A comprehensive, tri-national, cross-sectional analysis of characteristics and impact of pruritus in psoriasis.

BACKGROUND: Pruritus is prevalent in psoriasis but still many features of pruritus, its response to therapy and its burden in psoriasis remain to be better characterized. OBJECTIVE: To investigate characteristics and burden of pruritus in an international cohort of patients with psoriasis. METHODS: This cross-sectional study included a total of 634 patients and 246 controls from Germany, Poland and Russia. Physicians examined and interviewed participants, recording clinical characteristics, such as severity, therapy and localization of psoriatic lesions. Participants filled out self-reported questionnaires including questions on pruritus severity and impact, characteristics, and response to therapy, and quality of life (QoL). Localization patterns of pruritus and skin lesions were visualized using body heat maps. RESULTS: Most patients (82%) experienced pruritus throughout their disease, and 75% had current pruritus. The majority of patients (64%) perceived pure pruritus, and those who reported additional painful and/or burning sensations (36%) reported overall stronger pruritus. The scalp was the most frequently reported localization of pruritus, even in the absence of skin lesions. Body surface area (BSA) of pruritus was not linked to pruritus intensity, but to BSA of psoriatic lesions (rho = 0.278; P < 0.001). One third of patients (31%) reported impaired sex-life, and 4% had suicidal ideations due to pruritus. In up to one third of patients, psoriasis therapies had little or no effect on pruritus. The only therapeutic option offered to some of these patients were antihistamines, which appeared to be effective in most cases. CONCLUSION: Pruritus is highly prevalent in psoriasis and is linked to a significant burden. Current psoriasis therapies are frequently insufficient to control pruritus. Managing psoriasis should include the assessment and control of itch. Efficient antipruritic therapies should be developed and be made available for patients with psoriasis.

Unmet clinical needs and burden of disease in hidradenitis suppurativa: real-world experience from EU5 and US.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease characterized by painful deep lesions and associated with substantial disease burden. OBJECTIVES: The objective of this study was to describe physician- and patient-reported clinical unmet needs from a real-world perspective. METHODS: This study used data from the Adelphi HS Disease Specific Programme, a point-in-time survey of dermatologists and their patients with HS in Europe and the United States. Dermatologists completed patient record forms (PRFs) for 5-7 consecutively consulting patients with HS; patients or carers of patients also optionally completed a patient/carer self-completion questionnaire (PSC/CSC). Data collection included demographics, symptomatology and impact on quality of life (QoL). RESULTS: Dermatologists (N = 312) completed PRFs for 1787 patients with HS; patient- and carer-reported questionnaires (PSC/CSC) were completed for 33.1% (591/1787) of patients. The mean age was 34.4 ± 12.2 years and 57.6% of patients were female (1029/1787). Physician-judged disease severity at sampling was categorized as mild in 66.0% (1179/1787), moderate in 29.3% (523/1787) and severe in 4.7% (85/1787) of patients. Deterioration or unstable condition over the previous 12 months was described by 17.1% [235/1372] and 12.6% [41/325] of physician- and patient/carer-reported cases, respectively. Despite receiving treatment, high proportions of patients still experienced symptoms at sampling (general pain/discomfort [49.5%, 885/1787]; inflammation/redness of lesions/abscesses [46.1%, 823/1787] and itching [29.9%, 535/1787]); these symptoms were more frequent in patients with moderate or severe disease. Patients reported a mean Dermatology Life Quality Index score of 5.9 ± 5.4 (555/591; mild, 4.1 ± 4.3; moderate, 9.4 ± 5.4; severe, 13.3 ± 5.5) and a mean Hidradenitis Suppurativa Quality of Life score of 11.0 ± 10.6 (518/591; mild, 7.6 ± 8.3; moderate, 17.7 ± 10.0; severe, 31.0 ± 15.4) indicating a substantial impact on QoL. CONCLUSIONS: Patients with HS experienced a high disease burden despite being actively treated by a dermatologist. This study demonstrates that the burden of HS disease is generally poorly managed with a considerable impact observed on patients' QoL.

Prevalence and factors associated with sleep disturbance in adult patients with psoriasis.

BACKGROUND: Sleep, which is crucial for restoring of physiological functions and health, is reportedly impaired in psoriasis. The role of different potential sleep confounding factors, including detailed pruritus characteristics, and the complex interplay between psychological variables (anxiety and depression), pruritus and sleep disturbance in psoriasis remain insufficiently investigated. OBJECTIVES: To investigate sleep characteristics and to identify clinical, demographic and psychological factors associated with sleep disturbance in psoriasis. METHODS: This cross-sectional study included 334 psoriasis patients (response rate 86%) and 126 control subjects (response rate 82%). Measures included sleep quality [Pittsburgh Sleep Quality Index (PSQI)], psoriasis severity, pruritus characteristics, including average pruritus intensity [visual analogue scale (VAS)], severity of comorbidities, anxiety and depression (Hospital Anxiety and Depression Scale - HADS) and quality of life (Dermatology Life Quality Index - DLQI, and Short Form 12 - SF12). RESULTS: Fifty-nine per cent of patients and 34% of control subjects (P < 0.001) suffered from sleep disturbance (PSQI > 5). Patients slept 1 h less than control subjects (median 6 vs. 7 h, P < 0.001). Patients without pruritus had less impaired sleep (global PSQI) than patients with strong (P < 0.001) and very strong pruritus (P < 0.001). Anxiety (HADS-A) and depression (HADS-D) levels were the strongest predictors of sleep impairment, followed by pruritus exacerbation at night, age, female sex, pruritus exacerbation in the morning, average pruritus intensity (VAS), diagnosed depression and gastroesophageal reflux disease, altogether explaining 32%-37% of the variance in global sleep quality. Both anxiety (HADS-A) and depression (HADS-D) were significant mediators explaining the association between pruritus intensity (VAS) and sleep impairment in 42% and 37% respectively. CONCLUSIONS: Sleep disturbance in patients with psoriasis is highly prevalent. Patients with psoriasis should be assessed for sleep impairment, pruritus, anxiety and depression. Reduction in pruritus should be considered as an important therapeutic goal, along with therapies aimed at reducing anxiety and depression.

[Pathogenesis of hidradenitis suppurativa/acne inversa]. / Pathogenese der Hidradenitis suppurativa/Acne inversa.

Hidradenitis suppurativa/acne inversa (HS) has a multifactorial pathogenesis. In addition to a sporadic form, a familial form is reported in around 40% of patients, for whom an autosomal dominant (AD) inheritance with reduced gene penetrance is assumed. The phenotype of the disease with inflammatory nodules, abscesses and secreting sinus tracts suggests an infectious origin, but the exact role of the bacteria detected in HS pathogenesis remains unclear. Smoking and metabolic syndrome are regarded as important trigger factors in HS, with obesity and hormonal changes playing a pathogenic role in the latter. Ultimately, Toll-like receptors, antimicrobial peptides, immune cells and key cytokines are involved in the excessive inflammatory reaction of HS and are also the targets of future therapies.

Kinetics and tissue repair process following fractional bipolar radiofrequency treatment.

INTRODUCTION: Fractionated radiofrequency (RF) tissue tightening is an alternative method to fractionated laser treatment of skin wrinkling, laxity and acne scars, with reduced risk of scarring or persistent pigmentation. The aim of this study was to evaluate and quantify the wound healing process after RF treatment. MATERIALS AND METHODS: 12 patients were treated with a 64-pin fractional bipolar RF device with 60 mJ/pin applied energy. Confocal laser scanning microscopy (CLSM) examination was performed on day 1, day 2, day 7 and day 14 after treatment. Clinical wound healing process was measured and expressed as a percentage. RESULTS: All patients developed erythema, mild edema and crusts at the treated areas. Two weeks after treatment clinical symptoms resolved. During ablation patients reported moderate pain. Directly after ablation microscopic ablation zones could be detected in CLSM. Measurement of MAZ at epidermis, dermo-epidermal junction and papilary dermis showed a constant diameter until two weeks after treatment. Re-epithelization of the MAZ could be detected already 1 week after treatment. However, 2 weeks after ablation the honeycomb pattern of the epidermis was not yet completely restored. DISCUSSION: Bipolar fractionated RF treatment demonstrates clinically a rapid wound healing response. The subepidermal remodelling process still ongoing after 14 days, showing new granulation tissue. Therefore, treatment intervals of at least 14 days should be recommended to allow completion of the remodelling process.

[Drug therapy of acne inversa]. / Medikamentöse Therapie der Acne inversa.

Acne inversa is a chronic inflammatory destructive skin disease that affects about 1% of the population. The therapy should be personalized and consists of surgical and conservative procedures. Antibiotics are administered either topically or systemically. Combination therapy with clindamycin and rifampicin for 10-12 weeks can be very effective. Furthermore, TNF-α inhibitors show adequate efficacy and can be recommended. Adalimumab is the only approved drug product for systemic treatment of acne inversa. The efficacy of retinoids is controversial. Isotretinoin cannot be recommended for the treatment of acne inversa; however, acitretin has been proven to be more effective. Immune-modulating substances, like dapsone, cyclosporine A, methotrexate, colchicine, or corticosteroids, can be considered; however, the study data are insufficient for recommendation. Hormonal therapies can influence the course of the disease. Antiseptics are applied independent of the stage of disease. Patients should be informed about triggering factors.

[Acne inversa/hidradenitis suppurativa: An update]. / Acne inversa/Hidradenitis suppurativa: Ein Update.

Acne inversa (AI)/hidradenitis suppurativa is a chronic, recurrent, immune-mediated dermatosis characterized by deep inflammatory nodules, abscesses, fistulas, and undermined scars in skin areas bearing apocrine glands. In addition to the cutaneous manifestation, numerous AI patients show metabolic changes, spondyloarthritis, and depression. AI leads to a strong reduction in the quality of life and an impairment of the sexual life of affected individuals and often culminates in social withdrawal, stigmatization, unemployment, and suicidal thoughts. In this overview, we summarized the most important facts about AI and propose a simple algorithm for therapy.

A case report of combination treatment with potassium-titanyl phosphate laser and brimonidine topical gel in erythematotelangiectatic rosacea.

Laser therapies have been shown to provide symptom improvement in patients with erythema and telangiectasia of rosacea; however, they are associated with side effects such as erythema. Combinatorial treatment with pharmacological agents and laser have demonstrated better efficacy, fewer side effects and continued long-term remission compared with monotherapies. A case of moderate facial erythema that responded well to combination treatment with brimonidine 3 mg/g gel and a treatment course of potassium-titanyl phosphate (KTP) laser therapy is presented, showing a reduction from baseline, maintained after final laser session, by applying brimonidine 3 mg/g gel daily. Using brimonidine 3 mg/g gel to target post-laser treatment erythema is highly effective in minimising refractory erythema. Continued use of brimonidine 3 mg/g gel provides a sustained reduction of erythema, increasing the visibility of other signs and symptoms of rosacea that may be present. This can facilitate the treatment of these additional signs and symptoms.

[Systemic treatments for psoriasis and psoriatic arthritis]. / Systemische Therapien der Psoriasis und Psoriasisarthritis.

Psoriasis is one of the most common chronic dermatoses. More than 25 % of the affected individuals require effective systemic treatment because of severe symptoms and/or the significantly restricted quality of life. Thanks to intensive research and successful cooperation between academia and the pharmaceutical industry, the options for treating psoriasis have dramatically increased in recent years. Especially targeted therapies give us the opportunity for personalized regimen. This review describes the spectrum of the systemic treatments for psoriasis and psoriatic arthritis and discusses the efficacy, safety, and particular features of the individual substances.

Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions.

BACKGROUND: Psoriasis and psoriatic arthritis are treated very efficaciously with infliximab, a chimaeric human-murine antitumour necrosis factor (TNF)-α antibody. As we reported earlier, infliximab, besides its anti-inflammatory properties, induces a caspase-independent programmed cell death of psoriatic keratinocytes. OBJECTIVES: To elucidate this finding further, we investigated the epidermal expression of proteins involved in the mitochondria-dependent (intrinsic) pathway of cell death. METHODS: Quantification of proteins with pro- (p53, AIF, Bax) and anti-apoptotic functions (Bcl-2, Bcl-XL) and of NF-κB was performed by means of immunohistochemistry and digital image analysis of the staining of nonlesional skin and lesional psoriatic skin from patients treated with infliximab at weeks 0, 2 and 6. RESULTS: Serial biopsies from psoriatic plaques of samples taken at days 0, 5, 14 and 21 of therapy demonstrated a significant downregulation of anti-apoptotic proteins Bcl-2, Bcl-XL and NF-κB during treatment and, in parallel, a significant upregulation of pro-apoptotic proteins p53, Bax and AIF. These differences in expression correlated with decreases in epidermal thickness and clinical outcome (Psoriasis Area and Severity Index). At day 21, expression levels of apoptosis-related proteins in lesional skin approximated those found in nonlesional skin. CONCLUSIONS: Our data therefore suggest that TNF-targeting agents may induce the regression of psoriasis at least in part by normalizing the expression of apoptosis-related proteins in lesional keratinocytes.

The role of endothelial cell apoptosis in the effect of etanercept in psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with abnormal vascular expansion in the papillary dermis. Tumour necrosis factor (TNF)-α is a proinflammatory cytokine that can induce antiapoptotic proteins and endothelial cell activation factors in psoriasis. OBJECTIVES: The present study investigated the effect of the anti-TNF-α agent etanercept on the expression of endothelial nuclear factor-κB (NF-κB), angiogenic vascular endothelial growth factor (VEGF), endothelial cell marker CD31, antiangiogenic factor thrombospondin-1 (TSP-1), and antiapoptotic factors Bcl-2 and Bcl-xL in psoriasis. METHODS: Sixteen patients with moderate-to-severe psoriasis were included in the study and treated with etanercept 50 mg twice weekly subcutaneously for 12 weeks. Biopsies of lesional skin (baseline, weeks 3, 6 and 10) were obtained and immunohistochemically stained with antibodies for CD31, VEGF, TSP-1, NF-κB, Bcl-2 and Bcl-xL. Double immunofluorescence staining for VEGF and CD31 was evaluated with confocal laser microscopy. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was applied for apoptosis detection. RESULTS: Etanercept caused a statistically significant time-dependent reduction in the number of dermal blood vessels, the number of CD31+ cells and VEGF in psoriatic lesions, with induction of endothelial cell apoptosis and statistically significant upregulation of TSP-1 in psoriatic vessels. Immunohistochemical analysis showed significant reduction of NF-κB, Bcl-2 and Bcl-xL expression in endothelial cells during treatment. These changes were accompanied by a marked clinical response. CONCLUSIONS: The present findings suggest that treatment with etanercept induces apoptosis, reduces apoptosis-inhibiting factors in psoriatic endothelial cells, and decreases angiogenesis in psoriatic skin.

Two hsp23 genes in the Mediterranean fruit fly, Ceratitis capitata: structural characterization, heat shock regulation and developmental expression.

In the present study, we characterized a 3320-bp genomic DNA fragment encoding two medfly (Ceratitis capitata) homologues of the Drosophila melanogaster heat shock protein 23 (hsp23) gene, named Cchsp23-alphaand -beta. The two medfly hsp23 genes are transcribed in opposite directions and encode two almost identical proteins. Furthermore, the two genes exhibit a very high degree of similarity in their 5' untranslated and proximal promoter regions. Phylogenetic analysis indicated that the CcHsp23 proteins are orthologous to Drosophila Hsp23 and Sarcophaga crassipalpis Hsp23. Structural analysis of the 5' flanking regions of the Cchsp23 genes revealed the presence of several putative heat shock elements. Both CcHsp23 genes are induced by heat in a similar manner. In addition to heat-induction, the Cchsp23 genes are expressed at several stages of normal development as well as in ovaries and testes. In general, the developmental expression patterns of the medfly genes are similar, suggesting that they are under similar regulatory mechanisms. However, the expression of the Cchsp23 genes differs significantly from the expression of the Drosophila hsp23 gene in certain embryonic and larval stages, suggesting differential regulation of the hsp23 genes in the two dipteran species. The expression of both Cchsp23 genes in adult flies is increased with age, especially in males.

The hsp27 gene of the Mediterranean fruit fly, Ceratitis capitata: structural characterization, regulation and developmental expression.

In the present study, a genomic DNA clone encoding the medfly homolog of Drosophila melanogaster hsp27 gene, named Cchsp27, was isolated. We sequenced a part of the clone containing the coding region, the 5' untranslated region and approximately 2.8 Kb of the 5' flanking region of the gene. Phylogenetic analysis of several insect small heat shock proteins, suggested that CcHsp27 is orthologous to Drosophila Hsp27 and Sarcophaga crassipalpis Hsp25. The Cchsp27 gene was mapped at the 81A division of the sixth chromosome which coincides with one of the major heat shock puffs of medfly. Structural analysis of the 5' flanking region of the Cchsp27 gene revealed the presence of five putative heat shock elements and one putative ecdysone response element. In addition to heat induction, the Cchsp27 gene was expressed at several stages of normal medfly development. In general, the developmental expression pattern of the Cchsp27 gene was similar to the respective pattern of Drosophila hsp27 gene. However, there were some important differences in certain developmental stages suggesting differential regulation of the hsp27 gene in the two dipterans species. Salivary gland culture experiments showed that the Cchsp27 gene is regulated by 20-hydroxyecdysone.

Effect of heparin affin regulatory peptide on the expression of vascular endothelial growth factor receptors in endothelial cells.

BACKGROUND: Heparin affin regulatory peptide (HARP) is an 18-kDa secreted protein that has been implicated in tumor growth and angiogenesis, although the mechanisms involved remain largely unknown. In the present work, the effect of human recombinant HARP on the expression of the vascular endothelial growth factor (VEGF) receptors KDR, Flt-1 and neuropilin-1 was studied in cultured human umbilical vein endothelial cells (HUVEC). MATERIALS AND METHODS: The mRNA and protein levels of VEGF receptors were estimated by semi-quantitative RT-PCR and Western blot, respectively. Cell proliferation and migration were measured by MTT, direct counting of the cells and modified Boyden chamber assays. RESULTS: HARP decreased the expression of KDR but increased the expression of Flt-1 and neuropilin-1 at both the mRNA and protein level. The effect reached a maximum 4 h after the addition of HARP into the cell culture medium and was reversed at later time-points. When HARP was added to the culture medium 4 h before the addition of VEGF165, it inhibited VEGF165-induced proliferation and migration of HUVEC. CONCLUSION: These data suggest that HARP affects the expression of VEGF receptors and inhibits VEGF165-induced activation of HUVEC.

Cloning and characterization of CcEcR. An ecdysone receptor homolog from the mediterranean fruit fly ceratitis capitata.

In order to understand the role that 20-hydroxyecdysone plays during development of the Mediterranean fruit fly Ceratitis capitata (medfly), a major agricultural pest, we have cloned a Ceratitis ecdysone receptor (CcEcR) and studied its expression and its binding properties to an ecdysone response element. Using the conserved DNA binding region of the Drosophila melanogaster ecdysone receptor (DmEcR) B1 cDNA as a probe, we isolated a medfly cDNA clone containing the coding region, a part of the 5'-untranslated region and the complete 3'-untranslated region of a CcEcR. The deduced CcEcR polypeptide contained all five domains typical of a nuclear receptor. Alignment comparisons and phylogenetic analyses indicated that CcEcR most closely resembled the B1 isoform of DmEcR and Lucilia cuprina EcR homolog (LcEcR) relative to all other known ecdysone receptors. In situ hybridization analysis showed that the CcEcR gene is mapped in the region 53B of the 4R chromosome arm, while Northern hybridization analysis showed that CcEcR transcripts have a size of approximately 8 kb. Significant levels of CcEcR transcripts were detected in eggs, middle and late embryos, late third instar larvae and middle prepupae. The levels of the CcEcR transcripts during the other larval stages as well as during pupal and adult stages were much lower, while during the early stages of embryogenesis were very low. Electrophoretic mobility shift assays indicated that CcEcR binds specifically to the Drosophila hsp27 ecdysone response element as a heterodimer with Drosophila USP, the product of the ultraspiracle gene. Our structural and biochemical data suggest that CcEcR is the functional homolog of the B1 isoform of DmEcR.

Cloning and characterization of a cDNA encoding a male-specific serum protein of the Mediterranean fruit fly, Ceratitis capitata, with sequence similarity to odourant-binding proteins.

Male-specific serum proteins (MSSPs) are low molecular weight proteins which accumulate in high amounts in the haemolymph of adult males of the medfly Ceratitis capitata. By screening an expression library with anti-MSSP antibodies, we have isolated and determined the nucleotide sequence of a cDNA clone coding for one of the male-specific polypeptides (MSSP-alpha). The MSSP-alpha mRNA encodes a polypeptide of 144 amino acids with a secretory signal sequence of sixteen amino acids. Southern analysis indicated that there are multiple copies of MSSP genes in the medfly genome. Northern analysis showed that the MSSP mRNAs are synthesized only in adult males. The accumulation pattern of these mRNAs during development suggests that the expression of the MSSP genes is developmentally regulated at both transcriptional and translational levels. The predicted peptide sequence of MSSP-alpha shows significant similarity to a group of pheromone- and general odourant-binding proteins of insects.