FEBRUARY 2.003

                                              FEBRERO 2.003

Data-Medicos 
Dermagic/Express MEDermatology Journal
Febrero 2.003  February 2.003 
 

1.) Massive hepatocellular [correction of hepatocullular] necrosis: was it caused by Orlistat? XENICAL

Med Sci Law 2002 Oct;42(4):309-12

Lau G, Chan CL.

Health Sciences Authority, Centre for Forensic Medicine, Singapore, Republic of Singapore. [email protected]

Orlistat (tetrahydrolipostatin) is a lipase inhibitor which is used, in conjunction with appropriate dietary control, for the treatment of obesity. It is generally deemed to be a safe drug, which mainly exerts a topical action on the stomach and small bowel, with negligible systemic absorption and oral bioavailability. Consequently, its adverse effects have largely been limited to relatively mild gastrointestinal disorders.

However, there have been recent, published reports of non-fatal acute hepatitis and systemic hypertension associated with its use. The present case concerns a 62-year-old male who died from massive hepatocellular necrosis, consistent with drug-induced, fulminant hepatitis, associated with the use of oral orlistat, presumably administered at the recommended daily dose of 360 mg. It is postulated that this may represent a rare idiosyncratic reaction to the drug.

2.) Alefacept (Biogen). (Amevive ) PSORIASIS

Curr Opin Investig Drugs 2001 May;2(5):631-4

Bashir SJ, Maibach HI.

Department of Dermatology, University of California, San Francisco 94143-0989, USA. [email protected]

Alefacept (B-9273) is an LFA-3-Ig fusion protein CD2 antagonist under development by Biogen for the potential treatment of autoimmune diseases, including psoriasis and transplant rejection [270267]. It is in phase III trials for psoriasis [349467]. In October 2000, the company reported that Amevive was on track for regulatory filing in the second half of 2001 [385250], with a possible launch in the second half of 2002 [395628].

The company began a pivotal phase III trial in the US in December 1999, involving patients with chronic plaque psoriasis [349467]. A second phase III trial has also been initiated [362199], [374040]. Results from both trials are expected in mid-2001 [396544].

In April 2001, SalomonSmithBarney confirmed that a regulatory filing was expected in Europe and the US in the second half of 2001 and stated that alefacept would be critical to the future earnings growth of the company [407796]. In June 1999, Merrill Lynch estimated product launch in 2001 [327145], [344773]. Sales in 2001 and 2002 were anticipated to be US $20 million and US $100 million, respectively [327145].

3.) Medium-dose ultraviolet A1 therapy for pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica.

J Am Acad Dermatol 2002 Sep;47(3):410-4

Pinton PC, Capezzera R, Zane C, De Panfilis G.

Department of Dermatology, Azienda Spedali Civili di Brescia, Brescia, Italy.

BACKGROUND: Ultraviolet A1 (340-400 nm) was found to be effective in the treatment of cutaneous T-cell-mediated diseases.

OBJECTIVE: The purpose of the present study was to assess the efficacy of UVA1 phototherapy for pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC).

METHODS: Eight patients (3 with PLEVA and 5 with PLC) received 60 J/cm(2) UVA1 daily until remission. Four patients also had lesions inaccessible to UVA1 that were used as control lesions. Immunocytologic studies of skin infiltrates and circulating T cells were done.

RESULTS: Six patients showed complete clinical and histologic recovery. Two patients with PLC had a partial improvement. Unirradiated control lesions never improved. Serious short-term adverse effects were not encountered. No effects on circulating lymphocytes were reported.

CONCLUSION: UVA1 therapy is an effective and well-tolerated treatment for PLEVA and PLC. The therapeutic activity seems to be related to direct effects on cutaneous inflammatory infiltrates because the lesions in nonexposed cutaneous areas did not respond.


 
4.) Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated.

J Invest Dermatol 2002 Oct;119(4):876-87

Rappersberger K, Komar M, Ebelin ME, Scott G, Burtin P, Greig G, Kehren J, Chibout SD, Cordier A, Holter W, Richter L, Oberbauer R, Stuetz A, Wolff K.

Department of Dermatology, Division of General Dermatology, University of Vienna, A-1090 Vienna, Austria.

The ascomycin macrolactam pimecrolimus is a novel inflammatory cytokine release inhibitor that so far has not been administered systemically to humans. In this phase I/II randomized double-blind, placebo-controlled, multiple rising dose proof of concept study psoriasis patients were treated with oral pimecrolimus or placebo.

Gene profiling identified a common genomic profile with a downregulation of genes associated with inflammation but no changes in gene expression linked to drug-related side-effects. A steady state of pimecrolimus was reached after 5-10 d, Cmax, and area under the curve (0-24) was 54.5 ng per ml and 589.9 ng h per ml, respectively, at steady state at the highest dose.

There was clear clinical efficacy in patients receiving 20 mg pimecrolimus twice daily and 30 mg twice daily with a reduction of Psoriasis Area and Severity Index by 60% and 75%, respectively. Histopatho logically and immunopathologically there was a reversion of the psoriatic phenotype towards normal.

There were no notable clinical, laboratory, kidney function, or immunologic side-effects. We conclude that pimecrolimus taken orally is highly effective in a concentration-dependent manner in patients with psoriasis and on a short-term basis it is well tolerated and this is confirmed by its pharmacogenomic profile. The latter also indicates that pimecrolimus should be equally effective in other inflammatory skin diseases.
 

5.)  Risk of breast cancer in post-menopausal women using hormone replacement therapy.

J Med Assoc Thai 2002 May;85(5):583-9

Ratanawichitrasin A, Reansuwan W, Ratanawichitrasin S, Bhodhisuwan K, Kongpatanakul S.

Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

OBJECTIVE: To study the relationship of hormone replacement therapy (HRT) in post-menopausal women and risk of breast cancer.

PATIENTS AND METHOD: The authors conducted a case-control study comparing the proportion of HRT used between breast cancer and non-breast-cancer women. Cases were breast cancer patients who had natural menopause (excluded hysterectomy) and aged > or = 50-years-old from the Siriraj Breast Cancer database (1983-1996).

Controls were post-menopausal volunteers aged 50 year or older who visited Siriraj Hospital for other purposes such as elderly clinics, health check, etc. After informed consent, well-trained surgeons examined the women in the control group to exclude any potential breast cancer. Patient characteristics and risk factors were collected.

RESULTS: Of 1,913 patients in the database, 623 were included as the cases. Data from 679 volunteers were collected for controls from May to December 1999. Among 1,302 of the study population 58 women had ever used HRT (4.5%), which distributed to 3.2 per cent (20/623) in cases and 5.6 per cent (38/679) in controls.

From univariate analysis, age, age at menopause, number of children, habitat, education, contraceptive pills, familial history of breast cancer and HRT usage were associated with breast cancer (p-value<0.05). After multivariate forward stepwise logistic regression analysis, there was no association between HRT use and breast cancer (adjusted odds ratio (OR) = 0.61, 95% CI = 0.31-1.20). In subgroups analysis, women who had older age, higher education level, history of taking contraceptive pills, or positive familial history of breast cancer in second degree relatives had a decreased risk of breast cancer, while those living outside Bangkok had an increased risk.

CONCLUSION: Hormonal replacement therapy in post-menopausal women was not associated with increased risk of breast cancer.

6.) Safety and efficacy of an oral HIV vaccine (V-1 Immunitor) in AIDS patients at various stages of the disease.

HIV Clin Trials 2002 Jan-Feb;3(1):21-6

Jirathitikal V, Bourinbaiar AS.

Immunitor Corporation, Chachoengsao, Thailand, and Salang Bunnag Foundation, Bangkok, Thailand.

PURPOSE: To evaluate the safety and efficacy of an orally available, therapeutic HIV vaccine (V-1 Immunitor) in patients who were not treated with antiviral drugs.

METHOD: All entrants who had been tested at least once at entry and at postimmunization were considered for analysis. Main endpoints were vaccine safety and differential effects on CD4 and CD8 cell counts, plasma HIV RNA levels, and body weight change. Forty patients, 21 females (52%) and 19 males (48%), aged 22-65 years (mean/median age, 35/32 years) with a mean 225/mm3 CD4 cells at baseline were retrospectively analyzed. Patients self-administered two 850-mg pills containing inactivated HIV-1 antigens b.i.d. for 27 weeks (median, 24 weeks).

RESULTS: The treatment was well tolerated without significant adverse effects. The mean body weight gain was 2.2 kg (p =.0004). The mean increase in absolute CD4 and CD8 cells was 51 (18%; p =.0088) and 172 (16%; p =.0199) cells/mm3. Viral load was measured by polymerase chain reaction (PCR) in 8 individuals; although overall decrease did not reach standard cut-off statistical significance (Friedman p =.0588), the trend in reduction of viremia attributable to vaccine administration was highly significant (Spearman correlation test: r = 0.96, p =.0005).

CONCLUSION: Mucosal delivery of HIV antigens provides compelling results and deserves further evaluation in placebo-controlled clinical trials.

 
7.) [Valvular heart disease associated with benfluorex.] LIPASCOR-LIPAREX

Rev Esp Cardiol 2003 Feb;56(2):215-6

[Article in English, Spanish]

Rafel Ribera J, Casanas Munoz R, Anguera Ferrando N, Batalla Sahun N, Castro Cels A, Pujadas Capmany R.

Servicios de Cardiologia. Hospital del Sagrado Corazon. Barcelona. Espana.

We report the first case of valvular heart disease due to benfluorex. A 50-year-old woman who had been taking the anorectic agent benfluorex intermittently for one year developed severe fibrosis and regurgitation of the mitral, aortic and tricuspid valves. Clinical, echocardiographic and histopathological findings were analogous to those reported with fenfluramine and dexfenfluramine.

The similarity between the histopathological lesion documented in patients treated with the appetite suppressants fenfluramine, dexfenfluramine and benfluorex and the valvular lesions reported in valve disease associated with ergot alkaloid use and carcinoid heart disease suggest a common pathophysiological mechanism and a central role for serotonin in the development of the disease.

8.) Antidepressant-induced sexual dysfunction.

Ann Pharmacother 2002 Oct;36(10):1577-89

Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM.

The Lewin Group, Falls Church, VA 22042, USA.

OBJECTIVE: To review the evidence regarding antidepressant-induced sexual dysfunction and address implications for treatment strategy and health plan coverage policies for antidepressant medications.

DATA SOURCES: Primary articles were identified by a MEDLINE and HealthSTAR search to identify English-language studies published between January 1986 and July 2000. Search terms included sexual dysfunction or sexual function and antidepressants, fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, venlafaxine, nefazodone, bupropion, and mirtazapine. A cross-check of references cited in 10 published reviews yielded additional in-scope articles.

STUDY SELECTION AND DATA EXTRACTION: Approximately 200 articles were identified, including 8 randomized controlled trials and numerous open-label studies, case series, and case reports.

Of the randomized controlled trials, only 5 were designed to evaluate the incidence of sexual dysfunction associated with antidepressant treatment. Three additional randomized controlled trials included a structured assessment of sexual dysfunction within an efficacy trial. Data extraction excluded case reports, letters, and other limited study designs. A panel survey augmented published reports.

DATA SYNTHESIS: Sexual dysfunction is a relatively common adverse effect of many of the antidepressants in common use today. Rates of sexual dysfunction observed in clinical practice may be higher than those reported in the product information for several agents. Selective serotonin-reuptake inhibitors (SSRIs) appear to be the class of antidepressants most likely to cause sexual dysfunction.

Published studies suggest that between 30% and 60% of SSRI-treated patients may experience some form of treatment-induced sexual dysfunction. Bupropion and nefazodone appear to be much less likely to cause sexual dysfunction (<or=10% of patients). Mirtazapine also appears to be associated with a low rate of sexual adverse effects. Panel results largely reflect the consensus of the literature.

CONCLUSIONS: Sexual dysfunction is a common adverse effect of antidepressant treatment. Physicians should monitor their patients for antidepressant-induced sexual adverse effects, as these may affect compliance with therapy and ultimate treatment success. In addition to the consequences for patient health and well-being, managed-care organizations should be concerned with sexually related adverse effects of antidepressants, insofar as additional healthcare resources may be required to treat depressed patients in whom these adverse effects arise.

9.) [Chronic lupus erythematosus presenting as acneiform lesions]

Ann Dermatol Venereol 2002 Jun-Jul;129(6-7):883-5

[Article in French]

Deruelle-Khazaal R, Segard M, Cottencin-Charriere AC, Carotte-Lefebvre I, Thomas P.

Clinique dermatologique, Hopital Claude Huriez, CHRU, 59037 Lille Cedex, France. [email protected]

BACKGROUND: Cutaneous manifestations of lupus erythematosus are numerous but usually permit easy diagnosis. However, there are atypical lesions that can mimic benign dermatologic disorders. We report on a patient with lesions of acne leading to the diagnosis of chronic lupus erythematosus, and who subsequently developed systemic lupus erythematosus.

CASE REPORT: A 30-year-old woman presented with inflammatory lesions and comedos on the face. The eruption started after her last pregnancy and was refractory to local and general treatment. She also complained of arthralgia, Raynaud's phenomenon and diffuse alopecia.

Cutaneous biopsy was characteristic of chronic lupus erythematosus. Immunofluorescence microscopy of lesional skin showed a lupus band deposit. Antinuclear antibodies were highly positive. The patient was successfully treated with chloroquine. Three years later, the patient presented with photodistributed eruption. Antinuclear antibodies were still positive and in addition anticardiolipin antibodies were found. Final diagnosis was systemic lupus erythematosus.

DISCUSSION: Acneiform lesions are rarely reported in lupus erythematosus. Only three similar cases were reported in literature. Atypical and treatment-resistant eruptions should attract attention. Furthermore, the occurrence of systemic lupus in chronic lupus erythematosus is not an unfrequent phenomenon and the oestrogen-dependance of chronic lupus lesions may predict this association.


10.) [Thrombotic accidents induced by thalidomide: two cases]

Rev Med Interne 2002 Aug;23(8):724-7

[Article in French]

Gachon J, Grob JJ, Richard MA.

Service de dermatologie, hospital Sainte-Marguerite, CHU, 270, boulevard de Sainte-Marguerite, 13274 Marseille, France.

INTRODUCTION: First used as a sedative, thalidomide was taken out the market because of its teratogenicity. Despite other side effects, especially neuropathies, this drug is now again prescribed in various autoimmune and neoplasic diseases. Recently, venous or arterial thrombotic events have been described after the introduction of thalidomide.

EXEGESIS: In this report, we describe two new venous thrombosis cases occurring during a treatment with thalidomide. The first case is a 37-year-old man treated for a discoid lupus, who developed three deep-vein thrombosis and a massive pulmonary embolism, with recurrent thrombosis even with an efficient anticoagulation therapy until the final stop of thalidomide.

The second one is a 66-year-old woman treated with thalidomide for a multiple myeloma and a melanoma in therapeutic escape, who developed a deep-vein thrombosis two months after the beginning of her treatment.

Published reports suggest that most thrombotic events appeared under three months after the introduction of the treatment and that thalidomide could have acted as a precipitating or as a starting factor in a patient population already at risk of thrombosis. Those complications should be particularly severe, but the mechanism underlying thrombosis with thalidomide is unknown.

CONCLUSION: A complete coagulation check-up is advised before beginning a treatment with thalidomide.

================================================================== 
DATA-MÉDICOS/DERMAGIC-JOURNAL /FEBRUARY  2..003/ DR. JOSÉ LAPENTA  
==================================================================