Prognosis in early stage cutaneous T-cell lymphoma treated with psoralen plus ultraviolet A irradiation and low-dose interferon-α: Long-term efficacy and survival according to conventional and emerging clinical endpoints.

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1-30). Among the responders, only the 8% of patients had a relapse with major event. The median follow-up was 207 months (range, 6-295). Survival data showed a median overall survival (OS) not reached (95% CI; 235-NR months), a disease free survival (DFS) of 210 months (95% CI; 200-226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33-46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy.

Cadaveric dissection and clinical experience with 20 consecutive tunneled pedicled superficial temporal artery perforator (STAP) flaps for ear reconstruction.

INTRODUCTION: Reconstruction of anterior ear defects is poorly described, but using "like" tissue provides the optimal reconstruction. We present a cadaveric dissection and our experience with the pedicled superficial temporal artery perforator (STAP) flap for reconstruction of partial ear defects. MATERIALS AND METHODS: Two cadavers were dissected bilaterally (n = 4) following injection of latex and barium sulfate. A retrospective review of 20 consecutive patients undergoing reconstruction with the STAP flap from 2009 to 2012 was performed. Twenty patients underwent reconstruction of anterior ear defects following resection for non-melanoma skin malignancies using a tunneled pedicled STAP flap (scapha: 5, triangular fossa: 2, scapha and triangular fossa: 13). RESULTS: Two perforators were identified in all dissections with one perforator at the level of the tragus, and the second perforator within 1 cm cephalad to the tragus. Thirteen patients underwent reconstruction following basal cell carcinoma excision and seven patients were reconstructed following excision of squamous cell carcinoma. There were no flap losses, but four flaps (20%) developed congestion at the tip of the flap that resolved without need for flap delay, leeching, or vasodilators. No patients developed complications with the donor site, and no patients underwent revisions. With a mean follow-up of 27.3 months (range: 19-38 months), all patients were pleased with their aesthetic outcomes and alive without recurrent disease. CONCLUSION: The STAP flap is a pedicled perforator flap providing local "like" tissue that can be utilized for resurfacing of defects involving the anterior upper external ear with minimal donor site morbidity.

Switching from a biological therapy to another biologic agent in psoriatic patients: the experience of PsOMarche group.

BACKGROUND: Switching is a "hot" topic and the main reasons for switching prior biologic agent are for a primary failure, a secondary failure or drug intolerance, patient's dissatisfaction, physician decision. The aim of the study was to assess the optimization of the switching from a biologic agent to another. METHODS: Five Dermatological Units have participated to PsOMarche working group have studied thirty-eight patients affected moderate to severe chronic plaque psoriasis at time 0 (patient recruitment at time of switching from biological therapy to another), 8 weeks (T8), 16 weeks (T16). RESULTS: Twenty-eight males and 10 females were included in the study. At T0, 18 of 22 patients treated with etanercept had been switched to adalimumab and 4 to ustekinumab. Among 10 patients treated with adalimumab, 5 had been switched to ustekinumab, 2 to golimumab and 3 to certolizumab pegol. One patient treated with Infliximab and 5 patients treated with ustekinumab had been switched to adalimumab. Switching had been performed for primary inefficacy in 9 patients (23.6%) and a secondary failure was evidenced in 29 patients (73.4%). PASI75 was achieved in 53% and in 89.4% of patients after 8 weeks and 16 weeks of switching to the second biologic agent respectively; similarly, PsoDISK score significantly decreased at T8 and T16. CONCLUSIONS: The experience of PsOMarche group have shown that the switching to a biologic agent to another is a valuable treatment choice in patients with moderate to severe psoriasis experiencing a treatment failure with one biologic therapy, leading to a good improvement in skin disease and in patient's quality of life.

Pegylated liposomal doxorubicin in the treatment of primary cutaneous T-cell lymphomas.

Pegylated liposomal doxorubicin (Peg-Doxo) is a promising drug for advanced/recalcitrant primary cutaneous T-cell lymphomas (CTCLs). This prospective phase II trial enrolled 19 patients. We observed overall and complete response rates of 84.2% and 42.1% (with no significant differences between stage I-IIA and IIB-IV patients), and 11% grade III/IV toxicity. After a maximum 46 month-follow-up, median overall (OS), event-free (EFS) and progression-free (PFS) survival were 34, 18 and 19 months. OS, EFS and PFS rates at 46 months were 44%, 30% and 37% respectively. Peg-Doxo seems to be an active and safe principle that should be used in plurirelapsed, early stage-MF and in combination with other chemotherapeutic agents in advanced and aggressive CTCLs.

Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides.

INTRODUCTION: Bexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes. We aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS. METHODS: We followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. "Mini" and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS). RESULTS: After induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades. CONCLUSIONS: We observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.

The transitioning from conventional therapy to biological treatment in psoriatic patients: STRATOS, a project of Marche Region.

BACKGROUND: STRATOS is the acronym of the "STRuctured Approach to the Treatment of psOriatic patientS". The optimization of the psoriasis's therapeutic management is one of the most important goals for dermatologists. According to Mrowietz's consensus report, the transitioning from conventional therapy to biological therapy is mainly due to the lack/loss of efficacy and/or for safety reasons. The aim of the manuscript was to describe the principal results obtained by the Dermatologic Clinic of Polytechnic University of Marche Region and the Units of Dermatology of the Marche Region applying, in our regional reality, Mrowietz's protocol for the daily management of patients with moderate-to-severe plaque. METHODS: Forty-seven patients with moderate to severe chronic plaque psoriasis have been monitored during the six-months study period. RESULTS: Psoriatic patients with diabetes showed further concomitant comorbidities compared to non-diabetics, as hypertension and hypercholesterolemia. Moreover, based on WHO classification, overweight was diagnosed in female patients, whereas obesity was prevalent in male patients. This aspect confirms the strict link between the multifaceted aspects of psoriatic patient which is primarily related to the persistent low-grade inflammation. In our psoriatic group, 10% of monitored patients were affected by Crohn disease or ulcerative colitis. CONCLUSIONS: The Mrowietz's transitioning protocol is a useful, reliable and feasible tool to manage the therapeutic iter of psoriatic patients in an Italian clinical setting also at regional level.

Factitious disorders in adults: two cases of unusual skin ulcers.

The factitious disorders (FDs) include a large group of dermatological conditions characterized by skin lesions that patients themselves self-inflict but deny their active participation. FDs usually represent a diagnostic challenge, and their therapeutic management is usually based on a multidisciplinary approach because most FRD patients also suffer from undiagnosed behavior and personality disorders. We report two cases of FD: one patient that was suffering from severe depression and induced third-degree chemical burns on his own lower limbs, and another patient affected by obsessive-compulsive disorder and anorexia nervosa that presented with deep self-inflicted ulcers on her face. Our multispecialist approach, based on close cooperation between dermatologists and psychiatrists, led to a significant improvement of clinical conditions in both cases. Dermatologists need to be aware that FDs are complex disorders and a multidisciplinary approach is usually recommended to control their clinical course.

Lichen striatus in adults and pimecrolimus: open, off-label clinical study.

BACKGROUND: Lichen striatus is a well-known, acquired, self-healing, linear inflammatory dermatosis. Lichen striatus occurring in adults tends to be more extensive and itchy than in children, sometimes requiring symptomatic treatment. The therapeutic approach usually adopted is topical steroids, even though prolonged use may lead to several side-effects, particularly cutaneous atrophy. OBJECTIVE: To report the results of an open, off-label study on the use of pimecrolimus 1% in the treatment of diffuse, nonresponsive forms of lichen striatus. METHODS: Three adult patients suffering from relapsing or disseminated and itchy lichen striatus received topical application of pimecrolimus 1% cream (Elidel, Novartis Pharma, Basle, Switzerland) twice daily for 6 weeks, or until complete disappearance of the cutaneous lesions. RESULTS: All patients experienced rapid healing of the dermatosis, without any recurrence for at least 14 months. CONCLUSION: Our preliminary results show that pimecrolimus may represent a useful therapeutic alternative for lichen striatus, although further studies on a larger number of cases are needed to confirm its safety and efficacy in the treatment of this condition.

Atypical neurothekeoma: a new case and review of the literature.

BACKGROUND: Neurothekeoma is a rare neoplasm ascribed into the broad category of benign peripheral nerve sheath tumors. The atypical cellular variant of this neoplasm, showing a peculiar histological pattern, has been very rarely reported in literature. METHODS: The clinical, histopathological and immunohistochemical profile of a new case of atypical cellular neurothekeoma in a 32-year-old woman is reported. RESULTS: The described neoplasm showed the histological features of atypical variant of cellular neurothekeoma with high-rate mitotic activity and deep penetration into subcutaneous fat. CONCLUSIONS: Because only few cases of atypical neurothekeoma have been reported in literature, clinical and morphological available data on this neoplasm are very few, and its prognosis remains uncertain; anyway, dermatologists should be aware of histological features of this neoplasm for which a complete surgical excision is recommended.

Long-term experience with low-dose interferon-alpha and PUVA in the management of early mycosis fungoides.

OBJECTIVES: Combined high-dose Interferon-alpha and psoralen plus ultraviolet A irradiation (PUVA) have been reported to be effective in the treatment of early mycosis fungoides (MF); however, our study is the first controlled prospective study in the literature exploring the activity and tolerability of the combination with low dosages and evaluating further clinical outcome of early-MF patients. METHODS: We carried out a multicentric prospective Phase II clinical study on 89 patients with early-stage IA to IIA MF treated for 14 months with low-dose IFN-alpha2b (6-18 MU/wk) and PUVA. Treatment success was analysed in terms of freedom from treatment failure. RESULTS AND CONCLUSIONS: Complete remission (CR) was achieved in 84% and an overall response rate in 98% of cases: six-month CR was associated with a non-confluent skin infiltrate at histology (P = 0.044) and 14-month CR with high epidermal CD1a+ dendritic-cell density (P = 0.030). The combination protocol was successfully tolerated and the most common reason of 'failure' was related to relapse and not to toxicity. Sustained remissions were achieved in 20% of patients. High CD8+ lymphoid T-cell density was associated with a lower relapse rate (P = 0.002). We think that our combination therapy can be considered an alternative approach compared with other modalities. Good immunological host surveillance in the skin lesions seems to be an optimal basis for the therapeutic success.