Kowoon Joo

Serum Procalcitonin for Differentiating Bacterial Infection from Disease Flares in Patients with Autoimmune Diseases

Early differentiation between bacterial infections and disease flares in autoimmune disease patients is important due to different treatments. Seventy-nine autoimmune disease patients with symptoms suggestive of infections or disease flares were collected by retrospective chart review. The patients were later classified into two groups, disease flare and infection. C-reactive protein (CRP) and serum procalcitonin (PCT) levels were measured. The CRP and PCT levels were higher in the infection group than the disease flare group (CRP,11.96 mg/dL ± 9.60 vs 6.42 mg/dL ± 7.01, P = 0.003; PCT, 2.44 ng/mL ± 6.55 vs 0.09 ng/mL ± 0.09, P < 0.001). The area under the ROC curve (AUC; 95% confidence interval) for CRP and PCT was 0.70 (0.58-0.82) and 0.84 (0.75-0.93), which showed a significant difference (P < 0.05). The predicted AUC for the CRP and PCT levels combined was 0.83, which was not significantly different compared to the PCT level alone (P = 0.80). The best cut-off value for CRP was 7.18 mg/dL, with a sensitivity of 71.9% and a specificity of 68.1%. The best cut-off value for PCT was 0.09 ng/mL, with a sensitivity of 81.3% and a specificity of 78.7%. The PCT level had better sensitivity and specificity compared to the CRP level in distinguishing between bacterial infections and disease flares in autoimmune disease patients. The CRP level has no additive value when combined with the PCT level when differentiating bacterial infections from disease flares.

Digital thermography of the fingers and toes in Raynaud's phenomenon.

The aim of this study was to determine whether skin temperature measurement by digital thermography on hands and feet is useful for diagnosis of Raynauds phenomenon (RP). Fifty-seven patients with RP (primary RP, n = 33; secondary RP, n = 24) and 146 healthy volunteers were recruited. After acclimation to room temperature for 30 min, thermal imaging of palmar aspect of hands and dorsal aspect of feet were taken. Temperature differences between palm (center) and the coolest finger and temperature differences between foot dorsum (center) and first toe significantly differed between patients and controls. The area under curve analysis showed that temperature difference of the coolest finger (cutoff value: 2.2℃) differentiated RP patients from controls (sensitivity/specificity: 67/60%, respectively). Temperature differences of first toe (cutoff value: 3.11℃) also discriminated RP patients (sensitivity/specificity: about 73/66%, respectively). A combination of thermographic assessment of the coolest finger and first toe was highly effective in men (sensitivity/specificity : about 88/60%, respectively) while thermographic assessment of first toe was solely sufficient for women (sensitivity/specificity: about 74/68%, respectively). Thermographic assessment of the coolest finger and first toe is useful for diagnosing RP. In women, thermography of first toe is highly recommended. Graphical Abstract

Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use

Background/Aims Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. Methods Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). Results Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 ± 2.12 pg/mL at baseline to 2.51 ± 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). Conclusions RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Prevention of Comorbidity and Acute Attack of Gout by Uric Acid Lowering Therapy

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA≥6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis. Graphical Abstract

A comparison of three different guidelines for osteoporosis treatment in patients with rheumatoid arthritis in Korea.

Background/Aims Osteoporotic fractures are an important comorbidity with rheumatoid arthritis (RA). We determined the overall fracture risk as assessed by the World Health Organization (WHO)s FRAX® tool in Korean patients with seropositive RA. Additionally, we compared treatment eligibility according to the criteria of the Korean Health Insurance Review Agency (HIRA), FRAX, and the National Osteoporosis Foundation (NOF). Methods Postmenopausal women and men ≥ 50 years of age with seropositive RA were recruited from one rheumatism center in Korea. The FRAX score was estimated using the Japanese model. Patients were classified as eligible for treatment using the HIRA, NOF, and FRAX thresholds for intervention. Results The study of 234 patients included 40 men (17%). The mean age was 60 ± 9 years, and 121 (52%) patients had osteoporosis according to the WHO criteria. The overall median 10-year fracture risk was 13% for major osteoporotic fractures and 3.5% for hip fractures. HIRA guidelines identified 130 patients (56%) eligible for treatment, FRAX included 126 patients (54%), and 151 patients (65%) were included according to NOF guidelines. Older patients with a greater number of risk factors were included by FRAX compared to HIRA. The overall concordance between HIRA and FRAX, expressed as the kappa index, was 0.67, but was as low as 0.44 when limited to patients ≥ 60 years of age. Conclusions One-half of the patients had osteoporosis requiring treatment. RA patients have a high risk of fracture, and the adoption of a risk-scoring system should be considered.

Extensive Thrombosis in a Patient with Familial Mediterranean Fever, Despite Hyperimmunoglobulin D State in Serum - First Adult Case in Korea

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema. It is known to occur mainly among Mediterranean and Middle Eastern populations such as non-Ashkenazi Jews, Arabs, Turks, and Armenians. FMF is not familiar to clinicians beyond this area and diagnosing FMF can be challenging. We report a 22-yr old boy who presented with fever, arthalgia and abdominal pain. He had a history of recurrent episodes of fever associated with arthalgia which would subside spontaneously or by antipyretics. Autosomal recessive periodic fever syndromes were suspected. Immunoglobulin D (IgD) level in the serum was elevated and DNA analysis showed complex mutations (p.Glu148Gln, p.Pro369Ser, p.Arg408Gln) in the MEFV gene. 3D angio computed tomography showed total thrombosis of splenic vein with partial thrombosis of proximal superior mesenteric vein, main portal vein and intrahepatic both portal vein. This is a case of FMF associated with multiple venous thrombosis and elevated IgD level. When thrombosis is associated with elevated IgD, FMF should be suspected. This is the first adult case reported in Korea.

Improvement of vitiligo in a patient with rheumatoid arthritis after hydroxychloroquine treatment.

Dear Editor, Antimalarial agents are one of the most commonly prescribed drugs for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) has long-term treatment benefits in RA. Recent data suggest that HCQ may have more wide-reaching medical implications, including diabetes mellitus, dyslipidemias, infectious diseases, coagulopathies and malignancies, but HCQ has also been reported to cause pigmentary changes in approximately 10–25% of patients. Here, we present a case of vitiligo in a patient with RA that improved following HCQ treatment. A 39-year-old woman presented in December 2010 with a 3-months history of multiple joint pain. Physical examination showed tenderness and swelling in several joints. Laboratory findings were positive for anti-cyclic citrullinated peptide antibody and anti-Ro antibody, but negative for rheumatoid factor and anti-nuclear antibody. Erythrocyte sedimentation rate and C-reactive protein level were elevated to 35 mm/h and 0.64 mg/ dL, respectively. Serum thyroid-stimulating hormone and free T4 levels were normal. Bone scintigraphy showed increased uptake in both the wrists and small joints of the right hand. Chest computed tomography showed mild ground-glass opacity in the peribronchovascular and subpleural areas. She was diagnosed with seropositive RA and interstitial lung disease. The patient had a 20-year history of vitiligo on the face, trunk and extremities. Before RA diagnosis, she was treated with ultraviolet light (UV) for 6 months and experienced improvement of facial vitiligo. She reported no change in other areas of her body. In May 2011, HCQ (200 mg daily) and methotrexate (MTX) (7.5 mg weekly) were prescribed for the treatment of her RA. Glucocorticoids were not prescribed. HCQ was discontinued from September 2011 to November 2011 because of the patient’s wish due to improvement in her arthritis. The patient revisited the rheumatology clinic in December 2011 with worsening

A case report of alverine-citrate-induced acute hepatitis

Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity.

A case of migrating bone marrow edema syndrome in a patient with Behcet's disease.

Dear Editor, Bone marrow edema syndrome (BMES) refers to a transient clinical condition of unknown pathogenicity. In general, the course is self-limiting and symptoms resolve spontaneously over 6–12 months. Because of the lack of a specific diagnostic test and similar symptoms and imaging findings to those of other entities, differentiation of BMES from avascular necrosis (AVN), neoplasm and osteomyelitis is difficult. Early diagnosis is important for preventing overtreatment of benign conditions and for starting proper management in serious cases. Here, we present the first case of migrating BMES within the same foot in a patient with Behcet’s disease (BD). A 38-year-old woman with BD visited our clinic in February 2013 with a 10-day history of left ankle pain. She reported severe, progressive pain and tenderness in the left ankle. She had no history of a traumatic event. In 2009, she had been diagnosed with BD on the basis of findings of recurrent oral aphthous ulcers, genital aphthous ulcers, erythema nodosum and arthritis. She had been prescribed colchicine 0.6 mg daily, sulfasalazine 500 mg daily, and acetaminophen 1300 mg daily for 4 years. However, her drug compliance was poor, and she complained constantly of recurrent oral and genital ulcers. She took steroids only when the oral and genital ulcers were aggravated. She had a history of thyroid papillary carcinoma and had undergone a total thyroidectomy and radioiodine ablation 6 years before admission. She reported that she had been hospitalized for similar left ankle pain in November 2003 and July 2004. The magnetic resonance imaging (MRI) images obtained in 2003 demonstrated diffuse high signal intensity on T2-weighted images of the lateral portion of the calcaneus (Fig. 1a,b). Under consideration of a diagnosis of osteomyelitis, she had been treated with antibiotics for 50 days. The pain had subsided after 1 month. In 2004, the left foot and ankle pain developed again, and MRI revealed newly developed bone marrow edema at the talus and distal tibia, and the size of the previous lesion in the calcaneus had markedly decreased (Fig. 1c,d). Her doctor had suspected a recurrence of osteomyelitis and recommended a surgical (a) (b)