[FCP 15] Detection of mycobacterium tuberculosis from cutaneous lesions of sarcoidosis by reverse blot hybridization assay

( Hanil Lee ),( Eung Ho Choi ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.1

Sarcoidosis is a systemic granulomatous disease of unknown cause that primarily affects the lung, but often involves the skin. Many antigens have been suggested as provocative agents for the cascade of immunologic events that eventuate in sarcoidosis. Infectious agents such as Mycobacterium and Propionibacterium have been associated. To investigate the causality between Mycobacterium and sarcoidosis, we performed reverse blot hybridization assay (REBA) for detecting Mycobacterium with skin samples from 9 different patients with sarcoidosis. All the 9 cases were reviewed clinicopathologically to confirm the diagnosis. Among 9 patients, 7 were diagnosed as sarcoidosis involved in skin and lung, and the rest 2 as sarcoidosis limited to skin. As a result, 5 of 9 showed positive Mycobacterium Tuberculosis (MTB) on the REBA. There were not a few studies suggesting the possibility of MTB being a pathogen for sarcoidosis. A meta-analysis showed a 30% overall positivity of mycobacterial nucleic acids in sarcoid samples. Interestingly, there was a paper that suggested that sarcoidosis and tuberculosis (TB) might potentially be two opposing manifestations of the same disease with overlapping spectrum. This is the first study to detect MTB from the skin specimens of sarcoidosis using REBA. This study could strengthen the association between MTB and sarcoidosis, and support the hypothesis that sarcoidosis and TB are the diseases of same spectrum.

Incidence, prevalence and mortality of sarcoidosis in Korea from 2003 to 2015: a nationwide population-based study

( Ji-eun Park ),( Young Sam Kim ),( Min Jin Kang ),( Cheong Ju Kim ),( Chang Hoon Han ),( Sun Min Lee ),( Seon Cheol Park ) 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Background: Sarcoidosis is a granulomatous disorder involving multi-organ systems, however, the prevalence and incidence of sarcoidosis varies among geographical regions and races. The purpose of this study was to evaluate the incidence, prevalence, and mortality of sarcoidosis using a large nationwide population-based cohort in Korea. Methods: We used a National Health Insurance Service (NHIS) database, which is a large amount of health-related database of nearly all people living in Korea. Adults with sarcoidosis as a primary diagnosis using the International Classification of Disease-Tenth Revision (ICD-10) code were identified from 2003 to 2015. The incidence, prevalence, and mortality of sarcoidosis were analyzed by sex and age. Results: Among 38,231,290 individuals, a total of 6,376 had a primary diagnosis of sarcoidosis. The mean age was 50.8 years and the male was 41.4 %. The age-adjusted incidence and prevalence of sarcoidosis were 1.3 and 3.7 per 100,000 population, respectively. The incidence and prevalence showed an increased trend from 2003 to 2015. The all cause mortality rate was 11.8 per 1,000 sarcoidosis patients. The standardized mortality ratio of sarcoidosis patients to general population was 1.9 (95% CI, 1.7-2.0) from 2003 to 2015. Conclusions: This is the largest epidemiologic study of sarcoidosis in Asian population. In Korea, the annual incidence and prevalence of sarcoidosis were relatively low, and tended to increase over last 10 years. The overall mortality of patients with sarcoidosis was higher than the general population.

Association of HLA Variants with Sarcoidosis in Koreans

( Ho Jeong Kim ),( Kateřina Sikorová ),( Martin Petřek ),( Veronika Žižková ),( Su-jin Moon ),( Jin Woo Song ) 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Background Sarcoidosis is the immune-mediated disease and the role of HLA polymorphisms was implicated. However, the association between HLA polymorphisms and sarcoidosis in Koreans has not yet been investigated. The aim of this study was to investigate the role of HLA variation in the etiopathogenesis of sarcoidosis in Koreans using next-generation sequencing. Methods In this study, 63 patients diagnosed with sarcoidosis at Asan Medical Center, Seoul, South Korea, were enrolled. The diagnosis of sarcoidosis was based on the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) Assessment Instrument. We performed genotyping of 7 HLA loci (HLA-A, -B, -C, DRB1, -DQA1, -DQB1, -DPB1) by Omixon Holotype™ kit and Twin software™. HLA allele frequency of sarcoidosis patients was compared with data on healthy Koreans from the allelic frequency database (http://allelefrequencies.net, South Korea pop1 and pop3). Results Of total subjects, the mean age was 45.8 years, and 33.3% were men. The allele frequencies were different between the sarcoidosis cases and the healthy population, especially in HLA-class II. Alleles HLA-DQA1*05:08; DQB1*03:01 and DRB1*12:01 showed significantly higher frequencies in patients with sarcoidosis compared with healthy subjects (Figure 1). By contrast, alleles HLA DQA1*01:02; DQB1*03:02 and DRB1*13:02 were more common in healthy subjects than sarcoidosis cases. Alleles HLA-A*31:01; A*02:06 and DQB1*06:01 were significantly associated with treated patients. Conclusions In this pilot study, we found some sarcoidosis-associated variants in Koreans, especially in the HLA-class II. Korean patients showed different HLA variants compared with that in Western patients.

Review of Sarcoidosis in a Province of South Korea from 1996 to 2014

Kim, Min-Seok,Park, Cheol-Kyu,Shin, Hong-Joon,Seo, Hyeong-Won,Chang, Jinsun,Ahn, Seong,Kim, Tae-Ok,Lim, Jung-Hwan,Oh, In-Jae,Kwon, Yong-Soo,Kim, Yu-Il,Lim, Sung-Chul,Kim, Young-Chul The Korean Academy of Tuberculosis and Respiratory 2017 Tuberculosis and Respiratory Diseases Vol.80 No.3

Background: Since the introduction of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence of histopathologically-confirmed sarcoidosis has increased. Methods: The electronic medical records of Chonnam National University (CNU) Hospital and CNU Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis diagnosed between 1996 and 2014. Cases were selected using a combination of clinical, radiological, and pathological evidence. Of 115 cases with the relevant disease codes, 16 cases were excluded, as they had not been confirmed pathologically or had no definitive clinical features of sarcoidosis. Results: Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis, 42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of cases. Of the patients treated with systemic steroids, 69.6% showed improvement. The median duration of steroid treatment was 5 months. Conclusion: Following the introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has increased. Clinical features of sarcoidosis were similar to those previously reported. Spontaneous remission occurred in about one-third of patients, while one-fourth of patients required systemic steroid treatment.

Review of Sarcoidosis in a Province of South Korea from 1996 to 2014

( Min-seok Kim ),( Cheol-kyu Park ),( Hong-joon Shin ),( Hyeong-won Seo ),( Jinsun Chang ),( Seong Ahn ),( Tae-ok Kim ),( Jung-hwan Lim ),( In-jae Oh ),( Yong-soo Kwon ),( Yu-il Kim ),( Sung-chul Lim 대한결핵 및 호흡기학회 2017 Tuberculosis and Respiratory Diseases Vol.80 No.3

Background: Since the introduction of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence of histopathologically-confirmed sarcoidosis has increased. Methods: The electronic medical records of Chonnam National University (CNU) Hospital and CNU Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis diagnosed between 1996 and 2014. Cases were selected using a combination of clinical, radiological, and pathological evidence. Of 115 cases with the relevant disease codes, 16 cases were excluded, as they had not been confirmed pathologically or had no definitive clinical features of sarcoidosis. Results: Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis, 42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of cases. Of the patients treated with systemic steroids, 69.6% showed improvement. The median duration of steroid treatment was 5 months. Conclusion: Following the introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has increased. Clinical features of sarcoidosis were similar to those previously reported. Spontaneous remission occurred in about one-third of patients, while one-fourth of patients required systemic steroid treatment.

Scar sarcoidosis developed after blepharoplasty in acute lymphoblastic leukemia patient

( Sue Jeong Kim ),( Hae Eul Lee ),( Myung Im ),( Young Joon Seo ),( Jeung Hoon Lee ),( Young Lee ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Scar sarcoidosis is a rare form of cutaneous sarcoidosis where preexisting scars become infiltrated with non-caseating granulomas. Multiple events such as trauma, local injection, operation have been known to develop scar sarcoidosis. A 46-year-old woman presented with erythematous papules on her left upper eyelid. She was diagnosed as acute lymphoblastic leukemia (ALL) 10years ago and received blepharoplasty (double eyelid surgery) 20 years ago. To rule out the leukemia cutis, we performed the skin biopsy. Histological examination showed dense non-caseating granulomatous infiltration in entire dermis, with numerous epithelioid cells consistent with sarcoidosis. Chest X-ray and blood test showed no evidence of systemic sarcoidosis. There are several reports about the scar sarcoidosis after blepharoplasty and sarcoidosis developed in ALL patients, respectively. However, there is no report on the scar sarcoidosis occurring on blepharoplasty scar in ALL patients 20 years of after surgical procedure. When firm papules appear on the scar site in leukemia patients, the skin biopsy is needed to exclude the scar sarcoidosis.

유육종증에서 단핵구의 교원질에 의한 Procoagulant Activity와 종야괴사인자-α의 표현

전영준 啓明大學校 醫科大學 1993 계명의대학술지 Vol.12 No.2

이 연구는 간질성 폐질환에서 폐간질내에 축적된 교원질이 섬유소형성에 중요한 PCA와 육아종 형성에 중요한 TNF-α를 분비시켜서 염증반응을 지속시키는 지를 알아보고자 시행한 실험으로서 정상인과 유육종증환자의 말초혈액 단핵구와 폐포대식세포를 교원질로서 자극하여 PCA와 TNF-α를 측정하였다. PCA는 유육종증 환자의 말초혈액 단핵구와 폐포대식세포는 건강대조군에 비하여 기저치가 유의하게 높았으며(P<0.05), LPS는 건강대조군과 유육종증 환자의 말초혈액 단핵구와 폐대식세포를 자극하여 PCA 생성을 유의하게 증가시켰다. 교원질은 건강대조군의 말초혈액 단핵구와 폐포대식세포를 자극하여 PCA를 증가시켰으나 유육종증 환자에서는 말초혈액 단핵구는 자극할 수 있으나 폐포대식세포의 PCA생성은 자극시키지 못하였다. TNF-α는 PCA와 마찬가지로 건강대조군에 비하여 유육종증 환자의 말초혈액 단핵구, 폐포대식세포 모두에서 기저치가 높았으며(P<0.05), 말초혈액 단핵구는 건강대조군과 유육종증 환자 모두에서 교원질과 LPS에 의해서 TNF-α의 생성이 증가되었으나 유육종증 환자의 폐포대식세포는 교원질에 의해서 TNF-α의 생성이 증가되지 않았다. 이상의 성적으로 보아 유육종증은 전신질환이어서 말초혈액 단핵구도 이미 자극되어 PCA, TNF-a를 자극없이 분비할 수 있으며 교원질이 말초혈액 단핵구를 자극하여 PCA, TNF-α생성을 증가시키는 것으로 보아서 간질성 폐질환의 폐조직내에 침착된 교원질은 단핵구를 활성화시켜서 염증반응을 지속 시킬 수 있을 것으로 사료된다. 폐포대식세포는 폐조직내의 교원질과 같은 세포외기질에 이미 노출되어 더 이상 교원질에 의해서는 자극되지 않는 것으로 생각되며 LPS와 같은 강력한 자극에 의해서는 반응이 현저히 나타나는 것으로 생각된다. 단핵구 자극검사방법으로 PCA와 TNF-a의 반응 양상이 비슷하므로 검사방법이 비교적 용이하고 비용이 저렴한 PCA가 TNF-α assay를 대체시킬 수 있을 것으로 사료된다. Extracellular matrix deposition and granulomatous lesions are the hallmarks of a variety of diffuse interstitial lung diseases that can lead to loss of pulmonary function. Sarcoidosis is a systemic granulomatous disease which involves the lungs, lymph nodes, skin, central nervous system, liver and muskuloskeletal system. Activated macrophages and monocytes express procoagulant activity which is an initiator of extrinsic coagulation cascade for fibrin formation. And activated macrophages produce cytokines which are important for chemotaxis and differentiation of fibroblast to produce collagen and fibronectin, which in turn, stimulate monocyte/macrophage to produce interleukin-1. To understand the role of monocyte/macrophage and collagen in the pathogenesis of pulmonary sarcoidosis, ten sujects with pulmonary sarcoidosis (stage Ⅱ and Ⅲ) were investigated by bronchoalveolar lavge cells and peripheral blood mononuclear cells. Spontaneous release of PCA and TNF-αfrom AMs were significantly higher in patients than healthy individuals (p<0.05). Collagen could stimulate PBMCs from sarcoidosis patients and healthy PBMCs and AMs to produce PCA and TNF-αbut could not stimulate AMs from sarcoidosis patients. This dyscoordinate stimulation of AM/PBMC in sarcodosis seems to be related with activation with pre-exposure to the millieu in the collagen-deposited interstitium of sarcoidosis. This data demonstrated that in stage Ⅱ and Ⅲ sarcoidosis, PBMCs and AMs are actively produce cytokines and PCA, and collagen deposited in the sarcoidosis may play role in perpetuating the inflammatory process.

Association of Immune Related Genes with Sarcoidosis in Korean Population

( Hee-young Yoon ),( Martin Petřek ),( Kateřina Sikorová ),( Adam Strnad ),( Lenka Kocourková ),( Su-jin Moon ),( Jin Woo Song ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Background Sarcoidosis is the immune-mediated disease, characterized by the formation of non-caseating epithelioid granulomas. Genetic factors affecting immune and inflammatory reactions have important role in pathophysiology of sarcoidosis. However, genetic factors of sarcoidosis in Koreans were not well known. Thus, we investigated the variability in polymorphic variants in genes involved in inflammation, immune system and granulomas development. Methods Twenty Single Nucleotide Polymorphisms (SNP) in 141 Korean patients with sarcoidosis were genotyped using multiplexed MassARRAY® iPLEX assay based on MALDI-TOF mass spectrometry (Agena Bioscience, CA, USA). SNPs frequency data in patients were compared with SNPs frequencies of healthy East Asia population from a database (ensembl.org). Each SNP was tested for HWE (> 0.01). Association was determined using allelic model with Fischer’s exact test with Bonferroni’s correction for multiple comparisons. Results We found six SNPs associated with sarcoidosis after Bonferroni’s correction. Of them, three (TGF-β3 rs3917200, TAP2 rs3819717, and HLA-DRB1*03:01 rs2040410) were protective factors (odds ratio [OR]< 1. while other three) (TGF-β2 rs1891467, HLADRA, HLA-DRB5 rs1964995, and HLA-DQA1 rs2187668) were risk factors (OR >1) (Table 1). In addition, SNP rs2040410 HLADRB1* 03:01 was a protective factor extrapulmonary manifestation of sarcoidosis (OR: 0.319 [0.154-0.661], pcorr=0.006). Conclusions We report SNPs in TAP2, TGF-β and HLA class II genes associated with sarcoidosis in Koreans. Further work in extended cohort is required to validate these findings and investigate their possible relationship with clinical course of sarcoidosis.

Bone Marrow Involvement in Relapsed Sarcoidosis: A Case Report

이정민 대한진단검사의학회 2021 Laboratory Medicine Online Vol.11 No.3

Sarcoidosis can involve multiple organs and is characterized by non-caseating granuloma on biopsy, which is not pathognomonic of this disease. Therefore, diagnosis requires exclusion of other causes of granuloma, including malignant neoplasm, infections, autoimmune diseases, drug exposure, environmental causes, lymphoma, and tuberculosis. Herein, we present a rare case of a patient with a primary manifestation of sarcoidosis, with typical bilateral hilar adenopathy, and recurrence in the bone marrow. A 50-year-old female patient, who had been diagnosed with sarcoidosis at age 38, was admitted for petechia on both legs and pancytopenia. The patient was concluded to be “highly probable” for sarcoidosis, with at least 90% likelihood, according to the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) organ assessment instrument. Moreover, the patient had a bone marrow biopsy positive for granulomatous inflammation. Hence, all findings supported the diagnosis of sarcoidosis. Because sarcoidosis is difficult to definitively diagnose, it will be useful to better understand the application, interpretation, and limitations of the WASOG instrument for bone marrow involvement assessment.

A Solitary Papule on the Eyelid as the First Manifestation of Systemic Sarcoidosis

( Joon Min Jung ),( Ik Jun Moon ),( Mi Woo Lee ),( Sung Eun Chang ) 대한피부과학회 2017 大韓皮膚科學會誌 Vol.55 No.3

Sarocoidosis can affect several organs, including the skin, and demonstrates a broad range of clinical manifestations. The first manifestation of sarcoidosis may sometimes be difficult to recognize. Herein, we report a case of a patient who had a solitary papule on her eyelid as the first and only manifestation of sarcoidosis that caused a diagnostic challenge. A 54-year-old woman visited our clinic with a solitary well demarcated ovoid erythematous papule on her right upper eyelid (Fig. 1). The lesion developed about 6 months prior to her visit and she denied any symptoms. She had no particular medical history. Under the impression of a common benign cutaneous condition, such as a syringoma, wart, xanthoma or irritated seborrheic keratosis, skin biopsy was performed. Histologic findings revealed non-caseating granuloma in the dermis, which was consistent with sarcoidosis (Fig. 2). Multiple enlarged hilar and mediastinal lymph nodes were noted on computed tomography, which were suggestive of pulmonary sarcoidosis. Ophthalmologic examination found no evidence of ocular involvement of sarcoidosis. For further evaluation and treatment, she was referred to the Department of Pulmonology. After administration of oral hydroxychloroquine at a dose of 400 mg/day for 7 months, she is currently under regular follow up with no signs of relapse. Cutaneous involvement in cases of sarcoidosis occurs in 20∼35% of cases and may present in various forms, including as macule, papule, nodules, plaques, or single or multiple erythematous and brownish lesions. Lupus pernio is characterized by the presence of mid-face erythematous and infiltrated lesions, which may lead to disfigurement. Darier- Roussy nodules are thought to be associated with systemic diseases and are subcutaneous lesions where epithelioid gra-nulomas are observed^1-3. Other unusual forms include ul-cerated, psoriasiform, verrucous, rosaceiform, sclerodermiform, mimicking lipodermatosclerosis, lichenoid and erythrodermic lesions as well as alopecia that may present with cica- tricial^3,4. A solitary papule on the upper eyelid rarely requires a biopsy to confirm the diagnosis. Clinically, rather benign lesions, such as syringoma, verruca plana, xanthelasma or lupus lupus miliaris disseminatus faciei, are suspected, with little urge for the clinician to perform a histologic diagnosis. Routine treatment with ablative lasers could have led to negligence of systemic sarcoidosis. This case depicts the uncommonness of a solitary inflammatory papule being the sole clinical manifestation of multisystemic sarcoidosis. Even though histologic examinations for every single skin lesion on the eyelid seem virtually impossible, papules with atypical features on the eyelid, like the one described in this case, should be given special attention.