Minseok Lee

Resident and monocyte-derived Langerhans cells are required for imiquimod-induced psoriasis-like dermatitis model.

BACKGROUND Langerhans cells (LCs) are dendritic cells that reside in the epidermis and local inflammation results in an increased differentiation of monocyte-derived LCs. Only few studies have investigated on the role of LCs in psoriasis-like dermatitis model, but the results are variable and the exact role of LCs in psoriasis model remains to be elucidated. OBJECTIVE To explore the functional role of resident (rLCs) and monocyte-derived LCs (mLCs) in imiquimod (IMQ)-induced psoriasis-like inflammation using human Langerin-diphtheria toxin subunit A (huLang-DTA) mice. METHODS 5% IMQ cream was topically applied on the skins. Clinical and histopathological features were evaluated. Psoriasis-related gene expression was analyzed by quantitative polymerase chain reaction. The production of psoriasis-related cytokines including IL-17A and IL-22 by T cells were assessed by flow cytometry from the lesional skins. RESULTS huLang-DTA mice showed a common depletion of both rLCs and mLCs in the IMQ-treated skins. huLang-DTA mice had a reduced IMQ-induced psoriasis-like inflammation featuring erythema, scale, and thickness compared with wild-type mice. Psoriatic lesions from huLang-DTA mice had a decreased level of Il23a and accordingly demonstrated an attenuated cytokine production of IL-17A and IL-22 from γδlow T cells. mLCs revealed a significantly greater level of IL-23 expression compared to rLCs in response to topical IMQ treatment. CONCLUSION Although both rLCs and mLCs are involved in the development of IMQ-induced psoriasis-like dermatitis, inflammation-induced mLCs present a superior capacity for producing IL-23 in this murine experimental model of psoriasis.

Interleukin-21 receptor signalling is not critically required for imiquimod-induced psoriasiform dermatitis in mice

Psoriasis is largely mediated by interleukin (IL)‐23/T helper (Th) 17 axis, and IL‐21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously reported possible pathogenic roles of IL‐21 in human psoriasis, we found that IL‐21 receptor (IL‐21R) signalling was not crucial for imiquimod‐induced psoriatic inflammation, using IL‐21R−/− mice. The severity of imiquimod‐induced psoriatic manifestation and pro‐inflammatory Th17 cytokine levels, IL‐17A‐producing γδ T cells and CD4+ T cells, and in vitro IL‐17A production by γδ T cells after IL‐23 stimulation was comparable between wild‐type and IL‐21R−/− mice. Collectively, IL‐21R signalling was not critically involved in IMQ‐induced psoriatic inflammation despite an increased IL‐21 expression in the IMQ‐treated mouse skin. Our data may represent the significant differences between human psoriasis and murine psoriasis model, and further studies using other models will be required to elucidate the role of IL‐21 in psoriasis pathogenesis.

Thiopurine S-Methyltransferase Polymorphisms in Korean Dermatologic Patients

Background Thiopurine S-methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurines including azathioprine (AZA), 6-mercaptopurine, and 6-thioguanine. TPMT genotyping is widely used for screening of AZA-related toxicity during routine clinical practice in Korea. However, the data of TPMT genotypes and its AZA-related toxicity have not been studied in the field of dermatology. Objective The aim of this study was to evaluate the genetic basis of TPMT polymorphism in Korean dermatologic patients and subsequently to investigate the relationship between mutant TPMT and adverse responses to AZA treatment. Methods This study was retrospective, single-center study. One hundred forty-nine Korean dermatologic patients who underwent TPMT screening test were included. Each patients medical records, the result of TPMT screening test, dose and treatment period of AZA, and side effects, were reviewed. Laboratory tests were assessed at each visit in order to monitor adverse drug reactions. Leukopenia grading was used in accordance with the common terminology criteria for adverse events (CTCAE) ver. 4.03. Results Behçets disease was the leading disorder among the patients. The frequency of TPMT mutation was 4.0% (6/149) among the participants in this study. Four of the six patients with genetic alterations were treated with a low-dose AZA regimen, but no AZA-related adverse events were observed. Conclusion Our results suggest that 1) TPMT polymorphisms in Korean dermatologic patients are similar to those previously reported in Asian patients with the most common mutant allele being TPMT*3C and 2) AZA can be used in the patients with these polymorphisms under a careful dosing regimen.

A twist on piloleiomyoma: segmental cutaneous leiomyomatosis.

To the Editor, Leiomyomas are benign soft tissue neoplasms that arise from vascular, arrector pili, genital and mamillary smooth muscles.1,2 Despite the relatively consistent clinical characteristics of pilar leiomyomas as small dermal papules localized on extremities, an accurate clinical diagnosis is often difficult to make.3 Herein, we report a case of segmental cutaneous leiomyomatosis located on the face and neck area in the form of multiple grouped papulonodules, the clinical diagnosis of which was challenging owing to its multiplicity and unusual anatomic distribution. A 68-year-old Korean female patient presented with multiple grouped papulonodular lesions

Predictive value of bone scintigraphy for the detection of joint involvement in Behçet’s disease: Dermatologists’ perspectives

BackgroundBehçet’s disease (BD) is a multisystemic inflammatory disease with articular involvement. Non-specific arthralgia without objective signs of arthritis, such as swelling or effusion, is common in such patients. Thus, an accurate diagnosis of joint involvement may be challenging for dermatologists.ObjectivesTo evaluate the validity of 99mTc-methylene diphosphonate (Tc-99m-MDP) bone scintigraphy for joint involvement assessment in patients with BD.Materials and methodsIn 211 patients with BD who had scintigraphic evaluations due to joint symptoms, agreement between bone scintigraphy findings and clinically evaluated joint complaints was retrospectively assessed using Cohen’s kappa (ĸ) statistic. A patient subset (n = 104) showing agreement between joint complaints and scintigraphy results was re-evaluated by a rheumatologist to determine the level of diagnostic specificity attained by combining bone scintigraphy with clinical examinations of dermatologists.ResultsThe total kappa value (211 patients) was 0.604, indicating fair agreement between joint complaints and scintigraphy results. Individual analysis of eleven joint categories revealed statistically significant correlations for wrist (ĸ = 0.677), shoulder (ĸ = 0.661), and foot joints (ĸ = 0.618). Of the 104 referrals to a rheumatologist, 95 (91.34%) were confirmed as having BD-associated articular involvement. Joint acral areas (e.g., foot, hand, wrist and shoulder) that had the highest kappa value correlations also ranked highest in diagnostic specificity.ConclusionBone scintigraphy presents a simple and useful option for dermatologists to assess joint involvement in BD patients, especially for specific anatomic sites.