• Journal of Genetic Medicine
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• 제19권2호
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• pp.57-62
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• 2022

Systemic autoinflammatory diseases (SAIDs) are characterized by unprovoked inflammatory episodes such as recurrent/periodic fever, serositis, skin lesions, abdominal symptoms, arthritis/arthralgia, and central nervous system involvement. Genetic diagnosis of SAIDs has been challenging because disease manifestations overlap among themselves and with other immunological disease categories, such as infection and autoimmune diseases. However, the advent of next-generation sequencing (NGS) technologies and expanding knowledge about the innate immunity and inflammation have made the routine genetic diagnosis of SAIDs possible. Here, we review the recurrent/periodic fevers, other recently identified autoinflammatory diseases, and type I interferonopathies, and discuss the clinical usefulness of NGS targeted sequencing for SAIDs, and recent advance of understandings for this heterogeneous disease group as for underlying primary immunodeficiency.

• Clinical and Experimental Pediatrics
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• 제64권4호
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• pp.141-148
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• 2021

There are very scant data on the epidemiology of primary immunodeficiency diseases (PIDs) in Korea. Here we attempted to estimate the PID epidemiology and disease burden in Korea. A systematic review was performed of studies retrieved from the PubMed, KoreaMed, and Google Scholar databases. Studies on PIDs published in Korean or English between January 2001 and November 2018 were analyzed. The number of PID patients and the healthcare costs were estimated from Health Insurance Review and Assessment Service (HIRA) Korea data for 2017. A total of 398 PID patients were identified from 101 reports. Immunodeficiencies affecting cellular and humoral immunity were reported in 11 patients, combined immunodeficiency with associated or syndromic features in 40, predominantly antibody deficiencies in 144, diseases of immune dysregulation in 58, congenital defects of phagocytes in 104, defects in the intrinsic and innate immunity in 1, auto-inflammatory disorders in 4, complement deficiencies in 36, and phenocopies of PID in none. From the HIRA reimbursement data, a total of 1,162 outpatients and 306 inpatients were treated for 8,166 and 6,149 days, respectively. In addition, reimbursement was requested for 8,200 outpatient and 1,090 inpatient cases and $1,924,000 and $4,715,000 were reimbursed in 2017, respectively. This study systematically reviewed published studies on PID and analyzed the national open data system of the HIRA to estimate the disease burden of PID, for the first time in Korea.

• Tuberculosis and Respiratory Diseases
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• 제87권4호
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• pp.440-450
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• 2024

Bronchiectasis is a chronic respiratory disease characterized by abnormal dilation of the bronchi that causes cough, sputum, and recurrent infections. As it may be associated with various respiratory or systemic diseases, a critical aspect of managing bronchiectasis is to identify the underlying cause. Immunodeficiency is a rare but important cause of bronchiectasis, and its treatability is a significant trait for bronchiectasis management. While primary immunodeficiencies in bronchiectasis are well recognized, secondary immunodeficiencies remain under-reported and under-researched. Secondary immunodeficiencies may result from various diseases and conditions, such as hematologic malignancies, human immunodeficiency virus infection, renal transplantation, or the use of immunosuppressive drugs, and may contribute to the occurrence of bronchiectasis. Recurrent pulmonary and/or extrapulmonary infections in bronchiectasis may indicate the presence of secondary immunodeficiency in patients with these underlying conditions. For treatment, examining the underlying condition, managing bronchiectasis adequately, and prophylactic antibiotics (e.g., macrolide) and/or supplementary immunoglobulin G therapy may provide potential benefits. Considering the projected increase in the prevalence of secondary immunodeficiencies and bronchiectasis, future guidelines and research on the diagnosis and optimized treatment are needed.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제26권4호
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• pp.201-212
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• 2023

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5-204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

• Pediatric Infection and Vaccine
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• 제27권3호
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• pp.190-197
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• 2020

소아에서 후두기관지염이 진균에 의해 발생하는 경우는 매우 드물고 주로 선행 요인이 있는 환자에 보고된다. 또한, Aspergillus 감염에 의한 후두기관지염은 초기에 무증상이거나 가슴 X선 사진에서 특이점이 없는 경우가 많아 조기 진단이 어렵다. 저자는 피부증상과 비감염성 발열을 조절하기 위해 장기간 저용량 스테로이드를 사용했던 복용력이 있는 일차성 면역 결핍 질환이 의심되는 환자에서 점진적인 호흡 부전을 보였고 가막성 아르페르길루스증(Pseudomembranous aspergillosis)에 의한 후두기관지염으로 밝혀진 사례를 보고하여 Aspergillus 후두기관지염의 고위험 환자군에서 조기 진단을 통한 치료의 중요성을 알리고자 한다.

• Allergy, Asthma & Respiratory Disease
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• 제12권3호
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• pp.155-159
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• 2024

Good's syndrome is a rare cause of combined B- and T-cell immunodeficiency in adults with a history of thymectomy. The patients with Good's syndrome are susceptible to encapsulated bacterial infections and opportunistic viral/fungal infections. We report a 63-year-old female patient who was diagnosed with cerebral toxoplasmosis in the middle of monthly immunoglobulin treatment for Good's syndrome. She was referred owing to progressive dizziness for one week without any neurologic deficits. Although routine laboratory tests and toxoplasma serology exams were within the normal range, brain image studies suggested cerebral toxoplasmosis, which was confirmed by pathology of brain lesions. She was treated with pyrimethamine and sulfadiazine as well as with systemic corticosteroids, and improved without sequelae. Later, her medication was switched to trimethoprim/sulfamethoxazole as a second-line treatment due to sulfadiazine-related neuropathy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권1호
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• pp.1-6
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• 2021

Next-generation sequencing (NGS) technologies have changed the process of genetic diagnosis from a gene-by-gene approach to syndrome-based diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS). A priori information on the causative genes that might underlie a genetic condition is a prerequisite for genetic diagnosis before conducting clinical NGS tests. Theoretically, DPS, DES, and DGS do not require any information on specific candidate genes. Therefore, clinical NGS tests sometimes detect disease-related pathogenic variants in genes underlying different conditions from the initial diagnosis. These clinical NGS tests are expensive, but they can be a cost-effective approach for the rapid diagnosis of rare disorders with genetic heterogeneity, such as the glycogen storage disease, familial intrahepatic cholestasis, lysosomal storage disease, and primary immunodeficiency. In addition, DES or DGS may find novel genes that that were previously not linked to human diseases.

• Pediatric Infection and Vaccine
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• 제29권1호
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• pp.54-60
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• 2022

살모넬라 수막염은 소아청소년에서 흔하지 않은 병이나 심각한 신경학적 합병증을 일으킬 수 있다. 영아, 특히 3개월 미만의 연령과 악성 종양, 말라리아 감염, 인체면역결핍바이러스 감염과 같은 면역 저하 상태는 살모넬라 수막염의 위험인자로 알려져 있다. 본 증례에서는 고열과 구토, 의식 변화를 주소로 내원한 이전 특이병력 없던 건강한 8세 여아의 살모넬라 수막염 증례를 소개한다. 환자의 뇌척수액에서 D군 살모넬라가 배양되었으며, 뇌 자기공명영상 소견은 정상이었다. 면역 글로불린 수치와 림프구 수는 정상 범위였고, 차세대 염기서열 분석에서 원발성 면역결핍 질환을 일으키는 유전자 변이는 검출되지 않았다. 3세대 세팔로스포린 투약으로 환자의 증상은 빠르게 호전되었으며 합병증이나 후유증은 발생하지 않았다. 비장티푸스 살모넬라균은 면역이 정상인 소아에서 수막염을 일으킬 수 있으며 조기에 항생제를 투여하면 성공적으로 치료할 수 있다.

• Journal of Preventive Medicine and Public Health
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• 제49권6호
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• pp.394-405
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• 2016

Objectives: The survival outcomes of antiretroviral treatment (ART) programs have not been systematically evaluated at the state level in India. This retrospective study assessed the survival rates and factors associated with survival among adult human immunodeficiency virus (HIV)-infected patients in Andhra Pradesh, India. Methods: The present study used data from 139 679 HIV patients aged ${\geq}15$ years on ART who were registered from 2007 to 2011 and were followed up through December 2013. The primary end point was death of the patient. Mortality densities (per 1000 person-years) were calculated. Kaplan-Meier and Cox-regression models were used to estimate survival and explore the factors associated with survival. Results: The overall median follow-up time was 16.0 months (2.0 months for the deceased and 14.0 months for those lost to follow-up). Approximately 13.2% of those newly initiated on ART died during follow-up. Of those deaths, 56% occurred in the first three months. The crude mortality rate was 80.9 per 1000 person-years at risk. The CD4 count (adjusted hazard ratio [aHR],4.88; 95% confidence interval [CI], 4.36 to 5.46 for < $100cells/mm^3$ vs. > $350cells/mm^3$), functional status (aHR, 3.05; 95% CI, 2.82 to 3.30 for bedridden vs. normal), and body weight (aHR, 3.69; 95% CI, 3.42 to 3.97 for <45 kg vs. >60 kg) were strongly associated with the survival of HIV patients. Conclusions: The study findings revealed that high mortality was observed within the first three months of ART initiation. Patients with poor baseline clinical characteristics had a higher risk of mortality. Expanded testing and counseling should be encouraged, with the goal of ensuring early enrollment into the program followed by the initiation of ART in HIV-infected patients.

• Clinical and Experimental Pediatrics
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• 제59권sup1호
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• pp.57-59
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• 2016

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days -8 to -5), and the target area under the curve was $75,000{\mu}g{\cdot}hr/L$. Fludarabine ($40mg/m^2$) was administered once daily for 6 consecutive days from days -8 to -3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days -4 to -2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.