Off-label use of biologic agents in the treatment of dermatosis, part 2: etanercept, efalizumab, alefacept, rituximab, daclizumab, basiliximab, omalizumab, and cetuximab

In recent years, a series of new drugs have been developed through the application of molecular biology. These drugs act by blocking specific molecules of the immune system and have been developed to act on specific targets that play an important role in the pathophysiology of the diseases in which their therapeutic use has now been approved. Over time, experience has been accumulated in the use of these drugs in the treatment of skin diseases for which they have not been approved but in which the pathophysiology suggests that they could also be effective. The use of these drugs is increasing in difficult-to-treat cases of skin diseases for which the drugs are not approved. The second part of this review of off-label use of biologic agents in dermatology considers the use of etanercept, efalizumab, alefacept, rituximab, basiliximab, omalizumab, and cetuximab.     

Treatment of Paracoccidioidomycosis, Candidiasis, Chromomycosis, Lobomycosis, and Mycetoma with Ketoconazole

ABSTRACT: The authors present the use of ketoconazole in 27 cases of paracoccidioidomycosis, eight of mycetoma, seven of chromomycosis. four of systemic candidiasis and one of lobomycosis. The drug was administered orally in a dosage of 200 to 400 mg per day within a period of up to 90 days. The results of the treatment for paracoccidioidomycosis were of cicatrization of the cutaneous lesions in three to four weeks in 24 patients and in two, from six to seven weeks. Out of 27 patients, 14 presented pulmonary lesions. The evolution within a 90-day period showed radiological cure in one case, improvement in seven, and unaltered picture in five patients. In one there was no further control. In the three out of four cases of candidiasis there was clinical and mycological cure and in one case marked improvement. In seven cases of chromomycosis there was marked improvement in two moderate in four, and slight in one case. There was slight improvement in one case of lobomycosis, and in eight cases of mycetoma moderate improvement in three, slight in three and none in two, but the mycological examinations wore still positive. The drug tolerance was excellent.     

Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up

Vitiligo is an acquired pigmentary disorder of unknown etiology that is clinically characterized by the development of white macules related to the selective loss of melanocytes. The prevalence of the disease is around 1% in the United States and in Europe, but ranges from less than 0.1% to greater than 8% worldwide. A recorded predominance of women may reflect their greater willingness to express concern about cosmetically relevant issues. Half of all patients develop the disease before 20 years of age. Onset at an advanced age occurs but is unusual, and should raise concerns about associated diseases, such as thyroid dysfunction, rheumatoid arthritis, diabetes mellitus, and alopecia areata. Generalized vitiligo is the most common clinical presentation and often involves the face and acral regions. The course of the disease is unpredictable and the response to treatment varies. Depigmentation may be the source of severe psychological distress, diminished quality of life, and increased risk of psychiatric morbidity. Part I of this two-part series describes the clinical presentation, histopathologic findings, and various hypotheses for the pathogenesis of vitiligo based on past and current research.     

Typhus works of Rudolf Weigl,PhD, Ludwik Fleck,MD, and Eugeniusz Łazowski,MD, against the Nazis

Typhus has been present in Central Europe and Russia since the 19th century, but it was not until 1918 that it became an epidemic problem in Poland. Poverty, general devastation, unsanitary living conditions, and the extensive spread of the disease forced the Polish government to organize effective measures to improve the population's health. One such measure was the establishment of a typhus research center in Lviv. The center was led by Rudolf Weigl, who in the 1930s succeeded in elaborating a clinically effective vaccine. In September 1939, when the Germans invaded Poland, the problem of typhus returned, primarily due to the ghettos where the Nazis confined Jews in poor, crowded, and unsanitary conditions. Later, in 1941 when Nazis tried to invade the Soviet Union (where typhus was endemic), the typhus vaccine—the work of Weigl and Ludwik Fleck (also an employee of the Lviv institute)—was in high demand. The Germans feared typhus due to its persistence and speed of spread. The Nazi typhus phobia was also used by some Polish doctors who took advantage of this disease to protect their patients from being deported or located in camps. An example of such a doctor was Eugeniusz ?azowski, who even organized a "false pandemic" to save the local population.     

Association of auxotypes of Neisseria gonorrhoeae and susceptibility to penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam

Isolates of Neisseria gonorrhoeae from 304 patients attending a venereal disease clinic were examined by a plate dilution method for their susceptibility to six antibiotics: penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam. The isolates were also characterized by gonococcal auxotyping. The most frequent auxotypes were Nonrequiring, 58%; Pro-, 14%; Pro- Arg (Orn*) Ura-, 14%; Arg- Hyx- Ura-, 6%; and a miscellaneous group consisting of 8% of the isolates. If the entire group of isolates were examined, moxalactam was the most active of the antibiotics; 94% of the isolates were inhibited by less than or equal to 0.25 microgram/ml. The Pro- Arg (Orn*) Ura- isolates were relatively resistant to penicillin G and cefoxitin. The Arg- Hyx- Ura- group of isolates was the most susceptible of the auxotypes to all of the antibiotics except spectinomycin. The uncommon auxotype Arg (Orn*) Ura- has a requirement for arginine that is satisfied by citrulline but not by ornithine. The results of the present study indicate that the nutritional requirements of gonococci may be associated with their response to certain antibiotics.     

The Evaluation of the Impact of Age,Skin Tags,Metabolic Syndrome,Body Mass Index,and Smoking on Homocysteine,Endothelin-1, High-sensitive C-reactive Protein,and on the Heart

Background:

Skin tags (STs) are small, pedunculated skin-colored or brown papules that occur around any site where skin folds occur. The literature is short of comprehensive and controlled clinical studies aimed to evaluate the atherogenic risk factors in patients with STs.

Aim of Work:

The aim of this study is to evaluate the impact of age, STs, metabolic syndrome (METs), body mass index (BMI), and smoking on homocysteine (Hcy), endothelin-1 (ET-1), high-sensitive C-reactive protein (Hs-CRP), and on cardiovascular diseases.

Materials and Methods:

This study included 30 cardiac patients with STs, 30 non-cardiac patients with STs, and 30 healthy controls with neither heart disease nor STs. History of smoking, measurement of height, weight, BMI, waist circumference (WC), blood pressure, STs number, color, acanthosis nigricans, estimation of serum level of fasting glucose, triglycerides (TGs), cholesterol, high-dense lipoproteins (HDL), Hcy, ET-1, Hs-CRP, and the presence of the METs were elicited in the three groups.

Results:

Regarding the Hcy, ET-1, and Hs-CRP, the cardiac-STs group showed the highest levels and the control group showed the least (P < 0.001). The percents of patients with METs were 56.7% in the cardiac-STs, 40% in the non-cardiac-STs, and 0% in the control group (P < 0.001). Mean BMI exceeded the limit of obesity in the cardiac-STs group (30.9 ± 3.9) and the non-cardiac-STs group (32.6 ± 6) and was normal in the control group (24.7 ± 2.8). Hyperpigmented STs were present in 66.7% of the cardiac-STs group. Multivariate regression analysis for the independent effectors on Hcy level were the presence of STs (P < 0.001), METs (P = 0.001), and BMI (P = 0.024). Regarding ET-1, the effectors were the presence of STs and METs (P = 0.032). For Hs-CRP, effectors were the presence of STs (P < 0.001) and smoking (P = 0.040). Multivariate logistic regression of the predictors of cardiac disease showed that the independent predictors of the occurrence of cardiac disease were BMI (P < 0.001), STs (P = 0.002), and METs (P = 0.037).

Conclusion:

STs may act as a physical sign of underlying raised cardiac atherogenic factors. This may indicates an ongoing risk on coronary circulation which may indicate further corrective action, hopefully early enough. The association of ST with obesity and METs represents a Bermuda Triangle that act against the heart.     

Liquid injectable silicone: history,mechanism of action,indications, technique,and complications

Medical grade liquid injectable silicone can be used for soft tissue augmentation to correct and replace lost volumes of the subcutaneous tissue. It is potentially a permanent tissue augmentation agent and is the most effective filler for certain indications. This article presents the history, mechanism of action, indications and contraindications, technique, and the possible complications of silicone and their treatment.     

巨细胞病毒感染、包涵体形成与生精细胞凋亡及不育症

本文就巨细胞病毒感染的病原学、流行病学、传播途径、发病机制、细胞病变效应和包涵体侵入细胞过程进行了介绍.对血管内皮细胞脂质体的形成,多发性骨髓瘤浆细胞内包涵体类型,精液中生精细胞内检出的6种包涵体类型和形态特征进行了描述.由病毒感染对精子运动的影响和生精细胞凋亡与男性不育,进行报道.     

Effects of bepotastine, cetirizine, fexofenadine, and olopatadine on histamine-induced wheal-and flare-response, sedation, and psychomotor performance

Although many antihistamines are now in clinical use, few studies directly compare their pharmacodynamic and sedative activities in humans in vivo. We designed a double-blind, placebo-controlled, crossover study to compare the inhibitory effects of bepotastine, cetirizine, fexofenadine, and olopatadine on histamine-induced flare-and-wheal response. Systemic sedative effects and impaired psychomotor activities by these drugs were also evaluated. Bepotastine (10 mg twice a day), cetirizine (10 mg once a day), fexofenadine (60 mg twice a day), and olopatadine (5 mg twice a day) or placebo was given in a double-blind manner to seven healthy volunteers before histamine challenge by iontophoresis. At 0, 1, 2, 4, 8, 12, and 24 h following the oral administration of these drugs, histamine iontophoresis-induced wheal-and-flare response was measured. Sedative effects by the drugs were also evaluated by a visual analogue scale for subjective sedation, and by word processor test for psychomotor activity. Each volunteer was tested with all of the drugs (including placebo), administered in a random order with a washout period of at least 1 week. Histamine iontophoresis induced marked wheal-and-flare response in all participants. Bepotastine, cetirizine, fexofenadine, and olopatadine yielded significant reduction of histamine-induced wheal-and-flare response compared to placebo (P < 0.01). Among the drugs, olopatadine and cetirizine suppressed most markedly and persistently histamine-induced wheal-and-flare response, while bepotastine and fexofenadine produced a significant, but less persistent suppression. Olopatadine, fexofenadine, and cetirizine showed a significant systemic sedative effect in this order with bepotastine showing the least sedative effect. Moreover, olopatadine affected psychomotor performance most markedly, which was followed by fexofenadine and cetirizine. These results indicate that bepotastine, cetirizine, fexofenadine, and olopatadine inhibit histamine-induced wheal-and-flare response of humans in vivo and induce a variable systemic sedative effect and impaired psychomotor activity. Although olopatadine and cetirizine showed the strongest and most persistent suppression of histamine-induced wheal-and-flare response, olopatadine showed a considerable sedative effect with impaired psychomotor performance.     

Underdiagnosed and undertreated psoriasis: Nuances of treating psoriasis affecting the scalp,face, intertriginous areas,genitals, hands,feet, and nails

Psoriasis of the scalp, face, intertriginous areas, genitals, hands, feet, and nails is often underdiagnosed, and disease management can be challenging. Despite the small surface area commonly affected by psoriasis in these locations, patients have disproportionate levels of physical impairment and emotional distress. Limitations in current disease severity indices do not fully capture the impact of disease on a patient's quality of life, and, combined with limitations in current therapies, many patients do not receive proper or adequate care. In this review, we discuss the clinical manifestations of psoriasis in these less commonly diagnosed areas and its impact on patient quality of life. We also examine clinical studies evaluating the effectiveness of therapies on psoriasis in these regions. This article highlights the need to individualize treatment strategies for psoriasis based on the area of the body that is affected and the emerging role of biologic therapy in this regard.