Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

Take heart: bariatric surgery in obese patients with severe heart failure. Two case reports.

Bariatric surgery may be an effective treatment for obese heart failure patients, enabling access to cardiac transplantation and/or improvement of symptoms. We report the outcomes of two morbidly obese patients with end-stage heart failure, where obesity precluded cardiac transplantation and underwent laparoscopic gastric banding. A 42 year-old male with idiopathic dilated cardiomyopathy weighing 124.4 kg (BMI 42 kg/m(2)) lost 34 kg and was successfully transplanted 11 months later. A 40 year-old woman with familial dilated cardiomyopathy weighing 105 kg (BMI 40 kg/m(2)) lost 14 kg with sufficient symptomatic resolution to no longer require cardiac transplantation. In selected patients with severe heart failure and concomitant morbid obesity, bariatric surgery may be a reasonable treatment option.

Genetic differences based on a beef terminal index are reflected in future phenotypic performance differences in commercial beef cattle.

The increased demand for animal-derived protein and energy for human consumption will have to be achieved through a combination of improved animal genetic merit and better management strategies. The objective of the present study was to quantify whether differences in genetic merit among animals materialised into phenotypic differences in commercial herds. Carcass phenotypes on 156 864 animals from 7301 finishing herds were used, which included carcass weight (kg), carcass conformation score (scale 1 to 15), carcass fat score (scale 1 to 15) at slaughter as well as carcass price. The price per kilogram and the total carcass value that the producer received for the animal at slaughter was also used. A terminal index, calculated in the national genetic evaluations, was obtained for each animal. The index was based on pedigree index for calving performance, feed intake and carcass traits from the national genetic evaluations. Animals were categorised into four terminal index groups on the basis of genetic merit estimates that were derived before the expression of the phenotypic information by the validation animals. The association between terminal index and phenotypic performance at slaughter was undertaken using mixed models; whether the association differed by gender (i.e. young bulls, steers and heifers) or by early life experiences (animals born in a dairy herd or beef herd) was also investigated. The regression coefficient of phenotypic carcass weight, carcass conformation and carcass fat on their respective estimated breeding values (EBVs) was 0.92 kg, 1.08 units and 0.79 units, respectively, which is close to the expectation of one. Relative to animals in the lowest genetic merit group, animals in the highest genetic merit group had, on average, a 38.7 kg heavier carcass, with 2.21 units greater carcass conformation, and 0.82 units less fat. The superior genetic merit animals were, on average, slaughtered 6 days younger than their inferior genetic merit contemporaries. The superior carcass characteristics of the genetically elite animals materialised in carcasses worth €187 more than those of the lowest genetic merit animals. Although the phenotypic difference in carcass traits of animals divergent in terminal index differed statistically by animal gender and early life experience, the detected interactions were generally biologically small. This study clearly indicates that selection on an appropriate terminal index will produce higher performing animals and this was consistent across all production systems investigated.

Sebaceous gland tumors and systemic disease: a clinicopathologic analysis.

The association of sebaceous gland neoplasms with visceral carcinomas, first described by Muir and Torre, has become widely recognized. The purpose of our study was to determine the prevalence of malignancy, other associated diseases, and familial carcinoma in patients who had one or more cutaneous lesions within the spectrum of sebaceous adenoma, epithelioma, or carcinoma. Our histopathology files contained tissue from 59 such cases. Overlap between the categories was common, often precluding precise histologic classification. Of the 59 patients, 25 (42%) had one or more primary visceral malignancies. These totaled at least 49, of which 25 were colonic, 9 urogenital, 5 hematologic, 4 breast, and 6 miscellaneous. Fifteen patients (25%) had colonic polyps, most often multiple; and at least one primary carcinoma of the colon appeared in 10 of these, initially or later. Other less common findings included uterine fibroids, thyroid adenomas, and benign renal cysts. A family history of carcinoma was found in 72% of cases with visceral malignancy, most often of the colon and stomach. We conclude that sebaceous neoplasms form a histologic continuum, and strong associations with colonic polyps, internal malignancy, and a family history of carcinoma are apparent.

Systemic retinoids in dermatology.

Orally administered retinoids are synthetic derivatives of vitamin A. This new group of drugs (not yet available for general use in the United States) has been effective in experimental trials for treatment of a wide range of skin diseases. The current status of two of these drugs, isotretinoin (13-cis-retinoic acid) and etretinate (Ro 10-9359), is herein reviewed.

The evolution of Hodgkin's disease and necrobiotic xanthogranuloma syndrome.

We describe a woman in whom hypogammaglobulinemia and severe granulomatous cutaneous lesions had developed during childhood; subsequently, Hodgkin's disease and necrobiotic xanthogranuloma were diagnosed. This case illustrates an apparent association with disease activity and raises the question of a direct relationship of necrobiotic xanthogranuloma with lymphoproliferative disease.

Pseudosclerodermatous panniculitis after irradiation: an unusual complication of megavoltage treatment of breast carcinoma.

An unusual edematous and indurated erythema developed in four patients with breast carcinoma 1 to 6 months after conservative surgical treatment and irradiation. The radiation therapy consisted of megavoltage x-ray photon with or without either electron beam or iridium-192 interstitial boost. Several tissue biopsy specimens revealed pronounced lymphocytic dermal and fat inflammation in conjunction with focal areas of plasma cells. The connective tissue bundles were enlarged and hyalinized. Macrophages and isolated giant cells were noted in the dermis. One biopsy specimen showed elastic tissue in giant cell cytoplasm. No mucin, fibrin, formation of cysts, or calcification was present. Lipophages and hyaline connective tissue replaced some fat lobules. The radiation-induced changes of dilated and hyalinized blood vessels, endothelial cell hyperplasia, fibrosis associated with involution of epidermal appendages, and fibroblasts were present. This combination of radiation-related and inflammatory pathologic changes is unusual and emphasizes the remarkable qualities of this rare reaction. The clinical differential diagnoses of recurrent carcinoma, cellulitis, and connective tissue disease can be excluded by reviewing the pathologic characteristics.

Histopathologic features of the L-tryptophan-related eosinophilia-myalgia (fasciitis) syndrome.

Study of 18 biopsy specimens in 11 patients with L-tryptophan-related eosinophiliamyalgia (fasciitis) syndrome showed hyaline sclerodermoid changes. Dermal scleroderma was found in eight of nine punch biopsy specimens and eight of nine excisional biopsy specimens. Fascial scleroderma was found in eight excisional biopsy specimens. One specimen obtained by excision had no fascia present. Eleven biopsy specimens showed edema of the dermis, and 13 showed dilated lymphatic structures; thus, the clinical picture of edematous sclerosis was confirmed. Mucinous fasciitis was present in five excisional biopsy specimens, in conjunction with a large number of macrophages in four. Dermal mucinosis was present in 11 biopsy specimens. Lymphocytic and macrophage inflammation was minimal in 14 biopsy specimens and pronounced in only 4. Plasma cells were present in eight cases. Eosinophils were present in substantial numbers in three biopsy specimens and only occasionally in four. Eosinophilic spongiosis was observed in one patient. Lymphocytic inflammation was noted around a single muscle spindle and around large nerve trunks in three patients. No relationship was established between these pathologic features and the duration or dose of tryptophan, prednisone treatment, or duration of symptoms. Pathologic features of the L-tryptophan syndrome consist of hyaline sclerodermoid collagen in the dermis, the septa, and the fascia. Edema, focal mucinosis, and macrophage inflammation may be features that identify this event.

Development of neuron-specific enolase immunoreactivity in avian nervous tissue in vivo and in vitro.

Neuron-specific enolase (NSE) is a glycolytic isoenzyme that is primarily located in neurons and neuroendocrine cells. The development of NSE immunoreactivity in th avian nervous system at the level of the hind limb has been examined using immunocytochemical methods. NSE immunoreactivity is first detected in ventral horn motor neurons and dorsal root ganglion neurons at embryonic day 9-10. This is at least 2-3 days after some neurons in both these populations are capable of electrical activity. The glycogen body, a non-neuronal structure, also exhibits NSE (+) staining, but the onset of this immunoreactivity is earlier, at 8 days of embryonic development. NSE immunoreactivity was absent from the cell bodies of paravertebral sympathetic ganglia throughout development, but was present in cellular processes and terminals in the adult ganglia. NSE immunoreactivity also develops in tissue cultures containing cells of neural tube and neural crest origin.

Disabling pansclerotic morphea of children.

Fourteen children with generalized morphea involving all levels of the skin and soft tissues were examined. The term "acral pansclerotic morphea" describes the distribution and the multiple levels of sclerosis. Lymphocytic inflammation and hyaline pannicultitis were observed on biopsy specimens in some cases. Laboratory data were characterized by a polyclonal elevation of gamma-globulin level and by peripheral eosinophilia. Pulmonary changes in five patients and esophageal changes in one imply that acral pansclerotic morphea may be assoicated with mild nonprogressive visceral change. Although cyclophosphamide may retard the process, no satisfactory treatment for progressive, mutilating acral pansclerotic morphea has been found.

Cutaneous and subcutaneous inflammatory sclerosis syndromes.

Systemic scleroderma and localized scleroderma (morphea) show comparable changes on skin biopsy specimens, and a distinction has often been made on the basis of Raynaud's phenomenon, organ involvement, and laboratory abnormalities characteristically seen in systemic scleroderma. Critical evaluation not only of patients with localized scleroderma but also of those with eosinophilic fasciitis, morphea profunda, and acral pansclerotic morphea has disclosed Raynaud's phenomenon, organ involvement, and laboratory abnormalities typical of systemic scleroderma in a small percentage of patients. Histologically, all five conditions show similar inflammation and sclerosis of the skin, the primary difference being the depth at which these changes occur. These conditions may possibly be related, and the clinical and laboratory differences observed may result from variations in depth, nature, and intensity of the cutaneous and subcutaneous inflammatory sclerosis.

Nonvenereal perianal conditions.

A variety of conditions can affect the perianal tissues. Evaluation must include a thorough history, which should emphasize hygienic habits, use of topical and oral medications, and a review of systems with particular attention to gastrointestinal symptoms. Examination of other areas of the skin may provide clues to the correct diagnosis. Examination of scrapings for yeast, more rarely dermatophytes, and Tzanck preparations from the base of blisters or erosive lesions are useful office diagnostic techniques. In some conditions biopsy of the involved area can be diagnostic (e.g., Paget's disease); in others it may indicate the need for additional studies. Direct immunofluorescent evaluation and special stains may also be indicated. Culture is important to define deep fungal and mycobacterial infections as well as more common bacterial infections. Proctoscopy and roentgenographic studies may be an important part of evaluation, especially in patients who present with perianal suppuration, masses, or anal fissures. Serologic tests for syphilis cannot be overlooked when lesions are ulcerative, moist, or papillomatous. It must be remembered that the symptoms related to perianal eruptions are nonspecific. It is only with a high index of suspicion and careful evaluation that the correct diagnosis can be established.

Scleroderma: therapeutic options.

Although the cause of scleroderma remains elusive, pharmacologic advances and increased understanding of the pathophysiology of this disease provide therapeutic options. Therapy usually addresses the fibrotic, vascular, or immunologic alterations, but general measures can be helpful and should not be overlooked.

Clarinettist's cheilitis.

A 15-year-old clarinettist with a median lower lip cheilitis corresponding to the distribution of a cane reed is reported. Thorough patch testing was unsuccessful in demonstrating an allergic contact hypersensitivity. The cheilitis was probably due to irritant contact factors.

Allergic contact dermatitis. When to suspect it and what to do.

Allergic contact dermatitis is a common problem that can affect persons of all ages and in any state of health. A high index of suspicion and careful follow-through with patch testing and investigative work are needed to establish the diagnosis. Recognition of sources of exposure to the allergen and of important cross-reacting substances is the key to prevention of recurrences.

Pharmacoscintigraphy confirms consistent tamsulosin release from a novel triple-layered tablet.

Conventional modified release preparations of tamsulosin HCl have been linked to increased incidence of cardiovascular adverse events, possibly due to rapid drug peaks soon after ingestion. A 'flattened' absorption profile has been shown to reduce the occurrence of these unwanted effects while improving symptom control. The potential of a novel triple-layered tablet to effect prolonged release and continuous absorption of tamsulosin HCl in the gastrointestinal tract was investigated in this clinical study. Gastrointestinal (GI) transit behaviour was monitored by scintigraphic imaging of technetium-labelled tablets. Drug absorption levels were simultaneously determined through pharmacokinetic analysis of blood samples. A mean Cmax of 6 ± 3 ng/nL was achieved after 324 ± 184 min (mean tmax). The mean AUC0-24 was noted as 4,359 ± 1,880 ng/mL min. The mean gastric emptying and colon arrival times of the tablets were 105.2 ± 68.9 and 270.1 ± 32.0 min post-dose; giving a mean small intestine transit time of 164.9 ± 83.6 min. Variations in gastrointestinal transit did not appear to influence drug absorption. Correlation of scintigraphic and PK data indicated that tamsulosin HCl is released steadily throughout the entire GI tract, suggesting that the mechanism of drug release is independent of GI site allowing drug release even in the low moisture environment of the colon.

Modulation of gastric pH by a buffered soluble effervescent formulation: A possible means of improving gastric tolerability of alendronate.

Gastrointestinal side-effects of alendronate (ALN) are believed to be associated with oesophageal lodging of tablets and perhaps reflux of gastric contents with alendronate under strongly acidic pH conditions. This leads to unfavourable posture restrictions when dosing. This clinical study evaluated gastric emptying and gastric pH after administration of Fosamax(®) tablets and a novel effervescent ALN formulation with a high buffering capacity. This novel formulation, EX101, was developed to potentially improve gastric tolerance. Gastric pH was monitored by nasogastric probes. Gastric emptying was determined simultaneously by scintigraphic imaging of (99m)Tc-DTPA labelled formulations. Both formulations tested rapidly cleared the oesophagus and there were no statistically significant or physiologically relevant differences in gastric emptying times. Mean pH at time to 50% gastric emptying of the radiolabel was significantly higher in EX101-treated subjects compared to those treated with Fosamax(®). At time to 90% gastric emptying of the radiolabel, mean pH values were comparable. Mucosal exposure to ALN at pH less than 3 is irritating to gastro-oesophageal tissue. Ingestion of Fosamax(®) resulted in ALN being present in the stomach at a pH below 3 within minutes. EX101 minimised the possibility of exposing the oesophagus (in case of reflux) to acidified ALN.