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Many patients with moderate-to-severe plaque psoriasis do not respond adequately to methotrexate monotherapy. This pilot study, with a small patient population, was performed to evaluate the effectiveness and safety of etanercept and methotrexate combination in patients with plaque psoriasis and inadequate response to methotrexate. Outpatients with plaque psoriasis (Psoriasis Area and Severity Index > or = 8 and/or body surface area > 10%), despite methotrexate treatment (> or = 3 months; > or = 7.5 mg/week) were randomized to either etanercept with metho nottrexate tapered and discontinued (n = 28) or etanercept with continuous methotrexate (n = 31). Significantly more patients had a Physicians' Global Assessment of "clear"/"almost clear" in the combination group compared with etanercept/methotrexate taper (66.7 vs. 37.0%, respectively; p = 0.025). Adverse events were similar for both groups, with no cases of tuberculosis, malignancies or opportunistic infections reported. Addition of etanercept to methotrexate achieved significant improvement in psoriasis after 24 weeks.

The PSORS1 locus is the consistently replicated genetic risk factor for psoriasis. Clinical associations with the main marker allele of PSORS1, HLA-Cw6, have been addressed in a number of studies, but clinical associations have not been used as a way to distinguish the effects of the neighbouring candidate genes in PSORS1. Our results show that HLA-Cw6 and CCHCR1 risk allele associations with clinical features of psoriasis are predictably highly similar in a Finnish nationwide cohort of 379 psoriasis patients. The clinical profiling of a small group of patients (n=34) who were HLA-Cw6- but CCHCR1*WWCC positive suggested that no great differences existed between them and HCR-Cw6- patients. HCR+ genotype (as well as Cw6+ genotype) correlated for the first time positively with female sex and, in contrast with previous studies, negatively with disease severity. Presence of psoriatic arthritis was more pronounced in HCR- psoriasis (as well as in Cw6- psoriasis). Clinical profiling may be a useful approach to distinguishing genetic effects of candidate genes even within a locus in sufficiently large cohorts.

Keratinocyte hyperproliferation, inflammatory infiltrates, neoangiogenesis and alterations in cytokine levels are hallmarks of psoriatic skin. Matrix metalloproteinases (MMPs) have been associated with the remodeling of the extracellular matrix during inflammation, neovascularization, and malignant transformation. We have previously shown that particularly MMP-12 is abundantly expressed by macrophages and MMP-9 in macrophages and neutrophils of psoriatic lesions. In this work the expression of two novel metalloproteinases, MMP-19 and MMP-28, was investigated in psoriatic lesional and non-lesional skin. MMP-19 protein was detected by immunohistochemistry in 28/29 samples in keratinocytes in the same regions as Ki67 (marker of proliferating keratinocytes) and p63 (marker of keratinocyte stem cells). Immunosignaling was also seen in endothelial cells and fibroblasts. Furthermore, MMP-19 mRNA was upregulated in psoriatic keratinocytes and skin as assessed by quantitative real-time polymerase chain reaction. In lichen planus and lichenoid chronic dermatitis, MMP-19 staining was found in keratinocytes in areas where the basement membrane was abnormal. MMP-28 was not detected in psoriatic or non-lesional skin. Our results suggest that keratinocytes as well as the previously reported cell types (smooth muscle, endothelial and macrophages) can express MMP-19 in psoriasis and lichen planus. Upregulation of MMP-19 in keratinocytes may be influenced by changes in the architecture of the basement membrane zone.

Acne fulminans is a rare, severe type of acne with unknown etiology. Ulcerative acne lesions, fever and musculoskeletal pain are typical symptoms. In addition, osteolytic or even destructive osteomyelitis-like bone lesions occur in many patients with acne fulminans. In the present study the degradation product (ICTP) of type I collagen, the most abundant collagen of the skeleton, was measured from the sera of patients suffering from acne fulminans. In 3 of 4 acne fulminans patients with active disease, the ICTP concentrations were clearly higher than the range of concentrations in age-matched controls. The mean concentration of ICTP in the acne fulminans patients was 17.6 +/- 6.0 micrograms/I, whereas the corresponding concentration in 6 patients with severe nodular acne was 6.9 +/- 2.1 micrograms/I. Increased uptake of radionuclide in bone scans was observed in all of the 4 patients with acne fulminans. The present results suggest that ICTP is increased in acne fulminans, due to the destruction of bone collagen matrix. ICTP could thus be used for monitoring the activity of acne fulminans affecting the skeleton.

To investigate the inflammatory and immunological aspects of severe acne, we examined the luminol-enhanced chemiluminescence of whole blood, T-cell subsets and natural killer cell functions in 11 patients with severe nodular acne and 4 patients with acne fulminans. In patients with severe nodular acne, the active phase of the disease, compared to the values in remission (means 47 mV, SD 24.8 and 32 mV, SD 8.3, p < 0.05). The patients with acne fulminans also showed high values in the active phase of the disease (mean mV 68.3, SD3.5) compared to remission (mean 30.5 mV, SD 15.3). No marked alterations were seen in the percentages of T-helper cells, T-suppressor cells or DR-positive lymphocytes or in the levels of soluble interleukin 2 receptor. The percentages and activities of natural killer cells did not show any significant changes either. Five patients (4 with severe nodular acne and one with acne fulminans, accounting for 33% of all patients) carried HLA Cw6 antigen, which is a significantly increased frequency compared to health controls (pc = 0.015). The present chemiluminescence results suggest that peripheral blood neutrophils are activated in patients with severe acne.

Prednisolone combined with erythromycin was given to 6 patients with cystic acne. The treatment responses were compared to those in 6 patients with cystic acne receiving isotretinoin and erythromycin and also to those in 3 patients with acne fulminans treated with prednisolone and erythromycin. During the first 4 weeks cystic acne showed a clear improvement in 5 out of 6 patients in both treatment groups. A similar improvement occurred in all 3 patients with acne fulminans. When corticosteroid was stopped, 2 out of 5 patients with cystic acne had a relapse and needed isotretinoin for complete control. In the isotretinoin-treated group, one patient with cystic acne needed prednisolone because the acne worsened to an ulcerative form. Slightly elevated liver enzymes, possibly due to erythromycin treatment, were observed in 2 patients with cystic acne and in one patient with acne fulminans. The present results show that prednisolone combined with erythromycin is an effective treatment during the early stages of cystic and febrile acne, but isotretinoin is needed for long-term control.

We examined all babies born live (4346) at two Finnish hospitals in the course of one year to determine the frequency of birthmarks, specially pigmented lesions, among Finnish newborns. All birthmarks excluding common salmon patches on the forehead and neck were recorded and photographed at birth. The babies were re-examined at the age of three months. Various birthmarks were recorded for 241 of 4346 babies, i.e. for 5.5% of all newborns. Ninety-one (2.1%) infants had congenital pigmented skin lesions, 167 (3.8%) had various vascular lesions and 21 (0.5%) had other birthmarks. The frequency of congenital melanocytic naevi was 1.5%. Most of the naevi were less than 20 mm in diameter. Only one child had a giant naevus. The frequency of congenital naevi in our study was the same or somewhat higher than previously described (1-8) but fewer other pigmented skin lesions were found than in previous studies perhaps due to racial differences.