Pope JE, Krizova A, Garq AX, Thiessen-Philbrook H, Ouimet JM. Campylobacter reactive arthri tis: a systematic review. Semin Arthritis Rheum 2007; Mar 12. Epub. Press N, Fyfe M, Bowie W, Kelly M. Clinical and microbiological follow-up of an outbreak of Yersinia pseudotuberculosis serotype Ib. Scand J Infect Dis 2001; 33: 523 \200\2236. Internet sites Webpage on Spondylarthritis American College of Rheu- matology. Available at : www.rheumatology.org/public/ factsheets/ Sieper J, Fendler C, Laitko S, et al. No bene \201 t of long-term cipro- \202 oxacin tre atment in patients with ReA and undifferentiated oligoarthritis: a 3-month multicenter doub le-blind, randomized placebo-controlled study. Arthritis Rheum 1999; 42: 1386 \200\22396. ICD10 codes M02.1 M02.3 Post-dysenteric arthropathy Reiter \200\231s disease ENTEROPATHIC SPONDYLARTHROPATHY 230 Enteropathic spondylarthropathy De \201 nition The commonest extra-intestinal manifestations of in \202 am- matory bowel disease (IBD) are musculoskeletal. The condition has been variably referred to as enteric a rthritis, IBD arthropathy, enteric SpA, Crohn \200\231s, or colitis-related arthritis. Key clinical features in ESpA Musculoskeletal \200 \200 \200 \200 \200 \200 \200 In \202 ammatory spinal pain. Alternating buttock pains. Enthesopathy. Anterior chest wall pain. Dactylitis. Peripheral arthritis/arthralgia. Sacroiliitis (most commonly unilateral) . Epidemiology The reports of SpA in IBD have varied owing to de \201 nition of SpA and IBD case ascertainment but have suggested: \200 \200 SpA prevalence of about 20% in IBD patients. Dactylitis, enthesitis, isolated (often asympt omatic) sacroiliitis, and other SpA like lesions all appear to occur in up to 35%. Peripher al arthritis prevalence 5 \200\22320% in IBD. Non musculoskeletal extra-intestinal \200 \200 \200 \200 \200 Aphthous stomatitis. Psoriasis. Erythema nodosum. Uveitis. Urethritis/cervicitis. Etiology and pathophysiology Genetic factors \200 Where AS is clearly de \201 ned in IBD patients, an association with HLA B27 (50 \200\2237 0% patients) clearly exists. HLA B27 frequency may not be increased, however, where there i s peripheral arthropathy alone. Mutations in the CARD15/NOD2 gene confers suscep- tibility for Crohn \200\231s disease, but not AS. Key features in history \200 In patients without a prior diagnosis of IBD, a history of abdominal pain, recurrent diarrh ea (especially at night), fever, malaise/fatigue, and passing blood per rectum is consisten t with a diagnosis of IBD. Aphthous ulceration and fatigue are early IBD features. As with other SpAs, a history of in \202 ammatory spinal pains, buttock or anterior chest wall pai ns or previous insertional tendonitis (enthesitis) might point toward ESpA in patients with established IBD. \200 Environment \200 Intestinal bacteria may have an important role in triggering EspA in Crohn \200\231s diseas e. Compromised iliocaecal integrity is associated with increased musculoskeletal symptoms i n IBD and it has been hypothesized that gut (?luminal/?entero-adhesive) bacteria may play a role in generating arthritis in IBD. Key features on examination Sacroiliitis stress tests (see USpA chapter), and checking for dactylitis and enthesitis are important aspects. Immunopathology \200 Co-morbidities All SpA related features can occur in association with IBD and ESpA (e.g. uv eitis, psoriasis). \200 The immune response in Crohn \200\231s disease suggests CD4 Th1 cells become activated agai nst normal gut luminal bacterial \202 ora. In Crohn \200\231s mucosa there is increased I l-12, Il-6, Il-15, Il-18, TNFA and IFNG with apoptosis-resistant Th1 cells, activated macro phages and granulomata. There \200\231s a paucity of data directly linking enteral immunpat hology with immune processes in joints/entheses in ESpA. IBD-related features can occur and include mouth ulcers, erythema nodosum, pyoderma gangren osum. Bone fragility/osteoporosis is a common complication of IBD. Fracture incidence in IB D is markedly higher than the general population. Hypovitaminosis-D is common in the genera l population, associated with GC use and can lead to myalgia, subopti- mal calcium absorpti on from the gut and secondary hyperparathyroidism (SHPT). Malabsorption in IBD can include folate, B12, and calcium de \201 ciency. The latter causes SHPT. Tissue pathophysiology \200 The peripheral arthritis in IBD has not been adequately characterized to know whether lesio ns are predominantly synovitic or enthesitic. Axial SpA features in ESpA appear similar to lesions seen in other SpAs though this assertion is based on imaging, rather than direct ti ssue studies. Investigations Laboratory The interpretation of acute phase response and anemia requires in terpretation of the activity of any IBD. ESpA symptoms can be prominent with relatively lit tle or absent acute phase response. Clinical features Key clinical features \200 Various subtypes of IBD-related arthropathy have been described. Incomplete case ascertainm ent, suboptimal clinical assessments and insuf \201 cient con \201 rmatory imaging have h ampered clinical pattern recognition studies. A careful review of studies suggests SpA feat ures are consistently conspicuous in IBD patients. USpA can precede a diagnosis of IBD in 5 0% patients. ESpA symptoms and disease activity do not always correlate well with the activ ity of the IBD. Tests to rule out malabsorption may be necessary (e.g. B12, folate). Detailed bone biochemi stry is sensible (calcium, phosphate, ALP, Vit-D, PTH, Mg). Persistent low Vit-D can cause non-speci \201 c musculoskeletal aches. Imaging \200 \200 Pelvis radiographs may show sacroiliitis, osteitis pubis or enthesopathy (although enthesop athic features in ESpA have not been highlighted in the literature). CHAPTER 7 The spondylarthropathies 231 Many radiographic features recognized in ESpA are common to all SpAs. CT may disclose sacro iliitis in about a third of IBD patients; almost twice the detection rate with radio- graph s. Secondary hypertrophic osteoarthropathy is recognized, although unusual in adults and ch ildren with IBD. Azathioprine, although used frequently for severe IBD, and cyclophosphamide, and occasional ly for severe IBD, are not recognized as effective for ESpA. Mesalazine has weak activity a gainst ESpA, and SZP is not as effective for IBD as mesalazine and has more side effects. I f ESpA is the main problem and the IBD in remis- sion, it is reasonable to swap mesalazine for SZP. Current controversies Diagnostic issues \200 Typical features on radiographs in patients with ESpA \200 \200 In early ESpA-sine-IBD, which logically would be classi \201 ed as USpA under ESSG criteri a, are there predictors of the development of IBD? Uncertainty still remains as to the prev alence of ESpA in IBD. For example, SIJ disease is often asymptomatic. What might the preva lence of isolated enthesitis be? The role of MR needs clari \201 cation in early diagnosis of ESpA \200\223 as is the case in other SpAs. General: enthesopathic erosions and enthesophytes. Pelvis: sacroiliitis, osteitis pubis, de structive hip arthritis (symmetric joint space loss, cystic lesions, but distinguish from o steonecrosis). Spine: vertebral squaring; marginal and para-marginal syndesmophytes; discit is. Peripheries: oligoarticular synovitis; radiographic features often lack speci \201 cit y. Management/treatment issues There are no RCTs of SZP or methotrexate in ESpA. The pharmacol ogical management of ESpA is necessarily complicated by the presence of IBD: \200 Discitis presents a diagnostic dilemma. Sterile discitis is a feature of SpAs; however, the re is increased risk of septic lesions in IBD. Imaging features might not always distinguis h. Biopsy should be considered. NSAIDs can aggravate IBD symptomatically or potentially disturb its control by medications; Mesalazine, often used by gastro-enterologists for the IBD, is not known to control muscul oskeletal features. An intention to use SZP or MTX for the latter requires close liaison wi th the gastroenterologist. The worth of MTX or SZP is tricky to evaluate where GCs might be frequently used for the IBD. GCs will provide a partial therapeutic effect on ESpA lesions . Differential diagnosis \200 Vertebral osteoporotic fracture. IBD patients previously treated with GCs are at high risk. In \202 ammatory-type chronic back pain symptoms may occur occasionally with other disord ers (e.g. discogenic pain, axial CPPDD disease, etc.). Hypovitaminosis-D/osteomalacia (GC-i nduced or con- stitutional) and calcium (poor absorption), can cause non-speci \201 c musc uloskeletal pains. Widespread pain in IBD has been reported to be due to \201 bromyalgia (FM), although studies have not assessed patients for enthesitis. A recent study found no e vidence for an association with FM. Resources Guidelines and patient information Webpage on SpA: American College of Rheumatolo gy. Available at: www.rheumatology.org/public/ factsheets/ ICD10 codes M07.4* M07.5* M46.9 Treatment Objectives of disease management Liaise closely with a gastroenterologist. Arthropathy in Crohn \200\231s disease Arthropathy in ulcerative colitis In \202 ammatory spondylopathy, unspeci \201 ed Control pain and consider modifying immunosuppres- sants if peripheral articular symptoms a re severe or dis- abling or there is erosive/deforming joint disease. References MacDonald TT, DiSabatino A, Gordon JN. Immunopathogenesis of Crohn \200\231s disease. J Paren Enter Nutr 2005; 29: S118 \200\22325. Physical therapies As with AS, ESpA patients with in \202 ammatory spinal pains may bene \201 t from back physiotherapy, which should be used judiciously where vertebral fracture h as occurred. Mielants H, Veys EM, Goemaere S, Cuvelier C, De Vos M. A prospective study of patients with SpA with special reference to HLA B27 and to gut histology. J Rheumatol 1993; 20: 1353 \200\2238. Orchard TR, Jewell DP. The importance of ileocaecal integrity in the arthritic complication s of Crohn \200\231s Disease. In \202 Bowel Dis 1999; 5: 92 \200\2237. Control of pain/in \202 ammation NSAID can aggravate IBD and worsen anemia. \200 Orchard TR, Wordsworth BP, Jewell DP. Peripheral arthropathies in in \202 ammatory bowel d isease: their articular distribution and natural history. Gut 1998; 42: 387 \200\22391. Joint \202 uid aspiration and GC injection is a relatively simple, effective, and overall relatively safe option. Serial pamidronate infusions may help ESpA-related spinal osteitis pain and can treat GC-induced osteoporosis. Ibandronate 3 mg iv every 3 months and zoledro nate 5 mg iv yearly are untested in this respect. Palm O, Moum B, Jahnsen J, Gran JT. Fibromyalgia and chronic widespread pain in patients wi th in \202 ammatory bowel disease: a cross-sectional population survey. J Rheumatol 2001; 28: 590 \200\2234. Palm O, Moum B, Ongre A, Gran JT. Prevalence of AS and other SpAs among patients with in \202 ammatory bowel disease: a popula- tion study. J Rheumatol 2002; 29: 511 \200\22315. Immunosupression In keeping with other SpAs the usual immunosupressants associated with ef \201 cacy in ESpA are more bene \201 cial for peripheral compared with axial symptoms. \200 Resnick D. Enteropathic arthropathies arthritis. In: Resnick D (ed.). Diagnosis of Bone and Joint Disorders, 4th edn. Philadelphia: WB Saunders Co, 2002, 1127 \200\22355. Salvarani C, Vlachonikolis IG, van der Heijde DM, et al. Musculoskeletal manifestations in a population-based cohort of in \202 ammatory bowel disease patients. Scand J Gastroentero l 2001; 36:1307 \200\22313. GCs, sulphasalazine (SZP), and methotrexate (MTX) may be ef \201 cacious. None have been t ested in a RCT. JUVENILE SPONDYLARTHROPATHY/ENTHESITIS-RELATED ARTHRITIS 232 Juvenile spondylarthropathy/enthesitis-related arthritis Spondylarthropathy (SpA) in children can exist as a discrete clinical entity (e.g. juvenile AS or arthritis associ- ated with psoriasis or in \202 ammatory bowel disease), but it is often not well differentiated. The term enthesitis related arthritis (ERA) was introduced in 1995 as a category in the ILAR classi \201 cation of childhood arthritis. It de \201 n es a type of JIA, which has variously been referred to previously as seronegative enthesiti s arthritis (SEA) syndrome or juve- nile spondylarthropathy (JSpA). JPsA is considered by many a separate entity to JSpA- related (ERA) conditions in children. This is not unlike the situation in adults where some believe PsA sits slightly uneasily w ithin the SpA spectrum of disease. The situation is clearly not clear in adults and childre n! However, it is accepted that enthesitis/enthesopathy is a lesion associ- ated with psori asis in adults. Whether the presence or absence of enthesitis is a discriminating feature b etween PsA in adults and children remains to be seen. There are criteria for diagnosing PsA in children, which retain some utility, though do not list enthesopathy among the criteria for diagnosis. De \201 nition and classi \201 cation criteria The previous classi \201 cations of JSpA can be encompassed under the new ERA sub-classi \201 cation of juvenile arthritis (ILAR cl assi \201 cation. See p. 352). Vancouver 1989 criteria for the diagnosis of JPsAa De \201 nite JPsA Revised ERA Classi \201 cation Criteria 2004 Arthritis or enthesitis + at least two of: Arthritisb with typical psoriatic rash or Arthritisb with 3 of these 4 minor criteria: Presence or history of sacroiliac tenderness or in \202 ammatory lumbosacral pain. HLA B27 positive. Family history of HLA B27-related disease. Acute anterior uveitis. Onset of arth ritis in a male after his 6th birthday. If any of the following are present then the child is excluded from the category of ERA: \200 \200 \200 \200 \200 \200 \200 Dactylitis. Nail pittingc or onycholysis. Psoriasis-like rash. Psoriasis family history (1s t/2nd degree relatives). Probable JPsA Arthritisb with 2 of the 4 minor criteria: Presence of IgM rheumatoid factor on 2 occasions at least 3 months apart. Presence of syste mic JIA. Psoriasis or history of psoriasis in child or \201 rst- degree relative. aCriteria need not be present simultaneously. bDe \201 ned as joint swelling of \211 2 of the following: limited range of motion of joints, pain on movement, or tenderness persisti ng for at least 6 weeks. cDe \201 ned as \211 2 pits on the \201 ngernails at any exami nation. \200 Epidemiology Data on more than 16 000 pediatric patients from two North American disease re gistries, suggested that of 41% who were registered as having musculoskeletal disease, a th ird (12% of total) had been diagnosed with a SpA. \200 Although the adult ESSG SpA classi \201 cation criteria have been applied to JSpA with a s ensitivity of about 75% and speci \201 city of over 90%, childhood SpA does not always \201 t adult disease classi \201 cation criteria. Enthesitis-related arthritis (ERA) may \200\230capture \200\231 for de \201 - nition the diagnosis of children with undifferentia ted and early forms of SpA and includes children who might pre- viously have been considere d to have SEA syndrome. The overlap in descriptions of classi \201 cation is illustrated b y JPsA, a heterogenous clinical entity. In adolescents JPsA has features typically associat ed with a SpA \200\223 male gen- der, axial skeleton involvement, HLA B27-associated. In y oung children, most affected are girls, there is an associa- tion with antinuclear antibody and asymptomatic uveitis. Juvenile AS (JAS) cannot be classi \201 ed with conventional adult AS criteria (axial dise ase appears late, reference ranges of metrology indices for age are not available and imagi ng is often imprecise). Many children with early JAS can be classi \201 ed under other JIA de \201 nitions. Based on the percentage of adults who had juvenile onset of adult AS it has been estimated JAS has a preva- lence of 12 \200\22333/100 000 in Caucasians. In other racial groups, with a higher prevalence of HLA B27, JAS may be present in up to 40 \200\223 150/100 000. JAS occurs in males > females (5:1 to 9:1) mainly late in childhood/adolescent years. Reactive arthritis as a distinct entity is recognized, par- ticularly sexually acqu ired reactive arthritis in teenagers, although no major prevalence estimates exist. SpA is the most common non-intestinal manifestation of in \202 ammatory bowel disease (IBD) in ch ildren (10 \200\22320%). Axial disease occurs only in about 25% of children with both IBD a nd musculoskeletal manifestations. As with adults, juvenile psoriatic arthropathy (JPsA) is a heterogenous entity. Using the 1989 Vancouver criteria for JPsA the prevalence is though t to be about 10 \200\22315/ 100 000 children. ILAR de \201 nitions of JPsA restrict the d iagnosis of PsA in childhood compared with Vancouver. The characteristics of JSpA (/ERA) \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Males > females (up to 9:1). Late onset age usually > 10 years old. Family history of SpA. Axial skeleton involvement \200\223 often absent at outset. Sacroiliitis. Arthritis of low er limb joints. Enthesitis \200\223 particularly around the knee and foot. Frequently HLA B27 positive. Acute uveitis. In \202 ammatory bowel disease. Preceding (few days to some w eeks) gut infection (Yersinia, Salmonella, Shigella, Campylobacter). Negative ANA and rheum atoid factor. CHAPTER 7 The spondylarthropathies 233 Etiology and pathophysiology Genetic factors The frequent \201 nding of SpAs in families suggests a genetic basis for the disease. The relationship between disease and HLA B27 is a s striking in children as it is in adults. \200 Erythema nodosum is associated with in \202 ammatory bowel disease and Yersinia infection. Detailed ophthalmic examination is important in all JIA and JSpA/ERA patients. Uveitis may be asympto- matic. Unlike in adults, uveitis is not speci \201 c for SpA in children. Unl ike in adults, children with JSpA/ERA have few signs of restricted spinal movement. No distinct B27 subtypes have been found to segregate with JAS, or other JSpA or juvenile o nset of adult SpA compared with adult disease. HLA DR8 is been linked with JAS \200\223 it has been found in 39% of AS patients with onset <16 years compared with 20% of those with adult-onset AS. The role of HLA B27 in pathophysiology is discussed in the chapter on ankyl osing spondylitis. Co-morbidities \200 Psoriasis, in \202 ammatory bowel disease, uveitis can be associated with any SpA. JSpA/ER A might be misdiagnosed as chronic pain syndrome. There may be variable and probably overal l suboptimal appreciation of the occurrence of enthesitis as a manifestation of JSpA/ERA in children. Arthropathy is the commonest extra-intestinal co- morbidity in in \202 ammatory bowel disease (20% children). Environmental \200 Preceding infection with Yersinia enterocolitica (serotypes 3 or 9 especially), Campylobact er jejuni, Salmonella typhimurium or enteriditis, and Shigella \202 exneri can cause reac tive arthritis in children, as well as adults. Chlamydia trachomatis as a cause of reactive arthritis in adolescents should not be overlooked. They may well be sexually active! It is possible many children classi \201 ed as having ERA may have reactive arthritis. There is some evidence that mycoplasma and ureaplasma infections can trigger HLA B27-related reacti ve arthritis in children and adolescents. Klebsiella has been linked to JAS as in adults. Investigations Laboratory \200 An elevated acute phase response can be detected, although it is often modest and, often in early disease, markers are normal. Anemia is usually mild, and if severe, underlying IBD s hould be suspected. HLA B27 is associated with JAS (the differentiated disease) in about 90 % patients. RF and ANA are negative. Serology for Yersinia, Salmonella, and Shigella, where antecedent gastrointestinal infection are suspected as a cause of reactive arthritis (JSpA /ERA or SEA syndrome also). Yersinia is seldom identified in stool cultures, but Salmonella and Shigella can be. \200 Clinical features Key features in history Though ERA can occur in younger children, typical ly in JAS symptoms develop after the age of 10 years and frequently there is a family histo ry of SpA. \200 Pain and stiffness of or around one or two often-lower limb joints can indicate JSpA/ERA. S ymptoms are unlikely to be speci \201 c for ERA, SEA, JAS or JPsA. In \202 ammatory back pain is often not a prominent part of early JAS or JSpAs. Heel pain is an important symptom and may indicate enthesitis, although this may occur in any JSpA. A family history of psor iasis in a close relative may be a relevant feature when considering a diagnosis of JPsA. R ecurrent abdominal pain and episodic diarrhea can denote associated in \202 ammatory bowel disease. Reactive arthritis (oligoarticular joint, back or enthesial pains) is often prece ded (days to weeks) by enteric symptoms \200\223 usually mild, but can be severe and cause acute abdomen in an older child. Lumbosacral and/or sacroiliac pain is present in about 25 % cases of post-Yersinia reactive arthritis. Imaging \200 Radiographs are seldom helpful in making a diagnosis in early ERA; nevertheless, it is impo rtant to document baseline presence/absence of erosions and spur forma- tion may be present . Chronic or severe enthesitis lesions show characteristic enthesial erosions, calci \201 cation, hyperostosis, acceler- ated growth, or premature epiphyseal closure. If there are s ymptoms or signs of SI joint involvement these should be imaged. MRI scans are preferred to avoid radiation to pelvis, and can be helpful, but care must be taken not to over-interpre t changes associ- ated with the normal metabolic activity of growing bones. Differential diagnosis The differential diagnosis is wide and general principles should be considered. \200 Key features on examination Enthesial tenderness perhaps with soft tissue swelling, particu larly of knee and foot structures, is the hallmark lesion in children with SpAs. \200 A working knowledge of JIA classi \201 cations and their overlap is required. Establishing the family history with regard to psoriasis is important in linking the arthritis to JSpA and differentiat- ing the condition from ERA (see above). Uveitis screening is relevant for all children with arthritis, whatever the likely diagnosis. Small joint and wrist disease may discriminate JPsA from other JIA subtypes. Look for lower limb joint synovitis, dactylitis of the toes, and irritable hips on passive joint movement s. (see Plate 21) If chronic or severe, enthesitis can lead to bony overgrowth and/or prema ture closure at epiphyses. Psoriasis is often absent in JPsA; may be nail pitting. Abdomina l tenderness may be non-speci \201 c, but in \202 am- matory bowel disease may need exclu ding. Treatment The management plan for children and adolescents with JSpA/ERA, should be multidi sciplinary and address the many facets of disease. \200 JUVENILE SPONDYLARTHROPATHY/ENTHESITIS-RELATED ARTHRITIS 234 Resources British Society for pediatric and Adolescent Rheumatol- ogy (BSPAR) www.bspar.org .uk for guidelines on medica- tion and eye screening in childhood arthritis. Multidisciplinary approach to managing JSpA: addressing the many patient needs (see also pp . 352 \200\223358) \200 \200 \200 \200 \200 \200 \200 Psychological impact of disease. Social impact of disease. Vocational aspirations. Occupati onal therapy bene \201 ts. Physiotherapy bene \201 ts. Judicious use of medications. Time ly intervention with surgery. Guidelines Pediatric Rheumatology European Society (PReS). For professionals. Available at: www.pres.org.uk Patient organizations/resources PRINTO. Resource for parents of children with rheumatic dis eases. Available at: www.printo.it/pediatric- rheumatology/. This is a useful site with inf ormation about various pediatric rheumatic diseases and their treatment, weblinks to simila r European organizations and individuals who can be contacted by parents of JSpA children. The mainstay of pharmacological treatment is NSAIDs and judicious use of intra-articular gl ucocorticoid injections. If arthritis/enthesitis persists then it would be reasonable to co nsider sulphasalazine (25 mg/kg increased to 50 mg/kg/day if tolerated). Methotrexate (10 \200\22320 mg/m2) would offer a second-line option for failure to improve on sulphasalazine . Glucocorticoids are used for severe enthesitis, in short courses for 4 \200\2236 weeks (o ral: 0.5 \200\2231 mg/kg/day). Occasional intravenous pulses of methylprednisolone (10 \200 \22330 mg/kg/ day) can be used instead. Large RCT trials of sulphasalazine or methotrexate in children with JSpA/ERA are lacking, however. There is no evidence that antibiotics signi \201 cantly affect the severity or course of reactive arthritis in children. There is no evidence that one NSAID is superior to another in treating JSpAs/ERA. Intra-articular or pe ri-enthesial glucocorticoid injections are used to treat individual joints. In young childr en a light general anesthetic is required (avoids distress, maintains trust, facilitates fu rther investigations/ treatment). Older children may tolerate joint injections using good l ocal anesthesia. Methotrexate is an obvious choice for controlling both the joint and skin disease of JPsA. ICD10 codes M08.1 M08.9 Juvenile AS Juvenile arthritis, unspeci \201 ed References Creemers MCW, Franssen MJ, van de Putte LB, Gribnau FW, van Riel PL. Methotrxate in severe ankylosing spondylitis: an open study. J Rheumatol 1995; 22: 1104 \200\2237. Gensler L, Davis JC. Recognition and treatment of juvenile-onset spondyloarthritis. Curr Opin Rheumatol 2006; 18: 507 \200\22311. Heumer C, Malleson PN, Cabral DA, Huemer M, Falger J, Zidek T, Petty RE. Patterns of joint involvement at onset differentiate oligoarticular juveile psoriatic arthritis from pauciart icular juveil rheumatoid arthritis. J Rheumatol 2002; 29: 1531 \200\2235. Pepmueller PH, Moore TL. Juvenile spondyloarthropathies. Curr Opin Rheumatol 2000; 12: 269 \200\22373. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumato logy classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rh eumatol 2004; 31: 390 \200\2232. Prieur AM. Spondylarthropathies in childhood. Ballieres Clin Rheumatol 1998; 12: 287 \200\223307. Rosenberg AM, Petty RE. Spondylarthropathies in children and adolescents. In: Calin A, Taur og JD (eds) The Spondylarthritides. Oxford: Oxford University Press, 1998, 113 \200\22327. Saxena N, Misra R, Aggarwal A. Is the enthesitis-related arthritis subtype of JIA a form of chronic reactive arthritis. Rheum (Ox) 2006; 45: 1129 \200\22332. Prognosis Identi \201 cation of factors that might dictate progression of undifferentiated JSpA/ERA or the condition diagnosed as SEA, to a differentiated SpA, is of great importanc e. The main dif \201 culty in identifying such factors, however, is that axial features ca n take many years to develop in juvenile disease. Long-term studies of JSpA/ERA are limited . \200 Southwood TR, Petty RE, Malleson PN, et al. Psoriatic arthritis in children. Arthritis Rheum 1989; 32: 1007 \200\22313. Suschke HJ. Die behandlung der juvenilen spondylarthritis umd der reactiven arthritis mit s ulfasalzin. Monats Kinderheilkunde 1992; 140: 658 \200\22360. Toll ML, Lio P, Sundel RP, Nigrovic PA. Comparison of Vancouver and ILAR classi \201 catio n criteria for juvenile psoriatic arthritis. Arthritis Rheum 2007; 59: 51 \200\2238. Persistent severe disease of at least 5 joints in the \201 rst year of disease is a risk factor for progression to AS. Early axial symptoms/lesions may de \201 ne a subset of chil - dren who progress to AS (or develop the differentiated form of it from the outset). Monit oring of ERA closely is warranted in HLA B27 positive children \200\223 long-term problems are more likely. Involvement of the hip joint in JAS before the age of 19 years was a sign i \201 cant predictor for the need of hip replacement in studies done many years ago. This under- scores the importance of screening for hip disease, and considering treatment with sulphasalazine or meth- otrexate in adolescents affected. Tse SM, Burgos-Vargas R, Laxer RM. Anti-tumor necrosis factor alpha blockade in the treatme nt of juveile spondylarthropathy. Arthritis Rheum 2005; 52: 2103 \200\2238. Vesikari T, Iso lauri E, Maki M. Clinical and laboratory features of Yersinia, Campylobacte r and Salmonella infections in children. Klin Padiatr 1985; 197: 25 \200\2239. This page intentionally left blank SAPHO (LE SYNDROME ACN \211, PUSTULOSE, HYPEROSTOSE, OST \211ITE) 236 SAPHO (Le Syndrome Acn , Pustulose, Hyperostose, Ost ite) De \201 nition A number of terms have been used to describe a spectrum of features that co nsistently appear together in patients with acne/skin pustulosis and painful osteopathy par ticularly of the anterior chest wall. The commonest terms used in the literature are SAPHO, Acquired Hyperostosis Syndrome, pustulotic arthro-osteitis and sternocostocla- vicular hyp erostosis. Almost 50 synonyms have been used in the literature. \200 Musculoskeletal lesions can occur before the skin lesions and, on the face of it, many lesi ons are similar to those seen in the SpA. Spondylodiscitis can be an associated lesion. Key features in the history \200 Patients often complain of recurrent pains of the anterior chest wall. There may be more pe rsistent pains associ- ated with obvious bony swelling. Pains are mainly axial. Synovitis o f peripheral joints and limb bony lesions have been described, although are less usual than axial lesions. Discogenic back pain can be associated. A history of an acneiform or pustul ar skin rash is typical, but not invariable. Patients may often have accumulated different diagnoses or explanations for their symptoms from doctors or other healthcare workers. A ch ronic pain somatype therefore might be present (e.g. pain amplification, frustration, fatig ue, disproportionate disability given an objective review of features, etc.). Some previously-de \201 ned conditions may be part of the SAPHO spectrum of disease (e.g. recurrent multifocal osteomyelitis). In some publications, \200\230Synovitis \200\231 has been substituted for \200\230Le Syndrome \200\231, although it is unclear how deliberate a change this was in the name or an \200\230upgrading \200\231 of the name in light of feat ures being increasingly recognized as part of the condition (following the early key French description (Chamot et al., 1987). The syndrome \200\231s original description can probabl y be credited to K hler (K hler et al., 1975). There is controversy whether SAPHO is part of the SpA group of conditions. There is reasonable evidence that enthesitis occurs and so me evidence of triggering bacteria, but no known association with HLA B27. \200 Key features on examination Musculoskeletal \200 Bony swelling around manubrium, anterior costal cartilages, and sternum (look for asymmetry ). Tenderness of bony swellings (above) and tenderness of other anterior chest wall structu res, such as over the costoclavicular ligament (?enthesitis). Bony swelling and overlying t enderness anywhere else particularly on axial skeletal structures. Features of spondylodisc itis: focal or general back stiffness/ poor mobility; increased focal spinal pain in forwar d \202 exion of segment notably. Classi \201 cation criteria There are no validated classi \201 cation criteria for SAPHO though diagnostic criteria were suggested in 1988 (Benhamou 1988). Epidemiology The condition could be rare, although mild disease and disease characterized b y musculoskeletal lesions (not skin) alone is probably under-recognized. Etiology and pathphysiology \200 Skin \200 Most cases and case series have been reported with prominent acne lesions or obvious (palmo plantar or psoriatic) pustulosis. Skin lesions may not be concordant with the manifestation or detection of musculoskeletal lesions. Hidradenitis may be an associated feature, but ha s not been a consistent part of all descriptions of the condi- tion in the literature. Atte mpts to link the condition aetiopathologically to just one or two proprionibacterium specie s (infections or skin lesion \200\230colonization \200\231) might be too restrictive. SAPHO has been linked to skin lesion infection with Propionibacterium acnes in immunocompet ant people. P. acnes, an anaerobe, has been cultured from intervertebral disc and sternal l esions. The immunopathology and tissue pathological changes in SAPHO are virtually unknown. The principle features of SAPHO syndrome \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Anterior chest wall pain. Osteitis. Enthesopathy. Pustular skin lesions. Acneiform skin les ions. Hydradenitis. Hyperostosis. Within costal cartilages. Ankylosing axial arthritis of a nterior chest wall. Spondylodiscitis. Synovitis. Investigations Laboratory \200 Laboratory investigations are invariably normal although modest increases in ESR, CRP, or i mmunoglobulins can occur. Systemic neutrophilia has been reported. There is no known associ ation with HLA B27, but genetic association studies in large well-de \201 ned disease popu la- tions have not been done. Imaging Scintigraphy \200 Clinical features \200 Typical patterns of abnormality have been shown using 99mTc-MDP scintigraphy. Intense trace r localizing to structures around the upper sternum, viewed also from posterior chest acqui sitions, discriminate abnormal scans from false positive images. The most convincing combination of features are pustulosis or acneiform skin rash (acne ful minans, acne conglobata, or hidradenitis suppurativa) with pains and hyperostosis of anteri or chest wall structures. CHAPTER 7 The spondylarthropathies 237 MR spine may highlight other SAPHO-associated osteitis lesions. See Figure 7.12. Typical tracer uptake in manubrium and anterior part of the \201 rst ribs is referred to as \200\230the bullhorn sign \200\231. This is thought to be relatively speci \201 c for SAPHO. Biopsy and histology \200 Biopsy of bony or spondylodiscitis lesions and culture of material can show P. acnes growth . Data is derived from a few case reports only. Features seen in osteomyelitis can be prese nt. In one case, epithe- liod granulomas were seen. Differential diagnosis \200 Psoriatic arthritis or chronic sarcoidosis where pains are diffuse and suggestive of enthes itis/osteitis or periostitis lesions. Osteomyelitis and malignancy where there is clear pai nful soft-tissue and bone swelling. Septic or SpA-associated spondylodiscitis where there i s discogenic in \202 ammation. Treatment \200 An explanation of the condition at the outset is excep- tionally important especially to th ose who have had chronic unexplained symptoms or manifold explanations/ diagnoses given for their plight. NSAIDs, glucocorticoids, and analgesics have been used empirically. Antibiot ic use, most notably doxycycline, azithromycin, and clindamycin, have been reported as effe ctive in a few cases treated over a number of months. Where there is osteitis, particularly if biopsy shows an excessive number of multinucleate osteoclasts or features of increased bone turnover, bisphosphonate treatment may be a logical choice. A trial of a potent oral o r iv aminobisphosphonate in patients, recruited on the basis of osteitis lesions detected r eliably with imaging, is probably warranted. Figure 7.11 99mTc-MDP abnormality in SAPHO showing high tracer uptake in manubrium and manu briosternal joint. Prognosis and natural history SAPHO tends to cause chronic recurrent musculoskeletal sympto ms. Descriptions of the condition in the long-term are not available. Reports suggest the c ondition can persist for >20 years and follow an unpredictable course. References Ballara SC, Siraj QH, Maini RN, Venables PJW. Susteained response to doxycycline therapy on 2 patients with SAPHO syndrome. Arthritis Rheum 1999; 42: 819 \200\22321. Benhamou CL, Chamot AM, Kahn MF. Synovitis-acne-pustulosis- hyperostosis-osteomyelitis synd rome (SAPHO): a new syndrome among the spondylarthropathies? Clin Exp Rheumatol 1988; 6: 10 9 \200\22312. Chamot AM, Benhamou CL, Kahn MF, Beraneck L, Kaplan G, Prost A. Le syndrome acn pustulose hyperostose ost ite (SAPHO). R sultats d \200\231une enqu te nationale. 85 observations . Rev Rheum 1987; 54: 187 \200\22396. Figure 7.12 MR thoracic spine in SAPHO. Spondylodiscitis at contiguous levels. Note osteiti s at manubriosternal joint. Radiographs and CT \200 Dihlman W, Dihlmann SW, Hering L. Acquired Hyperostosis Syndrome \200\223 AHYS \200\223 ( sternocostoclavicular hyperostosis, pus- tulotic arthro-osteitis, SAPHO-syndrome): Bone sci ntigraphy of the anterior chest wall. Clin Rheumatol 1997; 16: 13 \200\22324. Hyperostosis lesions are characterized by sclerosing bone remodeling and erosions. Radiogra phs can show abnormal cartilage ossi \201 cation (e.g. costoclavicular ligament and anteri or rib). CT may be useful to help discriminate hyperostotic SAPHO lesions from tumors and o steomyelitis. K hler H, Uehlinger E, Kutzner J, et al. Sterno-kosto-klavikul re yperostose, ein bisher nicht beschriebenes Kranksheitsbild. Dtsch med Wschr 1975; 100: 1519 \200\22323. MR \200 SAPHO spondylodiscitis is not easily discriminated from other non-septic causes of discitis with MR. This page intentionally left blank 239 Chapter 8 Autoimmune connective tissue diseases Systemic lupus erythematosus 240 Sj gren \200\231s syndrome 254 Systemic sclerosis 264 Ant iphospholipid syndrome 274 Polymyositis 282 Dermatomyositis 290 Juvenile dermatomyositis 29 8 Inclusion body myositis 302 Undifferentiated (autoimmune) connective tissue disease 306 M ixed connective tissue disease 307 Overlap syndromes 308 Eosinophilic fasciitis 310 SYSTEMIC LUPUS ERYTHEMATOSUS 240 Systemic lupus erythematosus De \201 nition Systemic lupus erythematosus (SLE) is a systemic autoim- mune disease, whic h is associated with a plethora of autoan- tibodies including characteristic anti-nuclear a ntibodies. Table 8.1 ACR 1997 Revised criteria for the classi \201 cation of SLE Criterion Comments Malar rash Classi \201 cation The clinical manifestations of SLE are diverse and a series of classi \201 cation criteria have been published by the ACR, most recently in 1997 (Table 8.1). Alt hough the classi \201 ca- tion criteria were not designed as diagnostic criteria, they are frequently applied in this way. SLE may be diagnosed if a patient has four or more criteri a, serially, or simultaneously, providing they cannot be attributed to an alternative diag- nosis. When considering a diagnosis of SLE, it is important to note that: \200 Discoid rash Photosensitivity Oral ulcers Arthritis Serositis Oral or nasopharyngeal NB must be objective synovitis Pleurisy (pleuritic rub/effusion) Pericarditis History of pericarditis New pleural thickening