Does Elidel (a form of non-steroidal cream) for eczema cause cancer in children ?

A lot of parents of children with eczema (atopic dermatitis) have steroid-phobia (so are some Chemists and Doctors, dare I say)  and would avoid using topical steroid at any cost (including their children’s un-necessary suffering).

Elide creaml is marketed as an eczema treatment free of steroid.

The following is by Mary Wu Chang, MD Reviewing  Margolis DJ et al., JAMA Dermatol 2015 Feb 18; 

One of the largest prospective, longitudinal studies ever conducted in dermatology indicates NO increased risk.

Atopic dermatitis (AD or eczema ) affects up to 20% of children, but treatment options are limited. The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus (Elidel is the commercial name) were approved in 2000 and 2001 respectively for AD therapy. Systemic use of TCIs has been associated with increased malignancy risk, especially skin cancer and lymphoma. A black-box warning was added to topical pimecrolimus labeling in 2005.

The Pediatric Eczema Elective Registry (PEER) is an ongoing, nationwide longitudinal cohort study started in 2004 to gather post-marketing data in patients who used pimecrolimus cream for at least 42 days of the 180 preceding enrollment. Subsequent treatment is not required, and AD management is dictated by the patient’s physician. The primary outcome is onset of any malignancy after enrollment; participants are queried every 6 months about malignancy.

As of May 2014, five malignancies were reported in 7457 children enrolled and followed for 26,792 person-years (2 leukemias, 1 osteosarcoma, 2 lymphomas, no skin cancers). The overall rate of malignancy was 18.7/100,000 person-years. The standardized incidence ratio for all malignancies based on age-standardized SEER population was 1.2 (95% confidence interval, 0.5–2.8), a statistically insignificant risk. The authors conclude that increased malignancy risk is unlikely to be associated with topical pimecrolimus as used in the PEER cohort.

Comment

Topical calcineurin inhibitors such as Elidel were heavily marketed when they first came to market and were a welcome alternative to topical corticosteroids. The rapid rise in prescriptions coupled with malignancy concerns led to the black-box warning, which swung the pendulum to the other extreme. Physicians, pharmacists, and parents became afraid to use TCIs despite the lack of evidence associating them with malignancy. The PEER registry, one of the largest prospective, longitudinal studies ever conducted in dermatology, is nearing completion. Thus far, malignancy is no more frequent in this cohort than in the general pediatric population, a reassuring conclusion.

 

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Viagra and the risk of melanoma

From the Dermatologist’s forum :

“Just wondering what you tell patients about the melanoma risk with Viagra use? I’ve had 2 patients in the last week asking about it. The study was quite a decent prospective one but still the only one to my knowledge.

http://www.ncbi.nlm.nih.gov/m/pubmed/24710960/ ”

“This was mentioned at the World Congress of Skin Cancer in Edinburgh in September this year with no firm conclusion drawn. However the presenter also mentioned the result of a survey: 60+% of men thought it was worth the risk while 98% of women agreed it was worth the risk!!”

Just repeating, 98% of women agreed (that it was worth the risk) !

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Propecia (hair loss drug) and sexual dysfunction ?

From the Dermatologists’ chat room :

“Blogs and forums on the net about persistent sexual side effects post-finasteride have been around for a little while. People who write in these forums often have very convincing personal bad experiences with the drug, which are endorsed by others with strikingly similar experiences. – ?? a mass effect or a true phenomenon

The side effect of depression and suicidality has been FDA-listed although not as a direct effect of the drug, but as reactive depression in men who claim to have  “permanent sexual dysfunction” from finasteride – which is a very small proportion.

I haven’t been around long enough to see enough men who have come off finasteride for their hair to know if they experience permanent sexual S/Es. However, the few that I have seen come off finasteride have not reported any issues with any of the S/Es.

At this stage, the jury is still out on the true causality of finasteride and permanent sexual S/Es. I do warn patients about it but say it is uncommon and controversial at this stage. ”

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We are back ! mtk…

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The role of “golden stap” in eczema…

Golden Stap (Staphylococcus aureus) secretes a factor that causes mast cell (the so-called allergy cell) degranulation and activation of (Th2-type) allergic inflammation in the skin of atopic dermatitis.

Atopic dermatitis is caused by abnormal immunoglobulin-E–mediated Th2 immune responses (a type of immune reaction) in settings of barrier dysfunction. Defective barrier function is the reason why application of moisturiser is an important part of eczema management. Colonization of lesional skin by Staphylococcus aureus is a hallmark of active disease. S. aureus species produce exotoxins that can act as super antigens in disease models, but the precise mechanism by which S. aureus aggravates atopic dermatitis has been unclear.

Nakamura et al. have now identified the major mechanism by which S. aureus engages allergic-type Th2 T-cell responses in skin. Given the established role of IgE-mediated mast cell activation in atopic dermatitis, the researchers hypothesized that S. aureus secretes a factor that causes mast cell degranulation. Painstakingly, they identified δ-toxin as the mast cell degranulation–inducing factor produced by S. aureus in culture and in mouse skin. Using an antigen-driven mouse model of atopic dermatitis, they showed that colonization by normal S. aureus caused erythema and crusting, with interleukin 4 and IgE production, whereas a mutant S. aureus lacking δ toxin did not. Conversely, mice lacking mast cells were resistant to δ toxin–mediated inflammation and IgE production. Finally, they showed that S. aureus strains cultured from lesional skin of 26 patients with atopic dermatitis all expressed δ toxin.

COMMENT

These findings identify δ toxin as the critical factor elaborated by S. aureus that causes mast cell degranulation and activation of Th2-type allergic inflammation in the lesional skin of atopic dermatitis. The normal function of δ toxin is unknown, but it may contribute to the ability of S. aureus to kill competing bacteria. These results identify an important mechanism of pathogenesis in atopic dermatitis and perhaps identify another target for treating this common disease.

In other words, golden Stap makes eczema worse and eczema allows more golden Stap to colonise the skin. So treating golden Stap is another essential component of eczema management.

modified from NEJM Journal Watch

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Spontaneous resolution of warts in children…

The natural course of childhood warts includes resolution in half of patients.

The prevalence of warts among children ranges from 22% to 33%. Treatment failure is common, but benign neglect is frequently appropriate as spontaneous resolution often occurs. Studies of the natural history of childhood warts are scarce and old.

Investigators examined the hands and feet of 1134 students (age range, 4–12 years) in three schools in the Netherlands for warts. A total of 366 children had warts at baseline. Plantar warts were identified in 70% and common warts in 42%; 43% had multiple warts, and 37% had a wart measuring >1 cm diameter. Of the 333 children available for follow-up at a mean of 15 months, 38% had had wart treatment (over-the-counter agents, physician treatment, or both). Complete resolution was defined as the absence of palpable and visible warts (skin color and skin lines were reestablished). At follow-up, the complete resolution rate was 52 per 100 person-years (95% confidence interval, 44–60). When newly developed warts were excluded, the resolution rate was 90 per 100 person-years (95% CI, 79–100). Rates were similar for common and plantar warts. The likelihood of resolution was higher in younger children and those with non-Caucasian skin type. The authors conclude that half of primary school children with warts will have resolution within 1 year.

by Mary Wu Chang, MD in Journal Watch, reviewing Bruggink SC et al. Ann Fam Med 2013 Sep/Oct.

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How safe are topical steroids during pregnancy ?

An estimated 6% of pregnant women receive prescription topical corticosteroids (TCS), which are pregnancy risk category C. Animal studies show teratogenic effects, but data are limited and conflicting regarding use in pregnant women.

Investigators performed a retrospective cohort study using data from the U.K. National Health Service. They documented type and dosages of TCS prescriptions filled at pharmacies by 2658 pregnant women over a 7-year period, who were matched with 7246 unexposed pregnant controls. Mean dispensed quantity of potent or very potent topical steroids during the whole pregnancy was 64 grams (range, 15–490). Women who received corticosteroids via other routes during pregnancy and those with multiple pregnancy or assisted reproduction were excluded. A subgroup who received TCS during the first trimester was identified (the critical period for fusion of the lip/palate is the 5th–12th gestational week). Other outcomes studied included low birth weight (LBW, <2500 g), preterm delivery (<37 weeks’ gestation), fetal death, mode of delivery (vaginal vs. C-section), and low Apgar score (<7 at 5 minutes). Confounding concurrent diseases were noted.

Compared with no TCS use, maternal TCS exposure was NOT associated with orofacial cleft, LBW, preterm delivery, fetal death, low Apgar score, or mode of delivery. A separate analysis showed a significantly increased risk for LBW when the dispensed amount of potent or very potent TCS exceeded 300 g during the entire pregnancy.

COMMENT

Risks to the foetus from topical corticosteroid exposure appear to be lower than feared, but a dose-dependent relationship with low birth weight was seen. Many patients do not use up their prescriptions, and unaccounted-for TCS may have been received elsewhere, so the risks for adverse outcomes may be underestimated by this study design. Because LBW seems to correlate with quantity of potent TCS exposure, limited amounts of mild or moderate-strength TCS are safest in pregnant women. When potent or very potent TCS are indicated, the cumulative amount should be kept under 300 g, and fetal growth should be monitored.

by Mary Wu Chang, MD reviewing Chi C-C et al. JAMA Dermatol 2013 Sep 4.

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Acne (i.e. acne itself, not any medication) linked to suicidal ideation and depression in adolescents…

Adolescents with substantial acne have more frequent suicidal ideation and depression than those without the skin condition, say researchers who believe this is likely to be a result of the burden of acne rather than an adverse therapy-associated effect.

Writing in the Journal of Investigative Dermatology, Jon Halvorsen (University of Oslo, Norway) and colleagues report the results of a cross-sectional, questionnaire-based study of 3775 Norwegian 18-19 year olds.

Overall, 14% of the cohort had self-reported substantial acne, whereas the remaining participants had no or little acne.

Girls with substantial acne had twice as much suicidal ideation as girls with no or little acne, at 25.5% versus 11.9%, whereas boys with substantial acne had three times as much suicidal ideation as their peers without the condition, at 22.6% versus 6.3%.

Overall, substantial acne was associated with a significant 80% increase in relative risk for suicidal ideation.

In addition, relative risks for having mental problems (assessed by Strengths and Difficulties Questionnaire), low attachment to friends, not thriving at school, never having had sex, or a romantic relationship were increased 2.25-, 1.52-, 1.41-, 1.51-, and 1.35-fold, respectively, in adolescents with substantial acne compared with their acne-free counterparts.

“An association between isotretinoin therapy and increased risk of depression, suicidal ideation, and suicide has been claimed, but the current literature is conflicting and results from controlled studies are lacking,” say the researchers.

They believe that the adverse psychological events such as suicidal ideation and depression experienced by those with substantial acne may more accurately mirror the burden of substantial acne rather than the effects of acne medications.

“Our results are helpful for clinicians, as subjective complaints are important when choosing treatment,” write Halvorsen et al.

“Furthermore, these findings have public health implications because they underscore the need of appropriate health care for adolescent boys and girls in the community,” they conclude.

J Invest Dermatol, MedWire

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Having a dog reduces risk for childhood eczema (atopic dermatitis)…

A meta-analysis indicates that early exposure to dogs, but not cats, decreases risk for childhood atopic dermatitis by 25%.

The hygiene hypothesis was proposed in 1989 as a possible explanation for the rapidly increasing prevalence of atopic dermatitis (AD) and other allergic and autoimmune diseases in developed nations. This hypothesis posits that reduced exposure to infectious agents in early life alters immune system maturation. Findings on pet exposure and risk for (AD) in children are inconsistent. Therefore, researchers conducted a systematic review and meta-analysis of pooled data from 21 birth cohort studies (26 publications) that examined exposure to dogs, cats, or other pets during infancy or childhood and AD during infancy and childhood.

The pooled relative risk of AD was significantly reduced for exposure versus no exposure to dogs (0.72, 15 studies) and exposure to pets overall (0.75, 11 studies), but not for exposure to cats (0.94, 13 studies). Studies were moderately heterogeneous. Mitigating factors included geographic heterogeneity (Europe, 14 studies; U.S., 3 studies; Oceania, 3 studies; and Japan, 1 study), undefined pet-keeping practices (degree of exposure), inability to adjust for pet-avoidance behavior of parents (e.g., because of a family history of allergy), presence or absence of smoking, and education and income.

COMMENT

The conflicting results regarding a link between pet exposure and childhood atopic diseases (allergic rhinitis, asthma, atopic dermatitis) probably stem from different methodologies in the individual studies and various meta-analyses. Furthermore, pet exposure appears to affect the risk for the three atopic diseases differently. This careful meta-analysis indicates that early exposure to dogs significantly reduces risk for childhood atopic dermatitis. Although the protective effect of dogs and pets overall is consistent with the hygiene hypothesis, the lack of a protective effect from cat exposure indicates that the association is complex.

by Mary Wu Chang, MD in Journal Watch, NEJM

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Free Botox treatment for 10 patients with excessive underarm sweating…

There is no catch. Botox injection is THE most effective way to treat excessive sweating in the armpits. It is indeed one of those rare medical treatment which is BOTH safe and extremely effective. To qualify, you need to have tried other ways (e.g. topical aluminium hydroxide) without success. Call us on (02) 9580 1311.

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