Internet support Health protection agency center for infection control. Holborn,London. Ava ilable at: Erythema migrans Antibiotics should be initiated as soon as erythema migrans is diagnosed. The antibiotic of choice is doxycy- cline 200 mg daily for 14 \200\22321 days. http://www.hpa.org.uk/infections/about/ surveillance/surveillance_menu.htm. and www.cdc.gov/mmwR/review/mmwrhtml/mm5317a4.htm Arthritis and acrodermatitis Most patients will respond to oral antibiotics, although some will require antibiotics intravenously for up to 3 months to abolish joint symptoms. The be ne \201 t of doxycycline is that it also has a mild anti-in \202 ammatory effect, althoug h this should be borne in mind when planning antibiotic duration as it may mask ongoing joi nt symptoms. Acrodermatitis re- sponds well to oral antibiotics. Neurological involvement r equires intravenous antibiotic therapy. ICD-10 codes M01.2 Arthritis in Lyme disease References Blackwood T. The ubiquitous tick. Br Trav Health Ass J 2007; 10: 34. Luger SW, P aparone P, Wormser GP, et al. Comparison of cefurox- ime axetil and doxycycline in treatmen t of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents C hemother 1995; 39: 661 \200\2237. Neuroborelliosis 3 weeks of therapy is probably suf \201 cient in patients with neurologic al involvement. Oral therapy is adequate in facial palsy alone, although parenteral therapy is more appropri- ate in a patient with extensive disease. Mullegger RR. Dermatological manifestations of manifestations of Lyme borreliosis. Eur J Dermatol 2004; 14: 296 \200\223309. Schnarr S, Franz J, Krause A, Zeidler H. Lyme borreliosis. Best Pract Res Clin Rheumatol 2006; 20: 1099 \200\223118. Tonks, A. Lyme Wars. Br Med J 2007; 335: 910 \200\22312. Treatment resistant disease This needs to be distinguished from post-Lyme syndrome and cont inuing infection should be established by PCR VIRAL ARTHRITIS 468 Viral arthritis Arthralgia associated with viral infection is common and usually self-limiting over a perio d of weeks, although oc- casionally follows a more chronic course. Viral arthropathy is als o reported following vaccination. The pattern of joint involvement is usually a symmetrical polyarthropathy, with women more commonly affected than men or children. Permanent joint d amage is rare. Some viral infections are commonly associated with arthralgia, such as mumps or rubella, although it is less common in others, such as varicella or adenovirus. Virus i s seldom isolated from synovial \202 uid. IgG antibodies against B19 are within the range expected for age, and B19 DNA has been foun d within the tissues of patients with normal joints. Patients with acute parvovirus B19 inf ection can meet the criteria for rheumatoid arthritis, and may transiently become seroposit ive. B19 DNA has been isolated from synovial \202 uid and tissue from patients with rheum atoid arthritis, and those patients who express HLA-DR4 are more likely to develop chronic arthritis following parvo- virus infection. Investigations \200 Pathogenesis The pro-in \202 ammatory consequences of viral infection are complex and invo lve a number of different pathways. Different viruses modify or in \202 uence particular c ellular responses. The main effects of viral infection include: \200 Acute parvovirus B19 causes the presence of IgM anti- bodies and, later, IgG antibodies are detectable. PCR is useful in patients who are immunocompromised and unable to mount an ant iviral antibody response, but may be positive for over 12 months following infection making interpretation dif \201 cult. Target the cells of innate immunity, by infecting mono- cytes promoting pro-in \202 ammato ry cytokine secretion. Impairment of antigen presenting cell function, e.g. HIV, CMV, and E BV infection result in impaired B cell function. Induction of autoantibody production, e.g. EBV induced IgG production with cross-reactivity against lupus associ- ated autoantigens, and parvovirus B19 may induce anti- bodies against other cellular antigens. Induction of T cell immunity by depletion of thymic T cells, or modi \201 cation of autoreactive T cell f unction, a mechanism also implicated in the pathogenesis of autoimmune diseases such as rhe umatoid arthritis. Directly damage synovial cells, e.g. EBV, HTLV-1, rubella, and Ross Rive r virus may directly infect synovial cells, and with an increased expression of double stra nded RNA which is arthritogenic. Parvovirus B19, an extracel- lular virus, results in immun e complex formation and deposition within the joint resulting in an in \202 ammatory respo nse and antibody formation. Treatment Symptom relief is the mainstay of therapy, with either simple analgesics or non-s teroidal anti-in \202 ammatory drugs. There is no vaccine currently available. Alphaviral infections There are 26 viruses in the genus Alphavirus. These are spherical vir uses that contain an RNA-containing nuceleo- capsid surrounded by a lipid layer. Transmissi on is cyclical and occurs between arthropods (normally mosquitos) and mammalian hosts, such as humans. Infection rates rise when mosquitos are prevalent, usually in the monsoon sea- son. Recognizing a history of travel in patients with alpha- virus infection is paramount t o making the diagnosis. Ross River virus causes more than 8000 cases per annum in Australia and the West Paci \201 c. Barmah Forest virus is less prevalent in Australia and causes m yalgias, and occasionally arthritis. Ockelbo and Pogosta are prevalent in Scandana- via. Ch ikungunya is found mostly in Africa and Asia. Human parvovirus B19 Human parvovirus B19 is one of the Erythrovirus genus and is a small D NA virus. Transmission is usually via inhala- tion, but can occur via blood products or ver tically from mother to fetus. Infection is often seen in early spring. Clinical features \200 The most common symptoms include rash, fever, arthral- gia and systemic upset after an incu bation period of up to 10 days. Subclinical infections are thought to be common and childre n are often spared joint involvement. The joint involvement ranges from a mild migratory po l- yarthralgia to a systemic synovitis involving the small joints primarily. Myalgia may be prominent. Clinical features \200 \200 The majority of infections are subclinical. Most present 2 weeks after infection with fever and ery- thema infectiosum or a slapped cheek appearance. 50% of adults and 10% of child ren are reported to have a symmetrical small joint and knee arthralgia. Joint symptoms are commoner in women than men. Resolution of arthralgia within 3 weeks is usual, although 1 in 5 women have more prolonged symptoms. An erosive arthropathy is reported, but is rare. New presentations and \202 ares of lupus have been linked with infection due to parvovirus B 19. Non-rheumatological manifestations include hydrops foetalis and fetal death. Hematologi cal, neurological, and cardiac sequelae of infection have been reported. Diagnosis \200 \200 The history of travel is particularly important in patients with rash, fever, and arthralgi a/myalgia who have trav- elled to endemic areas. Paired sera are needed, as IgM speci \201 c for alphavirus may persist for years, and should be collected around 10 days apart. A 4- fold increase in the titre is usually characteristic. \200 Treatment of alphavirus Treatment is mainly supportive and consists of simple anal- gesia, non-steroidal anti-in \202 ammatory drugs, and mobiliza- tion as joint symptoms settle. The association of human parvovirus B19 and rheumatoid arthritis \200 Although an association between parvovirus B19 and rheumatoid arthritis has been postulated , the link remains tenuous. CHAPTER 16 Musculoskeletal infection 469 Mumps Mumps is more likely to affect men, with an incidence of 0.44%. paired sera collected 2 weeks apart is also indicative of recent infection. Treatment Vaccination programs are well established in the UK, and are now being introduced in a number of developing countries with a signi \201 cant reduction in rubella infection s and congenital rubella syndrome. However, one disadvan- tage of the vaccination program i s the frequency of self- limiting arthralgia, particularly in women. This is normally short lived and responds well to non-steroidal anti-in \202 am- matory drugs. Clinical features \200 The joint pain may start just before the onset of parotitis, but may be delayed for up to 1 5 days. Both large and small joints are affected. Arthralgia is the commonest presentation, although synovitis can occur. \200 Treatment Symptoms are usually self-limiting after a fortnight, but can persist for up to 3 months. Human immunode \201 ciency virus Human Immunode \201 ciency Virus (HIV) was \201 rst is olated in 1983, but has since caused a pandemic and has had particu- larly devastating cons equences in developing countries, such as Africa. It is now estimated that over 40 million people are infected worldwide and more than 3 million have died of AIDS. In the UK, at the end of 2006, 73 000 people were estimated to infected with HIV, and one-third were esti- ma ted to be unaware of their infection. In 2007, 6393 new cases were reported. Effective anti viral treatments, called HAART (highly active antiretroviral treatment) have pro- longed li fe, but have also resulted in a spectrum of rheuma- tological and autoimmune manifestations of HIV infection. Hepatitis B \200 Up to 20% of patients infected with hepatitis B report symptoms of arthritis, often with ur ticaria, between 2 days and 6 weeks before the onset of jaundice. The symptoms usually sett le spontaneously before or coinciding with the onset of jaundice. The small joints are most commonly affected, although knee and ankles involvement is recognized. Effusions are a rar e \201 nding. Hepatitis C Infection with this agent is only rarely associated with joint symptoms, unless associated with a cryoglobulinaemia. Transmission \200 Sexual contact is the commonest route of transmission and rectal intercourse, the presence of very early or advanced infection, concurrent genital ulcers or the presence of other sex ually transmitted disease make transmission more likely. Blood or blood product infusion is now a much less likely source of infection, since heat treatment and HIV testing is routin e. Intravenous drug abuse and shared needles carries sig- ni \201 cant risks of HIV transm ission. Rising HIV transmission rates were originally through homosexual intercourse and vi a blood products, although since 1999 heterosexual transmission has taken over as the main cause of rising HIV prevalence. Vertical transmission is the commonest route of infec- tion in children worldwide, although in the UK the intro- duction of HIV testing in pregnant wo men has diminished this route of transmission. Human T-lymphotropic virus type 1 A proliferative synovitis may occur in people infected wi th human T-lymphotropic virus type 1, which usually results in a chronic oligoarthritis. La rge joints are predominantly af- fected, and atypical lymphocytes are often found in the sy novial \202 uid. Rubella arthritis Rubella is a genus of the Togaviridae family of viruses. It has a single- stranded RNA and is a member of the Rubivirus subfamily. Transmission is by the airborne ro ute, but verti- cal transmission from mother to fetus is also possible. Clinical features \200 The incubation period is 1 \200\2232 weeks, and presents with lymphadenoapathy, followed by a rash 6 days later. Complications of rubella infection include encephalopa- thy, Guillain \200\223Barre syndrome, and rarely hematological abnormalities, such as thrombocytopenia a nd haemo- lytic anemia. 50% of adult women report joint symptoms, but this is less common i n girls or males, and usually follow the appearance of the rash. Joint symptoms are typical ly a symmetrical small joint polyarthritis, which may progress to larger weight bearing joi nts. The natural history is of a self-limiting illness, which resolves within a month. Howe ver, a more chronic course has been reported in some and following vacci- nation. Rubella i nfection in the fetus is particularly signi \201 cant in the \201 rst trimester of pregn ancy resulting in congenital rubella syndrome, characterized by congenital malfor- mation o f the nervous system, cardiac abnormalities, and ocular and auditory involvement. Pathogenesis \200 \200 HIV is a lentivirus from the family of retroviruses. The virus attaches to host cells by th e membrane pro- tein CD4 receptor on helper T lymphocytes, macro- phages and other antigen presenting cells. As viral replication occurs, signi \201 cant destruction of CD4 lymphocy tes occurs. Quantitative PCR is the most commonly available tech- nique for quantifying vir al load, which is usually higher during seroconversion, early on in infection, and also in late disease. Some 4 \200\2236 months after infection, control of viral replica- tion occur s and the viral load plateaus. The level of this plateau varies from individual to individu al and is called the set point . Those individuals with a lower set level are more likely to progress slowly towards AIDS de \201 n- ing illness than those with a higher set point. The set point rises slowly as infection progresses and during intercurrent illnesses. Diagnosis The most reliable way of con \201 rming infection is the detec- tion of IgM anti bodies to rubella. A rise in the IgM titre in VIRAL ARTHRITIS 470 Glucocorticoids normally result in a rapid lowering of CK and an improvement in symptoms in HIV associated poly- myositis. Immunsuppression with methotrexte and azathi- oprine has be en successful. Prognosis of HIV polymyositis is in general good. Pyomyositis is usually due to Staph. aureus and is rarely seen in the UK Clinical features \200 A severe decline in the number of CD4+ helper T lym- phocytes occurs during HIV infection a nd, as a result, cell-mediated immunity becomes signi \201 cantly impaired and results in opportunistic infection and malignancy. Hypergammaglobulinaemia occurs and is associated wi th the development of a number of different autoanti- bodies with clinical consequences, id iopathic cytopenias and severe drug allergies. Diffuse in \201 ltrative lymphocytosis syndrome (DILS) This is characterized by salivary g land involvement, with or without sicca symptoms and an associated lymphocytosis. DILS is e stimated to occur in 3 \200\2238% of HIV positive patients in the period before HAART was d eveloped. Biopsies re- veal a focal sialadenitis similar to that seen in Sjogren \200\231s syndrome, although there is less destruction in HIV associ- ated disease. Other manifestati ons of DILS include lym- phocytic interstitial pneumonitis, VII cranial nerve palsy, periph eral neuropathy and lymphoma. It is reported that those patients that develop DILS as a man ifestation of their HIV infection have a better survival and prognosis than other patients with HIV. Natural history Following infection there is an asymptomatic period of 2 \200\2234 weeks, w hich is then followed by a seroconversion illness, consisting of a 1 \200\2232-week self-li miting illness comprising mild glandular fever-like symptoms, with a sore throat, fever, ly mphadenopahy, and a non-itchy maculopapular rash. A period of latency then ensues and is of varying length, but is prolonged with the introduction of HAART. Finally, there is progres sion to AIDS, and opportunistic and life-threatening infection. Treatment Symptomatic treatment includes arti \201 cial tears and saliva. HAART is effecti ve at reducing the salivary gland swelling, and some of the extra-glandular features of DIL S, such as peripheral neuropathy. However, there maybe a role for prednisolone in a dose of 30 \200\22340 mg daily in those cases which are resistant. Rheumatological manifestations Arthralgia Arthralgia is reported in 5% of patients with HIV and can be disabling. Most do not progress to signi \201 cant arthritis. Treatment is wit h simple analgesia. Painful articular syndrome This is reported when HIV was \201 rst recognized, but is much less common now. Presentation is with self-limiting bone pain, but with no abnormalities o n examination. Treatment is with analgesia. Vasculitis associated with HIV A wide range of vasculitides have been reported in patients with HIV, including polyarteritis nodosa, Henoch \200\223Schon- lein purpura, Behcet \200 \231s disease, and hypersensitivity vasculi- tis. Treatment of HIV vasculitis is normally r esponsive to high dose glucocorticoids, although cytotoxics have a role in resistant diseas e. HIV associated arthritis \200 Arthritis associated with HIV infection is usually self-lim- iting (within 6 weeks) and pre sents with an oligoarticular arthritis, often involving weight-bearing joints, and with no long-term sequelae. A more chronic course is also recognized, resembling a seronegative pol yarthritis, often with entheitis and with progressive joint space narrowing on plain radiog raphs. Mucocutaneous involvement include keratoderma blen- orrhagicum and circinate balanit is (see Plate 10). Urethritis is also a feature. Axial involvement and uveitis are much les s common. Over 80% of patient with HIV and this pattern of involve- ment are HLA B27 positi ve. Treatment success is reported with sulphasalazine and hydroxychloroquine in more severe cases. Caution should be used with methotrexate and there is emerging evidence for success with anti-TNFA therapy. Autoantibody formation in HIV Rheumatoid factor and antinuclear antibodies are found in up to 17% of patients with HIV. IgG anticardiolipin antibod- ies are found in 95% of patients with AIDS and 20 \200\22330 of patients with HIV overall. They are probably of little clini cal signi \201 cance. Cryoglobulins (usually in association with Hepatitis C) and ANCA hav e also been reported. Effects of HAART on musculoskeletal system Symptoms include: \200 \200 \200 \200 \200 \200 \200 Zydovudine myopathy. Zydovudine rhabdomyloysis. Adhesive capsulitis. Duprytrens contracture . Tenosynovitis. Avascular necrosis (hyperlipdaemia, high dose glucocor- ticoids, APLS). Psoriasis and psoriatic arthritis Psorasis in HIV is often gutate in appearance and may be very extensive. The psoriatic rash in HIV infection often coincides with the point in disea se progression where op- portunistic infection starts to emerge. Success in treating the sk in disease is reported with HAART, as well as with ciclosporin, methotrexate, and etanercep t, although close monitoring of all these agents is advised. Resources Support groups www.hiv-aids-carers.org.uk www.dhiverse.org.uk/localsupport.htm ICD-10 codes B20 \200\223B24 Undifferentiated spondyloarthritis Enthesopathy without joint involvement is common, and th erapeutic success is reported with NSAIDs and sul- phasalazine. Success is also reported wi th HAART. References Chantler JK, Ford DK, Tingle AJ. Persistent rubella infection and rubella-associated arthritis. Lancet 1982; 1: 1323 \200\2235. HIV-associated muscle disease Myalgia, \201 bromyalgia, asymptomatic elevation in CK, pol y- myositis, and inclusion body myositis are recognized. Dalakis MC, Pereshkpour GH, Gravell M, Sever JL. Polymyositis associated with the AIDS retr ovirus. J Am Med Ass 1986; 256: 2381 \200\2233. CHAPTER 16 Musculoskeletal infection 471 long term follow up. A retrospective study of 54 patients. Clin Exp Rheumatol 1998; 16: 576 \200\2238. Poole BD, Sco \201 eld RH, Harley JB, James JA. Epstein \200\223Barr virus and molecular m imicry in systemic lupus erythematosis. Autoimmunity 2006; 39: 63 \200\22370. White DG, Mortimer PP, Blake DR, et al. Human parvovirus arthropathy. Lancet 1985; 1: 419 \200\22321. Schattner A. Consequences or coincidence? The occurrence, pathogenesis and signi \201 canc e of autoimmune manifestations after viral vaccines. Vaccine 2005; 23: 3876 \200\22386. Winchester R, Bernstein DH, Fischer HD, et al. The co-occurrence of Reiter \200\231s syndro me and acquired immunode \201 ciency. Annl Intern Med 1987; 106: 19 \200\22326. Speyer I, Breedveld FC, Dijkmans BAC. Human parvovirus B19 infection is not followed by in \202 ammatory joint disease during MYCOBACTERIAL INFECTION 472 Mycobacterial infection Tuberculosis Prevalence Approximately 80% of new cases of mycobacterium tuber- culosis (MTB ) occur in developing regions, such as sub- Saharan Africa and Asia. This may, in part, be related to the rising prevalence of HIV infection. In the UK, 44% of all cases are in Londo n, with the highest rates around 40 per 100 000 of the population, similar to those in some devel- oping countries. Emerging multi-drug resistant MTB is an increasing concern and is a worldwide issue. Extra-pulmo- nary MTB is also increasing, partly in patients with HIV, b ut also in patients who are immunosuppressed. are rare. A high index of suspicion is necessary to make the diagnosis. Tuberculous osteomyelitis Osteomyelitis due to mycobacterium accounts for 2 \200\2233% of m usculoskeletal infection. The short bones, such as meta- carpal, metatarsals, and phalanges are common involved. Onset is insidious with involvement of the diaphysis, which causes a fusiform, tender swelling. There may be abscess formation. The radiological appearances eve ntually con- \201 rm enlargement of the shaft of the bone due to new sub- periosteal bone formation. Prognosis is good as infection responds well to anti-tuberculous therapy. Classi \201 cation Musculoskeletal MTB is classi \201 ed as \200 \200 \200 \200 Pott \200\231s disease of the spine Tuberculous spondylitis was originally described by Per - cival Pott, a London surgeon in the 18th century. Infection may affect any part of the sp ine, but most commonly in- volves the thoracic spine, and may involve both vertebrae and in tervertebral disc (as demonstrated in Figure 16.2). Presenting symptoms include back pain, with systemic symptoms of fever, weight loss, and anorexia. Vertebral col- lapse causes def ormity and kyphosis. Neurological involve- ment may present with sensory or motor symptoms, or paraplegia due to spinal cord compression by the spinal abscess or vertebral collapse. Treatment with antitubercu- lous drugs is central, and surgical options include debride- me nt and drainage of the abscess and spinal stabilization. Spinal. Arthritis with synovial disease. Osteomyelitis. Soft tissue disease. Etiology \200 Mycobacterium tuberculosis is almost always the causa- tive agent in tuberculous infection. Atypical mycobacte- rial infection is rare. Primary MTB infection is transmitted via inhal ation of droplet nuclei released by the infected host on coughing, sneezing, or speaking. L ungs are therefore usually the site of primary infection with other sites more rarely invol ved. The endogenous host immunity in \202 uences the risk of infection. Mycobacteria that reach the lungs are phago- cytosed by macrophages within the alveolar tissue, resulting in release of a number of different interferons and cytokines, which up-regulate the innate im mune sys- tem. Intracellular growth of those bacteria that survive phagocytosis results in rupture of the macrophage with release into the blood and haematogenous spread to distant t issues. Granuloma formation occurs as a result of macrophage recruitment, which forms a Gho n focus, an important step in the development of immunity. It is estimated that 10% of infe cted individuals will develop active MTB eventually. The term primary MTB is used to descri be clinical infec- tion directly following exposure to MTB. Secondary MTB is the term used to describe infection within 2 years of that original exposure due to reactivation on a tub erculous focus. In joint and bone MTB, the infection is almost always secondary to haematog enous spread although rarely spread from an osteomyelitic focus may occur. Reactive arthritis (Poncet \200\231s disease) Poncet \200\231s disease is de \201 ned as a n aseptic polyarthritis as- sociated with extrapulmonary disease. The typical picture is of a large joint arthritis primarily affecting children or young adults, associated with syst emic features, often with effusion in the joints. Panniculitis associated with MTB The commonest manifestation of this is erythema nodo- sum. Erythema induratum is a form of lobular panniculitis associated with vasculitis. Response to anti-tuberculous therapy is good. Atypical mycobacterium Infection due to atypical mycobacteria is rare and is more likely to cause soft tissue than bone infection. M. kansaii infection is the commonest, although inf ection due to M. xenopi, M. marinum, M. avium intracellulare, M. chelonei, and M. fortuitum is reported. Investigation of mycobacterium tuberculosis Typically, an acute phase response in seen, alt hough this is a non-speci \201 c test. Synovial microscopy (20 \200\22340% yield), and cul ture (yield of 80%) should be undertaken, and if necessary, synovial biopsy (yield of 90%). The tuberculin skin test is useful in patients who have not had previous exposure to MTB o r had a previous BCG (Bacille Calmette \200\223Guerin) vaccination. Immunocompromise, how- ever, results in a high rate of false negative tests. A new commercial enzyme-linked immuno spot assay (T spot MTB) detects gamma interferon-producing T cells and is sensitive (sensit ivity of 97.2%) in detecting patients with active or latent MTB. Pathology The synovitis resulting from infection causes joint swelling, granulation tissue formation, and pannus, which in turn causes destruction of bone by eroding cartilage and su b- chondral bone. Necrosis, cold abscess formation, and \201 stu- lae may then result. Th is follows a much more indolent course than pyogenic infection. Tuberculous arthritis 85% of MTB arthritis presents with chronic monoarthritis, usually inv olving the hip or knee. However, unilateral sac- roiliac, shoulder, elbow, ankle, carpal, a nd tarsal involve- ment are reported. Oligo- or polyarticular presentations Imaging Juxta-articular osteoporosis, peripheral erosions, and grad- ual joint space loss a re the typical appearances seen on plain radiographs, and are termed Phemister \200\231s tr iad. CHAPTER 16 Musculoskeletal infection 473 for multi-drug resistance. Monitoring of liver function tests is important as transaminases may rise, and a level 5 \200\2236 times baseline is an indication for withdrawal of therap y and then gradual reintroduction when the liver function test have returned to normal. Avo idance of alcohol and other hepatotoxic drugs is recommended. Active liver disease preclude s use of iso- niazid and rifampicin. Pyrazinamide may precipitate attacks of gout. Rifampic in can cause orange discoloura- tion of urine and tears, so patients should be warned about this. A high success rate is achieved in treating osteoarticular MTB with multi-drug regim ens. The role of surgery Surgery may be required in speci \201 c circumstances: \200 \200 \200 \200 Synovial tissue biopsy to aid diagnosis. Joint lavage if there is thick purulent effusion. Drainage of cold abscesses. Surgical correction of deformity. Prognosis There is usually resolution of symptoms in those patients with musculoskeletal in fection who have good compliance with antituberculous therapy. Leprosy Mycobacterium leprae causes a spectrum of disease, pos- sibly in \202 uenced by ho st immunity, with the extremes of the clinical spectrum de \201 ned as: \200 Tuberculous disease: characterized by hypopigmented, desensitized skin. Lepromatous disease : characterized by severe, and often painful damage to nerves and other organs. In tubercul ous leprosy, characteristic granulomas are found at involved sites, with only a few bacilli demonstrated on biopsy. In lepromatous disease, infection results in car- tilage destructi on in the nose, ears, and larynx with large numbers of bacilli seen histologically. The ter m borderline leprosy is reserved for the majority of patients who lie between these two ext remes. Musculoskeletal manifestations of leprosy \200 \200 \200 \200 Neuropathic joints. Bacterial sepsis. Acute polyarthritis (associated with lepra reactions) . Chronic/subacute symmetrical polyarthritis, either as a result of direct infection or an autoimmune reaction. Erosions have been reported as has treatment success with sulphasalazi ne and hydroxychloroquine. Sacroiliitis and tenosynovitis are also reported. Figure 16.2 This is a post-contrast coronal T1 fat saturated MR showing bilateral psoas col lections and the collapsed L4 vertebra. The lateral view demonstrates the extension of the abscess posteriorly into the epidural space. Treatment \200 Early diagnosis and full assessment of the patient improves the prognosis. Multidrug regime ns are mandatory, partly because of drug resistance and secondly because of the different g rowth patterns of the bacilli. For example, some multiply rapidly and are vulnerable to par ticular anti-tuberculous therapy, and other are much slower and therefore respond to differ ent agents. There may be an increase in ef \201 cacy using different agents together, so t hat treatment regimes can be shortened to 6 \200\2239 months from the original 12 \200\2232 4-month treatment regimes. Combinations of antituberculous therapy include 3 or 4 agents fr om isoniazide, rifampicin, pyrazinamide, ethambutol, and streptomycin. Monitoring for compl iance and side effects is central to treatment. Poor compliance may in part be responsible Treatment Treatment of leprosy involves combination therapy includ- ing dapsone, rifampicin , and clofazimine. Lepra reactions (response to treatment) involve pain and swelling at the site of infection, especially in skin, nerves, eyes, and ears. Neuropathic deterioration i s often very marked. Leprosy is characterized by the response to treatment which can be div ided into two patterns of lepra reaction. Type 1 There is either a downgrading to tuberculous disease or up grading to lepromatous di sease in those patients with borderline leprosy, in both clinical and immunological terms. MYCOBACTERIAL INFECTION 474 Type 2 An immune complex syndrome, erythema nodosum lepro- sum, develops in patients with l epromatous or borderline lepromatous disease. ICD-10 codes M01.1, M49.0 References Meier T, Eulenbruch HP, Wrighton-Smith P, et al. Sensitivity of a new commercial enzyme-linked immunospot assay (T spot TB) for diagnosis of tuberculosis in clinical pract ice. Eur J Clin Microbiol Infect Dis 2005; 24: 529 \200\22336. Resources Internet support www.dh.gov.uk/en/Publicationsandstatistics/ Publications/Publica tionsPolicyandGuidance/DH_ 075621 This page intentionally left blank FUNGAL INFECTION 476 Fungal infection Sporotrichosis \200 Musculoskeletal infection due to fungal infection is rare and dif \201 cult to diagnose. T he majority occur mainly in the tropics and are rare in Europe. The course tends to be slow and prolonged, with skin and lung involvement. Sporothrix schenkii, the dimporphic fungus implicated in infection, is found in soil and de caying vegetation. This is the most common subcutaneous infection in South Africa and Mexic o. A monoarthritis occurs if infection involves lymph nodes. Disseminated infection occurs in the immunocompro- mised patient. Diagnosis is made histologically. Treatment is with amp hotericin B combined with keta- conazole. Histoplasmosis \200 Histoplasmosis capsulatum is endemic in Ohio and Mississippi in the USA, and is also found in Central and West Africa. The African species has larger spores than that found in the US A. Infection is caught by the inhalation of spores, which are found in soil. Those individu als particularly at risk of developing pul- monary histoplasmosis are those with underlying lung disease and those who are immunocompromised. Lung involvement, and lymphoreticular an d bone marrow involvement then occurs. Presentation is often a \202 itting polyarthralgia or polyar- thritis with erythema nodosum. Osteomyelitis and joint infection are rare in th e USA, but reported in 50% of African infections. Vertebral involvement may lead to spinal cord compres- sion and paraplegia. The differential diagnosis includes tuberculosis or, if widespread, sickle-cell osteomyelitis. Diagnosis is made on histology, which con \201 rms giant cell granulomas containing yeast cells. Treatment is with amphotericin B and \202 u conazole, or itraconozole. \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.