Immune checkpoint inhibitor-induced sarcoidosis-like granulomas.

Immune checkpoint inhibitors targeting the cytotoxic T lymphocyte-associated antigen-4 and programmed cell death-1 receptors have transformed the treatment of melanoma and other cancers. These therapies are associated with a number of side effects, including immune-related adverse events. Sarcoidosis-like granulomas (SLGs) are important immune checkpoint inhibitor-related reactions to recognize as SLGs can mimic disease progression and accordingly impact treatment decisions. We systematically review reports of immune checkpoint inhibitor-induced SLGs in cancer patients and discuss potential underlying pathophysiological mechanisms.

RimabotulinumtoxinB versus OnabotulinumtoxinA in the treatment of masseter hypertrophy: a 24-week double-blind randomized split-face study.

BACKGROUND: Masseter hypertrophy can be ameliorated by botulinum toxin. OBJECTIVE: To compare the efficacy and safety of RimabotulinumtoxinB (BTX-B) and OnabotulinumtoxinA (BTX-A) in the treatment of masseter hypertrophy. METHODS: Sixteen women with bilateral masseter hypertrophy received single injections of BTX-A or BTX-B at a dose ratio of 1:50 or 1:70 in a 24-week double-blind randomized split-face study. RESULTS: Both BTX-A and BTX-B produced significant improvements in masseter hypertrophy. The maximum volume reduction, as determined by computed tomography scanning, at week 12 was comparable between BTX-A and BTX-B at a dose ratio of 1:70 (15.6 and 14.2%, respectively). At week 24, only masseters treated with BTX-A maintained a significant volume reduction. Investigator ratings and patient satisfaction scores paralleled objective computed tomography measurements. CONCLUSION: Both BTX-A and BTX-B are effective in the treatment of masseter hypertrophy. BTX-B, at a dose ratio of 1:70, has a comparable efficacy but a shorter duration of action than BTX-A.

Monkey see, monkey do: contagious itch in nonhuman primates.

"Contagious itch" has been anecdotally reported and recently confirmed in a controlled setting in humans. Here, we investigated in adult rhesus macaques whether 'contagious itch' occurs spontaneously in monkeys. In a first experiment, the latency to scratch following cage-mate scratching was observed in pair-housed adult rhesus macaques. Scratching increased within the first 60 s and subsequently declined. In a second experiment, scratching behavior was recorded for individually caged adult rhesus macaques which where shown videos of monkeys scratching, but also neutral stimuli. A greater frequency of scratching was observed when monkeys viewed a video sequence of another monkey scratching as well as during the neutral stimulus immediately following the monkey scratching segment. In conclusion, viewing other monkeys scratching significantly increased scratching behavior in adult rhesus macaques.

Sleep disturbances in psoriasis.

BACKGROUND: Psoriasis negatively impacts sleep, but the factors that cause this sleep disturbance are not well characterized. PURPOSE: To assess sleep quality in subjects with psoriasis. METHODS: 35 outpatients diagnosed with chronic plaque psoriasis affecting at least 10 percent BSA and 44 controls completed the Pittsburgh Sleep Quality Index, Patient Health Questionnaire, Itch Severity Scale, Insomnia Severity Index, and Epworth Sleepiness Scale. For multiple testing, alpha was set at 0.008. RESULTS: Adjusting for age, BMI, and gender, patients with psoriasis had 4.3 times the odds to score in a higher insomnia category (OR 95% CI: 1.7, 11.2; p=0.01), a trend toward experiencing "poor sleep" (p=0.04), and no difference in odds to be "sleepy" (p=0.83). Patients with psoriasis had greater itch than those without psoriasis (mean ISS 8.5 vs. 2.0; p<0.0001). When adjusting for age, BMI, gender, and depression, those with psoriasis were not more likely to experience poor sleep quality (p=0.25), nor to score in a higher insomnia category (p=0.20) or be more "sleepy" (p=0.53). CONCLUSIONS: Patients with psoriasis suffer from sleep disturbances and pruritus more than those without psoriasis. Although sleep disturbances are more prevalent, this may be secondary to depression rather than related to a direct effect of psoriasis.

Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis.

Emerging data in mice and humans reveals a critical contribution of Th17-associated cytokines, particularly interleukin-(IL)-23 and IL-17, in the pathogenesis of psoriasis. The IL-23/Th17 pathway is a therapeutic target for biologic agents and systemic therapies in psoriasis treatment. A literature search was performed to review and summarize the current evidence on IL-17 and IL-23 as a basis for understanding the use of anti-IL-17 and anti-IL-23 agents for psoriasis therapy. Using PubMed, recent articles were identified pertaining to IL-17, IL-23, and psoriasis. Signaling via the heterodimeric IL-23 receptor induces production of IL-17, which stimulates production of proinflammatory keratinocyte cytokines that mediate the psoriatic response. An overexpression of IL-23, IL-17, or Th17 cells in transgenic mice is associated with the development of inflammatory disease. Both IL-17 knockout mice and humans with a genetic IL-17 deficiency are susceptible to extracellular and intracellular pathogens. This suggests a potential for adverse effects from clinical administration of anti IL-23-p40/IL-17 therapies. Anti-p40 antibodies, briakinumab and ustekinumab, were tolerated in clinical trials and substantially improved psoriasis. Further trials of anti IL-17 therapies are needed to assess their clinical use and potential for infection and other adverse events.

Trends in the use of topical over the counter products in the management of dermatologic disease in the United States.

BACKGROUND: Over the counter (OTC) products play an important role in treating and preventing disease in the U.S. Topical OTCs are widely used but use in dermatology is not well defined. OBJECTIVE: To characterize topical OTC use in the U.S. METHODS: The National Ambulatory Medical Care Survey was queried for physician visits in which topical OTCs were recorded. Physician specialty, patient demographics, and diagnoses were examined and linear regressions were performed to determine trends over time. RESULTS: From 1989 to 2008, there were an estimated 320 million visits documenting topical OTC recommendations; the majority of which were visits to a dermatologist (33.5%). Dermatologists most commonly recommended hydrocortisone (16.9%), benzoyl peroxide (13.3%), and sunscreen (7.4%). Dermatologists were more likely than other providers to use moisturizers in the treatment of dermatologic disease. Overall, topical OTC recommendations by all physicians has decreased over time (p < 0.0001). However, dermatologists' recommendations for moisturizers and sunscreens has increased significantly. CONCLUSION: Topical OTC products have an important role in the prevention and treatment of dermatologic disease. Topical OTC recommendations are decreasing over time whereas their use as complementary components (sunscreen/moisturizers) appears to be increasing. Increased awareness of the utility of these agents may help to improve patient outcomes.

Association of pain and itch with depth of invasion and inflammatory cell constitution in skin cancer: results of a large clinicopathologic study.

IMPORTANCE: This study highlights a simple bedside evaluation of itch and pain for suspicious skin lesions. OBJECTIVE: To examine the correlation of pain and itch with histologic features of skin cancers. DESIGN, SETTING, AND PARTICIPANTS: This large, prospective, clinicopathologic study enrolled patients who filled out questionnaires that assessed itch and pain intensity of their skin tumors at the time of excision. Study participants were from the patient population presenting to the Department of Dermatology surgical unit at Wake Forest University Baptist Medical Center from July 1, 2010, through March 31, 2011. Study participants included 268 patients, representing 339 histopathologically confirmed cutaneous neoplasms. The following skin cancer subtypes were represented in this analysis: 166 basal cell carcinomas, 146 squamous cell carcinomas, and 27 melanomas. MAIN OUTCOMES AND MEASURES: Itch and pain associated with skin cancer at the time of excision ranked on an 11-point (score range, 0-10) numerical visual analog scale and histopathologic analysis for each neoplasm (assessment of the amount and type of inflammation, ulceration, perineural invasion, and depth of invasion). RESULTS: The prevalence of itch and pain across all skin cancers was 36.9% and 28.2%, respectively. However, these symptoms were mostly absent in melanomas. Pain intensity was significantly associated with the degree of inflammation (mild or none vs moderate or marked; P < .001), presence of neutrophils in the inflammatory infiltrate (predominantly mononuclear vs mixed or neutrophilic; P = .003), presence of eosinophils (present vs absent; P = .007), ulceration (yes vs no; P = .003), perineural invasion (yes vs no; P < .001), depth of invasion (P = .001), and largest diameter length of skin lesion (P < .003). Itch intensity was significantly associated with the degree of inflammation (mild or none vs moderate or marked; P = .001) and the presence of eosinophils (present vs absent; P = .02). CONCLUSIONS AND RELEVANCE: These findings support the theory that itch emanates from the upper layers of the skin, whereas pain is associated with deeper processes. This study also reports that a simple bedside assessment for the presence and intensity of pain or itch is an easily implementable tool for physicians evaluating suspicious skin lesions.

Isotretinoin and oral contraceptive use in female acne patients varies by physician specialty: analysis of data from the National Ambulatory Medical Care Survey.

OBJECTIVE: To determine whether oral contraceptives (OCPs) are underutilized in the treatment of acne in women of reproductive age, how use of OCPs compares with use of isotretinoin and whether adequate use and documentation of OCPs is occurring with isotretinoin. MATERIAL AND METHODS: The National Ambulatory Medical Care Survey (NAMCS) was analyzed over the years 1993-2008 for isotretinoin and OCP use in females aged 12-55 with acne. RESULTS: Isotretinoin was prescribed more often than OCPs at both first visits (4.7% vs. 3.3%) and overall visits (13% vs. 2.6%) for acne. Documentation of OCP or other contraceptive use occurred only 4.1% of the time overall in patients treated with isotretinoin. Specialties varied in both OCP use for acne and contraceptive use with isotretinoin, with ob/gyn specialists most likely to prescribe OCPs and isotretinoin and to report contraceptive use in patients using isotretinoin, and dermatologists least likely to prescribe OCPs. CONCLUSIONS: The findings of the current study indicate that OCPs may be underutilized in women with acne. Underreporting of contraceptive use with isotretinoin and variations between specialties in OCP and isotretinoin use indicate a potential for education about the viability of OCPs in acne treatment and the importance of reporting contraceptive use with isotretinoin.

Retinoid plus antimicrobial combination treatments for acne.

BACKGROUND: Acne vulgaris is a chronic disease with several pathogenic factors. Multiple medications are typically used that can lead to nonadherence and treatment failure. Combination medications target multiple pathways of acne formation and may offer therapeutic benefit. PURPOSE: To explore the efficacy and tolerability of combination retinoid plus antimicrobial treatments in acne vulgaris. METHODS: A PubMed and Google search was conducted for combination therapies of clindamycin and tretinoin, with secondary analysis of related citations and references. Similar searches were completed for the combination medications of benzoyl peroxide plus clindamycin or erythromycin, and for the combination therapy of adapalene and benzoyl peroxide. RESULTS: Combination clindamycin phosphate and tretinoin gel was found to be more efficacious than monotherapy of either drug or its vehicle for acne, including inflammatory acne, and has a greater onset of action than either drug alone. Clindamycin phosphate and tretinoin gel was well-tolerated, and adherence to its use exceeded that of using both medications in separate formulations. Benzoyl peroxide-containing combination medications with clindamycin or erythromycin were both more effective in the treatment of acne than either drug alone. Both medications were well-tolerated, with dry skin being the most common adverse effect. CONCLUSIONS: Combination medications have superior efficacy and adherence, and have a similar tolerability profile compared with monotherapy of its components. Several studies have found antibiotic-containing combination products with a retinoid effective for acne. The use of antibiotic-containing combination medications for acne can lead to bacterial resistance. Due to this potential for bacterial resistance, benzoyl peroxide treatments are also recommended in combination with a retinoid.

Exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines.

There have been no long-term complications or life-threatening adverse effects related to botulinum toxin treatment for any cosmetic indications. Nevertheless, there are well-known, mild side effects of botulinum toxin treatment on the upper face, though most of them are self limited with time. However, excluding brow ptosis, reports about site specific side effects are few and anecdotal. We experienced cases of exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines, and report them here. In our cases, new appearance of a noticeable glabellar protrusion following botulinum toxin injection on the forehead was observed in 2 patients. Also, a new deep wrinkle on one side of the forehead just above the eyebrow appeared in another 2 patients. The exaggerated wrinkles nearly disappeared without treatment by week 4 in all subjects. These exaggerations of wrinkles may be caused by hyperactivity and overcompensation of untreated muscles. With the increasing availability of diverse botulinum toxin for cosmetic purposes, physicians and patients should be aware of this temporary change after therapeutic injections. We recommend explaining this possible effect prior to injection, for better understanding of treatment for cosmetic indications.