Vitiligo-like lesions in patients with advanced breast cancer treated with cycline-dependent kinases 4 and 6 inhibitors.

PURPOSE: Introduction of cyclin-dependent inhibitors was a milestone in therapeutics for patients with estrogen receptor+/HER2- metastatic breast cancer. Despite the wide use of such agents and remarkable improvement of survival rates, drug-related adverse events are not yet fully characterized. We describe vitiligo-like lesions as a new adverse event occurring in patients with advanced breast cancer treated with cyclin-dependent inhibitors. METHODS: We performed an international retrospective study including patients with advanced breast cancer who developed vitiligo-like lesions during treatment with cyclin-dependent kinases 4 and 6 inhibitors, in the period January 2018-December 2019. Patients > 18 years, both males and females, were recruited at six Dermatology Departments located in Italy (3), France (1) and Greece (2). We evaluated epidemiological and clinical characteristics, impact on quality of life and outcome of vitiligo-like lesions in patients treated with cyclin-dependent 4 and 6 inhibitors. The percentage of skin involved by vitiligo-like lesions was assessed using the Body Surface Area (BSA) score. Changes in patients' quality of life were investigated through the evaluation of the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: Sixteen women (median age: 62.5 years; range 40-79 years) treated with cyclin-dependent kinases 4 and 6 inhibitors for advanced breast cancer presented with vitiligo-like lesions during follow-up visits. Cutaneous lesions consisted of white, irregular macules and patches located mainly on sun-exposed areas in 11/16 patients or diffuse to the entire body surface in 5/16. Cutaneous lesions clearly impaired the quality of life of patients tested (DLQI ≥ 10). CONCLUSIONS: We present for the first time, to our knowledge, a case series of vitiligo-like lesions developing in patients with advanced breast cancer treated with cyclin-dependent kinases 4 and 6 inhibitors. We showed that such lesions further impair the patients' quality of life and their treatment is challenging.

Immune checkpoint-mediated psoriasis: A multicenter European study of 115 patients from the European Network for Cutaneous Adverse Event to Oncologic Drugs (ENCADO) group.

BACKGROUND: Immune checkpoint inhibitor (ICI)-mediated psoriasis poses significant diagnostic and therapeutic challenges. OBJECTIVE: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm. METHODS: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions. RESULTS: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P = .03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P < .001). Guttate psoriasis and grade 2 or 3 disease were significant positive predictors for antitumor response of ICI, whereas pruritus was a negative predictor. LIMITATIONS: Retrospective design. CONCLUSION: Acitretin, apremilast, and methotrexate are safe and effective modalities for ICI-mediated psoriasis. In most cases, ICI can be completed unhindered. A therapeutic algorithm is proposed.

Another window into tumor microenvironment: a case of Β-cell rich folliculotropic mycosis fungoides responding to rituximab.

The role of tumor infiltrating immune cells in cancer development and progression is a new, promising field in oncological research. An increasing number of novel anti-cancer agents are focussing on the tumor microenvironment. Various studies have reported on B-cell infiltrates in mycosis fungoides (MF), but despite the substantial volume of interesting findings, solid evidence regarding their specific role in cancer is still vague. We present a case of tumor stage  MF responding to rituximab. We support the hypothesis that lymphoma-infltrating B-cells have a significant impact on cutaneous lymphoma course and seem to be both an important and effective therapeutic target. The reduction of B-cell population led to disease's overall remission, probably by restoring patient's immunologic tumor control.

Lymphoprolipherative skin reactions induced by anti-TNFα: an open question.

Although anti-TNFα agents have revolutionized the treatment of many inflammatory diseases, various concerns have been reported regarding the risks of cancer development, as well as acceleration of the progression of subclinical, preexisting malignancies. In this case series, we investigated the provocative effect of anti-TNFα drugs in the development of cutaneous mycosis fungoides (MF)-like lymphoproliferative reactions. We describe five patients aged between 25-63 diagnosed with autoimmune disorders (psoriatic arthritis - one patient, Crohn's disease - one patient and ankylosing spondylitis - three patients) who received anti-TNFα agents before the development of a cutaneous lymphoproliferative reaction. Histological and immunophenotypical analysis was typical for mycosis fungoides in all of them. Anti-TNFα agents were stopped with regression of the skin rash. A direct effect of anti-TNFα agents in the development of lymphoproliferative reactions (including MF) is suggested and further analyzed. Treatment cessation can be therapeutic.

The different faces of mycosis fungoides: results of a single-center study.

BACKGROUND: Mycosis fungoides (MF) accounts for the majority of cutaneous lymphomas. Apart from the predominant Alibert-Bazin type, several clinicopathological variants of diverse prevalence and biological behavior have been described. Data on clinical and epidemiological aspects of MF clinical subtypes are still weak. AIM: To outline the clinical and epidemiological profile of the different MF types in a large volume of Greek patients. METHODS: Retrospective analysis of 688 MF cases treated in our lymphoma clinic. Epidemiological, clinical, pathological, and immunohistochemical data were retrieved. RESULTS: Six-hundred and thirty-six patients (416 males, 220 females) were included. The mean age at diagnosis was 60.2 years; the mean duration of disease prior to diagnosis was 63.2 months. Early-stage MF (I-IIA) involved 475 cases (74.7%). The prevalent type was classical MF (68.5%), followed by folliculotropic (17%), poikilodermic (5.5%), and psoriasiform (4.7%) MF. Atypical MF lesions as the sole manifestation of folliculotropic mycosis fungoides (FMF) - alopecia areata-like lesions (n = 10), keratosis pilaris-like lesions (n = 9) or acneiform rash (n = 4) - were also observed. Both poikilodermic and folliculotropic subtypes mainly involved younger patients. A significant diagnostic latency concerning poikilodermic and psoriasiform MF cases was recorded. Only 23 (3.3%) cases were of juvenile onset, with classical and poikilodermic MF equally affecting this age group, closely followed by FMF. CONCLUSIONS: Our study presents the whole clinical-epidemiological spectrum of MF in a large Greek cohort. The high prevalence of atypical MF manifestations characterized by early onset and indolent clinical course stood out among our FMF sample.

Anti-PD1/PDL1 induced psoriasis.

BACKGROUND: Immune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported. METHODS: We present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy. RESULTS: A total of 5 patients were overall included (4 males, 1 female mean age 65.8 years). Among them, 3 were diagnosed with nonsmall cell lung cancer, 1 with papillary urothelial carcinoma, and 1 with squamous cell carcinoma of the tonsil. Of all, 3 patients were treated with anti-PD1 (1 with pembrolizumab, 2 with nivolumab), whereas the remaining 2 with anti-PDL1 (durvalumab). Only 1 out of 5 patients had active psoriatic lesions at the time of treatment initiation, 2 shared a past history of psoriasis, and 1 reported a strong related family history (3/5 siblings). Four out of 5 patients experienced guttate lesions, though the most severe exacerbation was noted in the durvalumab group. Four out of 5 patients managed to continue treatment after close dermatologic monitoring, whereas 1 patient under durvalumab was forced to treatment delays owing to the severity of the skin reactions. Skin rashes appeared in all patients after the fourth cycle of immunotherapy. CONCLUSIONS: Both anti-PD1 and anti-PDL1 therapies can lead to psoriasis exacerbation although more severe flares were noted in patients treated with durvalumab. Not only personal but also related family history of psoriasis are significant risk factors and need to be outlined before treatment initiation. If such related history exists, strict skin surveillance can lead to the early diagnosis and treatment of any psoriatic exacerbations that could otherwise severely affect quality of life or even compromise therapeutic protocols and final prognosis.