The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 2. Management of H1-Antihistamine-Refractory Chronic Urticaria.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H1-antihistamines, even though the dose of H1-antihistamines is increased up to 4-fold. CSU that is not controlled with H1-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H1-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

Association of Pediatric Atopic Dermatitis and Cataract Development and Surgery.

Importance: There is a paucity of data addressing the risk of cataract development in pediatric patients with atopic dermatitis (AD). Objective: To investigate the association of AD with subsequent cataract development and cataract surgery in a Korean pediatric population. Design, Setting, and Participants: This population-based retrospective longitudinal cohort study used nationally representative data from the Korean National Health Insurance Service database from 2002 to 2013. Incident AD cases, consisting of patients younger than 20 years with AD and severe AD and were matched to 4 controls each using propensity score derived from age, sex, residential area, and household income. Main Outcomes and Measures: Incidence probabilities of cataract development and cataract surgery between the AD group and controls were compared using Kaplan-Meier methods and log-rank tests. Cox proportional hazard models were fitted for cataract and cataract surgery to determine the risk factors in the matched cohort. Results: Of 34 375 patients with incident AD (16 159 girls [47%]; mean [SD] age, 3.47 [4.96] years), there were 3734 severe AD cases (10.9%) with 137 500 matched controls. Development of cataracts was not different between the AD and control groups, (0.216% vs 0.227%; 95% CI, -0.041% to 0.063%; P = .32) or between the severe AD cohort and their controls (0.520% vs 0.276%; 95% CI, -0.073% to 0.561%; P = .06). Cataract surgery was performed more frequently in the AD cohort than in the control group (0.075% vs 0.041%; 95% CI, 0.017%-0.050%; P = .02) and in the severe AD cohort compared with their controls (0.221% vs 0.070%; 95% CI, 0.021%-0.279%; P = .03). Severe AD was associated with both development of cataract (adjusted hazard ratio, 1.94; 95% CI, 1.06-3.58, P = .03) and requirement for cataract surgery (adjusted hazard ratio, 5.48; 95% CI, 1.90-15.79, P = .002). Conclusions and Relevance: Absolute risk of cataract was rare, with or without AD, even after 10 years of observation. However, our results suggest that pediatric patients with AD have an increased risk for cataracts requiring surgery and that disease severity may increase the risk for cataract development and cataract surgery.

Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes.

Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1ß and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis.

Pulse in pulse intense pulsed light for melasma treatment: a pilot study.

BACKGROUND: A new type of intense pulsed light IPL with pulse-in-pulse (PIP) mode (multiple fractionated subpulses in one pulse width) has recently been developed. OBJECTIVE: To evaluate the clinical efficacy and safety of PIP IPL in patients with melasma. MATERIALS AND METHODS: Half of each patient's face was treated with IPL and six treatment sessions with a low-fluence quality-switched neodymium-doped yttrium aluminum garnet laser (IPL/T) every 2 weeks. The other half was treated with PIP IPL. Outcome assessments included photography, modified Melasma Area and Severity Index (MASI) score, and patient satisfaction. The melanin and erythema indices were used for objective evaluation. Patients were followed up for 6 months after the last treatment. RESULTS: All patients completed the study successfully. On both treated sides, the melanin index decreased significantly after treatment. The modified MASI score also fell 54.4% on the PIP IPL side and 50.0% on the IPL/T side. No patients reported serious aggravation of melasma for 6 months after the last treatment. Patients favored PIP IPL due to less discomfort during and after treatments. CONCLUSION: PIP IPL may be a safe and promising treatment for melasma.

Role of oral tranexamic acid in melasma patients treated with IPL and low fluence QS Nd:YAG laser.

BACKGROUND: Recently, tranexamic acid (TNA) containing oral medication has gained public attention, claiming for whitening effects. OBJECTIVE: This study was performed to evaluate the clinical efficacy and safety of oral TNA as an adjuvant to intense pulsed light (IPL) and laser treatment in melasma. METHODS: A total of 51 patients were included in the study. Patients who have been on oral TNA during IPL and laser treatments (group A) and those who were treated with only IPL and laser (group B) were analyzed (from winter to summer). Modified melasma area and severity index (mMASI) scores were blindly evaluated by two investigators using digital photographs taken at each visit. RESULTS: The mean modified MASI score decreased from 11.33 ± 7.07 to 6.21 ± 5.04 in group A and from 11.70 ± 6.72 to 8.93 ± 5.89 in group B (baseline vs. 2 weeks after the last treatment, p = 0.005). Modified MASI score right before and after IPL were more reduced in group A. No serious adverse effects were reported up to 8 months of oral TNA medication. CONCLUSION: Oral TNA may improve clinical efficacy in light- or laser-based melasma treatment especially during the period of relative high sun exposure without serious adverse effects.

Low level light could work on skin inflammatory disease: a case report on refractory acrodermatitis continua.

Low level laser or light treatment on the various clinical condition is getting considerable attention now. However, there has been no report about the clinical effect of low level polarized polychromatic noncoherent light (LPPL) on the inflammatory skin disease. We experienced a case of acrodermatitis continua in a pregnant woman refractory to any conventional treatment including the most potent topical steroid. She was successfully treated with LPPL. LPPL could be a possible treatment modality producing substantial clinical result in inflammatory skin condition without any side-effect.

Low-dose 1064-nm Q-switched Nd:YAG laser for the treatment of melasma.

BACKGROUND: Melasma is a common acquired pigmentary disorder which is sometimes hard to treat with conventional methods. Various kinds of modalities have been applied for the treatment of melasma but none shows constantly good results. OBJECTIVES: In this study, we would like to know the effect of low-dose 1064-nm Q-switched Nd:YAG laser (QSNYL) on melasma and want to evaluate the changes of skin after laser treatment. METHODS: Twenty melasma patients were enrolled. Two regions were evaluated from each patient; a total of 40 sites. The 1064-nm QSNYL at fluences of 2.0-3.5 J/cm(2) was used to treat the whole face, including the melasma lesions. The fluence was adjusted individually and increased until erythema was developed on the laser-treated area. The treatment was performed five times with a 1-week interval. Non-invasive measuring methods, including a chromatometer, mexameter, cutometer, visioscan and a corneometer, were used before and after treatment. RESULTS: The L-value from the chromatometer, which reflects the lightness of skin, was increased (0.86 +/- 1.67, p < 0.05). The melanin index from the mexameter was significantly decreased (-28.23 +/- 28.21, p < 0.001). The SEw value from the visioscan, which reflects the degree of wrinkling, decreased (-5.80 +/- 0.59, p = 0.040). None of the other measurement parameters showed significant changes. CONCLUSIONS: Low-dose 1064-nm QSNYL appears to be an effective treatment modality for melasma.

Short-term heat exposure inhibits inflammation by abrogating recruitment of and nuclear factor-{kappa}B activation in neutrophils exposed to chemotactic cytokines.

Cytokines, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-8 attract neutrophils into inflammatory sites. During emigration from the blood neutrophils interact with extracellular matrix proteins such as fibronectin. Fibronectin provides beta2-integrin co-stimulation, allowing GM-CSF and IL-8 to activate nuclear factor (NF)-kappaB, an effect that does not occur in suspension. We tested the hypothesis that exposure of mice to fever-like temperatures abrogates neutrophil recruitment and NF-kappaB activation in a mouse model of skin inflammation. Mice that were exposed to 40 degrees C for 1 hour showed strongly reduced GM-CSF- and IL-8-induced neutrophilic skin inflammation. In vitro heat exposure did not interfere with neutrophil adhesion or spreading on fibronectin but strongly inhibited migration toward both cytokines. Using specific inhibitors, we found that PI3-K/Akt was pivotal for neutrophil migration and that heat down-regulated this pathway. Furthermore, neutrophils on fibronectin showed abrogated NF-kappaB activation in response to GM-CSF and IL-8 after heat. In vivo heat exposure of mice followed by ex vivo stimulation of isolated bone marrow neutrophils confirmed these results. Finally, less NF-kappaB activation was seen in the inflammatory lesions of mice exposed to fever-like temperatures as demonstrated by in situ hybridization for IkappaBalpha mRNA. These new findings suggest that heat may have anti-inflammatory effects in neutrophil-dependent inflammation.