Extracorporeal photochemotherapy for the treatment of glomerulopathies with associated nephrotic syndrome.

INTRODUCTION: Patients with glomerulopathies associated with nephrotic syndrome have few effective treatment options. Here we report on the use of extracorporeal photochemotherapy (ECP) in 6 patients in whom glomerulopathy failed to respond to pharmacologic therapy. ECP is a promising immunomodulatory therapy associated with few side effects, that has been successfully used in the treatment of other immune-mediated conditions such as solid organ transplant rejection and graft-versus-host disease. METHODS: In this study, patients underwent 12 months of ECP. In all patients, progressive improvement in proteinuria was noted during the follow-up period, and total cholesterol and triglyceride levels also returned to near-normal values. RESULTS: In the 4 patients who had adequate renal function at study initiation, improvement of renal function was observed, as indicated by improved glomerular filtration rates (GFRs) and decreased proteinuria to creatininuria (Pru/Cru) ratios. In contrast, renal function progressively worsened in the 2 patients with inadequate renal function at study initiation. CONCLUSIONS: The results suggest that ECP is a feasible treatment for patients with glomerulopathies associated with nephrotic syndrome who have adequate baseline renal function. Additional clinical evaluation will have to be performed to better define the patient population in which ECP is most effective.

CXCL13 is highly produced by Sézary cells and enhances their migratory ability via a synergistic mechanism involving CCL19 and CCL21 chemokines.

Chemokine and chemokine receptors expressed by normal and neoplastic lymphocytes play a key role in cell recruitment into skin and lymph nodes. The aim of this study was to get further insights into the role of chemokines in pathogenesis and progression of cutaneous T-cell lymphoma (CTCL) with particular regard to Sézary Syndrome (SS), a CTCL variant with blood involvement. Here, we show that functional CXCL13 homeostatic chemokine is strongly up-regulated in SS cells, well-detectable in skin lesions and lymph nodes, and measurable at high concentration in plasma of SS patients, at different levels during disease progression. Furthermore, we show that the addition of CXCL13 to CCL19 or to CCL21, the selective CCR7 agonists responsible for lymph node homing, strongly enhances the migration of CCR7+ SS cells. We also show that neutralization of the CCR7 receptor strongly impairs CCL19/21-induced chemotaxis of SS cells both in the absence or presence of CXCL13. Additional experiments performed to investigate the survival, adhesion, and metalloproteases secretion indicate that CXCL13 combined with CCL19 and CCL21 mainly affects the chemotaxis of SS cells. Our findings suggest that this newly described CXCL13 expression in SS represents a new pathogenetic mechanism of diagnostic significance.

Health related quality of life assessment in the routine clinical practice of a dermatology unit.

A descriptive study in a Dermatological Research Institution in Rome, Italy, was conducted to test the feasibility and acceptability of health related quality of life (HRQoL) assessment in the daily routine. Quality of life, and psychosocial distress evaluations were obtained for each patient. Patients were invited to complete the Skindex-29, GHQ-12, and SF-36. Results were returned to the clinical staff using standardised feed-back forms with: a) "categories" of QoL scores to help interpreting Skindex-29 scores; b) "warnings" pointing out problems that patients experienced "all the time"; c) categories of GHQ-12 scores for minor psychiatric problems; d) the classical SF-36 graph depicting the patient's "QoL profile" with normative references. The clinical staff were trained, and then their attitudes and behaviours were surveyed using a standardised questionnaire. For all 170 participants enrolled (63% males, 35% age > 64 years), feed-back forms were provided within three hours from data collection. For patients with repeated hospitalisations time-trends in HRQoL measurements were also provided. The acceptability, both for patients and the clinical staff, was high but the actual impact on clinical activities was limited. The routine assessment of HRQoL in dermatology is feasible and well accepted both by patients and by the clinical staff. The application of these widely used questionnaires should be implemented in a larger scale and evaluated in different settings.

Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV.

Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin T-cell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26(-) phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26(+) CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26.

Recognition of depressive and anxiety disorders in dermatological outpatients.

Although mental disorders are frequent among dermatological patients, little is known about their recognition by dermatologists. This study aimed to assess dermatologists' ability to recognize depressive and anxiety disorders. All adult outpatients who visited four dermatologists on predetermined days (n=317) completed the 12-item General Health Questionnaire (GHQ-12) and the section on depressive and anxiety disorders of the Patient Health Questionnaire (PHQ). Dermatologists, masked to GHQ-12 and PHQ scores, rated patients' mental health status. The analysis was performed on 277 patients (87%) with complete data. With the PHQ as criterion standard, the dermatologists' assessment sensitivity was 33%, while specificity was 76%. In most cases of disagreement between the dermatologists and the PHQ, the GHQ-12 corroborated the PHQ classification. Anxiety disorders tended to be recognized better than depressive disorders. Among patients with a PHQ diagnosis, male gender tended to be associated with misclassification by dermatologists. Although limitations inherent in self-report psychiatric assessment should be considered, this study suggests that mental disorders often go unrecognized in dermatological patients. This issue might be addressed by implementing specific training programmes, using validated screening questionnaires for depression and anxiety, and developing rational consultation-liaison services.

Only limited support for a role of psychosomatic factors in psoriasis. Results from a case-control study.

OBJECTIVE: To investigate the role of stressful events, social support, attachment security and alexithymia in triggering or exacerbating psoriasis. METHODS: Outpatients experiencing a recent onset or exacerbation of psoriasis (n=40) were compared with outpatients with skin conditions in which psychosomatic factors are regarded as negligible (n=116). Stressful events during the last year were assessed with Paykel's Interview for Recent Life Events. Attachment style, alexithymia and perceived social support were assessed with the ECR questionnaire, the TAS-20 and the MSPSS, respectively. RESULTS: The mean number of recently experienced life events, or of undesirable, uncontrollable or major events was not different between psoriatic patients and controls. The only stress measure that showed a slight trend towards an association with psoriasis was having experienced four or more stressful events in the preceding year. There was a statistical trend towards an association between alexithymia and psoriasis, whereas there were no significant differences between patients with psoriasis and controls with respect to perceived social support and attachment security. Subgroup analysis suggested that the role of all psychosomatic factors studied might be more important in certain clinical types, such as guttate and diffuse plaque psoriasis. CONCLUSIONS: Our findings provide only limited support for a role of psychosomatic factors in psoriasis. Future studies should investigate chronic and daily stressors in addition to major life events, include measures of stress appraisal and include specifically patients with a recent onset of disease.

Purely follicular mycosis fungoides without mucinosis: report of two cases with review of the literature.

Follicular lesions can either associate with typical patch-/plaque-type mycosis fungoides or, more rarely, be the only clinical manifestation of the disease. We describe 2 adult patients who presented with alopecia and disseminated follicular erythematous papules, and comedones and cysts, respectively. In both patients, histology showed a folliculotropic infiltrate of atypical lymphocytes that spared the epidermis, in the absence of follicular mucinosis. Molecular genetic analysis confirmed the oligo/monoclonal nature of the T-cell infiltrate. Reported cases of purely follicular mycosis fungoides without mucinosis are reviewed.

Association of dissatisfaction with care and psychiatric morbidity with poor treatment compliance.

OBJECTIVES: To examine factors associated with compliance with dermatologic treatment. DESIGN: Longitudinal study. Quality of life and psychological well-being were measured before the dermatologic visit with a self-completed questionnaire. Telephone interviews were performed 3 days and 4 weeks after the visit to evaluate patient satisfaction and medication adherence, respectively. SETTING: Outpatient clinics of a large dermatologic hospital in Rome, Italy. PATIENTS: A total of 1389 outpatients were contacted and 722 (52%) agreed to participate. Among them, 424 responded to the inclusion criteria and were enrolled in the study. Of these, 396 (93%) completed the telephone interviews. MAIN OUTCOME MEASURE: Self-reported compliance with dermatologic treatment. RESULTS: The dermatologists' prescriptions were not exactly followed by 44% of patients. In multiple logistic regression analysis, treatment adherence was strongly associated with complete satisfaction. Poor quality of life on the emotions scale (indicating mainly high levels of shame and embarrassment) was also associated with medication adherence. On the contrary, a strong negative association was observed between psychiatric morbidity and compliance. CONCLUSIONS: This is the first longitudinal study on dermatologic patients showing that dissatisfaction with care and psychiatric morbidity are significantly and independently associated with poor medication adherence. To improve medication adherence, particular attention should be dedicated to the physician's interpersonal skills, which emerged as a major component of patient satisfaction. Moreover, our results highlight the need for a timely identification and appropriate management of psychiatric disorders in everyday dermatologic practice.