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Ann Intern Med 2003 Feb 4;138(3):197-207
Division of Infections Diseases, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 448, Baltimore, MD 21287-0003, USA.
Because of shared routes of transmission, hepatitis C virus (HCV) infection is common in HIV-infected persons, who have been experiencing increasing HCV-related morbidity and mortality since the advent of effective antiretroviral therapy. Infection with HIV appears to adversely affect the outcome of hepatitis C, leading to increased viral persistence after acute infection, higher levels of viremia, and accelerated progression of HCV-related liver disease. In addition, hepatitis C may affect the course and management of HIV infection. The medical management of hepatitis C in HIV-infected persons is complicated by immune suppression, potential drug interactions and toxicities, and other forms of liver disease. In addition, there is little published experience with the safety and efficacy of the best available anti-HCV medications in HIV-infected persons. Thus, current efforts must be directed at preventing HCV and HIV infections and applying the principles learned in treating persons with either infection to manage those with both. Future efforts should include studies of the pathogenesis of HCV infection in HIV-infected persons and large, prospective studies that demonstrate the optimal management of persons co-infected with HIV and HCV. Such efforts will help to eliminate HCV-related liver disease as an emerging threat to HIV-infected persons.
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PMID: 12558359, UI: 22446193
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Ann Pharmacother 2002 Jun;36(6):1104
Bay Area Health Clinic/Bay Medical Center, Bay City, MI 48706-2160, USA. joship@pol.net
PMID: 12058705, UI: 22052218
Arch Dermatol 2003 Jan;139(1):85-6
PMID: 12533173, UI: 22421032
Arch Dermatol 2003 Jan;139(1):77-81
Department of Dermatology, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL, USA. CPAMD@worldnet.att.net
PMID: 12533171, UI: 22421030
Arch Dermatol 2003 Jan;139(1):39-43
Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, FL 33136, USA.
BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare, life-threatening condition caused by certain medications. Keratinocytes affected by TEN have been found to undergo apoptosis mediated by Fas-FasL interactions. Treatment with intravenous immunoglobulin (IVIG) has been proposed to inhibit this interaction. OBJECTIVE: To demonstrate the effectiveness of IVIG therapy in reducing mortality in patients with TEN. DESIGN: A retrospective analysis of 16 consecutive patients with TEN who were treated with IVIG. The SCORTEN system, a validated predictor of TEN mortality, was used to analyze the data of these patients. Using SCORTEN, we compared the predicted mortality of our patient population with observed mortality. SETTING: Dermatology inpatient unit at a university-affiliated hospital. INTERVENTION: All 16 patients received IVIG treatment daily for 4 days. Fifteen patients received 1 g/kg per day and 1 patient received 0.4 g/kg per day. MAIN OUTCOME MEASURES: For each patient, causes of TEN and other medical problems were documented prior to IVIG therapy, as were the 7 independent SCORTEN risk factors. RESULTS: One patient died. Based on the SCORTEN system, 5.81 patients were expected to die. These mortality rates were compared using the standardized mortality ratio (SMR) analysis ([Sigma observed deaths/Sigma expected deaths] x 100) to determine the efficacy of this treatment, which showed that patients with TEN treated with IVIG were 83% less likely to die than those not treated with IVIG (SMR = 0.17; 95% confidence interval, 0.0-0.96). CONCLUSION: Based on comparison of our observed mortality rate with the SCORTEN-predicted mortality rate, treatment with IVIG significantly decreased mortality in patients with TEN.
PMID: 12533162, UI: 22421021
Arch Dermatol 2003 Jan;139(1):33-6
Department of Dermatology, Hopital Henri Mondor, Creteil, France. bachot.nicolas@wanadoo.fr
BACKGROUND: It has been proposed that Fas-Fas ligand interaction was responsible for the apoptosis of epidermal cells in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and that high doses of intravenous immunoglobulin (IVIG) could help patients by blocking the apoptosis. OBJECTIVE: To study the effects of IVIG on SJS and TEN. DESIGN: Prospective open trial. SETTING: Referral center of a university hospital. PATIENTS: Thirty-four consecutive patients admitted for SJS (n = 9), SJS-TEN (n = 5), or TEN (n = 20) a mean of 4.3 days after onset. INTERVENTION: A dose of 2 g/kg of IVIG was administered within 2 days (half doses or full doses over a longer period for patients with low creatinine clearance). MAIN OUTCOME MEASURES: Detached plus detachable proportions of the total body surface area measured before and after treatment and predicted death rate estimated on admission with a validated prognostic score. RESULTS: Epidermal detachment involved a mean +/- SD 19% +/- 16% of the total body surface area on admission and 32% +/- 26% after IVIG treatment (progression in 22 of 34 cases, including most patients referred early). The prognostic score predicted 8.2 deaths (24%); 11 were observed (32%; 95% confidence interval, 17%-51%). Most deaths occurred in elderly patients who had initially impaired renal function. CONCLUSIONS: The confidence interval of the observed death rate excludes a dramatic decrease in mortality. No measurable effect was observed on the progression of detachment or on the speed of reepidermalization. These results do not support the routine use of IVIG treatment for patients with SJS or TEN, especially in cases of impaired renal function.
PMID: 12533161, UI: 22421020
Arch Dermatol 2003 Jan;139(1):26-32
Department of Dermatology, Geneva University Medical School, Switzerland.
OBJECTIVE: To evaluate the effect of high-dose intravenous immunoglobulin (IVIG) in toxic epidermal necrolysis (TEN), parameters that may affect response to treatment, and the effect of different IVIG batches on Fas-mediated cell death. DESIGN: Multicenter retrospective analysis of 48 consecutive TEN patients treated with IVIG. SETTING: Fourteen university hospital dermatology centers in Europe and the United States. PATIENTS: Forty-eight patients with TEN (skin detachment >10% of their body surface [mean, 44.8%; range, 10%-95%]). INTERVENTIONS: Infusion of IVIG in all patients (range, 0.8-5.8 g/kg), and analysis of the ability of different IVIG batches to inhibit Fas-mediated cell death. MAIN OUTCOME MEASURES: Objective response to IVIG treatment, final outcome at day 45, parameters that may affect response to IVIG treatment, and tolerance. RESULTS: Infusion of IVIG (mean total dose, 2.7 g/kg [range, 0.65-5.8 g/kg]; mean consecutive days, 4 [range, 1-5 days]) was associated with a rapid cessation (mean, 2.3 days [range, 1-6 days]) of skin and mucosal detachment in 43 patients (90%) and survival in 42 (88%). Patients who responded to IVIG had received treatment earlier in the course of disease and, on average, higher doses of IVIG. Furthermore, analysis of 35 IVIG batches revealed significant batch-to-batch variations in the capacity of IVIG to inhibit Fas-mediated cell death in vitro. CONCLUSIONS: Early infusion of high-dose IVIG is safe, well tolerated, and likely to be effective in improving the survival of patients with TEN. We recommend early treatment with IVIG at a total dose of 3 g/kg over 3 consecutive days (1 g/kg per day for 3 days).
PMID: 12533160, UI: 22421019
Br J Dermatol 2002 Dec;147(6):1279-80
PMID: 12452897, UI: 22340862
Br J Dermatol 2002 Dec;147(6):1270-2
PMID: 12452889, UI: 22340854
Br J Dermatol 2002 Dec;147(6):1265-7
PMID: 12452885, UI: 22340850
Br J Dermatol 2002 Dec;147(6):1227-36
Department of Dermatology, University Hospital Charite, Humboldt University, Schumannstrasse 20-21, D-10117 Berlin, Germany.
BACKGROUND: Imiquimod 5% cream has been investigated for non-surgical treatment of superficial and nodular basal cell carcinoma (BCC) tumours. OBJECTIVES: Two studies were conducted to examine the effect of occlusion at low dosing frequencies on the safety and efficacy of topical imiquimod 5% cream for the treatment of superficial and nodular BCC. PATIENTS AND METHODS: Both open-label studies were conducted in Europe. Patients diagnosed with BCC were enrolled into either the superficial (93 patients) or nodular (90 patients) study, depending on the histological confirmation of the patient's tumour subtype. Patients were randomized to one of four groups to apply imiquimod 5% cream 2 or 3 days per week either with or without occlusion. Six weeks following a 6-week treatment period, the entire target tumour area was excised and histologically examined for evidence of residual tumour. RESULTS: In both studies, the highest histologically complete response rate was seen in the 3 days per week with occlusion groups, with complete response rates of 87% and 65% for the superficial and nodular studies, respectively. Occlusion did not have a statistically significant effect on response rate at either dosing frequency. Response rates for superficial and nodular BCC tumours treated 3 days per week without occlusion were 76% and 50%, respectively. CONCLUSIONS: In the superficial study, the complete response rate of 87% in the 3 days per week with occlusion group was similar to that of daily and 5 days per week dosing without occlusion in a previous 12-week study and one study of daily dosing without occlusion for 6 weeks. All treatment groups had acceptable safety profiles in both studies. Occlusion did not have a statistically significant effect on efficacy for either superficial or nodular BCC tumours.
PMID: 12452875, UI: 22340840
Br J Dermatol 2002 Dec;147(6):1166-70
Department of Dermatology and Allergology, University Hospitals, Rheinisch-Westfalische Technische Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. Claudia.Renn@post.de
BACKGROUND: Teenagers and young adults frequently develop maculopapular exanthema following amoxicillin intake within infectious mononucleosis. The underlying pathomechanisms are still largely unknown. OBJECTIVES: To investigate whether amoxicillin-induced exanthema in florid infectious mononucleosis is a disease-associated phenomenon or results from specific sensitization to the drug. METHODS: Four patients with amoxicillin-induced exanthema within infectious mononucleosis were analysed in vivo by prick, intradermal and patch tests and in vitro by means of the lymphocyte transformation test (LTT) employing amoxicillin, ampicillin, benzylpenicillin and phenoxymethylpenicillin. RESULTS: Drug-specific sensitization to amoxicillin in the LTT was observed in three patients, two of whom showed a side-chain-specific sensitization to amoxicillin and ampicillin. The in vitro results were confirmed in vivo by skin tests. CONCLUSIONS: These data suggest that real sensitization to amoxicillin and ampicillin may occur within infectious mononucleosis and may be detected in vivo and in vitro by means of skin tests and the LTT.
PMID: 12452866, UI: 22340831
Br J Dermatol 2002 Dec;147(6):1142-6
Department of Dermatology-Phlebology, CHRU Montpellier, Hopital Saint-Eloi, 80 avenue Augustin Fliche, 34265 Montpellier cedex 5, France. o-dereure@chu-montpellier.fr
BACKGROUND: Cutaneous side-effects of treatment with interferon alfa or interferon alfa plus ribavirin in patients with hepatitis C have already been reported but they are mostly local with inflammation and, much less frequently, necrosis at the injection points. By contrast, very few data are available with regard to distant skin reactions, particularly inflammatory lesions on other parts of the body. OBJECTIVES: To assess the clinical and histological pattern of inflammatory skin lesions outside the injection points in patients treated with interferon alfa and ribavirin for chronic hepatitis C. METHODS: Twenty patients attending a University Hospital in Southern France (secondary referral centre) were evaluated regard to clinical history, type and localization of lesions, progression and histology. Skin testing was performed in some patients and the relevance of the results was evaluated. RESULTS: Eczema-like skin lesions were mainly distributed on the extremities, sometimes associated with photosensitivity. They usually occurred between 2 and 4 months of treatment. Histology was nonspecific, with a dermal, mainly perivascular, mononuclear infiltrate. Skin testing was poorly informative and was not predictive of relapse. Treatment had to be interrupted in half the patients, of whom two of three relapsed on resuming therapy. CONCLUSIONS: The incidence of inflammatory skin lesions at a distance from injection sites in patients treated with interferon alfa and ribavirin for chronic hepatitis C is currently unknown, but this adverse event must be taken into consideration as it may lead to the transient or definitive interruption of treatment.
PMID: 12452863, UI: 22340828