Hugo Oliveira

Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-α levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy.

Background  Several cross‐sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis.

C-reactive protein and leucocyte activation in psoriasis vulgaris according to severity and therapy

Background  Psoriasis vulgaris is a chronic recurrent inflammatory skin disease and psoriatic lesions have shown leucocyte infiltration.

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index, severity and therapy

Background  Psoriasis vulgaris is associated with overweight/obesity and with increased C‐reactive protein (CRP), tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, leptin and resistin levels and decreased adiponectin levels.

Psoriasis Therapy and Cardiovascular Risk Factors

AbstractBackground: Psoriatic patients present with an increased frequency of cardiovascular events. Objective: To study the impact of psoriasis duration and therapy on traditional and new cardiovascular risk factors. Study Design: A longitudinal study performed between 2005 and the first trimester of 2008. Each patient was followed up for 12 weeks, and was observed before and 3, 6, and 12 weeks after starting therapy. Setting: Patients attending the Dermatology Service, University Hospital of Coimbra, Coimbra, Portugal were enrolled. Subjects: Thirty-four patients with psoriasis vulgaris and 37 healthy volunteers as controls. Main Outcome Measures: Psoriasis Area and Severity Index (PASI); lipid profile, oxidized low-density lipoprotein (oxLDL), oxLDL/low-density lipoprotein (LDL), total antioxidant status, lipid peroxidation, C-reactive protein (CRP), and circulating levels of adiponectin. Intervention: Ten patients started therapy with topical treatment, 11 with narrow-band UVB radiation (NB-UVB), and 13 with psolaren plus UVA (PUVA). Results: Before starting therapy, psoriatic patients presented with several risk changes in their lipid profiles, and significantly higher CRP, oxLDL, and oxLDL/LDL, and lower adiponectin levels (vs control subjects), which may further contribute to inflammation and atherogenesis. After treatment of the patients, although no significant differences were observed in the lipid profile compared with baseline, some changes suggested that the treatment could somehow alter lipid metabolism, as the reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A and the increase in the atherogenic index cholesterol/HDL-C maintained an even higher significance (as shown by p-values) when compared with the control group.After topical therapy, there was a significant reduction in thiobarbituric acid reactivity only, suggesting that the reduction in the hyperproliferative process within the lesions is important for lipid peroxidation. After NB-UVB therapy, oxLDL/LDL, cholesterol/HDL-C, lipoprotein (a) [Lp(a)], and CRP remained higher than in the control subjects, reflecting persistent inflammation and atherogenic risk. After PUVA treatment, there was a significant reduction in Lp(a), associated with an almost significant increase in apolipoprotein-B (p = 0.054); these changes were not observed after NB-UVB treatment. However, after PUVA and NB-UVB treatment, CRP and, in the NB-UVB group, oxLDL/LDL were persistently higher than controls. Conclusion: Our data show that psoriatic patients present with several lipid profile changes that seem to be related to the severity of the disease and/or the treatment used. Mild psoriasis patients receiving topical treatment presented before starting therapy with a lipid profile similar to controls, whereas those undergoing NB-UVB and PUVA, who had higher PASI scores, presented with several risk factors. Moreover, PUVA therapy seems to interact in a different way with lipids that might result from an interaction of psoralen with plasma lipids, namely Lp(a). Inflammation, a hallmark of psoriasis, also seems to be related to psoriasis severity. Both NB-UVB and PUVA were effective, as shown by the reduction in PASI score, as well as in the oxidative and inflammatory stress markers. However, after NB-UVB and PUVA, a low-grade inflammatory process still persisted, which might be related to the duration of remission of the disease.

Principal Determinants of the Length of Remission of Psoriasis Vulgaris After Topical, NB-UVB, and PUVA Therapy

BackgroundPeriods of remission and of exacerbation of psoriatic lesions are common in psoriasis. We recently reported C-reactive protein (CRP) as a marker of psoriasis severity and that some patients still presented with a residual inflammation after treatment. We wondered if this residual inflammation could underlie an earlier exacerbation of psoriasis.ObjectiveThe purpose of our study was to evaluate if there is a relationship between CRP levels, Psoriasis Area and Severity Index (PASI), and body mass index (BMI), at the end of psoriasis treatment, with the length of psoriasis remission.MethodsWe followed 46 patients studied at the end of treatment, to record the length of remission; 9 of the patients were treated with topical agents, 17 with narrow-band UVB (NB-UVB), and 20 with psoralen plus UVA (PUVA).ResultsWe found that the length of remission correlated with the values for PASI and CRP at the end of therapy. By performing a multiple linear regression analysis, CRP, PASI, and BMI were each significantly associated with length of remission. Patients with residual inflammation at the end of treatment presented with a significantly shorter length of remission. When considering patients grouped according to the used therapies, CRP and PASI also emerged as potential determinants of length of remission, especially in the case of patients treated with NB-UVB and topical therapy.ConclusionOur data suggest that CRP and PASI are important determinants of length of psoriasis remission for patients treated with phototherapy or topical therapy. Further studies with larger groups of patients are warranted to test this hypothesis. Moreover, we propose that, by the end of the treatment, the evaluation of CRP and PASI could be important to decide, when possible, if the treatment should be continued to achieve lower CRP values and longer periods of remission.

Fixed drug eruption to piroxicam. Positive patch tests with cross-sensitivity to tenoxicam

In our experience, fixed drug eruption (FDE) is not a rare example of cutaneous adverse drug reactions, but the identification of the drug responsible often remains a challenge. We report on a patient in whom piroxicam was identified as the cause of recurring lesions of FDE. Epicutaneous testing with the offending drug was positive on residual lesions, but not on uninvolved skin. Histopathological and immunohistochemical findings on the positive tests were identical to those in an acute lesion of FDE. Patch testing on lesional skin revealed cross-sensitivity between piroxicam and tenoxicam, but no reactivity to thiosalicylic acid. This suggests that the molecular moiety involved in FDE to piroxicam is shared by tenoxicam, in contrast to piroxicam photosensitivity where there is no cross-reaction between these two drugs and the offending moiety is antigenically and structurally similar to thiosalicylic acid.

Topical Provocation in Fixed Drug Eruption from Nonsteroidal Anti-Inflammatory Drugs

Objective: Evaluate the importance of topical lesional provocation in the study of fixed drug eruption (FDE) from nonsteroidal anti-inflammatory drugs (NSAID). Patients and Results: We studied 14 patients with FDE imputed with high probability to piroxicam (8 patients), nimesulide (5) and feprazone (1). One patient with FDE from piroxicam suffered lesion reactivation after intravenous tenoxicam. The suspected drug and related compounds were patch tested on residual lesional skin and on the normal back skin. Positive results were obtained, only in affected areas, in 13 out of 14 patients (92.9%): in all cases due to feprazone and nimesulide and in 7/8 cases of FDE due to piroxicam. The 7 patients reactive to piroxicam also had positive tests to tenoxicam, and 1 out of 5 reacted to meloxicam. None reacted to thiosalicylic acid. Comments and Conclusions: Topical lesional provocation is a safe, sensible and specific complementary method for drug imputation in FDE from these NSAID, namely for nimesulide, as it reproduced a positive test in the 5 patients. In the case of FDE from piroxicam, our studies confirm cross-reactivity with tenoxicam whereas in piroxicam-induced photosensitivity tenoxicam can be used safely. In photosensitivity the responsible moiety is a UVA photoproduct of piroxicam antigenically and structurally similar to thiosalicylic acid, a moiety which is not involved in FDE.

Cytotoxic and genotoxic effects of acitretin, alone or in combination with psoralen-ultraviolet A or narrow-band ultraviolet B-therapy in psoriatic patients

Acitretin is currently used alone or combined with PUVA (psoralen + UVA) or with narrow-band ultraviolet B (NBUVB), to treat moderate and severe psoriasis. However, little is known about the potential genotoxic/carcinogenic risk and the cytostatic/cytotoxic effects of these treatments. Our aim was to study the cytotoxic and genotoxic effects of acitretin - alone or in combination with PUVA or NBUVB - by performing studies with blood from patients with psoriasis vulgaris who were treated with acitretin, acitretin+PUVA or acitretin+NBUVB for 12 weeks, and in vitro studies with blood from healthy volunteers, which was incubated with acitretin at different concentrations. The cytotoxic and genotoxic effects were evaluated by the cytokinesis-blocked micronucleus test and the comet assay. Our results show that psoriatic patients treated with acitretin alone or with acitretin+NBUVB, did not show genotoxic effects. In addition, these therapies reduced the rate of proliferation and induced apoptosis and necrosis of lymphocytes; the same occurred with lymphocyte cultures incubated with acitretin (1.2-20μM). The acitretin+PUVA reduced also the proliferation rate, and increased the necrotic lymphocytes. Our studies suggest that therapy with acitretin alone or combined with NBUVB, as used in psoriatic patients, does not show genotoxic effects, reduces the rate of proliferation and induces apoptosis and necrosis of lymphocytes. The combination of acitretin with PUVA also reduces the proliferation rate and increases the number of necrotic lymphocytes. However, as it induced slight genotoxic effects, further studies are needed to clarify its genotoxic potential.

Portuguese Position Paper on the Use of Biosimilars in Psoriasis.

1. Consulta de Psoríase. Serviço de Dermatologia. Centro Hospitalar do Porto. Porto. Portugal. 2. Instituto de Ciências Biomédicas Abel Salazar. Universidade do Porto. Porto. Portugal. 3. Serviço de Dermatologia. Centro Hospitalar de Lisboa Central. Lisboa. Portugal. 4. Serviço de Dermatologia. Hospital da Luz. Lisboa. Portugal. 5. Unidade de Psoríase. Hospital Cuf – Descobertas. Lisboa. Portugal. 6. Serviço de Dermatologia. Centro Hospitalar de Leiria. Leiria. Portugal. 7. Serviço de Dermatologia. Clinica Laser de Belém. Lisboa. Portugal. 8. Serviço de Dermatologia. Centro Hospitalar de S. João. Porto. Portugal. 9. Departamento de Farmacologia e Terapêutica. Faculdade de Medicina. Universidade do Porto. Porto. Portugal. 10. Consulta de Fototerapia. Serviço de Dermatologia. Hospital de Santo António dos Capuchos. Centro Hospitalar de Lisboa Central. Lisboa. Portugal. 11. Serviço de Dermatologia. Centro Hospitalar e Universitário de Coimbra. Coimbra. Portugal. 12. Unidade Curricular de Dermatologia. Escola de Ciências da Saúde. Universidade do Minho. Braga. Portugal. 13. Unidade de Dermatologia. Hospital dos Lusíadas. Lisboa. Portugal. 14. Centro de Ambulatório. Centro Hospitalar de Vila Nova de Gaia e Espinho. Vila Nova de Gaia. Portugal. 15. Unidade de Fototerapia. Serviço de Dermatologia. Centro Hospitalar de Vila Nova de Gaia e Espinho. Vila Nova de Gaia. Portugal. 16. Sociedade Portuguesa de Dermatologia e Venereologia. Lisboa. Portugal. 17. Serviço de Dermatologia. Centro Hospitalar do Porto. Porto. Portugal. 18. Colégio de Especialidade de Dermatologia. Lisboa. Portugal. 19. Serviço de Dermatologia. Centro Hospitalar Lisboa Norte. Lisboa. Portugal. 20. Unidade Curricular de Dermatologia. Faculdade de Medicina. Universidade de Lisboa. Lisboa. Portugal. 21. Unidade de Investigação em Dermatologia. Instituto de Medicina Molecular. Universidade de Lisboa. Lisboa. Portugal.  Autor correspondente: Tiago Torres. torres.tiago@outlook.com Recebido: 16 de agosto de 2016 Aceite: 17 de agosto de 2016 | Copyright

Elastosis Perforans Serpiginosa and Wilson Disease: A Rare but Predictable Consequence of Long-term Therapy with D-Penicillamine

Elastosis perfurans serpiginosa is a rare perforating dermatosis found primarily in adolescents and young adults, characterized by transepidermal elimination of abnormal elastic fibers. The only drug known capable of inducing elastosis perfurans serpiginosa is D-penicillamine. We report the case of a 52 year-old woman with keratotic papules arranged in an annular pattern with central clearing and centrifugal growth, located in the anterior cervical region. The patient was chronically treated with D-penicillamine for Wilson disease. Lesion biopsy showed transepidermal elimination of thickened, eosinophilic, branched, sawtooth-like elastic fibers. The clinical and pathological findings were consistent with elastosis perfurans serpiginosa secondary to D-penicillamine. It is estimated that elastosis perfurans serpiginosa occurs in 1% of patients treated with D-penicillamine. By blocking directly or indirectly the desmosine cross-links between elastin molecules, D-penicillamine leads to the synthesis of abnormal dermal and extracutaneous elastic fibers. Elastosis perfurans serpiginosa may be the first manifestation of a multisystemic degenerative process of elastic connective tissue.