Kyung-Yil Lee

Mycoplasma pneumoniae pneumonia in children

Mycoplasma pneumoniae (MP), the smallest self-replicating biological system, is a common cause of upper and lower respiratory tract infections, leading to a wide range of pulmonary and extra-pulmonary manifestations. MP pneumonia has been reported in 10 to 40% of cases of community-acquired pneumonia and shows an even higher proportion during epidemics. MP infection is endemic in larger communities of the world with cyclic epidemics every 3 to 7 years. In Korea, 3 to 4-year cycles have been observed from the mid-1980s to present. Although a variety of serologic assays and polymerase chain reaction (PCR) techniques are available for the diagnosis of MP infections, early diagnosis of MP pneumonia is limited by the lack of immunoglobulin (Ig) M antibodies and variable PCR results in the early stages of the infection. Thus, short-term paired IgM serologic tests may be mandatory for an early and definitive diagnosis. MP infection is usually a mild and self-limiting disease without specific treatment, and if needed, macrolides are generally used as a first-choice drug for children. Recently, macrolide-resistant MP strains have been reported worldwide. However, there are few reports of apparent treatment failure, such as progression of pneumonia to acute respiratory distress syndrome despite macrolide treatment. The immunopathogenesis of MP pneumonia is believed to be a hyperimmune reaction of the host to the insults from MP infection, including cytokine overproduction and immune cell activation (T cells). In this context, immunomodulatory treatment (corticosteroids or/and intravenous Ig), in addition to antibiotic treatment, might be considered for patients with severe infection.

Pediatric respiratory infections by Mycoplasma pneumoniae

Mycoplasma pneumoniae is one of the most common agents of community-acquired pneumonia in children and young adults. Although M. pneumoniae is a small bacterium that can reproduce in an artificial culture medium and is known to be sensitive to certain antibiotics in vitro as well as in vivo, the immunopathogenesis of M. pneumoniae in the human host is not fully understood. The epidemiologic characteristics, including periodic epidemics, and some clinical characteristics of M. pneumoniae are similar to those observed in systemic viral infections. Many experimental and clinical studies have suggested that the pathogenesis of lung injuries in M. pneumoniae infection is associated with a cell-mediated immune reaction, including high responsiveness to corticosteroid therapy. This paper presents an overview of M. pneumoniae infections, with emphasis on epidemiology, pathogenesis and treatment.

Kikuchi-Fujimoto Disease With Prolonged Fever in Children

We reviewed 12 patients who had Kikuchi-Fujimoto disease (KFD) and presented with prolonged fever and lymphadenopathy. The clinical and laboratory aspects of the patients confirmed by excisional lymph node biopsy were analyzed. The mean age of the children was 11.0 ± 3.0 years (range: 6–15 years). The male-to-female ratio was 1.4:1. The median duration of fever before admission and the total duration of fever was 13 days (range: 7–65 days) and 19.5 days (range: 9–75 days), respectively. One patient had supraclavicular lymphadenopathy, 10 had cervical involvement, and 1 had axillary lymphadenopathy. All of the histologic findings of the lymph node biopsies showed the characteristic findings consistent with KFD, such as paracortical necrosis with karyorrhexis and an increase in the number of phagocytic histiocytes and atypical lymphocytes. As for the laboratory findings, leukopenia (3600 ± 900 per mm3), anemia (hemoglobin 11.4 ± 1.2 g/dL), an elevated erythrocyte sedimentation rate (44 ± 18 mm/hour), and a relatively low C-reactive protein level (1.3 ± 1.1 mg/dL) were noted. Eight patients received conservative therapy with antipyretics, and 3 patients were treated with prednisolone. KFD is a rare disease yet should be considered in the differential diagnosis for older children with prolonged fever and lymphadenopathy.

Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia

BackgroundM. pneumoniae pneumonia (MP) has been reported in 10-40% of community-acquired pneumonia cases. We aimed to evaluate the difference of clinical features in children with MP, according to their age and chest radiographic patterns.MethodsThe diagnosis of MP was made by examinations at both admission and discharge and by two serologic tests: the indirect microparticle agglutinin assay (≥1:40) and the cold agglutinins titer (≥1:32). A total of 191 children with MP were grouped by age: ≤2 years of age (29 patients), 3-5 years of age (81 patients), and ≥6 years of age (81 patients). They were also grouped by pneumonia pattern: bronchopneumonia group (96 patients) and segmental/lobar pneumonia group (95 patients).ResultsEighty-six patients (45%) were seroconverters, and the others showed increased antibody titers during hospitalization. Among the three age groups, the oldest children showed the longest duration of fever, highest C-reactive protein (CRP) values, and the most severe pneumonia pattern. The patients with segmental/lobar pneumonia were older and had longer fever duration and lower white blood cell (WBC) and lymphocyte counts, compared with those with bronchopneumonia. The patient group with the most severe pulmonary lesions had the most prolonged fever, highest CRP, highest rate of seroconverters, and lowest lymphocyte counts. Thrombocytosis was observed in 8% of patients at admission, but in 33% of patients at discharge.ConclusionsIn MP, older children had more prolonged fever and more severe pulmonary lesions. The severity of pulmonary lesions was associated with the absence of diagnostic IgM antibodies at presentation and lymphocyte count. Short-term paired IgM serologic test may be mandatory for early and definitive diagnosis of MP.

Kawasaki disease may be a hyperimmune reaction of genetically susceptible children to variants of normal environmental flora

Summary Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that occurs predominantly in children <5 years of age. For the etiopathogenesis of KD, there is no agreement even as to whether KD is an infectious disease or an immune-mediated disease. The epidemiologic characteristics of KD, including the strict predilection of age in all ethnic groups and the gradually increased incidence after the KD emergence, suggest that KD is affected by the immune maturation in early childhood that may be determined by genetic factors, and KD is also affected by the changed environmental circumstances such as improved public hygiene. We postulated that the pathogenesis of KD is a hyperimmune reaction in genetically susceptible children to the variants of normal flora, which are induced by the environmental factors. Using this hypothesis, we might partly explain the clinical and epidemiological characteristics of KD. We expect that this hypothesis may help to determine the causative agents for KD in the near future.

Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: A need for early immune-modulators for severe cases

Summary It has been believed that acute lung injury in influenza virus infections is caused by a virus-induced cytopathy; viruses that have multiplied in the upper respiratory tract spread to lung tissues along the lower respiratory tract. However, some experimental and clinical studies have suggested that the pathogenesis of acute lung injury in influenza virus infections is associated with excessive host response including a cell-mediated immune reaction. During the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a dramatic effect of immune-modulators (corticosteroids) on the patients with severe pneumonia who had significant respiratory distress at presentation and those who showed rapidly progressive pneumonia during oseltamivir treatment. We also found that the pneumonia patients treated with corticosteroids showed the lowest lymphocyte differential and that the severity of pneumonia was associated with the lymphocyte count at presentation. From our findings and previous experimental and clinical studies, we postulated that hyperactive immune cells (T cells) may be involved in the acute lung injury of influenza virus infections, using a hypothesis of ‘protein homeostasis system’; the inducers of the cell-mediated immune response are initially produced at the primary immune sites by the innate immune system. These substances reach the lung cells, the main target organ, via the systemic circulation, and possibly the cells of other organs, including myocytes or central nerve system cells, leading to extrapulmonary symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these substances that may be possibly toxic to host cells, the adaptive immune reaction may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of immune cells produces higher levels of cytokines which may be associated with acute lung injury, and may be controlled by early use of immune-modulators. Early initiation and proper dosage of immune-modulators with antiviral agents for severe pneumonia patients may reduce morbidity and prevent progressive fatal pneumonia.

Prevalence of primary immunodeficiency in Korea

This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea.

Epidemiological comparison of three Mycoplasma pneumoniae pneumonia epidemics in a single hospital over 10 years

Purpose Mycoplasma pneumoniae (MP) pneumonia epidemics have occurred in 3- to 4-year cycles in Korea. We evaluated the epidemiologic characteristics of MP pneumonia in Daejeon, Korea, from 2003 to 2012. Methods We retrospectively analyzed 779 medical records of children (0-15 years of old) with MP pneumonia admitted to our institution and compared the data from 3 recent epidemics. Results In 779 patients, the mean age and male-to-female ratio were 5.0±2.2 years and 1:1, and most cases were observed in autumn. There were three epidemics during the study period, in 2003, 2006-2007, and 2011. In our comparison of the three epidemics, we found no differences in mean age, the male-to-female ratio, hospital stay, or the rate of seroconverters during hospitalization. All three epidemics began in early summer and peaked in September 2003 and 2011 and in October 2006 and then gradually decreased until the next years spring season, although the 2006 epidemic extended further into 2007. The peak age groups in the children in 2003 and 2006 were 3-6 year-olds (57.5% and 56%, respectively), but in the 2011 epidemic, the peak group was 1-4 year-olds (46.5%). The proportion of the <2 years of age group was 20%, 15.7% and 28.8%, and >10 years of age group was 5.2%, 13.8%, and 14.8% of total patients, respectively. Conclusion MP pneumonia outbreaks occurred every 3-4 years. The pattern of 3 recent epidemics was similar in demographic characteristics and seasonality with some variations in each outbreak.

Features of Kawasaki disease at the extremes of age

Aim:  The diagnosis of Kawasaki disease (KD) in those outside the typical age range (6 months−4 years) is often delayed, potentially worsening prognosis. The features of KD in children ≤6 months and ≥5 years were compared with those presenting within the more typical age distribution.

A Common Immunopathogenesis Mechanism for Infectious Diseases: The Protein-Homeostasis-System Hypothesis

It was once believed that host cell injury in various infectious diseases is caused solely by pathogens themselves; however, it is now known that host immune reactions to the substances from the infectious agents and/or from the injured host cells by infectious insults are also involved. All biological phenomena in living organisms, including biochemical, physiological and pathological processes, are performed by the proteins that have various sizes and shapes, which in turn are controlled by an interacting network within the living organisms. The author proposes that this network is controlled by the protein homeostasis system (PHS), and that the immune system is one part of the PHS of the host. Each immune cell in the host may recognize and respond to substances, including pathogenic proteins (PPs) that are toxic to target cells of the host, in ways that depend on the size and property of the PPs. Every infectious disease has its own set of toxic substances, including PPs, associated with disease onset, and the PPs and the corresponding immune cells may be responsible for the inflammatory processes that develop in those infectious diseases.