Clara De Simone

Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis

BACKGROUND/AIMS The association between NAFLD and psoriasis has never been explored in prospective epidemiological studies. The aim of this 2-phase study was to study the clinical features of NAFLD in patients with psoriasis. METHODS Phase 1: Investigation of prevalence and characteristics of NAFLD in an unselected cohort of 142 adult Italian outpatients with psoriasis vulgaris. Phase 2: Comparison of the psoriasis cohort subgroup with NAFLD and an age- and body mass index-matched retrospective cohort of 125 non-psoriasis patients with biopsy proven NAFLD. RESULTS Based on histories, laboratory tests, and ultrasound studies, 84 (59.2%) received clinical diagnosis of NAFLD; 30 had factors potentially associated with liver disease other than NAFLD (e.g., viral hepatitis, significant ethanol, methotrexate use); and 28 (19.7%) had normal livers. Comparison of the normal-liver and NAFLD subgroups revealed that NAFLD in psoriasis patients (Ps-NAFLD) was significantly correlated with metabolic syndrome (p<0.05); obesity (p=0.043); hypercholesterolemia (p=0.029); hypertriglyceridemia (p<0.001); AST/ALT ratio >1 (p=0.019), and psoriatic arthritis (PsA) (p=0.036). The association with PsA remained significant after logistic regression analysis (OR=3.94 [CI, 1.07-14.46]). Compared with the retrospective non-psoriatic NAFLD cohort (controls), Ps-NAFLD patients (cases) were likely to have severe NAFLD reflected by non-invasive NAFLD Fibrosis Scores and AST/ALT >1. CONCLUSIONS NAFLD is highly prevalent among psoriasis patients, where it is closely associated with obesity (overall and abdominal), metabolic syndrome, and PsA, and more likely to cause severe liver fibrosis (compared with nonPs-NAFLD). Routine work-up for NAFLD may be warranted in patients with psoriasis, especially when potentially hepatotoxic drug therapy is being considered.

Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene

The PASH triad (pyoderma gangrenosum, acne, and hidradenitis suppurativa) has recently been described in 2 unrelated patients as a new entity within the spectrum of autoinflammatory syndromes.1- 2 PASH syndrome is similar to PAPA syndrome (pyogenic arthritis, acne, and pyoderma gangrenosum) but differs insofar as it lacks the associated arthritis and has a different genetic basis.3 PAPA syndrome is caused by mutations in the proline-serine-threonine-phosphatase protein 1 (PSTPIP1) gene (OMIM: 606347) that is involved in regulating innate immune responses, whereas no mutations have yet been detected in PASH syndrome.

Usefulness of ultrasound imaging in detecting psoriatic arthritis of fingers and toes in patients with psoriasis.

Background. Given that clinical evaluation may underestimate the joint damage and that early treatment can slow down psoriatic arthritis (PsA) progression, screening psoriasis patients with imaging tools that can depict early PsA changes would entail clear benefits. Objective. To compare the ability of X-ray and ultrasound (US) examination in detecting morphological abnormalities consistent with early PsA in patients with psoriasis, using rheumatological evaluation as the gold standard for diagnosis. Methods. Patients with chronic plaque psoriasis and no previous PsA diagnosis attending our outpatient dermatology clinic and reporting finger/toe joint and/or tendon pain underwent X-ray and US evaluation; they were subsequently referred to a rheumatologist for clinical examination and review of imaging findings. Results. Abnormal US and/or X-ray findings involving at least one finger and/or toe (joints and/or tendons) were seen in 36/52 patients: 11 had one or more X-ray abnormalities, including erosion, joint space narrowing, new bone formation, periarticular soft tissue swelling, and periarticular osteoporosis; 36 had suspicious changes on US. Conclusion. US proved valuable in detecting joint and/or tendon abnormalities in the fingers and toes of patients with suspicious changes. The dermatologist should consider US to obtain an accurate assessment of suspicious findings.

Achilles tendinitis in psoriasis: clinical and sonographic findings

BACKGROUND Involvement of the Achilles tendon is frequent in psoriatic arthritis, but it is easily missed at clinical examination. OBJECTIVE To seek evidence of Achilles tendon abnormalities by means of sonography in psoriatic patients and to correlate sonographic findings with clinical symptoms (tendon and soft-tissue swelling, pain, and difficulty in walking). METHODS Fifty-nine patients with plaque-type psoriasis (Psoriasis Area and Severity Index score, 3.7-34.7) and 50 healthy, aged-matched volunteers underwent clinical and sonographic evaluation of Achilles tendons and peritendinous structures. RESULTS Eighteen (30.5%) of the 59 patients had clinical symptoms of Achilles tendinitis. Thirty-five (59.3%) of the patients had sonographic abnormalities. Of these, 13 patients had clinically symptomatic abnormalities, and 11 had psoriatic arthritis. Degenerative tendinitis was the most frequent sonographic finding (76.9%) among patients with symptomatic conditions. Five patients with symptoms did not have sonographic alterations. None of the controls had clinical or sonographic changes. CONCLUSIONS In psoriatic patients Achilles tendon abnormalities cannot be excluded even when they are clinically absent.

Association of Pyoderma Gangrenosum, Acne, and Suppurative Hidradenitis (PASH) Shares Genetic and Cytokine Profiles With Other Autoinflammatory Diseases

AbstractThe association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1&bgr; and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1&bgr;, tumor necrosis factor-&agr;, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.

Array-based comparative genomic hybridization in early-stage mycosis fungoides: recurrent deletion of tumor suppressor genes BCL7A, SMAC/DIABLO, and RHOF.

The etiology of mycosis fungoides (MF), the most frequent form of cutaneous T cell lymphoma (CTCL), is poorly understood. No specific genetic aberration has been detected, especially in early‐stage disease, possibly due to the clinical and histological heterogeneity of patient series and to the different sources of malignant cells (skin, blood, or lymph node) included in most studies. Frozen skin biopsies from 16 patients with early‐stage MF were studied using array‐based comparative genomic hybridization. A DNA pool from healthy donors was used as the reference. Results demonstrated recurrent loss of 19, 7p22.1‐p22.3, 7q11.1‐q11.23, 9q34.12, 12q24.31, and 16q22.3‐q23.1, and gain of 8q22.3‐q23.1 and 21q22.12. The 12q24.31 region was recurrently deleted in 7/16 patients. Real‐time PCR investigation for deletion of genes BCL7A, SMAC/DIABLO, and RHOF—three tumor suppressor genes with a putative role in hematological malignancies—demonstrated that they were deleted in 9, 10, and 13 cases, respectively. The identified genomic alterations and individual genes could yield important insights into the early steps of MF pathogenesis.

Rapid Regression of Psoriasis in a Coeliac Patient after Gluten-Free Diet A Case Report and Review of the Literature

Background: Several skin disorders are present in patients affected by coeliac disease (CD) – among them, psoriasis has been described. However, at present the relationship between CD and psoriasis remains controversial since there are few and contrasting data on this topic. Method: Here we describe a case of psoriasis in a CD patient not responding to specific therapies for psoriasis. Result: The regression of skin lesions after gluten-free diet (GFD) was evident in a short time. Conclusion: The present case supports the association between CD and psoriasis and the concept that psoriasis in CD patients can be improved by GFD. Future studies are needed to clarify the possible mechanisms involved in this association.

Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue?

Introduction: Immunogenicity of antitumor necrosis factor-alpha (TNFα) agents has been proven to play a significant role in the variability of clinical responses among patients with chronic inflammatory diseases. However, its clinical impact on the outcome of patients with psoriasis and psoriatic arthritis receiving anti-TNFα treatment is not yet fully clear. Despite the high rates of efficacy of anti-TNFα agents in psoriasis, a substantial proportion of patients remain who experience a primary or secondary failure or significant side effects, which are potentially ascribable to immunogenicity. Areas covered: Topics include immunologic response elicited by anti-TNFα agents, the impact of immunogenicity on treatment response to anti-TNFα and the role played by immunogenicity in the lack of efficacy of anti-TNFα agents (infliximab, adalimumab and etanercept) in psoriasis. Expert opinion: Based on data available in the literature and the clinical experience of the authors, this article suggests the optimal approach to drug monitoring and antidrug antibody assay and the most effective use of biologic immunotherapies in this setting. Immunogenicity should be taken into account in the adoption of therapeutic choices in psoriatic patients, such as anti-TNFα agent intensification, or switching to another anti-TNFα agent or a drug with a different mechanism of action.

Efficacy and Safety of Systemic Treatments for Psoriasis in Elderly Patients

Management of psoriasis in elderly patients can be challenging, because of the impairment of immune system efficiency and the presence of comorbidities that contra-indicate systemic therapies. We studied the safety and efficacy of systemic traditional and biological treatments in 187 consecutive psoriatic patients aged > 65 years. At week 12 of therapy, Psoriasis Area and Severity Index 75 was achieved by 49%, 27%, 46% and 31% of patients who received methotrexate, acitretin, cyclosporine or PUVA, and 64.1%, 64.7%, 93.3%, 57.1% and 100% of patients who received etanercept, adalimumab, infliximab, efalizumab and ustekinumab. The rate of adverse events was 0.12, 0.32, 1.4 and 0.5 per patient-year in the methotrexate, acitretin, cyclosporine and PUVA groups and 0.11, 0.35, 0.19, 0.3 and 0.26 in the etanercept, adalimumab, infliximab, efalizumab and ustekinumab groups. Traditional drugs were less effective than biologics in our elderly population. Etanercept was associated with a lower rate of adverse events compared with other treatments.

Safety of etanercept in patients with psoriasis and hepatitis C virus assessed by liver histopathology: preliminary data.

in gut motility. Inflammatory bowel disease (IBD), in contrast, encompasses Crohn disease and ulcerative colitis, and is in fact related to chronic inflammation of the gut thatmay be autoimmune in nature. This clouds the results of the study, as it is unclearwhether patients were assessed for a historyof IBS, IBD,or both. In their article ‘‘Extracutaneous manifestations and complications of inherited epidermolysis bullosa’’ published in the September 2009 issue of the Journal, Fine et al also use the ambiguous term ‘‘irritable bowel disease’’ in Table IV. It is unclear whether the authors are actually referring IBS versus IBD versus some other entity. There is a need for greater precision in our use of these terms so that we are consistently referring to the same disorders.