Péter Holló

Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial

BACKGROUND We assessed the efficacy, safety, and tolerability of ponesimod, an oral, selective, reversible modulator of sphingosine 1-phosphate receptor 1, in patients with moderate to severe chronic plaque psoriasis. METHODS Between Sept 22, 2010, and Oct 24, 2012, patients with psoriasis area and severity index (PASI) scores higher than 10 were enrolled into this multicentre double-blind, phase 2 study. They received 20 mg or 40 mg ponesimod or placebo once daily for 16 weeks. Those with at least 50% reduction in PASI score at 16 weeks and who were receiving ponesimod were rerandomised to receive maintenance ponesimod therapy or placebo until week 28. The primary endpoint was reduction in PASI score from baseline of at least 75% (PASI75) at week 16. This study is registered with ClinicalTrials.gov, number NCT01208090. FINDINGS Of 326 patients initially randomised (20 mg ponesimod n=126, 40 mg ponesimod n=133, and placebo n=67) PASI75 was achieved at week 16 in 58 (46·0%), 64 (48·1%), and nine (13·4%), respectively. The treatment effect was significant for the two ponesimod doses (both p<0·0001). Of 219 patients who entered the maintenance period, PASI75 was achieved by week 28 in 35 (71·4%) of 49 who continued on 20 mg ponesimod and 41 (77·4%) of 53 on 40 mg ponesimod, and in 19 (42·2%) of 45 who swapped from 20 mg to placebo and 19 (40·4%) of 47 from 40 mg to placebo. Ponesimod was associated with dyspnoea, raised liver enzyme concentrations, and dizziness. INTERPRETATION Significant clinical benefit was seen at week 16 that increased with maintenance therapy. FUNDING Actelion Pharmaceuticals.

Circulating CLA+ T lymphocytes as peripheral cell biomarkers in T-cell-mediated skin diseases

T lymphocytes expressing the CLA antigen constitute a subset of effector memory lymphocytes that are functionally involved in T‐cell‐mediated cutaneous diseases. Skin‐seeking lymphocytes recirculate between inflamed skin and blood during cutaneous inflammation. Many studies in different T‐cell‐mediated inflammatory cutaneous diseases have clearly related their pathologic mechanisms to CLA+ T cells. Based on common features of these cells in different cutaneous disorders mediated by T cells, we propose that circulating CLA+T cells could constitute very useful peripheral cellular biomarkers for T‐cell‐mediated skin diseases.

Synchronous balneophototherapy is effective for the different clinical types of psoriasis

Background  The efficacy of synchronous balneophototherapy in clearing psoriasis is based on the multiple‐targeted effects of UVB light and Dead Sea salt. Their synchronous application produces a synergic effect.

Angiolymphoid hyperplasia with eosinophilia in pregnancy.

To the Editor Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign disorder of young adults with female predominance, characterized by solitary or multiple nodules on the head and neck region. Some cases associated with pregnancy have been reported earlier.1 During the first semester of the second pregnancy, the 28year-old female patient developed two subcutaneous, livid nodules 1–1.5 cm in diameter at the lateral side of the left eyebrow and in the left temporal region, as well as several smaller lesions on the scalp of the left parietal region. Sometimes they were spontaneously bleeding. The overlying skin was purplish or normal, larger lesions were pulsating (fig. 1). The two largest nodules were surgically removed. The histological picture showed circumscribed, lobuled lesions, oedematous endothelial cells in the dermal blood vessels and lymphocytic and eosinophilic infiltration (fig. 2). Routine laboratory investigations, peripheral eosinophil count revealed negative results. Direct immunofluorescent histology did not show overexpression of oestrogen or progesterone receptors in the lesions. Polymerase chain reaction (PCR) investigations of human herpesvirus 8 (HHV8) and human T cell lymphoma virus (HTLV) were also negative. After the patient has delivered, the lesions showed spontaneous regression. ALHE was originally described by Wells and Whimster in 1969.2 This rare benign tumour occurs with a female predominance, and most often affects the head and neck region. The typical clinical signs are solitary or multiple purplish, brownish papules and subcutaneous nodules. The histological picture is characterized by the proliferation of endothelial cells associated with lymphocytic and eosinophilic infiltrate. Results of immunohistological examinations, showed that perivascular infiltrating lymphocytes are mostly CD4 + positive. Proliferating endothel cells express adhesion molecules: VLA-1, -3, -5, ICAM-1, ELAM-1.3 Sometimes marked peripheral eosinophilia can be detected. Kimura’s disease was earlier thought to be related to ALHE, but nowadays it is considered a different clinical entity. The main differences between the two diseases were described by Chum et al. in 1992.4,5 Some earlier clinical entities with other names are identified as ALHE, some authors suggested the nomenclature of epithelioid haemangioma.6 The origin of the disease is not known, infection (HTLV or HHV8), hormonal background, or possible role of trauma are the mostly discussed possibilities. Increased expression of vascular endothelial growth factor (VEGF) and interleukin 5 (IL-5) was detected in some cases.7 Associated cases of the disease to pregnancy were already described. Moy et al. found oestrogen and progesterone receptor overexpression in the lesional skin of pregnant women.1 In our case, direct immunofluorescent histology did not show overexpression of oestrogen or progesterone receptors in the lesions. HHV8 and HTLV PCR investigations were also negative. The possible treatment modalities were intralesional steroid or IFN α, surgical excision, cryotherapy and laser therapy.8 Association of ALHE with nephrotic syndrome has also been described.9 The interest of our case makes the typical clinical picture and outcome of the rare disease. Its association with pregnancy suggests the pathogenetic role of immunological and endocrinological changes in the background.

Successful Treatment of Lichen Planus with Adalimumab

© 2012 The Authors. doi: 10.2340/00015555-1249 Journal Compilation

Moderate to severe psoriasis patients' subjective future expectations regarding health‐related quality of life and longevity

Unrealistic expectations regarding treatments and clinical outcomes may lead to disappointment about therapy and sub‐optimal compliance; nonetheless, these expectations have not been studied in psoriasis patients yet.

Cutaneous lymphocyte‐associated antigen as a novel predictive marker of TNF‐alpha inhibitor biological therapy in psoriasis

A considerable number of patients with psoriasis show secondary resistance during long‐term TNF‐alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte‐associated antigen (CLA) was investigated. Thirty‐eight severe patients with psoriasis were treated for a 24‐week‐long study period. Clinical responsiveness (PASI) and changes in flow cytometry–measured peripheral lymphocyte CLA expression (week 0–2–6) were statistically analysed. Regarding 24‐week‐long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearsons correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF‐alpha inhibitor therapy in psoriasis.

Disease burden of psoriasis associated with psoriatic arthritis in Hungary

INTRODUCTION Psoriasis is a frequent, chronic, systemic immune-mediated disease mainly affecting the skin and joints. AIM To assess health related quality of life and cost-of-illness in moderate to severe psoriasis associated with psoriatic arthritis. METHOD A cross-sectional questionnaire survey was conducted at two academic dermatology clinics in Hungary. RESULTS Fifty-seven patients (65% males) completed the survey with a mean age of 54.3±11.6 years and mean EQ-5D score of 0.48±0.4. Mean annual total cost was €8,977 per patient, of which 71% occurred due to biological therapy and 21% were indirect costs, respectively. Permanent work disability due to psoriasis accounted for €1,775 (95% of the indirect costs). Per patient costs of subgroups not receiving systemic therapy (21%), traditional systemic therapy (32%), and biological systemic therapy (47%) amounted to the sum of €1,729, €1,799, and €16,983, respectively. CONCLUSIONS Patients on biological therapy showed significantly better health related quality of life. As for health economics, the efficacy of systemic treatments is appropriate to be assessed together in patients with moderate to severe psoriasis associated with psoriatic arthritis, since actual health gain might exceed that reported in psoriasis or psoriatic arthritis separately.

A detailed analysis of ‘not relevant’ responses on the DLQI in psoriasis: potential biases in treatment decisions

Dermatology Life Quality Index (DLQI) is the most common health‐related quality of life measure in dermatology that is widely used in treatment guidelines for psoriasis. Eight of the 10 questions of the DLQI offer a ‘not relevant’ response (NRR) option that is scored as the item had no impact on patients’ life at all.

Tissue-Specific Homing of Immune Cells in Malignant Skin Tumors

Tissue-specific migration of immune cells involved both in physiological and pathological immune responses is a current research subject for medical science. Several homing molecules have been identified orchestrating extravasation of immune cells to certain peripheral non-lymphoid tissues such as gut, lung and skin. Regarding lymphocyte homing to skin, the first-line defense of human body cutaneous lymphocyte associated antigen (CLA) and a group of chemokine-chemokine receptor pairs are considered to be of crucial importance. The aim of the present review is to summarize existing knowledge about skin- and tumor-specific migration of immune cells playing a major pathogenetic role in host immune responses induced by non-lymphoid malignant skin tumors as well as in the development of primary cutaneous T-cell lymphomas (CTCL). Melanoma malignum, squamous and basal cell carcinoma evoke host immune responses and consequently a subset of reactive immune cells is recruited to site of the tumor. Regarding migratory process and exact functional role of these cells a growing number of data is available in literature. On the other hand tissue-specific immune cell homing is regarded as a key process in the pathogenesis of CTCL where malignant T-lymphocytes can be found in circulation and symptomatic skin. Hereby homing mechanism of malignant T-cells in mycosis fungoides and Sézary-syndrome as separate clinical entities of CTCL is discussed. A precise insight into the molecular background of skin- and tumor-specific immune cell migration can contribute to developing efficient vaccine therapies in non-lymphoid malignant skin tumors and beneficial treatment modalities in CTCL.