Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleotide-binding domain, leucine-rich repeat containing family (NLR) network has provided pivotal genetic and molecular insights into diseases that were hitherto regarded as autoimmune. The NLR-related disorders include rare monogenic autoinflammatory diseases collectively termed cryopyrin-associated periodic syndromes, Crohn's disease which is a common polygenic disease and also an association at the mechanistic level with gout and pseudogout. Unlike the classical autoimmune diseases where disease immunopathogenesis is played out primarily in the primary and secondary lymphoid organs, the immunopathogenesis of the NLR-related disorders is played out in the tissues where inflammation arises. As the genetic mutations or molecular cascades associated with the NLR-related disorders have a widespread cellular distribution, it has been somewhat enigmatic why these disorders attack certain territories, but not others. This implies that tissue-specific factors in the target organs themselves contribute to disease expression. Such examples include the high abundance of NOD2 expressing cells in the part of the gut most typically afflicted by Crohn's disease and the preferential deposition of crystals in the joints to where inflammation localises in gout and pseudogout. The NLR network is associated principally with increases in TNF or IL-1 production, both of which are key players in innate immunity. Therefore, the NLR network identifies at the genetic and molecular level a robust paradigm for innate immune activation against self. This tissue-specific-factor-associated inflammation is the diametric opposite of classical autoimmunity. Of note, the MHC class-I-associated diseases including psoriasis (HLA-Cw6) and ankylosing spondylitis (HLA-B27) show striking clinical overlaps with Crohn's disease and also some rare monogenic diseases. Thus, the NLR innate immune pathway allows the full spectrum of inflammation against self to be viewed along an immunological disease continuum with autoantibody-associated disease at one end, innate immune diseases at the other and MHC class-1-related disorders as an intermediate.
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PMID:The NLR network and the immunological disease continuum of adaptive and innate immune-mediated inflammation against self. 1780 42

This review will suggest an algorithm for standardised histopathological diagnosis of synovial biopsies and synovectomy specimens. In principal, changes of the synovial membrane can be inflammatory or non-inflammatory. To the latter group belong some benign tumors, such as tenosynovial giant cell tumor, lipoma or synovial chondromatosis. Rare non-inflammatory changes are the group of storage diseases. Inflammatory synovial diseases can be differentiated into crystal-induced arthropathy, such as gout and pseudogout, granulomatous diseases, such as tuberculosis, sarcoidosis and foreign body reactions and into the large group of non-granulomatous synovitis. This last group is by far the most common and often causes difficulties in assigning the histopathological findings to a definite diagnosis. Therefore, the synovitis score should be applied in these cases as a diagnostic means, leading to the diagnosis of low-grade synovitis (which is associated with degenerative and posttraumatic arthropathies) or high-grade synovitis (associated with rheumatic diseases), the sensitivity and specificity being 60.5% and 95.5%, respectively. In detritus synovitis the synovitis score is not applicable.
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PMID:[Diagnostic spectrum of synovitis]. 1821 Jan 34

Although joint aspiration is a basic clinical skill, aspiration of normal joints, or asymptomatic clinically quiescent joints, is only rarely undertaken. There are two main indications for this procedure. Firstly, for definitive diagnosis of crystal-associated arthritis (gout and pseudogout) during the intercritical period and for subsequent monitoring of treatment success of gout; and secondly, to obtain normal synovial fluid for biomarker research. The justification for these indications, the success rate and the technical aspects related to this procedure are presented in this article.
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PMID:Aspiration of normal or asymptomatic pathological joints for diagnosis and research: indications, technique and success rate. 1838 78

Most individuals seeking consultation at sports medicine clinics are young, healthy athletes with injuries related to a specific activity. However, these athletes may have other systemic pathologies, such as rheumatic diseases, that may initially mimic sports-related injuries. As rheumatic diseases often affect the musculoskeletal system, they may masquerade as traumatic or mechanical conditions. A systematic review of the literature found numerous case reports of athletes who presented with apparent mechanical low back pain, sciatica pain, hip pain, meniscal tear, ankle sprain, rotator cuff syndrome and stress fractures and who, on further investigation, were found to have manifestations of rheumatic diseases. Common systemic, inflammatory causes of these musculoskeletal complaints include ankylosing spondylitis (AS), gout, chondrocalcinosis, psoriatic enthesopathy and early rheumatoid arthritis (RA). Low back pain is often mechanical among athletes, but cases have been described where spondyloarthritis, especially AS, has been diagnosed. Neck pain, another common mechanical symptom in athletes, can be an atypical presentation of AS or early RA. Hip or groin pain is frequently related to injuries in the hip joint and its surrounding structures. However, differential diagnosis should be made with AS, RA, gout, psudeogout, and less often with haemochromatosis and synovial chondochromatosis. In athletes presenting with peripheral arthropathy, it is mandatory to investigate autoimmune arthritis (AS, RA, juvenile idiopathic arthritis and systemic lupus erythematosus), crystal-induced arthritis, Lyme disease and pigmented villonodular synovitis. Musculoskeletal soft tissue disorders (bursitis, tendinopathies, enthesitis and carpal tunnel syndrome) are a frequent cause of pain and disability in both competitive and recreational athletes, and are related to acute injuries or overuse. However, these disorders may occasionally be a manifestation of RA, spondyloarthritis, gout and pseudogout. Effective management of athletes presenting with musculoskeletal complaints requires a structured history, physical examination, and definitive diagnosis to distinguish soft tissue problems from joint problems and an inflammatory syndrome from a non-inflammatory syndrome. Clues to a systemic inflammatory aetiology may include constitutional symptoms, morning stiffness, elevated acute-phase reactants and progressive symptoms despite modification of physical activity. The mechanism of injury or lack thereof is also a clue to any underlying disease. In these circumstances, more complete workup is reasonable, including radiographs, magnetic resonance imaging and laboratory testing for autoantibodies.
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PMID:Rheumatic diseases presenting as sports-related injuries. 1893 22

Extra-articular crystalline deposition secondary to gout, and less commonly, pseudogout is a well known phenomenon. Despite this well-documented entity of extra-articular deposition, there have been few reports of infiltration of the flexor tendon sheath of the hand. Here, we present a case series of this unique occurrence, including surgical techniques, pathology, and the clinical outcomes of 5 patients. We encountered 2 cases of calcium pyrophosphate and 3 cases of uric acid deposition into the flexor tendon sheath masquerading as common tendonopathies. These include cases of carpal tunnel syndrome, nonsuppurative flexor tenosynovitis, trigger finger, and attrition rupture of the flexor tendons. Although, medical therapy is the cornerstone of treatment for diseases that result in crystal deposition, these cases emphasize the potential need for surgical therapy in the armamentarium of their management. This case series demonstrates the importance of inclusion of crystal deposition into the flexor tendon sheath in the differential diagnosis in patients that present with uncharacteristic symptomatology of common flexor tendonopathies.
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PMID:Crystal deposition disease masquerading as proliferative tenosynovitis and its associated sequelae. 1915 20

The current study assessed the feasibility of the application of Raman spectroscopy toward the diagnosis of gout and pseudogout. First, the lowest concentrations of monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD) crystals detectable by Raman spectroscopy were investigated by mixing known amounts of synthetic crystals with synovial fluid in the concentration range of 1 to 100 microg/mL. Second, a digestion protocol was developed for clinical samples to improve crystal extraction. The ensuing centrifugation of the digest congregated crystals at a well-defined point and allowed for point-and-shoot Raman analysis without having to conduct an extensive search for individual crystals. Finally, synovial fluid samples obtained from patients (n = 35) were cross-analyzed by polarized light microscopy (PLM) and the Raman method to compare and contrast the diagnoses of the two methods. It was found that Raman spectroscopy can detect MSUM and CPPD crystals with good sensitivity and specificity at concentrations as low as 5 microg/mL and 2.5 microg/mL, respectively, using the current method. This detection limit of Raman analysis is lower than that reported for PLM. Raman and PLM diagnoses of clinical samples agreed in 32 out of 35 samples in the entire sample pool. However, the rate of disagreement between PLM-based and Raman-based diagnoses was noteworthy within the subset of diseased samples (3 out of 10), indicating that PLM has limitations and that the confirmation by a secondary method is essential for a reliable outcome. The proposed protocol of sample preparation and Raman analysis ascribes baseline feasibility to the diagnosis of gout and pseudogout by Raman spectroscopy, thus justifying further studies using a larger clinical sample set for obtaining sensitivity and specificity.
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PMID:Analysis of crystals leading to joint arthropathies by Raman spectroscopy: comparison with compensated polarized imaging. 1936 2

A 9-yr-old male Basilisk lizard (Basilicus plumifrons) with a history of painful and limited mobility for approximately 4 mo, which had seemed to be more pronounced in the front limbs, was presented for necropsy. The animal had exhibited moderate weight loss and anorexia before euthanasia. Postmortem examination revealed yellow-to-white, soft-to-semifirm nodules within the periarticular fascia and musculature of the left and right shoulder joints, hip joints, and stifle joints. Several other joints, including the left and right tarsi, left and right elbow joints, and the left carpus had calcified, white material present on the articular surfaces. Histopathologic evaluation of representative sections of all organs and the joints confirmed tophaceous articular gout and articular pseudogout. The differentiation between articular gout and pseudogout was based on histologic appearance, histochemical staining for calcium, and birefringence under polarized light.
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PMID:Articular gout and suspected pseudogout in a Basilisk lizard (Basilicus plumifrons). 1974 77

Autosomal dominant polycystic kidney disease (ADPKD) is the most common of the inherited renal cystic diseases and constitutes 10% of the end stage kidney disease population. ADPKD is caused by PKD1 and PKD2 gene mutations in 85% and 15% of the cases respectively. Its high prevalence and negative impact on health outcomes fostered efforts to explain pathophysiologic pathways of cyst formation in kidneys. Among these are increased apoptosis, unopposed proliferation of tubule cells, impaired polarization and planar cell polarity, impaired cAMP pathway, cilier dysfunction, activated mTOR pathway, increased tumor necrosis factor-alpha (TNF-alpha) production. Many drugs have been tried in an attempt to halt cystogenesis in some point. Despite success to some extent in experimental studies, none reached clinical armamentarium yet. Colchicine, originally extracted from Colchicum autunale, is an anti-inflammatory drug that has been in continuous use for more than 3000 years. It has been used successfully to prevent attacks of familial mediterranien fever and amyloidosis, to treat gout and pseudogout attacks for a few decades. Colchicine principally is a microtubule inhibitor, thus prevents cell migration, division, and polarization. It also has anti-apoptotic, anti-proliferative and anti-inflammatory effects and down-regulates (TNF-alpha) receptors. As can easily be seen, many of the effects of colchicine have pathophysiologic counterparts in ADPKD. Thus, we hypothesized that colchicine would be beneficial to prevent or at least delay cyst formation in ADPKD patients. Indirect evidence also support our hypothesis, in which taxol and paclitaxel, other two microtubule inhibitors, were shown to delay cyst formation in experimental models of ADPKD. To our opinion, despite its narrow therapeutic index, widespread experience makes colchicine a suitable candidate for prolonged clinical use, should experimental studies show any benefit in ADPKD.
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PMID:Colchicine treatment in autosomal dominant polycystic kidney disease: many points in common. 1976 12

The interleukin 1 family is composed by the interleukin 1 (IL-1) and its natural occurring inhibitor, the interleukin 1 receptor antagonist (IL-1Ra). The role of both molecules in rheumatoid arthritis has been widely established, and in this sense new molecules blocking IL-1 actions are under investigation. Anakinra is the recombinant form of IL-1Ra, and has proven to be well tolerated and indicated in the treatment of rheumatoid arthritis. Nevertheless, other molecules such as mAb anti-IL-1 and IL-1 Trap are being developed. Moreover, the recent relation of IL-1 in the inflammasome and pathways of innate immunity has lead to new indications of anti-IL-1 molecules, especially in the autoinflammatory syndromes as well as in other inflammatory diseases. Herein we have performed a review of the literature, limited to English language journals (PUBMED search: combination of descriptors IL-1 and anakinra, systemic juvenile idiopathic arthritis, adult's onset Still's disease, autoinflammatory syndromes, gout, pseudogout, ankylosing spondylitis, and systemic lupus erythematosus from January 1985-December 2008) emphasizing the possible new indications. Although sufficient data is not yet available to fully assess the efficacy and safety of anti-IL-1 molecules in patients with inflammatory disorders other than rheumatoid arthritis, new data is promising.
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PMID:Anti-IL-1 molecules: new comers and new indications. 2004 71

There are many potential causes of joint pain in older patients. The most likely aetiology is OA. However, the differential diagnosis includes conditions which should not be missed such as septic arthritis and inflammatory disease. The pattern of joint involvement points to the diagnosis. Bilateral symmetrical small joint pain, swelling and stiffness should arouse the suspicion of RA. The wrist and knee are commonly affected by pseudogout and the first metatarsophalangeal joint or knee joint involvement may represent gout. Stiffness in the shoulder and hip girdles, worse in the morning, suggests polymyalgia rheumatica. In straightforward cases of OA no specific investigations are required. If doubt exists, however, tests may be necessary including FBC, ESR and CRP, uric acid for suspected gout and X-rays of the affected joints especially following trauma, or pseudogout. Patients with OA should be offered education and advice as well as strengthening exercises and aerobic fitness training (if physically possible). If the patient is overweight, weight loss is critical, especially in OA of the knee. Paracetamol and topical NSAIDs are the first-line drug treatments. Elderly onset RA differs from younger onset RA in the following ways: a more balanced gender distribution; a higher frequency of acute onset; an association with systemic features; more frequent involvement of the shoulder girdle and higher disease activity. DMARD therapy should be used according to disease severity, as in younger onset RA. The current approach is for early, intensive intervention with combination therapy. Corticosteroids may be very effective in the elderly, however, prolonged use and/or high dosage may lead to marked toxicity especially osteoporosis and diabetes.
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PMID:Diagnosing joint pain in the older people. 2019 31


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