Steps towards implementation of protocolized dose reduction of adalimumab, etanercept and ustekinumab for psoriasis in daily practice.

BACKGROUND: Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. OBJECTIVES: To evaluate the implementation of protocolized biologic DR in daily practice. METHODS: A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. RESULTS: The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. CONCLUSION: Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

Factors influencing current low-value follow-up care after basal cell carcinoma and suggested strategies for de-adoption: a qualitative study.

BACKGROUND: Providing follow-up to patients with low-risk basal cell carcinoma (BCC) can be considered as low-value care. However, dermatologists still provide substantial follow-up care to this patient group, for reasons not well understood. OBJECTIVES: To identify factors influencing current BCC follow-up practices among dermatologists and suggested strategies to de-adopt this low-value care. In addition, views of patients regarding follow-up care were explored. METHODS: A qualitative study was conducted consisting of 18 semistructured interviews with dermatologists and three focus groups with a total of 17 patients with low-risk BCC who had received dermatological care. The interviews focused on current follow-up practices, influencing factors and suggested strategies to de-adopt the follow-up care. The focus groups discussed preferred follow-up schedules and providers, as well as the content of follow-up. All (group) interviews were transcribed verbatim and analysed by two researchers using ATLAS.ti software. RESULTS: Factors influencing current follow-up care practices among dermatologists included complying with patients' preferences, lack of trust in general practitioners (GPs), financial incentives and force of habit. Patients reported varying needs regarding periodic follow-up visits, preferred to be seen by a dermatologist and indicated a need for improved information provision. Suggested strategies by dermatologists to de-adopt the low-value care encompassed educating patients with improved information, educating GPs to increase trust of dermatologists, realizing appropriate financial reimbursement and informing dermatologists about the low value of care. CONCLUSIONS: A mixture of factors appear to contribute to current follow-up practices after low-risk BCC. In order to de-adopt this low-value care, strategies should be aimed at dermatologists and GPs, and also patients.

Needs and preferences of patients regarding basal cell carcinoma and cutaneous squamous cell carcinoma care: a qualitative focus group study.

BACKGROUND: Despite the high and rising incidence rate of keratinocyte cancer (KC) and the importance of incorporating patient values into evidence-based care, few studies have focused on the perspectives of patients with KC. OBJECTIVES: To identify the needs and preferences of patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) regarding care. METHODS: A qualitative study was conducted consisting of three focus groups with patients with BCC and three focus groups with patients with SCC. In total 42 patients participated. In each focus group, the patients' needs and preferences regarding treatment and follow-up were discussed, using a predefined topic list. All sessions were transcribed verbatim and analysed by two researchers. RESULTS: The following needs and preferences were identified: (i) the need to receive all relevant, tailored information; (ii) a physician who takes you seriously and communicates well; (iii) a short waiting period and the best treatment with direct results; (iv) to be seen by the same physician; a preference for a dermatologist during (v) treatment and (vi) follow-up; (vii) a general need for structured follow-up care and (viii) a full-body skin examination during follow-up. Patients with BCC additionally expressed the need for openness and transparency and wanting to participate in shared decision making. CONCLUSIONS: It is advocated to organize skin cancer care that is better tailored to the needs of patients with KC, providing patient-centred care. This should include investing in the patient-physician relationship, and personalizing the type and form of information and the follow-up schedules. Adding the patient's perspective to current guidelines could facilitate this process.

Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening?

The association between human papillomavirus (HPV)-associated cervical cancer and cutaneous squamous cell carcinoma and codon 72 polymorphism in the p53 gene is not unequivocal. Especially, it is not known whether carriers of the arginine form have an increased risk of cancer that necessitates screening. The alternative is that the polymorphism is a tumor marker instead of a risk factor. We set out a case-control study to determine the risk of squamous cell carcinoma of the skin in individuals with the p53 codon 72 arginine genotype in order to establish the possible need for screening. The distribution of the different p53 codon 72 genotypes was examined in 86 subjects with a history of cutaneous squamous cell carcinoma and in 168 controls. Additionally, 121 subjects who had had histologically proven basal cell carcinoma and 108 subjects who had had non-familial malignant melanoma were tested. p53 polymorphism was evaluated by polymerase chain reaction (PCR) using DNA samples from peripheral blood lymphocytes. In a subgroup of patients with squamous cell carcinoma and controls, the presence of epidermodyplasia verruciformis human papillomavirus (EV-HPV) DNA was determined in plucked eyebrow hair. Differences in the distributions of the genotypes among cases and controls were calculated, and univariate and multivariate analyses were performed to assess the risk to develop cutaneous squamous cell carcinoma in the presence of the p53 codon 72 arginine genotype. Frequency distributions of the three different genotypes (homozygous for the arginine allele, heterozygous for the two alleles, and homozygous for the proline allele) were similar among the squamous cell carcinoma group and the control group: 47.1%, 46.0% and 6.9% versus 47.8%, 45.8% and 6.4%, respectively. Statistical analysis showed no significant differences between these groups. In patients with squamous cell carcinoma and controls who harbored EV-HPV DNA in their plucked eyebrow hair, similar results were obtained. The distributions of the p53 codon 72 genotypes in the basal cell carcinoma and malignant melanoma group were also not significantly different from the control group. p53 codon 72 arginine homozygosity does not appear to represent a significant risk factor for cutaneous squamous cell carcinoma and screening seems not to be indicated. Mol. Carcinog. 30:56-61, 2001.

Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair.

Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair and, independently of these, with cutaneous malignant melanoma. The association of MC1R gene variants with nonmelanoma skin cancer is largely unknown. A total of 838 subjects were included in the present study: 453 patients with nonmelanoma skin cancer and 385 subjects with no skin cancer. The coding sequence of the human MC1R gene was tested using single-stranded conformation polymorphism analysis followed by sequencing of unknown variants. Risk of skin cancer dependent on the various MC1R gene variants was estimated using the exposure odds ratio. We investigated whether subjects with MC1R variant alleles were at increased risk of developing nonmelanoma skin cancer and, if so, whether this increased risk was mediated by fair skin and red hair. A total of 27 MC1R gene variants were found. The number of carriers of one, two, or three MC1R gene variants was 379 (45.2%), 208 (24.8%), and 7 (0.9%), respectively. A strong association between MC1R gene variants and fair skin and red hair was established, especially the variants Arg151Cys and Arg160Trp (P < .0001). Carriers of two variant alleles were at increased risk for developing cutaneous squamous cell carcinoma (odds ratio 3.77; 95% confidence interval [CI] 2.11-6.78), nodular basal cell carcinoma (odds ratio 2.26; 95% CI 1.45-3.52), and superficial multifocal basal cell carcinoma (odds ratio 3.43; 95% CI 1.92-6.15), compared with carriers of two wild-type alleles. Carriers of one variant allele had half the risk. The highest relative risks of nonmelanoma skin cancer were found in carriers of the Asp84Glu, His260Pro, and Asp294His variant alleles, and the risk was only slightly lower for carriers of the Val60Leu, Val92Met, Arg142His, Arg151Cys, and Arg160Trp variant alleles. When subjects were stratified by skin type and hair color, analysis showed that these factors did not materially change the relative risks. These findings indicate that MC1R gene variants are important independent risk factors for nonmelanoma skin cancer.

Relation between smoking and skin cancer.

PURPOSE: Tobacco smoking is a risk factor for several cancers. The risk of cutaneous malignancies related to smoking, however, is relatively unknown. We investigated the possible association between smoking and skin cancer. PATIENTS AND METHODS: A hospital-based case-control study was performed that included 161 patients with squamous cell carcinoma, 301 with nodular basal cell carcinoma, 153 with superficial multifocal basal cell carcinoma, 125 with malignant melanoma, and 386 controls. Information on smoking history was collected in personal interviews. Relative risks were estimated using exposure odds ratios from cross-tabulation and logistic regression. RESULTS: An association between smoking and squamous cell carcinoma of the skin was found (relative risk, 2.3; 95% confidence interval, 1.5 to 3.6; P: = .0001), with a higher risk for current smokers (relative risk, 3.3; 95% confidence interval, 1.9 to 5.5) than for former smokers (relative risk, 1.9; 95% confidence interval, 1.2 to 3.0). After adjustment for age, sex, and sun exposure, the relative risk of squamous cell carcinoma was 2.0 (95% confidence interval, 1.2 to 3.2; P: = .008). There was a dose-response relationship with number of cigarettes and pipes smoked. No significant association was found between smoking and nodular basal cell carcinoma, superficial multifocal basal cell carcinoma, or malignant melanoma. CONCLUSION: Tobacco smoking is an independent risk factor for cutaneous squamous cell carcinoma.

Further evidence for an association of HLA-DR7 with basal cell carcinoma on the tropical island of Saba.

OBJECTIVE: To establish the association of HLA alleles (ie, HLA-DR1, HLA-DR4, and HLA-DR7) with individuals with skin cancer on the tropical island of Saba. This island was chosen because most of the white population has fair skin and excessive exposure to sunlight, which results in a high prevalence of skin cancer. DESIGN: HLA typing was performed in 124 white individuals with histologically proven basal cell and/or squamous cell carcinoma and in control subjects. Skin type, the presence of freckling, and the number of actinic keratoses were determined. SETTING: Population-based study. SUBJECTS: Inhabitants of Saba with and without skin cancer. MAIN OUTCOME MEASURE: Presence of HLA-DR1, HLA-DR4, and HLA-DR7 alleles. RESULTS: Associations of HLA alleles with basal cell and squamous cell carcinoma have been reported. The presence of the HLA-DR7 allele was positively associated with the development of basal cell carcinoma (odds ratio, 3.8; 95% confidence interval, 1.1-13.4). Adjustment for skin type, which is a potentially confounding factor for the association between HLA alleles and skin cancer, did not substantially alter this association. No other associations between HLA alleles and skin cancer were found, possibly because of the small size of the study population. CONCLUSION: This study presented further evidence for an association between HLA-DR7 and basal cell carcinoma. Arch Dermatol. 2000;136:1019-1022

Basal cell carcinoma on the dorsum of the hand: report of 11 cases.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy, although the appearance on the dorsum of the hand appears to be rare. OBJECTIVES: The purpose of this study was to identify and describe patients with BCC of the dorsum of the hand in a large cohort of BCC patients and to provide a review of the literature. METHODS: Eleven patients with a BCC on the dorsum of the hand were identified. Information on age at diagnosis, sex, treatment and follow up, presence of additional malignancies, etc., was gathered from medical records. RESULTS: Between January 1985 and December 1995, 2990 BCCs were registered, of which 11 were located on the dorsal aspect of the hand (0.37%). Nine patients were male and most patients had a history of multiple skin malignancies. Most of the BCCs were nodular or had a nodular component. Solar elastosis was frequently seen. The percentage of 0.37% compares well with BCC located on the dorsum of the hand in other studies, but also with other parts of the body per skin surface area (except the face and neck area). CONCLUSIONS: The density of BCC on the dorsum of the hand is much lower than in the face and neck area but compares well with other parts of the body.

Ephelides are more related to pigmentary constitutional host factors than solar lentigines.

Ephelides and solar lentigines are benign pigmented spots, which are currently associated with an increased risk of skin cancer. These two pigmented spots are known to be discriminated by their clinical, histological, and electron microscopic characteristics, even though occasional misclassification can occur because of their similarity. It has also been questioned whether these spots are not one and the same. In this study, we have attempted to differentiate between these two pigmented spots with the use of a standardized protocol for clinical examinations on 272 healthy volunteers, paying particular consideration to their pigmentary and constitutional host factors. We found that solar lentigines 1) are more prevalent than ephelides, 2) increase in prevalence and number with higher age, and 3) are most prevalent on the trunk and occur more frequently in males than in females. A trend is also observed whereby ephelides 1) loose their prevalence with age, 2) become equally distributed on the face, arms, and trunk, and 3) occur more frequently in females. An intimate association of ephelides, but not solar lentigines, has been found with hair color and skin type. All of these findings are in agreement with most of those reported in the literature, supporting the view that ephelides and solar lentigines are different types of pigmented lesions.

Differences in age, site distribution, and sex between nodular and superficial basal cell carcinoma indicate different types of tumors.

Basal cell carcinomas (BCC) are among the most common cancers in white subjects. Etiologic factors include ultraviolet and ionizing radiation, chemical carcinogens, and possibly infection with human papillomaviruses. Because of clinical and histologic differences, differential pathogenetic mechanisms have been suggested for different BCC subtypes. We studied the patient and tumor characteristics of all BCC diagnosed and/or treated at the departments of Dermatology and Plastic Surgery of our hospital between 1985 and 1996, and a review of the literature was carried out. Some important differences between patients with nodular BCC and patients with superficial BCC were observed. The frequency of superficial BCC was higher in females and was seen in younger patients as compared with nodular BCC. The latter occurred mainly in the head/neck region: in males they were seen more frequently on the ears, and in females they were predominantly seen on the eyelids, the lips, and in the neck. Superficial BCC occurred mainly on the trunk, and occurred significantly more often on the trunk in males than in females, where the legs were the most common site. These findings strongly suggest that the superficial subtype is a separate group within the clinical entity of BCC. Furthermore, our findings seem to support the etiologic role of sun exposure in these tumors; however, this role may be different for each subtype. Chronic sun exposure may be an etiologic factor in nodular BCC as compared with intermittent sun exposure in superficial BCC. Other factors, such as differences in site specific host factors and referral bias, may also play a role in the differences found between the subtypes.

[Side effects of minocycline in the treatment of acne vulgaris]. / Bijwerkingen van minocycline in de behandeling van acne vulgaris.

Minocycline is the most commonly used systemic antibiotic in the long-term treatment (weeks to months) of severe acne vulgaris. Currently much attention is being paid in the Dutch and international literature to the safety of minocycline, after several reports on serious adverse events. The clinical efficacy of minocycline in the treatment of acne vulgaris is better than that of tetracycline and equal to that of doxycycline. The serious adverse events of minocycline therapy described consist of hyperpigmentation of various tissues, autoimmune disorders (systemic lupus erythematosus, autoimmune hepatitis) and serious hypersensitivity reactions (hypersensitivity syndrome reaction, pneumonitis and eosinophilia, and serum sickness-like syndrome). In relation to the number of prescriptions, the number of serious adverse events of minocycline described is small. However, it is very important that prescribing doctors should be aware of the possibility of these adverse events occurring during long-term minocycline therapy and able to recognize the characteristic symptoms at an early stage.

Three cases of pemphigus vegetans: induction by enalapril--association with internal malignancy.

BACKGROUND: Pemphigus vegetans, a rare form of pemphigus vulgaris, consists of vegetating plaques localized to flexural areas. Two types, the Neumann and the Hallopeau type, are recognized with their own characteristics. METHODS: Three patients with pemphigus vegetans were examined, two with Hallopeau type and one with Neumann type. The microscopic and immunofluorescence findings were recorded. RESULTS: Two remarkable features were present. In one case pemphigus vegetans was possibly induced by the use of enalapril. Only in three previous cases has enalapril been described in relation to pemphigus. A second case was associated with a malignant lung tumor, a phenomenon which could not be traced in the literature. CONCLUSIONS: Two types of pemphigus vegetans must be distinguished. Induction of pemphigus (also vegetans) is an accepted side effect of captopril. The effect of enalapril on pemphigus is still in debate. To the best of our knowledge, this is the first time that a patient with pemphigus vegetans and a simultaneously occurring internal malignancy is described.