Site and nature of the initial insult in OA. Extent of matrix turnover and decompensation. Role of glucosamine sulfate. Ef \201 cacy of disease modifying OA therapy. Cardiovascular risk attributable to OA. Resources on OA Assessment tools OMERACT An organization originally set up to define outcom e measures for rheumatoid arthritis clinical trials recom- mended a core set of outcome mea sures for OA trials in 1997. This included both generic and disease speci \201 c assessmen t tools. Surgery \200 Hip and knee arthroplasty are established effective treat- ments for end-stage disease, wit h an effect size of more than 2- and 10-year arthroplasty survival of over 90% (although ar throplasty has never been subjected to randomized controlled trial). Generic tools Instruments developed to assess health status and quality of life in other co nditions: HAQ, SF-36 and EQ-5D. Download pain tools including Visual analog scale and OSTEOARTHRITIS 378 NHS direct: basic patient information and access to out of hours advice: http://www.nhsdire ct.nhs.uk/ articles/article.aspx?articleId=268 Wheeless \200\231 Textbook of Orthopedics. A vailable at: h t t p : / / w w w . w h e e l e s s o n l i n e . c o m / o r t h o / osteoa rthritis. SF-36 are available from http://www.painworld.zip.com.au/ articles/pain_tools.html Disease speci \201 c tools These tools have been developed and validated to a varying degr ee in OA. \200 WOMAC is probably the best validated tool for assess- ment of knee and hip OA. It measures 3 domains: pain, stiffness, and function, using either visual analog, numerical rating scal e or Likert scales. Lequesne index. Robust tool, but has some overlapping item options lead ing to some scoring ambiguity. Knee OA outcome score (KOOS) was developed for surgical asse ssment and outcome. Australian/Canadian Hand OA Index (AUSCAN). This tool is analogous in s tructure and rigor of development to WOMAC, but is for hand OA. ICD 10 codes Nodal/generalized OA M15.0 M15.1 M15.2 M15.4 M15.9 Primary generalized (osteo)arthrosis Heberden \200\231s nodes (with arthropathy) Bouchard \200\231s nodes (with arthropathy) Erosive (osteo)arthrosis Generalized osteoarthritis Hip OA M16.0 \200\22316.9 Hip OA codes ( \200\230coxarthrosis \200\231). Knee OA M17 \200\22317.9 Knee OA codes ( \200\230gonarthrosis \200\231). Priority scoring tools There are various tools that have been used for assigning priority f or patients to undergo total hip or knee replace- ment surgery. These include the New Zeala nd, NIH, Ontario, and Western Canada criteria. They include a com- bination of pain, and fu nctional and radiographic assess- ment, often with a degree of subjective assessment of ove rall disease state or requirement for surgery. They are not suitable for determining who sh ould receive surgery. Hand OA M18 \200\22318.9 1st CMC joint (and subcodes) References Altman RD & Gold G. Atlas of individual radiographic features in oste- oarthriti s. OARSI: 2007. Available at: http://www.oarsi.org/index2. cfm?section=Publications_and_New sroom&content=atlas Brandt KD, Doherty M, Lohmander LS. Osteoarthritis, 2nd edn. Resources Guidelines NICE Guideline CG59. OA: the care and management of adults with osteoa rthritis. Implementation tools: http:// www.nice.org.uk/CG059#implementation. OA Society In ternational (OARSI) recommendations for the management of hip and knee osteoarthritis. http :// www.oarsi.org/index2.cfm?section=Publications_ and_Newsroom&content=Indexes EULAR evide nced based recommendations for the management of hip and knee OA. MOVE consensus: evidence- based recommendations for the role of exercise in the management of OA of the hip or knee. Oxford: Oxford University Press, 2003. Dickson J, Hughes R, Marsh D. Royal: the New Science of Osteoarthritis \200\223 from Bench to Bedside. London: Royal Society of Medicine Publications, 2008. Doherty M, Jones A, Cawston T. Osteoarthritis. In: Maddison PJ, Woo P, Isenberg D, Glass D (eds) Oxford Textbook of Rheumatology, 3rd edn. Oxford: Oxford University Press (in press). Jordan KM, Arden NK, Doherty M, et al. EULAR recommendations 2003: an evidence based approa ch to the management of knee osteoarthritis: report of a Task Force of the standing committ ee for international clinical studies including therapeutic trials (ESCISIT). Ann Rheum Dis 2003; 62: 1145 \200\22355. NICE Guideline CG59. Osteoarthritis: the Care and Management of Adults with Osteoarthritis. London: HMSO, 2008. Available at: h t t p : / / w w w. n i c e . o r g . u k / g u i d a n c e / i n d e x . j s p ? a c t i o n = byID&o=11926 (accessed 28 March 2008). Moskowitz R, et al. Osteoarthritis: Diagnosis and Medical/Surgical Management, 4th edn. Phi ladelphia: Lippincott Williams & Wilkins, 2007. Patient organizations (UK) Arthritis Care. Head Of \201 ce: Arthritis Care, 18 Stephenson Way, London NW1 2HD. Telephone 020 7380 6500. E-mail: Info@arthritiscare.org.uk Roddy E, et al. Evidence-based recommendations for the role of exercise in the management o f osteoarthritis of the hip or knee- -the MOVE consensus. Rheumatology 2005; 44: 67 \200 \22373. Internet sites Arthritis Care: http://www.arthritiscare.org.uk/. Arthritis Research Campaig n (excellent patient and pro- fessional resources): http://www.arc.org.uk/ arthinfo/patpubs /6025/6025.asp. Patient information: http://www.patient.co.uk/ showdoc/23068795/, or http:/ /www.cks.library. nhs.uk/patient_information_leaflet/osteoarthritis. Clinical knowledge sum maries: osteoarthritis: http:// www.cks.library.nhs.uk/osteoarthritis; Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and k nee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systema tic review of current research evidence. Osteoarthritis Cartilage. 2007; 15: 981 \200\22310 00. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and k nee osteoarthritis. Part II: OARSI evidenced-based, expert consensus guidelines. Osteoarthr itis Cartilage 2008; 16: 137 \200\22362. This page intentionally left blank OSTEOARTHRITIS-RELATED DISORDERS 380 Osteoarthritis-related disorders Diffuse idiopathic skeletal hyperostosis Diffuse idiopathic skeletal hyperostosis (DISH, Fo restier \200\231s Disease) is a condition where calci \201 cation of the anterior spinal l igament occurs across at least 4 contiguous verte- brae leading to bony excrescences with a n appearance that has been likened to dripping wax. \200 There are no robust European epidemiological data. DISH affects 6 \200\22312% of the adult population in the USA, increasing to 28%of those over 80 years of age. There is a male prep onderance 2:1. Etiology unknown (hence, \200\230idiopathic \200\231), although an associat ion has been described with diabetes. Familial cases have been described. Distinct SNP poly morphisms in a candidate gene associ- ated with ossi \201 cation of the posterior longitud inal liga- ment (OPLL), collagen 6A1 (Col6A1), have been found in Japanese patients with DI SH. Findings have not been reproduced in other populations. The pathophysiology is not well understood. \200 Figure 12.6 Radiographic appearance of DISH. Neuropathic arthropathy Neuropathic arthropathy or \200\230Charcot \200\231s joint \200 \231 is a condition where peripheral (or central) neuropathy leads to secondary, painless, joint destruction. \200 Clinical features DISH may be asymptomatic, or present with variable degrees of pain and di sability. \200 Prevalence is about 15% in DM, 20% in tabes dorsalis, 25% in syringomyelia. The dominant hy pothesis is that loss of propio- and nociceptive input prevents protection the joint from e xcessive repetitive loading, leading to trauma, and progressive damage. The commonest clini cal scenario in Europe and N America is involvement of hindfoot joints in DM. Plain radiogr aphs show destruction of involved periph- eral joints, without features of osteomyelitis. E arly changes can mimic OA radiographically. Consideration should be given to potential meta bolic, drug, toxic, mitotic, and vasculitic causes (of neuropa- thy), and MR imaging if cen tral neurological disease suspected (e.g. multiple sclerosis, syringomyelia, spina bi \201 da, etc.) Other useful tests might include: \200 \200 \200 \200 \200 If large, the anterior cervical syndesmophytes can cause dysphagia, lead to dif \201 cult intubations, cause stridor, dysphonia, and contribute to ventilatory dif \201 culties. See Figure. 12.6. Spinal pain associated with DISH is thought to be due to mechanical damage a t segments of the spine where there is compensatory excessive movement, as segments affecte d by DISH stiffen. Myelopathy has been reported rarely; neck trauma in the context of DISH may have greater potential adverse consequences. Examination is characterized by restricted spinal mobility, which may be regional or global. Enthesophytes and bony spurs can form in the peripheral skeleton (e.g. plantar calcaneal spur). There is a recognized association w ith DM and possibly metabolic syndrome. Long-term, the spine can stiffen and cause similar postural problems as those in ankylosing spondylitis (AS). FBC, U&E, LFT, GGT, ESR, CRP; serum and urine protein electrophoresis; CXR; B12, blood suga r and HbA1c; complement, Igs RF, ANA, ENA, ANCA; tests for localizing lesions if paraneopla stic syndrome suspected, e.g. colonoscopy for change of bowel habit. Investigations Plain lateral radiographs of the spine are usually suf \201 cient to con \201 rm the diagnosis. In dif \201 cult cases it may be necessary to request: \200 \200 \200 Treatment Is of the underlying neuropathy where treatable. For example, optimizing diabetic control to minimize progression. Patients \201 nd orthotics and joint protection helpful . Immo- bilization of the foot in plaster cast can be tried. There are case reports of the success of intravenous bisphospho- nates, although controlled trial data is lacking for thi s and other therapies. In cases of hindfoot disease in DM failing to improve with conservat ive therapy, arthrodesis may be considered. ESR, CRP. HLA-B27 (a negative test might suggest against AS). AP pelvis or coned SIJ radiog raphs; if unclear, further imaging of the sacroiliac joint may be requested to con \201 rm they are spared (e.g. MR though CT scan shows SIJ erosions. Bone scintigraphy can be infor mative. The main differential is from AS, where marginal syndesmophytes are seen, together with sacroiliitis. Treatment There are no RCTs of analgesics or disease modifying therapy for DISH. Management is focused on pain control, exercises to maintain range of movement, and addressing rare c omplications related to compression of surrounding structures. CHAPTER 12 Osteoarthritis and related disorders 381 Typically, osteonecrosis presents with refractory pain in the affected joint, although this is often not severe and the index of suspicion therefore needs to be high in appropriate p atients. The affected bone may be tender if super \201 cial (e.g. Kienbock \200\231s disea se). Over time, range of movement and function can be progressively impaired if untreated. As collapse of the femoral head is quite common in end- stage hip disease, it can be imposs ible to discriminate whether the osteonecrosis is a primary or secondary process. If radiog raphs are uninformative (as is often the case in early disease) then bone scintigraphy, CT or, preferably, MRI should be performed. MR particularly can stage the lesion, monitor cons ervative management and can inform surgical approach. Major causes of neuropathic arthritis \200 \200 \200 Trauma. Paraneoplastic sensory neuropathy \200\223 induced. Endocrine and metabolic causes : \200 \200 \200 \200 \200 Leprosy. Neurological conditions: Syphilis; \200 Syr ingomyelia; \200 spina bi \201 da; \200 multiple sclerosis; \200 hereditary sensory- motor neuropathy; \200 \200 cord compression. In \202 ammatory conditions: \200 \200 \200 diabetes; pernicious anemia; Cushing \200\231s; Alcohol; Glucocorticoids. \200 Treatment Conservative management includes analgesia, NSAIDs, resting, and passive stretchi ng the affected joint. Surgical options include core decompression (for early hip disease), osteotomy, bone grafting, or arthroplasty. As with most other indications for surgery, con trolled evidence of bene \201 t is lacking. Amyloid; Scleroderma; other autoimmune CTDs. Resources Internet sites h t t p : / / w w w. o s t e o n e c r o s i s . o r g / n o f b r o c h u r e / nonf-brochure.htm. Khan NK. Neuropathic arthopathy. Available at: http:// ww w.emedicine.com/radio/topic476.htm Rothschild BM. Diffuse idiopathic skeletal hyperostosis. Available at: http://www.emedicine.com/orthoped/ topic74.htm; Center for Osteonecrosis Res earch. http://www. osteonecrosis.org/pages/osteo.html. Osteonecrosis (ischaemic necrosis; see also p. 433) This condition is also known as ischaem ic/avascular or aseptic necrosis, although there are eponymous syndromes depending on the s ites involved (e.g. Legg-Calv -Perthes disease of femoral head in children). See Table on p. 433 for full list). \200 The incidence has been estimated at 1 in 10 000 \200\22320 000 per year in the USA. Peak on set is from 20 to 50 years with an equal gender ratio. Osteonecrosis is usually idiopathic. The assumption is that vascular supply is compromised in bones prone to infarction \200 \223 those without adequate collateral arterial supply. The commonest secondary causes are: \200 See also CPPD Depositor disease Gout Osteonecrosis p. 388 p. 384 p. 433 fracture mechanically compromising blood supply (e.g. femoral neck); drugs \200\223 high d ose glucocorticoids (e.g. post trans- plant), excessive alcohol, cyclophosphamide therapy, intravenous bisphosphonates (jaw); diseases affecting blood \202 ow \200\223 vasculitis, sickle cell disease, HIV, cancer; low oxygen tension (Caisson \200\231s disease) . This page intentionally left blank 383 Chapter 13 Crystal arthritis Gout 384 Calcium pyrophosphate dihydrate disease 388 The basic calcium phosphate crystals 3 92 GOUT 384 Gout De \201 nition The term gout is used to describe an in \202 ammatory arthritis triggered by the crystallization of monosodium urate crystals in joints or soft tissue. The spectrum of disease is broad. Causes of hyperuricaemia Primary Secondary Causes of under excretion of urate \200 \200 \200 \200 \200 Classi \201 cation and spectrum of disease \200 Renal impairment. Hypertension. Hypothyroidism. Drugs, e.g. ethanol, aspirin, diuretics. Le ad toxicity. Asymptomatic hyperuricaemia, which may not progress to acute gout. Acute gout due to monoso dium urate deposition in joints or soft tissue. Recurrent attacks. Chronic tophaceous gout. Urolithiasis. Urate nephropathy (rare). \200 \200 \200 Causes of over production of urate \200 Malignancy: lymphoproliferative diseases, tumor lysis syndrome. Severe exfoliative psoriasi s. Excessive consumption. Drugs, e.g. ethanol, cytotoxics. Inborn errors of metabolism. \200 \200 \200 Diagnostic criteria The presence of monosodium urate crystals in a joint, either during an attack or in asymptomatic joints, is the gold standard diagnostic test. Six or more criteri a of the American College of Rheumatology guidelines make the diagnosis of gout highly like ly. Clinical presentation Key features in history Acute gout \200 Epidemiology \200 In the UK, gout has an overall prevalence of 1.39% (male: female ratio of 3.6:1). Gout is r are in pre-menopausal women. The incidence is more dif \201 cult to determine. The inci- d ence and prevalence of gout are both strongly age- related (prevalence >7% in men, and >4% in women, over the age of 75 years). First attacks of acute gout are usually monoarticular (up to 90% of patients) with the meta tarsophalangeal joint of the great toe affected in more than 50%. Joints other than the 1st metatarsophalangeal joint (MTPJ) include weight bearing joints, the wrist, the elbow and s mall joints of the hand. Axial involvement is rare in early disease. Attacks are usually se lf-limiting after 5 \200\2237 days. Onset is often late at night or in the early morning. L ow grade fever with malaise may occur. Precipitants of an attack include intercurrent illne ss, surgery and dehydration e.g. alcohol excess. Etiology and pathophysiology \200 \200 \200 \200 Hyperuricaemia is the most important risk factor for developing gout and, in most cases, re sults from impaired renal excretion rather than over-production. Not all people with hyperu ricaemia or monosodium urate within a joint develop gout, although the 5-year cumulative ri sk is around one-third for those with a serum uric acid of greater than 0.6 mmol/l (10 mg/d l). Monosodium urate crystals cause inflammation and induce an attack of synovitis, but can also be found in asymptomatic joints. In younger patients (<25 years) underlying causes sh ould be considered, such as myeloproliferative disease or rare inherited disorders, e.g. th e Lesch \200\223Nyhan syndrome or familial hyperuricaemia with renal failure. Tophi are for med from urate deposits in some patients in prolonged hyperuricaemia. They are usually subc u- tanous and are seen in late disease. They contain amor- phous urates, lipids, proteins, and calci \201 c deposits. Chronic gout \200 \200 Polyarticular gout is often a feature of chronic disease. Repeated attacks get closer toget her and become more prolonged. Repeated attacks may result in deformity, reduced range of j oint movement and chronic pain. Chronic gout is often associated with tophi. Key features on examination Acute gout \200 \200 A hot, swollen, exquisitely tender joint is typical. There may be involvement of the soft t issues, with cellulitis or tenosynovitis. Podagra is the term used to describe desquamation that occurs several days after the attack in the skin overlying the affected joint. It is not speci \201 c for gout. Bursitis may be present, most commonly affecting the olecranon bursa or prepatellar bursa. Risk factors A number of risk factors have been identi \201 ed, including: \200 \200 Overall body weigh or central obesity. Very rapid weight loss through dieting may cause hyp eruricaemia, and an acute attack. Hypertension. Loop and thiazide diuretics. Excessive alco hol intake. Occupations such as business executives or naval marine. Chronic gout \200 \200 \200 \200 Joints may become deformed by recurrent attacks, with consequential impaired function. Toph i are found subcutaneously, but can also occur in bone and end organs. Common sites for top hi are the bursa around elbows and knees, the pinna of the ear, the CHAPTER 13 Crystal arthritis 385 Achilles tendon, and over MCPJs on the dorsum of the hand. Tophi are not associated with an inflammatory response. Tophi are usually painless, although a urate-rich, thick white/crea my discharge may occur from tophi if the skin is breached. If the tophus is found in a joint, the typical appearance of the erosion is of a punched ou t lesion with a sclerotic border. Erosions are commonly found on the head of the \201 rst metatarsal. In acute gout, ultrasound is useful to identify synovitis within the joint and can aid accuracy guiding the needle into the joint if blind aspiration has been unsuccessf ul. A granular or sparky appearance of the synovial \202 uid has been described in patien ts with gout, but does not replace the need for joint aspiration for diagnosis. Natural history \200 Recurrent acute attacks can be prolonged and may not resolve without treatment. Untreated, recurrent acute attacks of gout progress to chronic polyarthritis and/or tophus formation, with tophi reported in 12% of patients at 5 years. Tophi can develop after only one or two acute attacks of gout, usually in elderly women and at the site of Heberden \200\231s nodes . Chronic tophaceous gout is more likely in those with early disease onset, alcohol misuse, persistent hyperuri- caemia, and poor drug compliance. The natural history of radiological progression and joint destruction in untreated recurrent gout has not been established in observational studies, but treatment may reduce disease progression. Gout is associated wit h a two-fold risk of renal calculi and is associated with high urinary urate excretion. Histology Gouty tophi can be surgically removed, although this is rarely necessary. The exu date from tophi contains mono- sodium urate, which can be identi \201 ed on polarized ligh t microscopy if the exudate is smeared onto a slide. Differential diagnosis Septic arthritis is the most important diagnosis to exclude, because of its associated mortality and morbidity. Other crystal arthropathies may result in simil ar clinical features, although the treatment modalities are less well de \201 ned in this group. Chronic gout may mimic nodal osteoarthritis, and polyarticular gout may mimic in \202 ammatory arthritis. As both are self-limiting, each may be confused with palin- dromic rheumatoid arthritis. General aims of treatment \200 Co-morbidities Compared with patients with osteoarthritis, patients with gout are more like ly to have coronary artery disease, hypertension, diabetes, insulin resistance, the metabol ic syndrome, and chronic renal failure. Serum urate may be an independent risk factor for b oth renal disease and coronary artery disease. Asymptomatic hyperuricaemia does not require treatment. Septic arthritis should be consider ed in any patient with an acutely hot, swollen joint. Pain relief with NSAIDs and simple an algesia should be commenced. Terminate the attack as soon as possible. Assess patients for recognized co-morbidities. \200 Investigations Blood tests \200 Management of acute gout \200 A mild to moderate leucocytosis is seen in acute gout, although not in chronic gout. An ele vation of acute phase proteins is typical in acute attacks of gout Serum creatinine will es tablish baseline renal function prior to treatment. Serum urate is unreliable during an acu te attack, as levels may fall, and may delay the diagnosis. Blood cultures will be negative but should be collected if septic arthritis is a possibility. Acute gout is intensely painful, but is usually self-limiting, resolving spontaneously in 1 \200\2232 weeks. There is a wide spectrum of attacks of gout from mild monoarthritis to se vere polyarticular \202 ares. Ice therapy, NSAIDs, colchicine, and glucocorticoids are ef fective. The affected joint should be rested. NSAIDs \200 Indometacin has been the traditional NSAID of choice, although there is no evidence for the superiority of any one NSAID over another, in either ef \201 cacy or safety in an acute a ttack. Most have an effect within 4 h of administration. NSAIDs should be avoided in patien ts with heart failure, renal insuf \201 ciency, or a history of previous peptic disease Synovial \202 uid Joint aspiration with synovial \202 uid analysis is the most importan t diagnostic test. Synovial \202 uid should be cultured even if monosodium urate crystals are identi \201 ed, as gout and sepsis can co-exist. Monosodium urate crystals are negati vely birefringent and needle-shaped under polarized light. Crystals may deteriorate and if there is any delay in microscopy, the synovial \202 uid should be refrigerated. \200 Colchicine \200 Most patients respond to colchicine within 18 hours and joint in \202 ammation subsides in 75 \200\22380% of patients. NSAIDs may work more quickly, but colchicine does have a role in patients in whom NSAIDs are absolutely contraindicated. BSR guidelines recommend doses o f 500 g 2 \200\2234 times daily, which are less likely to induce diarrhea than those doses recommended in the BNF but may be associated with a slower clinical response. Imaging \200 Plain radiographs are unhelpful in early gout. Soft tissue swelling may be seen, but is a n on-speci \201 c \201 nding. The hallmarks of radiographic gout are the presence of tophi , which appear eccentric and nodular, sometimes with calci \201 cation, in the soft tissue s near a joint. Erosions may occur if the tophus lies next to the cortex of the bone, with resulting new periosteal bone formation. The classical description is that of an erosion wi th an overhanging margin. GOUT 386 Glucocorticoids \200 resolution. A life-threatening allergic reaction may occur in 1:300, resulting in fever, ex foliative dermatitis, mucositis, vasculitis, hepatitis and renal damage. Drug interactions: warfarin and azathioprine. Glucocorticoids are useful in patients who cannot toler- ate or are not improving with NSAI Ds or colchicine. Intra-articular injections are effective in monoarthritis or oligoarthrit is. Oral, intramuscular or, more rarely, intravenous glucocorticoids are more appropriate i n patients with polyarticular gout. No consensus exists for the dose of oral glucocorticoid , but prednisolone for 20 \200\22350 mg daily for 2 weeks is appro- priate. Intramuscular d epomedrone in a dose of 120 mg is the standard dose for intramuscular glucocorticoids. Other uricostatic agents: a new xanthine oxidase inhibi- tor, febuxostat, is currently unde rgoing clinical trials. In those patients with allopurinol hypersensitivity, and who have a lso failed uricosuric therapy, oxipurinol, and thiopu- rinol are other options, although se vere hypersensitivity to allopurinol may also predict a severe reaction to these agents. Uricosuric agents Uricosuric agents are not widely prescribed in the UK, but are available for second line use in patients who are intolerant of or resistant to allopurinol. They car ry a risk of increased uric acid stone formation. \200 Management of further attacks In general, fewer subsequent attacks are seen in those with l ower plasma uric acid levels. 40% of patients will not experience any further attacks withi n a year of their \201 rst attack. Within 3 years some 80% of patients will have had a fu rther attack. Therefore, current guidance recommends patients with a \201 rst attack of g out should not be treated with serum urate lowering drugs unless they have a second attack within a year. However, there are speci \201 c groups where treatment is recommended follo wing a \201 rst attack of acute gout: \200 \200 Suphinpyrazone (Anturan, Novartis): 200 \200\223800 mg/day is only useful in patients with normal renal function. Side-effects: gastrointestinal (10 \200\22315%), inhibition of plate let function causing gastrointestinal hemorrhage, marrow failure. Probenecid: 0.5 \200\2232 .0 g/day can be obtained on a named patient basis, but is only effective in patients with a serum creatinine <200 mol/l. Side-effects: dyspepsia and re \202 ux oesophagitis (10%). B enzbromarone 50 \200\223200 mg/day in patients with mild or moderate renal insuf \201 cien cy (creatinine clearance 30 \200\22360 ml/min). Benzbromarone is unlicensed in the UK, but can be obtained on a named patient basis. It is the most potent of the uricosuric agents. S ide-effects: diar- rhoea (10%), rare hepatotoxicity, and fatal hepatic necro- sis. It is us eful in patients with renal impairment. Patients with visible gouty tophi. Patients with renal insufficiency (raised plasma creatin ine, Ccreat or GFR <80 ml/min). Patients with uric acid stones and gout. Patients who need require diuretics. \200 Treatment should be continuous and long-term. Allopurinol maintains low serum urate levels for at least 20 years, with no increase in side-effects. The main choice for speci \201 c uric acid-lowering drugs lies between agents inhibiting urate production (uricostati c agents) and those promoting urate excretion (uricosuric agents). Uricolytic agents Two forms of urate oxidase [uricozyme and rasburicase, (Fasturec)], are a vailable for treatment of chronic gout and are administered intravenously. Their use is lim ited by the formation of antibodies, which result in infusion reactions, but these drugs ma y be of use in patients who cannot tolerate allopurinol. Uricostatic agents Inhibitors of the enzyme xanthine oxidase inhibit produc- tion of urate from hypoxanthine and xanthine. Allopurinol: allopurinol is the drug of choice in long term treatment of gout. \200 Other agents Low dosage (500 g od/tds) colchicine has a role in long- term prophylactic t reatment and is effective in over 80%, but use can be restricted because of the risk of dia rrhea with high doses. Losartan, feno \201 brate, and to a lesser extent atorvastatin have a weak uricosuric effect, making these drugs useful in the treatment of gout in patients w ith other co-morbidities. Allopurinol should not be commenced during an acute attack, but should be introduced 1 \200 \2232 weeks later. However, if allopurinol results in a \202 are, it should be continued during the acute attack and prophylactic cover added. The current recommendation is to intr oduce low dose colchicine (500 g bd) for up to 6 months following introduction of allopur inol to avoid attacks of gout, or NSAIDs for 4 \200\2236 weeks in patients who are intolera nt of colchicine. The dose of allopurinol should be increased by 50 \200\223100 mg, in resp onse to changes in serum urate levels, and aiming for a serum urate half the upper limit of the normal range (less than 300 mol/l). Most patients will achieve a reduction in serum urate levels within 7 days and certainly within 4 weeks, allow- ing for adjustment of the a llopurinol dosage at short intervals. This may take longer in patients with tophi who have a higher total urate burden. A dose of up to 900 mg/day of allopurinol may be required to s uppress serum urate levels adequately in a few resistant cases. Side-effects: possible side -effects include transient rashes (2%), however a reduction in dose, usually results in Combination therapy Combination therapy with benzbromarone and allopurinol together is more effective at reducing plasma urate con- centrations than either drug alone and is therefor e useful in patients who cannot tolerate high doses of allopurinol. Physical therapies \200 \200 Ice packs help with symptomatic relief. Rest should be advised in acute attacks with mobili zation encouraged as the attack is settling. Following an attack, moderate physical exercis e aids gradual weight reduction, and reduces serum urate. However, intense exercise and joi nt trauma may precipi- tate a further acute attack. CHAPTER 13 Crystal arthritis 387 Follow-up \200 Alcohol can raise the serum urate both by enhancing urate production and by reducing renal clearance. Advice about alcohol consumption therefore should include: \200 Review at 4 \200\2236 weeks following the \201 rst acute attack of gout is recommended to assess lifestyle factors, blood pressure, serum urate, renal function, and blood glucose. In patients with recurrent attacks, 3-monthly serum urate and creatinine levels are indicat ed for the \201 rst year, followed by annual assessment. restricting alcohol consumption to less than 21 units per week (men) and 14 units/week (wom en); avoid beer, stout, port and similar forti \201 ed wines; have at least 3 alcohol-free days per week. \200 Resources Guidelines BSR. Prodigy Guidance on Gout 1999, updated 2004. EULAR Standing Commi ttee for International Clinical Studies including Therapeutics (ESCISIT). Subgroups requiring precautions \200 Patients with renal insuf \201 ciency. GFR, rather than serum creatinine should guide trea tment. Allopurinol causes more rashes and other adverse events in patients with renal insuf \201 ciency. Probenecid and sul \201 npyrazone are ineffective in renal failure, and col chicine and NSAIDs should be avoided in this patient group. Benzbromarone can be used in pa tients with a plasma creatinine up to 500 mol/l. Elderly patients may need lower doses of a llopurinol, and colchicine, and NSAIDs should be prescribed cautiously. Patient organizations UK Gout Society Internet sites www.ukgoutsociety.org http://www.prodigy.nhs.uk/gout/management/ quick_answers/scenario_acute_gout Table 13.1 Modi \201 cation of allopurinol dosage with reduced renal function http://www.prodigy.nhs.uk/gout/management/ quick_answers/scenario_preventing_gout GFR Usual dose of allopurinol http://rheumatology.oxfordjournals.org/cgi/ content/full/kem056av1 >80 ml/min 200 \200\223300 mg daily 60 \200\22380 ml/min 100 \200\223200 mg daily Controversies The NICE technology appraisal for Febuxostat is due in September 2008. 30 \200\22360 ml/min 50 \200\223100 mg daily 15 \200\22330 ml/min 50 \200\223100 mg alternate days ICD-10 codes M10.0 M10.1 M10.2 M10.3 M10.4 M10.9 On dialysis 50 \200\223100 mg weekly Idiopathic gout Lead-induced gout Drug-induced gout Gout due to impairment of renal functio n Other secondary gout Gout, unspeci \201 ed Patient advice \200 Dietary advice: avoid foods with very high purine con- tent such as shell \201 sh, offal, and sardines, and moderating intake of other foods with relatively high purine content, suc h as meat and game. Even though some vegetables are high in urate, vegetarian diets are les s associated with gout suggesting different metabolic pathways. Restricting protein intake to 70 g/day may also be bene \201 cial. Fluid intake: patients with nephrolithiasis should drink at least 2 l/day to reduce the risk of stone formation. Water, fruit juice, skimmed or semi-skimmed milk, sugar- free squashes, cordials, tea, and coffee are all suitable. Hig h intake of dietary fructose, which is found in sugar sweetened soft drinks, has recently b een associated with an increased risk of gout in men. References Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu T-F. Preliminary crit eria for the classi \201 cation of the acute arthritis of primary got. Arthritis Rheum 197 7; 20: 895 \200\223900. Zhang W, Doherty M, Bardin T, Pascual T, Barskova V, Conaghan P, et al. EULAR evidence base d recommendations for gout. Part I: diagnosis. Ann Rheum Dis 2006; 65: 1301 \200\22311.