CXCL12 Neutralizing Antibody Promotes Hair Growth in Androgenic Alopecia and Alopecia Areata.

We had previously investigated the expression and functional role of C-X-C Motif Chemokine Ligand 12 (CXCL12) during the hair cycle progression. CXCL12 was highly expressed in stromal cells such as dermal fibroblasts (DFs) and inhibition of CXCL12 increased hair growth. Therefore, we further investigated whether a CXCL12 neutralizing antibody (αCXCL12) is effective for androgenic alopecia (AGA) and alopecia areata (AA) and studied the underlying molecular mechanism for treating these diseases. In the AGA model, CXCL12 is highly expressed in DFs. Subcutaneous (s.c.) injection of αCXCL12 significantly induced hair growth in AGA mice, and treatment with αCXCL12 attenuated the androgen-induced hair damage in hair organ culture. Androgens increased the secretion of CXCL12 from DFs through the androgen receptor (AR). Secreted CXCL12 from DFs increased the expression of the AR and C-X-C Motif Chemokine Receptor 4 (CXCR4) in dermal papilla cells (DPCs), which induced hair loss in AGA. Likewise, CXCL12 expression is increased in AA mice, while s.c. injection of αCXCL12 significantly inhibited hair loss in AA mice and reduced the number of CD8+, MHC-I+, and MHC-II+ cells in the skin. In addition, injection of αCXCL12 also prevented the onset of AA and reduced the number of CD8+ cells. Interferon-γ (IFNγ) treatment increased the secretion of CXCL12 from DFs through the signal transducer and activator of transcription 3 (STAT3) pathway, and αCXCL12 treatment protected the hair follicle from IFNγ in hair organ culture. Collectively, these results indicate that CXCL12 is involved in the progression of AGA and AA and antibody therapy for CXCL12 is promising for hair loss treatment.

Efficacy and Safety of Precision Cryotherapy to Treat Seborrheic Dermatitis of the Scalp.

BACKGROUND: Recently, a new cryotherapy device that precisely controls skin temperature was developed. Precision cryotherapy (PC) can be a safe and alternative treatment modality for immune-related skin diseases that are difficult to treat by conventional cryotherapy because of serious adverse events. OBJECTIVE: To evaluate the efficacy and safety of PC in scalp seborrheic dermatitis (SD). METHODS: A single-arm, prospective trial was designed. Twenty-four patients with SD underwent 3 PC interventions 2 weeks apart. At the baseline, Week 6, and Week 8, overall improvements in Physician Global Assessment (PGA) and clinical severity scores were assessed. At each visit, the erythema index (EI) and transepidermal water loss were evaluated. The patients scored 9 subjective symptoms using a visual analog scale (VAS). RESULTS: The itch VAS score decreased by 50.4% at Week 8. Blinded investigators reported improvement of PGA scores from 2.86 ± 0.62 to 1.66 ± 0.61 and clinical severity scores from 4.55 ± 1.30 to 2.45 ± 1.37. The average EI decreased by 19.6% at Week 8 ( p < .05). CONCLUSION: This study not only demonstrated the efficacy and safety of PC in scalp SD but it also revealed insights for PC being a promising treatment modality in immune-related skin diseases.

Low-Grade Myofibroblastic Sarcoma on Back with Repeated Localized Recurrence and Regional Metastasis.

Low-grade myofibroblastic sarcoma (LGMS) is a rare spindle cell tumor with indolent course. Due to rarity and low-grade histologic features of LGMS, accurate diagnosis is challenging. We report a 63-year-old female patient with a three-month history of a 3.1 cm×2.5 cm sized, firm, skin-colored, painless, protruding left back mass. Initial excisional biopsy was performed and the mass was diagnosed as nodular fasciitis. After 18 months after excision, the mass recurred with pain and grew larger. Considering the clinical manifestations, diagnostic impression was changed as dermatofibrosarcoma protuberans not nodular fasciitis. Second wide excision was performed and the histopathology revealed proliferative atypical spindle cells with moderate nuclear atypia and a distinctive whorling pattern, which is suggestive of low-grade sarcoma. Additional computed tomography and positron emission tomography revealed no metastasis and suspicious residual viable malignant tissue. To remove suspicious residual tumor, third wide excision were performed and the diagnosis confirmed as LGMS. A microscopically clear resection was achieved with deep and lateral safety margin 0.6 cm each. Despite of postoperative radiotherapy with 35 times, recurrence of the tumor and lung metastasis was found after 7 months later. LGMS rarely metastasizes and occurs most commonly in the head and neck region. Thus, we report a rare case of LGMS on back which repeated localized recurrence and regional lung metastasis occurred despite wide excision and adjuvant radiotherapy.

Fixed Drug Eruption in a Patient Taking Valacyclovir without Cross-Reactivity to Acyclovir.

Fixed drug eruption (FDE) is a well-defined hyperpigmented patch that recurs in a fixed location each time a particular drug is taken. Common causative agents of FDE are non-steroidal anti-inflammatory drugs, non-narcotic analgesics, sedatives, anticonvulsants, sulfonamides, and tetracycline. We report a 33-year-old male who presented with a recurrent, localized, brownish-to-erythematous macule and papules on the peri-philtrum area two hours after taking valacyclovir. Three episodes of valacyclovir ingestion for treatment of Herpes simplex virus infection provoked a similar skin rash at the same site. Histopathology results showed vacuolar degeneration in the basal layer of the epidermis, pigmentary incontinence, and perivascular inflammatory cell infiltration in the papillary dermis. Although patch test and skin prick test showed negative responses to acyclovir and valacyclovir, an intradermal test showed a positive reaction only to valacyclovir. The oral provocation test to acyclovir and valacyclovir showed a positive reaction only to valacyclovir. Through drug history, histopathological examination, patch test, intradermal test, and oral provocation test, we established a final diagnosis of FDE due to valacyclovir without cross-reactivity to acyclovir. To find alternative therapeutic drugs, we suggest diagnostic tests with not only the suspected drugs, but also other drugs in the same class.

Insulin-Derived Cutaneous Amyloidosis: A Possible Complication of Repeated Insulin Injections.

Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of pathological fibril aggregation of proteins in the skin without systemic involvement. Macular amyloidosis, lichen (papular) amyloidosis, and nodular amyloidosis are three different subtypes of PLCA. Although the pathological mechanism of PLCA has not yet been clarified, it is assumed that a nucleus formation of amyloid fibril is formed due to repeated external stimulation, such as subcutaneous injection, which often poses diagnostic challenges. Herein, we present a 54-year-old Korean male patient with cutaneous localized amyloidosis which occurred after repeated local insulin injections, and discuss the relationship between insulin therapy in patients with diabetes mellitus and dermal amyloid deposition.

Clinical Evaluation of Conditioned Media of Human Umbilical Cord Blood Mesenchymal Stem Cells for Improvement of Symptoms of Sensitive Skin: Prospective, Single Blinded, Split-face Study.

BACKGROUND: The exact definition of sensitive skin is not established yet. Since its high prevalence and significant influence on quality of life, it has become an important topic of research. Among various ingredients, conditioned media from umbilical cord blood-derived mesenchymal stem cells (UCB-MSC-CM) can be a promising source for the treatment of sensitive skin. OBJECTIVE: We evaluated the efficacy and safety of UCB-MSC-CM on patients with sensitive skin. METHODS: We designed a randomized, single blinded, prospective, split-face comparison study and enrolled thirty patients. All patients underwent nonablative fractional laser over the entire face before UCB-MSC-CM or normal saline was applied. Each facial area was randomly assigned to undergo treatment with either UCB-MSC-CM or normal saline. We performed three sessions at two-week intervals, and final results were assessed on six weeks after the last session. As an outcome measure, we evaluated a five-point global assessment scale, transepidermal water loss (TEWL), erythema index (EI) and Sensitive Scale-10. Twenty seven subjects were included in final analysis. RESULTS: The treated side exhibited greater improvement compared to the untreated side based on a five-point global assessment scale. TEWL, EI of the treated side were significantly lower than those of the untreated side throughout study period. Sensitive Scale-10 was significantly improved after treatment. CONCLUSION: The application of UCB-MSC-CM resulted in improved skin barrier function and reduced inflammatory responsiveness, which could provide beneficial effect on sensitive skin.

Photothermal therapy using gold nanoparticles and a long-pulsed 755-nm alexandrite laser to treat facial photoaging in Asian skin: A prospective clinical trial.

BACKGROUND AND OBJECTIVES: Transdermally delivered gold nanoparticles (AuNPs) irradiated with near-infrared laser energy can create a photothermal effect within the sebaceous glands (SGs). Photothermal therapy (PTT) can be used clinically to reverse photoaging in SG-rich areas of the skin. Improvements in wrinkles and enlarged pores in Asian skin were assessed following AuNP-mediated PTT with a long-pulsed 755-nm alexandrite laser. STUDY DESIGN/MATERIALS AND METHODS: A single-arm, prospective trial was designed. Twenty Korean patients underwent three gold PTT interventions performed 4 weeks apart at laser hair-removal settings without cooling. At Week 20, changes in the wrinkle index (WI) and pore index (PI), size, and count were calculated using three-dimensional camera analyses. Overall improvements in wrinkles and pores (0-4 scale) were assessed by blinded investigators using standardized photographic comparisons. The subjects scored their satisfaction (0-10 scale) and treatment discomfort (0-10 scale). Safety data were also collected. RESULTS: There were significant reductions in the WI (8.3%, p < 0.01), pore size (23.1%, p = 0.035), and PI (19.9%, p = 0.034) in the periorbital areas at week 20 compared with baseline. The mean reductions in the size (22.5%, p = 0.027), count (16.5%, p = 0.048), and index (22.4%, p = 0.023) of the cheek pores were also significant. Investigators reported average scores of 3.2 ± 0.6 for improved wrinkle appearance, and 3.1 ± 0.7 for improvement in visible pores. Participants were moderately satisfied with the overall results (7.6 ± 1.8). Subjects felt moderate discomfort during treatment (4.7 ± 2.6). No serious or persistent adverse events occurred. CONCLUSIONS: AuNP-mediated PTT showed noticeable efficacy and tolerability in treating wrinkles and pores in Asian skin over a 12 week-follow-up. Further studies with a longer follow-up are needed to confirm the reduction in SG activity at the parameters used.

A Phase 3, Randomized, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Neu-BoNT/A in Treatment of Primary Axillary Hyperhidrosis.

BACKGROUND: Botulinum toxin type A is widely used to treat primary axillary hyperhidrosis and has proven to be an effective and safe approach. Onabotulinumtoxin A was approved by the FDA as a treatment for primary axillary hyperhidrosis. This study aimed to evaluate the efficacy and safety of Neu-BoNT/A in subjects diagnosed with primary axillary hyperhidrosis. METHODS: The Hyperhidrosis Disease Severity Scale, gravimetric measurement of sweat, and Global Assessment Scale were analyzed at weeks 4, 8, 12, and 16 to determine the effect of treatment. Adverse events, physical examination, and vital signs were monitored. RESULTS: Subjects treated with Neu-BoNT/A showed statistically significant improvement by all 3 methods at weeks 4, 8, 12, and 16 (P value = 0.00). There were no severe adverse events or significant changes in vital signs, physical examination, or laboratory tests. CONCLUSION: Neu-BoNT/A can be effectively and safely used for primary axillary hyperhidrosis. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Beneficial Effect on Pigmentation Using Laser Epilation as an Initial Treatment Approach for Becker's Nevus in Asian Skin.

Becker's nevus (BN) clinically presents as brown patches with hypertrichosis. The risk of pigmentary changes still remains a concern when using lasers to treat Asian patients with BN. We aimed to evaluate the outcomes on reduction of hairs and pigment of BN using the long-pulsed 1064-nm Nd:YAG (LPNY) and/or 755-nm alexandrite (LP-Alex), before treating pigment in earnest. A total of 13 subjects were treated with the LPNY (n = 8), the LP-Alex (n = 4), and both (n = 1). Improvements on hair removal and pigment reduction were assessed using a 5-point global assessment scale. Patient satisfaction was also assessed. Treatment parameters were within those commonly used for the purpose of epilation. The average follow-up period was 19.5 ± 12.3 weeks, and the mean total number of sessions was 2.0. Eleven subjects reported >50% improvement in hair removal (11/13, 86.7%), and pigment reduction of >50% improvement was observed in 9 subjects (9/13, 69.2%). Patient satisfaction showed >50% lesion clearance in 84.6%. Hair removal settings of LPNY and LP-Alex were effective in both hypertrichosis and pigment reduction in the initial strategy of treatment of BN in skin of color.

Effect of Tranexamic Acid Administration on Postoperative Ecchymosis and Edema in Excision of Lipomas.

BACKGROUND: Previous studies have shown that systemic tranexamic acid reduces bleeding during soft tissue surgeries and reduces postoperative ecchymosis and edema experienced by surgical patients. OBJECTIVE: To evaluate the effect of postoperative tranexamic acid administration on the reduction of ecchymosis and edema after lipoma surgery. MATERIALS AND METHODS: A total of 40 patients who underwent lipoma excision were included in the comparative analysis. In the tranexamic acid group (n = 20), 1 g of tranexamic acid was administered daily for 5 consecutive postoperative days. Tranexamic acid was not administered to the control group (n = 20). The severity of ecchymosis and edema at the first visit after surgery was rated on a 4-point scale by 2 blinded dermatologists. RESULTS: The mean interval of the initial visit after surgery was 1.1 ± 0.5 (range: 1-4) days. Mean ecchymosis scores were significantly lower in the tranexamic acid group (0.5 ± 0.8) than in the control group (1.2 ± 1.0) (p < .05). No statistical difference was seen in mean edema scores between groups (0.5 ± 0.6 in tranexamic acid vs 0.7 ± 0.8 in control). CONCLUSION: We observed that postoperative administration of tranexamic acid significantly decreased ecchymosis in lipoma excision.

Treatment of idiopathic onychodystrophy with a 1064 nm picosecond neodymium-doped:yttrium aluminum garnet laser: A retrospective study.

BACKGROUND: Laser treatment has emerged as a novel treatment modality for onychodystrophy. Only a few small series have assessed the efficacy of laser treatment in onychodystrophy, most of which were case reports. The therapeutic effect of the 1064 nm neodymium-doped:yttrium aluminum garnet (Nd:YAG) laser for onychodystrophy has been demonstrated. Recently, the picosecond Nd:YAG (PSNY) laser has been introduced to improve various skin disorders. AIMS: The aim of this study was to verify the efficacy of a 1064 nm PSNY in management of idiopathic onychodystrophy. METHODS: We present a case series of dystrophic nails treated with a PSNY for onychodystrophy improvement. Planimetry using ImageJ software was used to calculate lesion reduction and proximal clear nail growth. Clinical improvement was assessed using a 5-point Global Assessment Scale (GAS). Adverse events were also assessed. RESULTS: Twenty-five patients (11 males and 14 females) with a total of 128 nails (94 finger nails and 34 toe nails) were treated. The mean treatment number was 8.7 ± 6.2, and the mean total duration of treatment was 33.4 ± 34.6 weeks. The average proportion of the lesion area decreased significantly (from 65.9% to 46.6%) after PSNY treatment (P < .001). The mean GAS (3.16 ± 1.18) exhibited fair improvement, and there were no serious adverse events. CONCLUSION: The 1064 nm PSNY laser can provide fair improvement for onychodystrophy with a good prognosis at least during the follow-up period and optimal cosmetic results in Asian patients.

Hair growth promotion by necrostatin-1s.

Necrostatins (Necs) have been developed as a receptor-interacting protein kinase 1 (RIPK1) inhibitor, thus inhibiting necroptosis. In this current study, we have investigated the possible involvement of necroptosis in the hair cycle regulation and further examined its underlying molecular mechanisms. Diverse RIPK1/3 inhibitors and siRNA were tested in the human outer-root sheath (ORS) cells and animal models. The expression and hair cycle-dependent expression of RIPK 1, respectively, were investigated in the hair follicles (HF) of human, pig, and the mouse. Resulting from the experiment, Nec-1s was most effective in the hair growth promotion among several inhibitors. Nec-1s induced the ORS cell proliferation and migration, and increased the HF length in mouse and pig organ cultures. In addition, it accelerated the telogen-to-anagen transition and elongated the anagen period in the mouse model. Both apoptosis and necroptosis were detected in hair cycle. RIPK1 and RIPK3 were highly expressed in ORS cells during the hair regression period. Nec-1s upregulated the mRNA expression of Wnt3a and Wnt5b, and the activity of ß-catenin. Collectively, Nec-1s promotes hair growth through inhibiting necroptosis and activating the Wnt/ß-catenin pathway. Necroptosis is involved in hair cycle regression, and Nec-1s is a promising target for hair-loss treatment.

Epiregulin promotes hair growth via EGFR-medicated epidermal and ErbB4-mediated dermal stimulation.

OBJECTIVES: EREG (epiregulin), a member of the epidermal growth factor (EGF) family, plays a role in inflammation, wound healing, normal physiology and malignancies. However, little is known about its function on hair growth. MATERIALS AND METHODS: Cell growth assay, QPCR and immunostaining were carried out. Telogen-to-anagen transition and organ culture were conducted. ROS level was monitored by staining DCFDA. RESULTS: We investigated the hair inductive effect of EREG and the mechanism of stimulation on DPCs and ORS cells during hair cycling. Whereas EREG promoted hair growth, EREG knockdown inhibited hair growth as evidenced by telogen-to-anagen transition and organ culture models. EREG was expressed in epidermal cells including ORS cells in vivo. EREG activated phospho-ErbB4 in DPCs during hair cycling and stimulated DPCs via ErbB4 activation in vitro. In terms of the underlying mechanism, reactive oxygen species (ROS) played a key role in DPC stimulation. EREG also activated phospho-EGF receptor (EGFR) in epidermal cells including matrix and ORS cells in vivo and stimulated ORS cells via EGFR activation in vitro. CONCLUSIONS: EREG, which is released from ORS cells, activated EGFR and ErbB4 on epidermal cells and DPCs during hair cycling, respectively. As a result, EREG stimulated epidermal cells a positive feedback and DPCs via regulating ROS generation for hair growth. Therefore, EREG therapy may be a novel solution for hair loss treatment.

Auricular keloid management in Asian skin: Clinical outcome of intralesional excision and postoperative triamcinolone acetonide intralesional injection.

BACKGROUND: Various options such as surgical excision, steroid injection, cryotherapy, pressure dressing, and radiation therapy are available for the treatment of auricular keloids. In particular, auricular keloid therapy using surgical excision is important because recurrence rates are low compared with keloids occurring in other parts of the body. AIMS: We aimed to evaluate the clinical outcomes of intralesional excision followed by postoperative triamcinolone acetonide intralesional injection (TA ILI) as auricular keloid treatments. METHODS: We conducted a surgery records and chart review of patients who underwent auricular keloid treatment with intralesional excision and TA ILI. Reduction in height and volume was assessed by two blinded dermatologists. We also analyzed the recurrence rate over a 2-year period and evaluated patient satisfaction using an 11-point questionnaire (0-10). RESULTS: Eighteen Korean patients (2 males and 16 females) with a mean age of 26.5 years and a total of 20 lesions were evaluated. Lesion types by descending frequency were lobular (n = 10, 50%), anterior/posterior button (n = 3, 15%), wrap-around (n = 3, 15%), dumbbell (n = 2, 10%), and sessile (n = 2, 10%). The total recurrence rate was 5% (1/20) within the 24-month follow-up period. Significant reduction (> 50%) in height and volume was achieved in 95% of patients. No serious or persistent adverse events were reported during the follow-up period. CONCLUSION: We confirmed that TA ILI after intralesional excision can be effective for auricular keloid management. A low recurrence rate similar to that of postoperative radiation therapy was obtained with an effective surgical procedure and minimal postoperative treatment.