Immunologic biomarkers for clinical and therapeutic management of psoriasis.

BACKGROUND: The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-α inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon. Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. AIMS: To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. METHODS: An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-α agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS: Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. CONCLUSIONS: Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis.

hMena: altered expression in psoriatic skin.

Psoriasis is a chronic inflammatory skin disease, characterized by an enhanced proliferation and a deregulated differentiation of keratinocytes. hMena is an actin regulatory protein involved in the control of cell motility and adhesion. hMena results up-modulated in several human tumors with respect to normal tissues and its expression has been positively correlated to proliferation rate, tumor size and aggressiveness in response to mitogenic stimuli, such as epidermal growth factor. The hyperproliferation of keratinocytes observed in psoriasis prompted us to evaluate hMena expression on biopsies collected from involved and uninvolved skin of 12 patients with active plaque-type psoriasis with respect to healthy skin. We analyzed the expression of hMena at transcript and protein levels by quantitative RT-PCR and immunohistochemistry. We correlated the expression of hMena to Ki67 proliferation index and to keratin 10 (K10) and keratin 16 (K16) used as markers of keratinocyte differentiation and activation. We demonstrated the expression of hMena in a hyperproliferative skin condition not related to neoplastic transformation. Interestingly, we observed that hMena is not expressed in healthy skin, but it becomes detectable in non-lesional areas and it is even more expressed in lesional psoriatic skin. In addition, we found that hMena expression is correlated to the rate of keratinocyte proliferation and activation. Hence, our observations indicate hMena as a new possible player, involved in the development and/or maintenance of the hyperproliferative state of psoriatic keratinocytes.

The diagnosis of early psoriatic arthritis in an outpatient dermatological centre for psoriasis.

BACKGROUND: Most of the data currently available on early psoriatic arthritis (EPsA) derive from studies performed in rheumatological settings. However, in recent years, there has been an increase in the amount of data from dermatologic centres. OBJECTIVES: To describe the prevalence, clinical, laboratory and imaging characteristics of psoriatic patients with EPsA seen at a dermatological outpatient psoriasis centre. METHODS: From January 2007 to May 2010, all patients with psoriasis who visited the psoriasis centre were asked about inflammatory joint involvement. A diagnosis of psoriatic arthritis was made on the basis of clinical, laboratory and imaging studies. The patients were diagnosed with early PsA (EPsA) if their inflammatory articular symptoms had been present for ≤ 1 year. RESULTS: We diagnosed EPsA in 33 patients. Joint involvement was polyarticular (>5 joints involved) in 20 patients (60.6%) and oligoarticular (≤5 joints involved) in the remaining 13 patients. Quality of life due to skin involvement and the degree of functional impairment due to joint inflammation were only mildly affected, as measured by DLQI and HAQ, respectively. A direct correlation between the number of tender joints (ACR 68) and HAQ was found (r = 0.36; P = 0.04). Imaging studies showed that in spite of the absence of radiologic findings of peripheral joint damage, ultrasonography and contrast enhanced ultrasonography showed signs of articular inflammation in all patients. CONCLUSIONS: A diagnosis of EPsA can be correctly performed in a dermatologic outpatient facility. To do so, a close collaboration among dermatologists, rheumatologists and radiologists is necessary.

High prevalence of latent tuberculosis infection in autoimmune disorders such as psoriasis and in chronic respiratory diseases, including lung cancer.

The early diagnosis and treatment of individuals harboring M. tuberculosis is key to ensuring the effectiveness of health programs aimed at the elimination of tuberculosis (TB). Monitoring for TB also has other important health care implications for the related immune pathology caused by the chronic inflammatory response to M. tuberculosis. Moreover, the recent introduction of biologic therapies for the treatment of several immune-mediated inflammatory diseases has shown unexpected high frequencies of reactivation of latent TB. The present cross-sectional study is aimed at estimating the prevalence of latent tuberculosis infection (LTBI) in different groups of subjects, either undergoing a routine program of screening for TB or a clinical monitoring of autoimmune or lung disorders, by analyzing their immune response in vitro to a pool of different M. tuberculosis antigens through an IFN-gamma-release assay (IGRA). We consecutively tested 1,644 subjects including health care workers (931), healthy immigrants from different countries (93), patients with a diagnosis of psoriasis (405), patients with lung inflammatory disease (60) or lung neoplasia (32) and a group of HIV-1 infected Italian subjects (120). The prevalence of IGRAs positive responses among health care workers was 8.9 percent. In comparison, significantly higher frequencies were found in healthy immigrant subjects (33.3%), similar to those found in inflammatory broncho-pneumopathies (34.5%) or lung cancer (29.6%). Interestingly, an unexpected high prevalence was also found in patients affected by psoriasis (18.0%), while HIV-infected subjects had values comparable to those of health care workers (10.8%). An age cut-off was determined and applied for each group by receiver operating characteristic (ROC) curves in order to perform the statistical analysis among age-comparable groups. Multivariate analysis showed that the age and clinical conditions such as having a diagnosis of psoriasis or a lung inflammatory disease were independent risk factors for developing an IGRA positive response. This study highlights an unprecedented high prevalence of IGRA positive responses among patients affected by psoriasis and emphasizes the need for a preliminary assessment of LTBI before the administration of any biologic therapy based on cytokine antagonists such as anti-TNF-alpha. Moreover, screening for LTBI should be routinely performed in the presence of a chronic pulmonary disease.

Pulmonary sarcoidosis in a patient with psoriatic arthritis during infliximab therapy.

The occurrence of sarcoidosis during anti-TNF-alpha therapy has occasionally been published. We report the case of a psoriasis patient who developed pulmonary sarcoidosis during a cycle of therapy with infliximab.

Modì: a new mobile instrument for in situ double-pulse LIBS analysis.

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for in situ elemental analysis. A new mobile instrument for LIBS analysis, developed in a collaboration between Marwan Technology s.r.l. and the Applied Laser Spectroscopy Laboratory in Pisa, is presented, and some applications of it and results from it are outlined. The innovative experimental set-up, based on the use of two suitably retarded laser pulses and a standardless analysis procedure, which overcomes problems related to matrix effects, greatly improves the potential of this technique for accurate quantitative analysis.

Diagnosis of pigmented skin lesions by dermoscopy: web-based training improves diagnostic performance of non-experts.

BACKGROUND: Dermoscopy has been shown to enhance the diagnosis of melanoma. However, use of dermoscopy requires training and expertise to be effective. OBJECTIVES: To determine whether an Internet-based course is a suitable tool in teaching dermoscopy, and to evaluate the diagnostic value of pattern analysis and diagnostic algorithms in colleagues not yet familiar with this technique. METHODS: Sixteen colleagues who were not experts in dermoscopy were asked to evaluate the dermoscopic images of 20 pigmented skin lesions using different diagnostic methods (i.e. pattern analysis, ABCD rule, seven-point checklist and Menzies' method), before and after an Internet-based training course on dermoscopy. Mean +/- SEM sensitivity, specificity and diagnostic accuracy, and kappa (kappa) intraobserver agreement were evaluated for each diagnostic method before and after training for the 16 participants. Differences between mean values were assessed by means of two-tailed Wilcoxon rank-sum tests. RESULTS: There was a considerable improvement in the dermoscopic melanoma diagnosis after the Web-based training vs. before. Improvements in sensitivity and diagnostic accuracy were significant for the ABCD rule and Menzies' method. Improvements in sensitivity were also significant for pattern analysis, whereas the sensitivity values were high for the seven-point checklist in evaluations both before and after training. No significant difference was found for specificity before and after training for any method. There was a significant improvement in the kappa intraobserver agreement after training for pattern analysis and the ABCD rule. For the seven-point checklist and Menzies' method there was already good agreement before training, with no significant improvement after training. CONCLUSIONS: We demonstrated that Web-based training is an effective tool for teaching dermoscopy.

Local treatment of chronic cutaneous leg ulcers with recombinant human granulocyte-macrophage colony-stimulating factor.

AIM: To test the efficacy and safety of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in the treatment of chronic cutaneous leg ulcers. METHODS: Five patients with chronic cutaneous leg ulcers were recruited for this 4-month study using only rHuGM-CSF to treat the ulcers. One patient had a neuropathic-diabetic ulcer, and four had long-standing vascular leg ulcers. RESULTS: The patient with the neuropathic diabetic ulcer showed complete healing after 1 month of treatment. The other four patients with vascular leg ulcers with a long history of ulceration had a poor prognosis for healing. The first, with three venous ulcerative lesions, presented complete resolution of one ulcer and stabilization of the other two; the second and third patients, with large vascular ulcers, improved with more then 50% reduction of the mean diameter of the ulcers; the fourth patient, with one large venous ulcer, did not show any improvement. CONCLUSIONS: Pathogenesis, size and duration of the ulcers seemed to be the most important parameters regarding wound repairing capability of rHuGM-CSF. None of the ulcers increased in size and none of the patients developed clinical side-effects or peripheral blood cell count abnormalities during the treatment. All the results described were stable after 6 months of follow up. The absence of peripheral leucocyte count variation and the size-dependent therapeutic effect indicate that the drug exercises local rather than systemic actions.

Effect of metabolic control on nitrite and nitrate metabolism in type 2 diabetic patients.

1. The measurement of nitrite and nitrate levels in plasma and urine is an approach to assess the activity of the endogenous nitric oxide (NO) system. The aim of the present study was to evaluate whether metabolic control may affect plasma levels and urinary excretion of nitrates and nitrites in type 2 diabetic patients. 2. Twenty consecutive type 2 diabetic patients were studied twice: first (study 1), under poor metabolic control; and, second, after improved metabolic conditions. Determinations of the main metabolic parameters and of plasma nitrates and nitrites (NOX) were performed in the fasting state. A 24 h urinary specimen was obtained for glycosuria, NOX and creatinine. Diet compliance and home blood glucose monitoring was evaluated on a weekly basis until study 2 was performed after 32 +/- 7 days: then, an identical protocol was repeated (study 2). 3. Fasting plasma glucose was lower in study 2 (8.27 +/- 2.11 vs 10.77 +/- 3.88 mmol/L, respectively; P < 0.05); similarly glycosylated haemoglobin (HbA1c) improved significantly. Plasma NOX levels were similar between the first and second studies (14.3 +/- 7.8 vs 13.5 +/- 8.1 micromol/L, respectively); nor were any differences observed in urinary NOX excretion rates (726 +/- 607 vs 689 +/- 444 micromol/day, respectively). The urinary excretion fraction of NOX was higher during study 1 than during study 2 (3.22 +/- 2.38 vs 1.88 +/- 1.98%, respectively; P = 0.031). A relationship was observed between fasting plasma glucose levels and the urinary excretion fraction of NOX (r2 = 0.12; P = 0.026). 4. In type 2 diabetic patients, plasma and urinary levels of NOX do not change after improvement of metabolic control. A worse metabolic control is associated with an increased urinary fraction excretion of NOX: thus, changes in plasma NOX concentration may reflect the effect of hyperglycaemia in the renal handling of these compounds rather than the effects on the L-arginine-NO pathway.