P5941Expression of the serotonin transporter protein in psoriasis is correlatedwith the severity of the disease and chronic stress

Kristofer Thorslund, MD, PhD, Karolinska Institutet, Department ofMedicine Solna, Dermatology and Venereology Unit, Stockholm, Sweden;Ann Eriksson Dufva, Karolinska Institutet, Department of Medicine Solna,Dermatology and Venereology Unit, Stockholm, Sweden; Beni Amatya, MD,PhD, Karolinska Institutet, Department of Medicine Solna, Dermatology andVenereology Unit, Stockholm, Sweden; Klas Nordlind, MD, PhD, KarolinskaInstitutet, Department of Medicine Solna, Dermatology and VenereologyUnit, Stockholm, Sweden

Psoriasis may be worsened by stress and mood disorders. There is an increasedexpression of the serotonin transporter protein (SERT) in involved psoriatic skinas compared to noninvolved psoriatic skin and normal skin. The aim of this studywas to investigate if the increased expression of SERT in psoriasis correlates withthe severity of disease, chronic stress, and depression. Biopsy specimens frominvolved and noninvolved skin from the back of 20 patients with chronic plaquepsoriasis were immunohistochemically analysed, using a monoclonal antibody toSERT. The severity of psoriasis was assessed for each patient using the PsoriasisArea and Severity Index (PASI). Levels of depression and chronic stress weremeasured using Beck’s Depression Inventory (BDI) and the salivary cortisol test,respectively. A positive correlation (r ¼ 0.53; P \ .05) between PASI and thenumbers of SERT-positive dendritic cells in the epidermis of involved psoriaticskin was determined. We also observed a negative correlation (r ¼ -0.46; P\.05)between salivary cortisol ratio levels and the numbers of SERT-positive cells inthe epidermis of involved psoriatic skin, indicating a correlation between SERTexpression and chronic stress. The serotonergic system may be involved in thechronic inflammation evident in psoriatic skin. Through modulating the levels ofSERT, there might be a therapeutic possibility for reducing chronic inflammationin psoriasis.

APRIL 20

cial support: None identified.

Commer

P5951Hepatitis C may predispose to psoriasis by upregulating cathelicidin, Toll-like receptor-9, and interferon-gamma

Maryam Afshar, MD, University of California, San Diego, San Diego, California,United States; David Audish, University of California, San Diego, San Diego, CA,United States; Richard Gallo, MD, PhD, University of California, San Diego, SanDiego, CA, United States; Tissa Hata, MD, University of California, San Diego, SanDiego, CA, United States

Background: In the United States, up to 0.06% of people suffer from both psoriasisand hepatitis C. In the largest study to date of the prevalence of hepatitis C virus(HCV) infection and psoriasis, a positive association was found between these 2disorders, suggesting a causative effect. Innate immune genes, including theantimicrobial peptide cathelicidin (CAMP) and Toll-like receptor-9 (TLR9) arethought to play an important role in the pathogenesis of psoriasis since thecathelicidin peptide LL37 acts with self-DNA released after skin injury to triggerproduction of type 1 interferons (IFNs) from plasmacytoid dendritic cells andkeratinocytes. IFN production in turn can influence T-cell polarization towards aTH17 phenotype and drive autoimmunity. In addition, acute HCV infection leads toproduction of IFNg, a cytokine also strongly implicated in psoriasis development.We hypothesized that HCV infection may increase expression of innate immunegenes such as CAMP and TLR9, thereby explaining the increased prevalence ofpsoriasis with hepatitis C.

Objective: To study the expression of immune genes CAMP, TLR9, and INFg inlesional and nonlesional skin of patients with psoriasis with and without HCVinfection.

Methods: Skin was collected from 10 patients with psoriasis only and from 7 patientswith HCV and psoriasis not on IFNa therapy. CAMP, TLR9, and IFNg mRNAexpression were measured by quantitative reverse transcriptase-polymerase chainreaction. Demographic and clinical data was recorded. This study was supported bya National Psoriasis Foundation fellowship grant.

Results: CAMP, TLR9, and IFNg levels were significantly higher in nonlesional skin ofpatients with hepatitis C and psoriasis than in the nonlesional skin of patients withonly psoriasis (P\.001). In lesional skin, CAMP, TLR9, and IFNg levels were alsosignificantly higher in psoriasis patients with hepatitis C than patients with psoriasisonly (P\.01). IFNg was higher in lesional skin of HCV-positive psoriatic patientsthan in their nonlesional skin. No HCV-positive psoriasis patients had a history ofskin infection.

Conclusion: Patients with hepatitis C may be at increased risk for psoriasis becauseHCV infection increases cutaneous levels of cathelicidin, TLR9, and IFNg. Largerstudies are required to elucidate the role of innate immune genes in the associationbetween hepatitis C and psoriasis.

cial support: None identified.

Commer

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P5987Lipopolysaccharide-binding protein, adipocyte fatty acid-binding protein,and retinol-binding protein-4: Potential indicators of metabolic syndromein patients with psoriasis

Jorge Roman�ı, MD, PhD, Hospital Parc Taul�ı, Sabadell, Spain; Assumpta Caix�as,MD, PhD, Hospital Parc Taul�ı, Sabadell, Spain; Joan Vendrell, MD, PhD,Department of Endocrinology. Hospital Universitari Joan XXIII, Tarragona,IISPV, CIBERDEM, Tarragona, Spain; Jos�e Manuel Carrascosa, MD, PhD,Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Aut�onoma deBarcelona, Badalona, Spain; Mercedes Rigla, MD, PhD, Hospital Parc Taul�ı,Sabadell, Spain; Miquel Ribera, MD, PhD, Hospital Parc Taul�ı, Sabadell, Spain;Xavier Escot�e, PhD, Department of Endocrinology, Hospital Universitari JoanXXIII, Tarragona, IISPV, CIBERDEM, Tarragona, Spain

Psoriasis is a chronic inflammatory skin disease that has been associated withinsulin resistance, atherogenesis, and metabolic syndrome (MS). A relationshipbetween adipocytokines produced by adipose abdominal tissue and activation ofTH1 and TH17 lymphocytes characteristic of psoriatic skin has been described.Moreover, raised levels of circulating lipopolysaccharide (LPS) can trigger anincrease in chronic proinflammatory cytokines, which may mediate the devel-opment of insulin resistance and obesity. We aimed to study the expression ofseveral adipocytokines and circulating LPS in 50 patients with treatment-naivemoderate to severe psoriasis (PASI $ 10) and 50 controls matched by age,gender, and body mass index. Determinations of leptin, resistin, omentin, LBP(lipopolysaccharide binding protein), RBP4 (retinol-binding protein-4), AFABP(adipocyte fatty acid binding-protein), lipocalin-2, STNF1r (soluble receptor ofTNF type I), interleukin-6, and interleukin-17 were performed in patients andcontrols. Chronic inflammatory diseases and psoriatic arthritis were exclusioncriteria. 54% of patients and 42 % of controls fulfilled International DiabetesFoundation criteria for metabolic syndrome. Patients showed significantly higherserum concentrations of lipocalin-2, RBP4, leptin, and rTNF1. Psoriatic patientswith metabolic syndrome had higher LBP, RBP4, and AFABP serum concentra-tions than patients without MS, and these differences were not evident inmatched controls. Those detected differences confirm the role of psoriasis as anadded risk factor of developing MS, possibly through chronic inflammation,attraction of risk factors independent of body mass index, or a genetic linkage.LBP is a reliable indicator of circulating LPS, a marker of antibacterial inflamma-tory response, and its raised levels in psoriatic patients with MS could besuggestive of some unidentified microbial antigens taking part in the triggering ofpsoriatic cutaneous and systemic inflammation driving the patients towardsdevelopment of MS.

cial support: None identified.

Commer

P5991Prevalence of entheses abnormalities in patients with nail and cutaneouspsoriasis

Mar�ıa Castellanos Gonz�alez, MD, 12 de Octubre Hospital, Madrid, Spain;Francisco Vanaclocha Sebasti�an, MD, 12 de Octubre Hospital, Madrid, Spain;Jimena Sanz Bueno, MD, 12 de Octubre Hospital, Madrid, Spain; Raquel RiveraD�ıaz, MD, 12 de Octubre Hospital, Madrid, Spain

Background: The aim of the present study was to investigate the presence ofentheses abnormalities with power doppler ultrasonography (US) in distal inter-phalangeal joints (DIP) of hands in patients with cutaneous and nail psoriasiswithout psoriatic arthritis (PA).

Methods: We studied 10 patients with cutaneous and nail psoriasis recruited in ourhospital. None of them presented arthropathy neither received systemic therapy forthe last 3 months. They underwent a dermatologic assesment to determinate theonset time of their disease, the type of cutaneous and nail manifestation, and PASIand NAPSI. In addition, all patients were evaluated by US of the DIP of the fingers ofboth hands to determinate the presence of enthesitis, tenosynovitis, effusion, boneerosions, and/or bone proliferations.

Results: We found entheses abnormalities in 7 of 10 patients, 6 of thempresented with tenosynovitis, 4 with effusion, and 2 with signs of boneproliferations. We did not find bone erosion in any case. The ecographic findingswere detected in all patients with transverse groves (2/2) and splinter hemor-rhages (1/1; P ¼ .467 and P ¼ .700, respectively), in 75% (6/8) of patients with‘‘oil spot’’ phenomenon and with hyperkeratosis (3/4; P ¼ .533 and P ¼ .667,respectively), in 71% (5/7) of patients that showed pitting (P ¼ .708), and in 50%(1/2) of who had leukonychia and onicholysis (P ¼ .533 in both cases). We didnot find significant differences in relation to time of onset of disease and PASI.However NAPSI was significantly higher in those patients who had findings onimaging studies (P ¼ .07).

Discussion: There is increasing evidence that show how the enthesitis is oftenasymptomatic in the early stages of PA and can determinate the patients thatwould develop PA later. Bearing in mind that one of the psoriasis featuresassociated with higher risk of PA is nail manifestation and that the nail isfunctionally integrated with entheses associated with the distal phalanx, theauthors expected to find a high prevalence of entheses abnormalities in DIP ofhands in psoriatic patients with nail involvement. According to that, we detectedabnormalities in 7 of 10 patients, who did not have the diagnosis of PApreviously. In addition, the higher NAPSI the more common to find alterationsin IFD in our study, which establishes the importance of study nail manifestationsin our patients at clinical practice.

cial support: None identified.

Commer

J AM ACAD DERMATOL AB3