Recurrent focal myofasciitis of Behçet syndrome mimics infectious myofasciitis: a case report

Behçet syndrome (BS) is a chronic inflammatory disease with multiorgan manifestations. However, muscular involvement in BS has rarely been reported. Herein, we report the case of a 30-year-old male with BS who had recurring pain and swelling of the lower legs. The patient was administered antibiotics on several occasions as the condition was misinterpreted to be infectious myositis. Magnetic resonance imaging revealed myofascial involvement with focal necrotic lesions, and muscle biopsy revealed acute suppurative myositis with perivascular infiltration of polymorphonuclear leukocytes. His symptoms improved after treatment with corticosteroids. Azathioprine and colchicine therapy was beneficial for preventing further relapse after short-term corticosteroid treatment. Therefore, BS should be considered in the differential diagnosis of focal suppurative myofasciitis.

Assessment on Treatments With Conventional Synthetic Disease-modifying Drugs Before Initiating Biologics in Patients With Rheumatoid Arthritis in Korea: A Populationbased Study

Objective@#To assess pre-biologic treatments with conventional synthetic disease-modifying drugs (csDMARDs) prior to biologics initiation among patients with rheumatoid arthritis (RA). @*Methods@#Using Korea National Health Insurance database, we examined pre-biologic treatments of RA patients on the following four items: whether 1) initial methotrexate (MTX) therapy was given, 2) MTX dose was escalated up to ≥15 mg/week within 1-year post-diagnosis, 3) prednisone-equivalent glucocorticoid was used at a dose of ≤7.5 mg/day, and 4) glucocorticoid was discontinued within 6 months of treatment. Multivariable logistic regressions identified predictors of items 2) and 4) fulfillment. @*Results@#Among 6,986 biologics initiators with RA, 54.9% used MTX as the 1st csDMARD. Within 1-year post-diagnosis, 85.2% used MTX with half of them achieving a dose of ≥15 mg/week. The majority (75.2%) of patients used glucocorticoids initially and 64.5% were still on glucocorticoids at 6 months, mostly at a dose of ≤7.5 mg/day. csDMARD combination was observed in 85.7%. Item 2) fulfillment was associated with males, younger age, glucocorticoid, combination therapy, cyclo-oxygenase-2 inhibitors, and viral hepatitis. Item 4) fulfillment was associated with males, MTX dose of ≥15 mg/week, combination therapy, viral hepatitis, and hospitalizations. @*Conclusion@#RA patients in Korea were predominantly treated with MTX-based csDMARD combination plus glucocorticoids before initiating biologics, without sufficient MTX dose escalation or glucocorticoid discontinuation. Items 2) and 4) fulfillments were associated with patient age and gender, concomitant treatments, and comorbidities.

A Case of Macrophage Activation Syndrome During the Treatment of Adult-onset Still’s Disease With Tocilizumab

Macrophage activation syndrome (MAS) is a fatal complication of adult-onset Still’s disease (AOSD). Although anti-cytokine agents have been recommended for refractory AOSD or complicated with MAS, MAS cases have been rarely reported during anticytokine treatment. Herein, we describe the first AOSD case complicated with MAS during the treatment with tocilizumab in Korea. Two years after tocilizumab maintenance therapy, high fever and hypertransaminasemia recurred. MAS was diagnosed based on hyperferritinemia, elevated soluble IL-2 receptor levels, and the presence of hemophagocytic histiocytes in the bone marrow.However, she had normal white blood cell counts and acute phase reactant levels. High-dose glucocorticoid and anakinra therapies were not effective, but her disease improved with etoposide. This case shows that tocilizumab may not prevent MAS development and can modify clinical features making it challenging to diagnose. Cytotoxic therapy such as etoposide may be required in MAS cases that develop during anti-cytokine therapy.

Subclinical sacroiliitis detected by abdominopelvic computed tomography in Korean patients with Crohn’s disease

Background/Aims@#Sacroiliitis is a frequent extraintestinal manifestation of inflammatory bowel diseases (IBDs). This study aimed to assess the prevalence of sacroiliitis using a validated screening tool based on abdominopelvic computed tomography (APCT) in Korean patients with Crohn’s disease (CD) and examine potential associations between clinical characteristics and sacroiliitis. @*Methods@#One hundred five patients with CD undergoing APCT for any indication at an IBD clinic were matched 1:1 for age and sex with 105 controls without underlying chronic illnesses. Using a validated APCT screening tool that defines sacroiliitis as either ankylosis or a total erosion score (TES) ≥ 3, all computed tomography scans were assessed by two independent, blinded radiologists. We compared the prevalence of sacroiliitis between CD patients and controls and clinical characteristics between CD patients with and without sacroiliitis. @*Results@#The prevalence of sacroiliitis was significantly higher in CD patients than in controls (13.3% vs. 4.8%, p = 0.030). All subjects with sacroiliitis had a TES ≥ 3, but no ankylosis. The assessment of sacroiliitis in APCT showed excellent interreader reliability (Cohen’s kappa = 0.933 for presence of sacroiliitis). Sacroiliitis in CD patients was bilateral and asymptomatic. There were no significant associations between sacroiliitis and any demographic data or clinical characteristics in these patients. @*Conclusions@#The prevalence of APCT-detected sacroiliitis in CD patients was higher than that in controls, but the condition was asymptomatic. The clinical significance of asymptomatic sacroiliitis in Korean CD patients remains unclear.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Subclinical sacroiliitis detected by abdominopelvic computed tomography in Korean patients with Crohn’s disease

Background/Aims@#Sacroiliitis is a frequent extraintestinal manifestation of inflammatory bowel diseases (IBDs). This study aimed to assess the prevalence of sacroiliitis using a validated screening tool based on abdominopelvic computed tomography (APCT) in Korean patients with Crohn’s disease (CD) and examine potential associations between clinical characteristics and sacroiliitis. @*Methods@#One hundred five patients with CD undergoing APCT for any indication at an IBD clinic were matched 1:1 for age and sex with 105 controls without underlying chronic illnesses. Using a validated APCT screening tool that defines sacroiliitis as either ankylosis or a total erosion score (TES) ≥ 3, all computed tomography scans were assessed by two independent, blinded radiologists. We compared the prevalence of sacroiliitis between CD patients and controls and clinical characteristics between CD patients with and without sacroiliitis. @*Results@#The prevalence of sacroiliitis was significantly higher in CD patients than in controls (13.3% vs. 4.8%, p = 0.030). All subjects with sacroiliitis had a TES ≥ 3, but no ankylosis. The assessment of sacroiliitis in APCT showed excellent interreader reliability (Cohen’s kappa = 0.933 for presence of sacroiliitis). Sacroiliitis in CD patients was bilateral and asymptomatic. There were no significant associations between sacroiliitis and any demographic data or clinical characteristics in these patients. @*Conclusions@#The prevalence of APCT-detected sacroiliitis in CD patients was higher than that in controls, but the condition was asymptomatic. The clinical significance of asymptomatic sacroiliitis in Korean CD patients remains unclear.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Seasonal Variations and Associated Factors of Gout Attacks: a Prospective Multicenter Study in Korea

Background@#We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. @*Methods@#We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. @*Results@#Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. @*Conclusion@#In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.

Diabetic Muscle Infarction in a Young Patient with Prader-Willi Syndrome and Type 2 Diabetes Mellitus / 임상당뇨병

Diabetic muscle infarction (DMI), also known as diabetic myonecrosis, is a rare complication of diabetes mellitus (DM); hence, it is often underdiagnosed. Thus, timely diagnosis and treatment are essential for a better prognosis. We describe a 24-year-old woman with Prader-Willi syndrome and an 8-year history of uncontrolled type 2 DM, who presented with a sudden onset of fever and subacute painful swelling of her left thigh. She was finally diagnosed with DMI based on magnetic resonance imaging and muscle biopsy after excluding other infectious and inflammatory diseases of proximal muscles. The patient was treated with bed rest, strict glycemic control, and analgesics, and her symptoms gradually resolved. DMI should be considered in the differential diagnosis of patients with poorly controlled DM, who present with subacute pain and swelling of lower extremity muscles, without a history of trauma.

Diabetic Muscle Infarction in a Young Patient with Prader-Willi Syndrome and Type 2 Diabetes Mellitus / 임상당뇨병

Diabetic muscle infarction (DMI), also known as diabetic myonecrosis, is a rare complication of diabetes mellitus (DM); hence, it is often underdiagnosed. Thus, timely diagnosis and treatment are essential for a better prognosis. We describe a 24-year-old woman with Prader-Willi syndrome and an 8-year history of uncontrolled type 2 DM, who presented with a sudden onset of fever and subacute painful swelling of her left thigh. She was finally diagnosed with DMI based on magnetic resonance imaging and muscle biopsy after excluding other infectious and inflammatory diseases of proximal muscles. The patient was treated with bed rest, strict glycemic control, and analgesics, and her symptoms gradually resolved. DMI should be considered in the differential diagnosis of patients with poorly controlled DM, who present with subacute pain and swelling of lower extremity muscles, without a history of trauma.

Longitudinal Changes in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index in Real-Life Practice

OBJECTIVE: To investigate longitudinal changes in the European League Against Rheumatism (EULAR) Sjögren's syndrome patient reported index (ESSPRI) and to study the clinical features associated with favorable ESSPRI changes in primary Sjögren's syndrome (pSS). METHODS: At baseline and after a median period of 6.6 years, 41 pSS patients were evaluated using the ESSPRI, EULAR Sjögren's syndrome disease activity index (ESSDAI), short-form 36, xerostomia inventory (XI), and visual analog scale (VAS) scores for symptoms. The favorable subgroup included patients who were stable or showed improved to satisfactory symptom status (ESSPRI<5) and the unfavorable subgroup included those with stable or worsening to an unsatisfactory symptom status (ESSPRI ≥5). RESULTS: Median ESSPRI increased from 4.11 to 5.33 (p<0.05), although XI scores (p=0.01) and oral dryness (p<0.05) were significantly decreased. Serum immunoglobulin G level was significantly reduced (p<0.001) but ESSDAI scores were unchanged. Six (14.6%) patients showed clinical improvement in ESSDAI, and 11 (26.8%) showed improvement in ESSPRI. On comparing the favorable (n=17) and unfavorable (n=24) subgroups, the former exhibited significantly lower VAS scores for sicca and depression and XI and ESSPRI scores at baseline (all p<0.05) and more lacrimal flow (p<0.05). The favorable subgroup received a significantly lower cumulative dose of pilocarpine and glucocorticoids (both p<0.05). CONCLUSION: About 25% of pSS patients showed clinically significant ESSPRI improvement and about 40% showed a favorable ESSPRI course. Because the favorable subgroup had more lacrimal flow and less sicca symptoms at baseline, long-term patient-derived outcomes could depend on residual exocrine function at pSS diagnosis.

Follicular Bronchiolitis Mimicking Lung Cancer in a Patient with Primary Sjögren's Syndrome

Follicular bronchiolitis (FB) is an uncommon pulmonary lymphoproliferative disorder that is characterized by the presence of peribronchiolar hyperplastic lymphoid follicles with reactive germinal centers. FB could be associated with systemic illnesses including immunodeficiency, infection, and autoimmune diseases. In Korea, a single case of FB with rheumatoid arthritis was recently described but there has been no report on FB associated with other rheumatic diseases. Herein, we describe the first case of FB presenting nodular ground-glass opacities (GGO), which mimicked lung cancer, in patients with primary Sjögren's syndrome (SS). The differential diagnosis of nodular GGO lesions should include FB although it is a rare manifestation in SS patients.

Performance of the 2015 American College of Rheumatology/European League against Rheumatism Classification Criteria for Gout in Korean Patients with Acute Arthritis

BACKGROUND: We aimed to assess the performance of the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for gout in Korean patients with acute arthritis and to compare the performance of the ACR/EULAR criteria to that of other sets of criteria for gout classification. METHODS: Patients with acute arthritis who underwent diagnostic arthrocentesis at one of the four participating rheumatology clinics were consecutively enrolled between February and December 2017. Crystal-proven gout was diagnosed upon confirming the presence of monosodium urate (MSU) crystals in patients with a clinical impression of gout as judged by the rheumatologist. The performance of the ACR/EULAR and other gout classification criteria, including the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria, was analyzed regardless of the presence/absence of MSU crystals. RESULTS: The study enrolled 118 gout patients (all crystal-proven) and 95 non-gout patients. According to the area under the curve, the diagnostic performance was the highest for the ACR/EULAR classification criteria (sensitivity, 80.5%; specificity, 95.8%; area under the curve, 0.966), followed by the Netherlands, Rome, ARA, New York, and Mexico criteria. All six sets of criteria demonstrated lower sensitivity in patients exhibiting the first episode of acute arthritis. CONCLUSION: In Korean patients with acute arthritis, the ACR/EULAR classification criteria outperformed other sets of gout classification criteria even in the absence of information regarding the presence of MSU crystals. However, to enhance diagnostic sensitivity, synovial fluid analysis should be considered in patients with the first episode of acute arthritis.

Impact of sleep quality on clinical features of primary Sjögren's syndrome

BACKGROUND/AIMS@#This study aimed to investigate the inf luence of poor sleep quality on clinical features of primary Sjögren’s syndrome (pSS).@*METHODS@#Sleep quality was cross-sectionally assessed using the Pittsburgh Sleep Quality Index (PSQI), and demographic, clinical, and laboratory data were collected from 115 Korean patients with pSS. The patients completed questionnaires on the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI), quality of life (EuroQOL five dimensions questionnaire [EQ-5D]), fatigue (fatigue severity score [FSS]), and depression (Beck Depression Inventory [BDI] II]). Symptoms and patient global assessment (PGA) were evaluated with a 100-mm visual analogue scale (VAS). The EULAR sicca score (ESS), ESSPRI, and EULAR SS Disease Activity Index (ESSDAI) were calculated at study enrollment.@*RESULTS@#Fifty-three patients (46.1%) had poor sleep quality and 32.4% of 71 patients without depression were poor sleepers. Poor sleepers had a significantly lower EQ-5D or ESSDAI and a significantly higher FSS, BDI-II, PGA, ESS, ESSPRI, or VAS scores for extra-glandular symptoms than good sleepers. Neutrophil and lymphocyte counts were significantly higher and immunoglobulin G levels tended to decrease in poor sleepers. Additionally, PSQI was negatively correlated with EQ-5D and ESSDAI and positively with ESS, FSS, BDI-II, PGA, VAS scores for their symptoms, and ESSPRI. Multivariate analysis revealed that poor sleep quality remained the independent determinants of the unsatisfactory symptom state (ESSPRI ≥ 5).@*CONCLUSIONS@#Our results showed that poor sleep quality could significantly affect the patient-oriented outcomes and physician-reported activity index of pSS patients through the various effects of sleep quality on the psychological or somatic symptoms and the immune system.

Acute Eosinophilic Monoarthritis in a Patient with Toxocariasis / 대한내과학회지

Eosinophilic synovial effusion is rarely observed in patients with inflammatory nature of synovial fluid, and the differential diagnosis includes parasitic arthritis. Toxocariasis is the one of the most common forms of helminthiasis worldwide and has been reported as a common cause of peripheral blood eosinophilia in Korea. However, joint involvement has been rarely reported in adults with toxocariasis in the English-language literature. Here, we report the first Korean case of a female presenting with acute monoarthritis with an increased number of eosinophils in the peripheral blood and synovial fluid, who was finally diagnosed with toxocariasis.

Case of Idiopathic Hypereosinophilic Syndrome with Articular Involvement

Idiopathic hypereosinophilic syndrome (IHES) is a rare disease that is characterized by otherwise unexplained persistent eosinophilia and organ damage caused by eosinophilic infiltration. Its manifestations are highly variable but clinically apparent arthritis is uncommonly observed. Although Korean cases of severe eosinophilia in patients with rheumatoid arthritis (RA) or IHES concurrent with RA have been published, there are no reports of IHES with joint involvement. This paper reports a case of IHES presenting with persistent peripheral eosinophilia, fever, skin rash, multiple lymphadenopathy, and polyarthritis, including the distal interphalangeal joints of the hands.

SOCS1 suppresses IL-1β-induced C/EBPβ expression via transcriptional regulation in human chondrocytes

CAAT/enhancer-binding protein-beta (C/EBPβ) is a transcription factor that regulates interleukin-1β (IL-1β)-induced catabolic pathways, including the expression of matrix metalloproteinases (MMPs), in chondrocytes. We previously reported that suppressor of cytokine signaling 1 (SOCS1) inhibits IL-1β signaling in chondrocytes. However, the effect of SOCS1 on C/EBPβ has not been explored. To investigate the interaction between SOCS1 and C/EBPβ, we established human SW1353 cells with overexpression or knockdown of SOCS1 or C/EBPβ. Both SOCS1 and C/EBPβ were involved in transcription of MMP-3 and MMP-13. When stimulated with IL-1β, C/EBPβ levels were significantly increased by SOCS1 knockdown and decreased by SOCS1 overexpression. A similar change in IL-1β-induced C/EBPβ expression was observed in SOCS1-transfected human articular chondrocytes. However, C/EBPβ overexpression or knockdown did not change the levels of IL-1β-induced SOCS1. SOCS1 regulated the levels of C/EBPβ mRNA by ubiquitination of C/EBPβ as well as transcriptional regulation. Furthermore, it suppressed the phosphorylation of cAMP response element-binding protein (CREB), an active transcription factor of C/EBPβ. In addition, p38 mitogen-activated protein kinases, a target of SOCS1, was involved in CREB phosphorylation. The chromatin immunoprecipitation assay confirmed that SOCS1 overexpression led to reduced binding of C/EBPβ to the MMP-13 promoter. Taken together, our results demonstrate that SOCS1 downregulates the p38-CREB-C/EBPβ pathway resulting in increased expression of MMPs in chondrocytes.

A Case of Acute Calcium Pyrophosphate Crystal Arthritis in the Lumbar Facet Joint

Calcium pyrophosphate dihydrate deposition disease most commonly presents with acute arthritis of the peripheral joints. Infrequently, a mass effect of this disease can cause axial symptoms, such as spinal stenosis, radiculopathy, or myelopathy. Herein, we report on the first Korean case of acute arthritis in the lumbar facet joint due to calcium pyrophosphate dihydrate crystal deposition disease. A 73-year-old female presented with acute fever, severe lumbago, and knee arthralgia, 11 days after partial parathyroidectomy. Plain radiographs showed multiple chondrocalcinosis, while a bone scan, computed tomography, and magnetic resonance imaging showed right L5-S1 facet arthritis. In synovial fluid from the facet and knee joints, positively birefringent calcium pyrophosphate dihydrate crystals were observed under polarized light microscopy. Under the diagnosis of acute calcium pyrophosphate dihydrate crystal arthritis (formerly known as 'pseudogout') in the facet joint, an intra-articular triamcinolone injection was administered, which resulted in dramatic improvement of the symptoms within 24 hours.

Three Cases of Spondyloepiphyseal Dysplasia Tarda in One Korean Family

Spondyloepiphyseal dysplasia (SED) tarda is an inherited skeletal arthropathy. Because SED tarda involves the joints and resemble the clinical findings of chronic arthropathies, this disease is frequently misdiagnosed as juvenile idiopathic arthritis (JIA). We report here on three patients (father and his two daughters) in one family with SED tarda. All patients had back pain and polyarthralgia. Their radiographs revealed typical changes for SED tarda including platyspondyly and dysplastic bone changes. This rare disease has major clinical importance in that it is similar with JIA or rheumatoid arthritis.

Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.