Cyclosporine regimens in plaque psoriasis: an overview with special emphasis on dose, duration, and old and new treatment approaches.

Cyclosporine A (CsA) is one of the most effective systemic drugs available for the treatment of psoriasis, as evidenced by the results of several randomized studies and by a prolonged experience in dermatological setting. In clinical practice, CsA is usually used for the induction of psoriasis remission at a daily dose included in the range of 2.5-5 mg/kg and with intermittent short-term regimens, lasting on average 3-6 months. The magnitude and rapidity of response are dose dependent, as well as the risk of development of adverse events. Therefore, the dose should be tailored to patient's needs and general characteristics and adjusted during the treatment course according to both the efficacy and tolerability. Some studies support the feasibility of pulse administration of CsA for a few days per week for both the induction and the maintenance of response in psoriasis patients. This paper will review the data on CsA regimens for plaque-type psoriasis and will focus the attention on dose, treatment duration, novel schedules, and role in combination therapies, including the association with biologicals.

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg·kg body weight-1·day-1) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin.

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg · kg body weight(-1) · day(-1)) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

Severe psoriasis treated with a new macrolide: everolimus.

Psoriasis is an immune-mediated disease with a chronic relapsing course, and the particularly severe forms that are refractory to traditional therapies are often difficult to manage. Everolimus (Certican; Novartis, Basel, Switzerland) is a new rapamycin-derived macrolide that is used in the prophylaxis of rejection in heart and kidney transplant patients. The mechanism underlying its immunosuppressant and antiproliferative activity is different from, but complementary to, that of calcineurin inhibitors such as ciclosporin. We describe a woman with severe psoriasis treated with everolimus combined with subtherapeutic doses of ciclosporin.

Relapses of onychomycosis after successful treatment with systemic antifungals: a three-year follow-up.

BACKGROUND: Data about relapses of onychomycosis after treatment with the new systemic antifungals vary among the different studies, with figures ranging from 3 to 20% for terbinafine and from 21 to 27% for itraconazole, depending on the follow-up duration. OBJECTIVE: To determine the prevalence of relapses of onychomycosis cured by terbinafine compared with that of onychomycosis cured by itraconazole. METHODS: We followed up 47 patients whose toenail onychomycosis had been mycologically cured in an open randomized study comparing intermittent itraconazole treatment with continuous terbinafine treatment and intermittent terbinafine therapy. Patients were examined every 3 months for up to 3 years after the end of therapy. At each visit clinical and mycologic (direct microscopy and cultures) evaluations were performed. RESULTS: Eight of the 36 patients (22.2%) who completed the study had a relapse of onychomycosis during the follow-up period, including 2 patients of the terbinafine 250 mg group, 2 patients of the terbinafine 500 mg group and 4 patients in the itraconazole 400 mg group. As the original infection, the relapse was caused in all cases by Trichophyton rubrum. CONCLUSIONS: This study shows that 22.2% of patients with onychomycosis successfully treated with systemic antifungals experienced a relapse. The relapse rate increased from 8. 3% at month 12 to 19.4% at month 24 and to 22.2% at month 36. Relapses were more common in patients treated with pulse itraconazole (4/11) than in patients treated with continuous (2/12) or intermittent (2/13) terbinafine. Statistical analysis did not reveal any significant difference between relapse rates in the three groups.

Refractory pulmonary aspergillosis: compassionate trial with terbinafine.

The frequency of bronchopulmonary aspergillosis is increasing due to the growing number of patients requiring steroids or other immunosuppressive therapies. Conventional treatments are ineffective in some patients and side-effects are an important issue. The aim of this work was to evaluate the effectiveness and safety of terbinafine, a new allylamine antimycotic drug, in three immunocompetent patients affected by lower respiratory tract aspergillosis [one chronic empyema due to Aspergillus fumigatus (AF) and two chronic necrotising aspergillosis] not responsive to the usual antimycotic therapies. In in vitro and animal model systems, terbinafine is as active as amphotericin B and itraconazole. Patients received terbinafine at doses ranging from 5 to 15 mg/kg per day, according to clinical status, for 3-5 months, depending on the clinical course of the disease and compliance. In patient 1 a negative anti-AF precipitin was obtained together with eradication of AF from the pleural cavity, which allowed a successful intrathoracic myo-omento-mammoplasty. In patients 2 and 3, AF was eradicated, anti-AF immunoprecipitins decreased, and clinical and radiological findings significantly improved. On the basis of the effectiveness of terbinafine demonstrated in this preliminary work, large studies to evaluate the use of terbinafine in bronchopulmonary aspergillosis are warranted. Moreover, the drug is not associated with resistance or significant side-effects.

Treatment of dermatophyte nail infections: an open randomized study comparing intermittent terbinafine therapy with continuous terbinafine treatment and intermittent itraconazole therapy.

BACKGROUND: terbinafine persists in the nail at effective concentrations for several weeks after discontinuation of treatment. OBJECTIVE: Our purpose was to verify whether intermittent terbinafine therapy is effective in dermatophytic onychomycosis and to compare the results of intermittent terbinafine with those of intermittent itraconazole and continuous terbinafine treatment. METHODS: An open, randomized study of 63 patients was performed with three treatment regimens: terbinafine, 250 mg daily (21 patients); terbinafine, 500 mg daily for 1 week every month (21 patients); or itraconazole, 400 mg daily for 1 week every month (21 patients). Treatment was continued for 4 months in toenail infections (60 patients) and 2 months in fingernail infections (3 patients). RESULTS: At the end of the follow-up period (6 months after discontinuation of treatment) 16 of the 17 patients (94.1%) with toenail onychomycosis were mycologically cured in the terbinafine 250 mg group, 16 of 20 (80%) in the terbinafine 500 mg group, and 15 of 20 (75%) in the itraconazole group. CONCLUSION: The percentage of patients who were mycologically cured was higher in the continuous terbinafine group than in the intermittent terbinafine and itraconazole groups, but statistical analysis did not reveal any significant difference between these cure rates.

Terbinafine in the treatment of non-immunocompromised compassionate cases of bronchopulmonary aspergillosis.

Conventional treatments of broncho-pulmonary aspergillosis are often ineffective and result in associated side-effects. Terbinafine (a new allylamine derivative), although as active against Aspergillus in vitro as amphotericin B and itraconazole, is less effective in rodent models because of a rapid hepatic first-pass effect. As terbinafine is metabolized differently in humans, the aim of this work was to evaluate this drug, for the first time, in the treatment of seven immunocompetent patients with lower respiratory tract mycotic infections unresponsive to the usual antimycotic drugs. Diagnosis was based on identification of fungal isolates, worsening of respiratory function tests, chest radiographs and computerized tomographic (CT) scan changes, positive skin test, aspergillin precipitins and clinical history. Terbinafine was administered at doses ranging from 5 to 15 mg kg-1 day-1 depending on the clinical severity of the disease, and was given for 90-270 days depending on clinical progress and compliance. In three patients A. fumigatus was suppressed with resolution of signs and symptoms; four patients showed transitory A. fumigatus suppression with marked clinical and radiological improvement. During relapses no resistance to terbinafine was observed. No significant side-effects were detected. Terbinafine appeared to be as effective as amphotericin B and itraconazole in the treatment of bronchopulmonary aspergillosis in nonimmunocompromised patients. These preliminary results suggest that controlled studies are warranted.

Clinical efficacy and tolerability of terbinafine in patients with pityriasis versicolor.

The antifungal efficacy and tolerability of 1% terbinafine cream vs. 1% bifonazole cream were assessed in a single blind randomized trial in patients with pityriasis versicolor. Terbinafine, a drug of the allylamines group, a new class of anti-mycotic agents, blocks sterol biosynthesis in the pathogen through inhibition of squalene epoxidase and consequent squalene accumulation, a primarily fungicidal process. Forty pityriasis versicolor patients, (18 M, 22 F; mean age 32.4 years; min. 16, max. 65), used 1% terbinafine cream or 1% bifonazole cream for a maximum of 4 weeks. All patients were followed-up weekly both clinically and mycologically. Clinical cures, defined as negativization of each clinical parameter, were recorded for 20 terbinafine patients (100%) and 19 bifonazole patients (95%), with routine microscopy and Wood's light tests both negative. By the 2nd week of treatment, 2 terbinafine patients were mycologically cured (10%). By the 3rd week, 14 terbinafine patients (70%) and 5 bifonazole patients (25%) were mycologically cured. The present controlled clinical trial consequently demonstrates that terbinafine is rapidly effective and well tolerated for treatment of pityriasis versicolor.

[Use of salmon calcitonin nasal spray in the prevention of corticosteroid-induced osteoporosis in bullous diseases]. / Uso della calcitonina di salmone spray nasale nella prevenzione dell'osteoporosi indotta da corticosteroidi nelle malattie bollose.

Osteoporosis becomes a common pathologic feature in patients given a long-term corticosteroid treatment: actually, bone formation proves decreased, and bone resorption increased. Said reduced bone formation is ascribable to an inhibited osteoblastic function: on the contrary, increased bone resorption may be ascribed to a suppressed intestinal calcium absorption with a consequent secondary increase in the parathyroid hormone secretion. The present trial had the purpose of assessing the BMC (Bone Mineral Content) in 10 patients with bullous diseases, such as pemphigus and pemphigoid, in the course of treatment with corticosteroid agents and nasal spray salmon calcitonin (sCT). The patients, 3 males and 7 females, mean age 62.9 years (min 33, max 93) were given intranasal sCT at the dosage regimen of 200 IU/day/6 months. No patients had previously received corticosteroid treatment. Six patients were given betamethasone, and 4 methylprednisolone, compared thereafter with hydrocortisone; the minimum dose was 70 mg and the maximum dose 400 mg. To evaluate the BMC, the patients were subjected to a single photon absorption densitometry (SPA). Distal radius determinations were reasonably related with the axial skeleton BMC. Determinations were carried out at the start of the trial, at the 3rd month as well as the end of treatment. At the start of the trial, the mean BMC was 0.765 (+/- SE 0.056) calculated at the radial distal end; at the 6th month of treatment the mean BMC resulted to be 0.847 (+/- SE 0.059). Actually, as reported by various investigators, BMC may attain an over 10% loss in the course of a corticosteroid treatment, an evidence that is not encountered in the case of an intranasal sCT administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[A thioridazine-dihydroergotoxine combination in the treatment of senile pruritus]. / Associazione tioridazina-diidroergotossina nel trattamento del prurito senile.

Senile itching, a peculiar clinical situation consisting of a cutaneous senile involution associated with a relevant neurogenic component, still keeps being a difficult therapeutic problem. For the purpose, a clinical trial, carried out with a combination of thioridazine and dihydroergotoxine on 19 patients carriers of the affection, could show a relevant decrease in all parameters assessed, ie itching, muscle tension and skin temperature measured by biofeedback. The combination also showed a good tolerance.

[Evaluation of the efficacy of a new antimycotic molecule for topical use: naftifine]. / Valutazione dell'efficacia di una nuova molecola antimicotica per uso topico: la naftifina.

The antifungal efficacy and tolerability of naftifine (cream, gel, 1% solution), were tested in an open, mycologically controlled study in 29 patients (mean age 32.7 +/- 2.8 years; 15 males, 14 females) with dermatomycosis caused by dermatophytes and yeasts. Particularly, 16 patients were affected with Tinea corporis; 11 patients by Pityriasis Versicolor and 2 other by cutaneous candidiasis. The mean treatment period was 32.9 days in a range from 1 to 44 days. Only one patient, with cutaneous candidiasis dropped out on the first day, because of a primary irritative dermatitis. All the remaining patients (96.4%) were recovered, and the severity of clinical symptoms, particularly erythema and itching, showed a very rapid decline. Two weeks after the treatment, a relapse emerged from a fungal growth culture, only in 2 patients (6.8%) affected with Microsporum canis. Local side effects, mostly burning, were recorded in 2 patients (6.8%).