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AIM: To investigate the clinical implications of a genetic polymorphism in glycoprotein 96 (GP96), by analyzing the association between the genotype and haplotype of GP96 with systemic lupus erythematosus (SLE). METHOD: We analyzed cell-surface expression of GP96 in peripheral blood mononuclear cells (PBMCs) and serum titer of anti-GP96 antibody of SLE patients. Single nucleotide polymorphisms and deletion mutants of GP96 were detected by two-dimensional gene scanning (TDGS). Odds ratios with 95% confidence intervals (CI) were determined for each genotype and haplotype through the chi-square test. RESULTS: In total, 216 Korean SLE patients and 215 age- and sex-matched healthy controls were enrolled. In SLE patients, as opposed to healthy controls, cell-surface expression of GP96 among human leukocyte antigen-DR+ PBMCs (76.4% vs 45.5%, respectively, P < 0.001) and serum anti-GP96 antibody titers (0.98 vs 0.50, respectively, P = 0.012) increased. TDGS revealed six polymorphic sites in GP96, two of which were significantly associated with SLE (exon 1, g.-7C>G, odds ratio [OR] 1.78, 95% CI 1.16-2.75, P = 0.009; exon 17, g.17009_17011del, OR 1.76, 95% CI 1.18-2.64, P = 0.006). Two haplotypes (121111, 211212) were strongly associated with SLE (OR 8.92, 95% CI 1.10-72.6, P = 0.041; OR 3.03, 95% CI 1.22-7.50, P = 0.017, respectively) and specific clinical manifestations (discoid rash, arthritis, renal disorder, neurologic disorder, and hematologic disorder). Haplotype-based analysis revealed a stronger association between GP96 and SLE than did genotype-based analysis. CONCLUSION: The two polymorphisms, each in exons 1 and 17 of GP96 are potential genetic risk factors of SLE. Two haplotypes 121111 and 211212 are related to not only SLE but also specific clinical manifestations.
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Lupus Eritematoso Sistémico/genética , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple , Eliminación de Secuencia , Adulto , Estudios de Casos y Controles , Exones , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Fenotipo , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Patients with RA have an increased risk of atherosclerosis and cardiovascular (CV) diseases compared with the general population. The aim of this study was to evaluate the role of inflammatory burden in the formation of carotid plaques in patients with RA. METHODS: We performed carotid artery US to measure the carotid intima-media thickness (IMT) and plaques in 406 patients with RA and 209 age- and sex-matched healthy controls. To assess the inflammatory burden, the area under the curve (AUC) of ESR over time was calculated. RESULTS: The carotid plaque frequency and mean IMT were significantly increased in patients with RA relative to controls. After adjustment for age and gender, the presence of carotid plaques in patients with RA was associated with HAQ score, tender joint count (TJC), swollen joint count (SJC), 28-joint DAS, ESR, CRP, LEF use, current corticosteroid dose and the number of conventional CV risk factors. After multivariate regression analysis, the factors significantly associated with plaque formation were TJC (P = 0.002), ESR (P = 0.002) and the number of conventional CV risk factors (P = 0.041). Among 194 RA patients with ESR AUC data, the presence of carotid plaque was independently associated with both the ESR AUC and number of conventional CV risk factors, which showed a synergistic interaction. CONCLUSION: Cumulative inflammatory burden contributes to the development of carotid atherosclerosis through a synergistic interaction with conventional CV risk factors in patients with RA.
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Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Grosor Intima-Media Carotídeo , Estenosis Carotídea/epidemiología , Inflamación/sangre , Inflamación/complicaciones , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Arterias Carótidas/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: We investigated the electromyography (EMG) findings and demographic, clinical, and laboratory features that may predict the development of malignancy in patients with idiopathic inflammatory myopathy (IIM). METHODS: In total, 61 patients, 36 with dermatomyositis and 25 with polymyositis, were included. Patients were divided into those with and without malignancies, and comparisons were made between the groups in terms of their demographic, clinical, laboratory, and EMG findings. RESULTS: The frequencies of malignancies associated with dermatomyositis and polymyositis were 22% and 8%, respectively. Patients with malignancies showed a significantly higher incidence of dysphagia (odds ratio [OR], 21.50; 95% confidence interval [CI], 3.84 to 120.49), absence of interstitial lung disease (ILD; OR, 0.12; 95% CI, 0.01 to 0.98), and complex repetitive discharge (CRD) on the EMG (OR, 26.25; 95% CI, 2.67 to 258.52), versus those without. After adjustment for age, dysphagia and CRD remained significant, while ILD showed a trend for a difference but was not statistically significant. Multivariate analysis revealed that the CRD conferred an OR of 25.99 (95% CI, 1.27 to 531.86) for malignancy. When the frequency of malignancy was analyzed according to the number of risk factors, patients with three risk factors showed a significantly higher incidence of malignancy, versus those with fewer than two (p = 0.014). CONCLUSIONS: We demonstrated for the first time that CRD on the EMG was an additional independent risk factor for malignancy in IIM. Further studies on a larger scale are needed to confirm the importance of CRD as a risk factor for malignancy in IIM.
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Dermatomiositis/diagnóstico , Electromiografía , Músculo Esquelético/inervación , Neoplasias/etiología , Polimiositis/diagnóstico , Potenciales de Acción , Adulto , Anciano , Dermatomiositis/complicaciones , Dermatomiositis/fisiopatología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Músculo Esquelético/patología , Oportunidad Relativa , Polimiositis/complicaciones , Polimiositis/fisiopatología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We investigated the clinical and endoscopic features of gastrointestinal lesions in adults with Henoch-Schönlein purpura (HSP) causing gastrointestinal bleeding. The study included 24 adult HSP patients with gastrointestinal hemorrhage who underwent both upper gastrointestinal endoscopy and colonoscopy. The controls were 27 adult HSP patients without gastrointestinal hemorrhage. Patients with gastrointestinal bleeding showed higher frequencies of purpura on the upper extremities and trunk, and of elevated serum C-reactive protein (CRP). The rate of concurrent lesions in both the upper and lower gastrointestinal tracts was 91.7 %. The second portion of duodenum and terminal ileum were most frequently and severely involved. Leukocytoclastic vasculitis was detected in severe lesions and was significantly associated with mucosal ischemic changes. Most lesions (95.7 %) dramatically improved after corticosteroid therapy. This study suggests that both upper and lower gastrointestinal examinations are necessary for proper evaluation of gastrointestinal bleeding in patients with HSP.
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Enfermedades del Colon/etiología , Enfermedades Duodenales/etiología , Endoscopía Gastrointestinal , Hemorragia Gastrointestinal/etiología , Vasculitis por IgA/complicaciones , Enfermedades del Íleon/etiología , Adolescente , Adulto , Antiinflamatorios/uso terapéutico , Proteína C-Reactiva/metabolismo , Enfermedades del Colon/sangre , Enfermedades del Colon/patología , Colonoscopía , Enfermedades Duodenales/sangre , Enfermedades Duodenales/patología , Femenino , Hemorragia Gastrointestinal/sangre , Hemorragia Gastrointestinal/patología , Humanos , Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/patología , Enfermedades del Íleon/sangre , Enfermedades del Íleon/patología , Mucosa Intestinal/irrigación sanguínea , Isquemia/etiología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Retrospectivos , Torso , Extremidad Superior , Adulto JovenRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organs. Chemokines and their receptors play an important role in the pathogenesis of SLE. Lymphocytes expressing CXCR3, chemokine receptors of CXCL4, 9, 10, and 11, increase in patients with SLE and animal models, particularly in those with skin manifestations and nephritis. We investigated CXCR3 genetic polymorphisms in patients with SLE and their association with clinical manifestations. METHODS: A total of 346 patients with SLE and 540 healthy controls were investigated for CXCR3 intron 1 polymorphisms rs2280964 and rs34334103 by Taqman analysis. RESULTS: rs2280964 and rs34334103 were not associated with all patients with SLE, but rs34334103 showed a significant association with male patients with SLE. Among the clinical manifestations, pleuritis was associated with the rs34334103 polymorphism. CONCLUSION: The CXCR3 polymorphism rs34334103 was associated with male gender and pleuritis in patients with SLE.
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Predisposición Genética a la Enfermedad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/genética , Pleuresia/etiología , Polimorfismo Genético , Receptores CXCR3/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores Sexuales , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was to determine the clinicopathologic characteristics of granulomatosis with polyangiitis (Wegener's) (GPA) in Korean patients. METHODS: The medical records of 45 patients with GPA treated in a single tertiary referral hospital were retrospectively analyzed with respect to clinical manifestations, including histology, ANCA positivity, disease stage, and disease activity. Patients were categorized into granulomatous, vasculitic, or mixed form based on an immunopathologic scoring system of granulomatous-vasculitic activity. RESULTS: Thirty-one patients (68.9 %) showed ANCA positivity (C-ANCA/P-ANCA, 42.2 %/20.0 %, proteinase-3 (PR3) ANCA/myeloperoxidase (MPO) ANCA, 44.1 %/16.1 %), and these patients (female 48.4 %) were found to be associated with a higher frequency of renal involvement (51.6 vs. 7.1 %, p = 0.004), elevated serum creatinine (29.0 vs. 0 %, p = 0.018), and higher mortality (29 vs. 7.1 %, p = 0.041) than ANCA-negative patients. Thirty-three patients (73.3 %, female 60.6 %) had the granulomatous form, whereas 8.9 and 17.8 % had the vasculitic and mixed forms, respectively. Patients with the granulomatous form were diagnosed earlier in their lives (mean age 51.2 vs. 62.3, p = 0.002) and had a lower frequency of renal involvement (21.2 vs. 100 %, p = 0.005) compared with those with the vasculitic form. Initial remission (69.7 vs. 25.0 %) and relapse (60.8 vs. 0 %) rates were higher for the granulomatous than for the vasculitic form. CONCLUSIONS: Taken together, in Korean patients with GPA, the granulomatous form was predominant and associated with a younger age at diagnosis and a lower frequency of renal involvement than the vasculitic form. ANCA positivity was found in 68.9 % and associated with renal involvement and higher mortality.
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Anticuerpos Anticitoplasma de Neutrófilos/sangre , Granulomatosis con Poliangitis/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
A 73-year-old man with a history of hypertension and ascending aortic dissection was hospitalized for aggravated abdominal pain and general ache for 3 months. Follow-up CT showed aggravated abdominal aortic hematoma with aneurysm, atherosclerotic periaortitis and bilateral hydronephrosis. An initial laboratory finding showed elevated levels of inflammatory markers and renal dysfunction. Positron emission tomography-CT showed an increased standardized uptake values level in the aortic arch, descending thoracic aorta, major branch, abdominal aorta, and common iliac artery. For bilateral hydronephrosis, a double J catheter insertion was performed. Tissue specimens obtained from previous surgery on the aorta indicated the infiltration of lympho-plasma cells without granuloma formation in the aortic wall. After a combined therapy of high dose steroid therapy with azathioprine, the patient's initial complaints of abdominal pain, weakness and azotemia improved. This case was diagnosed as chronic periaortitis based on aortic inflammation at biopsy, which was complicated with retroperitoneal fibrosis and ureteric obstruction.
RESUMEN
Mannose-binding lectin (MBL) serum levels or genetic polymorphisms are known to be associated with autoimmune diseases. We investigated MBL2 genetic polymorphisms in 95 patients with ankylosing spondylitis (AS) and in 252 healthy controls. MBL2 promoter polymorphisms at -550 (H/L), -221 (Y/X), +4 (P/Q), and exon polymorphisms at codon 52 (Arg/Cys), 54 (Gly/Asp, or A/B), and 57 (Gly/Glu) were investigated using polymerase chain reaction and restriction fragment length polymorphism. Genetic polymorphisms were analyzed using SPSS (ver 12.0) and Haploview (ver 4.2). MBL2 single-nucleotide polymorphisms (SNPs) were not significantly different between patients with AS and controls. By haplotype analysis, LYPB frequency was significantly lower in AS (10.7% vs. 21.3%, OR 0.441, 95% CI: 0.266-0.733, P value = 0.001, Pc value = 0.008). The frequency of LYPA (15.4% vs. 9.2%, OR 1.802, 95% CI: 1.097-2.961, P value = 0.019, Pc value = 0.101) and HYPB (3.5% vs. 0.8%, OR 4.457, 95% CI: 1.289-15.409, P value = 0.011, Pc value = 0.060) tended to be higher in AS. Clinical characteristics of AS were not associated with any MBL2 SNP or haplotype. In summary, haplotypes of MBL2 genetic polymorphisms were found to be associated with AS, which suggests that MBL2 genetic polymorphisms may play a role during the development of AS.
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Pueblo Asiatico/genética , Haplotipos , Lectina de Unión a Manosa/genética , Espondilitis Anquilosante/genética , Adulto , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Exones , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , República de Corea/epidemiología , Medición de Riesgo , Factores de Riesgo , Espondilitis Anquilosante/etnología , Adulto JovenRESUMEN
The aim of this study was to investigate T-cell immunoglobulin and mucin domain 3 (TIM3) genetic polymorphisms and rheumatoid arthritis (RA) according to the shared epitope (SE) status. Six single nucleotide polymorphisms (SNPs: rs11742259 [C/T], rs10515746 [C/A], rs35960726 [A/G], rs1036199 [A/C], rs4704846 [A/G], and rs11134551 [A/G]) in the TIM3 gene from 366 RA patients and 389 healthy controls were investigated using the real-time polymerase chain reaction method. Associations between these SNPs and clinical manifestations (including SE status) were investigated using the SPSS program and Haploview. Polymorphisms of rs35690726 (AG+ GG vs AA: 8.2% vs 1.8%, p(c) < 0.001) were significantly associated with RA with or without SE (p(c) < 0.001 or p(c) = 0.009, respectively). Polymorphisms of rs11742259 (p(c) = 0.003) and rs1036199 (p(c) = 0.012) were significantly different in RA patients with SE, but not in those without SE. In haplotype analysis with a permutation test for the first 4 SNPs (rs11742259, rs10515746, rs35690726, and, rs1036199), CCAA, CCGA, CCGC, and CAAA haplotypes were significantly associated with RA. The clinical characteristics of RA patients were not significantly associated with any TIM3 polymorphism. TIM3 genetic polymorphisms may have a role in the development of RA regardless of a shared epitope status.
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Artritis Reumatoide/genética , Epítopos/genética , Estudios de Asociación Genética , Antígenos HLA/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Linfocitos T/metabolismo , Adulto , Alelos , Artritis Reumatoide/inmunología , Estudios de Casos y Controles , Epítopos/inmunología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA/inmunología , Haplotipos , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , República de Corea , Programas Informáticos , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
Shared epitope (SE) and anti-cyclic citrullinated peptide (CCP) antibody are known to be associated with rheumatoid arthritis (RA). The authors investigated their adjusted effects on RA from Korean population. Clinical features were evaluated in 226 RA patients; 164 healthy controls were enrolled. HLA-DRB1 typing for SE was done by polymerase chain reaction. Anti-CCP antibody levels were determined by enzyme linked immunosorbent assay. Logistic regression analysis method was used for adjusted effects. SE and anti-CCP antibody were associated with RA susceptibility. Anti-CCP antibody was associated with RA susceptibility independent of SE [odds ratio, OR 179.9 (95% confidence interval, CI 40.8-792.2), P < 0.001]. Anti-CCP antibody was associated with radiographic erosive changes independent of SE or rheumatoid factor [OR 3.9 (95% CI 1.1-13.3), P = 0.032]. Anti-CCP antibody was strongly associated with RA susceptibility and radiographic erosion of RA patients, independent of SE in Korean.
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Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Epítopos/inmunología , Péptidos Cíclicos/inmunología , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico por imagen , Femenino , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Péptidos Cíclicos/sangre , Radiografía , Estudios Retrospectivos , Factor Reumatoide/sangreRESUMEN
To investigate the association between functional promoter polymorphisms of matrix metalloproteinase-9 (MMP-9) and systemic lupus erythematosus (SLE), we analyzed MMP-9 promoter -1562 C>T and MMP-9 -90 (CA)(n) repeat polymorphisms in 135 Korean SLE patients (mean age, 34.7 years; 124 female and 11 male) and in 135 gender- and age-matched healthy controls (mean age, 35.4 years). Clinical and laboratory findings were collected during the follow-up period (mean, 63.5 months; range, 3-252 months), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Indexes were calculated. The levels of total MMP-9 were measured in sera of SLE patients and controls by enzyme-linked immunoabsorbent assay. The serum levels of MMP-9 in SLE patients were significantly lower than those of controls (mean +/- standard error of the mean, 1421.6+/-177.4 vs 3731.4+/-441.4 ng/ml, p=1.2 x 10(-5) by t test). Both functional polymorphisms were under the Hardy-Weinberg equilibrium state except (CA)(n) repeat polymorphisms in SLE patients (p=2.6 x 10(-5) by chi(2) goodness-of-fit test). The distribution of the MMP-9 promoter polymorphisms or haplotypes was not significantly different in SLE patients and controls. However the frequency of alleles with low numbers of CA repeats (n<21, 11.9% vs 7.0%, p=0.06 by the chi(2) test; odds ratio=1.78, 95% confidence interval=0.99-3.20) and the prevalence of low CA repeats homozygote tended to be higher in patients than in controls (5.2% vs 0.7%, p=0.07 by logistic regression, odds ratio=7.29, 95% confidence interval=0.88-60.10) in the recessive model. No relationship was found between MMP-9 polymorphisms and clinical features or damage as indicated by SLICC/ACR Damage Index in the study subjects. These results suggest that genetic polymorphisms of the MMP-9 promoter regions are not associated with the development of SLE in Korea.
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Lupus Eritematoso Sistémico/genética , Metaloproteinasa 9 de la Matriz/genética , Regiones Promotoras Genéticas , Adulto , Anciano , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Corea (Geográfico) , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
Scleroderma (SSc) renal crisis has been reported to be associated with anti-RNA polymerase I and III (RNAP I/III) antibodies in Caucasians and the Japanese. However, no report is available for Korean SSc patients. Here, we describe the case of a 65-yr-old female SSc patient who developed renal crisis and whose serum contained anti-RNAP I/III antibodies. She was finally diagnosed as having diffuse cutaneous SSc based on skin thickening proximal to the elbows and knees. Sudden hypertension, oliguria, and pulmonary edema were features of her renal crisis. Despite the use of captopril and adequate blood pressure control, her renal function deteriorated. Subsequent renal biopsy findings showed severe fibrinoid necrosis with luminal obliteration in interlobar arteries and arterioles consistent with SSc renal crisis. Serum anti-RNAP I/III antibodies were detected by radioimmunoprecipitation. This is the first report of a renal crisis in a Korean SSc patient with RNAP I/III antibodies.
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Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/inmunología , Autoanticuerpos/sangre , ARN Polimerasa III/inmunología , ARN Polimerasa I/inmunología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/inmunología , Lesión Renal Aguda/enzimología , Anciano , Cuidados Críticos , Femenino , Humanos , Corea (Geográfico) , Esclerodermia Sistémica/enzimologíaRESUMEN
We describe a case of a 54-yr-old AL amyloidosis patient who developed femoral compressive neuropathy due to iliopsoas pseudohypertrophy. The patient, who presented with end stage renal disease, was referred to our clinic because of lower extremity weakness and polyarthritis. Finally, he was diagnosed as having kappa-AL amyloidosis, complicated by femoral compressive neuropathy, hypertrophic amyloid myopathy, amyloid arthropathy, carpal tunnel syndrome, and end stage renal disease. Femoral compressive neuropathy has never been reported in association with amyloid induced iliopsoas hypertrophic myopathy. This report expands the clinical spectrum of AL amyloidosis.
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Amiloidosis/patología , Neuropatía Femoral/patología , Síndromes de Compresión Nerviosa/patología , Resultado Fatal , Humanos , Hipertrofia , Fallo Renal Crónico/patología , Masculino , Persona de Mediana Edad , Músculos Psoas/patologíaRESUMEN
Epithelioid hemangioendothelioma is a rare vascular tumor, which occurs in the lung, liver, bone, and soft tissue. Hypertrophic osteoarthropathy is a syndrome characterized by subperiosteal new bone formation, joint effusion and clubbing, and may be associated with cyanotic heart disease, chronic pulmonary disease, liver disease, and other miscellaneous diseases. The activation of endothelium and platelets has been suggested to be involved in the development of hypertrophic osteoarthropathy. We report a rare case of hypertrophic osteoarthropathy, which developed in association with hepatic epithelioid hemangioendothelioma with pulmonary metastasis. We also discuss the role of vascular endothelial growth factor in its pathogenesis.