More sunscreen, less wrinkles…

Daily use of sunscreen can slow skin aging associated with middle age.

Regular sunscreen use protects against cutaneous squamous cell carcinomas and invasive melanomas, but its effect on cutaneous photoageing has received much less attention, despite a popular preoccupation with ageing and a multibillion dollar industry focused on reversing its effects.

Investigators conducted a randomized, double-blind, controlled trial in 604 subjects younger than 55, most fair-skinned, to evaluate whether regular sunscreen use prevented photoaging of the skin. Approximately half of the participants were randomized to daily application of an SPF15 sunscreen (containing 8% ethylhexyl-p-methoxycinnamate and 2% 4-tert-butyl-4′ methoxy-4-dibenzoylmethane); the other half were given no instructions and applied sunscreen at their own discretion. The groups were similar in skin color and amount of sun exposure. To evaluate photoaging, silicone impressions of the back of the left hand were made at baseline and 4.5 years.

Experienced assessors graded the imprints on a validated scale. After adjustments for differences in sunburn and photoaging of the neck, the daily sunscreen group was 24% less likely to exhibit evidence of progressive photoaging of the skin than those who used sunscreens at their own discretion (relative odds, 0.76; 95% confidence interval, 0.50–0.98). Some patients also received beta carotene, which had no effect on photoaging compared with placebo.

Comment: The findings convincingly demonstrate that regular sunscreen use protects against photoaging, and the beneficial effects can be detected after only 4 years. This effect may persuade individuals more concerned about their appearance than about skin cancer to regularly apply photoprotection. Sunscreens used in this study conducted in the mid-1990s primarily protected against ultraviolet B wavelengths — now, many available products also block UVA, and UVA is known to contribute significantly to photoaging. Therefore, modern broad-spectrum sunscreens may be even more beneficial than the older types used in this study.

— Craig A. Elmets, MD

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Sunscreen protection of moles (aka melanocytic nevi)…

Melanocytic nevi (moles) are considered melanoma precursors, and people with many melanocytic nevi are at increased risk for melanoma. Sun exposure, as well as being an etiologic agent for melanoma, also produces clinical, histological, and dermatoscopic changes in melanocytic nevi. Two study groups investigated whether topical sunscreens and opaque barriers prevented alterations in melanocytic lesions.

Carrera and colleagues covered half the area of 23 dysplastic nevi with either an opaque barrier or a broad-spectrum sun protection factor 50 sunscreen and exposed the lesions to ultraviolet B light at twice the minimal erythema dose. Seven days after exposure, erythema, pigmentation, and scaling were increased compared with preexposure. These effects were at least partially prevented in sunscreen- or barrier-treated portions. Ultraviolet (UV)-induced changes were identified on dermatoscopic examination in some nevi, including diffuse pigmentation, blurring of the pigment network, dotted vessels, and erythema. Some nevi also had changes in the size of dots and globules and increases in regression structures. Surprisingly, many dermatoscopic changes were also found in the protected nevi halves. Only blurring of the pigment network was significantly less common in protected areas. On histological examination, unprotected portions were more likely to have marked lentiginous melanocytic hyperplasia, suprabasal solitary melanocytes, and prominent and elongated melanocytic dendrites. Unprotected areas also stained more intensely for melanocytic markers HMB-45 and Melan-A, although changes in markers were observed even in protected lesion halves. Similar findings were reported by Massone and colleagues.

Comment: Unquestionable evidence links sun exposure and tanning bed use to melanoma, and sunscreens reduce these effects. Results of both studies indicate that subclinical changes (i.e. changes in the moles that are not noticeable to the naked eye) occur in nevi exposed to sunlight and that sunscreens and physical barriers protect melanocytic nevi from some, but not all, UV-related changes. Changes in the protected nevi halves may represent indirect effects of exposure on unprotected skin cells adjacent to the nevi or result from exposure to segments of the visible or infrared spectra not filtered by sunscreens. The significance of these changes and how long they persist are unknown. From the dermatologist’s perspective, the findings suggest that biopsies performed in recently sun- or tanning bed–exposed skin may produce worrisome histologic findings. These results reinforce the deleterious effects of sun exposure on nevi.

— Craig A. Elmets, MD

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Aspirin may prevent melanoma in postmenopausal Caucasian women…

In contrast to some earlier reports, in this large study, low-dose aspirin seemed to usefully reduce melanoma risk.

Melanoma incidence is increasing, and safe, effective methods of prevention are highly sought. Whether nonsteroidal anti-inflammatory drugs (NSAIDs) confer any benefit as chemopreventive agents is controversial. A study of 92,125 Caucasian women in the Nurses’ Health Study did not find reduced risk for melanoma with NSAID use (Cancer Causes Control 2012; 23:1451), and other large studies showed only marginal benefits or none. Aspirin has been demonstrated to lower the risk for gastric, colorectal, and breast cancers; its role as a preventive agent for melanoma has not been adequately studied.

Using data from the Women’s Health Initiative Observational Study (WHI OS), these authors studied the association between NSAID use and cutaneous melanoma risk in postmenopausal women. Melanoma diagnosis was adjudicated by confirmation of pathology reports and medical record review. Just under 60,000 women were eligible for inclusion, and median follow-up was 12 years.

Of 548 incident melanomas in these women, 289 were in situ, 255 were invasive, and 4 could not be classified. The melanoma incidence rate was 21% lower in aspirin users than in those taking nonaspirin NSAIDs or those not taking NSAIDs. In women taking aspirin for 5 or more years, the risk of developing melanoma was 30% lower. There was no benefit on melanoma risk from acetaminophen use. The vast majority of melanomas (94%) developed in patients without a prior history of melanoma.

Among the limitations of this study are that medication use was self-reported, and that information on family history of melanoma and on hair and eye color was lacking. Strengths of the study include detailed information on skin type, sun-exposure and sun-protection habits, and prior history of skin cancer. Additional pluses are the large cohort with geographic diversity, long follow-up, and relatively large number of confirmed melanoma cases.

Comment: This is an important finding. One wonders whether these observations might hold true for pre- and perimenopausal women, other ethnic groups, or men. The primary risk from daily low-dose aspirin is gastrointestinal bleeding. There is clear evidence that low-dose daily aspirin is beneficial for the prevention of colorectal cancer in Lynch syndrome. Unless there is a contraindication, I will tell a patient who asks my advice that low-dose aspirin seems to usefully reduce melanoma risk. Left unstated in this study was whether aspirin users who developed melanomas had a difference in lesion thickness.

— Jeffrey P. Callen, MD in Journal Watch Dermatology

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The Hand-Held Dermatologist…

Smartphone apps for detecting skin cancer are not very accurate, but over-the-counter accessibility may be the future of many medical tests.

 There are now several smartphone applications (apps) that make claims regarding skin cancer detection. Each app evaluates photographs of skin lesions and provides information as to the likelihood of malignancy. These apps are relatively inexpensive when compared to a doctor’s visit and are not subject to validation or government oversight. Although the limitations of such apps are disclosed, some consumers may be misled by the conclusions of these untested algorithms and may be harmed in the process. A team at the University of Pittsburgh set out to test the effectiveness of four such apps that were publicly available.

The researchers submitted digital clinical images of 60 melanoma lesions (44 invasive; 16 in situ) and 128 benign lesions (lentigo, nevi, seborrheic keratoses, hemangioma, dermatofibroma) that had been obtained before biopsy and were histologically confirmed by a dermatopathologist. Three of the apps used algorithms that assessed the risk of the lesion. The lesions were assessed as follows:

  • App 1: “problematic” versus “okay”
  • App 2: “melanoma” versus “looks good”
  • App 3: “high risk,” “medium risk,” or “low risk”

The fourth app claims to submit the image to a board-certified dermatologist (identity unknown) for review.

Sensitivity ranged from 6.8% to 98.1%. App 3 had the lowest sensitivity, even when “medium” risk was considered positive (54.2%; 95% confidence interval, 40.8%–67.1%). App 4 had the highest sensitivity (98.1%; 95% CI, 88.8–99.9) compared with the others. Specificity ranged from 30.4% to 93.7%; app 3 had the highest specificity. The positive and negative predictive values ranged from 33.3% to 42.1% and from 65.4% to 97.0%, respectively.

Comment: In this study, apps 1, 2, and 3 are considered diagnostic tools, and app 4 is essentially a store-and-forward dermatology tool. App 4 was the most expensive and had the highest sensitivity and the lowest specificity. Although one may be drawn to compare the performance of these tools with that of a professional device like Melafind (sensitivity, 98.3%; specificity, 9.9%), usage is very different. These smartphone apps are aimed at the consumer audience, whereas Melafind is used for lesions prescreened by dermatologists. Overall, we need to understand the goal of these devices. High sensitivity, which is probably desirable in a consumer-based technology, will undoubtedly drive up demand for office visits in this already access-limited field. One can envision a secondary agenda, wherein the smartphone automatically locates available dermatologists based on the GPS position of the phone, perhaps becoming a marketing tool for physicians. Nevertheless, medicine is moving toward over-the-counter accessibility, as even HIV tests, which used to be considered incredibly sacrosanct, can now be found in local drug stores.

—by  Hensin Tsao, MD, PhD in JournalWATCH

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Putting on a happy face: botulinum toxin (e.g. Botox) to treat depression ?…

Several classic studies demonstrate that activation of specific facial muscles (e.g., clenching a pencil between one’s teeth to activate the smiling muscles) can alter mood. These researchers examined whether clinical improvement is associated with decreased depressive facial expression through the use of botulinum toxin type A in the glabellar region.

Inclusion criteria were ongoing major depressive disorder, Hamilton Rating Scale for Depression (HRSD) score of 15 or higher, and a moderate-to-severe vertical glabellar line during maximum frowning. Patients were taking one or two antidepressants or had not responded to at least one previous antidepressant. The investigators assessed 263 patients for eligibility and accepted 30 (23 women; average age, 51; mean HRSD, 20; illness duration, 16 years; current episode, 29 months). Patients received injections of botulinum toxin or placebo and were assessed biweekly.

To mask treatment assignment, patients wore caps covering the affected area during assessments. HRSD scores significantly improved at 6 weeks in the active group (HRSD change, –10.07 vs. –1.73 with placebo; response rate [≥50% decrease in HRSD], 60% vs. 13%). The treatment was identified by 60% of raters and 90% of subjects. Opinion about the cosmetic change was not linked to response.

Comment : These thought-provoking results raise a skeptical eyebrow. Very few screened subjects were enrolled, and group assignment was obvious. The authors claim that exclusion rates were high because of psychiatric comorbidity, medication history, and patient refusal (recruitment information did not identify the protocol). Still, in these subjects with moderate and chronic major depressive disorder unresponsive to at least one medication, botulinum toxin demonstrated an effect similar to medication and greater than transcranial magnetic stimulation. The results appear to confirm the connection between facial expression and feelings. Botulinum toxin may have a therapeutic role in depression, although larger clinical trials are necessary to confirm this initial finding.

— Jonathan Silver, MD

Published in Journal Watch Psychiatry 2012

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Over 50 ? Got your prostate checked yet ?

I did.

“The man with the rubber glove was surprisingly gentle!”

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Moles are a risk factor for basal cell carcinoma (BCC)…

Patients with multiple naevi (moles) have probably had considerable sun or tanning bed exposure and should be examined for BCC.

 Naevi are a risk factor for melanoma, and the number in an individual grows with increasing ultraviolet radiation. Investigators asked whether the number of nevi might also forecast a predisposition to basal cell carcinoma (BCC).

The researchers recorded the number of naevi on the forearms and hands of volunteers from Queensland, Australia, in 1986, and the number on the backs of the same individuals in 1992. The subjects were followed prospectively for the development of new BCCs from 1992 through 2007. A total of 1339 individuals were evaluated for the duration of the study or until they died. In all, 1202 histologically confirmed BCCs were diagnosed in 401 subjects. Patients with naevi on the forearms and hands were more likely to develop BCCs than those without naevi (odds ratio, 1.5; 95% confidence interval, 1.1–1.9). Interestingly, presence of naevi on the hands and forearms was associated with BCCs on the head and neck, but not on the trunk or limbs. There was no association between naevi on the back or naevi on both the forearms and the back and BCC.

Comment: Confronted with a patient with large numbers of naevi, we tend to focus on identifying lesions suspicious for melanoma, but these patients are likely to have had significant sun or tanning bed exposure, rendering them susceptible to other types of skin cancer as well. Thus, evaluations of patients with multiple naevi, especially on the forearms and hands, should also include examination for basal cell carcinomas.

— Craig A. Elmets, MD, Published in Journal Watch Dermatology October 19, 2012

English version of the above :

If you have a lot of moles (naevi), it is likely that you also had a lot of sun exposure; making you more prone to non-melanoma skin cancers (in addition to a higher risk of melanoma). The commonest type of non-melanoma skin cancer (or any skin cancer) is basal cell carcinoma (BCC). Therefore, if you have a lot of moles, you are also prone to have BCCs as well.

Dr Ken Ho

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A link between vitamin D and vitiligo (the “Michael Jackson disease”)…

Vitiligo is an acquired depigmenting disorder of uncertain etiology. Anecdotal reports imply that the disease responds to topical vitamin D analogs, suggesting that vitamin D may be involved in its pathogenesis. To investigate the relationship between vitamin D and vitiligo, investigators in China looked at polymorphisms (different versions of the gene) in vitamin D receptor genes in 749 vitiligo patients and 763 control subjects.

Polymorphisms in the BsmI, ApaI, and TaqI alleles (i.e. different versions of these genes) were significantly less frequent in vitiligo patients than in controls. A fourth allele (A 4th gene version), FokI (don’t ask !), was not associated with predisposition to vitiligo. In addition, serum 25(OH) vitamin D levels were measured in 171 vitiligo patients and 150 controls. There was a dose–response relationship between higher 25(OH) vitamin D levels and protection from vitiligo.

Comment: One of dermatologists’ great needs is a reliable treatment for vitiligo. Study results on the role of vitamin D analogs in vitiligo have conflicted. These results indicate that the variability may result from genetic polymorphisms in the vitamin D receptor, which would allow some patients, but not others, to respond to vitamin D analogs. Future studies evaluating the efficacy of vitamin D analogs are warranted, but with consideration of these polymorphisms in the efficacy analysis. The findings may also explain why phototherapy, which is known to increase vitamin D levels in the skin, is effective in some, but not all, vitiligo patients. The results also suggest that it may be possible to reduce the incidence or progression of vitiligo by ensuring that at-risk patients do not become vitamin D deficient.

— Craig A. Elmets, MD, Published in Journal Watch Dermatology October 5, 2012

ENGLISH VERSION of the Above :

Vitiligo, the so-called Michael Jackson disease, is a distressing skin problem for a lot of patients. Some treatments of vitiligo, which also raise the vitamin D level in those treated, seem to work in some patients but not the others. Why ? It is possible that the vitamin-D raising therapies only work in a sub-group of vitiligo patients with a particular genetic make-up.

In the near future, when genetic studies become dirt cheap and fast, patient with vitiligo may get a swab in the mouth, pay a few bucks, wait for 2 days, get a report and say, “Hey Dr., these vitamin D therapies may work on my white skin spots, let’s give it a go.” And we’ll all live happily ever after…

Dr Ken Ho

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Wet dressing : cheap, effective, “natural”…

Wet wrap (aka wet dressing) is an underused and intensive topical treatment which is highly effective for severe atopic dermatitis (eczema). It could easily be done at home simply with cotton bandage or just an old towel !

Wet dressings placed over topical steroids work well to reestablish control in patients with widespread eczema.

A recent retrospective analysis reviewed the cases of 218 patients with atopic dermatitis (age, <18 years) hospitalized at Mayo Clinic (Rochester, Minnesota) over a 30-year period. Closed, nonoccluded, wet dressings were applied over topical corticosteroid creams applied twice daily. Dressings remained in place about 3 hours, with a 30- to 45-minute interval between changes. The topical corticosteroid creams were triamcinolone 0.025% (3% of patients), 0.05% (27%), or 0.1% (24%) cream, or hydrocortisone 1% (7%) or 2.5% (39%) cream. The regimen was as follows: (1) daily tub bath, (2) application of topical steroid creams, (3) application of wet dressing, usually soaked with warm tap water but occasionally with dilute aqueous solutions of acetic acid, (4) application of cotton flannel clothing over the wet dressings to help retain moisture, and (5) placement of warm blankets for patient comfort. Antibiotics were given to 72% of patients for skin or other infections.

Mean duration of hospitalization was 3.61 days. All patients improved, and about 80% had moderate or marked improvement.

Comment: When hospitalization was more common, I hospitalized many children with atopic dermatitis for this sort of treatment, but I nearly always used 1% hydrocortisone as my steroid. The predictable, rapid, and dramatic response proved to the parents, children, and me that plain old 1% hydrocortisone cream was a very useful topical drug when used under wet compresses. The combination therapy improved dermatitis and reduced itching and sleepless nights. For home, I recommended wet sweat shirts and wet sweat pants as dressings to keep the skin wet, and plastic mattress pads to keep the mattress dry. To make it easier, it would still be effective even it is just left on for 30 mins.

modified from Mark Dahl MD, Published in Journal Watch Dermatology

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More than 5% of melanomas are caused by tanning bed use…

The International Agency for Research on Cancer, a unit of the World Health Organization, concluded in 2009 that sun beds, like radiation and cigarette smoke, are carcinogenic to humans. Since the meta-analysis that led to this conclusion, another eight epidemiologic studies have been performed. These investigators conducted a larger meta-analysis to explore this relationship in greater detail. They included 27 case-control, cohort, and cross-sectional studies involving 11,428 patients, performed in the U.S., Canada, Europe, and Australia between 1981 and 2012.

They found a statistically significant 20% increase in melanoma risk among ever users of tanning beds and a 42% increase among heavy users. Tanning bed use before age 35 increased melanoma risk by 87% compared with never use — a 12% increase even from the elevated risk reported in 2009. The risk for developing melanoma appears to increase with time. The authors estimate that 5.4% of melanomas and nearly 800 melanoma deaths annually in Europe can be attributed to artificial tanning.

Comment: This study provides new information about the relationship between tanning bed use and melanoma, and the numbers are rising rather than leveling off. A worrisome finding of this study is that the risk for developing melanoma increases over time from the first tanning bed exposure, which suggests that we will see greater numbers and percentages of past and present sun bed users developing melanoma. We must vigilantly monitor current and past tanning bed users for melanoma as well as continue our ongoing efforts to counsel patients and lobby for restrictions on tanning bed use.

by Craig A. Elmets, MD, Published in Journal Watch Dermatology August 10, 2012

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