Predictors of perceived stigmatization in patients with psoriasis.

BACKGROUND: The physical appearance of psoriasis can be cosmetically disfiguring, resulting in a substantial social burden for patients. An important aspect of this burden is the experience of stigmatization. While stigmatization is known to be disabling and stressful for patients, little is known about its correlates, and effective interventions are lacking. OBJECTIVES: To examine predictor variables for perceived stigmatization in psoriasis. METHODS: Questionnaires were administered to 514 patients with psoriasis in a cross-sectional study. Zero-order correlation and multiple-regression analyses were conducted including sociodemographic, disease-related, personality, illness cognitions and social support predictor variables. RESULTS: Stigmatization was experienced by 73% of patients to some degree, and correlated with all five categories of predictor variables. In multiple-regression analyses, stigmatization was associated with higher impact on daily life; lower education; higher disease visibility, severity and duration; higher levels of social inhibition; having a type D personality; and not having a partner. CONCLUSIONS: The results indicate that perceived stigmatization is common in psoriasis, and can be predicted by sociodemographic, disease-related and personality variables. These predictor variables provide indications of which patients are especially vulnerable regarding perceived stigmatization, which might be used in treatment.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. METHODS: We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. RESULTS: HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. CONCLUSIONS: HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.

Deep brain stimulation in tinnitus: current and future perspectives.

Chronic tinnitus, also known as ringing in the ears, affects up to 15% of the adults and causes a serious socio-economic burden. At present, there is no treatment available which substantially reduces the perception of this phantom sound. In the past few years, preclinical and clinical studies have unraveled central mechanisms involved in the pathophysiology of tinnitus, replacing the classical periphery-based hypothesis. In subcortical auditory and non-auditory regions, increased spontaneous activity, neuronal bursting and synchrony were found. When reaching the auditory cortex, these neuronal alterations become perceptually relevant and consequently are perceived as phantom sound. A therapy with a potential to counteract deeply located pathological activity is deep brain stimulation, which has already been demonstrated to be effective in neurological diseases such as Parkinson's disease. In this review, several brain targets are discussed as possible targets for deep brain stimulation in tinnitus. The potential applicability of this treatment in tinnitus is discussed with examples from the preclinical field and clinical case studies.

Acitretin treatment of premalignant and malignant skin disorders in renal transplant recipients: clinical effects of a randomized trial comparing two doses of acitretin.

INTRODUCTION: After renal transplantation, the incidence of premalignant and malignant skin lesions is high. Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas, but treatment is hampered by frequent side effects. No optimal long-term dosing advice is available. METHODS: A total of 26 long-term renal transplant recipients were randomized to 1-year treatment with acitretin, either 0.4 mg/kg/d throughout the whole year or 0.4 mg/kg/d during the first 3 months followed by 0.2 mg/kg/d for the remaining 9 months. At 9 different time points, the number of actinic keratoses and tumors was counted, and erythema and thickness of the lesions, and severity of side effects were scored. Patient's judgment was recorded using visual analog scores. RESULTS: In both groups, the number of actinic keratoses decreased by nearly 50%, but the number of new malignant tumors during the study year was similar to the number of tumors in the year before the study. Thickness of the keratoses decreased significantly in both groups. Acitretin dose had to be reduced in most patients because of the frequent occurrence of mucocutaneous side effects, such as cheilitis, excessive peeling of the skin, and hair disorders. In the 14 patients randomized to continuous treatment with a dose of 0.4 mg/kg/d, this dose could be maintained in 3 of 14 patients only. Temporary interruption of acitretin therapy was necessary in 7 of 26 patients. Patients' contentment about the aspect of their skin increased significantly, with no differences between groups. CONCLUSIONS: Acitretin therapy decreased the number of actinic keratoses in renal transplant recipients at a low maintenance dose of 0.2 mg/kg/d and significantly decreased the degree of thickness of the lesions. However, the incidence of new skin malignancies remained unchanged. Despite the high incidence of mucocutaneous side effects, patient's contentment with the aspect of their skin increased significantly.

A multiparameter flow cytometric analysis of the effect of bexarotene on the epidermis of the psoriatic lesion.

BACKGROUND: A new retinoid, bexarotene (Targretin), was recently investigated in a large multicentre trial for its efficacy and safety in psoriasis. Bexarotene is a novel retinoid X receptor (RXR)-selective ligand. OBJECTIVES: The aim was to study the effect of bexarotene in psoriasis by analysing markers for epidermal differentiation, proliferation and inflammation in epidermal single cell suspensions from lesions of patients with psoriasis treated with various doses of bexarotene. METHODS: Thirty-four patients with moderate to severe plaque psoriasis participated in this study and were assigned in sequence to four different dose regimens: 0.5, 1, 2 and 3 mg kg-1 once daily. Before and after 12 weeks of bexarotene treatment, punch biopsies were taken from lesional skin from which epidermal single cell suspensions were prepared using an optimized thermolysin protocol. A sum of scores was determined for each biopsy site, based on a four-point scale for erythema, induration and desquamation. An improved multiparameter flow cytometric assay was used that enabled simultaneous assessment of epidermal proliferation, various aspects of differentiation and epidermal inflammation. The following variables were measured simultaneously: relative DNA content, relative cell size, keratin (K) 10, K6 and vimentin expression. RESULTS: The psoriasis area and severity index (PASI) and sum of scores for the individual psoriatic lesion each showed a statistically significant decrease of 28% after 12 weeks of bexarotene treatment (P < 0.001). However, no significant dose-response effect was found. The total percentage of K10+ cells showed a significant increase of 43% (P < 0.01). The total population of K6 expressing cells did not show significant changes. Regarding the subpopulations of K6 single, K10 single and K6 and 10 co-expressing cells, a significant increase of 77% was seen in the K10+ K6- cells (P < 0.05), a significant decrease of 33% in K10- K6+ cells (P < 0.01), and no significant changes in the remaining population of K10+ K6+ cells. After 12 weeks of treatment with bexarotene no significant changes in epidermal proliferation and inflammation were shown. CONCLUSIONS: The present study indicates a direct effect of RXR activation by bexarotene on the transition of proliferation-associated keratinization into normal keratinization. Although no direct effect of bexarotene on DNA content in the total K10- cells was shown, further studies on subpopulations within the germinative layer such as stem cells and transit amplifying cells might be worthwhile.

Effects of oral bexarotene (targretin) on the minimal erythema dose for broadspectrum UVB light.

Photo(chemo)therapy and oral retinoid therapy for psoriasis or cutaneous T-cell lymphoma are frequently combined to obtain an enhanced therapeutic effect with lower safety risks. Bexarotene, a new RXR-selective retinoid (rexinoid), has been developed for the treatment of cutaneous T-cell lymphoma and has recently been investigated in the treatment of psoriasis. In the present study the UV-modulating properties of bexarotene were evaluated by assessment of the minimal erythema dose (MED) for UVB light. In 11 patients participating in a phase II study of oral bexarotene 0.5 mg/kg/day (7 patients) or 3.0 mg/kg/day (4 patients) for plaque-type psoriasis, MED tests were performed on uninvolved psoriatic skin on the lower back of the subjects before and after 12-week treatment. Clinical scores of erythema and determination of the MED 24 h after irradiation did not show statistically significant changes between the exposed areas before and after bexarotene treatment or between the two doses tested. No photosensitizing reactions were observed. This study demonstrates that a single exposure to UVB irradiation is well tolerated in patients treated with bexarotene 0.5-3.0 mg/kg/day and suggests that it is not necessary to take precautions with respect to short-term effects of sun exposure during bexarotene treatment. Further study of bexarotene photo(chemo)therapy in cutaneous T-cell lymphoma and psoriasis is warranted.