A Case of Sjogren's Syndrome Associated with Common Variable Immunodeficiency / 대한내과학회지

Common variable immunodeficiency (CVID) is a heterogeneous group of primary immune deficiencies in adults characterized by hypogammaglobulinemia, recurrent bacterial infections, and a higher incidence of autoimmune diseases. More than 25% of CVID patients also have autoimmune diseases such as autoimmune hemolytic anemia, immune thrombocytopenic purpura, rheumatoid arthritis, and systemic lupus erythematosus. However, the pathogenesis of autoimmunity in CVID remains obscure. We report a 56-year-old woman with CVID and Sjogren's syndrome. In addition to a long history of recurrent upper respiratory infections, acute gastroenteritis, and cellulitis, she has also suffered from persistent xerostomia and xerophthalmia for the past 10 years. Serologic studies revealed hypogammaglobulinemia (low levels of IgG, IgA, and IgM in serum) and the presence of anti-Ro antibodies, and salivary scintigraphy indicated salivary gland involvement. These findings led to a diagnosis of CVID and Sjogren's syndrome, which was treated by monthly intravenous immunoglobulin therapy.

Systemic Lupus Erythematosus with Initial Presentation of Ascites / 이화의대지

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown etiology and is characterized by presence of variable pathogenic auto-antibodies and multiple organ involvement. Serositis is common in SLE, but peritoneal involvement is relatively rare. This is a case report of 28-year-old female who initially presented with abdominal pain and ascites. After ruling out many other possibilities such as liver cirrhosis, neoplasm, and infectious etiologies, we confirmed SLE with clinical features, serologic tests and radiological findings. To conclude, her abdominal pain and ascites were caused by lupus peritonitis. After administration of corticosteroid therapy, her symptoms fairly improved.

Splenic Infarction as the Initial Manifestation of Antiphospholipid Syndrome in a Systemic Lupus Erythematosus Patient / 대한내과학회지

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. In patients with SLE, the prevalence of antiphospholipid antibodies is considerably higher, and is largely responsible for thrombosis. Splenic infarction is a rare complication of arterial thrombosis in patients with SLE. It is important to consider splenic infarction in a patient with SLE complaining of left upper quadrant (LUQ) pain because of the possibility of severe infarction-related complications, such as subcapsular hemorrhage and splenic rupture. We report a case of solitary splenic infarction in a patient with SLE. The only symptom was LUQ pain of 3-day duration. Lupus anticoagulant activity was positive and abdominal-pelvic computed tomography (CT) was consistent with splenic infarction. She did not show any other evidence of thrombotic events. The patient was diagnosed with antiphospholipid syndrome that presented as a splenic infarction in a SLE patient.

A Case of Renal-limited Lupus-like Nephritis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is clinically heterogeneous and affects multiple organs particularly the kidney. Lupus nephritis is a common and severe manifestation of SLE in which immune-mediated inflammation can lead to permanent damage within the kidney, resulting in end stage renal failure. Recently a renal biopsy showed lupus nephritis on a 40-year old female without any other features of SLE such as clinical symptoms and autoantibodies including antinuclear antibody and anti-dsDNA. The renal biopsy showed that histopathological change of global and segmental sclerosis of glomeluri, diffuse proliferative nephritis with crescent formation compatible with class IV lupus nephritis. She was treated with systemic corticosteroids and pulse cyclophosphamide, followed by mycofenolate mofetil. During two years of follow-up, there have been no clinical or laboratory findings to meet the diagnostic criteria of SLE, suggesting that isolated lupus nephritis could occur without SLE.

Usefulness and Limitation of 2010 ACR/EULAR Classification Criteria in Korean Patients with Early RA

OBJECTIVE: The 2010 New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) was raised to identify patients with early RA and replaced the 1987 ACR classification criteria. The aims of this study are to assess the availability of new classification criteria and to evaluate its potential limitation. METHODS: A total of 408 patients with newly diagnosed RA were included from 13 secondary or tertiary hospitals in South Korea. The symptom duration was less than 12 months before the diagnosis of RA. RA was defined as either 1987 ACR classification criteria or new 2010 ACR/EULAR criteria. We compared the full details of both classification criteria. RESULTS: The mean symptom duration was 5.1 months. The majority (76.2%) of the patients were female. Two hundred and seventy three patients (66.9%) fulfilled both of the 2010 and 1987 classification criteria. Forty-seven (14.7%) of the 320 patients fulfilling the 1987 criteria did not fulfill the new classification criteria. On the other hand, eighty-eight (24.4%) of the 361 patients fulfilling the 2010 ACR/EULAR classification criteria did not fulfill the 1987 ACR criteria. Thirty-six (55.4%) of the 65 patient with seronegative RA failed to meet the 2010 classification criteria. In case of seropositive RA (n=343), 85 additional patients (24.8%) could be diagnosed as RA using new classification criteria. CONCLUSION: The new 2010 ACR/EULAR classification criteria enable physicians to diagnose more patients with early RA via the help of serology. However, the sensitivity for the diagnosis of seronegative RA is projected to decrease.

Characterization of antiphospholipid antibodies in chronic hepatitis B infection / 대한혈액학회지

BACKGROUND: Many infections are associated with antiphospholipid antibodies (aPLs). The purpose of this study was to investigate the prevalence, persistence, clinical significance, and characteristics of aPLs in hepatitis B virus (HBV)-infected patients. METHODS: This study included 143 patients with HBV infection and 32 healthy individuals as controls. The presence of anticardiolipin antibodies (aCL Ab), anti-beta2-glycoprotein I antibodies (beta2GPI Ab), and lupus anticoagulant (LA) was assessed. RESULTS: The total prevalence of aPLs in HBV-infected patients was 12.6% (18 of 143). Of these 18 patients, 15 had low to medium titers of aCL Ab (10 with IgM, 4 with IgG, and 1 with both isotypes). beta2GPI Ab and LA were detected in 3 (2.1%) and 2 (1.4%) patients with HBV infection, respectively. In follow-up specimens from 14 patients with elevated levels of aCL Ab or beta2GPI Ab, 10 (71.4%) showed the persistent presence of aPLs. No clinical manifestations related to aPLs were identified. CONCLUSION: In HBV-infected patients, the most frequently detected antiphospholipid antibodies were IgM aCL Ab, which have a weak association with the clinical manifestations of APS. Unlike the transient presence reported for other infection-associated aPLs, most aPLs were persistently detected over a 12-week period in patients with HBV infection.

Diagnosis and treatment of systemic lupus erythematosus / 대한내과학회지

No abstract available.

Cutaneous Leg Ulcer Mimicking Pyoderma Gangrenosum in Patient with Secondary Antiphospholipid Syndrome / 대한류마티스학회지

Antiphospholipid syndrome(APS) is characterized by vascular thrombosis in association with elevated titers of antiphospholipid antibodies. Leg ulcers are a considered to be a cutaneous manifestation of APS due to thrombosis of small to medium sized vessels. We report a case of necrotic non-healing, ankle ulcers mimicking pyoderma gangrenosum associated with APS in 50-year-old man. He had a past history of autoimmune thrombocytopenia and cerebral infarction. Laboratory findings showed a circulating lupus anticoagulant, positive anticardiolipin antibodies as well as anti-dsDNA and anti-Sm antibodies. Skin biopsy of ulcer lesions showed thrombotic vasculopathy of medium sized vessels with minimal leukocyte infiltration. Ulcers were successfully treated with surgical debridement and subsequent skin graft along with anticoagulation therapy.

Elevated Serum Osteoprotegerin Levels in Systemic Lupus Erythematosus / 대한류마티스학회지

OBJECTIVE: To determine the serum levels of soluble osteoprotegerin (OPG), decoy receptor of receptor activator of nuclear factor kB ligand (RANKL), in patients with systemic lupus erythematosus (SLE) and to assess the its relationships with certain clinical manifestations. METHODS: Serum levels of OPG in 60 patients with SLE and 30 healthy controls were determined by enzyme-linked immunosorbent assay. At the time of serum sampling, clinical manifestations and lupus disease activity index (SLEDAI) were assessed. RESULTS: Serum levels of OPG in 60 patients with SLE were significantly higher than in 30 healthy controls (1,058+/-699 versus 806+/-113 pg/mL, p=0.008). Patients with active disease had higher levels of OPG levels than those with inactive disease (1,355+/-837 versus 760+/-113 pg/mL, p<0.001). Serum OPG levels correlated with SLEDAI (gamma=0.588, p<0.0001), anti-dsDNA antibody titers (gamma=0.337, p=0.009) and serum MCP-1 levels (gamma=0.485, p<0.0001). In particular, serum OPG levels were found to be significantly increased in patients with neurological manifestation compared to those without (1,504+/-1,152 versus 918+/-376 pg/mL, p=0.004). CONCLUSION: The results of this study suggest that serum OPG levels are increased in patients with SLE. Serum OPG has a role as marker for disease activity and its increased levels reflect the involvement of neurological manifestation.

Urinary Excretion of Rantes is Elevated in Lupus Nephritis / 대한류마티스학회지

OBJECTIVE: Infiltrating T cells and monocytes have been implicated in the pathogenesis of lupus nephritis (LN). Chemokines may play a key role in the recruitment of these cells. We investigated whether RANTES (regulated on activation normal T cell expressed and secreted), one of the CC chemokine family, may be involved in the pathogenesis of LN. METHODS: We measured the levels of RANTES in sera and urine from 87 systemic lupus erythematosus (SLE) patients and 78 healthy controls using ELISA. Clinical and laboratory assessment including SLE disease activity index (SLEDAI) were performed at the time of sampling. RESULTS: Serum RANTES levels were significantly higher in the patients with SLE than in healthy controls (115.0+/-5.6 vs. 91.5+/-4.0 pg/ml, p=0.001, mean+/-SEM). Serum RANTES levels correlated well with anti-dsDNA antibody titer (r=0.29, p<0.05) and inversely with serum complement C4 level (r=-0.28, p<0.05). Urinary RANTES/creatinine ratios were significantly higher in patients with nephritis than those without (3.4+/-0.4 vs. 2.2+/-0.3, p=0.004), while serum RANTES level was not different between patients with nephritis and those without. Moreover, urinary RANTES/creatinine ratio positively correlated with urine protein/creatinine ratio (r=0.41, p<0.001). CONCLUSIONS: Our results demonstrate that serum RANTES was elevated in patients with SLE and urinary excretion of RANTES was strongly associated with presence of nephritis. These data suggest that RANTES may be expressed in renal inflammatory sites and may participate in the pathogenesis of LN possibly by augmenting the recruitment of T cells and monocytes.

T cell Proliferative Response to Type II collagen is related to Inflammatory Process and Joint Damage in Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: To investigate the role of T cell responses to type II collagen (CII) in disease progression in rheumatoid arthritis (RA). METHODS: T cell proliferative responses to bovine CII by peripheral blood mononuclear cells (PBMC) from early RA patients (duration or =2) had higher levels of CRP and ESR than those (n=21) not showing T cell responses. The number of damaged joints (by Steinbrocker's method) and damaged joint scores (by Sharp's method) were significantly higher in patients with positive T cell responses than in those without. The joint space narrowing scores correlated well with T cell responsiveness to CII. Patients (n=15) with both positive T cell responses and RA-susceptible allotypes, HLA-DR1 or DR4, had greater damaged joint scores than the rest of patients (n=24). CONCLUSION: T cell proliferative responses to CII are associated with inflammatory activity and radiographic severity in RA. Our data suggest that CII reactive T cells may play an important role in the pathogenic process of joint damage.

Elevated serum interleukin 15 (IL-15) in Behcet's disease / 대한류마티스학회지

OBJECTIVE: To evaluate clinical significance of interleukin 15 (IL-15) in patients with Behcet's disease (BD). METHODS: Serum samples were obtained from 31 patients with BD and 29 healthy controls. BD patients were divided into active and inactive group according to the presence of clinical manifestations on the day of sampling. Serum levels of IL-15 and IL-8 were measured by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of IL-15 and IL-8 were significantly higher in BD patients than in healthy controls (117.2+/-26.2 pg/ml versus 51.8+/-15.4 pg/ml, p<0.01, 287.7+/-100.9 pg/ml versus 138.5+/-17.2 pg/ml, p<0.01, respectively). There was a significant correlation between serum levels of IL-15 and IL-8 IL-15 levels compared with those without it (161.1+/-68.8 pg/ml versus 96.4+/-3 4 . 8pg/ml, p<0.05). Serum levels of IL-15 and IL-8 tended to be higher in active group than in inactive group, but didn't reach statistical significance. CONCLUSION: Serum level of IL-15 was elevated in patients with BD, especially those with uveitis, but it did not seem to be useful as a marker of disease activity in BD.

Increased Serum Concentration of Monocyte Chemoattractant Protein-1 in Systemic Lupus Erythematosus Patients with Antiphospholipid Syndrome / 대한류마티스학회지

OBJECTIVE: To determine the association of serum monocyte chemoattractant protein-1 (MCP-1) concentration and clinical variables of antiphospholipid syndrome (APS). METHODS: We investigated the serum concentration of MCP-1 in systemic lupus erythematosus (SLE) patients by ELISA. The clinical features of APS were evaluated in SLE patients, and anticardiolipin antibody (aCL) was determined at the time of blood sampling. RESULTS: Serum MCP-1 levels (median [range]) in 76 SLE patients were significantly higher than those in 99 healthy controls (192 pg/ml [116, 560] versus 91 pg/ml [26~251], p3 years) had higher levels of MCP-1 than those without (263 pg/ml [166,534] versus 196 pg/ml [116,322], P=0.023). Furthermore, serum MCP-1 levels correlated well with IgG aCL titers (r=0.62, p<0.001). CONCLUSION: Serum MCP-1 levels were elevated in SLE patients, particularly in those with APS, and correlated well with titers of IgG aCL and thrombosis. Our data suggest that increased MCP-1 may play a critical role in the development of APS in SLE patients.

Inhibition of Vascular Endothelial Growth Factor Expression in Cultured Rheumatoid Synoviocytes by Nonsteroidal Anti-inflammatory Drugs / 대한류마티스학회지

OBJECTIVE: Vascular endothelial growth factor (VEGF),a potent angiogenic, permeability-enhancing cytokine plays an important role in chronic inflammatory process of rheumatoid arthritis (RA).Nonsteroidal anti-inflammatory drugs (NSAIDs)are the most widely used drugs for the treatment of RA.However, the effect of NSAIDs on angiogenesis in rheumatoid synovium is unclear.In this study,we investigated the effects of NSAIDs such as indomethacin (IDC) on TGF-beta-induced VEGF production in rheumatoid synoviocytes. METHODS: Fibroblast-like synoviocytes (FLS)from RA were stimulated with T G F -beta(10 ng/ml)for 24hr in the presence of the various concentrations of IDC. The levels of VEGF were measured in culture supernatant by ELISA.In addition, COX-2 and VEGF mRNA expression of cultured FLS were evaluated by RT-PCR. RESULTS:VEGF production from FLS was significantly increased in the presence of TGF-beta.IDC exerted a dose-dependent inhibitory effect on the production of VEGF induced by TGF-beta.RT-PCR analysis showed that IDC also inhibited TGF-beta-induced COX-2 and VEGF mRNA expression in cultured FLS by a dose-dependent manner. CONCLUSION:Our results demonstrate that NSAIDs inhibit VEGF production and the expression of its mRNA and COX-2 mRNA in synovial cells of RA patients.These findings suggest that NSAIDs may suppress progression and perpetuation of rheumatoid synovitis by anti-angiogenic activity.