The following represent additions to UpToDate from the past six
months that were considered by the editors and authors to be of
particular interest. The most recent What's New entries are at the top
of each subsection.
ACNE AND ROSACEA
Serum potassium monitoring during spironolactone therapy for acne (March 2015)
Spironolactone
is an androgen receptor antagonist that is effective for the treatment
of acne in females. Although periodic monitoring of serum potassium
levels is often performed during treatment with spironolactone, there is
uncertainty about the need for monitoring in young, healthy acne
patients. A large retrospective study comparing the rate of hyperkalemia
during treatment with spironolactone with baseline rates of
hyperkalemia in women with acne (ages 18 to 45) did not find increased
rates of hyperkalemia during spironolactone therapy, suggesting that
periodic monitoring of serum potassium in healthy women is not necessary
[
1].
These results cannot be applied to patients who may be at increased
risk for hyperkalemia due to heart failure, renal disease, concomitant
medical therapy, or other conditions. (See
"Hormonal therapy for women with acne vulgaris", section on 'Side effects'.)
ATOPIC DERMATITIS AND OTHER DERMATITIS
Acute worsening of atopic dermatitis due to aeroallergen exposure (July 2015)
Environmental
allergens are a trigger of atopic dermatitis (AD) in a small subset of
children and adults. Patients who have environmental allergies as a
trigger of AD have persistent disease with chronic exposure to an
allergen in the environment. A small study of adults with AD
demonstrated that exposure to grass pollen in an environmental challenge
chamber for two consecutive days resulted in a significant worsening of
AD on exposed skin for the five days after challenge compared with
exposure to clean air (placebo) [
2]. This study shows that an isolated exposure to an aeroallergen can cause an acute flare of AD in sensitized individuals. (See
"Role of allergy in atopic dermatitis (eczema)", section on 'Aeroallergens'.)
Pimecrolimus for atopic dermatitis in infants and young children (May 2015)
Topical
calcineurin inhibitors have been approved in the United States as
second-line therapies for the treatment of mild to moderate atopic
dermatitis (AD) in adults and children ≥2 years. However, they have been
used off-label as first-line treatment for AD in younger children and
infants, in the absence of long-term studies evaluating their efficacy
and safety. A five-year randomized, open-label trial evaluated the
safety and long-term efficacy of pimecrolimus 1% cream compared with low
or mid-potency topical corticosteroids in over 2400 infants with mild
to moderate AD [
3]. After five
years, overall treatment success was achieved in approximately 90
percent of children in both groups. Growth, immune function, and cancer
rates were similar in the two groups, as were overall rates of adverse
events. However, episodes of bronchitis, infected eczema, impetigo, and
nasopharyngitis were slightly more frequent in the pimecrolimus group,
and the rates of cutaneous adverse events (eg, skin irritation, atrophy,
telangiectasias) were not reported. Thus, the advantage of using
pimecrolimus rather than low to mid-potency topical corticosteroids in
this age group remains unclear. (See
"Treatment of atopic dermatitis (eczema)", section on 'Off-label use in infants'.)
Unclear association between atopic dermatitis and lymphoma (May 2015)
The
association between atopic dermatitis and lymphoma is controversial. A
2015 systematic review and meta-analysis of four cohort studies and 18
case-control studies found a modest increase in the risk of lymphoma in
patients with atopic dermatitis compared with the general population [
4].
The risk increase was significant in the meta-analysis of the cohort
studies but not in the case-control studies. However, the large
heterogeneity of case-control studies in study design and diagnostic
criteria does not allow any definite conclusion. In particular, due to
overlapping clinical features, cases of cutaneous T cell lymphoma may
have been initially misdiagnosed and treated as severe atopic
dermatitis. (See
"Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Risk of lymphoma'.)
Depression and anxiety disorders in patients with atopic dermatitis (April 2015)
Several
lines of evidence suggest that the incidence of psychiatric
comorbidities, including major depression and anxiety disorders, is
increased among patients with atopic dermatitis and may be influenced by
factors such as perceived disease severity and quality of life. A
longitudinal cohort study evaluated the risk of developing major
depression or anxiety disorders later in life among more than 8000
adolescents and adults with atopic dermatitis and age- and sex-matched
controls [
5].
Patients with atopic dermatitis had a six- and fourfold increased risk
of developing major depression or anxiety disorders, respectively. These
findings suggest that the identification and treatment of psychiatric
comorbidities are important aspects of the management of patients with
atopic dermatitis. (See
"Pathogenesis,
clinical manifestations, and diagnosis of atopic dermatitis (eczema)",
section on 'Depression and anxiety disorder'.)
AUTOIMMUNE AND SYSTEMIC DISEASES
Benefit of long-term management on risk for vulvar carcinoma in women with vulvar lichen sclerosus (June 2015)
Vulvar
lichen sclerosus is a chronic disease associated with an increased risk
for vulvar carcinoma. The findings of a prospective cohort study of 507
women with vulvar lichen sclerosus suggest that topical corticosteroid
therapy, used both to achieve disease control and for long-term
maintenance treatment, may reduce cancer risk [
6].
Women who reported consistent adherence to treatment instructions had a
lower incidence of vulvar carcinoma or vulvar intraepithelial neoplasia
than women who reported less consistent adherence (0 versus 4.7
percent). In addition, patients who adhered to treatment had better
symptom control and reduced risk for vulvar scarring. These findings
suggest that consistent treatment rather than an "as needed" approach to
the long-term management of vulvar lichen sclerosus may improve patient
outcomes. (See
"Vulvar lichen sclerosus", section on 'Topical corticosteroids'.)
Effects of rituximab in systemic sclerosis (May 2015)
In
patients with systemic sclerosis (SSc), B cell infiltration has been
demonstrated within skin and lung biopsies. Earlier case reports
suggested that B cell depletion could attenuate skin and lung fibrosis,
and now a larger study of 63 SSc patients and 25 matched controls has
evaluated the therapeutic effects of rituximab [
7].
After a follow-up period of approximately seven months, patients
treated with a single course of rituximab demonstrated a significant
improvement in the modified Rodnan skin score (mRss). Among SSc patients
with interstitial lung disease, rituximab also prevented a further
decline in forced vital capacity compared with matched controls. There
were no serious adverse events among rituximab-treated patients.
However, this study had many limitations, and additional studies are
needed to establish the long-term efficacy of rituximab for skin and
lung fibrosis in systemic sclerosis before routine use can be
recommended. (See
"Immunomodulatory and antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)", section on 'Rituxumab'.)
Apremilast for oral ulcers in Behçet’s disease (April 2015)
There
remains a need for effective therapy for recurrent oral ulcers in
patients with Behçet’s syndrome. Preliminary data suggest that
apremilast, an orally administered phosphodiesterase-4 inhibitor known
to modulate several inflammatory pathways, is beneficial in treating
oral ulcers. A randomized, phase II trial including over 100 patients
with Behçet’s syndrome found that patients who received apremilast had a
significant reduction in the number of oral ulcers at 12 weeks, as
compared with those in the placebo group [
8].
There was also a significant reduction in pain from oral ulcers.
Nausea, vomiting, and diarrhea were more common than in the placebo
group, which is similar to findings seen in previous studies of
apremilast for the treatment of psoriasis and psoriatic
arthritis. Additional studies are needed to determine the long-term
efficacy and safety of apremilast for oral ulcers before routine use can
be recommended. (See
"Treatment of Behçet’s syndrome", section on 'Oral aphthae and genital ulcers'.)
INFECTIONS AND INFESTATIONS
Updated recommendations for pediatric head lice (May 2015)
Pediculosis
capitis is a common condition that can lead to physical discomfort and
social stigmatization. An update to the 2010 clinical report on head
lice published by the American Academy of Pediatrics incorporates new
therapies (spinosad and topical ivermectin), clarifies diagnosis and
treatment protocols, and provides guidance for the management of
children with pediculosis capitis in the school setting [
9].
Examples of major points in the update include recommendations that no
child should be excluded from school because of head lice or nits and
that pyrethroids remain reasonable first-line therapies for primary
treatment of pediculosis capitis in communities where resistance to
pyrethroids is unproven. (See
"Pediculosis capitis", section on 'Pediculicide selection'.)
The efficacy of an inactivated vaccine to prevent zoster (April 2015)
The
live attenuated zoster vaccine reduces the risk of herpes zoster with a
reported vaccine efficacy of 60 to 70 percent in adults 50 years and
older, but it cannot be used in immunocompromised individuals and may
have decreased efficacy in adults 70 years and older. A randomized,
placebo-controlled trial evaluated the efficacy of
HZ/su,
an experimental recombinant inactivated zoster vaccine administered in
two doses two months apart, among 15,411 adults 50 years and older [
10].
After three years of follow-up, the overall vaccine efficacy against
herpes zoster was 97.2 percent (95% CI 93.7-99.0), and efficacy among
adults 70 years and older was similar to that seen in adults between 50
and 69 years of age. (See
"Prevention of varicella-zoster virus infection: Herpes zoster", section on 'Inactivated vaccines'.)
PEDIATRIC DERMATOLOGY
Stevens-Johnson syndrome outbreak associated with M. pneumoniae (August 2015)
Stevens-Johnson
syndrome/toxic epidermal necrolysis
(SJS/TEN)
is a rare, severe blistering mucocutaneous reaction, most commonly
triggered by medications, characterized by extensive necrosis and
detachment of the epidermis and mucosa.
Mycoplasma pneumoniae and cytomegalovirus infections are the next most common trigger of
SJS/TEN, particularly in children. Between September and November 2013, an outbreak of eight pediatric cases of
M. pneumoniae-associated
SJS/TEN was reported in Colorado, likely related to high levels of
M. pneumoniae infection in the region [
11].
All children had severe oropharyngeal mucositis; the conjunctiva was
involved in seven children and the genital mucosa in five. (See
"Stevens-Johnson
syndrome and toxic epidermal necrolysis: Pathogenesis, clinical
manifestations, and diagnosis", section on 'Infection'.)
PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS
Secukinumab, an anti-IL17A antibody, for psoriatic arthritis (August 2015, MODIFIED August 2015)
Secukinumab,
an anti-interleukin (IL)-17A antibody, is available for the treatment
of psoriasis in the United States and other countries, and has been
evaluated for psoriatic arthritis (PsA) using various routes of
administration and dosing regimens. In a multicenter randomized trial,
involving almost 400 patients with active PsA, secukinumab (300, 150, or
75 mg administered subcutaneously weekly for four weeks and every four
weeks thereafter, consistent with the regimen for psoriasis) was
superior to placebo in achieving significant improvement in joint and
skin disease, and in physical function and quality of life [
12].
Responses by weeks 12 to 16 were similar to those at week 24 (ACR20
responses of 54, 51, and 29 versus 15 percent), and benefit was
sustained at 52 weeks. The drug was well-tolerated and may have a future
role in the treatment of psoriatic arthritis. (See
"Treatment of psoriatic arthritis", section on 'IL-17 blockade'.)
Comparative efficacy of secukinumab and ustekinumab for plaque psoriasis (July 2015)
Secukinumab,
a fully human anti-interleukin-17A monoclonal antibody, is a highly
effective new treatment for psoriasis that was superior to etanercept in
earlier trials. In the first randomized trial to compare
secukinumab with ustekinumab, another established psoriasis therapy,
secukinumab was more effective than ustekinumab for moderate to severe
plaque psoriasis [
13].
Safety profiles for the two drugs were similar. The expanding
literature on the comparative efficacy of psoriasis therapies will
provide valuable information for therapeutic decision making. (See
"Treatment of psoriasis", section on 'Secukinumab'.)
Phase III trial support for oral tofacitinib for plaque psoriasis (July 2015)
Oral
therapy for psoriasis is advantageous because of the ease of
administration compared with topical medications, injected or infused
medications, and phototherapy. Tofacitinib, an oral janus kinase (JAK)
inhibitor used for the treatment of rheumatoid arthritis, is under
investigation for the treatment of psoriasis. A phase III trial that
compared two different doses of tofacitinib with etanercept and placebo
found that the higher dose of tofacitinib (10 mg twice daily) was
superior to placebo and non-inferior to etanercept in the treatment of
moderate to severe plaque psoriasis [
14]. Other phase III randomized trials also support the efficacy of tofacitinib therapy [
15]. Tofacitinib represents a potential addition to the armamentarium for psoriasis therapy. (See
"Treatment of psoriasis", section on 'Future therapies'.)
Risk for vascular complications of diabetes in patients with psoriasis (June 2015)
Psoriasis
may be associated with increased risk for vascular complications of
diabetes. A retrospective cohort study that compared risk for
microvascular and macrovascular complications in diabetic patients with
psoriasis with risk for these complications in diabetic patients without
psoriasis found a modest increase in risk for both types of
complications in patients with psoriasis [
16]. Additional study is needed to confirm these findings. (See
"Comorbid disease in psoriasis", section on 'Implications'.)
SKIN CANCER
Sonidegib approved for advanced basal cell carcinoma (July 2015)
Targeted
inhibition of the Hedgehog pathway has antitumor activity against
advanced basal cell carcinoma. Based upon the results of a phase II
trial [
17],
sonidegib was approved at a dose of 200 mg orally once a day by the US
Food and Drug Administration for patients with locally advanced basal
cell carcinoma that has recurred following surgery or radiation therapy,
or who are not candidates for surgery or radiation therapy [
18]. Sonidegib provides an additional treatment option for these patients. (See
"Systemic treatment of advanced cutaneous squamous and basal cell carcinomas", section on 'Sonidegib'.)
Weak association between citrus fruit and melanoma (July 2015)
An
analysis of data from over 100,000 individuals participating in the
Nurse’s Health Study found a modest 36 percent increase in melanoma risk
associated with high dietary intake of citrus fruit or juice, after
adjusting for known risk factors for melanoma, such as family history of
melanoma, phenotypic characteristics, number of nevi, and lifetime
number of blistering sunburns [
19].
A potential explanation for this association is that citrus fruits are a
source of psoralens, chemical compounds present in plants known to be
photosensitizers. However, the results of this study need further
confirmation, because, given the small increase in risk, residual
confounding cannot be excluded. In the meanwhile, changes in dietary
advice to the public are not warranted. (See
"Risk factors for the development of melanoma", section on 'Other proposed risk factors'.)
Melanoma incidence in the United States (June 2015)
A report
from the Centers for Disease Control and Prevention indicates that
melanoma incidence rates doubled in the United States over the three
decades from 1982 to 2011, while the mortality rates remained constant
over time [
20]. The
annual number of cases is expected to double over the next 15 years.
Based upon findings from SunSmart, an Australian community-wide skin
cancer prevention program designed to raise awareness, change personal
behaviors, and influence institutional policy and practices, the report
estimates that a comprehensive skin cancer prevention program in the
United States could prevent 20 percent of melanoma cases between 2020
and 2030. (See
"Risk factors for the development of melanoma", section on 'Incidence'.)
Topical 5-fluorouracil for the long-term control of actinic keratoses (May 2015)
Topical
5-fluorouracil (5-FU) is used as a field treatment in patients with
multiple actinic keratoses (AKs) and may be effective for the long-term
control of AKs. In a randomized trial, 932 participants with multiple
AKs on the face and ears were treated with 5% 5-FU cream or vehicle
twice daily for four weeks and followed-up for an average time of 2.6
years [
21].
Compared with the control group, patients in the 5-FU group had a
significantly higher rate of complete clearance at six months and fewer
AKs at 42 months. (See
"Treatment of actinic keratosis", section on 'Topical 5-fluorouracil'.)
SURGICAL AND COSMETIC DERMATOLOGY
Effect of needle diameter on patient discomfort during facial injection of botulinum toxin (September 2015)
Although
previous data on the impact of injection needle diameter on patient
discomfort has been equivocal, studies evaluating this issue have had
various methodological flaws. A small randomized trial designed to
minimize such flaws found that patients receiving facial injections of
botulinum toxin A for forehead wrinkles were less likely to experience
clinically significant pain when injected with a 32-gauge needle than
with a 30-gauge needle [
22].
This finding suggests that use of a smaller diameter needle may benefit
patients who experience significant pain during facial injections. (See
"Overview of botulinum toxin for cosmetic indications", section on 'During treatment'.)
Cyanoacrylate glue for the ablation of incompetent superficial veins (March 2015)
Several
methods are available for the ablation of incompetent superficial
veins. A system that ablates the treated vein using a
cyanoacrylate adhesive agent has been approved for use in the United
States [
23].
The procedure is performed like radiofrequency and laser ablation, but
without the need for tumescent anesthesia. In a randomized trial
comparing this system with radiofrequency ablation, short-term outcomes
at three months were similar [
24]. Longer term follow-up is needed to determine the durability of the results. (See
"Liquid, foam, and glue sclerotherapy techniques for the treatment of lower extremity veins", section on 'Cyanoacrylate glue'.)
OTHER DERMATOLOGY
Afamelanotide for protoporphyria (August 2015)
Erythropoietic
protoporphyria (EPP) and X-linked protoporphyria (XLP) are cutaneous
porphyrias that present in childhood with painful, non-blistering
photosensitivity within minutes of sun exposure. Affected individuals
must avoid sunlight, often with substantial reduction in their quality
of life. Afamelanotide is a new therapy for EPP and XLP that is
administered as a subcutaneous implant every other month. The mechanism
involves increased melanin production; there are no effects on porphyrin
levels. Two multicenter randomized trials in adults with EPP or XLP
(168 patients total) found that afamelanotide substantially reduced
photosensitivity and improved sunlight tolerance, with minimal
toxicities [
25].
Thus, for adults with EPP or XLP, we suggest afamelanotide. This
therapy is available in Europe but not in the United States. Dosing and
safety data in children have not been reported. (See
"Erythropoietic protoporphyria and X-linked protoporphyria", section on 'Afamelanotide'.)
Eosinophilia during prolonged antibiotic therapy (June 2015)
Eosinophilia
is not uncommon in patients receiving prolonged intravenous
(IV) antibiotics, but the prevalence and significance has not been
extensively studied. In a prospective cohort study of 824 patients
receiving prolonged intravenous antibiotic therapy, eosinophilia
developed in 25 percent, appearing at a median of 15 days of therapy and
peaking at a median absolute count of
726/mL (500 to
8610/mL) [26].
Although most patients with eosinophilia completed their courses
without complications, one-third developed a hypersensitivity reaction
involving rash or hepatic or renal involvement. Medication-associated
eosinophilia does not mandate discontinuation of therapy but warrants
close monitoring for evidence of hypersensitivity and consideration of
alternative medications that could be substituted without compromising
care. (See
"Approach to the patient with unexplained eosinophilia", section on 'Medications and over the counter remedies'.)
Sunscreen use among adults in the United States (June 2015)
Although
regular sunscreen use is a key message of sun-safety campaigns
worldwide, data on the pattern of sunscreen use in the general
population are limited. In the United States, a survey of over 4000
adults found that approximately 14 percent of men and 30 percent of
women regularly used sunscreen on the face and other exposed skin when
outside in the sun for more than one hour [
27].
Regular use of sunscreen was associated with having sun-sensitive skin,
higher annual household income, performing aerobic activity, and having
children younger than 18. However, the use of sun protection measures
other than sunscreen (eg, wearing hat or protective clothing) was not
investigated. The results of this study indicate a need for sun-safety
interventions targeting men, individuals with a lower perceived
susceptibility to sun damage, and those for whom cost may be a barrier
to sunscreen use. (See
"Selection of sunscreen and sun-protective measures", section on 'Patterns of use'.)
