Adverse Cosmetic Effects Research Articles

Topical 3% diclofenac in 2.5% hyaluronic acid gel: a review of its use in patients with actinic keratoses.

Topical 3% diclofenac in 2.5% hyaluronic acid (HA) gel (diclofenac HA gel; Solaraze) is an NSAID approved for the treatment of actinic keratoses (AK). The efficacy of diclofenac HA gel (0.5g applied twice daily to each 5cm x 5cm treatment area) in patients with AK has been evaluated in three randomized, double-blind, HA gel vehicle-controlled trials. In each trial, efficacy was assessed 30 days after the end of treatment because an earlier study revealed that resolution of lesions was greater when measured after a 4 week interval, rather than at the end of treatment. In two fully published multicenter trials, there was no difference in baseline characteristics of the study groups. In a further single center study (not yet published), patients randomized to diclofenac HA gel had a significantly higher mean number of target lesions at baseline compared with HA gel vehicle. In the two published studies, the efficacy of diclofenac HA gel increased with increased treatment duration. When compared with HA gel vehicle recipients, significant improvements in total lesion number scores (TLNS), cumulative lesion number scores (CLNS), patient global improvement indices (PGII) and investigator global improvement indices (IGII) were obtained in patients treated for 60 and 90 but not 30 days with diclofenac HA gel. Fifty percent of patients treated for 90 days with diclofenac HA gel (vs 20% in HA gel vehicle recipients) and 33% of those treated for 60 days (vs 10%) had TLNS and CLNS of zero at the end of follow-up. In the third trial, in which treatment was applied for 90 days, there was no statistically significant difference in the proportion of patients with TLNS or CLNS of zero at the end of follow-up. However, when controlling for the significant difference in mean baseline target lesion scores by calculating the mean change from baseline in lesion counts, TLNS and CLNS were significantly lower in recipients of diclofenac HA gel than HA gel vehicle at the end of follow-up. Pruritus was the most frequently reported adverse event in all trials and the incidence was generally similar or lower in patients treated with diclofenac HA gel than HA gel vehicle. In conclusion, diclofenac HA gel produces significant reductions in the number of AK lesions, and can produce complete clearance of lesions when applied twice daily for 60 or 90 days. The product is well tolerated and did not produce serious adverse cosmetic effects in clinical trials. Thus, diclofenac HA gel represents a useful addition to the array of pharmacologic treatments available for AK.

Strategies for optimizing immunosuppression in adolescent transplant recipients: a focus on liver transplantation.

Adolescence is a difficult time for transplant recipients; they must learn to take responsibility for their own behavior and medication, and to balance their developing sexuality in a body that has been transformed by the adverse effects of immunosuppression. More than 80% of children survive transplantation to adolescence and adulthood, thus long-term outcome and tailoring of immunosuppression is of great importance. To date, the most experience with long-term immunosuppression regimens is cyclosporine, which is well tolerated and effective. Long-term adverse effects include hypertension, nephrotoxicity, and post-transplant lymphoproliferative disease (PTLD). The recent development of tacrolimus has improved the cosmetic adverse effects related to cyclosporine, but has similar rates of hypertension and nephrotoxicity, and possibly a higher rate of PTLD. There has been a recent, welcome development in renal sparing drugs, such as mycophenolate mofetil, which has no cosmetic adverse effects, does not require drug level monitoring and is thus particularly attractive to teenagers. Recent surveys demonstrate recovery of renal function with mycophenolate mofetil, if started prior to irreversible renal dysfunction. There are currently little published data on the use of sirolimus (rapamycin) in the pediatric population, but preliminary studies suggest that the future use of interleukin-2 receptor antibodies may be beneficial for immediate post-transplant induction of immunosuppression. It is important when planning immunosuppression for adolescents to consider the effects of drug therapy on both males and females in order to maintain fertility and to ensure safety in pregnancy. Noncompliance is a problem in this age group, but adequate practical measures and support should reduce noncompliance, and allow good, long-term graft function.

Anti-Interleukin-2 Receptor Antibodies for the Prevention of Rejection in Pediatric Renal Transplant Patients

The anti-interleukin-2 receptor (anti-IL-2R) antibody therapy is an exciting approach to the prevention of acute rejection after renal allograft transplantation whereby immunosuppression is exerted by a selective and competitive inhibition of IL-2-induced T cell proliferation, a critical pathway of allorecognition. The anti-IL-2R antibodies specifically block the alpha-subunit of the IL-2R on activated T cells, and prevent T cell proliferation and activation of the effector arms of the immune system. The anti-IL-2R antibodies are used as induction therapy, immediately after renal transplantation, for prevention of acute cellular rejection in children and adults. During acute rejection, the IL-2Ralpha chain is no longer expressed on T cells; thus, the antibodies cannot be used to treat an existing acute rejection. Two anti-IL-2R monoclonal antibodies are currently in clinical use: daclizumab and basiliximab. In placebo-controlled phase III clinical trials in adults, daclizumab and basiliximab in combination with calcineurin inhibitor-based immunosuppression, significantly reduced the incidence of acute rejection and corticosteroid-resistant acute rejection without increasing the risk of infectious or malignant complications, and neither antibody was associated with the cytokine-release syndrome. Children who receive calcineurin inhibitors and corticosteroids for maintenance immunosuppression, as well as children who receive augmented immunosuppression to treat acute rejection, are at increased risk of growth impairment, hypertension, hyperlipidemia, lymphoproliferative disorders, diabetes mellitus, and cosmetic changes. In older children, the cosmetic adverse effects frequently reduce compliance with the treatment, and subsequently increase the risk of allograft loss. Being effective and well tolerated in children, the anti-IL-2R antibodies reduce the need for calcineurin inhibitors while maintaining the overall efficacy of the regimen; thus, the anti-IL-2R antibodies increase the safety margin (less toxicity, fewer adverse effects) of the baseline immunosuppression. Secondly, the anti-IL-2R antibodies decrease the need for corticosteroids and muromonab CD3 (OKT3) in children as a result of decreased incidence of acute rejection. The recommended pediatric dose of daclizumab is 1 mg/kg intravenously every 14 days for five doses, with the first dose administered within 24 hours pre-transplantation. This administration regimen maintains daclizumab levels necessary to completely saturate the IL-2Ralpha (5-10 microg/mL) in children for at least 12 weeks.The recommended pediatric dose of basiliximab for recipients <35 kg is 10 mg, and 20 mg for recipients > or =35 kg, intravenously on days 0 and 4 post-transplantation. This administration regimen maintains basiliximab levels necessary to completely saturate the IL-2Ralpha (>0.2 microg/mL) in children for at least 3 weeks.

Mascaras may cause irritant contact dermatitis

The majority of adverse effects of cosmetics have been attributed to soaps in Dutch and English studies, but to eye makeup in a recent Swedish study. The reactions may be caused by irritants or by sensitizing substances. The aim of the present study was to evaluate the irritation potential of commercially available mascaras. The mascaras were exposed to the skin in aluminium chambers. The skin reaction was evaluated using both visual assessments of erythema and non-invasive measurements of the skin reaction. Seven mascaras were tested on 15 healthy individuals in a randomized and blinded fashion. Two of the seven tested mascaras induced pronounced skin inflammation, when applied to normal skin under occlusion. These two mascaras were based on volatile petroleum distillate, in contrast to the other five mascaras that were conventional emulsions with stearate as the main emulsifier. The findings suggest that solvent-based mascaras might induce contact dermatitis due to its content of irritating substances.

Book Review: Women's Dermatology: From Infancy to Maturity

The concept of a textbook devoted to dermatology in females is at first thought rather odd. Isn't skin more or less the same in males and females? Dr Parish and his co-editors argue that gender differences in dermatology have been largely neglected to date and their book is an attempt to explore the ‘differences that entitle girls and women to gender-specific health care measures’. The work offers historical aspects, multicultural views plus detailed descriptions of dermatological conditions; and, reflecting the predominantly American authorship, it gives much space to cosmetic body-beautiful issues. Some chapters achieve the woman-oriented approach better than others. The nail chapter by Baran and the chapter on pregnancy dermatoses by Vaughan Jones hit the mark exactly. The historical section gives a fascinating insight into women's attempts to retain youthful beauty through the centuries. The taste for pallor, which continued into the twentieth century, resulted in use of toxic whitening pastes of brimstone, white lead and mercury that cracked terribly when the hapless wearer forgot not to smile. Milk, ground bones and even blood from birds were applied to the skin. Many women suffered terribly from smallpox scars. (Queen Elizabeth I survived smallpox unscathed because she did not follow the practice of the time in lancing the spots; instead she treated them by the Arabic method of applying red cloths and filling the bed chamber with red objects.) A large cosmetics section explains the science behind the formulations of cosmetics, including the differences in the four types of facial foundation creams—oil-based, water-based, oil-free and water-free. Oil-free facial foundations contain no animal, vegetable or mineral oils but do contain other oily substances such as silicones. These non-comedogenic foundations will be of interest to acne sufferers and people with oily skins. The adverse effects of cosmetics, including contact dermatitis (both irritant and allergic), are highlighted. A particular hazard is bacterial contamination of eyeliner and mascara, which can cause devastating Pseudomonas eye infections; we probably should all check our cosmetic drawer and throw out any products more than three months old. Another large section is devoted purely to cellulite and will have the female readership leaping to the bathroom mirrors to do the pinch test. A ‘quilted’ or ‘mattress’ appearance of the skin when pinched or at rest is due to the presence of fibrous retinacula that connect skin and fascia between the fat lobes. In addition, prominent follicular openings may result in an orange peel appearance. The mainstay of treatment remains weight loss, and the authors conclude, as many doctors will have long suspected, that topical creams and systemic drugs have no effect. There do, however, seem to be some benefits from lymphatic massage, and we read of a new operation of subcision where the fibrous retinacula are sectioned. These cosmetic items sit uncomfortably with chapters on the special problems of African, Indian, Korean and expatriate women. For many such women more pressing matters than cellulite are the hope of a normal life-span, enough food to eat and the privilege of not losing one's children in childbirth or in infancy. The contributors discuss differences in skin type between races and how these considerations may affect treatment. For instance, it could be inappropriate to suggest daily hair-washing to an African woman with scalp psoriasis since her hair might not cope. African hair is structurally different from Caucasian hair and more prone to weathering (wear and tear cuticular damage). Cultural differences and practices are covered—for instance the traction alopecia from tight plaiting or braiding that gives severe permanent hair loss around the hair margins in African women, and the alopecia resulting from the practice of hotcombing in African-American women. Vulval dermatology should be prominent in a book of this sort and here I noted some omissions. For instance, there is no mention of vulval psoriasis or seborrhoeic dermatitis, both frequent diagnoses in the vulval clinic. After initial scepticism I ended up won over by this text. It could be of interest to gynaecologists and general practitioners as well as dermatologists. If you want straightforward descriptions of dermatological conditions a standard text will suffice. But, if you want a bit more insight into the special problems of women, to be entertained and to learn a little more of the history of beauty you will not be disappointed.

Bodyweight gain and anticonvulsants: a comparative review.

Bodyweight gain is a common and frequent undesirable effect associated with the use of anticonvulsant drugs. This has been observed for many years with valproic acid (sodium valproate) and carbamazepine, and also, more recently, with some of the newer anticonvulsants such as vigabatrin and gabapentin. Very often bodyweight gain in children, adolescents and adults with epilepsy taking such anticonvulsants results in cosmetic adverse effects. On the other hand, bodyweight gain is disturbing to general health, with a possible increase in the risk of diabetes mellitus or heart disease. Other potential adverse effects, such as the association of obesity with polycystic ovaries, have been reported with the use of valproic acid. Potential mechanisms of anticonvulsant-associated bodyweight gain are not yet clear and differ between drugs used. The involvement of lowered blood glucose level, which may stimulate eating through an effect on the hypothalamus, constitutes one of the possible mechanisms. Lowered blood glucose levels may result from a competition between the binding of the drug and long chain fatty acids. An increased availability of the latter stimulates insulin production and lowers the serum glucose levels. Another possible explanation for lowered blood glucose may be a deficiency in carnitine directly caused by the drug, that would result in a reduction of fatty acid metabolism and an increase in glucose consumption. An enhancing effect of gamma-aminobutyric acid-mediated neurotransmission may increase appetite for carbohydrates and reduce energy expenditure. An antidiuretic hormone-like effect or effects on norepinephrine (noradrenaline) or serotonin-mediated neurotransmission are more rarely considered. Many studies on anticonvulsant-associated bodyweight gain illustrate how we could better define the risk factors for the development of anticonvulsant-induced bodyweight gain and uncover the mechanisms behind it.

Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC). However, some patients show an incomplete response to UDCA therapy. Treatment with corticosteroids may be of benefit although at the expense of systemic side effects. Budesonide, a corticosteroid with an extensive first-pass hepatic metabolism appeared promising for the treatment of PBC. The aim of this study was to evaluate the safety and estimate the efficacy of budesonide in patients with PBC, who have shown a suboptimal response to UDCA. Twenty-two patients with PBC, 16 women, median age of 50 who had been on UDCA (13-15 mg/kg/d) for a mean of 46 months (range 6-108 months) and had shown a persistent elevation of alkaline phosphatase activity at least 2 times the upper limit of normal were enrolled. Oral budesonide, 9 mg daily was administered for 1 year and patients continued on the same dosage of UDCA. There was a significant, but transitory improvement in serum levels of total bilirubin (P =.001) and a significant, but marginal improvement in serum alkaline phsophatase (P =.001) with combination therapy. The Mayo risk score increased significantly (P =.02) and there was a significant loss of bone mass (P <.001) of the lumbar spine. Budesonide-induced hyperglycemia and cosmetic adverse effects were noted in 2 patients. In conclusion, oral budesonide appears to add minimal, if any, additional benefit to UDCA, and it is associated with a significant worsening of osteoporosis in patients with PBC.

New Immunosuppressive Agents for Maintenance Therapy in Organ Transplantation

Traditional cyclosporin-based immunosuppressive protocols are associated with relatively high incidences of early acute rejection and late graft loss due to chronic rejection. In addition, long-term immunosuppression with cyclosporin and corticosteroids has been associated with significant metabolic, infectious, malignant and cosmetic adverse effects. In the last decade, the goals of immunosuppression strategies have included not only short-term survival but also graft acceptance, with a low incidence of early acute rejection and minimal long-term toxicity. Tacrolimus and mycophenolate mofetil are 2 new immunosuppressive agents that have recently been approved for use. The mechanism of action and toxicity profile of tacrolimus are similar to that of cyclosporin. Tacrolimus reduces early acute rejection and is also effective in salvage of allografts with refractory rejection. A wide spectrum of adverse effects, including nephrotoxic, neurotoxic, gastrointestinal, metabolic and hematological effects, has been reported in association with tacrolimus but, unlike cyclosporin, this agent is not associated with hirsutism or gingival hyperplasia. Mycophenolate mofetil, an antimetabolite, has been effective in reducing early acute rejection and in treatment of refractory rejection when used in combination with cyclosporin instead of azathioprine. Its myelosuppressive and gastrointestinal toxicities are mild and reversible, but it may be associated with an increased risk of infections. Both agents permit early corticosteroid withdrawal. Other new immunosuppressive agents that act on different stages of the cell cycle but that have not yet been introduced for wide clinical use, including sirolimus (rapamycin), brequinar, mizoribine and gusperimus, are also discussed in this review.

A comparative review of the adverse effects of anticonvulsants in children with epilepsy.

Phenobarbital (phenobarbitone) and phenytoin are the most useful anticonvulsants in neonates because adverse effects are most readily reversed when these drugs are used. Most anticonvulsants are very rarely associated with haematological adverse effects. Platelet function is particularly vulnerable to valproic acid (sodium valproate) therapy. Barbiturates and phenytoin can precipitate metabolic bone disease. Although very infrequent, lymphadenopathy is most common with phenytoin, and lupus-like illnesses with ethosuximide. Valproic acid may precipitate underlying metabolic disorders. Nephrolithiasis can occur with topiramate. Liver disease is most likely with felbamate or valproic acid, but can occur with other anticonvulsants. Valproic acid and ethosuximide are the main precipitants of gastrointestinal symptomatology; while valproic acid and vigabatrin are frequently associated with excessive bodyweight gain. Rash is most likely to occur with barbiturates, but there is a high risk of this adverse effect if large doses of lamotrigine are given with valproic acid. Adverse cosmetic effects are most likely with phenytoin, but valproic acid may cause alopecia. All anticonvulsants may cause unwanted neurological effects: when they occur, diplopia is usually precipitated by carbamazepine; tremor by valproic acid; and other motor disturbances are probably most common with phenytoin. Most anticonvulsants can cause drowsiness. Phenobarbital leads anticonvulsants as a cause of behavioural difficulties. Effects of anticonvulsants on cognitive function are difficult to assess, but subtle changes have been reported for all anticonvulsants in use up to the 1980s. Compared with other anticonvulsant drugs, phenytoin and felbamate are more often discontinued as a result of unwanted effects.

Adverse effects of cosmetics and toiletries reported to the Swedish Medical Products Agency 1989-1994.

In Sweden, a cosmetic control system was introduced in 1989 at the Medical Products Agency (MPA). It consists of a register of importers, manufacturers and their products, and a voluntary adverse reaction reporting system identical to that concerning drugs. Between 1989 and 1994, MPA evaluated 191 reports concerning adverse effects of 253 cosmetics and toiletries. 90% of the reports concerned women and the top-ranking product category was moisturizers, followed by hair care products and nail products. The majority of the adverse effects reported involved only the skin, and 90% were eczematous reactions. 70% of the eczemas were classified as contact allergic, as patch tests were positive to the product as is, and in 1/2 of these products, 1 or more relevant allergens could be identified when tests were made with individual cosmetic ingredients. The most common offending ingredients were fragrances, toluenesulfonamide-formaldehyde resin and preservatives. The number of reports is small in relation to the expected number of cosmetic adverse effects, which can be explained by under-reporting. Efforts are being made to persuade Swedish physicians to report more often.

Invasion and metastasis.

The invasive character of squamous cell carcinoma of the head and neck represents a major challenge to the clinician since most often these tumors require extensive surgical resection impairing important physiological functions including speech and swallowing. Additionally, in many cases costly reconstructive surgery is required to repair the adverse cosmetic effects of the resective surgery. Thus, there is an urgent need to understand the molecular mechanism(s) which underlie the local and regional spread of this disease. Since the ability of tumor cells to invade into surrounding structures requires hydrolytic action much effort has been spent on identifying the hydrolases involved in this process. Some of the enzymes which have been implicated in the spread of head and neck cancer include the urokinase-type plasminogen activator and several members of the collagenase family such as type I and IV collagenases and the stromelysins synthesized either by the tumor cells or in the surrounding fibroblasts. More recent studies have addressed the mechanism(s) by which these hydrolases are overexpressed in invasive cancer. In the tumor cells themselves, work has focused on defining the transcriptional requirements for enzyme synthesis and addressing how the appropriate transcription factors are activated by signal transduction pathways. In contrast, where the hydrolases (e.g. stromelysin-2 and stromelysin-3) are produced by the fibroblasts, current investigations are directed at identifying tumor-derived growth factors which lead to the inducible expression of the enzymes in the stromal cells. The ultimate goal of these studies is to develop novel therapeutic interventions which decrease the invasive capacity of head and neck cancer leading to longer survival times and enhanced quality of life for patients afflicted with this disease.

Adverse effects of cosmetics and toiletries: a retrospective study in the general population

Synopsis Of 1609 individuals who were interviewed and asked whether they had experienced adverse reactions to cosmetics or toiletry products in the preceding 5 years, 196 (12.2%) claimed to have experienced some such reaction. Females (n= 124) mostly attributed their complaints to soap (41%), facial creams (33%), deodorant (25%), shampoo (16%) and eye shadow (11%). Men (n= 72) complained about adverse effects from soap (49%), aftershave (22%), deodorant (19%) and shower foam (12%). Both in women and in men, most reactions were localized on the face (60% resp. 33%), followed by the hands (19% resp. 21%) and the axillae (18% resp. 14%). The majority of patients could solve the problem by stopping the use of the suspected product and purchasing a different brand. Nevertheless, medical consultation was sought by more than 30% of all patients. Presumably, the majority of all adverse effects were caused by irritation; contact allergic reactions are infrequent.