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Background: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60–85%. Objective: To investigate prophylactic topical treatment for EGFRI-induced rash. Methods: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. Results: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. Conclusions: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

Background Real-life efficacy data on the recently approved once daily application of chlormethine gel (CG) for mycosis fungoides (MF) is limited, and detailed characterization of the side effects and their management are strikingly sparse. Objective To evaluate the efficacy and particularly the side effect profile of CG in early-stage MF patients in a real-life setting. Methods We performed a single-center retrospective analysis of 66 early-stage MF adult patients treated with CG in 2016-2019. Results Treatment with a once-daily application (52%), or at lower frequencies (48%), in some with topical corticosteroids (TCS) (40%), resulted in an overall response rate of 50%, with no significant difference between stage IA and IB. Cutaneous side effects (56%) included irritant or allergic contact dermatitis (36%, mostly mild/moderate and manageable by reducing application frequency and/or adding TCS or interrupting treatment), unmasking effect (9%), hyperpigmentation (14%), and pruritus (9%). Withdrawal due to side effects occurred in 19.6% of patients (15% for contact dermatitis). Conclusion In real-life management, flexible regimens of CG sometimes with TCS, show efficacy in early-stage MF and may reduce the rate of contact dermatitis, the main treatment-limiting side effect. Practical recommendations with emphasis of the types, time of appearance, and management of side effects are provided.

Recent studies suggest that folliculotropic mycosis fungoides (FMF), the most common variant of mycosis fungoides (MF), presents with 2 distinct clinicopathological stages: early indolent stage and more aggressive advanced/tumour stage. To further characterize these stages, miR-155 expression was studied with qRT-PCR and found to be significantly higher in biopsies of tumour-stage FMF compared with early-stage FMF and inflammatory dermatoses. There was no statistically significant difference in miR-155 expression between early-stage FMF and early-stage MF, nor between tumour-stage FMF and tumour-stage MF. Immunohistochemical analysis revealed a significantly increased number of dermal Ki-67+ proliferating lymphocytes in tumour-stage FMF, together with an increased number of CD20+ B cells and CD68+ macrophages compared with early-stage FMF. Thus, similar to classic MF, miR-155, Ki-67 tumour cell immunoreactivity, and certain tumour-infiltrating inflammatory cells are differentially expressed in early- vs tumour-stage FMF. The results of this study corroborate the notion that FMF presents with 2 distinct stages.

Data on the treatment of early folliculotropic mycosis fungoides, a recently defined clinicopathological subgroup of folliculotropic mycosis fungoides with an indolent course, is limited. Treatment outcomes were studied in a retrospective cohort of 47 adults with early folliculotropic mycosis fungoides, with a focus on psoralen plus ultraviolet A (PUVA) monotherapy, including dosimetric data, and the findings were compared with data for PUVA in 18 adults with early-classic mycosis fungoides. PUVA was given to 27 patients with early folliculotropic mycosis fungoides: 70% achieved complete response and 26% partial response. Significantly more treatments were needed to achieve complete response in stage IB compared with stage IA. There was no significant difference in the complete response rate from classic plaque-stage disease, although the early folliculotropic mycosis fungoides group required more treatments to achieve complete response, and a higher cumulative dose of UVA. Thus, PUVA is an effective treatment for early folliculotropic mycosis fungoides. Its complete response rate might be equal to early-classic mycosis fungoides; however, a longer induction phase is needed to achieve complete response.

Cancer cells are known to reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) to act as tumor supporters. The presence and role of CAFs in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, are unknown. This study sought to characterize CAFs in MF and their cross talk with the lymphoma cells using primary fibroblast cultures from punch biopsies of patients with early-stage MF and healthy subjects. MF cultures yielded significantly increased levels of FAPα, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and matrix metalloproteinase 2. Cultured MF fibroblasts showed greater proliferation than normal fibroblasts in ex vivo experiments. A coculture with MyLa cells (MF cell line) increased normal fibroblast growth, reduced the sensitivity of MyLa cells to doxorubicin, and enhanced their migration. Inhibiting the CXCL12/CXCR4 axis increased doxorubicin-induced apoptosis of MyLa cells and reduced MyLa cell motility. Our data suggest that the fibroblasts in MF lesions are more proliferative than fibroblasts in normal skin and that CAFs protect MF cells from doxorubicin-induced cell death and increase their migration through the secretion of CXCL12. Reversing the CAF-mediated tumor microenvironment in MF may improve the efficiency of anticancer therapy.

Microneedling fractional radiofrequency (FRF) and chemical peels are widely used for skin rejuvenation.The authors aimed at evaluating the efficacy and safety of FRF and trichloroacetic acid 20% (TCA20%) peel in different combinations for determining the optimal treatment protocol.In this prospective clinical comparison of 4 protocols (FRF alone, TCA20% alone, TCA20% before FRF [TCA→FRF], and TCA20% following FRF [FRF→TCA]), the patients underwent 3.8 ± 1.2 successive treatments of one protocol at 4- to 6-week intervals. The patients and 2 dermatologists evaluated improvement of pigmentation and dyschromia, erythema and blood vessels, laxity and wrinkling, and skin imperfections using a global aesthetic improvement scale (GAIS) and a 1 to 5 scoring system. The patients rated their satisfaction and reported adverse effects and reduced activity. Skin impedance and histological changes following the different protocols were also evaluated on 3 additional volunteers.Sixty-seven patients (age range 22-80 years) were studied. TCA→FRF caused skin impedance to decrease, yielding a more superficial and less-efficient penetration of FRF energy. FRF→TCA produced more significant improvement in overall facial skin appearance (GAIS) and most evaluated skin parameters. Adverse effects and satisfaction rates were similar for all approaches.FRF→TCA had the best synergistic effect on skin rejuvenation compared with FRF or TCA20% alone and TCA→FRF.

An increasing number of minimally invasive cosmetic procedures, such as filler or botulinum toxin injections, are performed annually. These procedures are associated with a high risk of post-procedure bruising or ecchymosis. Ecchymoses arise following hemorrhage and extravasation of red blood cells into the subcutaneous tissue, leading to local skin discoloration. Although ecchymoses generally resolve within 14 days, their appearance is cosmetically bothersome, and they may be painful and cause major distress to patients. Recent clinical evidence suggests that light/laser technology with pulsed dye laser (PDL) or intense pulsed light (IPL) can dramatically alleviate and minimize bruising when delivered within 24-72 hr of the injection. This article, will review reports of treatment of ecchymosis by lasers and IPL.

Retinoids exert their biologic effects by binding to intracellular retinoic-acid receptors (RARs) and/or retinoid X receptors (RXRs). Early-stage mycosis fungoides (MF) has been effectively treated with bexarotene, an RXR-agonist, with overall response (OR) rates 54-67% and complete response (CR) rates 7-27%. Data on RAR-agonist monotherapy are limited.To analyze the effectiveness of RAR-agonist monotherapy for early-stage MF.Data on patients with early-stage MF treated with acitretin/isotretinoin monotherapy at a tertiary cutaneous lymphoma clinic in 2010-2017 were collected retrospectively from the medical files.Thirty-five patients (26 males) of median age 50 years (range 8-83) with early-stage MF (IA 9, IB 26) underwent 37 treatment events: 25 acitretin and 12 isotretinoin at a median dosages of 0.3 mg/kg (range 0.2-0.9) and 0.2 mg/kg (range 0.1-0.7), respectively. Median time to maximal response was 6 months for both (range 1-10 for acitretin, 3-16 for isotretinoin); median treatment duration was 10 months (range 3-46) for acitretin, and 9 months (range 3-55) for isotretinoin. OR was 64% for acitretin and 80% for isotretinoin, and CR, 4% and 8%, respectively. Side-effect profiles were as previously reported for retinoids.Early-stage MF patients may benefit from low dose RAR-agonist monotherapy, although the CR rate is low.

10092Background: Epidermal growth factor receptor inhibitors (EGFR-I), which are indicated for various tumor types, are associated with acneiform rash on the face/torso in approximately 90% of pati...

Background It is generally accepted that folliculotropic mycosis fungoides (FMF) is usually typified by indurated plaques and tumors mainly on the head/neck and an aggressive course. However, its clinical manifestations have long been recognized to be quite variable, and some studies indicate a better prognosis for certain presentations. Objective We sought to summarize our experience with the clinicopathological presentations of FMF and impact on prognosis. Methods Data were collected retrospectively for adults with FMF followed up prospectively at a tertiary medical center in 1995 through 2014. Results In all, 34 patients presented with follicle-based patch/flat plaques, keratosis pilaris–like lesions, and/or acneiform lesions, defined clinically as early stage (IA, IB), and 15 presented with follicle-based infiltrated plaques and/or tumors, defined as advanced stage (IIB). The head/neck was involved in all tumor-stage cases, whereas early-stage lesions involved mainly the trunk/limbs. The tumor stage was characterized by more pruritus, heavier perifollicular infiltrates, greater vertical depth, and more frequent presence of eosinophils. On multivariate analysis, infiltrate density was the only significant histopathological discriminator between the stages. Estimated 5-year survival was 0.94 in the early-stage group and 0.69 in the tumor-stage group. Limitations Lack of long-term follow-up and relatively small sample are limitations. Conclusion FMF presents with 2 distinct patterns of clinicopathologic features, early stage and advanced stage, each with different prognostic implications.

Melanoma is an “immunogenic tumor”, often highly infiltrated with lymphocytes, which are capable of inducing regression of the primary tumor. The commonly observed phenomenon of regression suggests substantial cross-talk between immune cells and transformed melanocytes. An immune response to melanocyte differentiation antigens common to transformed and normal melanocytes manifests clinically at distant sites as melanoma associated vitiligo or halo nevi. Despite similar antigenic targets, the pathogenesis and prognosis differs between the different melanoma associated leukodermas. Understanding immunologic cross-talk between melanocytes and the immune system will aid the development of approaches to combat melanoma.

Acute generalized exanthematous pustulosis (AGEP) is an acute pustular eruption with unique clinical features, a rapid clinical course and a typical histopathology. The causative agents are mostly drugs but other triggers have also been described.A 52 year-old woman with a history of diabetes mellitus type II, dyslipidemia and osteomyelitis was treated for about a year with metformin (Glucophage) and simvastatin (Simovil) tablets. Due to the osteomyelitis, the patient was started on a regimen of intravenous vancomycin as well as furosemide tablets (Fusid) for pedal edema. About seventeen days after beginning treatment with vancomycin and a week after starting furosemide the patient was hospitalized due to an acute pruritic pustular eruption, involving most of her body surface area. Both vancomycin and furosemide treatment were discontinued, and topical treatment was provided. The clinical course was rapid with spontaneous resolution of the pustules followed by a characteristic pin-point post-pustular desquamation. The morphological, clinical and histological findings suggested a definite case of AGEP based on the EuroSCAR scoring system. The latent period between the initiation of medication intake and the appearance of AGEP, as well as a literature search, suggest that furosemide might be the incriminated drug.We have described a rare case of typical AGEP most probably induced by furosemide.