Papers by Marina Papoutsaki
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Investigative Dermatology, 2006
Journal of the European Academy of Dermatology and Venereology, 2020
Few studies have investigated the long‐term outcomes of secukinumab in real‐life psoriasis treatm... more Few studies have investigated the long‐term outcomes of secukinumab in real‐life psoriasis treatment where diverse patient profiles require a personalized approach.
Molecular diagnosis & therapy, Jun 28, 2017
The genetic basis of predisposition to psoriasis is recognised; however, the response to psoriasi... more The genetic basis of predisposition to psoriasis is recognised; however, the response to psoriasis treatment in patients with different genetic predisposition is poorly understood. To analyse the presence of the HLA-C*06:02 polymorphism in psoriatic patients treated with adalimumab. Genomic DNA was extracted from whole blood of 122 patients with moderate-to-severe psoriasis treated with adalimumab for 3 years. Genotyping was performed using PCR. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at day 0 and after 1, 3, 6, 12, 24 and 36 months. Logistic regression was used to evaluate the association between dependent variables (including HLA-C*06:02 status) and achievement of PASI 50, 75 and 90. No difference was observed after adalimumab treatment between C*06:02 positive (HLA-C*06:02-POS) patients (n = 46) and C*06:02 negative (HLA-C*06:02-NEG) patients (n = 76) over the 3-year follow-up period in terms of PASI response or time-course when PASI response...
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2016
Systemic lupus erythematosus (SLE) is a complex disease characterized by different types of autoa... more Systemic lupus erythematosus (SLE) is a complex disease characterized by different types of autoantibodies. B cells seem to play an important pathogenetic role in SLE, and many authors have advocated B cell-depleting strategies (mainly used in the treatment of lymphomas) in the treatment of this disease. We report the case of a 50-year-old female patient who was admitted to our institution for evaluation of painful, reticulate, violaceous and erythematous lesions with central areas of necrosis. The patient had had two spontaneous abortions, 13 and 12 years earlier, followed by successful artificial insemination (10 years earlier). Shortly (6 months) after giving birth to a healthy infant, mild symptoms consistent with Raynaud’s phenomenon, precipitated by cold temperatures during the winter months, were observed. At that time, the patient did not undergo evaluation. Four years ago, she was diagnosed with follicular CD20+ non-Hodgkin lymphoma and received CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for six months, followed by rituximab infusions administered once every other month for two years (12 cycles, at a dose of 375 mg/m2). Following completion of treatment, she was regularly evaluated by her oncologist and found to be in complete remission. No other systemic diseases were reported, and at the time of admission, the patient was not on any type of medication. The family history was unremarkable. The patient presented with an irregular, branched, violaceous reticulate pattern with central areas of necrosis (Figure 1). The eruption had first appeared one month prior to admission. Initially limited to both feet, it slowly spread and eventually affected the entire lower extremities and the dorsal aspects of both hands. Small areas of atrophie blanche were noted on both feet. Diascopy revealed the lesions to be only partly blanchable, and only slight improvement was observed after application of heat. The patient complained of severe lower extremity pain, combined with numbness and paresthesias. The eruption was described as livedo racemosa and further workup was performed. All tests and associated results are summarized in Table 1. In addition, sun exposure resulted in an aggravation of symptoms and development of erythema. The diagnosis of SLE was made, as the patient met five of the SLICC criteria for SLE (photosensitivity, renal manifestations, positive ANA, positive anti-dsDNA, and lymphopenia on more than two occasions) [1]. Subsequently, appropriate treatment was initiated (Figure 2). Direct immunofluorescence findings are shown in Figure 3. The patient had received both rituximab and cyclophosphamide therapy prior to the manifestation of SLE. There are two possible scenarios: either Raynaud’s phenomenon was an early symptom of subclinical lupus erythematosus or it was completely coincidental. No initial testing was performed, and although the first scenario is more likely, a causal relation between B cell manipulation and SLE manifestation cannot be ruled out. In addition, there are no clinical differences between idiopathic and drug-induced LE [2]. B cells play an important role in the pathogenesis of SLE. They cause antibody-dependent cytotoxicity, propagate immune responses via specific types of autoantigens and toll-like receptors, and – at the same time – they protect from autoimmunity by regulating T-cell function [3]. Rituximab destroys all mature B cells and B-cell precursors, causing B-cell repopulation similar to that observed after bone marrow transplantation [4]. This could mean that the production of new, nonautoreactive, B cells may be possible. For this reason, rituximab has been used in the treatment of a number of autoimmune diseases, including SLE, rheumatoid arthritis, bullous diseases, and vasculitides, with mostly satisfactory results. However, in case of SLE, large studies such as the EXPLORER and LUNAR trials [5, 6] have yielded disappointing results, contradicting those of other smaller trials or case series [7]. Interestingly, there have been a few isolated cases of patients developing autoimmunity after rituximab therapy. These include psoriasis, autoimmune
Proceedings of the National Academy of Sciences of the United States of America, 2008
Clinical and experimental rheumatology
Annali di igiene : medicina preventiva e di comunità
Acta dermato-venereologica, 2008
Journal of the European Academy of Dermatology and Venereology, 2007
Pityriasis rubra pilaris (PRP) is a rare chronic skin disease classified into five groups differi... more Pityriasis rubra pilaris (PRP) is a rare chronic skin disease classified into five groups differing in clinical features, course, and prognosis. 1 Type III is classic juvenile-onset PRP and is considered prognostically favourable. Systemic retinoids, methotrexate, ciclosporin, vitamin D analogues, keratolytics, and phototherapy are commonly used with varying degrees of success. A 33-year-old woman presented with a 25-year history of erythematous, scaly patches, and plaques with follicular papules involving the whole body (fig. 1). Several typical 'islands of sparing' with perifollicular erythema were observed. Palms, soles and nails were also involved. In particular, the hands showed palmoplantar keratoderma with fissuring and onychodystrophy with subungual hyperkeratosis. Intense itching and skin dryness were also present. The patient's medical history was unremarkable, and there was no personal or family history of skin disease. Histologic examination revealed moderate acanthosis, with a few broad rete ridges, diffuse hyperkeratosis, and parakeratosis. The parakeratosis alternated with the orthokeratosis, vertically and horizontally. Focal epidermal
Journal of the American Academy of Dermatology, 2009
Journal of Dermatological Treatment, 2008
Generalized pustular psoriasis (GPP) is a rare form of psoriasis that may either be preceded by p... more Generalized pustular psoriasis (GPP) is a rare form of psoriasis that may either be preceded by plaque psoriasis or arise de novo, classically after withdrawal of systemic glucocorticosteroids. Adalimumab is a fully human, anti-TNF-alpha monoclonal antibody that specifically blocks the interaction of TNF-alpha with the p55 and the p75 TNF-alpha cell surface receptors. To demonstrate the efficacy and tolerability of adalimumab in the treatment of GPP. A 50-year-old woman had suffered from severe pustular psoriasis for 10 years and psoriatic arthritis for 8 years and received treatment with adalimumab, in monotherapy, 40 mg subcutaneously once a week for 72 weeks. DLQI, PDI and SKINDEX 29 score were used to assess patient compliance and satisfaction. In our case, control of disease manifestations was rapid and clinical remission persisted during the treatment course until the 72th week. Treatment tolerability and compliance were consistent. The patient experienced a dramatic improvement of quality of life instruments. In this case, adalimumab has been demonstrated to be effective, safe and appropriate for long-term use, indicating a beneficial effect on quality of life parameters.
Expert Review of Dermatology, 2008
Dermatology, 2009
Background: Biological therapy for moderate to severe psoriasis includes tumour necrosis factor (... more Background: Biological therapy for moderate to severe psoriasis includes tumour necrosis factor (TNF) blockers (infliximab, etanercept and adalimumab) and T-cell-targeting agents (efalizumab, alefacept) that act in different steps of a common pathogenic pathway. Large amounts of data coming from clinical trials indicate each of these drugs as highly effective and safe. However, little is known about the efficacy of a second biological therapy after the failure of the first. Objective: To evaluate whether the response to efalizumab in psoriasis patients was influenced by previous treatment with other biological agents. Patients and Methods: We have retrospectively analyzed a group of 155 psoriasis patients treated with efalizumab during the last 5 years and determined its efficacy in patients previously treated with anti-TNF drugs comparing it with the efficacy and safety observed in patients previously treated with traditional systemic drugs instead. Results: Efalizumab was shown to...
Dermatology, 2010
Background: Psoriasis affects about 2–3% of the Caucasian population. Biologics such as inflixima... more Background: Psoriasis affects about 2–3% of the Caucasian population. Biologics such as infliximab, etanercept, adalimumab and ustekinumab are efficacious treatments of plaque-type psoriasis. Critical to monitoring drug efficacy and safety is availability of long-term data. Despite the chronic nature of psoriasis, to date limited long-term clinical data have been available, as challenges are inherent in conducting a long-term analysis. With increasing time, it is more likely that the number of patients discontinuing treatment will also increase, due to loss of efficacy, adverse events or loss to follow-up. Interpretation of these data becomes confounded when one must consider missing data. Several approaches to analysing long-term data exist, and each accounts for missing data differently. Objective: To demonstrate that the choice of a particular analysis method to account for missing data has great impact on the assessed response rate. Methods: We used data from an open-label study...
Cell Cycle, 2006
The p53 family of transcription factors plays a pivotal role in the control of the cellular respo... more The p53 family of transcription factors plays a pivotal role in the control of the cellular response to DNA damaging agents. In addition to pro-apoptotic molecules such as p53, TAp73 and TAp63, this gene family also encodes for the anti-apoptotic molecules ∆Np73, ∆Np63, ∆Np53, and p53 mutants are often found in tumor cells, that have the role to limit and to modulate the pro-apoptotic side of the family. The ratio between the different members of the family is critical to make the life or death decision following DNA damage and is tightly regulated by post-translational and transcriptional mechanisms. In this study we have uncovered a novel positive feedback that involves the transcriptional activation of the anti-apoptotic molecule ∆Np63 by the anti-apoptotic molecules ∆Np73 and mutant p53, and that is put into motion upon treatment with a subset of DNA damaging agents such as Doxorubicin and 5-FU. ∆Np73 and mutant p53 associate with the ∆Np63 promoter inducing its transcription and this is enhanced by doxorubicin treatment. Furthermore we have observed that ∆Np73and mutp53-mediated activation of the ∆Np63 promoter requires the functionality of the proximal CCAAT boxes of this promoter, being hampered by mutation of CCAAT boxes or by dominant negative NFYA expression. This mechanism may serve as an additional control of the response of a normal cell to DNA damage or as an anti-apoptotic barrier of cancer cells subjected to DNA damage.
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Papers by Marina Papoutsaki