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1.  Multiple Intramuscular Gouty Tophi Mimicking Deep Tissue Abscesses: A Case Report 
Introduction:
Gout is a common metabolic disorder resulting from supersaturation of uric acid in extracellular fluid and deposition of monosodium urate monohydrate crystals in tissues triggering inflammatory response. Depositions of uric acid crystal outside articular structures cause tophi and are commonly found at peripheral areas of the body which have a lower temperature. Deposition of uric acid crystals in the central area of the body is not uncommon and may be overlooked.
Case presentation:
A 55-year-old Pacific Islander man with a history of chronic tophaceous gout was admitted because of acute right knee pain. Physical examination revealed signs of inflammation over the right knee. Arthrocentesis was performed but no synovial fluid obtained. The patient was empirically treated with prednisone, colchicine, and febuxostat. On the next day, there was progression of inflammation up to the right mid-thigh. MRI of the right femur was obtained to exclude abscess and necrotizing faciitis. Multiple pockets of abscesses were identified within the vastus medialis and vastus intermedius adjacent to the femoral shaft. This prompted immediate surgical consultation and incision and drainage. Intraoperative findings revealed healthy muscles and deposition of soft-tan material in the vastus medialis and vastus intermedius along and above the shaft of the femur. Culture of the surgical aspirate was negative and pathology showed needle-shaped structures consistent with uric acid crystals. Empiric antibiotic was discontinued. The patient's condition improved after treatment for acute gout. Pegloticase was also added to the treatment regimen during an outpatient follow up visit with his rheumatologist. At six month follow up, the patient reported excellent improvements in clinical symptoms.
Discussion:
Atypical presentations of chronic tophaceous gout can be a great mimicker, causing diagnostic challenges for clinicians. Our patient who had multiple intramuscular tophi presented with abrupt signs and symptoms of inflammation of lower extremity resembling cellulitis, abscess, or necrotizing fasciitis. On MRI, tophi typically exhibit low signal on T1-weighted images and medium to high signal on T2-weighted images, indicating the presence of cellular tissues surrounding or infiltrating the crystalline mass. The vascularity of this tissue influences the degree of MRI post-contrast enhancement on T2-weighted images. With varying degrees of cellular response and vascularity, distinguishing tophi from abscesses by MRI is still difficult.
Conclusion:
Our report focuses on the fact that tophi can also trigger acute inflammatory responses mimicking those of acute infection. At atypical locations, it can lead to misdiagnosis and inappropriate treatment. MRI is not a sensitive tool to differentiate abscess from tophaceous gout. Tissue diagnosis obtained from biopsy or aspiration is warranted to guide appropriate treatment and distinguish these different entities.
PMCID: PMC4175947
2.  Clinicopathologic characterization of visceral gout of various internal organs -a study of 2 cases from a venom and toxin research center 
Diagnostic Pathology  2015;10:23.
Background
Gout is a metabolic disorder that results in hyperuricemia and the deposition of positively birefringent monosodium urate crystals in various parts of the body. The purpose of this study was to characterize the incidence and diagnostic features of visceral gout found at necropsy in two patients.
Case presentation
The authors present an unusual report of untreated gout leading to major structure destructions in visceral organs. Gross post-mortem examination revealed a white powdery substance and display needle-like crystalline symmetry under the macroscopic on the visceral surfaces. Microscopically, the presence of crystalline deposits (urate tophi) were detected in visceral organs, such as; kidney, liver, lung and mesentery. Irrespective of its location, gout was observed, by H&E, as intracellular and extracellular eosinophilic deposits that compressed surrounding tissues. Moreover, numerous necrotizing granulomas of multifarious sizes were observed that were compounded by large aggregations of eosinophilic material (gout), surrounded by epithelioid macrophages, lymphoplasmacytic cells, foreign body multinucleated giant cells, fibrosis, fibroplasia and few edema. On the other hand, our results revealed that granulomatous nodules in the mesentery and kidney contained large numbers of gout foci compared with lung and liver. Furthermore, the immediate cause of death in these cases were not identified, but appeared to result from multiple factors, including the visceral gout due to unsuitable environmental conditions.
Conclusion
In summary, we have identified a valid histopathologic damage index for use in laboratory studies of visceral gout. This system provides a feasible method of representing visceral damage in gout, and may allow for better understanding of the natural history, pathophysiology and the management of acute attacks of gouty visceral in this disease. Finally, to the best of our knowledge, understanding of the distribution of monosodium urate crystals within the body can aid clinical diagnosis and further understanding of the resulting pathology.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1293547351151638.
doi:10.1186/s13000-015-0251-y
PMCID: PMC4399704  PMID: 25884935
Gout; Visceral; Snake; Pathology; Cells
3.  Paraspinal Abscess Communicated with Epidural Abscess after Extra-Articular Facet Joint Injection 
Yonsei Medical Journal  2007;48(4):711-714.
Facet joint injection is considered to be a safe procedure. There have been some reported cases of facet joint pyogenic infection and also 3 cases of facet joint infection spreading to paraspinal muscle and epidural space due to intra-articular injections. To the author's knowledge, paraspinal and epidural abscesses after facet joint injection without facet joint pyogenic infection have not been reported. Here we report a case in which extra-articular facet joint injection resulted in paraspinal and epidural abscesses without facet joint infection. A 50-year-old man presenting with acute back pain and fever was admitted to the hospital. He had the history of diabetes mellitus and had undergone the extra-articular facet joint injection due to a facet joint syndrome diagnosis at a private clinic 5 days earlier. Physical examination showed tenderness over the paraspinal region. Magnetic resonance image (MRI) demonstrated the paraspinal abscess around the fourth and fifth spinous processes with an additional epidural abscess compressing the thecal sac. The facet joints were preserved. The laboratory results showed a white blood cell count of 14.9 × 109 per liter, an erythrocyte sedimentation rate of 52mm/hour, and 10.88mg/dL of C-reactive protein. Laminectomy and drainage were performed. The pus was found in the paraspinal muscles, which was communicated with the epidural space through a hole in the ligamentum flavum. Cultures grew Staphylococcus aureus. Paraspinal abscess communicated with epidural abscess is a rare complication of extra-articular facet joint injection demonstrating an abscess formation after an invasive procedure near the spine is highly possible.
doi:10.3349/ymj.2007.48.4.711
PMCID: PMC2628056  PMID: 17722247
Complication; infection; injection; facet joint
4.  Validity of gout diagnosis in Swedish primary and secondary care - a validation study 
Background
The diagnostic golden standard for gout is to detect monosodium urate (MSU) crystals in synovial fluid. While some gout classification criteria include this variable, most gout diagnoses are based on clinical features. This discrepancy between clinical practice and classification criteria can hinder gout epidemiological studies. Here, the objective was to validate gout diagnoses (International Classification of Diseases (ICD)-10 gout codes) in primary and secondary care relative to five classification criteria (Rome, New York, ARA, Mexico, and Netherlands). The frequency with which MSU crystal identification was used to establish gout diagnosis was also determined.
Methods
In total, 394 patients with ≥1 ICD-10 gout diagnosis between 2009 and 2013 were identified from the medical records of two primary care centers (n = 262) and one secondary care center (n = 132) in Gothenburg, Sweden. Medical records were assessed for all classification criteria.
Results
Primary care patients met criteria cutoffs more frequently when ≥2 gout diagnoses were made. Even then, few primary care patients met the Rome and New York cutoffs (19 % and 8 %, respectively). The ARA, Mexico, and Netherlands cutoffs were met more frequently by primary care patients with ≥2 gout diagnoses (54 %, 81 %, and 80 %, respectively). Mexico and Netherlands cutoffs were met more frequently by the rheumatology department patients (80 % and 71 %, respectively), even when patients with only 1 gout diagnosis were included. Analysis of MSU crystals served to establish gout diagnoses in only 27 % of rheumatology department and 2 % of primary care cases.
Conclusions
If a patient was deemed to have gout at ≥2 primary care center or ≥1 rheumatology-center visits according to an ICD-10 gout code, the positive predictive value of this variable in relation with the Mexico and Netherlands classification criteria was ≥80 % for both primary care and rheumatology care settings in Sweden. MSU crystal identification was rarely used to establish gout diagnosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s12891-015-0614-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s12891-015-0614-2
PMCID: PMC4466844  PMID: 26077041
Gout; Classification criteria; Validity of diagnosis
5.  Tophaceous Gout of the Spine Causing Neural Compression 
Korean Journal of Spine  2013;10(3):185-188.
Gout is a common metabolic disease in which monosodium urate crystals called tophi develop. Spinal involvement in gout resulting in neural compression is unusual. We describe a case of a 64-year-old man with a history of gouty arthritis of the knee. The patient presented with thoracic myelopathy and radiculopathy. Imaging of the spine revealed an extradural mass lesion with bony erosion of the thoracic spine. A decompressive operation was performed, and a chalky white material was found. Histopathological examination confirmed a gouty tophus. The symptoms of spinal gout vary and its radiological features are not sufficiently specific to provide a definite diagnosis. Therefore, in patients with a history of gouty arthritis who present with neural compressive symptoms of the spine, spinal gout should be strongly suspected.
doi:10.14245/kjs.2013.10.3.185
PMCID: PMC3941767  PMID: 24757485
Gout; Spine; Myelopathy; Radiculopathy
6.  Gout, Have We Met before? No, Not Like This… 
LEARNING OBJECTIVES
Extra-articular symptoms could be the first manifestation of gouty arthritis (GA); polyarticular GA can mimic an infectious arthritis; infection can complicate GA.
CASE
A 66-year-old male with a history of gout presented with high fever and excruciating bilateral calf pain for 1 day. Examination revealed chronic knee effusions; range of motion in both knees was limited by calf pain. Joint aspiration showed negatively birefringent intracellular crystals and normal gram stain.
HOSPITAL COURSE
While receiving empiric antibiotics fever continued and he developed bilateral knee, right ankle, and shoulder pain. After demonstration of urate crystals and exclusion of infection, antibiotics were discontinued and steroids initiated. Fever, calf pain, and polyarthritis quickly resolved.
DISCUSSION
Polyarticular gouty attack is an uncommon presentation of gout, and can mimic several other conditions. An exceptional presentation of this entity is excruciating calf pain, probably caused by tenosynovitis or referred pain preceding an acute polyarticular gouty attack.
doi:10.1111/j.1525-1497.2006.00606.x
PMCID: PMC1924738  PMID: 17105518
gout; polyarticular; calf pain
7.  Frequency of chondrocalcinosis of the knees and avascular necrosis of the femoral heads in gout: a controlled study. 
An association between urate gout and chondrocalcinosis has been suggested in several studies, but the situation remains ill-defined because of lack of appropriate controls, small numbers of patients studied, or retrospective investigation. An association has also been claimed between gout and avascular necrosis of the femoral head. 138 patients with gout and 142 non-gouty control subjects were carefully matched for age and x-rays were taken of the knees and pelvis. Chondrocalcinosis of the knees was detected in 8 patients with gout (5.8%), no cases being found in the control group. The difference is significant (P less than 0.025). Deposits were linear or irregular. Six of the 8 patients gave a history of acute synovitis of the knees; fluid had been aspirated in 2 of them, urate crystals being found in one and no crystals in the other. Six of 8 patients showed evidence of chondrocalcinosis elsewhere. No association was apparent between chondrocalcinosis and the presence of tophaceous deposits or renal impairment, though the duration of gout appeared to be longer in the patients with chondrocalcinosis than in the other gout patients and osteoarthrosis of the knees commoner. There was no evidence of other metabolic disorders commonly associated with chondrocalcinosis. No cases of avascular necrosis of the femoral head were found.
Images
PMCID: PMC1000461  PMID: 7377863
8.  MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis 
Introduction
Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis.
Methods
Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured in vitro with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti–SHIP-1 antibody. A C57BL/6 J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines.
Results
The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-α and IL-1β. Consistent with in vitro observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice.
Conclusions
Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.
doi:10.1186/ar4531
PMCID: PMC4060367  PMID: 24708712
9.  Application of a Novel Diagnostic Rule in the Differential Diagnosis between Acute Gouty Arthritis and Septic Arthritis 
Journal of Korean Medical Science  2015;30(6):700-704.
Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to < 8) and low probability (≤ 4). In this retrospective study, we applied this diagnostic rule to 136 patients who presented as acute monoarthritis and were subsequently diagnosed as acute gout (n = 82) and septic arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P < 0.001). Patients with acute gout had significantly more 'high', and less 'low' probabilities compared to those with septic arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.
Graphical Abstract
doi:10.3346/jkms.2015.30.6.700
PMCID: PMC4444468  PMID: 26028920
Gout; Arthritis, Infectious; Diagnosis, Differential; Diagnostic Test
10.  Imaging Appearances in Gout 
Arthritis  2013;2013:673401.
Gout is an ancient disease. Last decade has brought about significant advancement in imaging technology and real scientific growth in the understanding of the pathophysiology of gout, leading to the availability of multiple effective noninvasive diagnostic imaging options for gout and treatment options fighting inflammation and controlling urate levels. Despite this, gout is still being sub-optimally treated, often by nonspecialists. Increased awareness of optimal treatment options and an increasing role of ultrasound and dual energy computed tomography (DECT) in the diagnosis and management of gout are expected to transform the management of gout and limit its morbidity. DECT gives an accurate assessment of the distribution of the deposited monosodium urate (MSU) crystals in gout and quantifies them. The presence of a combination of the ultrasound findings of an effusion, tophus, erosion and the double contour sign in conjunction with clinical presentation may be able to obviate the need for intervention and joint aspiration in a certain case population for the diagnosis of gout. The purpose of this paper is to review imaging appearances of gout and its clinical applications.
doi:10.1155/2013/673401
PMCID: PMC3621383  PMID: 23585966
11.  Psoriasis and gout 
Postgraduate Medical Journal  1982;58(682):477-480.
Ten cases of gouty arthritis are described in association with psoriasis. Eight were receiving intensive inpatient treatment for their skin condition. Diagnosis was based on clinical grounds or, in 3 cases, by compensated polarizing microscopy (CPM) of synovial fluid. All patients were male and 5 of them had conditions other than psoriasis known to predispose to hyperuricaemia. The patients appeared to fit into three groups: five had typical lower limb gout occurring in conjunction with long-standing extensive psoriasis; 3 patients had preceding features of inflammatory synovitis, one of whom subsequently developed typical distal interphalangeal involvement of peripheral psoriatic arthritis; two patients appeared to have coincident gout and psoriasis.
We believe that an association of gout with extensive long-standing psoriasis may exist particularly in male patients with an additional cause for hyperuricaemia. Long-term studies of a large population of psoriatics are required. Previous reports may have underestimated the incidence of gout because of failure to examine synovial fluid for crystals particularly from those patients with a subacute large joint arthropathy.
PMCID: PMC2426549  PMID: 7134085
12.  Imaging of tophaceous gout: computed tomography provides specific images compared with magnetic resonance imaging and ultrasonography 
Methods: Four male patients with chronic gout with tophi affecting the knee joints (three cases) or the olecranon processes of the elbows (one case) were assessed. Crystallographic analyses of the synovial fluid or tissue aspirates of the areas of interest were made with polarising light microscopy, alizarin red staining, and x ray diffraction. CT was performed with a GE scanner, MR imaging was obtained with a 1.5 T Magneton (Siemens), and ultrasonography with colour Doppler was carried out by standard technique.
Results: Crystallographic analyses showed monosodium urate (MSU) crystals in the specimens of the four patients; hydroxyapatite and calcium pyrophosphate dihydrate (CPPD) crystals were not found. A diffuse soft tissue thickening was seen on plain radiographs but no calcifications or ossifications of the tophi. CT disclosed lesions containing round and oval opacities, with a mean density of about 160 Hounsfield units (HU). With MRI, lesions were of low to intermediate signal intensity on T1 and T2 weighting. After contrast injection in two cases, enhancement of the tophus was seen in one. Colour Doppler US showed the tophi to be hypoechogenic with peripheral increase of the blood flow in three cases.
Conclusion: The MR and colour Doppler US images showed the tophi as masses surrounded by a hypervascular area, which cannot be considered as specific for gout. But on CT images, masses of about 160 HU density were clearly seen, which correspond to MSU crystal deposits.
doi:10.1136/ard.61.1.52
PMCID: PMC1753862  PMID: 11779759
13.  Bone destruction by receptor activator of nuclear factor κB ligand-expressing T cells in chronic gouty arthritis 
Arthritis Research & Therapy  2011;13(5):R164.
Introduction
The purpose of this study was to analyze the cellular expressions of pro-resorptive cytokines in gouty tophus tissues, to determine the capacity of monosodium urate monohydrate (MSU) crystals to induce these cytokines, and to understand the mechanisms of bone destruction in chronic gout.
Methods
Fourteen fixed, paraffin-embedded, uninfected tophus samples were analyzed immunohistochemically. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro with MSU crystals, and gene expression was assessed by reverse transcription-polymerase chain reaction. In vitro osteoclastogenesis was performed using PBMCs and synovial fluid mononuclear cells (SFMCs).
Results
CD4+ T cells, CD8+ T cells, CD20+ B cells and mast cells infiltrated tophus tissues. Tartrate-resistant acid phosphatase (TRAP)+ osteoclasts were present around tophi and in osteolytic lesions. Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha were produced from infiltrated mononuclear cells, whereas receptor activator of nuclear factor κB ligand (RANKL) was strongly expressed in T cells. However, osteoprotegerin (OPG) was not or was weakly expressed in tophus tissues. MSU crystals induced the expressions of IL-1, IL-6, TNF-alpha and RANKL in PBMCs, but inhibited OPG expression. In addition, the pro-resorptive cytokines were highly expressed in SFMCs of gouty arthritis patients. Furthermore, in vitro osteoclastogenesis was enhanced in SFMC cultures, but inhibited in T cell-depleted SFMC cultures.
Conclusions
Our study demonstrates that RANKL-expressing T cells and TRAP+ osteoclasts are present within gouty tophus tissues, and that infiltrating cells express pro-resorptive cytokines. Furthermore, our data show that MSU crystals have the potential to induce pro-resorptive cytokines, and T cells are involved in osteoclastogenesis in chronic gout.
doi:10.1186/ar3483
PMCID: PMC3308097  PMID: 21992185
14.  Acute gouty bursitis: report of 15 cases. 
Annals of the Rheumatic Diseases  1979;38(4):326-328.
Fifteen cases of acute gouty bursitis were seen among 136 crystal-proved cases of gout. Bursal aspirate yielded yellow or pink fluid in 10, chalky white fluid in 1, and a small amount of bloody fluid in 4. Monosodium urate crystals were present in all. Bursal fluid leucocyte counts averaged 2.9 X 10(9)/1 compared with synovial fluid leucocyte counts that averaged 25.5 X 10(9)/1 in cases of articular gout (P less than 0.05). Gouty, septic, and idiopathic (traumatic) bursitis share clinical features, and detailed bursal fluid analysis is crucial for diagnosis.
PMCID: PMC1000363  PMID: 496446
15.  The relationship of apolipoprotein B and very low density lipoprotein triglyceride with hyperuricemia and gout 
Introduction
Gout results from an innate immune response to monosodium urate (MSU) crystals deposited in joints. Increased very low-density lipoprotein (VLDL) has been associated with gout. The apolipoprotein B (apo B), which is present on VLDL, regulates neutrophil response to MSU crystals and has been positively associated with gout. Furthermore, the gene (A1CF) encoding the complementation factor for the APOB mRNA-editing enzyme is associated with urate levels. However, the relationship of apo B and VLDL with gout and hyperuricaemia (HU) is still unclear. Therefore, we tested the association of VLDL and apo B with HU and with gout compared to HU.
Methods
New Zealand European (n = 90) and Māori and Pacific Island (Polynesian) (n = 90) male gout case and control sample sets were divided into normouricaemia (NU), asymptomatic HU and gout groups. Size exclusion chromatography and enzyme-linked immunosorbant assay was used to measure VLDL and apo B. Multivariate logistic regression was used to assess the risk of gout and HU per unit change in VLDL and apo B.
Results
Increased levels of VLDL triglycerides (Tg) were observed in the gout sample set compared to NU and HU in Europeans (P = 1.8 × 10-6 and 1 × 10-3, respectively), but only compared to NU in Polynesians (P = 0.023). This increase was driven by increased number of VLDL particles in the European participants and by the Tg-enrichment of existing VLDL particles in the Polynesian participants. Each mmol/L increase in VLDL Tg was significantly associated with gout in the presence of HU in Europeans, with a similar trend in Polynesians (OR = 7.61, P = 0.011 and 2.84, P = 0.069, respectively). Each μmol/L increase in total apo B trended towards decreased risk of HU (OR = 0.47; P = 0.062) and, conversely, with increased risk of gout compared to HU (OR = 5.60; P = 0.004).
Conclusions
Increased VLDL Tg is associated with the risk of gout compared to HU. A genetic approach should be taken to investigate the possibility for causality of VLDL in gout. Apolipoprotein B may have pleiotropic effects in determining HU and gout.
doi:10.1186/s13075-014-0495-z
PMCID: PMC4265487  PMID: 25432151
16.  Time required for disappearance of urate crystals from synovial fluid after successful hypouricaemic treatment relates to the duration of gout 
Annals of the Rheumatic Diseases  2007;66(8):1056-1058.
Objectives
To determine whether hypouricaemic treatment results in the disappearance of urate crystals from gouty joints and to define the time required.
Methods
In 18 patients with monosodium urate (MSU) crystal proven gout, and after the initiation of successful serum uric acid (SUA)‐lowering treatment, an arthrocentesis of the asymptomatic signal joint (11 knees, 7 first metatarsophalangeal joints) was performed every 3 months to obtain a synovial fluid (SF) sample. The sample was then analysed for the presence of MSU crystals, and the number of crystals/400× field was noted. SUA levels and the duration of gout were also noted.
Results
MSU crystals disappeared from the SF of all 18 joints after reduction of SUA to normal levels. The time required for disappearance ranged from 3 to 33 months; disappearance time correlated with the duration of gout (rs = 0.71; p<0.01). The median number of MSU crystals in the SF samples before urate‐lowering treatment was 7.5 (2.5–11) crystals/400× field, reducing to 3 (1–6.5) crystals/400× field (p<0.05) at 3 months. Crystal counts continued to decrease after 3 months.
Conclusions
In gout, reduction of SUA to normal levels results in disappearance of urate crystals from SF, requiring a longer time in those patients with gout of longer duration. This indicates that urate crystal deposition in joints is reversible. Normalisation of SUA levels results in a decrease in the concentration of MSU crystals in SF in the asymptomatic gouty joints. This may partially explain the reduced frequency of gouty attacks when a patient has been treated with SUA‐lowering drugs.
doi:10.1136/ard.2006.060368
PMCID: PMC1954685  PMID: 17223663
gout; monosodium urate crystals; synovial fluid; gout treatment
17.  A case of gouty arthritis following percutaneous radiofrequency ablation for hepatocellular carcinoma 
Percutaneous radiofrequency thermal ablation (RFA) is considered an effective technique for providing local control in the majority of Hepatocellular carcinoma (HCC) patients. Although RFA is generally well tolerated, recent studies have reported complications associated with RFA. We describe a case of acute gouty arthritis in a 71-year-old man with chronic renal failure who was treated with RFA for a HCC lesion and who had hepatitis B-associated cirrhosis and mild renal insufficiency. Regular surveillance of the patient detected a 3.5 cm HCC lesion. Because the patient had declined surgery, RFA was chosen for therapy. On the third post-procedural day, the laboratory results showed increases in his uric acid and potassium levels, which were compatible with a tumor lysis syndrome. On the 6th post-procedural day, the patient complained of new right knee pain. Subsequent joint aspiration revealed monosodium urate monohydrate crystals. We made the diagnosis of acute gouty arthritis arising from tumor lysis and liver infarction caused by HCC ablation, which was aggravated by acute renal insufficiency. After adequate hydration and administration of oral colchicines, the patient’s right knee pain subsided and the uric acid serum level returned to normal. This is the first described case of acute gouty arthritis after RFA for a HCC lesion in a patient with underlying chronic renal insufficiency. To avoid hyperuricemia and an acute attack of gout after RFA therapy for HCC, early identification of patients at risk is warranted, such as those with a large tumor, rapid tumor growth, and renal insufficiency, and preventative measures should be considered.
doi:10.3748/wjg.v16.i6.778
PMCID: PMC2817069  PMID: 20135729
Radiofrequency thermal ablation; Hepatocellular carcinoma; Gout; Tumor lysis syndrome; Complications
18.  Veterans Affairs databases are accurate for gout-related health care utilization: a validation study 
Arthritis Research & Therapy  2013;15(6):R224.
Introduction
The aim of this study was to assess the accuracy of Veterans Affairs (VA) databases for gout-related health care utilization.
Methods
This retrospective study utilized VA administrative and clinical databases. A random sample of gout patients with visits (outpatient, inpatient or emergent/urgent care) with or without the diagnosis of gout (International Classification of Diseases, ninth revision, common modification ICD-9-CM code of 274.x or 274.xx) at the Birmingham VA hospital was selected. A blinded abstractor performed a review of VA electronic health records for the documentation of gout or gout-related terms (gouty arthritis, tophaceous gout, tophus/tophi, acute gout, chronic gout, podagra, urate stones, urate or uric acid crystals and so on) in the chief complaint, history of present illness or assessment and plan for the visit; this constituted the gold standard for gout-related utilization. The accuracy of database-derived gout-related claims was assessed by calculating sensitivity, specificity, and positive and negative predictive values (PPV and NPV).
Results
Of 108 potential visits, 85 outpatient, inpatient or urgent care/emergency room visits to a health care provider (85 patients: 84 men and 1 woman with a mean age of 63 years) and retrievable data from medical records constituted the analyzed dataset. Administrative claims for gout-related utilization with ICD-9 code for gout were accurate with a PPV of 86%, specificity of 95%, sensitivity of 86% and NPV of 95%.
Conclusions
VA databases are accurate for gout-related visits. These findings support their use for studies of health services and outcome studies. It remains to be seen if these findings are generalizable to other settings and databases.
doi:10.1186/ar4425
PMCID: PMC3979008  PMID: 24377421
19.  Neutrophil Extracellular Trap Formation Is Associated with IL-1β and Autophagy-Related Signaling in Gout 
PLoS ONE  2011;6(12):e29318.
Background
Gout is a prevalent inflammatory arthritis affecting 1–2% of adults characterized by activation of innate immune cells by monosodium urate (MSU) crystals resulting in the secretion of interleukin-1β (IL-1β). Since neutrophils play a major role in gout we sought to determine whether their activation may involve the formation of proinflammatory neutrophil extracellular traps (NETs) in relation to autophagy and IL-1β.
Methodology/Principal Findings
Synovial fluid neutrophils from six patients with gout crisis and peripheral blood neutrophils from six patients with acute gout and six control subjects were isolated. MSU crystals, as well as synovial fluid or serum obtained from patients with acute gout, were used for the treatment of control neutrophils. NET formation was assessed using immunofluorescence microscopy. MSU crystals or synovial fluid or serum from patients induced NET formation in control neutrophils. Importantly, NET production was observed in neutrophils isolated from synovial fluid or peripheral blood from patients with acute gout. NETs contained the alarmin high mobility group box 1 (HMGB1) supporting their pro-inflammatory potential. Inhibition of phosphatidylinositol 3-kinase signaling or phagolysosomal fusion prevented NET formation, implicating autophagy in this process. NET formation was driven at least in part by IL-1β as demonstrated by experiments involving IL-1β and its inhibitor anakinra.
Conclusions/Significance
These findings document for the first time that activation of neutrophils in gout is associated with the formation of proinflammatory NETs and links this process to both autophagy and IL-1β. Modulation of the autophagic machinery may represent an additional therapeutic study in crystalline arthritides.
doi:10.1371/journal.pone.0029318
PMCID: PMC3241704  PMID: 22195044
20.  A Case of Tophaceous Gout in the Lumbar Spine: A Review of the Literature and Treatment Recommendations 
Study Design Case report.
Objective The objective of this study is to report the occurrence of tophaceous gout in the lumbar spine.
Methods Using a case report to illustrate the key points of gout in the spine, we provide a brief review of gout in the literature as it relates to its orthopedic and spinal manifestations as well as guidelines for management.
Results This case report details the occurrence of a large and clinically significant finding of tophaceous gout in the lumbar spine in a 24-year-old man with a known history of gout and a 3-year history of progressive back pain.
Conclusion A high index of suspicion can assist in diagnosis of patients presenting with back pain or neurologic findings with a history of gout. A previous history of gout (especially the presence of tophi), hyperuricemia, and the radiological characteristics presented here should aid the clinician in making the diagnosis of spinal gout. Early diagnosis has the potential to prevent the need for surgical intervention.
doi:10.1055/s-0034-1366979
PMCID: PMC3969431  PMID: 24715872
gout; hyperuricemia; radiculopathy; lower back pain
21.  Acute camptocormia induced by olanzapine: a case report 
Introduction
Camptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder.
Case presentation
A 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L). Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later.
Conclusions
Camptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug-induced rhabdomyolysis, in patients presenting with acute-onset bent spine syndrome. Although rare, the occurrence of camptocormia induced by olanzapine must be considered.
doi:10.1186/1752-1947-4-192
PMCID: PMC2904791  PMID: 20579377
22.  Functional Polymorphisms of the ABCG2 Gene Are Associated with Gout Disease in the Chinese Han Male Population 
Background
Gout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population.
Methods
Peripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K.
Results
For Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95% confidence interval (CI): 1.77–2.74, p = 8.99 × 10−13). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95% CI: 1.49–5.68, p = 1.57 × 10−3). The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43–0.71, p = 2.55 × 10−6). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk (OR = 2.30 and 2.71, respectively). Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases.
Conclusion
The ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk.
doi:10.3390/ijms15059149
PMCID: PMC4057780  PMID: 24857923
gout; uric acid; polymorphism; ABCG2
23.  Tophaceous Gout and Renal Insufficiency: A New Solution for an Old Therapeutic Dilemma 
Case Reports in Medicine  2011;2011:397646.
The prevalence of gout is increasing with increased life expectancy. Approximately half of the patients with gout have some degree of renal impairment. If both conditions persistently coexist, and in severe tophaceous gout, in particular, treatment has been difficult. We here report on the case of an 87-year-old woman, who had been suffering from recurrent gouty arthritis over 4 years. Monthly polyarthritis attacks were accompanied by subcutaneous tophi. Serum uric acid levels were constantly above 600 μmol/L (10 mg/dL). Allopurinol was no option because of intolerance, while benzbromarone was ineffective because of renal impairment. Therefore, the novel xanthin oxidase inhibitor febuxostat was started, achieving rapid control of serum urate levels (<360 μmol/L). After initial worsening of inflammation in the first weeks, gouty attacks stopped and all tophi resolved within the following 10 months. Renal function remained stable.
doi:10.1155/2011/397646
PMCID: PMC3099210  PMID: 21629805
24.  Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study 
Annals of the Rheumatic Diseases  2014;74(6):1072-1077.
Objectives
To assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using polarising microscopy of synovial fluid (diagnostic yield).
Methods
Diagnostic single-centre study of 40 patients with active gout, and 41 individuals with other types of joint disease. Sensitivity and specificity of DECT for diagnosing gout was calculated against a combined reference standard (polarising and electron microscopy of synovial fluid). To explore the diagnostic yield of DECT scanning, a third cohort was assembled consisting of patients with inflammatory arthritis and risk factors for gout who had negative synovial fluid polarising microscopy results. Among these patients, the proportion of subjects with DECT findings indicating a diagnosis of gout was assessed.
Results
The sensitivity and specificity of DECT for diagnosing gout was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All false negative patients were observed among patients with acute, recent-onset gout. All false positive patients had advanced knee osteoarthritis. DECT in the diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30 patients (46.7%).
Conclusions
DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT has a significant impact on clinical decision making when gout is suspected, but polarising microscopy of synovial fluid fails to demonstrate the presence of MSU crystals.
doi:10.1136/annrheumdis-2013-205095
PMCID: PMC4431329  PMID: 24671771
Gout; Dual energy CT scanning; accuracy
25.  Crystal deposition in the knee and great toe joints of asymptomatic gout patients. 
Crystal deposition in asymptomatic knee and first metatarsophalangeal (MTP) joints has been studied in 31 patients with previously proven gout. All had had clinical gout in their MTP joints but their knee joints had never been the site of acute gout. Knee arthroscopy was performed permitting synovial membrane inspection, photography and biopsy. Crystalline material was seen in 9 knees (28%) and confirmed histologically as monosodium urate (MSU) in 4 (12.5%). Synovial fluid analysis on 26 samples using a polarizing light microscope demonstrated MSU crystals in 4 (12.5%) and calcium pyrophosphate dihydrate (CPPD) in 2 (6%). Fluid aspirated from 27 of the metatarsophalangeal joints revealed MSU crystals in 14 (52%) and no CPPD crystals.
Images
PMCID: PMC1440018  PMID: 6481756

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