Jong Myung Lee

Causes and Treatment Outcomes of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in 82 Adult Patients

Background/Aims Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are predominantly known as medication-induced diseases. However, at our institution, we have experienced more cases of non-drug-related SJS and TEN than expected. Therefore, we studied the difference between non-drug-related and drug-related SJS and TEN in terms of clinical characteristics and prognoses. Methods The etiologies, clinical characteristics, and treatment outcomes for 82 adult patients with SJS and TEN were retrospectively reviewed. Results A total of 71 patients (86.6%) were classified as having SJS, and the other 11 patients (13.4%) were classified as having TEN. Drug-related cases were more common (43, 52.4%) than non-drug-related cases (39, 47.6%). Anticonvulsants (12/82, 14.6%) and antibiotics (9/82, 11%) were the most common causative medications. Anemia (p = 0.017) and C-reactive protein of ≥ 5 mg/dL (p = 0.026) were more common in the drug-related cases than in the non-drug-related cases. Intravenous steroid therapy was used as the main treatment regimen (70/82, 85.4%). Of the 82 patients, 8 (9.8%) died during the clinical course. A univariate analysis for mortality showed statistical significance for the following: kidney function abnormality, pneumonia, hemoglobin of < 10 g/dL, and combined underlying diseases. In a multivariate analysis, only pneumonia was statistically significant (odds ratio, 25.79; p = 0.009). Conclusions Drugs were the most frequent cause of these diseases. However, non-drug-related causes also contributed to a significant proportion of cases. Physicians should keep this in mind when documenting patient history. In addition, early recognition and treatment may be important for better outcomes.

Polymorphisms in interleukin-1B and its receptor antagonist genes and the risk of chronic obstructive pulmonary disease in a Korean population: a case–control study

BACKGROUND Although several studies have evaluated the association between interleukin-1B (IL1B) polymorphisms and the risk of chronic obstructive pulmonary disease (COPD), most of these studies have focused on -511C-->T and -31T-->C polymorphisms, and the results of these studies have been inconsistent. This study was conducted to investigate the association between four potentially functional polymorphisms of the IL1B gene (-3737C-->T, -1464G-->C, -511C-->T, and -31T-->C) and the risk of COPD. In addition, we examined a potential interaction of the IL1B polymorphisms with the VNTR polymorphism of the IL-1 receptor antagonist (IL1RN) gene in determining the risk of COPD. METHODS The IL1B and IL1RN genotypes were determined in 311 COPD patients and 386 healthy controls. RESULTS Individuals with at least one variant allele of the -511C-->T and -31T-->C polymorphisms were at a significantly increased risk for COPD when compared to carriers with each homozygous wild-type allele [adjusted odds ratio (OR) 1.53, 95% confidence interval (CI) 1.03-2.26, P=0.03; and adjusted OR 1.50, 95% CI 1.02-2.24, P=0.04, respectively]. When the COPD cases were stratified according to disease severity, the presence of at least one -511T and -31C alleles was significantly associated with severe COPD (adjusted OR 2.80, 95% CI 1.47-5.33, P=0.002; and adjusted OR 2.33, 95% CI 1.24-4.40, P=0.01, respectively), however, there was no significant association between the -511C-->T and -31T-->C genotypes and mild-to-moderate COPD. In addition, individuals carrying at least one IL1RN*2 allele were at a significantly lower risk for COPD compared to subjects carrying no IL1RN*2 allele (adjusted OR 0.51, 95% CI 0.26-0.98, P=0.04). In haplotype/diplotype analyses, individuals with one or two copies of the IL1B CCTC haplotype that carried the risk allele at all of the -3737C-->T, -1464G-->C, -511C-->T, and -31T-->C loci, were at a significantly increased risk of severe COPD when compared with subjects with zero copy of the CCTC haplotype (adjusted OR 1.96, 95% CI 1.16-3.29, P=0.01). CONCLUSION These findings suggest that polymorphisms in the IL1B and IL1RN genes might be useful markers for determining genetic susceptibility to COPD in a Korean population.

Diagnosis and Management of Immediate Hypersensitivity Reactions to Cephalosporins

Cephalosporins can cause a range of hypersensitivity reactions, including IgE-mediated, immediate reactions. Cephalosporin allergy has been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other β-lactam antibiotics. Unlike penicillins, the exact allergenic determinants of cephalosporins are less well understood and thus, standardized diagnostic skin testing is not available. Nevertheless, skin testing with diluted solutions of cephalosporins can be valuable in confirming IgE-mediated hypersensitivity reactions. In vitro tests are in development using recent technological advances and can be used as complementary tests. However, they are not commonly used because of their reduced sensitivity and limited availability. In selected cases of inconclusive results in both skin tests and IgE assays, a graded challenge or induction of drug tolerance with the implicated cephalosporin should be performed.

Comparison of Antiretroviral Regimens: Adverse Effects and Tolerability Failure that Cause Regimen Switching

Background The efficacy of antiretroviral therapy (ART) has improved, and the adverse effects of antiretroviral drugs have been reduced. However, these adverse effects still significantly influence patient compliance, increasing the risk of tolerability failure. Therefore, we investigated the adverse effects and tolerability failure causing changes in the first ART regimen, and identified the regimens that were most vulnerable to switching. Materials and Methods We enrolled patients with human immunodeficiency virus (HIV) who commenced their first ART between January 1, 2011 and July 30, 2014. Patients who started their first ART regimen at the Kyungpook National University Hospital were included in the study if they were aged ≥18 years and were followed-up for ≥12 weeks. The primary dependent variable was the duration of treatment on the same ART regimen. We analyzed the maintenance rate of the first ART regimen based on the treatment duration between these groups using survival analysis and log rank test. The frequency of the adverse effects of ART regimens was analyzed by multiple response data analysis. Results During the investigation period, 137 patients were enrolled. Eighty-one patients were maintained on the initial treatment regimen (59.1%). In protease inhibitor (PI)-based regimen group, 54 patients were maintained on the initial treatment regimen (54/98, 55.1%). In non-nucleoside reverse transcriptase inhibitor (NNRTI)-and integrase inhibitor (II)-based regimen group, 15 (15/26, 57.7%) and 12 (12/13, 92.3%) patients were maintained on the initial treatment regimen, respectively. Adverse effects that induced ART switching included rash (16/35, 45.7%), gastrointestinal discomfort or pain (7/35, 20%), diarrhea (7/35, 20%), hyperbilirubinemia (6/35, 17.1%), headache or dizziness (3/35, 8.5%). Among the treatment regimens, the group receiving an II-based regimen showed the least switching. The group receiving PI-and NRTI-based regimens were most likely to switch due to adverse effects during the early treatment period. However, after about 18 months, switching was rarely observed in these groups. Among the PI drugs, darunavir/ritonavir showed fewer drug changes than atazanavir/ritonavir (P = 0.004, log rank test) and lopinavir/ritonavir (P = 0.010). Among the NNRTI drugs, rilpivirne produced less switching than efavirenz (P = 0.045). Conclusions Adverse effects to ART resulted in about a quarter of patients switching drugs during the early treatment period. II-based regimens were advantageous because they were less likely to induce switching within 18 months of treatment commencement. These findings indicated the importance of considering and monitoring the adverse effects of ART in order to improve adherence.

Serum IgE Levels in Korean Patients with Human Immunodeficiency Virus Infection

Background Human immunodeficiency virus (HIV) infection results in a selective CD4+ T cell depletion and an impairment of T cell regulation. Despite the immune depletion, the progression of HIV infection is accompanied by the stimulation of antibody synthesis. Thus, the prevalence and amplitude of the increase of total serum IgE level and the relationship between the IgE levels and the degree of immunodeficiency were evaluated in patients with HIV infection. Method Twenty-six Korean adults infected with HIV, in different stages, were evaluated for serum IgE level and CD4+ T cell count. Serum IgG, IgM and IgA levels were also determined. All subjects enrolled in this study denied an individual and familial history of atopic diseases. The possibility of parasitic infestation was also excluded by history and stool examination. Results The mean serum IgE level was 473.5 IU/L with a standard deviation of 671.4 IU/L (range: 15.9–2000 IU/L) and increased serum IgE levels (>200 IU/L) were found in 38.5% of the study population. The mean serum IgG, IgA and IgM levels were 1,939.5±588.6 mg/dL (normal: 751–1,560 mg/dL), 388.9±216.7 mg/dL (normal: 82–453 mg/dL) and 153.6±75.3 mg/dL (normal: 46–304 mg/dL), respectively. The CD4+ T cell count was inversely correlated to the serum IgE level (r=−0.429, p<0.05), but not to the other isotypes of immunoglobulin. Conclusion Serum IgE levels are increased in adults with HIV infection and could be useful as a marker of disease progression. Further study is needed to elucidate the causes and clinical significance of these findings.

Hemophagocytic Syndrome Associated with Bilateral Adrenal Gland Tuberculosis

We report a case of a patient who presented with hemophagocytic syndrome (HPS) and adrenal crisis associated with bilateral adrenal gland tuberculosis, and resulted in a poor outcome. A 50-year-old man was transferred to our hospital from a local clinic due to fever, weight loss, and bilateral adrenal masses. Laboratory findings showed leukopenia, mild anemia, and elevated lactate dehydrogenase. Computed tomography (CT) of the abdomen revealed bilateral adrenal masses and hepatosplenomegaly. CT-guided adrenal gland biopsy showed numerous epithelioid cells and infiltration with caseous necrosis consistent with tuberculosis. Bone marrow aspiration and biopsy showed significant hemophagocytosis without evidence of malignancy, hence HPS associated with bilateral adrenal tuberculosis was diagnosed. During anti-tuberculosis treatment the patient showed recurrent hypoglycemia and hypotension. Rapid ACTH stimulation test revealed adrenal insufficiency, and we added corticosteroid treatment. But pancytopenia, especially thrombocytopenia, persisted and repeated bone marrow aspiration showed continued hemophagocytosis. On treatment day 41 multiple organ failure occurred in the patient during anti-tuberculous treatment and steroid replacement.

Awareness and Acceptance of HIV Pre-exposure Prophylaxis among Medical Personnel and Men Who Have Sex with Men in Korea

Background We aimed to investigate the awareness of human immunodeficiency virus (HIV) infection among high-risk individuals, including men who have sex with men (MSM) and medical personnel (MP) in Korea through a cross-sectional survey, identify possible obstacles hindering their access to pre-exposure prophylaxis (PrEP). Methods In 2016, the first questionnaire survey was sent to randomly selected MSM and MP. To compare the changes in attitudes and knowledge of MSM, a second questionnaire survey was conducted in August 2017. Results More than half of MSM (61.3% in 2016, 88.6% in 2017) were aware of PrEP. However, MP who offered PrEP had less knowledge regarding PrEP (23.4%). The background knowledge and experience with PrEP among MSM and MP in this survey was low (3.4% in 2016 and 5.7% in 2017, 1.9% in MP). The major obstacles that MSM reported were lack of insurance coverage (29% in 2016 and 32% in 2017), concern regarding adverse effects of PrEP (19% and 21%), and risk of exposing HIV-positive status to other people (15% and 18%). Among MP, lack of knowledge regarding the efficacy of PrEP was the most common obstacle (30%), followed by lack of insurance coverage (22%), and concern regarding adverse effects (20%). Conclusion Our study showed that PrEP is required among MSM in Korea; however, most MP were not aware of PrEP. Lack of insurance coverage and knowledge regarding PrEP were major hindrances in the access to PrEP; therefore, further studies on how to make PrEP information more accessible are needed to help prevent HIV infection.

The Incidence and Clinical Characteristics of Acute Serum Creatinine Elevation more than 1.5 mg/dL among the Patients Treated with Tenofovir/Emtricitabine-containing HAART Regimens

Background The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been the first choice nucleoside reverse transcriptase inhibitor (NRTI) according to many reliable antiretroviral treatment (ART) guidelines because of its high efficacy. However, TDF-related renal toxicity reported in Western countries is a challenging issue regarding clinical use. We conducted this study to evaluate the incidence and characteristics of an acute increase in serum creatinine (Cr) level > 1.5 mg/dL among TDF/FTC-based highly active antiretroviral treatment (HAART)-treated patients. Materials and Methods We retrospectively reviewed the medical records of 205 HIV-infected patients treated with TDF/FTC-containing regimens between 1 February 2010 and 30 April 2014. Three groups of TDF/FTC + ritonavir-boosted protease inhibitor (PI/r), TDF/FTC + non-nucleoside reverse transcriptase inhibitor (NNRTI), and TDF/FTC + integrase strand transfer inhibitor (INSTI), and three PI/r subgroups of TDF/FTC + lopinavir (LPV)/r, TDF/FTC + atazanavir (ATV)/r, TDF/FTC + darunavir (DRV)/r were evaluated. Results A total 136 patients (91 in the TDF/FTC + PI/r group, 20 in the TDF/FTC + NNRTI group and 25 in the TDF/FTC + INSTI group) were included in the statistical analysis. Four cases (4.9%; all in the TDF/FTC + PI/r group) among 136 patients showed an acute increase in serum Cr more than 1.5 mg/dL, so the overall incidence was 2.8 cases per 100 patient-years. One case was a patient treated with TDF/FTC + LPV/r, and the others were treated with TDF/FTC + ATV/r. No case of an acute increase in serum Cr was observed in the TDF/FTC + DRV/r group. The incidence of serum Cr increase more than 1.5 mg/dL in TDF/FTC + PI/r group was 4.0 cases per 100 patient-years. Conclusion Although only a small number of patients were evaluated retrospectively from a single center, the TDF/FTC + PI/r regimen may have been related with relatively higher tendency of increment of serum Cr level. These findings reinforce the importance of close follow-ups of HIV-infected patients treated with the TDF/FTC + PI/r regimens.

A 2011-2012 survey of doctors' perceptions of korean guidelines and empirical treatment of community-acquired pneumonia.

Background The causative pathogens of and prevalence of antibiotic resistance in community-acquired pneumonia (CAP) varies across countries. We evaluated the patterns of antibiotic prescriptions for adult CAP patients, and physician satisfaction with the form and content of the 2009 Korean CAP treatment guidelines. Materials and Methods We designed an online survey for clinical physicians who treat CAP (infectious disease specialists, pulmonologists, and other physicians). We e-mailed the online survey to physicians and gathered results from December 2011 to January 2012, and then analyzed their responses. Results A total of 157 physicians responded to our survey: 61 (38.9%) infectious disease specialists, 33 (21.0%) pulmonologists, and 63 (40.1%) other physicians. Two-thirds (96/157, 61.2%) had positions in tertiary and secondary hospitals; the others (61, 38.8%) worked in primary clinics (hospitals and private clinics). One hundred and eight (68.8%) were aware of the Korean CAP clinical guidelines; of these, 98 (62.4%) applied the guidelines to their practice. Among physicians using them, 86.7% (85/98) reported the guidelines to be most useful for empirical selection of antibiotics, and 75.2% (118/157) said the guidelines were useful and satisfactory. Sixty-eight (43.3%) respondents indicated that they had not used aminoglycosides as an initial empirical CAP treatment, while 51 (32.5%) had combined aminoglycosides with other antibiotics to treat patients with CAP. Seventy-three (46.5%) physicians often combined macrolides with β-lactam antibiotics for empirical treatment of CAP, and 21 (13.4%) reported using macrolide monotherapy (which is not recommended in the 2009 Korean CAP treatment guidelines) for CAP patients. The most commonly used β-lactams were third-generation cephalosporins (72, 45.9%) and ampicillin/sulbactam or amoxicillin/clavulanate (28, 17.8%). Conclusions Some physicians remain unaware of the 2009 Korean treatment guidelines for CAP and do not use them in clinical practice. In addition, aminoglycoside combination therapy is frequently and inappropriately used in practice. In some cases, CAP is treated with macrolide monotherapy. Thus, the Korean CAP clinical guidelines must be more aggressively and continuously publicized.

Clinical Features of Hereditary Angioedema in Korean Patients: A Nationwide Multicenter Study

Background: Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea. Methods: Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed. Results: A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far. Conclusions: The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.