The CCR4 receptor is a pivotal target in cutaneous T-cell lymphoma (CTCL) therapy due to its role in impairing immune responses against malignant T-cells and expression profiles. Monoclonal antibodies like mogamulizumab effectively bind to CCR4, reducing tumour burden and enhancing patient outcomes by inhibiting the receptor\'s interaction with ligands, thereby hindering malignant T-cell migration and survival. Combining CCR4 antibodies with chemotherapy, radiation, and other drugs is being explored for synergistic effects. Additionally, small-molecular inhibitors, old pharmacological agents interacting with CCR4, and CAR-T therapies are under investigation. Challenges include drug resistance, off-target effects, and patient selection, addressed through ongoing trials refining protocols and identifying biomarkers. Despite advancements, real-life data for most of the emerging treatments are needed to temper expectations. In conclusion, CCR4-targeted therapies show promise for CTCL management, but challenges persist. Continued research aims to optimise treatments, enhance outcomes, and transform CTCL management. This review aims to elucidate the biological rationale and the several agents under various stages of development and clinical evaluation with the actual known data.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the implementation of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs. (2) Methods: Single-center retrospective study in patients with ADRs after mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines). (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculopapular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular predominantly lymphocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred after the second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% of patients and maculopapular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients. (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. Interestingly, in about half of our patients, ADRs were self-limited, whereas ADRs extended beyond a month in the other half.

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A cutaneous horn, referred to as a cornu cutaneum in Latin, presents as a mound of keratinizing epithelium. The etiology of the cutaneous horn is associated with the lesion at its base. In addition to numerous benign and malignant neoplasms, cutaneous horns may be related to infections and skin conditions. The features of a 22-year-old woman with a cutaneous horn associated with a recalcitrant verruca vulgaris on her left fifth toe are described. In addition, the characteristics of a 57-year-old man with an inverted follicular keratosis-related cutaneous horn on his upper lip are reported. In order of decreasing frequency, a cutaneous horn is most associated with either an actinic keratosis (25%), a squamous cell carcinoma (19%), a seborrheic keratosis (19%-20%), or a verruca vulgaris (18%). Adnexal neoplasms, epithelial lesions, fibrous lesions, granular cell tumors, hamartomas, histiocytic lesions, melanocytic nevus, premalignant keratoses, a subungual lesion, and vascular lesions comprise the benign neoplasms that have been observed at the base of a cutaneous horn. Dermatologic conditions that have been associated with a cutaneous horn include discoid lupus erythematosus (three patients) and one patient with either palmoplantar keratoderma, psoriasis, or sarcoidosis. Human papillomavirus infection presenting as a verruca vulgaris is the most commonly associated infection; pox virus-related molluscum contagiosum is another viral infection that is less often observed associated with a cutaneous horn. Leishmaniasis, rhinosporidiosis, and cutaneous tuberculosis are rare cutaneous horn-related infections. A malignant tumor-associated cutaneous horn is most frequently caused by squamous cell carcinoma; other less common cancers include basal cell carcinoma, sebaceous carcinoma, verrucous carcinoma, and malignant melanoma. A cancer-related cutaneous horn has only been described in two patients with Kaposi sarcoma and one patient with either Merkel cell carcinoma or Paget disease of the breast or metastatic renal cell carcinoma. In summary, a cutaneous horn is potentially related to a tumor, an infection, or a skin disorder; an adequate evaluation of the base of the cutaneous horn is usually required to establish the associated diagnosis.

Refractory cutaneous manifestations constitute a significant unmet need in patients with cutaneous lupus (CLE), even in the setting of systemic lupus erythematosus (SLE) with otherwise good control of inflammatory manifestations. Anifrolumab, an anti-interferon I receptor monoclonal antibody has recently been approved for serologically positive SLE with or without CLE, but real-life efficacy and safety data are currently limited. In addition, relatively limited evidence exists about the spectrum of cutaneous manifestations potentially benefitting from anifrolumab treatment and about the optimal clinimetrics to monitor treatment efficacy. While summarising current evidence on the topic in the literature, we report on four patients with SLE and refractory CLE who were successfully treated with anifrolumab. We also describe the potential usefulness and complementarity of the cutaneous lupus activity investigator\'s global assessment (CLA-IGA) in assessing cutaneous activity in patients treated with anifrolumab.

Cutaneous endometriosis, characterized by the presence of endometrium or endometrial-like tissue outside of the uterine cavity, is an uncommon and chronic disease. Depending on a patient\'s history, cutaneous endometriosis is classified as either primary cutaneous endometriosis (PCE) or secondary cutaneous endometriosis (SCE). We report a case of SCE presenting with the classic triad of previous caesarean section, subcutaneous nodules at the site of the scar, and pain associated with menstruation. Considering histopathology as the standard, we confirmed a diagnosis of cutaneous endometriosis by ultrasound and histopathology. Furthermore, we compared and analyzed the clinical characteristics of PCE and SCE, the study included 20 and 14 patients with cutaneous endometriosis diagnosed with PCE and SCE respectively. In the PCE group, the mean age of patients at the onset was 33.7 years, while it was 40.6 years in the SCE group. The mean disease-duration time of PCE was shorter than that of SCE (1.3 vs. 2.8 years, P > 0.05). The most common clinical presentation of PCE and SCE was a nodule (90% vs. 86%). The PCE was mainly bleeding with pain (45%), whereas the SCE of only pain and bleeding with pain accounted for the same proportion (45%). The most common sites of PCE and SCE were in the umbilical region (90% vs. 57%, P < 0.05). In our study, some statistically significant difference was found between different types of CE and it may contribute to improve clinicians\' understanding of the disease, and perform early diagnosis and treatment.

[This corrects the article DOI: 10.3389/fonc.2023.1216725.].

UNASSIGNED: Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In this study, we aimed to compare the risks of cutaneous adverse events between imatinib- and second-generation TKI-treated patients with CML.
UNASSIGNED: Paired reviewers independently obtained studies from PubMed, Embase, and Cochrane Library published until 15 March 2022. The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. Two independent reviewers screened the results and selected articles on cutaneous adverse events. RevMan 5.4 and the Cochrane Collaboration tool were used to perform the meta-analysis and risk of bias assessment.
UNASSIGNED: Eleven trials involving 4502 patients were analyzed in this study. Patients treated with second-generation TKIs were significantly more likely to experience cutaneous adverse events than those treated with imatinib with a relative risk (RR) of 1.62 (95% confidence interval [CI], [1.25-2.09]). Except dasatinib (RR [95% CI], 1.39 [0.75-2.56]), the risk of adverse events was more with second-generation TKIs than with imatinib as follows: nilotinib (2.11 [1.53-2.90]), bosutinib (1.41 [1.07-1.86]), and radotinib (1.87 [1.33-2.63]). Rash was the most common cutaneous adverse event that was observed in 21.6% of cases across all grades, followed by pruritus (5.7%) and alopecia (4.3%). In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.

Crohn\'s disease (CD), an inflammatory bowel disease that involves the gastrointestinal tract, is observed in daily hospital practice. On the other hand, metastatic Crohn\'s disease (MCD) is a rare entity in which cutaneous lesions are found in regions apart from the digestive system. This article describes a rare case of cutaneous CD in a Saudi female, which manifested initially as vulvar and perianal skin lesions. The diagnosis was proven by skin biopsy, and adalimumab offered effective treatment. Although cutaneous MCD is rare, it is an important cutaneous manifestation, as early detection creates the possibility of accessing effective management.