Papular Mycosis Fungoides Is a Distinctive Variant of Early-stage Mycosis Fungoides: Extended Retrospective Study With Long-term Follow-up.

Papular mycosis fungoides (PMF) is a rare variant of mycosis fungoides (MF). The exact nosology and prognosis of PMF are still unclear. We retrospectively identified cases of PMF from the files of the Department of Dermatology of the Medical University of Graz, Austria, and checked the follow-up data. The patients comprised 13 men and 5 women (median age: 57.5 y; range 13 to 77 y). In 4 patients, an initial clinicopathologic diagnosis of atypical pityriasis lichenoides was made; these cases were subsequently reclassified as PMF due to the onset of conventional patches of MF during follow-up. Follow-up data of our cases showed that 2 patients died of disease progression 50 and 199 months after the first presentation, respectively. Two patients are alive with progressive disease after 215 and 300 months, respectively. Ten patients are alive with stable disease (median: 70 mo). Four patients were in complete remission at last follow-up visit (median: 215 mo; 2 of them died of unrelated causes). Our data confirm that PMF represents a clinicopathologic variant of early MF with prognosis similar to conventional presentations of the disease. Familiarity with PMF and distinction from other cutaneous papular lymphoid proliferations is necessary for a precise diagnosis and management of these patients.

Designing CXCL8-based decoy proteins with strong anti-inflammatory activity in vivo.

IL (interleukin)-8 [CXCL8 (CXC chemokine ligand 8)] exerts its role in inflammation by triggering neutrophils via its specific GPCRs (G-protein-coupled receptors), CXCR1 (CXC chemokine receptor 1) and CXCR2, for which additional binding to endothelial HS-GAGs (heparan sulphate-glycosaminoglycans) is required. We present here a novel approach for blocking the CXCL8-related inflammatory cascade by generating dominant-negative CXCL8 mutants with improved GAG-binding affinity and knocked-out CXCR1/CXCR2 activity. These non-signalling CXCL8 decoy proteins are able to displace WT (wild-type) CXCL8 and to prevent CXCR1/CXCR2 signalling thereby interfering with the inflammatory response. We have designed 14 CXCL8 mutants that we subdivided into three classes according to number and site of mutations. The decoys were characterized by IFTs (isothermal fluorescence titrations) and SPR (surface plasmon resonance) to determine GAG affinity. Protein stability and structural changes were evaluated by far-UV CD spectroscopy and knocked-out GPCR response was shown by Boyden chamber and Ca2+ release assays. From these experiments, CXCL8(Δ6F17KF21KE70KN71K) emerged with the most promising in vitro characteristics. This mutant was therefore further investigated in a murine model of mBSA (methylated BSA)-induced arthritis in mice where it showed strong anti-inflammatory activity. Based on these results, we propose that dominant-negative CXCL8 decoy proteins are a promising class of novel biopharmaceuticals with high therapeutic potential in inflammatory diseases.