Treatment with a PPARgamma agonist appears to be a promising therapeutic principle in PsA, but the use of PPARgamma ligands might be limited by side-effects such as increase in weight and fluid retention.

An angiostatic approach was used to assess the impact of anti-inflammatory therapy in combination with metronomic low-dose chemotherapy. A randomized multi-institutional phase II trial was designed to select metronomic chemotherapy (arm A: trofosfamide 50 mg orally three times daily, day 1+) or combined anti-inflammatory/angiostatic treatment (arm B: trofosfamide as above mentioned plus rofecoxib 25 mg orally, day 1+, and pioglitazone 60 mg orally, day 1+) for further evaluation. A total of 76 patients, mostly (>60%) refractory to at least one previous chemotherapy with maximum tolerated doses, and progression of metastatic melanoma were included. The estimated progression-free survival (PFS) rates at one year were 0% for metronomic chemotherapy (A), but 9% for additional anti-inflammatory therapy (B). Vice versa the hazard ratio for the intent-to-treat analysis of A versus B was 1.9 (P=0.008). By Cox analysis, the impact of anti-inflammatory therapy on PFS achieved significance (P=0.016) as well as C-reactive protein response on overall survival (P=0.045). WHO grade 3 (no grade 4) toxicities were reported in arm A/B in 19 and 28%, respectively. In conclusion, control of tumour-associated inflammatory processes (C-reactive protein response) is associated with longer PFS than achieved with metronomic chemotherapy alone in metastatic melanoma.

Background and objectives: The pathogenesis of acquired nephrogenic systemic fibrosis recently described for patients with renal insufficiency and a history of exposition to gadolinium-based magnetic resonance contrast agents is not completely understood. A role for circulating fibroblasts in the fibrosing tissue is hypothetical, and the mechanism of the assumed trigger function of gadolinium remains elusive.Design, setting, participants, & measurements: A skin lesion on a 76-yr-old man with symptoms of nephrogenic systemic fibrosis lasting 5 mo was studied at the ultrastructural level. After confirmation of he diagnosis by histopathologic methods, the presence and distribution of gadolinium, iron, calcium, and magnesium by energy filtering transmission electron microscopy was also examined.Results: The performed electron spectroscopic imaging and electron energy loss spectroscopic analyses on deparaffinized samples revealed deposition of gadolinium in irregular small aggregates that adhered to cell profiles and collagen fibers of the connective tissue, forming a perivascular "gadolinium-deposit zone" in the skin. Traces of iron signal were demonstrated in singular gadolinium-positive deposits, and iron presence was found in adjacent connective tissue. The ultrastructural cell analysis of the lesion showed among numerous poorly differentiated fibrocytes also higher differentiated cells with myofibroblastic characteristics, including bundles of intermediate filaments and attachment plaques in the cell periphery, indicating an ability of lesional fibroblasts to differentiate into myofibroblastic cells.Conclusions: These findings support the pivotal role of gadolinium chelates in the development of nephrogenic systemic fibrosis.

The authors have indicated no significant interest with commercial supporters.H amartomas with eccrine differentiation occur rarely. So far, six variants of eccrine hamartoma (eccrine nevus) have been described: purely eccrine nevus, eccrine vascular hamartoma, acrosalpingian nevus, comedo nevus of the palms, linear eccrine nevus with comedones, and porokeratoticeccrine ostial and dermal duct nevus (PEODDN). 1 PEODDN is diagnosed by histology. 2 We present a 49-year-old woman with PEODDN present since childhood that developed Bowen's disease (BD) in her lesions. Therapy of choice for both lesions was CO 2 laser therapy. Case ReportA 49-year-old woman reported the occurrence of hyperkeratotic skin lesions on her left sole since the age of 12. There was no family history of similar lesions. Therapies with topical keratolytics and calcipotriol had resulted in only temporary improvements. The permanent exertion due to the patient's occupation as physical education teacher had caused frequent inflammations in the area of the PEODDN. Physical examination revealed numerous linear keratotic papules and plaques on the left sole. For several months, one plaque had shown superficial ulceration sized 2 Â 2 cm without any tendency to heal ( Figure 1A). A diagnostic biopsy was taken from the ulcerated area.The histologic examination showed in one part a cornoid lamella associated with eccrine ducts. Another part showed parakeratosis, psoriasiform hyperplasia, full-thickness atypia of the epidermis, mitoses, and dyskeratotic cells (Figure 2), and a diFigure 1. (A) Keratotic plaques on the left sole with a superficial ulceration. (B) A 6-month postoperative checkup showed no recurrence.

Differential diagnosis of an axillary tumor should include ectopic breast tissue.