Think You Kim

Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE.

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations.Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin–angiotensin and kallikrein–kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion= deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement.We evaluated vascular involvement by the presence or absence of hypertension, Raynauds phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynauds phenomenon compared to those without Raynauds phenomenon (P=0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43–5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12–0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P=0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05–0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID=34.5§ 10.8, II ‡ DD=25.6§ 10.2, P=0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7§ 8.4, ID ‡ DD=21.3§ 9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P=0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynauds phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynauds phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.

Mixed Connective Tissue Disease Associated with Skin Defects of Livedoid Vasculitis

Abstract: A 21-year-old woman who had a 2-year history of mixed connective tissue disease (MCTD) developed rapidly evolving ulcers consistent with livedoid vasculitis (LV) in all distal extremities. She presented clinically with Raynaud’s phenomenon, polyarthritis and swollen hands; serologically with high titres of ANA and anti-nRNP; and immunogenetically with HLA-DR4 and HLA-DR53. Although there was initial success in treatment except for the skin defects over the ankles, the patient died from disseminated intravascular coagulation. We suggest that LV may be a poor prognostic manifestation in MCTD.

Lupus flare associated with growth hormone

This case illustrates a young man with an 11 y history of systemic lupus erythematosus who developed lupus flare after a 9-month use of growth hormone (GH) for the treatment of growth retardation. The course of disease was improving after GH cessation and treatment with high dose corticosteroids and intravenous cyclophosphamide pulse therapy.

Seronegative Spondyloarthropathy Initiated by Physical Trauma

Abstract: We undertook this study to demonstrate the pattern of onset and the course of arthritis on the traumatised joint in spondyloarthropathy (SpA) initiated by physical trauma. Among 288 patients with SpA, 12 (4.2%) whose arthropathies were associated with trauma were reviewed retrospectively. There were seven patients with ankylosing spondylitis (AS), three with juvenile onset AS and two undifferentiated SpA. The type of trauma was direct injury to the joint and injuries at other sites, except in spinal surgery, for example. In eight cases the initial evidence of disease was peripheral arthritis. The disease first occurred in traumatised joints in five cases. Only three cases showed recurrent inflammatory episodes in the traumatised joints throughout the disease course. SpA initiated by trauma initially manifested as peripheral arthritis at the traumatised joints in about half of the cases. Inflammatory episodes preferentially involved other joints apart from the traumatised joints throughout the whole course of the disease.

Relative adrenal insufficiency in chronic liver disease: its prevalence and effects on long‐term mortality

The relationship between relative adrenal insufficiency (RAI) and chronic liver disease is unclear.

Education and imaging. Gastrointestinal: Sigmoidocecal fistula diagnosed with colonoscopy.

A 42–year–old woman underwent a colonoscopy for evaluation of abdominal bloating of three months’ duration. Colonoscopic view revealed a large collapsed fistulous opening of the sigmoid colon. The ileocecal valve was identified when the colonoscope was passed through the fistulous opening connecting with the sigmoid colon. When the colonoscope reached the cecum through the conventional intra-luminal technique, white numbers corresponding to the colonoscope insertion length markings could be seen through the fistulous opening (Fig. 1). The appendiceal orifice opening was normal. To confirm the fistulous opening, indigocarmine dye was sprayed into the cecum. The blue dye was found in the sigmoid colon confirming the fistulous connection (Fig. 2). Double contrast barium enema and abdominal computed tomography (CT) scan were also performed. The barium enema also demonstrated the fistulous opening with contrast connecting the mid sigmoid colon and the cecum. Abdominal CT scan also demonstrated an air–filled fistulous tract that extended from the mid sigmoid colon to the cecal pole. However, there were no pericolic inflammation, mesenteric infiltration or bowel wall thickening around the lesion. Colocolonic fistulas are usually a complication of an inflammatory or neoplastic process. However, she had no prior history of any of the predisposing factors related to colocolonic fistulas. A thorough search of English literatures revealed only two cases of sigmoidocecal fistula due to sigmoid diverticulitis or granulomatous colitis. A radiologic study with contrast media is usually used to diagnose intra-abdominal fistulas. In addition, the primary role of colonoscopy may directly visualize the lesion that caused the fistula, and if needed, confirm through histopathologic review. In this case, chromoendoscopy was utilized to prove the presence of the sigmoidocecal fistula during the colonoscopy.

Gastrointestinal: Sigmoidocecal fistula diagnosed with colonoscopy

A 42–year–old woman underwent a colonoscopy for evaluation of abdominal bloating of three months’ duration. Colonoscopic view revealed a large collapsed fistulous opening of the sigmoid colon. The ileocecal valve was identified when the colonoscope was passed through the fistulous opening connecting with the sigmoid colon. When the colonoscope reached the cecum through the conventional intra-luminal technique, white numbers corresponding to the colonoscope insertion length markings could be seen through the fistulous opening (Fig. 1). The appendiceal orifice opening was normal. To confirm the fistulous opening, indigocarmine dye was sprayed into the cecum. The blue dye was found in the sigmoid colon confirming the fistulous connection (Fig. 2). Double contrast barium enema and abdominal computed tomography (CT) scan were also performed. The barium enema also demonstrated the fistulous opening with contrast connecting the mid sigmoid colon and the cecum. Abdominal CT scan also demonstrated an air–filled fistulous tract that extended from the mid sigmoid colon to the cecal pole. However, there were no pericolic inflammation, mesenteric infiltration or bowel wall thickening around the lesion. Colocolonic fistulas are usually a complication of an inflammatory or neoplastic process. However, she had no prior history of any of the predisposing factors related to colocolonic fistulas. A thorough search of English literatures revealed only two cases of sigmoidocecal fistula due to sigmoid diverticulitis or granulomatous colitis. A radiologic study with contrast media is usually used to diagnose intra-abdominal fistulas. In addition, the primary role of colonoscopy may directly visualize the lesion that caused the fistula, and if needed, confirm through histopathologic review. In this case, chromoendoscopy was utilized to prove the presence of the sigmoidocecal fistula during the colonoscopy.

424 PLATELET COUNT/SPLEEN DIAMETER RATIO IS MORE ACCURATE FOR PREDICTION OF SIGNIFICANT AND EXTENSIVE FIBROSIS THAN AST-TO-PLATELET RATIO INDEX (APRI) IN PATIENTS WITH CHRONIC HEPATITIS C

Background and Aims: The platelet count/spleen diameter ratio [P/S ratio (N/mm)/mm)] was reported as a useful non-invasive marker to predict the presence of esophageal varices in cirrhotic patients. This study was aimed to investigate the P/S ratio and to compare with AST-to-platelet ratio index (APRI) for the prediction of significant and extensive fibrosis in patients with chronic hepatitis B (CHB) and C (CHC). Methods: We reviewed the data of 258 patients (male 165, female 93, mean age 41.7±12.7 years; CHB 190, CHC 68), who underwent liver biopsy (2001–2008) and in whom spleen size was simultaneously measured as the longest diameter by ultrasound. Liver fibrosis was staged according to METAVIR scoring system. Diagnostic accuracies of P/S ratio and APRI for predicting hepatic fibrosis were evaluated using area under ROC curves (AUC) analysis. Results: The numbers of CHB and CHC patients with F0–F1 were 30 and 14, F2 58 and 18, F3 59 and 22, and F4 43 and 14, respectively. Both P/S ratio and APRI were significantly correlated with fibrosis stage (all, p < 0.001). The AUC values of the two parameters for predicting significant (F2–4) and extensive (F3–4) fibrosis were shown in Table 1. The 2200 cutoff value of P/S ratio had 81.5% sensitivity, 71.4% specificity, 91% positive predictive value, 50% negative predictive value, 2.85 positive likelihood ratio, and 0.26 negative likelihood ratio for the diagnosis of significant fibrosis in CHC patients. Conclusion: The P/S ratio is more accurate than APRI for the prediction of significant and extensive fibrosis in patients with CHC, but not in CHB.

A Case of Anti-reticulin Antibody-positivity in Metachronous Double Primary Cancer

Dear Editor, Several studies have demonstrated the relationship between autoantibodies and tumors [1]. The anti-reticulin antibody (ARA) was first identified in 1971 and was used as a specific marker for gluten-sensitive enteropathy [2, 3], playing a supportive role in the diagnosis of celiac disease. However, anti-tissue transglutaminase antibody detection has replaced the ARA method as the single test to diagnose celiac disease. To date, ARA has only been identified in patients with autoimmune enteropathy and other types of autoimmune diseases. However, we observed its presence in a patient who was diagnosed as having metachronous double primary cancer. We evaluated the relationship between ARA and malignancy. A 77-year-old man achieved complete recovery of papillary urothelial carcinoma of the bladder after undergoing transurethral resection of the bladder tumor in October 2003 at Hanyang University Medical Center, Seoul, Korea. In June 2013, he was diagnosed as having adenocarcinoma as a second primary cancer with involvement of multiple lymph nodes and bone metastases. The patient was maintained with hormone therapy and conservative treatment. In October 2014, biochemistry test results showed an alkaline phosphatase level of 176 U/L and AST/ ALT levels of 149/166 U/L, both of which were higher than normal levels. The results of viral hepatitis test and complete blood cell count were normal. To differentially diagnose toxic hepatitis, hormone therapy was discontinued. An antinuclear antibody (ANA) test performed to differentially diagnose autoimmune hepatitis was negative. The test tissue was negative for anti-smooth muscle antibody (ASMA) but was positive for R1-ARA (Fig. 1). At that time, the patient had elevated AST/ALT levels due to nonalcoholic fatty liver disease, for which he was solely treated with analgesics. In this case, the second primary cancer developed nine years and eight months after the primary cancer. Although this is a relatively long period, detection of the autoantibody in a patient with double primary cancer may be of general significance. ARA is generally detected by indirect immunofluorescence using three types of rat tissues (stomach, kidney, and liver), and its immunofluorescent patterns are classified into five types (R1, R2, RKC, RAC, and Rs) [4]. Among these, R1-ARA is specific to untreated celiac disease [5, 6]. The R1 pattern is immunopositive in the perivascular area of the stomach, kidney, and liver; the area between the gastric glands; the periglomerular and peritubular areas of the kidney; and the areas surrounding the liver parenchyma, sinusoid, and portal vein of the liver. Natural autoantibodies regulate the immune system. Therefore, it is possible that various types of autoantibodies may be detected in conditions, in which homeostasis is disrupted, in-

Gastrointestinal: Sigmoidocecal fistula diagnosed with colonoscopy: Images of Interest

A 42–year–old woman underwent a colonoscopy for evaluation of abdominal bloating of three months’ duration. Colonoscopic view revealed a large collapsed fistulous opening of the sigmoid colon. The ileocecal valve was identified when the colonoscope was passed through the fistulous opening connecting with the sigmoid colon. When the colonoscope reached the cecum through the conventional intra-luminal technique, white numbers corresponding to the colonoscope insertion length markings could be seen through the fistulous opening (Fig. 1). The appendiceal orifice opening was normal. To confirm the fistulous opening, indigocarmine dye was sprayed into the cecum. The blue dye was found in the sigmoid colon confirming the fistulous connection (Fig. 2). Double contrast barium enema and abdominal computed tomography (CT) scan were also performed. The barium enema also demonstrated the fistulous opening with contrast connecting the mid sigmoid colon and the cecum. Abdominal CT scan also demonstrated an air–filled fistulous tract that extended from the mid sigmoid colon to the cecal pole. However, there were no pericolic inflammation, mesenteric infiltration or bowel wall thickening around the lesion. Colocolonic fistulas are usually a complication of an inflammatory or neoplastic process. However, she had no prior history of any of the predisposing factors related to colocolonic fistulas. A thorough search of English literatures revealed only two cases of sigmoidocecal fistula due to sigmoid diverticulitis or granulomatous colitis. A radiologic study with contrast media is usually used to diagnose intra-abdominal fistulas. In addition, the primary role of colonoscopy may directly visualize the lesion that caused the fistula, and if needed, confirm through histopathologic review. In this case, chromoendoscopy was utilized to prove the presence of the sigmoidocecal fistula during the colonoscopy.