Myelodysplastic syndromes and overlap syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological neoplasms characterized by ineffective hematopoiesis, morphologic dysplasia, and cytopenia. MDS overlap syndromes include various disorders, such as myelodysplastic/myeloproliferative neoplasms and hypoplastic MDS with aplastic anemia characteristics. MDS overlap syndromes share the characteristics of other diseases, which make differential diagnoses challenging. Advances in genomic studies have led to the discovery of frequent mutations in MDS and overlap syndromes; however, most of the mutations are not specific for the diagnosis of these diseases. The molecular characteristics of the overlap syndromes usually do not show a just “in-between” form but rather heterogeneous features. Established diagnostic criteria for these diseases based on clinical, morphologic, and laboratory features are still useful when combined with genomic data. It is expected that further studies for MDS and overlap syndromes will place emphasis on the roles of mutations as therapeutic targets and prognostic indicators.

Myelodysplastic syndromes and overlap syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological neoplasms characterized by ineffective hematopoiesis, morphologic dysplasia, and cytopenia. MDS overlap syndromes include various disorders, such as myelodysplastic/myeloproliferative neoplasms and hypoplastic MDS with aplastic anemia characteristics. MDS overlap syndromes share the characteristics of other diseases, which make differential diagnoses challenging. Advances in genomic studies have led to the discovery of frequent mutations in MDS and overlap syndromes; however, most of the mutations are not specific for the diagnosis of these diseases. The molecular characteristics of the overlap syndromes usually do not show a just “in-between” form but rather heterogeneous features. Established diagnostic criteria for these diseases based on clinical, morphologic, and laboratory features are still useful when combined with genomic data. It is expected that further studies for MDS and overlap syndromes will place emphasis on the roles of mutations as therapeutic targets and prognostic indicators.

Increment of Serum Free Light Chain Kappa/Lambda Ratio in Patients with Renal Dysfunction

BACKGROUND: Since free light chain (FLC) is metabolized in the kidney, serum FLC concentration and kappa/lambda ratio are increased in patients with decreased renal function, even in the absence of monoclonal protein. In this study, we measured serum FLC levels to investigate the change in kappa/lambda ratios in relation to the severity of renal dysfunction. METHODS: Serum FLC concentrations were measured in 92 archived serum samples from patients diagnosed with chronic kidney disease using the Freelite assay (The Binding Site Group Ltd., UK), and kappa/lambda ratios were calculated. Serum creatinine levels were assayed to calculate estimated glomerular filtration rate (eGFR), and patients were divided into subgroups according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines. We analyzed the difference in serum FLC levels and kappa/lambda ratios between subgroups. RESULTS: Serum FLC levels and kappa/lambda ratios increased depending on the severity of renal dysfunction. When patients were classified by setting cut-off value of eGFR as 60 mL/min/1.73 m2 (group A: eGFR ≥60 mL/min/1.73 m2, group B: < 60 mL/min/1.73 m2), the kappa/lambda ratio of group B was significantly higher than that of group A (group B: 1.60±0.46 vs. group A: 1.35±0.27, P=0.018). Serum FLC kappa/lambda ratios were within the previously determined renal reference interval (0.37–3.1). CONCLUSIONS: When interpreting results of serum FLC kappa/lambda ratio, renal function status should be considered in addition to hematological findings. If renal function deteriorates, a wider renal reference interval is preferred instead of the usual reference interval.

Comparison of YD URiSCAN PluScope Urine Microscopic Analyzer and Sysmex UF-1000i Flow Cytometry Systems

BACKGROUND: Urinalysis is one of the most commonly performed tests in clinical laboratories. In this study, we compared YD URiSCAN PluScope (PluScope; YD Diagnostics Corp., Korea) and Sysmex UF-1000i (UF-1000i; Sysmex Corp., Japan) for urine microscopic sediment analysis. METHODS: A total of 404 fresh urine samples were collected and analyzed using PluScope, UF-1000i, and manual microscopy. Quantitative correlation analyses for red blood cells (RBCs), white blood cells (WBCs), epithelial cells (EC), and casts were performed using Spearman's correlation. We evaluated agreement among the three systems by using weighted Cohen's κ and calculating concordance rates within one grade of difference for semiquantitative and qualitative parameters. RESULTS: There were moderate-high correlations between PluScope and UF-1000i for RBCs, WBCs, and ECs (r=0.542, 0.714, and 0.571, respectively) but negligible correlation for casts (r=0.186). There were moderate-high correlations between manual microscopy and automated devices for RBCs, WBCs, and ECs (r=0.550–0.745) but negligible correlations for casts (PluScope: r=0.247; UF-1000i: r=0.223). The pairwise concordance rates within one grade difference among the three methods were good for RBCs, WBCs, and ECs (95.0%–99.0%, κ=0.41–0.74). For casts, the concordance rate between PluScope and manual microscopy was fair (96.8%, κ=0.25), but concordance rates between UF-1000i and manual microscopy and between the two automated devices were poor (81.2% and 81.7%; κ=0.04 and 0.06, respectively). CONCLUSIONS: The two automated urine sediment analyzers showed a moderate-high correlation and concordance rate. They showed good correlations and concordance rates for RBCs, WBCs, and ECs. However, manual microscopic examinations are still needed for reviewing and confirming the presence of pathologic particles in urine, such as casts and crystals.

Usefulness of Serum Thymidine Kinase 1 as a Biomarker for Aggressive Clinical Behavior in B-cell Lymphoma

BACKGROUND: The cell cycle-dependent enzyme thymidine kinase 1 (TK1) is known to increase during cancer cell proliferation and has been reported as a prognostic marker for various hematologic malignancies and solid tumors. This study aimed to determine the reference interval in Korean healthy controls and to evaluate the usefulness of TK1 as a biomarker for aggressive clinical behavior in B-cell lymphoma patients. METHODS: We enrolled 72 previously untreated patients with B-cell lymphoma and 143 healthy controls. Serum TK1 levels were measured by chemiluminescence immunoassay (Liaison(R), DiaSorin, USA). We established the reference intervals in healthy controls. The diagnostic performance of serum TK1 was studied using receiver operating characteristic (ROC) analysis, and the correlation between the cutoff level for serum TK1 and clinical characteristics of B-cell lymphoma was evaluated. RESULTS: The reference range (95th percentile) of serum TK1 in healthy controls was 5.4-21.8 U/L. There was a clear difference in TK1 levels between patients with B-cell lymphoma and healthy controls (40.6+/-68.5 vs. 11.8+/-4.4 U/L, P or =15.2 U/L) correlated with the advanced clinical stage (P<0.001), bone marrow involvement (P=0.013), international prognostic index score (P=0.001), lactate dehydrogenase level (P=0.001), low Hb level (<12 g/dL) (P=0.028), and lymphocyte count (P=0.023). CONCLUSIONS: The serum TK1 level could serve as a useful biomarker for aggressive clinical behavior in B-cell lymphoma patients.

Test Guidelines for Initial Diagnosis of Hematologic Neoplasms

The standardization committee of the Korean Society for Laboratory Hematology sought to establish standardized testing guidelines for the diagnosis of hematologic malignancies. The guidelines were developed on the basis of survey results and international guidelines, including the National Comprehensive Cancer Network Guidelines and European LeukemiaNet recommendations. The committee expects that the diagnostic guidelines presented here will enhance diagnostic test standardization and clinical decision making and that the novel developments due to new molecular technologies will be integrated into the diagnostic algorithms through ongoing consensus initiatives.

A Rare Case of Pediatric T Lymphoblastic Leukemia With t(11;17)(q23;q21) Involving Mixed-Lineage Leukemia Gene Rearrangement

No abstract available.

Prevalent factor XII deficiency in cancer patients with isolated aPTT prolongation

No abstract available.

Comparison of Serum Fibrin-Fibrinogen Degradation Products with Carcinoembryonic Antigen as Biomarkers for Colon Cancer / 임상검사와정도관리

BACKGROUND: Colon cancer is the second most common cancer in males and fourth most common in females in Korea. The levels of serum fibrin-fibrinogen degradation products (FDP) are elevated in many malignancies due to haemostatic alterations resulting from carcinogenesis. We compared serum FDP with carcinoembryonic antigen (CEA) to assess whether FDP has a diagnostic value for colon cancer. METHODS: A total of 177 serum samples from 95 colon cancer patients and 82 healthy controls were provided by the Korea Cancer Center Hospital biobank. Serum FDP levels were measured using the DR-70 detection kits (AMDL, USA) and the levels of serum CEA were measured using the Roche E170 Analytics (Roche Diagnostics, Germany). RESULTS: The mean serum FDP and serum CEA levels were significantly higher in the cancer patient group (FDP, 1.65+/-1.44 microg/mL; range, 0.36 to 9.48; CEA, 99.99+/-321.74 ng/mL; range, 1.46 to 2,170.00) than in the control group (FDP, 0.58+/-0.46 microg/mL; range, 0.02 to 3.27, P<0.05; CEA, 1.66+/-1.18 ng/mL; range, 0.20 to 6.38, P<0.05). The receiver operating characteristic curve for FDP showed 80% clinical sensitivity and 83% specificity with an optimal cut-off of 0.81 microg/mL, while that for CEA exhibited 84% sensitivity and 94% specificity with a cut-off of 3.51 ng/mL. The area under the curve was 0.87 and 0.96 for serum FDP and CEA, respectively. A combination of the two markers showed 90% clinical sensitivity and 92% specificity for colon cancer. CONCLUSIONS: The diagnostic sensitivity for colon cancer was increased by using a combination of FDP and CEA.

Utilization of Mean Peroxidase Index for Discrimination of Pseudoneutropenia

BACKGROUND: Autoanalyzer ADVIA2120 uses intracellular peroxidase concentration to perform white blood cell (WBC) differential. Therefore, in specimens containing neutrophils with low peroxidase concentration, neutrophils can be miscounted as monocytes or large unstained cells resulting in pseudoneutropenia. Myeloperoxidase deficiency can be detected by the mean peroxidase index (MPXI). The aims of this study are to establish the reference interval of MPXI and define a cut off value for manual slide review to discriminate pseudoneutropenia. METHODS: We calculated reference intervals as mean+/-2SD according to the indirect method of CLSI C28-A3 guideline from MPXI data of 5,802 individuals who took routine health checkup from April 2010 to June 2012. We performed manual slide review on specimens with low MPXI and compared neutrophil differential count of manual method with that of autoanalyzer. When neutrophil differential in manual slide review was >20%P higher than autoanalyzer result, it was regarded as a pseudoneutropenia. We performed ROC analysis using the MPXI results of samples with and without pseudoneutropenia to define a cutoff to discriminate pseudoneutropenia. RESULTS: The reference intervals of MPXI in total population, male, and female were -4.9 to 7.5, -5.5 to 7.3, and -4.5 to 7.5, respectively. The mean value of MPXI was significantly higher in female than in male and there was no difference by age. Twenty-two pseudoneutropenia samples from 7 patients were identified. ROC analysis yielded cutoff value of -20.7 with 94.9% of sensitivity and 77.3% of specificity. CONCLUSIONS: MPXI may be used in the manual slide review guideline for detecting pseudoneutropenia.

A Case of Hereditary Spherocytosis Coexisting with Gilbert's Syndrome / 대한소화기학회지

We recently encountered a case of hereditary spherocytosis coexisting with Gilbert's syndrome. Patient was initially diagnosed with Gilbert's syndrome and observed, but other findings suggestive of concurrent hemolysis, such as splenomegaly and gallstones were noted during the follow-up period. Therefore, further evaluations, including a peripheral blood smear, osmotic fragility test, autohemolysis test, and red blood cell membrane protein test were performed, and coexisting hereditary spherocytosis was diagnosed. Genotyping of the conjugation enzyme uridine diphosphate-glucuronosyltransferase was used to confirm Gilbert's syndrome. Because of the high prevalence rates and similar symptoms of these 2 diseases, hereditary spherocytosis can be masked in patients with Gilbert's syndrome. In review of a case and other article, the possibility of the coexistence of these 2 diseases should be considered, especially in patients with unconjugated hyperbilirubinemia who also have splenomegaly and gallstones.

Influence of Pathogen Inactivation on the Quality of Platelet Rich Plasma Derived Platelets / 대한수혈학회지

BACKGROUND: Pathogen inactivation (PI) is a proactive approach to overcome the limitations of the current testing system and donor questionnaires. Effect of PI on non-leukoreduced platelet rich plasma derived platelets (PRP-PLTs) suspended in plasma has not yet been evaluated. This study was conducted in order to evaluate the effect of PI on the quality of non-leukoreduced PRP-PLTs suspended in plasma. METHODS: PRP-PLTs treated with the Mirasol PRT System and the Intercept Blood System were tested for PLT count, blood gas, PLT activation, and apoptosis on days 3, 5, and 7 of storage. RESULTS: PLT number showed a decrease after PI. No difference in pH was observed until day 5. At day 7, PLTs treated with Mirasol had a lower pH value (6.5), however, it satisfied the quality control criteria. PLTs treated with Mirasol had a lower pO2 compared to pre-inactivation PLTs. pO2 during storage differed significantly between the two PI groups. pCO2 showed a decrease after inactivation and both groups showed a significant difference, compared with the control. PLTs treated with Mirasol had increased P-selectin expression after inactivation; however, difference of P-selectin during storage was not significant compared to the control. P-selectin of PLTs treated with Intercept was significantly different compared to those treated with Mirasol and control. Annexin V showed an increase after inactivation in Mirasol treated PLTs and difference during storage was significant compared to control and Intercept. CONCLUSION: As both PI systems showed satisfactory pH values, the criteria showing a high correlation with in vivo PLT viability and generally applied to monitor quality of PLTs, quality of PRP-PLTs after PI appears not to be negatively affected.

A Case of Hepatosplenic T-cell Lymphoma Diagnosed by Bone Marrow Examination

Hepatosplenic T-cell lymphoma (HSTL) is a condition in which lymphoma cells infiltrate the sinusoids of the liver, spleen, and bone marrow, without lymph node involvement. We encountered a case of hepatosplenic T-cell lymphoma in a Vietnamese woman. The patient was hospitalized with epigastric pain and nausea. Splenomegaly and multiple poorly defined, low-attenuating nodular lesions in the liver were visualized on computed tomography (CT), and thrombocytopenia was noted. The lymph nodes were not significantly enlarged. Splenic biopsy could not be performed because of severe thrombocytopenia. Neoplastic lymphoid cells were present in bone marrow aspirates. Bone marrow sections revealed infiltration of CD3(+) and CD20(-) neoplastic lymphoid cells in the sinusoids. A clonality assay (IdentiClone T-Cell Receptor Delta Gene Clonality Assay; Invivoscribe Technologies, USA) showed gene rearrangements in the T-cell receptor delta gene. Thus, we made a confirmatory diagnosis of HSTL. When splenic biopsy is not available, bone marrow aspirates and clonality assessment may become useful diagnostic tools.

A Case of Heterozygous alpha(+)-Thalassemia Diagnosed in a Korean Family by Using Multiplex Ligation-Dependent Probe Amplification / 임상검사와정도관리

Alpha-thalassemia (alpha-thalassemia), which is prevalent in the Mediterranean region, is caused by deficient synthesis of the alpha-globin chains. It is commonly caused by HBA1 and/or HBA2 gene deletion and is diagnosed by DNA sequence analysis. The proband was a 38-year-old woman who was found to have microcytic and hypochromic anemia on a routine health checkup. Results of the Hb electrophoresis (EP) and direct sequencing of the HBA1 and HBA2 genes were found to be normal. As multiplex ligation-dependent probe amplification (MLPA) for the HBA1 and HBA2 genes revealed heterozygous deletion, she was diagnosed with heterozygous alpha+-thalassemia. Although routine laboratory tests revealed similar findings in the proband's father, brother and niece, MLPA revealed heterozygous deletions of the HBA1 or HBA2 gene in her brother and niece. In summary, we report a case of heterozygous alpha+-thalassemia in a Korean family that was detected by MLPA. We recommend that patients with suspected hemoglobinopathies should be followed-up further with MLPA, especially when Hb EP shows a normal pattern.

A Draft Proposal for Korean Classification and Coding System for In Vitro Diagnostic Medical Devices

BACKGROUND: The Global harmonization task force (GHTF) recommends a separate regulation system for in vitro diagnostic medical devices (IVDD), because false test results can pose a risk to individual and/or public health. However, in Korea, many reagents for IVDD are not monitored, although IVD analyzers and some reagents are monitored under the Medical Device Act and Pharmaceutical Affairs Act, respectively. Our aim was to propose a draft for a Korean coding and classification system for IVDD. METHODS: For preparing the draft, we reviewed the Korean Current Procedural Terminology for Health Insurance and principles of the coding and classification system for IVDD of the GHTF, the USA, Japan, Canada, Australia, and the EU. The draft was reviewed by consultants from relevant societies, such as Korean Medical Association, Korean Society for Laboratory Medicine, The Korea Association of Medical Technologists, and Korea Association for Diagnostic Laboratory Reagents, and was then publicly discussed at a conference. RESULTS: IVDD were classified into 4 classes on the basis of the risks they pose to individual (IR) and public health (PR): class 1 (low IR and low PR), class 2 (moderate IR and low PR), class 3 (high IR and/or moderate PR), and class 4 (high IR and high PR). IVD analyzers, reagents and other general laboratory equipments were categorized and coded using the letter D and 7 (2+3+2) digits. CONCLUSIONS: This draft for the Korean IVDD classification and coding system could be used for effective management and regulation of IVDD in Korea.

A Draft Proposal for Korean Classification and Coding System for In Vitro Diagnostic Medical Devices

BACKGROUND: The Global harmonization task force (GHTF) recommends a separate regulation system for in vitro diagnostic medical devices (IVDD), because false test results can pose a risk to individual and/or public health. However, in Korea, many reagents for IVDD are not monitored, although IVD analyzers and some reagents are monitored under the Medical Device Act and Pharmaceutical Affairs Act, respectively. Our aim was to propose a draft for a Korean coding and classification system for IVDD. METHODS: For preparing the draft, we reviewed the Korean Current Procedural Terminology for Health Insurance and principles of the coding and classification system for IVDD of the GHTF, the USA, Japan, Canada, Australia, and the EU. The draft was reviewed by consultants from relevant societies, such as Korean Medical Association, Korean Society for Laboratory Medicine, The Korea Association of Medical Technologists, and Korea Association for Diagnostic Laboratory Reagents, and was then publicly discussed at a conference. RESULTS: IVDD were classified into 4 classes on the basis of the risks they pose to individual (IR) and public health (PR): class 1 (low IR and low PR), class 2 (moderate IR and low PR), class 3 (high IR and/or moderate PR), and class 4 (high IR and high PR). IVD analyzers, reagents and other general laboratory equipments were categorized and coded using the letter D and 7 (2+3+2) digits. CONCLUSIONS: This draft for the Korean IVDD classification and coding system could be used for effective management and regulation of IVDD in Korea.

Clinical Significance of Oligoclonal Bands in Patients with Multiple Myeloma after Autologous Stem Cell Transplantation

BACKGROUND: Oligoclonal bands or isotype switch detectable by serum immunofixation electrophoresis (IFE) has been reported following chemotherapy and stem cell transplantation in patients with multiple myeloma (MM). We studied the significance of oligoclonal bands appearing after chemotherapy and autologous stem cell transplantation (ASCT) in Korean MM patients, and its impact on relapse. And we investigated the serial serum free light chain (FLC) ratio to establish its possible relationship with the relapse of MM. METHODS: We conducted a retrospective analysis of the serial serum IFE and FLC ratio in 16 MM patients treated with chemotherapy and ASCT. RESULTS: Eleven out of 16 patients (68.8%) had oligoclonal bands with or without isotype switch after ASCT and the median interval from transplantation was 2.0 months. And relapse or persistence rate of monoclonal gammopathy was lower in patients with oligoclonal bands (27.3% vs. 60.0%), though without statistical significance (P=0.299). In eight patients who developed oligoclonal bands and did not relapse, the serial serum FLC ratio was normal in range. But one patient who developed oligoclonal bands and showed increase of plasma cells in bone marrow, the serial serum FLC ratio was abnormal in range. CONCLUSIONS: The occurrence of oligoclonal bands after chemotherapy and ASCT in Korean MM patients is not significantly associated with adverse consequence of relapse or persistence of monoclonal gammopathy. Therefore oligoclonal bands may be not bad prognostic criterion. And the measurement of serum FLC ratio may be a useful indicator to predict relapse in MM patients who developed oligoclonal bands.

Type Distribution of Unexpected Red Cell Antibodies in Patients with Malignancy / 대한수혈학회지

BACKGROUND: Performance of antibody screening and identification tests before blood transfusion is important because the unexpected presence of red cell antibodies may cause hemolytic transfusion reactions. Many patients with malignancy undergo transfusion in order to overcome pancytopenia due to disease itself or chemotherapy. We investigated the type distribution of unexpected red cell antibodies in cancer patients and compared our results with those of other institutions. METHODS: From January 2008 to June 2011, 30,989 serum samples were screened using a LISS/Coombs card and ID-DiaCell I, II (DiaMed AG, Morat, Switzerland). Data-Cyte Plus Reagent Red Blood Cells (Medion Diagnostics, Dudingen, Switzerland) were used in performance of antibody identification tests. RESULTS: Out of 30,989 serum samples, 180 cases (0.58%) showed screening-positive results, and unexpected antibodies were identified in 72 cases. The type of unexpected antibody observed most often in cancer patients was a member of the Rh antibody group, anti-E in 17 cases (29.8%), followed by anti-Lea in five cases (8.8%) and anti-e in three cases (5.3%). While Rh group antibodies were observed in the colon cancer group, non-Rh group antibodies were observed in the rectal cancer group. And, in the genitourinary cancer group, Lewis group antibodies were more frequently detected than others. CONCLUSION: Findings from our study demonstrated a type distribution of unexpected red cell antibodies that was similar to those reported in previous studies. Compared with non-cancerous patients, no difference in type distribution of unexpected red cell antibodies was observed in cancer patients. Some antibodies were frequently observed in certain cancer groups. Further comprehensive research on unexpected antibodies based on location or histologic type of cancer is needed.

Association between Tumor Necrosis Factor-alpha Gene Polymorphism and Bronchopulmonary Dysplasia in Preterm Infants

PURPOSE: Several factors including prolonged inflammatory response are thought to contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The clinical findings can be explained by an increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha). We investigated the relationship between susceptibility to BPD and TNF-alpha promoter polymorphisms to identify genetic factors of the disease. METHODS: Thirty-eight preterm infants who had developed BPD and 55 controlled infants with a birth weight <1,500 g were analyzed for TNF-alpha genotypes. The alleles of five promoter sites (-1031/-863/-857/-308/-238) of TNF-alpha gene were determined using Taqman(R)-based allelic discrimination assays. RESULTS: Gestational age (27(+5)+/-2(+0) wk vs. 29(+2)+/-1(+4) wk, P<0.0001) and birth weight (990+/-270 g vs. 1,220+/-230 g, P<0.0001) were lower in the BPD group compared to the control group. The incidence of respiratory distress syndrome (71.1% vs. 49.1%, P=0.035) and patent ductus arteriosus (71.1% vs. 50.9%, P=0.052) was higher in the BPD group compared to the control group. The frequencies of the alleles and genotypes of five promoter sites (-1031/-863/-857/-308/-238) of TNF-alpha gene did not show differences between the BPD group and the control group. CONCLUSION: TNF-alpha promoter polymorphisms are not associated with susceptibility to BPD in Korean preterm infants.

A Case of Cimetidine-induced Immune Hemolytic Anemia / 대한수혈학회지

There have been 5 case reports about immune hemolytic anemia related with cimetidine, but there has been no such report in Korea. A sixty-four-year-old woman was admitted to the emergency department in a coma. She was diagnosed with diffuse large B-cell lymphoma 5 years ago and she achieved a complete remission after treatment. She was in a state of shock, and her blood pressure was 70/40 mmHg. The laboratory test results were consistent with hemolytic anemia (HA) as follows: hemoglobin: 1.9 g/dL, corrected reticulocyte count: 2%, total/conjugated bilirubin: 6.4/2.1 mg/dL, lactate dehydrogenase: 1,083 U/L and haptoglobin <10 mg/dL. She had a history of taking the drugs including cimetidine, acetaminophen and etizolam for two days. She urgently received transfusion of 3 units of packed red blood cells and then she regained consciousness. To investigate the relation between cimetidine and HA, we subsequently performed a drug-induced immune complex test and an antibody test by using cimetidine, AB serum and phosphate-buffered saline. The results proved that cimetidine was the cause of the HA. Patient was treated with steroid, and the following laboratory tests showed rapid improvement. This is the first case report from Korea that shows the causal relationship between cimetidine and immune HA.