SPRR1B, SPRR3 and LELP-1 mRNA were determined by qRT-PCR, while protein levels were examined using the ELISA method in skin samples. We have found that mRNA levels of FLG, FLG2, LOR, CRNN and SPRR3v1 were decreased (p ≤ 0.04), whereas mRNA levels of RPTN, HRNR and SPRR1Av1 were increased in lesional and nonlesional AD skin compared to the healthy control group (p ≤ 0.04). The levels of FLG, FLG2, CRNN, SPRR3v1 mRNA increased (p ≤ 0.02) and RPTN, HRNR and SPRR1Av1 mRNA decreased (p ≤ 0.005) in CTCL skin compared to the lesional AD skin. There was a strong correlation between the stage of CTCL and increased SPRR1Av1 gene expression at both mRNA (R = 0.89; p ≤ 0.05) and protein levels (R = 0.94; p ≤ 0.05). FLG, FLG2, RPTN, HRNR and SPRR1A seem to play a key role in skin barrier dysfunction in CTCL and could be considered a biomarker for differential diagnosis of AD and CTCL. SPRR1Av1 transcript levels seem to be a possible marker of CTCL stage, however, further studies on a larger study group are needed to confirm our findings.

Clinicopathologic retrospective analysis of blastic plasmacytoid dendritic cell neoplasms.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one of the aggressive rare hematopoietic malignancies with predilection to the skin, primarily found in adults. The precise incidence of BPDCN is difficult to estimate due to constantly changing nomenclature and lack of precise defining criteria prior to the 2008 WHO classification system. There are not many cases described in the literature, what makes the diagnostic process challenging. Skin lesions such as erythematous infiltrates and nodules are usually the first manifestation of the disease. Therefore, in doubtful diagnostic cases, dermatologists should perform histopathological and immunohistochemistry examinations along with hematological and oncological cooperation, as early diagnosis and appropriate treatment is essential for improvement of the disease course. This analysis, despite the small number of patients may provide useful information on the clinical and histopathological features of this rare malignancy.

The role of polymorphism of interleukin-2, -10, -13 and TNF-α genes in cutaneous T-cell lymphoma pathogenesis.

INTRODUCTION: As the pathogenesis of cutaneous T-cell lymphomas (CTCL) is not fully understood, inherited gene polymorphisms are considered to play a role in the development of lymphomas. AIM: To investigate whether certain gene polymorphisms might be involved in the development of CTCL. MATERIAL AND METHODS: In the case-control study we compared the frequency of nine selected single nucleotide polymorphisms (SNP) of seven genes (rs1800587/-889 C/T of interleukin (IL)-1α, rs2069762/-330G/T) and rs2069763/+166G/T of IL-2, rs1800925/-1112 C/T of IL-13, rs1800896/-1082 A/G of IL-10, rs4073/-251 A/T of IL-8, rs5370/K198N, rs180054/-1370T/G of endothelin-1 and rs1800629/-308 G/A of TNF-α) in 43 CTCL and Polish cases using the amplification refractory mutation system polymerase chain reaction method. RESULTS: We have found that two genotypes, -330GG of IL-2 and -1112TT of IL-13 both promoter variants associated with "hypertranscription phenotype", were over-represented in CTCL patients compared to healthy controls, and they increase the risk of malignancy development (OR = 5.82, p = 0.001 for IL-2 -330 GG, and OR = 5.67, p = 0.0024 for IL-13 -1112 TT). On the other hand, high transcription -308A allele of the TNF-α gene and -1082GG of IL-10 genotype is less frequent in lymphoma patients and has protective effects on the development of CTCL (OR = 0.45, p = 0.0466 for -308A of TNF-α, and OR = 0.35, p = 0.0329 for -1082GG of IL-10 genes). CONCLUSIONS: Our results indicate that hypertranscription promoter variants of IL-2 and IL-13 genes could be estimated as the risk factor for development of CTCL, while TNF-α and IL-10 variants have a protective effect.