Sun Young Moon

Insulin-Like Growth Factor-1 Increases the Expression of Inflammatory Biomarkers and Sebum Production in Cultured Sebocytes

Background Acne vulgaris has been linked to the Western diet. Hyperglycemic diet increases insulin and insulin-like growth factor (IGF)-1. Deeper insights into IGF-1-mediated signal pathway are critical importance to understand the impact of Western diet. Objective We investigated the effect of IGF-1 on the expression of inflammatory biomarkers and sebum production in cultured sebocytes. Methods Polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure changes in the expression of inflammatory biomarkers including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), IGF1R, IGFBP2, sterol response element-binding protein (SREBP), and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) after the treatment of cultured sebocytes with 10−7 M or 10−5 M IGF-1. Sebum production was evaluated after the treatment of cultured sebocytes with 10−7 M or 10−5 M IGF-1 using lipid analysis. Results The expression levels of IL-1β, IL-6, IL-8, and TNF-α in cultured sebocytes after treatment with 10−7 M or 10−5 M IGF-1 were increased. Increased gene expression levels of NF-κB in cultured sebocytes were also shown after 10−7 M or 10−5 M IGF-1 treatments. Gene expression of these inflammatory biomarkers was decreased after 10−7 M or 10−5 M IGF-1 treatment in the presence of 100 nM NF-κB inhibitor. Treatment with 10−7 M or 10−5 M IGF-1 increased the gene expression levels of IGF1R, IGFBP2, SREBP and PI3KCA in cultured sebocytes. Sebum production from cultured sebocytes treated with 10−7 M or 10−5 M IGF-1 was also increased. Conclusion It is suggestive that IGF-1 might be involved in the pathogenesis of acne by increasing both expression of inflammatory biomarkers and also sebum production in sebocytes.

Systematic review and quality analysis of studies on the efficacy of topical diphenylcyclopropenone treatment for alopecia areata

REFERENCES 1. Craiglow BG, King BA. Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J Invest Dermatol. 2014;134(12):2988-2990. 2. Kennedy Crispin M, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776. 3. Mackay-Wiggan J, Jabbari A, Nguyen N, et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016;1(15):e89790. 4. Kavanaugh AF, Geier J, Bingham C, et al. Real world results from a post-approval safety surveillance of tofacitinib (Xeljanz): over 3 year results from an ongoing US-based rheumatoid arthritis registry. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington, DC. 5. Craiglow BG, Tavares D, King BA. Topical ruxolitinib for the treatment of alopecia universalis. JAMA Dermatol. 2016;152(4): 490-491.

House Dust Mite Increases pro-Th2 Cytokines IL-25 and IL-33 via the Activation of TLR1/6 Signaling

House dust mites have been implicated in the etiology and exacerbation of atopic dermatitis. Diverse factors contribute to house dust mite allergenicity through the activation of innate immunity. We investigated whether Dermatophagoides farinae extract (DFE) allergens mediate innate immune activation through specific toll-like receptors (TLRs) in epidermal keratinocytes, a DFE-induced murine atopic dermatitis model, and human atopic dermatitis lesions. DFE activated the expression of TLR1, TLR6, IL-25, and IL-33 in human primary keratinocytes and HaCaT cells. Knockdown of TLR6 inhibited DFE-induced upregulation of IL-25 or IL-33. In addition, the suppression of TLR1 inhibited the release of IL-33. DFE induced the expression of IL-25 and IL-33 by upregulation of IL-1 receptor-associated kinase 1, transforming growth factor-β activated kinase-1, IκB kinase, and NF-κB pathways. Tlr6-/- mice did not show DFE-induced upregulation of IL-25 and IL-33. Furthermore, DFE-induced upregulation of IL-25 was not induced in Tlr1-/- mice. We also identified upregulated mRNA and protein expression of TLR1, TLR6, IL-25, and IL-33 in human atopic dermatitis skin lesions with high house dust mite sensitization. We found that DFE-induced activation of TLR1 and TLR6 may cause polarization toward a T helper type 2 immune response via the release of IL-25 and IL-33.

Coexistence of psoriasis and epidermolysis bullosa acquisita: Evaluation of the integrity of the basement membrane

1. Roh NK, Hahn HJ, Lee YW, Choe YB, Ahn KJ. Clinical and histopathological investigation of seborrheic keratosis. Ann Dermatol. 2016; 28:152-158. 2. Neuhaus IM, LeBoit PE, McCalmont TM. Seborrheic keratosis with basal clear cells: a distinctive microscopic mimic of melanoma in situ. J Am Acad Dermatol. 2006;54:132-135. 3. Haspeslagh M, De Schepper S, De Wispelaere I, Degryse N. Seborrheic keratosis with basal clear cells: a peculiar microscopic mimic of melanoma in situ. J Cutan Pathol. 2013;40:768-769. 4. Takashi A, Takaya F, Tetsunori K. Two cases of seborrheic keratosis with basal clear cells. J Dermatol. 2017;44(3):339-342. https://doi.org/ 10.1111/1346-8138.13641. 5. Barr RJ, Alpern KS, Santa Cruz DJ, Fretzin DF. Clear cell basal cell carcinoma: an unusual degenrative variant. J Cutan Pathol. 1993; 20:308-316. 6. Gaertner EM. Incidental cutaneous reaction patterns: epidermolytic hyperkeratosis, acantholytic dyskeratosis, and Hailey-Hailey-like acantholysis: a potential marker of premalignant skin change. J Skin Cancer. 2011;2011:645743. https://doi.org/10.1155/2011/645743. 7. Lacz NL, Schwartz RA, Kihiczak G. Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event. Int J Dermatol. 2005;44:1-6.

Pityriasis versicolor atrophicans: Is it true atrophy or pseudoatrophy?

To the Editor , Pityriasis versicolor classically presents as round to oval macules that can be hypopigmented, hyperpigmented or erythematous, whereas its atrophic variant is rarely encountered. The atrophic variant is characterized by oval to roundish lesions with a typically depressed appearance.1 The etiology of cutaneous atrophy is unclear, although a few hypotheses have been suggested.2–4 Moreover, whether it is a true atrophy or pseudoatrophy is unknown yet. We encountered one case of pityriasis versicolor atrophicans, also called atrophying pityriasis versicolor, and investigated the histopathological characteristics of this cutaneous atrophy. A 35-year-old man presented with multiple depressed brownish macules and patches on the back (Fig. 1A). Initially, pruritic erythematous papules developed on the back 3 years before presentation. To treat the skin lesions, the patient used topical steroids intermittently for 1 year. One year before presentation, because multiple depressed scar-like lesions had developed and gradually worsened, the patient visited our clinic. Our first clinical impressions of the skin lesions were primary or secondary atrophoderma, pityriasis versicolor atrophicans and Schweninger–Buzzi anetoderma. Skin biopsies were performed from the lesional skin and the perilesional normal skin. Hematoxylin and eosin (H&E), diastase-periodic acid-Schiff (D-PAS), Masson’s trichrome and Verhoeff elastic staining were performed. The H&E and D-PAS stained sections revealed many roundish spores and short hyphae within the stratum corneum (Fig. 1A, inset). The patient was treated with topical amorolfine ointment. After 3 months, the skin atrophy was Fig. 1. Clinical and histopathological findings. A) Before treatment (inset: spores and short hyphae visible in the stratum corneum). B) After treatment (inset: no spores or hyphae were found in the stratum corneum).

Alopecia Areata Progression Index, a Scoring System for Evaluating Overall Hair Loss Activity in Alopecia Areata Patients with Pigmented Hair: A Development and Reliability Assessment

Background: No scoring systems to evaluate overall hair loss activity in alopecia areata (AA) have been established. Objective: We sought to develop a measurement tool (Alopecia Areata Progression Index, AAPI) for the evaluation of overall hair loss activity in AA patients with pigmented hair. Methods: The scalp surface area was divided into 4 quadrants. In each quadrant, hair loss activity was scored on the basis of the percentage of alopecic area, clinical findings associated with hair loss. The AAPI was measured in 17 patients with different severities of AA. Results: Interobserver and intraobserver reliabilities were assessed by 4 investigators. A significant correlation of the total AAPI was found among the 4 investigators. In addition, intraobserver reliability was excellent, and interobserver reliability was statistically reliable. Conclusion: The AAPI seems to represent a system capable of truly quantifying overall hair loss activity in AA patients with different severity, demonstrating trustworthy interobserver and intraobserver reliability.

Mildly heated forceps: A useful instrument for easy and complete removal of ticks on the skin

SURGICAL CHALLENGE Physical methods, such as slow, steady pulling on the tick, have been suggested as a standard technique for removing ticks. However, excessive and uncontrolled external force can leave part of the tick’s body in the skin. Leaving the tick’s body parts behind may result in localized inflammation and infection, which can lead to foreign body granulomas and abscesses in severe cases. In this case, retained parts should be removed surgically. However, surgical removal around dangerous and cosmetically problematic lesions such as lower eyelid is not easy and there is a possibility of serious cosmetic complications.

Long-Term Prognosis of Alopecia Totalis and Alopecia Universalis: A Longitudinal Study with More than 10 Years of Follow-Up: Better than Reported

Background: In alopecia totalis (AT) and alopecia universalis (AU), the chance of full hair regrowth is known to be less than 10%. However, this information is based on a few older studies conducted in the 1950s and 1960s. Objective: We investigated the current long-term prognosis of individuals with AT/AU. Methods: A retrospective chart review was performed in patients with AT/AU between 1994 and 2005. Outcome data were collected by reviewing outpatient clinical files or by phone interviews. Finally, the long-term assessment of 70 patients with valid outcome data was performed. Results: Twelve out of 70 patients with AT/AU (17.1%) had complete hair regrowth. Five out of 24 patients with AT (20.8%) showed complete hair regrowth, and 7 of 46 patients with AU (15.2%) achieved complete regrowth. Seventeen out of 70 patients with AT/AU (24.2%) reported hair regrowth greater than or equal to 90%. Thirty patients with AU (65.2%) remained in an alopecic state without improvement, while 5 patients with AT (20.8%) showed no hair regrowth. Conclusion: Our results suggest that the long-term prognosis of AT/AU is more favorable than previously thought. However, the clinical burden of AT/AU is still substantial.

Pathological evidence of foreign body reaction induced by bee sting therapy.

To the Editor , Bong-Chim, otherwise known as live bee sting therapy, is used for treatment of chronic recalcitrant neuralgia, arthralgia and dermatitis in Korean traditional medicine.1 Live bee sting therapy involves direct injection of the bee sting into the lesion from a live bee. Live bee sting therapy intentionally leave the venom sac in the tissue for therapeutic purposes. For this reason, various clinical reactions, from mild live

Increased blood levels of NKG2D+CD4+ T cells in patients with alopecia areata

did not affect serum CXCL10 levels, consistent with observations in our mouse model (Supplemental Fig 2; available at http://www.jaad.org). The most common side effects of simvastatin were self-limited myalgia in 4 participants and diarrhea in 2 participants. Three participants had mild, transient transaminitis and 4 had mild creatine phosphokinase elevations, none requiring dose modifications. Only 1 withdrawal, because of vertigo, was thought to be treatment-related. Our study does not support the use of oral simvastatin for the treatment of vitiligo. Disparate findings in this study compared with our mouse model may be a result of dosing limitations in humans because of potential toxicity, which is not a concern in mice. Our failure to show efficacy may also have been influenced by long-standing disease in our participants (responses are best in those with recent onset), small sample size, or lack of sensitive measures of treatment response. The VASI relies on an estimation of affected BSA, with limited sensitivity to change ([4.7% BSA). Newer outcome measures may provide more sensitive options for monitoring responses. Simvastatin may induce myopathy at higher doses; however, topical treatment may allow the delivery of sufficiently high local concentrations without systemic toxicity and could be tested in larger studies.