Martin Inzinger

Psoriasis alters HDL composition and cholesterol efflux capacity

Psoriasis, a chronic inflammatory skin disease, has been linked to increased myocardial infarction and stroke. Functional impairment of HDL may contribute to the excess cardiovascular mortality of psoriatic patients. However, data available regarding the impact of psoriasis on HDL composition and function are limited. HDL from psoriasis patients and healthy controls was isolated by ultracentrifugation and shotgun proteomics, and biochemical methods were used to monitor changed HDL composition. We observed a significant reduction in apoA-I levels of HDL from psoriatic patients, whereas levels of apoA-II and proteins involved in acute-phase response, immune response, and endopeptidase/protease inhibition were increased. Psoriatic HDL contained reduced phospholipid and cholesterol. With regard to function, these compositional alterations impaired the ability of psoriatic HDL to promote cholesterol efflux from macrophages. Importantly, HDL-cholesterol efflux capability negatively correlated with psoriasis area and severity index. We observed that control HDL, as well as psoriatic HDL, inhibited dihydrorhodamine (DHR) oxidation to a similar extent, suggesting that the anti-oxidative activity of psoriatic HDL is not significantly altered. Our observations suggest that the compositional alterations observed in psoriatic HDL reflect a shift to a pro-inflammatory profile that impairs cholesterol efflux capacity of HDL and may provide a link between psoriasis and cardiovascular disease.

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry.

Background  Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis.

Treatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial

Background  Treatment with the interleukin‐12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque‐type psoriasis.

Anti-Psoriatic Therapy Recovers High-Density Lipoprotein Composition and Function

Psoriasis is a chronic inflammatory disorder associated with increased cardiovascular mortality. Psoriasis affects high-density lipoprotein (HDL) composition, generating dysfunctional HDL particles. However, data regarding the impact of anti-psoriatic therapy on HDL composition and function are not available. HDL was isolated from 15 psoriatic patients at baseline and after effective topical and/or systemic anti-psoriatic therapy and from 15 age- and sex-matched healthy controls. HDL from psoriatic patients showed a significantly impaired capability to mobilize cholesterol from macrophages (6.4 vs. 8.0% [(3)H]cholesterol efflux, P<0.001), low paraoxonase (217 vs. 350 μM(-1) minute(-1) mg(-1) protein, P=0.011) and increased Lp-PLA2 activities (19.9 vs. 12.1 nM(-1) minute(-1) mg(-1) protein, P=0.028). Of particular interest, the anti-psoriatic therapy significantly improved serum lecithin-cholesterol acyltransferase activity and decreased total serum lipolytic activity but did not affect serum levels of HDL-cholesterol. Most importantly, these changes were associated with a significantly improved HDL-cholesterol efflux capability. Our results provide evidence that effective anti-psoriatic therapy recovers HDL composition and function, independent of serum HDL-cholesterol levels, and support to the emerging concept that HDL function may be a better marker of cardiovascular risk than HDL-cholesterol levels.

Methotrexate vs. fumaric acid esters in moderate-to-severe chronic plaque psoriasis: data registry report on the efficacy under daily life conditions.

Objective  To compare the clinical efficacy of methotrexate (MTX) vs. fumaric acid esters (FAE) in psoriasis treated under daily life conditions.

Allopurinol in the treatment of acquired reactive perforating collagenosis

Acquired reactive perforating collagenosis is a perforating dermatosis usually associated with different systemic diseases, mainly diabetes mellitus and/or chronic renal insufficiency. Different therapies have been tried but treatment is not standardized yet and remains a challenge. In the last few years, allopurinol has been reported as a good therapeutic option for acquired reactive perforating collagenosis. We describe the case of a 73-year-old man affected by acquired reactive perforating collagenosis associated with diabetes type 1 and chronic renal failure with secondary hyperparathyroidism. The patient was successfully treated with allopurinol 100mg once/day p.o..

Neonatal lupus erythematosus and its clinical variability

Neonatal lupus erythematosus (NLE) is a rare disease affecting newborns that is caused by maternal autoantibodies transmitted across the placenta. The disease may affect the skin, the heart, and rarely the hepatobiliary or hematological systems. A serious complication affecting some patients with NLE is atri‐oventricular heart block (AV block).

Psoriasis Area and Severity Index 75 rate of classical inpatient dithranol therapy under daily life conditions

DEAR EDITOR, Dithranol (known in the U.S.A. as anthralin and in Germany as cignolin) is one of the oldest and safest longterm topical antipsoriatic treatments. However, established evidence for dithranol’s therapeutic efficacy is scant, and data regarding the extent to which dithranol may reduce the Psoriasis Area and Severity Index (PASI), the current standard parameter for assessing therapeutic efficacy in treated patients with psoriasis, are minimal. To help fill this gap, the aim of this study was to analyse retrospective data on the efficacy of classical dithranol therapy (CID) in terms of PASI reduction under daily life conditions. Data from 110 patients [75 men (68 2%) and 35 women (31 8%)] were reported to the Psoriasis Registry Austria (http://www.psoriasisregistry.at) and analysed retrospectively. Full details of the methods are provided in Data S1 (see Supporting Information). The median patient age was 48 3 years (range 13 4–97 7). Median body mass index (BMI) was 27 0 (range 18 1–38 8). Psoriasis types included chronic plaque psoriasis in 77 patients (70 0%) and guttate psoriasis in 33 (30 0%). Median disease duration was 10 2 years (range 0 1–84 0), and the median PASI score at treatment initiation was 13 0 (range 2 8–40 0). A family history of psoriasis was reported in 28 patients (25 4%), no family history of psoriasis in 36 (32 7%) and an uncertain family history in 46 (41 8%). Comorbidities included obesity in 40 patients (36 4%), fatty liver disease in 28 (25 4%), insulinor noninsulin-dependent diabetes mellitus in 16 (14 5%), hyperlipidaemia in 16 (14 5%), arterial hypertension in 30 (27 3%), coronary heart disease in six (5 4%) and kidney disease in three patients (2 7%). CID was administered in the formulations described in Table S1 (see Supporting Information). Seventy-seven patients (70 0%) received CID alone and 33 (30 0%) received CID in combination with ultraviolet (UV) B irradiation at 311 nm. The median number of UV exposures was five (range 1–11). Other than a between-group difference in the relative percentage of patients with plaque vs. guttate psoriasis (i.e. 75 3% vs. 24 7% in the monotherapy group compared with 57 6% vs. 42 4% in the combination therapy group; Fisher’s exact test P = 0 07), there were no major differences in clinical characteristics between the treatment groups. Ninety-one patients (82 7%) completed treatment with CID and achieved ≥ 75% reduction in PASI score (PASI 75; Fig. 1). The median time to PASI 75 was 14 days (range 3–25 days). In 19 patients (17 3%), treatment with CID was terminated early (i.e. before achieving PASI 75) for reasons including lack of efficacy [i.e. PASI reduction < 50% after at least 10 days of therapy (n = 5; 4 5%)]; local irritation [burning sensation of the skin and erythema (n = 3; 2 7%); and patient decision (n = 11; 10 0%). The median time to early treatment termination in those 19 patients was 5 days (range 2–19) (Fig. 1). Analysis revealed no difference in the rates of efficacy (i.e. PASI 75) and early treatment termination between the monotherapy and combination (irradiated) treatment group (data not shown), and therefore they were pooled for analysis. There was a weak but statistically significant positive correlation between baseline PASI and time to PASI 75 (P < 0 01; Fig. 2). This became particularly evident for patients with a PASI score < 10 at start of treatment, as visualized by the strong slope of the LOWESS line for this range (Fig. 2). The median time to reach PASI 75 was 10 2 days in patients with a PASI score < 10 (n = 30) and 13 6 days in patients with a PASI score > 10 (n = 61) (Wilcoxon test P < 0 01).

UV‐induced alterations of the skin evaluated over time by reflectance confocal microscopy

Ultraviolet radiation (UVR) induces various alterations of the skin and plays a decisive part regarding the development of melanoma and non‐melanoma skin cancer. For a closer examination of these phenomena in vivo reflectance confocal microscopy (RCM) is one of the most eligible options as it represents a diagnostic tool that allows a non‐invasive examination of the skin, showing microanatomical structures and individual cells.

Hair repigmentation in melanoma

noticed 4 days earlier. She had also noticed progressive repigmentation of otherwise completely white hair at the same site (fi gure). The repig mentation started with a few strands of reddish hair about 10 years ago. Within a few years, the colour of the repigmented hair changed again from reddish to dark black, and fi nally to light brown. Interestingly, the patient never had red dish, black, or light brown hair before. Her natural hair colour as a young adult was light blonde.Examination of the patient’s scalp showed a coarse black nodule measuring 8 mm in diameter and several satellite lesions (fi gure). A patch of pigmented hair around the nodule was surrounded by mainly white hair. Histological investigation of the excised nodule showed a melanoma with a tumour thickness of 3·5 mm. Atypical melanocytes were seen in all layers of the epidermis including sheets and nests extending down to the deep dermis and invading the hair follicles (appendix). Masson-Fontana staining revealed dendritic melanocytes in the hair bulbs (appendix) and melanin deposit in the shaft of the normal skin hair follicles around the lesion (appendix). We specu-lated that the melanoma might have activated hair follicle melano cytes via paracrine secretion of mediators. This possibility is supported by the fact that several neural and immune networks and mediators can activate the receptor tyrosine kinase KIT and activate melanogenesis within the hair bulb.