Clinical management of Anti-TNF-alpha-induced psoriasis or psoriasiform lesions in inflammatory bowel disease patients: a systematic review.

Tumor necrosis factor alpha inhibitors (anti-TNF-α) completely revolutionized the treatment of inflammatory bowel disease (IBD). However, anti-TNF-α-induced cutaneous side effects have been increasingly reported in the literature. Particularly, psoriasis and the recently recognized psoriasiform lesions are of particular concern, as anti-TNF-α agents are also used in the treatment of psoriasis, seemingly reflecting an immunological paradox. The clinical management of these cutaneous lesions is particularly challenging, owing to the potential need of anti-TNF-α discontinuation and scarcity of other therapeutic options. Therefore, optimization of current topical and systemic therapies and incorporation of new therapeutic agents is of great interest. Our aim is to review data in the literature regarding the clinical management of these cutaneous lesions and provide a therapeutic algorithm, supported by our experience as a tertiary referral center for IBD. Although in older reports no distinction was made, anti-TNF-α-induced psoriasiform lesions are not only more prevalent but also bear notable differences from classical psoriasis, possibly reflecting a different nosological entity. Onset of lesions has been related to periods of IBD remission, as supported by low levels of fecal calprotectin. Psoriasiform lesions can be adequately managed either by topical (glucocorticoids, calcineurin inhibitors, and antibiotics) or systemic (phototherapy, acitretin, glucocorticoids, and antibiotics) therapies and/or switch to other anti-TNF-α agents. Data referring to patients who were able to continue on the same IBD therapy ranged from 30.7 to 100%, reinforcing the importance of an adequate control of these lesions. The recently approved ustekinumab offers another step in the management of anti-TNF-α-intolerant patients.

Cloning and characterization of the genes encoding the high-affinity iron-uptake protein complex Fet3/Ftr1 in the basidiomycete Phanerochaete chrysosporium.

MCO1, a multicopper oxidase from Phanerochaete chrysosporium exhibiting strong ferroxidase activity, has recently been described. This enzyme shows biochemical and structural similarities with the yeast Fet3p, a type I membrane glycoprotein that efficiently oxidizes Fe(II) to Fe(III) for its subsequent transport to the intracellular compartment by the iron permease Ftr1p. The genome database of P. chrysosporium was searched to verify whether it includes a canonical fet3 in addition to mco1, and single copies of fet3 and ftr1 orthologues were found, separated by a divergent promoter. Pc-fet3 encodes a 628 aa protein that exhibits overall identities of about 40 % with other reported Fet3 proteins. In addition to a secretion signal, it has a C-terminal transmembrane domain, characteristic of these cell-surface-attached ferroxidases. Structural modelling of Pc-Fet3 revealed that the active site has all the residues known to be essential for ferroxidase activity. Pc-ftr1 encodes a 393 aa protein that shows about 38 % identity with several Ftr1 proteins from ascomycetes. Northern hybridization studies showed that the mRNA levels of both genes are reduced upon supplementation of the growth medium with iron, supporting the functional coupling of Fet3 and Ftr1 proteins in vivo.