Safety and efficacy of adapalene 0.1% / benzoyl peroxide 2.5% in the long-term treatment of predominantly moderate acne with or without concomitant medication - results from the non-interventional cohort study ELANG.

BACKGROUND: Acne is a chronic inflammatory disease requiring long-term treatment. The fixed-dose combination adapalene 0.1%/benzoyl peroxide 2.5% (adapalene-BPO) is indicated for the once-daily topical treatment of Acne vulgaris when comedones, papules and pustules are present. OBJECTIVE: The main objectives of this non-interventional study were to assess long-term efficacy and safety of adapalene-BPO in moderate to severe acne with and without concomitant medication. METHODS: Patients with moderate to severe acne received adapalene-BPO alone or in combination with concomitant medication over a course of 9 months. The primary efficacy endpoint was changes in acne severity according to the Leeds Revised Acne Grading System; secondary endpoints included treatment success assessed by the patient and safety. RESULTS: In total, 5131 patients were eligible for efficacy and 5141 for safety evaluation. The majority of patients (78.8%) received adapalene-BPO alone. About 21.2% received adapalene-BPO in combination with another agent, mostly topical antibiotics (8.8%) or systemic antibiotics (8.7%). Mean (±SD) acne severity improved from 5.6 ± 1.5 at baseline to 3.3 ± 1.9 at month 3, and further to 1.9 ± 1.9 at month 9 (both P < 0.0001). The degree of improvement correlated significantly with the severity at baseline. After 3 and 9 months of treatment, the facial skin was cleared completely (no more visible acne lesions) in 420 (8.2%) and 1326 patients (25.8%), respectively. A therapeutic effect was noted by the patients after a median time of 3 weeks (range: from 1 day to 12 weeks). No serious adverse events were reported. Facial skin irritations, mostly mild to moderate, occurred in 49.5% of patients and led to discontinuation in only 1.7% of cases. CONCLUSION: In consistence with previous clinical findings, the use of adapalene-BPO in daily practice routine is safe and effective in the long-term management of patients with moderate to severe acne.

Effect of adapalene 0.1%/benzoyl peroxide 2.5% topical gel on quality of life and treatment adherence during long-term application in patients with predominantly moderate acne with or without concomitant medication - additional results from the non-interventional cohort study ELANG.

BACKGROUND: In addition to physical long-lasting effects such as permanent scarring and disfigurement, acne has acute and long-term psychosocial effects that affect the individual's quality of life. As with other chronic diseases, treatment success is often compromised by poor adherence. OBJECTIVE: Two main objectives of this non-interventional study were to assess the long-term effect of the fixed-dose combination adapalene 0.1%/benzoyl peroxide 2.5% (adapalene-BPO gel) on quality of life and treatment adherence. METHODS: Patients with moderate to severe facial acne receiving adapalene-BPO alone or in combination with other drugs were enrolled in this non-interventional study. Data were documented at baseline and after 3 and 9 months of adapalene-BPO treatment. The secondary outcomes reported here include quality of life determined by the Cardiff Acne Disability Index (CADI), treatment adherence assessed by the ECOB (Elaboration d'un outil d'evaluation de l'observance des traitements medicamenteux) questionnaire, and patient satisfaction. RESULTS: In total, 5131 patients were included in the efficacy evaluation. After 9 months, mean (±SD) quality of life (CADI) improved significantly from 5.9 ± 3.0 to 2.4 ± 2.7 (P < 0.0001). Patients with more severe acne at baseline tended to achieve a greater improvement in quality of life. Long-term adherence was found to be good in 83.9% of patients. Adherence had a significant effect on efficacy and quality of life (P < 0.0001 respectively). The vast majority of patients (92.1%) reported subjective improvement at the interim analysis. Accordingly, most patients (84.8%) were satisfied or very satisfied with adapalene-BPO by the end of the observation period. CONCLUSION: The clinical improvement of the disease led to an increase in quality of life among acne patients. The treatment success may be a motivation factor for patients to stay adherent over the long-term treatment course, indicating the qualification of adapalene-BPO topical gel as an appropriate medication also in the long-term usage.

German S3-guidelines on the treatment of psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance (Richards et al. in J Am Acad Dermatol 41(4):581-583, 1999). To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis first published in 2006 and now updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. This short version of the guidelines presents the resulting series of therapeutic recommendations, which were based on a systematic literature search and discussed and approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs, as well as detailed information on how best to apply the treatments described (for full version please see Nast et al. in JDDG Suppl 2:S1-S104, 2011 or http://www.psoriasis-leitlinie.de ).

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

Failure to recognize rapidly growing mycobacteria in a proficiency testing sample without specific request--a wider diagnostic problem?

Fifty participants in the Swiss External Quality Control Program in Bacteriology/Mycology received a diagnostic sample containing Mycobacterium fortuitum. Only 31 used some sort of acid-fast stains, and 13 reported the diagnosis of M. fortuitum or rapidly growing mycobacteria. We conclude that the presence of 'rapid growers' in routine bacteriology samples is underestimated, and that acid-fast stains should be performed on suspicious Gram-positive rods.

Antileukoprotease in human skin: an antibiotic peptide constitutively produced by keratinocytes.

Antileukoprotease (ALP), also known as mucous protease inhibitor or secretory leukoprotease inhibitor, resembles one of the major antiproteases present in human body fluids. It is capable of preventing proteolytic degradation of extracellular matrix proteins by neutrophil-derived serine proteases. ALP was isolated from human callus and detected in supernatants of cultured human primary keratinocytes. ALP mRNA was constitutively expressed in keratinocytes and the expression was not significantly affected by TNF alpha or Interferon gamma stimulation. In microbicidal assays recombinant ALP exhibited antimicrobial activity against several human skin associated microorganisms like P. aeruginosa, S. aureus, S. epidermidis, and C. albicans, indicating that ALP may actively participate in mechanisms allowing homeostasis of bacterial and yeast colonization on human skin. Thus, ALP represents a major soluble serine protease inhibitor and antimicrobial agent expressed in human skin and seems to contribute to the high resistance of the epidermis against proteolysis and infections.

Coryneform bacteria in throat cultures of healthy individuals.

Throat swabs from 113 healthy individuals from Hamburg, Germany, and Zurich, Switzerland, were investigated for coryneform bacteria with nonselective and selective media. Ninety specimens contained 123 strains. Surprisingly, 76% of them were strains of Corynebacterium durum (47%) and Rothia dentocariosa (29%). Only two were strains of Corynebacterium pseudodiphtheriticum, and none were strains of C. striatum, C. amycolatum, or C. diphtheriae.

Diversity of coryneforms found in infections following prosthetic joint insertion and open fractures.

In a 5-year period, 73 coryneform isolates from prosthetic joint and open fracture infections in 60 patients treated in a hospital specialized in orthopedic surgery were speciated. The most frequent species were Corynebacterium amycolatum, Corynebacterium striatum, Corynebacterium diphtheriae biotype mitis, and Corynebacterium jeikeium. At least 14 isolates were deemed clinically significant as sole agents of infection.

Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria pigmentosa and systemic mastocytosis.

BACKGROUND: Previous studies have shown that oral PUVA is effective in urticaria pigmentosa. Long-term results, however, are unknown. OBJECTIVE: We studied the long-term effectiveness of oral PUVA treatment in urticaria pigmentosa as well as in systemic mastocytosis. In addition, the success of bath PUVA was examined in these diseases. METHODS: Twenty patients with urticaria pigmentosa and systemic mastocytosis treated by oral PUVA were examined retrospectively for a time period of up to 18 years. We studied the duration of improvement and correlated these results with the total PUVA dose, the skin type and the age of onset. Four patients were treated by bath PUVA therapy. RESULTS: In oral PUVA therapy an improvement was seen in 14 out of 20 patients (70%). There was no difference in the response rate between urticaria pigmentosa and systemic mastocytosis and there was no correlation with the total PUVA dosage. The duration of the treatment's success ranged from a few weeks to more than 10 years. 25% of the patients showed an improvement for more than 5 years. Patients with onset during childhood and early adolescence and patients with skin types I and II responded favourably to the treatment. Bath PUVA therapy was without effect in our 4 patients. CONCLUSION: Oral PUVA is very effective for the long-term treatment of urticaria pigmentosa as well as systemic mastocytosis.

Treatment of psoriasis with polyethylene sheet bath PUVA.

BACKGROUND: Bath PUVA has been shown to be an effective alternative treatment for psoriasis with fewer systemic side effects than oral methoxsalen (8-MOP). The cost of 8-MOP and the need for a bath unit have prevented wider use of this treatment. OBJECTIVE: We investigated the safety and efficacy of sheet bath PUVA by restricting the volume of the psoralen/bath water solution to 10 L with the aid of a polyethylene sheet. METHODS: Fifty-eight patients with chronic plaque-type psoriasis were treated with bath PUVA in a concentration of 0.5 mg of 8-MOP per liter of water. RESULTS: The group required a median of 17 baths (95% confidence interval [CI], 14-20) for clearance. Total UVA dose for the entire group was 26 J/cm2(95% CI, 18-47). CONCLUSION: Sheet bath PUVA is safe, efficient, and easy. This regimen can significantly reduce the amount of 8-MOP required, thereby resulting in a favorable cost/benefit ratio.

Foil bath PUVA in the treatment of prurigo simplex subacuta.

Prurigo simplex subacuta is a chronic pruritic condition of unknown aetiology. The skin lesions respond to topical corticosteroids, UV-A and UV-B therapy only to a limited degree. Ten patients suffering from prurigo simplex subacuta were treated with foil bath PUVA at a concentration of 0.5 mg 8-methoxypsoralen/l. Using the foil bath method the volume of the psoralen/bath-water solution is restricted to 10 l with the aid of polyethylene foil. The group required a median of 13 (95% CI: 9-19) baths for clearance. The total UV-A dose for the whole group was 19 (95% CI:5-30) J/cm2. Bath PUVA is a safe and well-tolerated therapy in the treatment of prurigo simplex subacuta.

Human eosinophils lack human leukocyte elastase.

Recently, human leukocyte elastase has been detected in human eosinophils. Reinvestigating these findings, 2.5 pg active human leukocyte elastase (E.C. 3.4.21.37) were found per neutrophil isolated from peripheral blood, whereas the elastase activity of eosinophil preparations was linearly correlated with the content of contaminating neutrophils. Also spontaneous or stimulated release of active elastase was absent in eosinophils. By immunohistochemistry no elastase immunoreactivity could be demonstrated in human eosinophils. Therefore, we conclude that human eosinophils do not contain considerable amounts of human leukocyte elastase.

Antiprotease activity in urine of patients with inflammatory skin disorders.

Polymorphonuclear leukocytes contain well-defined proteolytic enzymes in their azurophilic granules that can be released into tissues during inflammation, producing a localized excess of proteases that causes a protease-antiprotease imbalance with subsequent tissue destruction. The antiproteolytic compounds of the epidermis, such as the protease inhibitors elafin and antileukoprotease, are thought to counteract the proteolytic tissue damage. We investigated the urine of patients suffering from inflammatory skin conditions (e.g., erysipelas, psoriasis) for the presence of urinary antiprotease activities. Purification of elastase-inhibitory activities from pooled urine samples by cation exchange high-performance liquid chromatography and preparative and analytical reverse-phase high-performance liquid chromatography yielded two different types of inhibitors. One was a cationic, acid-stable, and elastase-specific inhibitor of M(r) 6,000 by size-exclusion high-performance liquid chromatography. N-terminal amino acid sequence analysis of the first 28 residues showed identity with elafin, an elastase-specific inhibitor recently isolated from psoriatic scales. The second anti-protease activity was due to two forms of urinary bikunin, the inhibitory subunit of inter-alpha-inhibitor. Both bikunin fragments, with M(r) 4,000 and 16,000, were identified by N-terminal amino acid sequence analysis of the first 10 residues and were characterized by an antiproteolytic profile against human leukocyte elastase, cathepsin G, and trypsin. Urinary protease inhibitors may serve as diagnostic markers of inflammatory diseases.

Development of a new selective plating medium for Rhodococcus equi.

A new selective plating medium for Rhodococcus equi containing ceftazidime (20 mg/l) and novobiocin (25 mg/l) on a Mueller-Hinton agar basis is described. It proved to be less inhibitory for R. equi than selective plating media devised earlier and grew only very few other nocardioform bacteria.

[Innovative balneotherapy with reduced bath volume: foil baths]. / Innovative Balneotherapie mit reduzierten Badevolumina: Folienbäder.

Balneo-phototherapy, in which salt baths are followed by UV-B irradiation, has proved successful in the treatment of psoriasis. Because of practical problems, the major one of which is the large turnover of bath solution volumes, balneotherapy has so far been limited to specialized treatment centres. With the aid of a polyethylene foil the volume of bathing solutions needed can be reduced to a total of 41 per bath. Balneotherapy using small bath solution volumes for total body treatment can now be applied as an outpatient regimen for salt bath and bath-PUVA therapy. The methods for establishing balneotherapy with restricted water volumes and the advantages of bath-PUVA over conventional oral psoralen therapy are described.

Crude liver membrane fractions and extracellular matrix components as substrata regulate differentially the preservation and inducibility of cytochrome P-450 isoenzymes in cultured rat hepatocytes.

The influence of cell-substrata interactions on the preservation of basal or in-vivo-induced microsomal cytochrome P-450 isoenzyme contents in cultured rat hepatocytes and on the adaptive responses after exposure to phenobarbital or 3-methylcholanthrene in vitro, was investigated. Hepatocytes from untreated or phenobarbital-treated rats were cultured in serum-free, aprotinin-supplemented culture medium in 96-well microtiter plates coated with collagen type I (COL), laminin, fibronectin or crude liver membrane fractions/collagen type I (CMF/COL). Basal cell functions were characterized by measuring the total protein content and lactate dehydrogenase release. The relative contributions of CYP1A1/2, CYP2B1/2, CYP2C6, CYP2C11, CYP3A and CYP4A isoenzymes were determined with ELISA using monoclonal antibodies raised against purified cytochromes P-450 from rat liver microsomes. The characterization of the CMF revealed that contaminations with mitochondria, nuclei and lysosomes are relatively low. Among these, membranes derived from the endoplasmic reticulum appeared to be the major organelle contaminant of the CMF. The matrix components laminin, fibronectin and collagen type IV were found in appreciable amounts. Hepatocytes from untreated rats, cultured for up to nine days on CMF/COL-coated plates, retained their relative cytochrome P-450 contents at 1.5-3-fold higher levels when compared to cells cultured on COL, fibronectin or laminin. Similarly, hepatocytes from phenobarbital-treated rats preserved the contents of barbiturate-inducible CYP2B1/2 and CYP3A proteins best when cultured on CMF/COL. After exposure of hepatocytes cultured on CMF/COL to phenobarbital from days 3-6, CYP3A proteins were enhanced more than twofold and CYP2B1/2, depending on the exposure level, increased 1.3-6-fold. After exposure to 3-methylcholanthrene, a threefold increase of CYP1A proteins was found in CMF/COL and laminin cultures. These results indicate that CMF/COL, as a substratum in rat hepatocyte cultures, regulates gene expression of cytochromes P-450 isoenzymes for up to 9 days and provides a matrix which enables the cells to respond qualitatively similar to the response observed in different zones of the liver. This activity cannot be replaced by single-matrix components.

Lesional elastase activity in psoriasis, contact dermatitis, and atopic dermatitis.

Human leukocyte elastase (HLE) is a broad spectrum serine protease derived from neutrophils and macrophages. We developed an assay to determine HLE activity on the skin surface in patients with inflammatory skin diseases. HLE activity was absent in the skin of healthy controls. A massive increase of HLE activity was found in lesional skin of psoriasis (31 times), allergic contact dermatitis (55 times), and atopic dermatitis (35 times), but not in uninvolved skin of diseased patients. Therefore, this assay appears to represent a useful biochemical marker of epidermal inflammation. The presence of proteolytically active HLE in diseased epidermis, which is known to contain specific inhibitors of this enzyme, suggests a pathophysiologic role of this enzymatic activity in psoriasis, contact dermatitis, and atopic dermatitis.

[Liberation of human leukocyte elastase by hypertonic saline baths in psoriasis]. / Freisetzung von humaner Leukozytenelastase durch hypertone Salzbäder bei Psoriasis.

Human leukocyte elastase, a proteolytic enzyme of neutrophils, can be determined by a highly sensitive enzymatic assay. Bathing in hypertonic salt solutions allowed considerable amounts of human leukocyte elastase to be eluted from psoriatic lesions. Optimal elution was achieved with sodium chloride concentrations of 1 M and higher. Thirty patients with psoriasis of varying degrees of severity released significantly increased amounts of human leukocyte elastase following a 10-min bath in salt water. During daily treatment with salt water baths and UV-B radiation the elutable amounts of elastase decreased dramatically within a few days, reaching normal levels when the skin had cleared. Determination of human leukocyte elastase in salt water eluates of psoriatic skin seems to be useful for quantification of therapeutic effects. It appears conceivable that human leukocyte elastase plays a role in the psoriatic tissue reaction.