Chiara Delfino

Clinical and epidemiological comparison of patients affected by palmoplantar plaque psoriasis and palmoplantar pustulosis: a case series study

Summary Background  In 2007 the International Psoriasis Council proposed that palmoplantar pustulosis (PPP) should be considered a separate condition from psoriasis, despite the presence of certain phenotypes common in both diseases.

Hidradenitis suppurativa: are tumour necrosis factor-α blockers the ultimate alternative?

was used by fewer than half of the patients (531, 44Æ4%). Response to phototherapy was insufficient in 79Æ0% of all cases. In contrast, ciclosporin and methotrexate had sideeffects or were contraindicated in more than 65% of the patients. The relatively infrequent use of ciclosporin and methotrexate may have resulted from the fact that many patients actually did receive these therapies, but did not completely fulfil the required criteria for dosage and treatment duration. Remarkably, methotrexate was used by fewer than half of the patients. This may be due the fact that patients did not reach the required dosage of 22Æ5 mg per week, because of side-effects at lower dosage. Furthermore, many patients with psoriasis requiring systemic treatment may be successfully treated with methotrexate, and consequently do not need biological therapy. In total, 1254 (94Æ5%) of all initial treatment applications and 812 of all follow-up applications were approved by LABAG. This validates the conclusion that dermatologists are familiar with the demanded criteria for reimbursement of biological therapies. The remaining 442 follow-up applications were not received or were rejected, mainly as a result of a < 50% decrease in PASI at week 12. A PASI 50 response at week 12 was achieved by 69Æ0% of all patients with an approved initial treatment application for etanercept, and by 50Æ0% of all patients with an approved initial treatment application for efalizumab. These results are slightly lower than randomized controlled trial data (etanercept 76%, efalizumab 55%), but are comparable with the results of daily practice cohort studies, in which the efficacy of etanercept and efalizumab treatment in daily practice were evaluated. The mean reduction in PASI relative to baseline at week 12 was 53Æ1% for etanercept, compared with 35Æ5% for efalizumab, after carrying forward the baseline PASI to week 12 in cases of missing follow-up PASI. When analysing only ‘responding’ patients, i.e. patients with approved initial and follow-up applications, mean reduction in PASI relative to baseline was 75Æ0% and 68Æ3% for etanercept and efalizumab, respectively (Table 2). However, in the first analysis treatment efficacy is underestimated, whereas the second analysis leads to an overestimation of treatment efficacy. The real values should be in between the results of both analyses. Three times more applications were received for etanercept than efalizumab. Apparently, dermatologists have a preference for etanercept as first-choice biological therapy. The fact that etanercept is approved for the treatment of psoriatic arthritis as well, whereas efalizumab is not, might account for this. Furthermore, according to the presented data, the efficacy of etanercept is superior to that of efalizumab. However, the presented data are unsuitable for objective comparison between etanercept and efalizumab. The present analysis demonstrates that, as a consequence of strict adherence to reimbursement criteria, only 0Æ4% of Dutch patients with psoriasis are treated with etanercept or efalizumab. The question arises whether it is indicated to broaden these criteria, in particular considering the long-term and presumably safe control of psoriasis by biologics.

Tolerability and safety of biological therapies for psoriasis in daily clinical practice: a study of 103 Italian patients.

Studies comparing the safety and tolerability of biological therapies for psoriasis in the long-term and in daily clinical practice are lacking. Most published studies are of selected patients with short-term (3-6 months) follow-up. We performed a retrospective cohort study of 103 patients in order to describe the frequency and the clinical features of adverse events, and to evaluate and compare the tolerability and safety of efalizumab, etanercept, infliximab, and adalimumab in clinical practice. A total of 136 courses of biological therapies were administered, with a mean duration of 16 months/patient; 55 patients received efalizumab, 45 etanercept, 33 infliximab, and 3 adalimumab. Infliximab had an incidence rate ratio of suspension due to severe adverse events 5.9 times (95% confidence interval (95% CI) 1.9-18, p < 0.001) higher than etanercept and 9.8 times (95% CI 3.2-30.1, p < 0.001) higher than efalizumab. Safety profiles for efalizumab and etanercept were more favourable than for infliximab. Concerning tolerability, we found that more patients responded to infliximab, but long-term tolerability was higher for both efalizumab and etanercept due to the better safety profile and a higher compliance to therapy.

Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy.

Santi R, Cetica V, Franchi A, Pepi M, Cesinaro A M, Miracco C, Paglierani M, De Giorgi V, Delfino C, Difonzo E M, Pimpinelli N, Bianchi S, Sardi I, Santucci M & Massi D
(2011) Histopathology58, 455–466
Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy

Role of bexarotene in the treatment of cutaneous T-cell lymphoma: the clinical and immunological sides

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoid neoplasms. The incidence of CTCLs has risen over the last three decades. The most common CTCLs are mycosis fungoides and Sèzary syndrome. Therapies for CTCLs are various and range from skin-directed therapy to chemotherapy. Retinoids have been used in CTCL treatment since the 1980s with good results. Bexarotene is the first retinoid approved by the US FDA for CTCL therapy. Since then, numerous experiences of both its efficacy and mechanism of action have been reported. The aim of this paper is to review bexarotene action on CTCLs, as well as to highlight its immunological targets.

Rituximab plus liposomal pegylated doxorubicin in the treatment of primary cutaneous B‐cell lymphomas

In primary cutaneous B‐cell lymphomas (PCBCL), radiotherapy – or surgery in a minority of cases – is the first‐line treatment in follicle center lymphoma (PCFCL) and marginal zone B‐cell lymphoma (PCMZL). Conversely, patients with multifocal skin involvement or relapsed/refractory disease deserve a systemic chemotherapy. In diffuse large B‐cell lymphoma, leg type (PCLBCL‐LT), due its poorer outcome, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)‐like regimens are the most commonly used frontline, although hard to propose in elderly patients. In this regard, the association of rituximab (R) and pegylated liposomal doxorubicin (PLD) can be considered a promising, alternative approach.

Adaptive evolution of secretory cell lines in vertebrate skin

Abstract The embryonic horny layer of vertebrates contains distinctive cell lines that account for the remarkable, diverse secretory performances of their cutaneous apparatuses. Aquatic classes (jawless, cartilaginous and bony fishes) possess single gland cells, scattered among ordinary epidermal cells, that manufacture proteinaceous or mucous substances. This dichotomy is retained in adult amphibians, although the secretory cells in anamnionic tetrapode begin to be arranged in complex glands located in the loose dermis. In the Amniota, intensive keratinisation involving the epidermis results in the loss of the ancestral secretory lines, accompanied by the onset of a novel, lipid- producing gland type, which in mammals is flanked by the exclusive sweat gland apparatus. In this concise up-to-date review, we attempt to phylogenetically narrow the large variety of secretory structures in vertebrate skin into a few basic schemes, in the light of the close relationships between environmental challenges and ecological, ethological as well as physiological roles of the cutaneous apparatus.

Different response rates between palmoplantar involvement and diffuse plaque psoriasis in patients treated with infliximab.

ejd.2011.1567 Auteur(s) : Alexandra Maria Giovanna Brunasso1,2 giovanna.brunasso@gmail.com, Matteo Puntoni3, Chiara Delfino4, Cesare Massone5 1 Department of Enviromental Dermatology and Venereology, Medical University of Graz, Auenbruggerplatz 8, A-8036 Graz-Austria 2 Department of Dermatology, Galliera Hospital, Genoa, Italy 3 Department of Oncology and Biostatistical research, Galliera Hospital, Genoa, Italy 4 Department of Dermatological Sciences, Florence, Italy 5 Department of Dermatology, Medical [...]

Maintenance phase in psoralen–ultraviolet A phototherapy of early-stage mycosis fungoides. A critically appraised topic

A 65‐year‐old patient affected by mycosis fungoides (MF) stage IB achieved complete remission (CR) after a cycle of PUVA phototherapy. The U.S. Cutaneous Lymphoma Consortium (USCLC) guidelines suggest that the patient should be kept in the maintenance phase, defined as a ‘period of gradual decrease of frequency of UVL [ultraviolet light] while in clinical remission before discontinuation of phototherapy’ by slowly tapering the number of psoralen–ultraviolet A (PUVA) applications over time up to clinical relapse. The USCLC guidelines also suggest a standardized schedule for the maintenance phase. Alternatively, the patient could end PUVA therapy and go straight to follow‐up.

Efalizumab Rebound Response to a Sequential Therapy of Infliximab Followed by Efalizumab

weak response after 10 days of ciclosporin and the immediate need to control the systemic disease. After 4 weeks, the patient was free of pustules but a slight erythema was still present. At week 14, the patient was free of lesions, and, after the 5th infusion, she requested the suspension of infliximab. Efa lizumab was reintroduced with the maintenance of the excellent results (PASI-100) until the last follow-up visit 100 weeks after the first infliximab infusion and 58 weeks from the second cycle of efalizumab ( fig. 2 ). The generalized pustular eruption seen 5 weeks after the efalizumab withdrawal might be classified either as generalized pustular psoriasis (GPP), i.e. a rebound phenomenon after efalizumab suspension, or as a GPP relapse (second episode). We favour the rebound hypothesis because of the time of onset (5 weeks). In fact, rebound is defined as the development of new widespread pustular, erythrodermic or more inflammatory psoriasis lesions occurring within 8 weeks from treatment discontinuation in responding patients [2] . Approximately 13% of treated patients develop a rebound phenomenon [2] , although GPP after efalizumab withdrawal has rarely been reported. Gaylor and Duvic [3] reported a case of GPP occurring 2 weeks after efalizumab withdrawal, which may have been triggered by a concomitant herpes zoster infection. Infliximab has been successfully used in patients with GPP, reporting a rapid and positive response without any significant side effects [4, 5] , but, in the literature, infliximab and methotrexate resistant rebounds, as well as a paradoxical flare of pustular psoriasis with TNFantagonists, have been reported [6] . Our case showed not only an excellent response of GPP to infliximab,