Dermatotoxicologic clinical solutions: clinical management of fragrance mix #1 #2 patients?

Today’s fragrances are present in more than just perfumes, having become ubiquitous in skin care products such as creams, shampoos, sun tan lotion and deodorants. While aromatics can arouse the senses, aromatic compounds applied to skin can also cause allergic contact dermatitis. This article describes diagnosis, limitations of patch testing for fragrance mix 1 and fragrance mix 2, the relevance of fragrance concentration in products, use testing of common consumer products and our current recommendations in regards to the management of fragrance contact allergy.     

Dermatotoxicology of sulfur mustard: Historical perspectives from World War I

Sulfur mustard has been used as a chemical warfare agent for the past century. After its introduction by the Germans in World War I, investigators quickly began studying its impact on the human body including its deleterious effects on skin. This review focuses on two groups in particular who conducted experiments from 1917 to 1918: the United States Army at the American University Experiment Station Laboratories and Torald Sollmann at Western Reserve University. Through this work, these researchers proved far ahead of their time by anticipating dermatologic phenomena not described in the literature until later in the twentieth century. These include regional variation of percutaneous penetration, effect of vehicle on penetration and predicting immunologic contact urticaria. The work conducted by these researchers set the groundwork for much of twentieth century dermatotoxicology.     

Cutaneous adverse reactions linked to targeted anticancer therapies bortezomib and lenalidomide for multiple myeloma: new drugs,old side effects

Context: Cutaneous toxicity is a frequent side effect of new anticancer targeted therapies. Skin reactions can severely impact the patient’s physical, psychological and social well-being and may sometimes lead to discontinuations either treatment dose reductions.

Objective: This study evaluates the impact of cutaneous adverse drug reactions (cADR) of the new therapies bortezomib and lenalidomide and presents a review of their skin side effects.

Materials and method: Type, frequency, severity, time of onset and management of cADR were collected and the medical records of all multiple myeloma patients receiving bortezomib or lenalidomide in the Hematology and Medical Oncology Institute of the University of Bologna, were analyzed.

Results: A total of 17 cADR occurred in 10 patients of 17 (58.8% of patients) treated with bortezomib: 5 rashes, 3 events of pruriginous rash, 1 purpuric rash, 2 records of mouth swelling, 1 stomatitis-mucositis, 3 cases of edema in the lower limbs, 1 patient referred pruritus and another telogen effluvium. Eight skin manifestations were due to lenalidomide in 7 patients of 25 treated (28%): 2 pruriginous rashes, 3 cases of edema, 2 records of pruritus, 1 case of stomatitis-mucositis. Three adverse events linked to bortezomib and 4 to lenalidomide forced to a complete withdrawal of the drug, while 3 reactions due to bortezomib mandated a dose reduction. Dermatological evaluation was performed only in 2 patients treated with bortezomib and 1 with lenalidomide.

Discussion: Evaluations of cADR due to bortezomib and lenalidomide were performed. There are no other reports focused on skin events in patients treated with the triple regimen velcade (bortezomib)-thalidomide-dexamethasone (VTD) up to date. Our study suggests that cutaneous toxicities, when researched by Dermatologists, are a side effect even more frequent than the reported data.

Limitations: As it is a single institute and retrospective study, ongoing cADR were rarely evaluated by dermatologists; thus, it is possible that cutaneous reactions (especially mild) may have been under reported by Hematologists and Oncologists in clinical records.

Conclusions: Even with the development of new drugs for cancer treatment, “old” cutaneous side effects may still be present, compromising patients’ quality of life. Physicians prescribing bortezomib and lenalidomide should monitor their patients for the spectrum of cADR, and they should involve dermatologists in consultations and management of these events. A multidisciplinar approach is necessary to oncologic patient in order to provide a tailored supportive clinical care.     

Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial

Background and aims  The perioperative use of a single course adjuvant portal vein infusion chemotherapy in patients with potentially curable colorectal cancer has been shown to significantly improve overall survival but did not reduce the occurrence of liver metastases (SAKK 40/81) [Swiss Group for Clinical Cancer Research (SAKK) Lancet 345(8946):349–353, 1995]. The objective of the present prospective, three-arm randomized multicenter trial was to assess whether peripheral venous administration of adjuvant chemotherapy regimen based on 5-fluorouracil (5-FU) and mitomycin C decreases the occurrence of liver metastases as well as prolongs disease-free and overall survival. Materials and methods  Stages I–III colorectal cancer patients (n = 753) were randomized to receive either surgery alone (control arm), surgery plus postoperative portal venous infusion of 5-FU 500 mg/m² plus heparin given for 24 hours for seven consecutive days plus mitomycin C 10 mg/m² given on the first day (arm 2), or surgery and the same chemotherapy regimen administered by peripheral venous route (arm 3). Results  The 5-year disease-free survival for the three treatment groups were 65% (control group), 60% (portal vein infusion, hazard ratio 1.18, p = 0.23), and 64% (intravenous infusion, hazard ratio 1.04, p = 0.76); the 5-year overall survival was 72% (control group), 69% (portal vein infusion, hazard ratio 1.21, p = 0.2), and 74% (intravenous infusion, hazard ratio 1.03, p = 0.86), respectively. A significant accumulation of early deaths were observed in the portal vein infusion group (p = 0.015). Conclusions  The present prospective randomized multicenter trial provides compelling evidence that short-term perioperative chemotherapy does not improve disease-free and overall survival in patients with potentially curative colorectal cancer. In contrary, the chemotherapy regimen administered in the present investigation seems to have potentially harmful effects, a finding which should be carefully considered in the planning of future trials. Postoperative short-term administration of 5-FU plus mitomycin C either through portal infusion or a central venous catheter is not recommended for routine use in patients with potentially curable colorectal cancer. M. Lorenz deceased.     

Comparative antibacterial efficacy of a 2-minute surgical scrub with chlorhexidine gluconate, povidone-iodine, and chloroxylenol sponge-brushes

Chlorhexidine gluconate (Hibiclens), povidone-iodine (E-Z Scrub 201), and chloroxylenol (ParaSoft) sponge-brushes were compared for antibacterial efficacy in 2-minute surgical scrubs. Thirty-nine volunteers completed a 7-day baseline period and a 5-day treatment period. Thirteen participants were assigned to a chlorhexidine group, 12 to a povidone-iodine group, and 14 to a chloroxylenol group. Subjects followed a standardized protocol, performing 11 scrubs during the treatment period. Bacterial counts were taken by the glove-juice procedure immediately after scrubbing and at 3 and 6 hours later on days 1, 2, and 5. The use of chlorhexidine achieved significantly (p less than 0.01) greater adjusted mean log10 bacterial count reductions than did povidone-iodine and chloroxylenol at all sampling times, with greater reductions as the study progressed.     

Restriction of bacterial growth under commercial catheter dressings

The effect on the normal cutaneous flora after iodine and alcohol disinfection of the skin of three commercially available moisture-permeable polyurethane dressings was compared with that of a gauze-and-tape dressing. Dressings also were evaluated clinically for membrane adhesion and skin erythema, pruritis, hyperpigmentation, vesiculitis, and tenderness. Each of 50 healthy volunteers and 49 long-term inpatients, 25 of whom were receiving antibiotic therapy, received simultaneously on their volar forearm patches of Op-Site, Tegaderm, Uniflex, and gauze dressings. Controls consisted of one exposed skin site and one covered with moisture-retaining vinylidene film (Saran Wrap). Although after 3 days of adhesion, commercial dressings prevented indigenous flora from returning to normal population densities, no significant quantitative differences were found between them and the gauze-and-tape dressing. Generally, all clinical dressings maintained normal flora at one tenth the population of the uncovered site; the Saran Wrap control supported 100-fold more bacteria than the exposed site. No differences were discovered in the levels of gram-negative bacteria, or among patient groups and between patients and healthy subjects, except for the lower incidence of erythema and itching among patients compared with healthy subjects.     

Multiple sclerosis: serial study of gadolinium-enhanced MR imaging

Thirteen patients with definite multiple sclerosis (MS), studied 16-24 months previously with magnetic resonance (MR) imaging with and without enhancement by intravenously administered gadolinium diethylenetriaminepentaacetic acid (DTPA) dimeglumine, were reexamined with a similar protocol. Assessment of enhancement and clinical activity in both studies revealed that enhancement was observed in 13 of 14 cases in which clinical activity had changed within 4 weeks of the study and thus appeared more sensitive than clinical examination in determining active disease. The 3-minute postinjection, short repetition time image (TR) was the most efficient for depicting enhancement. Enhancing lesions (active plaques) arose from previously hyper- or isointense regions on long TR images. Previously active lesions reverted to areas of iso- or hyperintensity on long TR images. Serial comparison of long TR images in this population reveals a decrease in high-intensity lesions on long TR images in some cases and an increase in others. The findings of high-intensity regions on long TR images and previously enhancing lesions both becoming isointense suggests that transient inflammatory changes with concomitant edema without demyelination and/or with significant remyelination may occur in some MS lesions. MS lesions are dynamic; both active and inactive lesions may show dramatic change on longitudinal MR imaging studies.     

Skin tolerability associated with transdermal drug delivery systems: an overview

As transdermal patches become more widely prescribed, it is important that clinicians understand: (a) the common causes of skin reactions with these medications; (b) how to minimize these reactions; and (c) how to manage the signs and symptoms. Here we review published data for skin reactions with patch medications approved within the past decade. Overall, the most common application site signs and symptoms appear to be localized redness (erythema) or itching, sometimes accompanied by swelling (edema). Typically, these are mild to moderate in severity, transient in nature, and occur in 20% to 50% of patients. Most are localized to the area of application, and resolve spontaneously within several days following patch removal. Discontinuations due to these types of event are infrequent, ranging from 1.7% to 6.8% in the 6-month trials reviewed here. Based on expert opinion, the majority of these skin reactions would be a form of irritant contact dermatitis, with infrequent cases of allergic contact dermatitis. These types of reactions usually cause minimal pain or discomfort to the patient, and are unlikely to be of medical concern. Signs and symptoms of irritant contact dermatitis may be minimized by rotation of the application site, careful removal of the patch, and appropriate use of moisturizers and topical corticosteroids. In conclusion, the potential advantages of transdermal patches usually outweigh any additional skin issues; however, further research into treatment and management strategies is required.