Elisabetta Colombo

Perianal Fistulae Following Infliximab Treatment Clinical and Endosonographic Outcome

BackgroundManagement of perianal and rectovaginal fistulae complicating Crohn’s disease (CD) is unsatisfactory. Infliximab is effective in the treatment of fistulating CD. However, reopening of fistulae is frequent, suggesting the persistence of deep fistula tracts despite superficial healing. In this study, the clinical and endosonographic behavior of perianal fistulae were evaluated following infliximab infusions, as well as the role of anal endosonography (AE) in predicting their outcome. MethodsThirty CD patients presenting with perianal and/or rectovaginal fistulae received an infusion of infliximab at a dose of 5 mg/kg at weeks 0 (entry into the study), 2, and 6. Laboratory and clinical assessments were repeated at same intervals and at week 10. AE was performed at entry and at week 10. Thereafter, the perianal region was re-examined every 6 months, and patients were investigated regarding draining of the fistula in the previous months. ResultsFifteen patients (53.6%) showed closure of the fistulae at week 10, but only 5 patients had the fistula tracts disappeared at AE. Clinical and AE closure of rectovaginal fistulae was less prevalent than that of perianal fistulae [14.3% versus 63.6% at week 6 (p = 0.035); 28.6% versus 59.1% at week 10 (p = 0.21); 14.3% versus 22.7% at AE (p = 1.00)]. The behavior of fistulae was not affected by their number and AE classification, presence of rectal disease, or setons. Twenty patients with perianal fistulae were followed for a median of 15.5 months. Patients with closed perianal fistulae at week 10 and disappearance of fistulae tract at AE showed a lower relapse rate than those with endosonographic persistence of fistula tract. ConclusionsInfliximab can heal perianal and rectovaginal fistulae in approximately 60% and 30% of patients, respectively. Despite closure, most fistula tracts are still detectable at AE. Persistence of the internal tract is a condition at higher risk of fistula recurrence.

Infliximab-induced lupus in Crohn's disease: a case report

An 18-year-old male patient was under treatment with infliximab at a dose of 5 mg/kg at Weeks 0, 2 and 6 for refractory Crohns disease. In June 2002, the patient was admitted to the Outpatient Clinic of the Rheumatology Unit for arthralgia affecting the small joints, non-pruritic crops of purple skin lesions and malar rash in the face. Serum antinuclear antibodies were positive (1:640 speckled pattern), and anti-double-stranded DNA was positive (1:80); moreover, positivity of anti-extractable nuclear antigen was observed. Antihistone antibodies, lupus anticoagulant and anticardiolipin antibodies were negative. A diagnosis of infliximab-induced lupus was made and the drug treatment was withdrawn. However, 3 months after withdrawal of treatment, the patient still showed clinical and laboratory symptoms of systemic lupus erythematosus. After 6 months of treatment, systemic lupus erythematosus-related symptoms disappeared and anti-double-stranded DNA returned to normal. The patient is currently under treatment with prednisone 20 mg/day for systemic lupus erythematosus and with oral mesalazine 2.4 mg/day for Crohns disease. Treatment with infliximab is known to produce an increase of autoantibodies (antinuclear antibodies, anti-double-stranded DNA), but not clinical disease. This is the first case, to our knowledge, of onset of prolonged infliximab-induced lupus.

Multidrug resistance 1 gene polymorphism and susceptibility to inflammatory bowel disease

Background Several studies have evaluated the role of the multidrug resistance 1 gene (MDR1) polymorphism, which encodes the membrane‐bound efflux transporter P‐glycoprotein 170, in determining susceptibility to and disease behavior in inflammatory bowel disease (IBD), but with conflicting results. Methods A total of 211 patients with Crohns disease (CD), 97 patients with ulcerative colitis (UC), and 212 control subjects were investigated for the presence of MDR1 G2677T/A and C3435T polymorphisms. Genotype frequencies of CD and UC patients were compared to those observed in a control population. Genotype–phenotype correlations with major clinical features were also established and estimated risks (odds ratio [OR] with 95% confidence interval [CI]) for the mutations were calculated by a logistic regression analysis and multiple correspondent analysis. Results No significant difference was observed for genotype frequencies for both MDR1 G2677T/A and C3435T polymorphisms on overall disease susceptibility for either CD or UC patients compared with control subjects. A significant association was found between the MDR1 C3435T polymorphism and patients with ileo‐colonic CD (OR = 3.34; 95% CI: 1.34–8.27). Interestingly, a negative association was found between MDR1 C3435T polymorphism in patients with a positive family history for IBD (OR = 0.44; 95% CI: 0.20–0.95) and articular manifestations (OR = 0.29; 95% CI: 0.13–0.68). Both susceptible and protective effects were identified. No significant association between G2677T/A polymorphism and any specific subphenotypes was found, nor was there any association with subphenotypic categories of UC and both single nucleotide polymorphisms. Conclusions The results of our study suggest that MDR1 gene polymorphism could have a role in determining susceptibility to IBD. The variability of this possible effect in the several studies reported so far may be the indirect expression of the complex role played by the MDR1 gene and its product, P‐glycoprotein 170, in the regulation of host–bacteria interactions and in the pathogenesis of IBD. (Inflamm Bowel Dis 2007)

CARD15 gene variants and risk of reoperation in Crohn's disease patients.

OBJECTIVES:Several studies have investigated, with conflicting results, the risk factors for reoperation in Crohns disease (CD) patients. CARD15 gene variants have been identified as a major genetic risk factor for CD patients and associated with ileal disease, stenosis, and risk of surgery. However, data regarding the association between these variants and the need for reoperation are very few and conflicting. This study evaluated the risk factors of reoperation, including CARD15 gene variants.METHODS:A total of 253 consecutive CD patients, recruited in four Italian tertiary-care inflammatory bowel disease (IBD) referral centers, who had submitted to surgery for CD, were included in the study. Clinical characteristics of CD patients, time and main indications for surgery, type of operation, postoperative therapy, and time to second surgery were recorded. CARD15 gene variants were determined by DNA sequencing analysis in each center. Factors related to surgical recurrence, including CARD15 variants, were estimated by Cox proportional hazard regression.RESULTS:In all, 89 patients (35.1%) showed at least one surgical recurrence. Reoperation was significantly correlated with stenosis as indications at initial surgery only. CARD15 variants were found in 36.0% of patients, but did not correlate significantly with the demographic and clinical characteristics of the patients, rate of first surgical recurrence, and time to second operation. CARD15 variants did not significantly affect the reoperation rate, irrespective of indications for surgery.CONCLUSIONS:Reoperation for CD is correlated with stenosis at initial surgery, but not with CARD15 gene variants. This finding does not justify more aggressive prophylactic therapy on the basis of CARD15 genotype.

Siegel metric and curvature of the moduli space of curves

We study the curvature of the moduli space Mg of curves of genus g with the Siegel metric induced by the period map j : Mg! Ag. We give an explicit formula for the holomorphic sectional curvature of Mg along a Schiffer variationP, for P a point on the curve X, in terms of the holomorphic sectional curvature of Ag and the second Gaussian map. Finally we extend the Kahler form of the Siegel metric as a closed current on M g and we determine its cohomology class as a multiple of �.

On totally geodesic submanifolds in the Jacobian locus

We study submanifolds of Ag that are totally geodesic for the locally symmetric metric and which are contained in the closure of the Jacobian locus but not in its boundary. In the first section we recall a formula for the second fundamental form of the period map Mg ↪ Ag due to Pirola, Tortora and the first author. We show that this result can be stated quite neatly using a line bundle over the product of the curve with itself. We give an upper bound for the dimension of a germ of a totally geodesic submanifold passing through [C] ∈ Mg in terms of the gonality of C. This yields an upper bound for the dimension of a germ of a totally geodesic submanifold contained in the Jacobian locus, which only depends on the genus. We also study the submanifolds of Ag obtained from cyclic covers of ℙ1. These have been studied by various authors. Moonen determined which of them are Shimura varieties using deep results in positive characteristic. Using our methods we show that many of the submanifolds which are not Shimura varieties are not even totally geodesic.

Density of elliptic solitons

(cf. [TV1]). These Solutions in turn correspond to points of the Segal-Wilson Grassmannian Gr [SW]. The third author called this class Gr2 [P] and conjectured that it be dense in Gr, in analogy with Grx and Gr0, since an elliptic curve may be deformed into (the one-point compactification of ) a cylinder (one period) and a disc (no periods). The density of Gr0 follows from its characterization: Wz Gr0 iff 3q s.t. zH+ c Wer z~ H+ . In other words, if Ware thought of s graphs H+ -> H_ (compact), the matrices corresponding to Gr0 have a finite number of nonzero entries. Thus, Gr0 is dense in Gr and yet it is an infinite union of nested, finite dimensional Zariski closed cells. Likewise, Grt is the set of W such that p(z)H+ c: Wc q~(z)H+, for suitable polynomials p and q (matrices of finite rank). It is harder to give a characterization of the elements of Gr2, although from [TV 2] and [K] one can deduce an expression for their Baker function and the property

Del Pezzo Moduli via Root Systems

Coble defined in his 1929 treatise invariants for cubic surfaces and quartic curves. We reinterpret these in terms of the root systems of type (E_6) and (E_7) that are naturally associated to these varieties, thereby giving some of his results a more intrinsic treatment. Our discussion is uniform for all Del Pezzo surfaces of degree 2, 3, 4, and 5.

Hyperplane sections of abelian surfaces

By a theorem of Wahl, the canonically embedded curves which are hyperplane section of K3 surfaces are distinguished by the non-surjectivity of their Wahl map. In this paper we address the problem of distinguishing hyperplane sections of abelian surfaces. The somewhat surprising result is that the Wahl map of such curves is (tendentially) surjective, but their second Wahl map has corank at least 2 (in fact a more precise result is proved).

The Chow group of the moduli space of marked cubic surfaces

Naruki gave an explicit construction of the moduli space of marked cubic surfaces, starting from a toric variety and proceeding with blow-ups and contractions. Using his result, we compute the Chow groups and the Chern classes of this moduli space. As an application we relate a recent result of Freitag on the Hilbert polynomial of a certain ring of modular forms to the Riemann–Roch theorem for the moduli space.