Phase I/II trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate-to-severe atopic dermatitis.

BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: To investigate the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase I open-label trial followed by a phase II randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase I, intravenous (IV) administration of hcMSCs at two doses (1×106 and 5×105 cells/kg) was safe and well-tolerated in 20 subjects. Since there was no difference between the two dosage groups (P=0.9), it was decided to administer low-dose hcMSCs only for phase II. In phase II, subjects receiving three weekly IV infusions of hcMSCs at 5x105 cells/kg showed a higher proportion of an eczema area and severity index (EASI)-50 response at week 12 compared to the placebo group (P=0.038). The differences between groups in the dermatology life quality index and pruritus numerical-rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: Our findings demonstrate that hcMSCs treatment resulted in a significantly higher rate of achieving EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSCs treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.

Factors Associated With Achieving Complete Skin Clearance Compared to Almost Complete Skin Clearance in Patients With Moderate to Severe Psoriasis Treated With Biologics: A Retrospective Chart Review.

BACKGROUND: Biologics have demonstrated high efficacy in achieving 'almost complete' skin clearance in patients with moderate to severe psoriasis. Nonetheless, achieving 'complete' skin clearance remains a treatment goal for some highly biologics-resistant patients, as residual lesions impact their quality of life. OBJECTIVE: The risk factors for failure to achieve a Psoriasis Area and Severity Index (PASI) 100 response in patients with good response to biologics remain unknown. METHODS: This retrospective study evaluated the risk factors by comparing patients who achieved complete skin clearance (PASI100) with those who achieved almost complete skin clearance (PASI90). A database of 131 psoriasis patients treated with biologics, who achieved a PASI90 or PASI100 response, was reviewed from a tertiary referral hospital in South Korea. The patients were classified into PASI90 and PASI100 groups according to their PASI response. RESULTS: The PASI100 group had a lower prevalence of smoking history (adjusted odds ratio [OR], 0.34; 95% confidence interval [CI], 0.14-0.85; p=0.021) and psoriasis on the anterior lower legs at baseline (adjusted OR, 0.18; 95% CI, 0.03-0.99; p=0.049) than patients in the PASI90 group. CONCLUSION: This study suggested that smoking history and psoriatic skin lesions on the anterior lower legs are considered as the risk factors for the failure to achieve a PASI100 response in psoriasis patients treated with biologics.

Relationships of Serum Homocysteine, Vitamin B12, and Folic Acid Levels with Papulopustular Rosacea Severity: A Case-Control Study.

Background: Rosacea is a chronic inflammatory skin disease with a multifactorial etiology. Recently, associations between serum homocysteine (Hcy) levels and inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa, have been reported. However, no study has explored the levels of serum Hcy, folic acid, and vitamin B12 in patients with rosacea. Objective: To investigate serum Hcy, vitamin B12, and folic acid levels in patients with papulopustular rosacea (PPR), we characterized the association of these levels with PPR severity. Methods: This case-control study included 138 PPR patients and 58 healthy controls. The serum levels of Hcy, vitamin B12, and folic acid were measured. A correlation was assessed between disease severity and serum levels of Hcy, vitamin B12, and folic acid. Results: Serum vitamin B12 and folic acid levels were significantly lower in PPR patients than in the healthy controls (p = 0.011 and p = 0.0173, respectively). Although serum Hcy levels did not significantly differ between PPR patients and healthy controls, PPR severity was positively correlated with serum Hcy levels (p < 0.001). Conclusions: Our results suggest a possible association between hyperhomocysteinemia and vitamin B12 deficiency in patients with PPR.

Association between Skin Cancer and Systemic and Ocular Comorbidities in South Korea.

BACKGROUND: In this study, we investigated the associations between various systemic and ocular comorbidities and skin cancer, in a nationwide cohort of South Koreans. METHOD: We reviewed the data of 1,103,302 individuals in the South Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2015. Of these, 1202 individuals diagnosed with skin cancer from 2004 were included in the study group. The control group was matched in a 1:5 ratio based on propensity scores. RESULTS: The prevalence rates of melanoma and non-melanoma skin cancer increased from 2004 to 2015. Multivariate logistic regression analysis revealed that, among the various systemic conditions, hypertension was significantly associated with skin cancer, while among ocular comorbidities, macular degeneration showed a significant association with skin cancer. CONCLUSIONS: This is the first study to demonstrate associations between skin cancer and various systemic and ocular comorbidities. The results suggest that hypertension and macular degeneration may increase the risk of skin cancer development, or vice versa. Further studies are needed to evaluate the causal relationships between these conditions.

Clinicopathologic Features and Prognostic Factors of Primary Cutaneous Melanoma: a Multicenter Study in Korea.

BACKGROUND: Malignant melanoma is a cutaneous malignancy with a high mortality rate and high potential for metastases. Detailed information on the clinicopathologic characteristics and prognostic factors of cutaneous melanoma is currently limited in Korea. This study aimed to identify the epidemiological and clinicopathologic characteristics of primary cutaneous melanoma in Korean patients, and to assess which prognostic variables could influence both the development of metastases in primary cutaneous melanoma and overall survival (OS). METHODS: A total of 261 patients diagnosed with primary cutaneous melanoma in seven medical centers between 1997 and 2017 were retrospectively investigated with regard to clinical presentation, localization of the tumor, histopathologic subtype, and survival time. RESULTS: The nodular histologic subtype, ulceration, and Breslow thickness were significantly associated with the development of metastasis; and overweight and obesity (body mass index > 23) were significantly associated with increased Breslow thickness. The location of the metastases appeared to influence OS: brain metastases were associated with the highest risk of death, followed by gastrointestinal, lung, and extra-regional lymph node metastases. CONCLUSION: In this study, tumor thickness, nodular histologic subtype, and ulceration predicted metastatic spread of primary cutaneous melanoma. In addition, OS was associated with the location of metastases. Obesity was related to the prognosis of primary cutaneous melanoma. Clinicians should bear these findings in mind when forming a diagnosis because of the risk of a poor prognosis.

Cataract, Glaucoma, and Dry Eye Disease in Adults with Atopic Dermatitis: A Nationwide Cross-Sectional Study from the Republic of Korea.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disorder characterized by relapsing eczema with intractable itching. Ocular diseases in patients with AD, including cataract, retinal detachment, blepharitis, glaucoma, keratoconjunctivitis, and keratoconus, have frequently been reported worldwide. However, only a few studies using a large-sample, population-based study design have been reported so far. OBJECTIVE: We investigated the association between cataract, glaucoma, and dry eye disease and AD in an adult population in the Republic of Korea. METHODS: A total of 14,900 adults who participated in the Korean National Health and Nutrition Examination Survey, a nationwide, population-based, cross-sectional survey, between 2010 and 2012 were included in the study. Multiple logistic regression analyses identified the possible association between cataract, glaucoma, and dry eye disease and AD relative to matched controls. RESULTS: After we adjusted for confounding factors in patients with AD, cataract and glaucoma were significantly associated with AD. Moreover, patients with AD had a higher prevalence of ophthalmic surgery compared to those without AD. CONCLUSION: Dermatologists should therefore be aware of possible ocular disorders in patients with AD and should recommend regular ophthalmic screening for early detection.

Case Series of Morbihan Disease (Extreme Eyelid Oedema Associated with Rosacea): Diagnostic and Therapeutic Approaches.

Morbihan disease (MD) is a rare form of rosacea that presents with chronic erythema and solid oedema on the upper half of the face. A diagnosis of MD can be made only after eliminating diseases that are similar in terms of clinical and histopathological presentation. The cause of MD remains unclear and no standardised treatment is yet available. MD often tends to be recalcitrant to therapies commonly used to treat rosacea, including systemic corticosteroids, antibiotics, isotretinoin, and topical regimens. Thus, surgical interventions have been attempted but most cases have exhibited unsatisfactory responses. We treated six patients with extreme eyelid lymphoedema without any other cutaneous manifestation. Surgical eyelid reduction was performed in all patients, because ptosis and narrowing of the visual field were the major complaints. Histopathological tests revealed various extents of perivascular and perifollicular inflammation, and dermal oedema. After surgery, patients with severe inflammatory cell infiltration (including mast cells) exhibited a tendency toward recurrence. Other patients with severe dermal oedema exhibited better responses to surgical reduction, and thus no recurrence. We propose that MD should be included in the differential diagnosis of persistent, chronic eyelid oedema even if eyelid oedema is the only manifestation; the histological features may aid in the selection of appropriate therapeutic strategies. We suggest that eyelid reduction surgery can be a useful treatment option for MD patients when there is no massive mast cell infiltration.

Treatment of Hidradenitis Suppurativa Patient with Klinefelter Syndrome by Adalimumab.

Hidradenitis suppurativa (HS) is a chronic, inflammatory and painful skin disease with recurrent nodules and tracts involving the intertriginous regions. It is known that the patient with HS shows an increased risk of metabolic disorders such as diabetes, metabolic syndrome and autoimmune diseases. Klinefelter syndrome (KS) is a sex chromosomal disorder occurring in males due to an abnormality of sexual differentiation, characterized by 47, XXY karyotype. Also, KS is related with somatic comorbidities such as metabolic syndrome, autoimmune and rheumatologic disorders as HS is. We report a HS patient with KS who shows a big improvement while on tumor necrosis factor-alpha inhibitor treatment.

Disseminated Superficial Actinic Porokeratosis in a Patient with Psoriasis, after Long-Term Narrowband Ultraviolet B Phototherapy.

Porokeratosis is a rare epidermal disorder characterized by annular or linear hyperkeratotic plaques with slightly raised thread-like borders, and in most cases, atrophic centers. Disseminated superficial porokeratosis and disseminated superficial actinic porokeratosis (DSAP), which primarily involve sun-exposed areas, are common types of porokeratoses. Histologically, a column of parakeratotic cells, a so-called cornoid lamella, is a hallmark of porokeratosis. Porokeratosis is considered to result from the inability to eliminate an abnormal keratinocyte clone induced by genetic factors and various stimuli, including sunlight, artificial ultraviolet light, viral infections, immunosuppressive conditions (hematologic malignancies, organ transplants, or autoimmune disease), and immunosuppressive therapies. Here, we report a 59-year-old Korean woman with DSAP that developed after narrowband ultraviolet B (NB-UVB) therapy for psoriasis. Our case emphasizes the occurrence of DSAP due to NB-UVB that is able to induce local immunosuppression at the irradiated site; the pathogenesis of DSAP remains unclear.

Psoriasis, Vitiligo and Crohn's Disease Co-Existing in a Single Patient: A Variant Type of Multiple Autoimmune Syndrome?

Multiple autoimmune syndrome (MAS) is a rare condition, in which at least three well-defined autoimmune diseases co-occur in a single patient. Although the pathogenesis of MAS remains poorly understood, genetic, immunological, hormonal, and environmental factors may all play a role. Although three classic subtypes of MAS are well known, several cases that could not be placed into any of these three categories have recently been reported. To the best of our knowledge, the co-existence of psoriasis, vitiligo, and Crohn's disease has been reported in only one patient, who had a total of five autoimmune diseases (alopecia areata and oral lichen planus in addition to the three conditions mentioned). We herein describe a rare case of MAS presenting with psoriasis, vitiligo, and Crohn's disease, and suggest that tumor necrosis factor-α may be associated with the pathogenesis of all three conditions.

Folliculocystic and Collagen Hamartoma: A New Entity?

Folliculocystic and collagen hamartoma is a newly described complex hamartoma characterized by abundant collagen deposition, concentric perifollicular fibrosis, and keratin- filled infundibular cysts that are visible on histopathological examination. Here, we report the case of a 19-year-old Korean man who had large brownish infiltrated plaques with numerous follicular comedo-like openings and subcutaneous cystic masses on his right temporal scalp and ear since birth. Histopathological examination showed abundant collagen deposition in the dermis that extended up to the subcutaneous fat layer, multifocal infundibular cysts packed with keratin, and perifollicular inflammation and fibrosis. Hence, we describe a new type of hamartoma with folliculocystic and collagen components but without tuberous sclerosis.

Treatment of melasma by low-fluence 1064 nm Q-switched Nd:YAG laser.

BACKGROUND: Low-fluence 1064 nm Q-switched Nd:YAG laser has recently been shown to be effective for the melasma treatment. OBJECTIVE: The purpose of this study is to evaluate the clinical efficacy and safety of low-fluence 1064 nm Q-switched Nd:YAG laser treatment of melasma in Asian patients. METHODS: Fifty patients with melasma underwent 15 weeks of weekly treatments, using a Q-switched Nd:YAG laser (RevLite®; HOYA ConBio®, Freemont, CA, USA) at 1064 nm with an 8-mm spot size, and a fluence of 2.8 J/cm(2). Patients and investigators subjectively evaluated the intensity of pigmentation after completion of 15 weekly treatments. The objective assessment was also performed with digital photographs and a pigment imaging tool (Janus®, PSI Co., Ltd., KOREA). RESULTS: Both patients and investigators rated the treatment outcome as "good improvement" on average with improvement rate of 50-74%. The pigment imaging technology system also confirmed the improvement of the pigmentation level on all three locations of the face. None of the 50 patients showed any signs of severe side effects during the course of the treatment. CONCLUSION: Low-fluence 1064 nm Q-switched Nd:YAG laser is an effective method to treat melasma without serious side effects in Asian patients.

Painful eccrine spiradenoma containing nerve fibers: a case report.

An eccrine spiradenoma is a rare benign tumor most often seen in the head, neck and upper trunk of young adults. Although spontaneous pain or tenderness is a typical symptom of eccrine spiradenomas, the underlying mechanism has not been fully elucidated. Here, we report the case of a 47- year-old woman who had a spiradenoma in the subcutaneous tissue of her posterior neck accompanied by agonizing pain which was triggered by pressure. Multiple nodular lesions were excised and the typical histopathological findings of spiradenoma were seen. The histopathological architecture of a disorganized nerve fiber encasing the tumor nodules appeared to correlate with the unique clinical symptom of pain.

Childhood granulomatous periorificial dermatitis.

Childhood granulomatous periorificial dermatitis (CGPD), also known as facial Afro-Caribbean childhood eruption (FACE), is a distinctive granulomatous form of perioral dermatitis. It is a condition of unknown etiology, characterized by monomorphous, small, papular eruptions around the mouth, nose and eyes that histopathologically show a granulomatous pattern. It affects prepubescent children of both sexes and typically persists for several months but resolved without scarring. We report a 9 year-old girl with multiple, discrete, monomorphic, papular eruptions of 2-months duration on the perioral and periocular areas. Histopathological examination demonstrated upper dermal and perifollicular granulomatous infiltrate.

An unusual case of congenital dermal melanocytosis.

Dermal melanocytosis is characterized by the presence of ectopic melanocytes in the dermis. The most common forms include the Mongolian spot, blue nevus, nevus of Ota, and nevus of Ito. Some types of dermal melanocytosis do not fit into any of these morphologic categories, however. Our case demonstrated an extensive amount of uniform deep blue patches of nevi with unilateral distribution on the left face, neck, chest, shoulder, and back. On histopathologic examination, a number of elongated melanocytes scattered throughout the dermis were found. We herein report a case of congenital unilateral dermal melanocytosis.