A Case of Infectious Mononucleosis-like Syndrome Induced by Ceftriaxone and Isepamicin in a Patient with Systemic Lupus Erythematosus / 대한류마티스학회지

A severe adverse reaction to certain drug could be associated with hypersensitivity syndrome, showing the clinical features of infectious mononucleosis including maculopapular rash, fever, lymphadenopathy, leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance. We report a systemic lupus erythematosus patient who developed infectious mononucleosis-like syndrome with administration of ceftriaxone/isepamicin for the treatment of pneumonia. This case warrants careful attention to infectious mononucleosis-like syndrome associated with antibiotics administration, especially in febrile patients with known autoimmune diseases such as systemic lupus erythematosus.

A Case of Septic Arthritis in Patient with Wiskott-Aldrich Syndrome / 대한류마티스학회지

The Wiskott-Aldrich syndrome is a rare disease characterized by thrombocytopenia, recurrent eczema and a marked vulnerability to recurrent infection. Patients with Wiskott-Aldrich syndrome have frequent infections by bacteria which have polysaccharide capsules such as Pneumococcus, Hemophilus influenzae and Neisseria meningitidis due to poor antibody response to polysaccharide antigens. We experienced a 21 years old man with septic arthritis combined with Pneumococcal pneumonia, multifocal abscesses in back and iliacus muscle. After treatment with antibiotics for one month, he was treated successfully.

A Case of Infectious Mononucleosis-like Syndrome Induced by Sulfasalazine / 대한내과학회지

Sulfasalazine, one of disease modifying anti-rheumatic drugs, is widely used in various rheumatic diseases. Very rarely, sulfasalazine causes drug-associated hypersensitivity syndrome that resembles infectious mononucleosis. Clinical signs include fever, lymphadenopathy, maculopapular skin rash and multivisceral involvement which appear 2 to 5 weeks after administration of drug. Atypical lymphocytosis, liver dysfunction and splenomegaly are also frequently observed. Severe infectious mononucleosis-like syndrome in sulfasalazine treated patients can be caused by reactivation of viruses such as human herpes virus-6, that often result in hypersensitivity syndrome. We report a case of patient who developed infectious mononucleosis-like syndrome after administration of sulfasalazine for the treatment of rheumatoid arthritis. This case warrents careful observation for infectious mononucleosis-like syndrome after sulfasalazine treatment.

Increased plasma endothelin-1 and abnormal nailfold capillaroscopic findings in patients with connective tissue diseases / 대한내과학회지

BACKGROUND: Since the endothelin-1 may be implicated in the pathogenesis of peripheral vascular diseases associated with connective tissue diseases (CTDs), we examined the plasma endothelin-1 level in association with quantitative nailfold capillaroscopy in patients with CTDs. METHODS: We investigated 79 patients with connective tissue diseases (54 systemic lupus erythematosus (SLE), 18 systemic sclerosis (SSc), 4 mixed connective tissue disease, 3 polymyositis/dermatomyositis). Plasma samples were obtained and endothelin-1 levels were measured by sandwich enzyme-linked immunosorbent assay. The presence and duration of Raynaud phenomenon as well as nailfold capillaroscopy were evaluated in each patient. To examine the quantitative nailfold capillaroscopy, we measured the length of apical limb width, capillary width and capillary length. RESULTS: According to the presence or absence of Raynaud phenomenon, there was no statistically increased plasma endothelin-1 level between two groups (2.433 +/- 2.259 pg/mL n=33, vs. 1.905 +/- 1.371 pg/mL n=46, p=non specific). All the SSc patients had Raynaud phenomenon and according to the presence of abnormal capillaroscopic findings, there were increased level of endothelin-1 in abnormal capillaroscopy group compared to normal capillaroscopy group (3.940 +/- 3.335 pg/mL (n=12), vs 1.573 1.006 pg/mL (n=6), p<0.05). As compared quantitative examination of nailfold capillaroscopy with plasma endothelin-1 level, in SSc patients the endothelin-1 level correlated well with the length of apical limb width (r(s)=0.577 p<0.05). In SLE patients the endotheliln-1 level correlated well with the length of apical limb width and capillary width (r(s)=0.425 p<0.01, rs=0.278 p<0.05, respectively). CONCLUSION: Our data demonstrate that the presence of abnormal capillaroscopic findings reflect increased plasma endothelin-1 level in patients with connective tissue diseases, and quantitative analysis of nailfold capillaroscopy can be useful to predict the disease activity with the evidence of increased plasma endothelin-1.

Comparison of Clinical Efficacy between Nonsteroidal Anti-inflammatory Drugs and Acetaminophen in Knee Osteoarthritis according to Ultrasonographic Findings / 대한류마티스학회지

OBJECTIVE: To compare the clinical efficacy between nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen in knee osteoarthritis according to ultrasonographic findings. METHODS: We administered 12 mg of NSAIDs (lornoxicam) plus misoprostol 300microgram or 1,950 mg of acetaminophen in 40 randomly selected patients who fulfilled the ACR criteria for knee osteoarthritis. The effectiveness of these drugs on osteoarthritis was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. In addition, we performed ultrasonography of the knee joints and assessed length of capsular distension, length of medial and lateral osteophyte, amount of joint effusion, and the presence of synovial proliferation. RESULTS: There were significant correlations between WOMAC score and length of capsular distension and length of medial/lateral osteophyte. At 6 weeks, both lornoxicam and acetaminophen-treated patients had significant lower levels of WOMAC score compared to the entry into the trial (p or =0.7 cm) or severe medial osteophyte (length of osteophytes > or =0.4 cm) showed better responses to lornoxicam than to acetaminophen in terms of the reduction of WOMAC score (p=0.008 for severe capsular distension, p=0.03 for severe medial osteophyte). However, in the subgroup with mild forms of capsular distension (<0.7 cm) or medial osteophytes (<0.4 cm), no difference was found in the reduction of WOMAC score 6 weeks after treatment with lornoxicam versus acetaminophen. CONCLUSIONS: Patients with osteoarthritis of the knee had significantly greater improvements in pain score over 6 weeks with lornoxicam than with acetaminophen, particularly in patients with severe forms of capsular distension and medial osteophyte on joint ultrasonography. Ultrasonography could be an useful tool to determine the usage of NSAIDs versus acetaminophen in knee osteoarthritis patients.

Feedback Control of Cyclooxygenase-2 Expression by Prostaglandin E2 in Rheumatoid Synoviocytes

Objective: The role of prostaglandin E2 (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. METHODS: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-kappaB binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. RESULTS: PGE2 (10(-11) to 10(-5) M) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-1beta, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-kappaB in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. CONCLUSION: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.

Tuberculosis in Patients with Systemic Lupus Erythematosus: Single Center Retrospective Study / 대한류마티스학회지

OBJECTIVE: To compare the incidence and clinical characteristics of tuberculosis (tbc) between patients with systemic lupus erythematosus (SLE) and kidney transplantation (KT) recipients. METHODS: Six hundreds and twenty-two patients who were diagnosed as SLE from 1990 to 2001 in Kang-Nam St. Mary's hospital were reviewed, retrospectively. As a control group, 347 kidney transplant recipients in the same center were evaluated. The extent of tbc was categorized into two groups: (1) limited disease (2) extensive disease. Cumulative steroid dosage and disease activity index including SLEDAI, serum complement levels, and anti-dsDNA titers were compared between the two groups. RESULTS: The cumulative incidence rate of tbc was similar in both groups (37 cases and 5.7% in SLE versus 17 cases and 4.9% in KT). Mean interval from SLE diagnosis or KT to tbc development was not different between the two groups. The most common site of tbc was lung/pleura, and the others included lymph nodes (2 cases), knee joint (1), bone marrow (1), central nervous system (1), kidney (1), colon (1), liver (1), and skin (1) in SLE. In contrast, most of tbc (16/17) developed exclusively in the lung and pleura in KT recipients. Cumulative doses of prednisolone 1 or 6 months before tbc diagnosis were not different between the two groups. Interestingly, extensive disease tended to be more frequent in SLE patients than in KT recipients although immuno-suppressants such as cyclosporine and azathioprine were more frequently administered in KT recipients. There were no differences in disease activity index including SLEDAI, complement levels, and anti-ds DNA titers at the time of tbc diagnosis as well as in the cumulative doses of steroid between extensive and limited diseases of tbc in SLE. CONCLUSION: The cumulative incidence rate of tbc was higher in SLE patients than in general population. The patterns of tbc tended to be more extensive in SLE compared to KT recipients in whom a stronger immuno-suppression was required, suggesting that immune dysfunction implicated by SLE itself may play an important role in determining the incidence and patterns of tbc infection.

Elevated monocyte chemoattractant protein-1 in patients with Behcet's disease / 대한내과학회지

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) belongs to C-C subfamily of chemokines, which stimulates the migration of monocytes. MCP-1 exerts various effects on the monocytes, including the induction of integrin and tissue factor, and synthesis of proinflammatory cytokines and arachidonic acid. In this study, we measured the MCP-1 levels in patients with Behcet's disease and evaluated the associations between the levels of MCP-1 and the level of other chemokines and various clinical features of Behcet's disease. METHODS: Serum samples were obtained from 67 patients with Behcet's disease and 30 healthy controls. Simultaneously, whole blood was isolated from patients (n=25) with Behcet's disease and healthy controls (n=11) and cultured in 24 well plates for 48 hours in the absence or presence of lipopolysaccharide (LPS) 5 microgram/mL, phytohaemagglutinin (PHA) 5 microgram/mL, phorbol 12-myristate 13-acetate (PMA) 50 ng/mL + ionomycin 5 microgram/mL. The MCP-1 concentrations were measured in the sera and culture supernatants by enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of serum MCP-1 were 2.5 times higher in patients with Behcet's disease than healthy controls. The patients with Behcet's disease had also higher levels of MCP-1 in the culture supernatants of whole blood cells, stimulated with LPS, but not with either PHA or PMA plus ionomycin, compared to healthy controls. Serum MCP-1 levels (n=67) were strongly correlated with serum RANTES, MIP-1alpha, IL-8 levels in Behcet's disease. In addition, the production of MCP-1 by whole blood culture from Behcet's disease patients (n=25) were also correlated well with those of RANTES, MIP-1alpha, and IL-8, when stimulated with LPS. However, MCP-1 levels in the sera and culture supernatants did not show any association with various clinical features of Behcet's disease including oral ulcer, genital ulcer, erythema nodosum, arthritis, uveitis, intestinal involvement, central nervous system involvement, and vascular thrombosis. CONCLUSION: In the sera and culture supernatants of whole blood stimulated with LPS, MCP-1 levels were higher in patients with Behcet's disease than controls and correlated well with RANTES, MIP-1alpha, IL-8 levels. These results suggest that the activation and migration of monocytes triggered by the increased production of MCP-1 may play a role in the pathogenesis of Behcet's disease.

Studies on the Cellular Immune Response in Animal Model of Arthritis after the Induction of Oral Tolerance

Oral administration of antigen has long been considered as a promising alternative for the treatment of chronic autoimmune diseases including rheumatoid arthritis (RA), and oral application of type II collagen (CII) has been proven to improve pathogenic symptoms in RA patients without problematic side effects. To further current understandings about the immune suppression mechanisms mediated by orally administered antigens, we examined the changes in IgG subtypes, T-cell proliferative response, and proportion of interleukin (IL)-10 producing Th subsets in a time course study of collagen induced arthritis (CIA) animal models. We found that joint inflammation in CIA mouse peaked at 5 weeks after first immunization with CII, which was significantly subdued in mice pre-treated by repeated oral administration of CII. Orally tolerized mice also showed increase in their serum level of IgG1, while the level of IgG2a was decreased. T-cell proliferation upon CII stimulation was also suppressed in lymph nodes of mice given oral administration of CII compared to non-tolerized controls. When cultured in vitro in the presence of CII, T-cells isolated from orally tolerized mice presented higher proportion of CD4+ IL-10+ subsets compared to non-tolerized controls. Interestingly, such increase in IL-10 producing cells were obvious first in Peyer's patch, then by 5 weeks after immunization, in mesenteric lymph node and spleen instead. This result indicates that a particular subset of T-cells with immune suppressive functions might have migrated from the original contact site with CII to inflamed joints via peripheral blood after 5 weeks post immunization.

Serum Levels of Zinc and Copper are Associated with Disease Activity in Patients with Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: To investigate the relationship between serum trace element levels with disease activity in Korean patients with rheumatoid arthritis (RA). METHODS: The serum levels of zinc, copper and ceruloplasmin were measured by inductively coupled plasma atomic emission spectrometers in 80 patients th , 26 osteoarthritis (OA), and 30 healthy controls (HC). We also measured the levels of zinc and copper in the synovial fluid (SF) of patients with RA. We nvestigated the clinical parameters simultaneously obtained at sampling of serum and analyzed correlation between serum levels of trace elements and disease activity in RA. RESULTS: In RA, the levels of serum zinc were significantly lower than that of HC, and thelevels of serum copper and ceruloplasmin were significantly higher than those of HC. In active RA, the levels of serum zinc were more decreased , and the levels of serum copper and ceruloplasmin were more increased than those of inactive group of RA. The levels of both copper and ceruloplasmin showed positive correlation with the levels of serum ESR and CRP. On the other hand, the levels of serum zinc showed negative correlation with the levels of serum ESR and CRP. CONCLUSION: Serum zinc levels are significantly lower and serum copper levels significantly higher in patients with active RA and these trace elements were useful parameter of disease activity in RA.

A case of bypass arthritis-dermatitis syndrome after bypass gastrojejunostomy / 대한내과학회지

Bypass surgery, as therapy for morbid obesity, was introduced in 1952. Multiple complications such as arthritis and dermatitis as well as liver dysfunction, renal injury, diarrhea, malnutrition and electrolyte imbalance were reported after bypass surgery. Recently, we have experienced a case of bypass arthritis-dermatitis syndrome in a patient after pyloric exclusion and bypass gastrojejunostomy due to traumatic duodenal perforation. He complained arthralgia of left knee, both wrist and both ankle and developed erythematous maculopapular rash over lower extremities. He was successfully treated with NSAIDs and clindamycin.