Safety, Efficacy, and Drug Survival of Colchicine in Recurrent Aphthous Stomatitis in a Real-World Setting

Background@#Recurrent aphthous stomatitis (RAS) is a common disorder characterized by episodic ulcerations in the oral mucosa. Although colchicine has been a common systemic treatment for RAS, there is still considerable uncertainty regarding its efficacy and drug survival in this setting. @*Objective@#We aimed to study drug survival, efficacy, and safety of colchicine for the treatment of RAS, especially in the real clinical setting. @*Methods@#Between 2012 and 2016, 150 patients given colchicine for RAS were selected for a single-centre retrospective study of real-world efficacy and drug survival. @*Results@#Among the 114 patients who qualified, 81.6% showed moderate or substantial responses (>25% improvement). Gastrointestinal complications (16.7%), neutropenia (3.5%), and liver enzyme elevation (4.4%) were reported within 2 weeks after initiating treatment.Delayed adverse manifestations were rare. One year after onset, colchicine use was sustained in roughly one-half (49.5%) of patients, whereas many (30.3%) had discontinued the drug, primarily due to lack of efficacy or adverse events. In Cox proportional hazard analysis, minor ulcers were identified as potential determinants of longer drug survival owing to less probability of non-efficacy. However, major ulcers had emerged as predictors of early discontinuation due to lack of efficacy. @*Conclusion@#In patients with RAS, colchicine may be an effective and safe treatment amenable to long-term maintenance. Monitoring of adverse events within 2 weeks after initiating treatment is advisable to ensure safe administration.

Clinical and Radiographic Characteristics of Neuro-Behçet's Disease in South Korea

BACKGROUND AND PURPOSE: Neurological involvement in Behçet's disease [neuro-Behçet's disease (NBD)] is uncommon, but it is worth investigating since it can cause substantial disability. However, difficulties exist in understanding the clinical features of NBD due to regional variations and the lack of studies utilizing well-established diagnostic criteria. We therefore analyzed the clinical features of patients with NBD based on the recent international consensus recommendation. METHODS: We retrospectively searched electronic databases for patients with Behçet's disease (BD) between 2000 and 2017, and reviewed their medical records. Based on the recent international consensus recommendation, patients with definite or probable NBD were included. RESULTS: Of 9,817 patients with the diagnosis code for BD, 1,682 (17.1%) visited the neurology clinic and 110 (1.1%) were classified as NBD. Ninety-eight patients exhibited parenchymal NBD and 12 exhibited nonparenchymal NBD. Their age at the onset of NBD was 37.6±10.6 years and the male-to-female ratio was 1.24:1. Brainstem syndrome (43.9%) was the most common condition in the 98 patients with parenchymal NBD, followed by multifocal (32.7%) and spinal cord (12.2%) syndromes. 72.4% exhibited acute NBD and 27.6% exhibited a progressive disease course. Frequent manifestations included pyramidal signs (52.0%), headache (45.9%), dysarthria (42.9%), and fever (31.6%). A frequent pattern in brain MRI was an upper brainstem lesion extending to the thalamus and basal ganglia. CONCLUSIONS: Approximately 1% of the patients with suspected BD exhibited NBD. Neurologists must understand the clinical characteristics of NBD in order to perform the differential diagnosis and management of these patients.

Centennial History of Yonsei University Dermatology in Korea: 1917 to 2017

Yonsei Dermatology celebrated its centennial in 2017, marking 100 years since Kung Sun Oh established the first Department of Dermatology and Urology in Korea in 1917. Following the footsteps of Kung Sun Oh, a pioneer of Korean dermatology, its members united and worked to provide the best medical service and achieve academic milestones in dermatology. Over the past hundred years, Yonsei Dermatology has played a pivotal role in the advancement of medical science and academia in Korea. The main activities of the department include medical care, education, and dermatologic research. Its research activities have encompassed a wide spectrum of dermatologic manifestations from skin immunology and pathology to introduction of newly developed treatment technologies. As Kung Sun Oh was the first Korean professor of dermatology at Severance Medical School and a passionate educator, we continue to serve his will by nurturing medical students and dermatology specialists to serve as global medical leaders. The Kung Sun Oh Memorial Lecture, first hosted in 1977, was the beginning of mutual international academic exchange in the field of dermatology in Korea. The memorial lecture has played a major role in advancing the academic status of Korean dermatological science by inviting distinguished dermatologists from around the world as guest lecturers. Yonsei Dermatology has played a key role in the history of modern medicine and dermatology in Korea over the last 100 years and continues to make an impact.

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 patient's 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: Behçet's 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.

Early Roots of Western Medicine and a Pioneer of Social Work in Korea: Dr. Kung Sun Oh (1878-1963)

No abstract available.

Carpal Tunnel Syndrome in Behcet's Disease

PURPOSE: Behcet's disease (BD) is a chronic inflammatory disease characterized by orogenital ulcers, skin and ocular lesions, in addition to articular, vascular, and neurologic symptoms. Carpal tunnel syndrome (CTS), can also occur in BD patients secondary to inflammation in the connective tissues, vessels, and tendons, as well as nerve involvement in BD itself. However, reports of patients who have CTS in BD are rare. The aim of this study was to evaluate the clinical characteristics of CTS in BD patients. MATERIALS AND METHODS: Retrospective analysis of the medical records of 1750 BD patients, and 14 (0.8%) BD patients who were diagnosed with CTS was performed at the BD Specialty Clinic of Severance Hospital. Patient demographics, disease activity/severity for both diseases, and the clinical characteristics of CTS in BD were recorded and analyzed. RESULTS: All 14 BD patients with CTS were women. Twelve patients (85.7%) were diagnosed with active BD. The CTS was mild in 8 patients (57.2%), moderate in 3 patients (21.4%), and severe in 3 patients (21.4%). Ten patients (71.4%) had BD prior to the diagnosis of CTS, and these 10 patients all had active BD. CONCLUSION: CTS can occur as a result of the inflammation associated with BD and can also be the presenting symptom of nerve involvement in BD. CTS can also develop as the initial symptom of BD. Therefore, a higher degree of suspicion should be maintained for CTS in patients with BD and vice versa; however, the exact relationship is uncertain.

Renal Manifestations in 2007 Korean Patients with Behcet's Disease

PURPOSE: Behcet's disease (BD) theoretically affects all sizes and types of blood vessels and results in multi-organ involvement. However, renal BD has not been fully characterized, though the kidneys are histologically rich in blood vessels. MATERIALS AND METHODS: A total of 2007 patients who fulfilled the diagnostic criteria for BD were enrolled in this study. We reviewed the medical records and test results of the BD patients and used univariate and multivariate logistic regression analyses to determine the clinical significance of renal involvement in BD. RESULTS: Among the 2007 BD patients, we noted hematuria in 412 (20.5%) and proteinuria in 29 (1.4%). Univariate analysis showed that the BD patients with hematuria were predominantly female and older, had higher erythrocyte sedimentation rates (ESRs), and more frequently presented with genital ulcerations. BD patients with proteinuria had higher ESR levels compared to BD patients without proteinuria. In the multivariate analysis, age, sex, and ESR were found to be significantly associated with hematuria in BD patients, whereas only ESR was associated with proteinuria in BD patients. We also found that IgA nephropathy was the most common pathologic diagnosis in 12 renal BD patients who underwent renal biopsies. CONCLUSION: We suggest that routine urinalysis and serum renal function tests be performed for the early detection of renal BD, especially in older female BD patients with recurrent hematuria, high ESR levels, and frequent genital ulcers, as well as in BD patients with proteinuria and high ESR levels.

Unilateral Nevoid Telangiectasia Associated with Ipsilateral Melorheostosis

Melorheostosis is a rare disorder characterized by irregular, flowing hyperostosis in long bones, commonly described on radiographs as wax flowing down a candle. In addition to bony sclerosis, cutaneous manifestations overlying the involved bones have been reported including linear scleroderma, neurofibromatosis, and vascular and lymphatic malformations. Unilateral nevoid telangiectasia (UNT) is a rare primarily cutaneous condition characterized by linearly arranged small dilated blood vessels in dermatomal or Blaschkoid patterns on the skin. Here, we present the case of a nine-year-old Korean male with UNT associated with ipsilateral melorheostosis.

Retraction: Basal Cell Nevus Syndrome Showing Several Histologic Types of Basal Cell Carcinoma

No abstract available.

Anti-Cyclic Citrullinated Peptide Antibodies and Joint Involvement in Behcet's Disease

PURPOSE: We aimed to determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in a large group of Korean patients with Behcet's disease (BD), with and without joint involvement, and to compare these findings with the prevalences of anti-CCP antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We tested 189 patients with BD, 105 with RA, and 36 with SLE for anti-CCP antibodies and IgM rheumatoid factor in serum. We reviewed the medical records of patients with BD to investigate their personal and clinical characteristics as well as their laboratory test results. RESULTS: Anti-CCP antibodies were detected in seven of the 189 BD patients (3.7%), at a mean titer of 30.6+/-44.4 U/mL, in 86 of the 105 RA patients (81.9%) with a mean titer of 198.8+/-205.7 U/mL, and in nine of the 36 SLE patients (25%) with a mean titer of 180.4+/-113.9 U/mL. One of the seven anti-CCP-positive BD patients fulfilled the diagnostic criteria for both BD and RA. Five of the seven anti-CCP-positive BD patients (71.4%) had polyarticular joint involvement, and the other two patients (28.6%) had oligoarticular involvement. CONCLUSION: We determined the prevalence of anti-CCP antibodies in a large group of Korean BD patients with and without joint involvement. Negative anti-CCP test in patients with BD may help to differentiate BD from RA and SLE, all of which present with similar clinical features.

New Insights in the Clinical Understanding of Behcet's Disease

Behcet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behcet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behcet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness.

Expression of Pro-inflammatory Protein S100A12 (EN-RAGE) in Behcet's Disease and Its Association with Disease Activity: A Pilot Study

BACKGROUND: S100A12 is a member of the S100 family of calcium-binding proteins and is secreted either in inflamed tissues or in the bloodstream by activated neutrophils. Expression of S100A12 has been reported in various diseases, especially non-infectious inflammatory diseases, such as Kawasaki disease, giant cell arteritis and inflammatory bowel disease. OBJECTIVE: This study was conducted to determine both the tissue expression and the serum levels of S100A12 in Behcet's disease (BD) patients and the correlation of the S100A12 serum level with disease activity of BD. METHODS: We included in this study ten BD patients who fulfilled the criteria for diagnosis, according to the International Study Group for BD. The activity of BD was calculated using the BD Current Activity Form. The serum concentrations of both S100A12 and interleukin-8 were measured by the enzyme-linked immunosorbent assay, before and after treatment. Immunohistochemical studies were also performed to detect S100A12 expression in the skin. RESULTS: The serum S100A12 level was significantly increased in the active BD period (p<0.001), in the inactive BD period (p=0.041) and in patients with active Kawasaki disease (p=0.028), compared with the serum level in the healthy controls. The serum S100A12 level decreased significantly from baseline, compared to post-treatment (p=0.017). The activity score of BD was significantly correlated with the serum level of S100A12 (Spearman's coefficient=0.464, p=0.039). Immunohistochemical studies showed that S100A12 was strongly expressed in the erythema nodosum-like skin lesions of patients. CONCLUSION: S100A12 contributes to the pathogenesis of BD related to neutrophil hyperactivity and reflects the disease activity in BD patients.

Experience with a Simulation Drill for Novel Influenza A (H1N1) / 병원감염관리

BACKGROUND: It is important that hospitals conduct disaster drills to ensure prompt response in case of a pandemic and thereby prevent a biological disaster. METHODS: In a university hospital of Seoul, a drill was arranged by the members of the drill preparation team who were a part of the response team for infection control of novel influenza A (H1N1). The drill preparation team designed the scenario for the drill, made plans to resolve the potential problems that could occur during that scenario, and organized a survey team and a survey methodology. The scenario consisted of 2 modules: (1) for an intensive care unit and (2) for an emergency care center. The surveyors and field participants were evaluated after the drill exercise. RESULTS: This drill was conducted to improve the response to outbreaks of new infectious diseases. The drill event showed that the communication among the members responsible for the infection control was effective. However, the drill revealed certain drawbacks in the process; this drawbacks involved availability of adequate quarantine space, education on using personal protective equipments, assignment of medical and nonmedical staff, management of visitors, and installment of air-conditioners, heaters, and ventilation units in the areas with H1N1 outbreak. CONCLUSION: This drill helped to improve the process of infection control and overcome the drawbacks in the current process, and thereby helped in achieving positive outcome during the actual pandemic situation when the number of hospital visits and admissions because of H1N1 pandemic had rapidly increased. Although disaster plans and drills are not actively performed, the drill for infection control is essential because the risk for an outbreak of a new infectious disease is increasing.

Evaluation of the Articular Involvement of Behcet's Disease Via Bone Scintigraphy / 대한피부과학회지

BACKGROUND: Behcet's disease (BD) is a chronic relapsing inflammatory disease that involves various organ systems. Articular involvement was reported to be present in approximately 50% of Korean BD patients. The joint symptoms of BD patients have usually been described as intermittent, self-limiting and non-erosive, and they are mostly monoarticular and oligoarticular arthritis. OBJECTIVE: The purpose of our investigations was to evaluate the usefulness of bone scintigraphy for detecting the articular involvement of BD. METHODS: We reviewed the medical records, laboratory findings and bone scintigraphy findings of 89 patients who were diagnosed with BD from January 2005 to June 2007. RESULTS: Of the 89 BD patients, 14 patients were male and 75 patients were female with a mean age of 43.92+/-8.49 yr. The most frequently involved site on bone scintigraphy was the wrist (44.9%) with the decreasing order of frequency as follows: the feet (39.3%), the hands (25.8%), the knee (24.7%), the sacroiliac joint (22.4%), the shoulder (18%), the ankle (16.9%), the hip (12.6%), the spine (10%) and the elbow (3%). The pattern of involvement, which was defined as the number of joints showing hot uptake on the bone scintigraphy at one episode of arthropathy, was monoarticular in 5.6%, oligoarticular in 44.9%, polyarticular in 38.2% and there was no uptake in 11.2%. Among 130 joints, 63.1% of the joints showed close correlation between the clinical symptoms and the bone scintigraphy uptake. CONCLUSION: We suggest that bone scintigraphy can be a useful tool to determine the presence and site of articular involvement. However, more studies are needed to exclude non-specific bone scintigraphy uptake and to determine the correlation between clinical symptoms and the bone scintigraphy findings.

A Case of Psoriasis with a Chronic Oral Ulcer / 대한피부과학회지

Psoriasis is a chronic inflammatory disease with epidermal hyperplasia. Th 1 cells are thought to be important in the pathogenesis of psoriasis and Behcet's disease. However, both diseases rarely develop in the same patient. We report here a case of a 50-year-old man who was diagnosed with psoriasis 15 years prior. During the last three years, ulcers and erosions had recurrently developed on the perianal area and oral mucosa. In addition, the patient had mild arthralgia on the both knees and hand for two years. In this case, Behcet's disease accompanying psoriasis was suspected.

A Case of Bart's Syndrome / 대한피부과학회지

Aplasia cutis congenita is a rare congenital skin defect that presents with sharply outlined ulcerations. The most common site of this disease is the scalp, yet when other areas of the body are involved, there is higher incidence of concomitant congenital diseases or malformations. Bart's syndrome is a rare inherited condition with congenital skin defects that are associated with epidermolysis bullosa. An infant presented with congenital skin defects on the leg, and the infant had recurrent bullous skin lesions on the both hands, feet, wrists and ankles. The skin defect caused only small scar formation and no handicap regarding function and appearance, yet continuously new bullous lesion developed and healed on the both distal extremities. He was diagnosed as suffering with epidermolysis bullosa with the histological findings of epidermal cleavage and negative direct immunofluorescence findings. Herein, we report on a case of Bart's syndrome that displayed aplasia cutis congenita over the lower extremities and skin blistering.

A Clinical Study of 55 Cases of Geographic Tongue / 대한피부과학회지

BACKGROUND: Geographic tongue (GT) is an inflammatory disorder of the oral mucosa. The clinical characteristics of GT have not been studied in Korea. OBJECTIVE: The purpose of this study was to investigate the clinical characteristics, associated factors, and treatment outcomes of GT. METHODS: We reviewed the medical records and clinical photographs of 55 cases who had been diagnosed with GT during the last 5 years. RESULTS: Of the 55 cases, 15 were male and 40 were female. The average age of onset was 29.3 years, and the highest incidence occurred in the 10~19 age group. The clinical type without circinate border was found in 67.3% of the cases and the clinical type with circinate border in 32.7% of the cases. Fissured tongue was found in 40% of the cases. Except for the 11 asymptomatic cases, the rest of the cases complained of various symptoms related to pain, irritation, and sensory changes. Hot, spicy or salty food acted as an aggravating factor in 74.5% of the cases and fatigue or stress in 61.8% of the cases. The majority of our cases (80.0%) were treated with topical steroid or steroid gargle or with a combination of both, and improvement was observed in 75.0% of this group. CONCLUSION: This is the first clinical study of GT in Korean literature. This study showed differences with previous studies in the proportion of cases with symptoms and aggravating factors. This study also suggested that topical steroid or steroid gargle could be the treatment of choice for GT.

Two Cases of Acute Leukopenia Induced by Colchicine with Concurrent Immunosuppressants Use in Behcet's Disease

Colchicine-induced leukopenia usually occurrs in intentional or accidental overdoses or inappropriate use in combination with intravenous and oral colchine; however, there have been several reports of hematologic toxicity in short-term and small-dose colchicine medication courses. We present two cases of leukopenia induced by colchicine use concurrent with immunosuppressants in Behcet's disease. We postulate that the mechanism of colchicine-induced leukopenia might be the destruction of circulating leukocytes and an inhibition of leukocyte production by the immediate and direct toxic effect of colchicine on idiosyncrasies unique to each patient. The concurrently administered immunosuppressant might decrease the threshold for hematologic toxicity of colchicine in the leukocytes and their precursor cells.

The Behcet't Disease Quality of Life: Reliability and Validity of the Korean Version

PURPOSE: The Behcet's Disease Quality of Life (BD-QoL) is a BD-specific measure developed in the UK. The aim of this study was to adapt the BD-QoL for use in Korea. PATIENTS AND METHODS: The translation was based on the guidelines for cross-cultural adaptation. A total of 201 Korean patients with BD participated in this study. To evaluate the psychometric properties, internal consistency and test-retest reliability were used. Factor analysis was performed to examine the construct validity. To provide further evidence for validity, the correlation of BD-QoL with the Clinical Activity Form for Korean Patients with BD (BDCAF-K) and the Center for Epidemiologic Studies-Depression (CES-D) scales was assessed. RESULTS: The Korean version had high internal consistency (Cronbach's alpha, 0.93) and test-retest reliability (r = 0.835). Factor analysis of the questionnaire revealed one interpretable factor as a general health-related quality of life factor. The Korean version significantly correlated with scores of CES-D (r = 0.749, p = 0.000), self-rating scale of well-being over the past 28 days (r = 0.446, p = 0.000), and BDCAF-K score (r = 0.502, p = 0.000). CONCLUSION: Adaptation of the BD-QoL for use in Korea was successful. Together with the BDCAF-K, it may be a valuable tool for assessing the influence of interventions in BD patients and outcome in clinical trials.

Expression of Macrophage Migration Inhibitory Factor in Behcet's Disease / 대한피부과학회지

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a unique protein, participating in inflammation, immune response, and cell growth. Previous reports showed that MIF-polymorphisms are associated with an increased risk for various inflammatory diseases. OBJECTIVE: This study was designed to investigate the effect of MIF polymorphisms on Behcet's disease (BD). METHODS: A total of 362 patients with BD and 290 healthy controls were genotyped. We also performed RT-PCR analysis, ELISA, and immunohistochemical stain for MIF. RESULTS: We could not find statistically significant differences in the genotype frequencies of the MIF-794[CATT]5-8 repeat polymorphism or MIF-173 G>C polymorphism between BD patients and controls. Immunohistochemical analysis showed that MIF protein was diffusely distributed throughout epidermis and subcutaneous fat tissue from the skin lesions of patients with BD and erythema nodosum. CONCLUSION: Contrary to earlier reports, serum MIF levels were decreased in patients with BD, and the prescence of polymorphisms in the MIF promoter region was not associated with disease susceptibility. Nevertheless, MIF may play a role in cutaneous inflammation in BD.