 \200 Blastomycosis \200 Blastomycosis dermatitidis is found in North and South America and Africa. Infection occurs following inhalation. Dissemination results in skin involvement in 80% and osteolytic lesi ons in 60%. Differential diagnosis in the spine includes tuberculosis. Monoarthritis is rar e, resulting from spread from local bone involvement. Histology from synovial tissue or bon e may be diagnos- tic, although Blastomycosis dermatitidis can also be seen in synovial \202 uid. Treatment is with surgical debridement, drainage and amphotericin B. \200 \200 Penicilliosis \200 Cryptococcosis \200 Penicillium marneffei is endemic in Thailand and Southern China. Presentation is usually wi th a chronic mono or oligoar- thritis. Osteomyelitis and subcutaneous abscesses can also oc cur. The diagnosis is con \201 rmed when encapsulated yeast is seen on microscopy of smear s, stained with Wrights stain. The differential diagnosis includes histoplasma capsulatum. Cryptococcus neoformans causes initial infection in the lung. Dissemination is rare and usu ally only in patients with immunocompromise. In this situation, presentation is often with meningitis. Vertebral osteomyelitis is rare. The differential diagnosis includes tuberculos is. Arthritis due to cryptococcal infection is rare. Diagnosis is made histologically. Trea tment is with amphotericin B or \202 uconazole and 5- \202 uorocytosine. Surgical debrid ement is often necessary. \200 \200 \200 \200 Mycetoma This term encapsulates a group of chronic infections of subcutaneous tissue, bones and joints. Paracoccidioidomycosis \200 Actinomycetes. These are aerobic bacteria that resemble fungi. They cause chronic suppurati on with sinus formation. Paracoccidioides brasiliensis is the fungus which causes paracoccidioidomycosis, also calle d \200\230South American blastomycosis \200\231 as it is found in central and southern Ame rica. The primary infection involves the lungs and is often asymptomatic. Dissemination occ urs to both skin and lymphoreticular tissue. Presentation may be with chronic skeletal mani festations involving scapula, acromium, clavicle, rib, humerus, radius, or phalanges. Sympt oms include slowly progressive bone pain and signs of inflammatory arthritis if infection s preads to a joint. Differential diagnosis includes tuberculosis, histoplasmo- sis, sarcoido sis, and malignancy. Diagnosis is made histologically. Treatment is with amphotericin or tr imethoprim for musc- uloskeletal disease and may be required for up to 4 years. Fungi Madurella mycetomatis is one example and causes maduro- mycetoma. These infections ar e generally treatment resistant. Parastic infection An oligo/polyarthritis may result as an immune phenome- non following in fection with helminths, \201 lariasis, or Ban- croftian \201 liariasis. Chylous arthritis Chyle within a joint is caused by lymphatic obstruction due to Wuchereria bancrofti, a nematode worm. The effusion is normally sterile, but can look creamy and may resemble pus. Treatment is with diethylcarbamazine. \200 CHAPTER 16 Musculoskeletal infection 477 Loiasis \200 Strongyloides This may result in a reactive arthritis or vasculitis. This is caused by the worm Loa-Loa and is found in the African rainforests and in South Ame rica. The micro \201 laria migrate under the skin, appearing as Calabar swellings. Arthrit is results from micro \201 laria within the joint and mimics septic arthritis. Treatment i s with diethylcarbamazine. Echinococcus (hydatid disease) Cysts may form in bone and muscle and in \202 ammatory arth ritis may also occur. Trichinosis Trichinella spiralis results in an eosinophilic myositis. Myosi- tis is associa ted with cystericercosis. Onchocerciasis \200 Protozoa Both arthritis and myositis are described. Infection with the nematode Onchocerca volvulus from black \202 y results in dermatitis w ith nodules, river blind- ness, and a monoarthritis. The joint involvement may worsen with diethylcar- bamazine. Resources Internet support Health protection agency center for infection control, Holborn, London. Available at: Guinea worm \200 An eosinophilic synovitis occurs following ingestion of the worm Dracunculus medinensis, wh ich is found in drinking water. The worm invades the joint, resulting in synovitis. Ulcerat ion and sinus formation with superimposed bac- terial sepsis may result. Treatment is dif \201 cult and surgical removal of the worm is necessary. http://www.hpa.org.uk/infections/about/sur- veillance/surveillance_menu.htm. ICD-10 codes M01.6, M01.8 Reference Blackwood T. The ubiquitous tick. Br Trav Health Ass J 2007; 10: 34 Gnathosostomiasis The nematode Gnathostoma spinigerum causes abscess for- mation in muscle. Schistosomiasis Two species of nematode \202 uke are describe: S. mansoni and S. haemotob ium, which can cause a reactive arthritis with enthesitis. This page intentionally left blank 479 Chapter 17 Chronic pain Chronic pain 480 Fibromyalgia syndrome 484 Complex regional pain syndrome type I 488 CHRONIC PAIN 480 Chronic pain Background Pain of more than 3 months is de \201 ned as chronic even though the features t hat characterize chronic pain can occur much more quickly. It is the commonest reason for a patient to seek consultation with a rheumatologist. Per- haps more than any other medical condition, it epitomizes the biopsychosocial model of healthcare. Brain stem The peripheral pain \200\230message \200\231 divides into two and is car- ried primarily through contralateral, anterolateral, and dorsolateral pathways. One pathway, the \200\230somatic \200\231 experi- ence of pain, is modulated through the brainstem, where it activates the reticular formation before going on to the thalamus and somatosensory cort ex. This pathway is needed to localize pain. The other pathway, the \200\230emotional \200 \231 component of pain also passes through the thalamus before going into the anterior cing ulate and frontal cortex. The characteristics and management of arthritis or in \202 ammatory pain; cancer pain; pai n associated with nerve lesions; and acute pain are speci \201 cally not discussed for the purposes of this chapter. Descending pathways Interconnections between the ascending pathways at the level of the med ulla and midbrain activate the peri-aque- ductal gray, raphe nucleus, and the rostroventral medulla to excite descending pathways that release noradrenaline and serotonin. Diffuse no xious inhibitory control (DNIC) is another descending spinal pathway probably opioid-me- di ated. The International Association for the Study of Pain de \201 nes any pain as all of the following: \200 An unpleasant sensory experience. \200 An unpleasant emotional experience. \200 An experience associated with actual or po tential tissue damage, or described in terms of such damage. Always subjective. Brain The primary and secondary somatosensory cortex, insular, anterior cingulated, and pre frontal cortex invariably acti- vate following an acutely painful stimulus in functional br ain imaging using MRI or PET scanning. Bilateral brain activa- tion can also be seen, as we ll as activity in the amygdale, hippocampus, basal ganglia, and posterior parietal lobe de- pending upon patient and protocol. Patients with chronic pain demonstrate disrupted neural network dynamics when compared with controls. The integrative properties of the brain allo ws the \200\230perceptual categorization \200\231 resulting from this neuromatrix activity to interact with pre-existing \200\230value-category memory \200\231 to generate a consci ous awareness or qualia. Many people with chronic pain report pain in the absence of tissue damage or any likely pat hophysiological cause. As a general approach: It is important to identify cases where there are speci \201 c trea tments. Pain needs to be distinguished from \200\230distress \200\231 (i.e. the emotional response). Sleep and mood disturbances are common. It can be helpful to address these. Pain interrupts attention and causes cognitive dysfunction, such as memory loss. It can be help ful to recognize this. The consequences of pain may be more problematic than pain itself. I t can be helpful to focus on this. Epidemiology Pain that lasted more than 3 months was estimated to affect about 14% of the p opulation \200\230signi \201 cantly \200\231 and 6% \200\230severely \200\231 in a commu nity survey in the Grampian region. This survey described all forms of chronic pain and did not differentiate between regional and widespread. People were more likely to indicate sig ni \201 cant chronic pain if they were: \200 \200 \200 \200 \200 Treatment options Pharmacological therapies No single strategy will \200\230cure \200\231 the problem. It is necessary to have a number of different treatment options and to empower the patient to think laterally. Rotating treatments; concentrating on function, rather tha n pain; goal setting; and keeping a diary, as an objective re \202 ection may be helpful. Unable to work (odds ratio 11.1). Older than 75 years (4.4). Achieved no educational quali \201 cations (2.9). Lived in rented council housing (2.2). Female (1.3). Conventional analgesics A pain ladder approach is appropriate, although this has no evidenc e-base in chronic non-malignant pain. Paracetamol/NSAIDs \200 Paracetamol is preferred by a minority of patients with rheumatoid arthritis, osteoarthriti s, and \201 bromyalgia for its effectiveness and side effect pro \201 le. In one study 1 4% rated paracetamol more effective than non-steroidal anti-in \202 ammatory drugs (NSAIDs ), 26% the same and 60% less effective. This is a poorly researched area. NSAIDs are useful for chronic arthritis and there is no evidence to distinguish any bene \201 t or harm in head- to-head trials conducted between them. Anecdotally, if one NSAID doesn \200\231t work , another NSAID may be helpful. Long-term use needs to be weighed against the serious risks to a patient, in particular gastrointestinal (GI) bleeds, renal, and cardiovascular diseas e. Pathophysiology Peripheral pain \201 bres These are slowly conducting C and AD \201 bre s that release glutamate, substance P, and calcitonin gene-related peptide (CGRP). Patients with \201 bromyalgia have 3 times the spinal level of substance P in their CSF obtained from lumbar puncture when compared with healthy volunteers. Spinal cord The spinal gate is controlled by local spinal mechanisms [glutamate, glycine and G-aminobut yric acid (GABA)] and descending pathways releasing serotonin and noradrena- line). Opioids are effective at blocking spinal transmission. Patients with chronic pain demonstrate \200\230wind-up \200\231 and central sensitization of the spinal cord. CHAPTER 17 Chronic pain 481 A proton pump inhibitor or higher dose histamine (H2) antagonist should be prescribed if on e or more of the following risk factors for gastrointestinal bleeding is present: \200 \200 \200 \200 \200 Cyclo-oxygenase-II (COX-II) inhibitors are associated with a red uced incidence of upper GI adverse events, but have signi \201 cant cardiovascular risk pr o \201 les. It is unclear whether this applies to all NSAIDs or is a spe- ci \201 c featu re of COX-II inhibitors. NSAID use is a complex area and the patient needs to be consulted in how to manage their chronic pain. Two- thirds of patients with osteoarthritis were willi ng to accept increased risk of heart attack, stroke, or stomach bleeding for a 2/10 point r eduction in pain. Half would accept risk at the level of 1 in 50. Pain is the area of healt h that almost 70% of rheumatoid arthritis patients would most like improved. The problems with administering strong opioids in patients with chronic pain are: \200 opioids are not as effective for chronic pain as they are for acute pain, especially where pain is secondary to a damaged nervous system; opioids also may not be given in adequate do ses due to the fears of addiction. age over 65 years; previous history of GI bleed; serious co-morbidity; prolonged use of hig h NSAID doses; aspirin or anticoagulants. Opioid-like drugs [Tramadol and (dextro) propoxy- phene] combine opioid actions with seroto nergic actions and this dual effect allows them theoretical bene \201 t over traditional o pioids. Slow-release strong opioids, including the use of patches, can be used in the treat ment of chronic pain. Adjunct medications The following drugs have been demonstrated to improve pain relief, alth ough were not developed primarily for analgesia. Such drugs include anti-depressants and an ti-convulsants. \200 Antidepressants, such as amitriptylline, nortriptylline and imipramine, selective serotonin re-uptake inhibitors (SSRIs), and serotonin-norepinephrine re-uptake inhibi- tors (SNRIs), such as \202 uoxetine, duloxetine, and venlafax- ine. For neuropathic pains, the number needed to treat (NNT) is about 3 for a 50% reduction in pain. 4% have to stop treatment, ho wever, due to adverse reactions. Anticonvulsants, such as gabapentin, pregabalin, carbe- ma zepine, valproate, lamotrigine, clonazepam, and phenytoin may have a role to play. A system atic review of the ef \201 cacy of tetrahydrocan- nabinol in the management of pain sugges ts it is roughly equivalent to codeine 50 mg, but with a higher incidence of psychotropic a dverse effects. Opioid for moderate- to-severe pain nonopioid adjuvant therapy Pain persisting or increasing Topical rubs Topical NSAIDs provide effective pain relief with a NNT \201 gure of 3.1 (2. 7 \200\2233.8) for at least 50% pain relief at 2 weeks after beginning treatment. \200 Opioid for mild-to-moderate pain + nonopioid adjuvant therapy Topical application of NSAIDs is not associated with serious side effects. Topically applie d capsaicin is useful in alleviating the pain associated with diabetic neuropathy, osteoart hritis and psoriasis with NNT \201 gures of 4.2 (2.9 to 7.5), 3.3 (2.6 \200\2234.8) and 3 .9 (2.7 \200\2237.4), respectively. Lidocaine patches may also have a role for local chroni c pain syndromes. Pain persisting or increasing Nonopioid adjuvant therapy Non-pharmacological therapies Transcutaneous electrical nerve stimulation (TENS) TENS may b e useful, but there is no conclusive evidence that TENS is effective for chronic pain. \200 PAIN Figure 17.1 The WHO Pain Ladder. There are 19 randomized trials of TENS, including one of a parallel cross-over design invol ving 658 patients and using Sham-TENS and other controls looking at a variety of outcomes. Most of the TENS trials were small and dif \201 cult to blind as active TENS gives a tingl ing feeling. 10/15 studies using inactive controls gave a positive treatment effect. The WHO Pain Ladder Opioids Codeine is a pro-drug that is metabolized by the liver (cytochrome P450 enzyme CYP2D6) to m orphine. \200 About 6 \200\22310% of Caucasians do not have this enzyme and codeine will not be effective for them yet they will still get side effects. Randomized, controlled studies of various o pioids given to adults with arthritis and other causes of chronic pain have demonstrated th eir ef \201 cacy and safety. Relaxation Relaxation does not appear to be effective in relieving chronic non-malignant pa in. Although some trials report bene \201 t with relaxation, it is unclear whether this is clini- cally meaningful. There appear to be no demonstrable long-term bene \201 ts of rel axation. It may be useful as part of combined therapies program. CHRONIC PAIN 482 Psychological-based treatments Cognitive behavioral therapy, behavioral therapy, and biofee dback. are effective in reducing the pain experience, and improving positive behavior expre ssion, appraisal, and coping in individuals with chronic pain. Guidelines Guidelines on Pain Management, National Library for Health. http://www.library.n hs.uk/guidelinesfinder/ Evidence-based medicine for pain management. Bandolier. http://www. jr2.ox.ac.uk/bandolier/ British Pain Society \200\231s 2007 Guidelines on Pain Management P rograms for Adults. http://www.britishpainsociety. org/book_pmp_main.pdf Complementary therapies There are a host of complementary therapies, the com- monest in the UK being acupuncture, homeopathy, herbal medicines, and topical devices (magnets, bracelet s, crystals). There is no good evidence for the ef \201 cacy of any comple- mentary therap y. Some points need to be made: \200 Patient organizations Action on Pain, Tel: (Helpline) 0845 603 1593. Available at: www.acti on-on-pain.co.uk/ Arthritis Care HelpLine, Tel: 0808 8004050. Available at: www.arthritisca re.org.uk NHS patient support. Available at: www.patient.co.uk Pain Concern, Tel: 01620 822 572. Available at: www. painconcern.org.uk Pain Association Scotland, Tel (enquiries only): 0800 783 6059. Available at: www.chronicpaininfo.org NHS expert patients. Available at: ww w.expertpatients. nhs.uk Talking Life, Tel (enquiries): 0151 632 1206. Available at: www.ta lkinglife.co.uk CRUSE Bereavement Helpline 0844 477 9400. Available at: www.crusebereavemen tcare.org.uk Unwind Helpline is 0191 384 2056 Politically active groups include www.paincoa lition. org.uk There is known harm for some complementary therapies (herbal remedy drug interactions, acup uncture needle infections). There is a de \201 nite cost. The placebo effect is linked to patient expectation. Some people \201 nd complementary therapies helpful. \200 \200 Clinical tips \200 Patients value the time to give their history and appreci- ate a thorough examination. The following clinician characteristics have been demon- strated to help patients with unexplai ned medical symp- toms (irritable bowel): \200 \200 questions concerning symptoms, relationships, lifestyle; how the patient understands the \200\230cause \200\231 and \200\230meaning \200\231 of the symptoms; warm, friendly manner , active listening, empathy, and positive expectation. Understanding and describing pain as a functional nervous disturbance can lead to a change in the \200\230number needed to offend \200\231 (NNO) from 2 to 10 when compared with othe r strategies for explaining to patients the cause of their symptoms. Aiming for control, ra ther than a cure can be helpful. Changes in both pharmacological and non-pharmaco- logical interventions may lead to improvements. Be aware of common causes of distress and attempt t o address these with either onward referral via primary or secondary care or empowering the patient to self-refer to direct-access services. Honesty is the best policy. Western medic ine does not have the solution to every patient \200\231s symptoms. Complementary therapies , providing they do no harm, can be helpful. Pain pathways can be divided into two broad ar eas \200\223 somatic localizing acute pain and ill-de \201 ned emotional distress. A sing le peripheral insult activates both of these. Re \202 ecting this to the patient in a non- judgemental fash- ion can be helpful. Internet sites Pain Web for Health Professionals. Available at: www. thepainweb.com Interna tional Association of Pain. Available at: www. iasp-pain.org British Pain Society. Availabl e at: www.britishpainsociety. org Royal National Hospital for Rheumatic Disease, Bath. Avai lable at: www.bath.ac.uk/pain-management/ INPUT, Guy \200\231s and St Thomas \200\231 Hospi tals, London. Available at: www.gstt.nhs.uk/services/acutepatient/peri- operative/pain/inpu t.aspx ICD-10 codes R52.2; R52.9 References Baliki MN, Geha PY, et al. Beyond feeling: chronic pain hurts the brain, disrupt ing the default-mode network. J Neurosci 2008; 28: 1398 \200\223403. Caldwell J, Hale ME, et al. Treatment of osteoarthritis pain with controlled release oxycod one or \201 xed combination oxycodone plus acetaminophen added to nonsteroidal antiin \202 ammatory drugs: a double blind, randomized, multicenter, placebo control- led trial. J Rheumatol 1999; 26: 862 \200\2239. Resources Assessment tools Brief Pain Inventory. Available at: http://www. mdanderson.org/p df/bpilong.pdf SF-36. Available at: http://www.sf-36.org/tools/SF36. shtml British Pain Soc iety \200\231s Good practice guide to assessing pain in older people> Available at: http:// www. britishpainsociety.org/book_pain_older_ people.pdf Campbell FA, Streetcar r MA, et al. Are cannabinoids an effective and safe treatment optio n in the management of pain? A qualitative systematic review. BMJ 2001; 323: 13 \200\22316. Carroll, D, Moore RA, et al. Transcutaneous electrical nerve stimu- lation (TENS) for chron ic pain (Cochrane Review), in: The Cochrane Library 2002; Issue 2, Update software, Oxford. CHAPTER 17 Chronic pain 483 Moore RA, Carroll D. A systematic review of topically-applied non-steroidal anti-in \202 a mmatory drugs. BMJ 1998; 316: 333 \200\2238. Morley S, Eccleston C. systematic review and m eta-analysis of randomized controlled trials of cognitive behavior therapy and behavior the rapy for chronic pain in adults, excluding headache. Pain 1999; 80: 1 \200\22313. Dickenson AH. Gate control theory of pain stands test of time. BJA 2001; 88: 755 \200\2237. Eckardt K, Li S, Ammon S, et al. Same incidence of adverse drug events after codeine admini stration irrespective of the genetically determined differences in morphine formation. Pain 1998; 76: 27 \200\22333. Edelman GM. Naturalizing consciousness: a theoretical framework. Richardson CG, Chalmers A, et al. Pain relief in osteoarthritis: patients \200\231 willingn ess to risk medication-induced gastrointestinal, cardiovascular, and cerebrovascular compli cations. J Rheumatology 2007; 34: 1579 \200\22385. PNAS 2003; 100: 5520 \200\2234. Furlan AD, Sandoval JA, et al. Opioids for chronic noncancer pain: a meta-analysis of effec tiveness and side effects. CMAJ 2006; 174: 1589 \200\22394. Smith BH, Elliott AM, et al. The impact of chronic pain in the community. Fam Pract 2001; 18: 292 \200\2239. Heiberg T, Kvien KV. Preferences for improved health examined in 1024 patients with rheumat oid arthritis: pain has highest priority. Arthritis Rheum 2002; 47: 391 \200\2237. Stone J, Wojcik W, et al. What should we say to patients with symp- toms unexplained by dis ease? The \200\230number needed to offend \200\231. BMJ 2002; 325: 1449 \200\22350. Jadad AR, CarrolD, et al. Morphine responsiveness of chronic pain: double-blind crossover s tudy with patient controlled analgesia. Lancet. 1992; 339: 1367 \200\22371. Wolfe F, Zhao S. Preference for nonsteroidal antiin \202 ammatory drugs over acetaminophen by rheumatic disease patients. Arthritis & Rheum. 2000; 43: 378 \200\22385. Kaptchuk TJ, Kelley JM, et al. Components of placebo effect: randomized controlled trial in patients with irritable bowel syndrome. BMJ 2008; 336: 999 \200\2231003. Zhang WY, Li Wan Po A. The effectiveness of topically applied capsaicin. A meta-analysis. E ur J Clin Pharmacol 1994; 46: 517 \200\22322. McQuay H, Carroll D. Anticonvulsant drugs for management of pain: a systematic review. BMJ 1995; 311: 1047 \200\22352. FIBROMYALGIA SYNDROME 484 Fibromyalgia syndrome De \201 nition Fibromyalgia syndrome (FMS) is de \201 ned as chroni c wide- spread (bilateral, axial, and above and below waist) unex- plained pain associated with at least 11 of 18 speci \201 ed tender points. Characteristic features include: fatig ue, sleep disturbances, subjective memory loss, swelling (e.g. lymph nodes), paraesthesiae, stiffness. Etiology and pathophysiology Central pain pathways are sensitized in patients with FMS. The brain \200\231s pain neuromatrix is active in patients with FMS in a different way to heal thy controls. Furthermore, Sub- stance P, a key neuropeptide in pain transmission pathways, is three times elevated in the cerebrospinal \202 uid (CSF) of patients with FMS compare d with healthy age- and sex- matched controls. \200 History Froriep described \200\230rheumatic \200\231 patients with hard tender muscles 190 4 Gowers used term \200\230 \201 brositis \200\231 to describe patients with sleep distur bances, fatigue, and sensitivity to touch. Disturbed sleep clearly has an interesting relationship with unexplained pain both in clini cal anecdotes and in the laboratory. Large, well-controlled studies are required. Hormonal pro \201 ling is consistent with a chronic stress reaction with evidence of low urinary fr ee cortisol lev- els, decreased cortisol response to cortisol-releasing hormone, low neurop eptide Y plasma levels, and low growth hormone levels. Growth hormone, insulin growth facto r-1 (IGF-1) and prolactin levels may also be different in FMS patients. Although major depr essive illness occurs more com- monly in patients with FMS and, more commonly, in their fam ily members, there is no evidence for a speci \201 c per- sonality type predisposed to dev eloping FMS and evi- dence that pain contributes to the development and maintenance of the depression. Muscle abnormalities have been described in patients with FMS including type II \201 bre atrophy, changes in glyco- gen and lipids and mitochondrial abnormalities. Howe ver, these are likely to be secondary to inactivity and pain. 1930s Lewis and Kellgren injected saline into deep muscles of healthy volunteers who descri bed non-dermato- mal, but consistent patterns of pain 1970s Smith and Moldofsky described tender points in pa- tients with stage 4 sleep disturba nces. They then showed the onset of symptoms and muscle tender- ness similar to that seen i n patients with \201 bromyal- gia by sleep-depriving healthy volunteers. Several investig ators corroborated these \201 ndings in the 1980s. 1990 American College of Rheumatology criteria for the classi \201 cation of \201 bromya lgia. 293 patients with FMS, and 265 age- and sex-matched controls with a rheu- matic disor der were evaluated by blinded assessors using the de \201 nition provided above. This gave a sen- sitivity of 88% and speci \201 city of 81%. Clinical features Key points in the history The presence of co-morbidities related to FMS s hould alert the physician and increase the pre-test probability for FMS. Epidemiology The reporting of chronic widespread pain appears higher now than in 1950s. The point prevalence of chronic wide- spread pain in a community-based questionnaire survey in Manchester, UK, was about 5% with associations with: \200 \200 \200 \200 \200 \200 Co-morbidities \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Fatigue (Risk ratio 3.8). Mental disorder (anxiety, panic disorder) (3.2). Psychological di sturbance (2.2). Low levels of self-care (2.2). Reporting of other somatic symptoms (2.0). Reporting multiple symptoms aged 7 (1.5). Chronic fatigue. Chronic spinal pain. Chronic regional pain syndromes. Irritable bowel. Irr itable bladder. Restless legs. Endometriosis. Anxiety. Depression. Joint hypermobility synd rome. Although classically described as a diagnosis of exclusion, Ethnic minorities have also reported higher prevalence of chronic pain and this may re \202 ect social, cultural and psy- chological differences. Around Manchester these include: \200 \200 \200 \200 \200 Indian. Pakistani. Bangladeshi. African (not speci \201 ed). Caribbean. features of the syndrome usually include the following: \200 \200 \200 Low mood (pain that causes tearfulness). Subjective memory loss. Disturbed or unrefreshed s leep. A higher tender point count (>4) is associated with low levels of self-care with the follow ing risk factors: \200 \200 There are several other useful questions that might include feeling. Abuse (Odds ratio 6.9). Adverse childhood experiences (2.1). CHAPTER 17 Chronic pain 485 Differential diagnosis \200 Key points on examination Examination focuses around identifying secondary causes (e.g. hyp othyroidism) and the tender points. Endocrine disease (e.g. hypothyroidism, vitamin D insuf- \201 ciency/de \201 ciency). Au toimmune disease (e.g. SLE, RA). Anemia, renal disease or hepatic disease. All locations are bilateral: Occiput: suboccipital muscle insertions. Low cervical: anterio r aspects of intertransverse spaces at C5 \200\2237. Trapezius: midpoint of upper border. S upraspinatus: above scapula spine near medial border at origins. Second rib: second costoch ondral junction. Lateral epicondyle: 2 cm distal to epicondyles. Gluteal: upper outer quadr ant in anterior fold of muscle. Greater trochanter: posterior to trochanteric promi- nence. Knee: medial fat pad proximal to the joint line. \200 \200 Treatment Objectives of management \200 \200 \200 \200 \200 Functioning. Mood. Pain experience. Coping skills. \200 \200 \200 Physical therapies Aerobic exercise may be helpful for both pain and func- tioning, and cer tainly has bene \201 cial effects on other sys- tems, chie \202 y cardiovascular. It is l ikely that greater success will be afforded if the program is tailored to the indi- vidual needs of the patient and paced. Investigations Laboratory To rule out secondary \201 bromyalgia, the following blood test s should be taken: \200 \200 \200 \200 \200 \200 Heated pool therapy is effective in improving pain and functioning for patients with FMS. Pharmacological therapies Simple analgesics and NSAIDs can be helpful. \200 FBC. Urea and electrolytes. Creatinine. LFTs. ESR. TSH. Tramadol may be of value, and been has demonstrated improved pain and functioning in patien ts with FMS. Careful consideration of the risk-benefit ratio for NSAIDs and COX-II inhibito rs should be used. Further consideration is important if prescribing strong opioids. Other blood tests to consider include: vitamin D, PTH, serum ACE, CRP, ANA, RF, 9am cortiso l, synacthen, fasting glucose. Antidepressants These are useful and valid studies have been published mainly using amitrip tylline and \202 uoxetine. Both appear to improve pain and functioning within 6 \200\2231 2 weeks. \200 Imaging No imaging modality rules in or out the diagnosis of FMS and, therefore, imaging is not helpful unless another diagnosis is being investigated. Duloxetine (NNT 6 to reduce pain by more than 50%) and milnacipran, both dual selective ser otonin-noradren- aline reuptake inhibitors may be helpful. Moclobemide and pirlindole, reve rsible inhibitors of monoamine oxidase A, also reduce pain. Function was not assessed, but side effects were low and non-serious. Anticonvulsants Gabapentin may be useful. There was a NNT of 5 to achieve 30% reduction in pain, and also help sleep and func- tioning. Tender points were not affected and it was gen er- ally well tolerated. Pregabalin also reduces pain (NNT 6 for more than 50% pain reducti on), but functioning was not assessed and this could be used if there are side effects with gabapentin. Pramipexole and tropisetron Pramipexole is a non-ergoline dopamine agonist shown to improve pain scores. Tropisetron, a 5-HT3 antagonist, also reduces pain scores with no effect on f unctioning. Glucocorticoids (GCs) GCs may help in the short-term, but can not be justi \201 ed given t he long-term potential side effects. Intravenous lignocaine Intravenous lignocaine may be effective in FMS, but no long-term stu dies have been done and there are signi \201 cant side effects, including some cardiovascu lar. Figure 17.2 FMS: The tender points FIBROMYALGIA SYNDROME 486 Psychological treatments Cognitive-behavioral therapy (CBT) CBT is likely to be of bene \201 t, although there is an absence of good quality evidence. Multi-method CBT may be more effective than targeted approaches. Multi-disciplinary pain management programs in either primary or secondary care are perhaps most effective. Results from the 1958 British Birth Cohort Study. Arth Rheum 2007; 56: 1669-1675. Allison TR, Symmons DPM, et al. Musculoskeletal pain is more gen- eralised among people fro m ethnic minorities than among white people in Greater Manchester. Ann Rheum Dis 2002; 61: 151 \200\2236. Arnold LM, Goldenberg DL, et al. Gabapentin in the treatment of \201 bromy algia: a randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum.2 007; 56: 1336 \200\22344. Arnold LM, Keck PE. Antidepressant treatment of \201 bromyalgia: a Relaxation Relaxation and education programs are less likely to induce improvement in pain, functioning, and mood unless combined with other modalities. meta-analysis and review. Psychosomatics 2000; 41: 104 \200\22313. Arnold LM, Lu Y, et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of \201 bromyalgia patients with or without major depressive disorder. Arthritis Rheum 2004; 50: 2974 \200\22384. Complementary therapies There is no good evidence to support any of the comple- mentary the rapies in patients with FMS. Nevertheless, some patients \201 nd complementary therapies helpful for their symptoms. Sadly, most patients who attend such therapies are not informed of potential side effects, the industry remains unregulated and there is uncertainty as to the long-term impact of their interventions. Arnold LM, Rosen A, et al. A randomized, double-blind, placebo- controlled trial of duloxet ine in the treatment of women with \201 bromyalgia with or without major depressive disor der. Pain 2005; 119: 5 \200\22315. Benjamin S, Morris S. The association between chronic widespread pain and mental disorder. A population-based study. Arth Rheum 2000; 53: 561 \200\2237. Carroll D, Seers K. Relaxation for the relief of chronic pain: a sys- tematic review. J Adv Nurs 1998; 27: 476 \200\22387. Prognosis and natural history Only 15% of patients who reported chronic widespread pain in a postal survey reported no pain when the survey was repeated after 7 years. Poorer prognos is was associ- ated with being >50 years old, reporting dry eyes or mouth, and daytime tire dness. Cowan D, Wilson-Barnet J, et al. A randomized, double-blind, placebo-controlled, cross-over pilot study to assess the effects of long-term opioid drug consumption and subsequent abst inence in chronic non-cancer pain patients receiving controlled-release morphine. Pain Med 2005; 6: 113 \200\22321. Crofford LJ, Pillemer SR, et al. Hypothalamic-pituitary-adrenal axis perturbations in patie nts with \201 bromyalgia. Arthritis Rheum 1994; 37: 1583 \200\22392. Current controversies The genetics of pain suggests that many hundreds of genes, if not tho usands are involved suggesting that mechanisms are even more complex than outlined here. Me chanistic- based approaches for helping patients with chronic pain appear some way off. Crofford LJ, Rowbotham MC, et al. Pregabalin for the treatment of \201 bromyalgia syndrome. Arthritis Rheum 2005; 52: 1264 \200\22373. Goldenberg DL. Fibromyalgia and related syndromes. In: Klippel JH, Dieppe PA (eds) Rheumato logy, 2nd edn. New York: Mosby, Section 4.15, 1 \200\22312. G tzsche PC. Reporting of outcomes in arthritis trials measured on ordinal and interval sc ales is inadequate in relation to meta- analysis. Ann Rheum Dis. 2001; 60: 349 \200\22352. Serotonergic descending pathways from the brainstem and midbrain that are thought to be \200\230raising \200\231 the spinal gate to prevent spinal cord sensitization may, in fact, be \200\230lower- ing \200\231 it and cause such central sensitization. Gracely R, Petzke F, et al. Functional magnetic resonance imaging evidence of augmented pai n processing in \201 bromyalgia. Arthritis Rheum. 2002; 46: 1333 \200\22343. Patients with chronic pain have a higher incidence of mortality although this may be accoun ted for by adjusting for smoking and obesity confounders. Hunt IM, Silman AJ, et al. The prevalence and associated features of chronic widespread pai n in the community using the \200\232Manchester de \201 nition of chronic widespread pain . Rheumatology 1999; 38: 275 \200\2239. Resources Guidelines Carville SF, Arendt-Nielsen A, et al. EULAR evidence based recommendat ions for the management of FMS. Ann Rheum Dis 2007. E-pub Oct 3. Jain AK, Carruthers BM, et al. Fibromyalgia syndrome: Canadian clinical working case de \201 nition, diagnostic and treatment protocols \200\223 a consensus document. J Musculo- skel Pain 2003;11: 3 \200 \223107. US-based National Guideline Clearing House, 2005. Available at: http://www.guideli ne.gov/summary/ summary.aspx?doc_id=7352 Kalso E, Streetcar r MR, et al. Systemic local anesthetic type drugs in chronic pain: a systematic review. Eur J Pain 1998; 2: 3 \200\22314. Main CJ, Waddell G. Behavioral responses to examination. A reap- praisal of the interpretat ion of \200\230nonorganic signs \200\231. Spine 1998; 23: 2367 \200\22371. McBeth J, MacFarlan GJ, et al. The association between tender points, psychological distres s, and adverse childhood experi- ences. A community-based study. Arthritis Rheum 1999; 42: 1397 \200\223 404. Papgeorgiou AC, Silman AJ, Macfarlance GJ. Chronic Widespread pain in the population: a sev en year follow-up study. Ann Rheum Dis; 2002; 61: 1071 \200\2234. Russell IJ, Orr MD, et al. Elevated cerebrospinal \202 uid levels of sub- stance P in pat ients with the \201 bromyalgia syndrome. Arthritis Rheum 1994; 37: 1593 \200\2231601. Patient organizations Fibromyalgia Association UK Helpine 0845 345 2322. Available at: www.fibromyalgia-associati onuk.org Arthritis Research Campaign. Available at: www.arc.org.uk See also www.ukfibromyal gia.com; www.myopain.org Tofferi JK, Jackson JL. Treatment of \201 bromyalgia with cyclobenz- aprine: a meta-analysis. Arthritis Rheum 2004; 51: 9 \200\22313. Wolfe F, Smythe Ha, et al. The ACR 1990 criteria for the classi \201 cation of \201 brom yalgia. Report of the Multicentre Criteria Committee. Arthritis Rheum 1990; 33: 160 \200 \22372. ICD-10 codes M79.0; M79.7 References Jones GT, Silman AJ, et al. Are common symptoms in childhood associated with chr onic widespread body pain in adulthood? This page intentionally left blank COMPLEX REGIONAL PAIN SYNDROME TYPE I 488 Complex regional pain syndrome type I Background As common as rheumatoid arthritis this condition affects peripheral and central nervous systems, and all of the tis- sues in the affected limb. The result is intractable p ain, de- formity, loss of function, and even amputation. Clinical features Key features in the history \200 \200 Rule out other causes of syndromes similar to CRPS. Assess for risk factors such as co-morb idities. A large sample of patients meeting IASP criteria for CRPS report: \200 \200 \200 \200 \200 \200 \200 History 1864 Silas Weir Mitchell described causalgia in wounded Color and temperature asymmetry (87%). Spontaneous burning or stinging pain (81%). Hyperaes thesia (61%). Sweating asymmetry (53%). Altered skin (24%). Altered nail growth (21%). Hair growth (18%). soldiers of the US Civil War. 1900 Sudek described localized osteoporosis in the condition. 1947 Evans coined the term \200\230re \202 ex sympathetic dystrophy \200\231. 1959 Curtis s and Kincaid described 3 cases of transient osteoporosis. Other features related to cortical plasticitv may be re- ported by the patient. These might include a change in the perception of their body schema: \200 1994 International Association for the Study of Pain (IASP) recommended the terms Complex r egional pain syndrome (CRPS) type I (no nerve damage) and CRPS type II (nerve damage).