Chronic granulomatous disease (CGD) is one of congenital immunodeficient disease and a rare X-linked or autosomal recessive disease characterized by recurrent life- threatening infections and granuloma formation. We observed clinical features, laboratory findings and genetic subgroups of 33 children who were diagnosed with chronic granulomatous disease in the Department of Pediatrics, Seoul National University Children's Hospital. There were 23 males and 10 females. Activated NBT test of all patients revealed 0% positive cell and mothers of 15 patients had 25%- 75% normal neutrophils in the activated NBT test. According to the result of activated NBT test and family history, the ratio of X-linked and autosomal recessive inheritance was 2:3. There was a significant difference for the age at onset of the first infection in the different genetic subgroups. The X-linked group had the mean onset at 1.98 months of age and autosomal recessive group had a mean onset as late as 3.82 months (p<0.05). The most common type of the first infection was lymphadenopathies (41%) and other infections were skin pustules, fever, perianal abscess, pneumonia and chronic diarrhea. However, the age at diagnosis was not significant in the different genetic subgroups. Lymphadenitis (27%) was the most common infection, and pneumonia, gastrointestinal tract infection, skin infection were also common. The most common infectious agent was Candida sp. (5%) and other microorganisms involved were BCG, coagulase-negative staphylococcus, S. aureus, K/ebsiella pneumoniae, Aspergi/lus sp., and Enterococcus faecium. Chronic condition associated with CGD were hepatomegaly (59%), splenomegaly, and anemia of chronic disease, underweight, and lymphadenopathy. The leukocyte count of patients at diagnosis was within normal limit except in three patients and leukopenia was not observed in any of the patients. The humoral and cellular immunity and complement system were normal, but the level of Ig E in four patients was elevated. Early diagnosis of CGD can be made by suspicion if there are lymphadenitis after BCG vaccination and recurrent pyogenic infections under the first year of age. Though progression in the treatment of CGD, like gene therapy, is concerned, genetic counseling and prenatal diagnosis by carrier detection and molecular genetic analysis is thought to be necessary.
Abscess ; Anemia ; Candida ; Child ; Chronic Disease ; Complement System Proteins ; Diagnosis ; Diarrhea ; Early Diagnosis ; Enterococcus faecium ; Female ; Fever ; Gastrointestinal Tract ; Genetic Counseling ; Genetic Therapy ; Granuloma ; Granulomatous Disease, Chronic* ; Hepatomegaly ; Humans ; Immunity, Cellular ; Korea* ; Leukocyte Count ; Leukopenia ; Lymphadenitis ; Lymphatic Diseases ; Male ; Molecular Biology ; Mothers ; Mycobacterium bovis ; Neutrophils ; Pediatrics ; Pneumonia ; Prenatal Diagnosis ; Seoul ; Skin ; Splenomegaly ; Staphylococcus ; Thinness ; Vaccination ; Wills

Chronic granulomatous disease (CGD) is a rare inherited disorder of a defective NADPH oxidase enzyme, resulting in very low or no production of superoxide and subsequent reactive oxygen species. Consequently, patients with CGD are highly susceptible to severe bacterial and fungal infections. CGD is a genetically heterogeneous disease caused by defects in any one of the genes encoding the NADPH oxidase components. CGD generally affects about 3-4 per 1,000,000 individuals; thus, it is surprising that the prevalence of CGD on Jeju Island is 34.3 per 1,000,000 individuals. At present, 20 patients with CGD from 14 unrelated families on Jeju Island have been identified; nine males and 11 females. All patients with CGD tested on Jeju Island had an identical and homozygous mutation (c.7C>T in CYBA, p.Q3X in p22phox). Therefore, all patients were autosomal recessive form of CGD. This strongly suggests that the unique and identical mutation in CYBA may be inherited from a common proband. Using mutation-specific primers to detect the mutated allele in CYBA, the frequency of subjects carrying a mutated allele was 1.3% of enrolled subjects from Seogwipo City. Further studies are necessary to elucidate how frequently this mutant allele occurs in the population on Jeju Island. Additionally, it is important to construct a national registry system to understand the pathophysiology of CGD and develop a strategy for long-term therapy.
Alleles ; Female ; Granulomatous Disease, Chronic ; Humans ; Korea ; Lifting ; Male ; NADPH Oxidase ; Prevalence ; Reactive Oxygen Species ; Superoxides

OBJECTIVE: This study was aiming at estimating the joint effects of various risk factors associated with uterine cervix cancer in Korea. METHODS: Data obtained from a case-control study were analyzed with a multiplicative model. RESULTS: After adjustment for age and husband's educational attainments, the family history of cervical cancer (OR=2.1, 95% CI=1.2-3.9), unstable marital status due to separation, by death or divorce, etc. (OR=2.8, 95% CI=1.7-4.6), and a large number of deliveries (> or = 3 vs. nulliparous OR=6.5, 95% CI=1.4-29.9) increased the risk of uterine cervix cancer. Conversely, first sexual intercourse at an older age (> or = 25 years vs. <19 years OR=0.4, 95% CI=0.2-0.6) and husband's circumcision (OR=0.7, 95% CI=0.5-1.0) decreased the risk. In the multiplicative model, the highest joint risk (OR=39.2, 95% CI 5.9-258.9) was observed in women with a family history of uterine cervical cancer, an unstable marital status, where the ex-husband was not circumcised, with 3 or more delivery experiences, and having her first sexual intercourse when younger than 19 years of age. However, women without a family history of uterine cervix cancer, married to a circumcised husband, having had her first sexual intercourse at 25 years or older, and nulliparous, showed the lowest joint effect (OR=0.3, 95% CI=0.1-0.5). CONCLUSION: As carcinogenesis is a complex action involving various factors, we consider a joint effects approach to be appropriate in an epidemiological study on risk factors for uterine cervix neoplasms.cervix neoplasm.
Carcinogenesis ; Case-Control Studies ; Cervix Uteri* ; Circumcision, Male ; Coitus ; Divorce ; Epidemiologic Studies ; Female ; Humans ; Joints* ; Korea* ; Male ; Marital Status ; Models, Statistical ; Risk Factors ; Spouses ; Uterine Cervical Neoplasms

No abstract available.
Arthritis, Juvenile Rheumatoid ; Herpesvirus 4, Human

PURPOSE: To determine the clinical association of diagnostic criteria and the prevalence of autoantibodies in newly diagnosed children with juvenile dermatomyositis(JDM). METHODS: Thirty-two children with JDM were identified at Seoul National University Children's Hospital from March 1985 to March 1999 by retrospective review. The diagnosis of JDM was based of the criteria proposed by Bohan and Peter. We investigated for the presence of several autoanti bodies: antinuclear(ANA), double-stranded DNA, anti-Sm, anti-ribonucleoprotein(RNP), anti-SSA/ SSB, anti-Jo1, anti-Scl-70 antibodies and rheumatoid factor(RF). RESULTS: Sex ratio and age at diagnosis were similar to data published in other studies. All the newly diagnosed children with JDM had a typical rash(100%) and proximal muscle weakness(100%); 17(53%) had muscle pain or tenderness; 10(31%) calcinosis; eight(25%) dysphagia; eight(25%) arthritis, and seven(22%) fever. Muscle enzymes were elevated in 90% of the patients. Of the 27 patients who had an electromyogram, 20(70%) had diagnostic results. Sixteen(70%) of biopsied patients had appropriated results for JDM. Patients were negative for all autoantibodies except ANA and RF. ANA and RF were detected in 47% and 7% of the patients respectively. CONCLUSION: Although the sensitivity of the criteria proposed by Bohan and Peter is superior, each of these criteria has possible confounding factors. Additional criteria may be needed for early diagnosis of JDM. Based on our findings of autoantibodies in JDM, we do not recommend routine testing for autoantibodies in children with typical JDM.
Antibodies ; Arthritis ; Autoantibodies* ; Calcinosis ; Child* ; Deglutition Disorders ; Dermatomyositis* ; Diagnosis ; DNA ; Early Diagnosis ; Fever ; Humans ; Myalgia ; Prevalence ; Retrospective Studies ; Seoul ; Sex Ratio

PURPOSE: Patients with chronic granulomatous disease (CGD) have genetic mutations in a component of the NADPH oxidase enzyme that is necessary for the generation of the superoxide anion. The profound defect in innate immunity is reflected by the patients susceptibility to catalase-positive bacteria and fungi. In addition, CGD patients display signs of persistent inflammation, which is not associated only with deficient superoxide anion production. The aim of this study was to elucidate the cytokine responses in CGD patients after TNF-alpha stimulation. METHODS: Heparinized blood samples were collected from 8 CGD patients and 10 healthy volunteers. Monocytes (1x10(6) cell/well) isolated by the magnet cell isolation system were incubated with a constant amount of TNF-alpha (10 ng/mL) at 37degrees C for 6 h. Incubated cells were harvested at 60-min intervals for IL-8 and IL-10 mRNA analysis, and the supernatant was collected at the same intervals to determine IL-8 and IL-10 expression. Monocytes from healthy volunteers were also incubated with antioxidants followed by TNF-alpha stimulation for IL-8 and IL-10 expression. RESULTS: In CGD patients, a high expression of IL-8 together with a significantly higher IL-10 expression than in the healthy controls was seen after TNF-alpha stimulation. Moreover, normal monocytes treated with antioxidants exhibited increased IL-8 responses. CONCLUSION: The absence of phagocyte-derived reactive oxidants in CGD might be associated with a dysregulated production of pro- and antiinflammatory cytokines. Additional research related to reactive oxidants is needed to clarify the role of cytokines in CGD patients.
Antioxidants ; Bacteria ; Cell Separation ; Cytokines ; Fungi ; Granulomatous Disease, Chronic ; Heparin ; Humans ; Immunity, Innate ; Inflammation ; Interleukin-10 ; Interleukin-8 ; Magnets ; Monocytes ; NADPH Oxidase ; Oxidants ; RNA, Messenger ; Superoxides ; Tumor Necrosis Factor-alpha

PURPOSE: Several recent studies have shown a significant association of angiotensin converting enzyme(ACE) gene polymorphism with systemic lupus erythematosus(SLE). The association has not been consistently confirmed; moreover, the association of ACE genotype with SLE in children has never been evaluated. The aim of this study is to evaluate the association of ACE gene polymorphism with SLE in Korean children. METHODS: Eighty-four children with SLE and 171 controls were recruited in this study. The ACE genotypes were determined by polymerase chain reaction. The serum levels of anti-double stranded (ds)-DNA antibody and serum complement levels(C3 and C4) were measured in all patients for disease activity of SLE. The SLE disease activity index(SLEDAI) were scored for the clinical activity of SLE. RESULTS: The frequency of the ACE genotype DD, DI, and II in children with SLE were 13%, 52%, and 35%, respectively, similar to those in controls(16%, 48%, and 36%, respectively). The disease activity of SLE in children among the three groups of each genotype was independent of the ACE gene polymorphism. CONCLUSION: The result of this study did not show a significant association between the ACE polymorphism and the disease activity of SLE in Korean children.
Angiotensins ; Child* ; Complement System Proteins ; Genotype ; Humans ; Lupus Erythematosus, Systemic* ; Polymerase Chain Reaction

Merkel cell carcinoma (MCC) is an uncommon neuroendocrine cutaneous tumor with poor prognosis. It has the high rate of recurrence, mortality, regional nodal involvement, and distant metastases. It is difficult to diagnose MCC because of its non-specific clinical findings. It usually occurs on sun-exposed areas of the skin, mostly at head and neck. There is a difference in the incidence and prognosis according to site in the head and neck. However, there is no consented site-specific diagnosis, treatment or follow-up protocol for MCC at the head and neck. We herein report a case of MCC arising in the right earlobe of an otherwise healthy young man who has been diagnosed early, thereby successfully treated. With our closed follow-up, there was no tumor recurrence or complication at 33 months after diagnosis.
Carcinoma, Merkel Cell* ; Diagnosis ; Follow-Up Studies ; Head ; Incidence ; Mortality ; Neck ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Prognosis ; Recurrence ; Skin

Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defective nicotinamide adenine dinucleotide phosphate oxidase enzyme and characterized by recurrent bacterial and fungal infections. Although liver abscess is a common manifestation of CGD, its management in CGD patients is not well-defined. In addition, the generalized guidelines for treating liver abscesses do not necessarily apply to CGD patients. Corticosteroids are commonly used to control granulomatous complications, such as inflammatory gastrointestinal and genitourinary lesions, in patients with CGD, Corticosteroids have also been used in combination with antimicrobials to treat refractory infections in patients with CGD. Because corticosteroids are capable of suppressing symptomatic inflammation, all potential infections must be adequately controlled prior to corticosteroid initiation. We report 3 typical CGD cases with liver abscesses refractory to conventional treatments that were successfully treated with the concomitant use of corticosteroid and antimicrobials. It remains unclear whether corticosteroid therapy is required for liver abscesses in CGD refractory to conventional treatments. However, based on our observations, use of corticosteroids in combination with optimal antimicrobials should be considered for refractory liver abscesses in CGD.
Adrenal Cortex Hormones ; Granulomatous Disease, Chronic* ; Humans ; Inflammation ; Liver Abscess* ; Liver* ; NADP ; Oxidoreductases

PURPOSE: This study investigated the long-term clinical outcomes of patients with p22(phox)-deficient chronic granulomatous disease (CGD) on Jeju Island and retrospectively evaluated the effects of interferon-gamma (IFN-gamma) prophylaxis. METHODS: The medical records of 15 patients with CGD were retrospectively reviewed. The efficacy of IFN-gamma prophylaxis was evaluated by comparing the frequency of severe infections before and after starting continuous prophylaxis with IFN-gamma. RESULTS: At the time of the analysis, 14 patients were alive, with a median age of 14.3 years. The diagnosis of CGD was made at a median age of 2.4 years, and the median age at onset of severe infection was 0.3 years. Thirteen of the 15 patients had their first severe infection within the first year of life. The overall incidence of severe infection was 1.36 infections per patient-year; pneumonia, suppurative lymphadenitis, and skin and subcutaneous abscesses were the most common infections. Aspergillus species were the most frequently isolated microorganisms, present in 15.8% of isolates. IFN-gamma did not significantly change the rate of severe infection. The survival rate for patients after 2 years of age was 93%; there was a prolonged survival plateau beyond the age of 2. CONCLUSION: Compared with cases of X-linked CGD reported in other studies, patients with CGD on Jeju Island did not show obviously different clinical manifestations, but they had a significantly higher survival rate. Further studies with a substantially longer period of observation, and with more patients under intensive surveillance are necessary to elucidate the prophylactic efficiency of IFN-gamma.
Abscess ; Aspergillus ; Diagnosis ; Granulomatous Disease, Chronic* ; Humans ; Incidence ; Interferon-gamma ; Korea ; Lymphadenitis ; Medical Records ; Pneumonia ; Retrospective Studies ; Skin ; Survival Rate