82 CASE HISTORIES IN RHEUMATOLOGY Stroke Study demonstrated no difference in the risk of thrombotic events in patients treate d with warfarin and aspirin, and no difference in the risk of bleeding for patients with or without LA or aCL. Patients with a single event may be treated with aspirin 325 mg daily o r moderate-intensity warfarin (INR 1.4 \200\2232.8). Women with APS and a history of two or more early pregnancy losses or one or more late preg nancy loss with no prior history of thrombosis should have com- bination aspirin and hepari n during pregnancy. Aspirin should be started with attempted conception and heparin when a viable intra-uterine pregnancy is documented and continued until late in the third trimeste r. This case was initially treated with aspirin 75 mg and carbamazepine, and her chorea slowly resolved. Following a further event and MRI evidence of a high signal lesion, likely to be due to ischaemia, indefinite anticoagulation with warfarin was commenced with a target INR of 2.0 \200\2233.0. Her SLE was treated with azathioprine and hydroxychloroquine, with res olution of her thrombocytopenia and anemia. She will need advice to reduce her risks of thr omboembolic disease including discussion of contraception, smoking, and weight gain. She sh ould be aware of the risks of warfarin including interaction with other drugs such as alcoh ol. She should avoid the estrogen-containing combined oral contraceptive pill, but it shoul d be safe for her to use the progesterone-only pill. She will need counseling about the inc reased risk of thrombosis in pregnancy. In view of her mitral valve lesions, she was advise d to have prophylaxis for endocarditis. Further reading APASS Writing Committee ( 2004 ). Antiphospholipid antibodies and subsequent thrombo- occlusive events in patients with ischaemic stroke. JAMA ; 291 : 576 \200\223 84. Buller HR , Agnelli G , Hull RD , Hyers TM , Prins MH, Raskob GE ( 2004 ). Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic an d Thrombolytic Therapy . Chest ; 126 ( 3 Suppl): 401S \200\22328S . Cervera R , Boffa M-C , Khamashta MA , Hughes GRV ( 2009 ). The Euro-Phospholipid Project: epidemiology of the antiphospholipid syndrome in Europe . Lupus ; 18 : 889 \200\223 93 . Cohen D , Berger SP , Steup-Beekman GM , Bloemenkamp KWM, Bajema IM ( 2010 ). Diagnosis and management of the antiphospholipid syndrome. BMJ ; 340 c2541. Lim W , Crowther MA , Eikelboom JW ( 2006 ). Management of antiphospholipid antibody syndrome: a systematic review. JAMA ; 295 : 1050 \200\223 7. Miyakis S , Lockshin MD , Atsumi T , et al . ( 2006 ). International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J T hromb Haemost ; 4 : 295 \200\223 306. Ticani A , Branch W , Levy RA, et al . ( 2003 ). Treatment of pregnant patients with antiphospholipid syndrome . Lupus ; 12 : 524 \200\223 9 . 83 CASE 14 Case 14 A 30-year-old female sustained a right tibial fracture whilst walking. She had a history of JIA diagnosed at the age of 4 years which had been difficult to control. She had required prolonged courses of oral corticosteroids and was subsequently treated with methotrexate, a lendronate, and calcium and vitamin D supplementation. She was thin, with a BMI of 17 kg/m 2 , and had active synovitis of her wrists. Her menstruation was erratic but she did not ha ve amenorrhea. Her fracture failed to unite, and she required multiple surgical procedures including a bone graft following an infected non-union. Investigations showed the following: \227\206 Hb 11.0 g/dL; WCC 4.73 \227 109/L; platelets 234 \227 109/L \227\206 CRP 13 mg/L; creatinine 43 umol/L; ALP 237 IU/L; ALT 15 IU/L \227\206 Calcium 2.3 mmol/L; phosphate 1.23 mmol/L; albumin 44 g/L; parathyroid hor- mone 2.6 pmol/L (1.3 \200\2237.6) \227\206 Hormone and thyroid function tests (TFTs) were normal \227\206 DEXA scan results: spine \200\224 T score \200\2231.7; Z score \200\2231.5 hip \200\224 T score \200\2231.9; Z score \200\2231.9. Questions 1. What factors may have contributed to her fracture? 2. How should she be investigated? 3. What should be considered in planning her treatment? 84 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What factors may have contributed to her fracture? The most likely cause of her low-impact fracture is osteoporosis since she has a low BMD an d normal bone markers. Her DEXA scan results show her bone density to be in the osteopenic range but other contributory risk factors are: \227\206 JIA \227\206 prolonged courses of corticosteroids \227\206 low BMI and poor nutritional intake. Low BMD and fragility fractures are recognized complications of JIA which may persist into adulthood, causing an increased fracture risk compared with the healthy population. It is d ue to a combination of factors including prolonged inflammation, growth impairment, and red uced physical activity as well as treatment with corticosteroids. Oral glucocorticoid use is associated with a significant increase in fracture risk which ri ses rapidly after the onset of treatment and declines after stopping. The increase in fract ure risk is over and above the effect of low BMD. Mechanisms include osteoblast dysfunction , osteocyte apoptosis, and disturbed calcium home- ostasis. This patient had stopped her tr eatment with steroids more than a year prior to fracture, but it is not possible to quantif y the effect of years of steroid treatment during growth periods. Other causes of low-impact fracture include osteomalacia and, in an older patient, malignan cies including myeloma. Methotrexate-related osteopathy may be considered as a rare and idi osyncratic triad of severe distal tibial pain, oste- oporosis, and multiple compression fra ctures. 2. How should she be investigated? The main principles in investigating and managing a case of osteoporosis are: \227\206 exclusion of diseases mimicking osteoporosis \227\206 identification of the causes and contributory factors \227\206 assessment of the risk of subsequent fracture \227\206 selection of treatment. Investigations should be selected to confirm the diagnosis of osteoporosis and identify any contributory factors to her low bone density. This is important in planning her treatment to promote bone healing and prevent further fractures. Investigations may include a serum h ormone profile (prolactin, oestradiol, proges- terone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid- stimulating hormone (TSH)) and a 24-hour cortisol \200 \223dexamethasone suppression test. In men with osteoporosis, serum testosterone and sex-ho rmone-binding globulin (SHBG) should be measured. Coeliac disease should be excluded with e ndomysial or tissue transglutaminase antibodies. Her urinary calcium excretion should be me asured and markers of bone turnover, such as P1NP, may be used in assessing her response to treatment. Further imaging, including X-ray or MRI of 85 CASE 14 the lumbar or thoracic spine or isotope bone scans, may be relevant in patients with osteop orosis if further lesions are suspected. Published guidelines on investigation and treatment of osteoporosis have gener- ally addres sed the condition in post-menopausal women and men over 50 years of age. The fracture risk assessment tool (FRAX TM ) uses clinical risk factors to pro- vide a 10-year probability of a major osteoporotic fracture (spine, hip, forearm, or humerus). It gives guidance on the need for further assessment by DEXA scan and on treatment. The more recently published QFra ctureScores extend risk assess- ments to the younger population. There are few data on mana ging the condition in young women, where the adaptation of available guidelines also needs to consider the long-term effects of treatment on bone health and potential placental trans fer of drugs. Clinical risk factors used for the assessment of fracture probability include age, gender, BMI, previous fragility fracture or parental history of hip fracture, current glucocorticoi d treatment, smoking, alcohol intake, and secondary causes of oste- oporosis. These include inflammatory arthritis (e.g. rheumatoid arthritis and in this case uncontrolled JIA), untr eated hypogonadism, prolonged immobility, organ transplantation, type 1 diabetes, hyperthyr oidism, gastrointestinal or chron- ic liver disease, and chronic obstructive pulmonary dise ase. 3. What should be considered in planning her treatment? Treatment includes advice on lifestyle and pharmacological management. Lifestyle measures t o increase bone density should be recommended to all patients with low bone density: weight -bearing exercise, an adequate calcium intake, and avoidance of smoking and excessive alcoh ol consumption. The main pharmacological treatments of osteoporosis are the bisphosphonates, strontium rane late, raloxifene, and parathyroid hormone (PTH) peptides. These should all be prescribed wi th calcium and vitamin D (see p. 7). Alendronate is the first-line treatment in most cases and is approved for the prevention and treatment of glucocorticoid-induced osteoporosis. Th ere are concerns about the lack of data on the long-term use of bisphosphonates in young wo men, including the risk of placental transfer. Bisphosphonates treat osteoporosis by inhibiting osteoclasts and thereby reducing bone reso rption. PTH analogs such as teriparatide stimulate the formation and action of osteoblasts responsible for bone formation and promote increases in bone tissue. They are contraindicat ed for patients at risk of developing osteosar- coma and patients with hyperparthyroidism o r hypercalcaemia. Since this patient was pre-menopausal, all treatment for osteoporosis was unli- censed. She was given advice on improving her nutrition, particularly maintaining a calcium intake of 1000 mg/day, a vitamin D intake of 800 IU/day, and a protein intake of 1 g/kg body weight. She was advised to increase her BMI to > 19 kg/m 2 . Measures were taken to improve control of her inflammatory disease. She had previously taken alendronate for 2 years prior to her fracture. Following non- union of her fracture she was treated with teriparatide. 86 CASE HISTORIES IN RHEUMATOLOGY Further reading Hippisley-Cox J , Coupland C ( 2009 ). Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores. BMJ ; 339 : b4229 doi: 10.1136/bmj.b4229 . Kanis JA , Johnell O , Odan A , Johannson H , McCloskey E ( 2008 ). FRAX and the assessment of fracture probability in men and women from the UK . Osteoporos Int ; 19 : 385 \200\223 97. National Osteoporosis Guideline Group ( 2008 ). Guideline for the Diagnosis and Management of Osteoporosis in Postmenopausal Women and Men from the Age of 50 Years in the UK . Available online at: www.shef.ac.uk/NOGG. Royal College of Physicians, Bone and Tooth Society of Great Britain, National Osteoporosis Society ( 2002 ). Glucocorticoid-induced Osteoporosis: Guidelines for Prevention and Treatm ent . London : Royal College of Physicians . Thornton J , Ashcroft D , O \200\231Neill T , et al . ( 2008 ). A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease managemen t . Health Technol Assess ; 12 : 1 \200\223 208 . 87 CASE 15 Case 15 A one-year-old child presented to the pediatric on-call team with a 5-week history of high spiking temperatures, weight loss, marked irritability, a widespread rash, and a limp. On e xamination, his heart rate was 140 beats/min and his temperature was 38.2 C. Chest exami nation was otherwise normal. He had hepatomegaly and symmetrical bilateral wrist swelling. Investigations showed the following: \227\206 Hb 9 g/dL; WCC 39.27 \227 109/L; platelets 806 \227 109/L; ESR 46 mm/h \227\206 CRP 160 mg/L; ferritin 1650 g/L; ALT 31 U/L; ALP 390 U/L; triglycerides 0.9 mm ol/L A CT scan of the chest is shown in Fig. 15.1 . Fig. 15.1 CT scan of chest. 88 CASE HISTORIES IN RHEUMATOLOGY He was admitted to hospital and started treatment. Ten days later he remained extremely unw ell and irritable. His temperature was now persistently raised above 39 C. Investigations now showed the following: \227\206 Hb 7.9 g/dL; WCC 67.37 \227 109/L; platelets 230 \227 109/L; ESR 9. \227\206 CRP 120 mg/L; ALT 1171 U/L; ALP 1226 U/L. \227\206 PT 28.7 s; partial thromboplastin time (PTT) 41.7 s. 89 CASE 15 Questions 1. Give some causes of pyrexia in a child? What is the most likely diagnosis in this child at presentation? 2. What does the CT scan show? 3. What is the management of the initial condition? 4. What is the likely cause of his deterioration and what is the management of this complication? 90 CASE HISTORIES IN RHEUMATOLOGY Answers 1. Give some causes of pyrexia in a child? What is the most likely diagnosis in this child at presentation? Causes of pyrexia in a child include: \227\206 Infection \227\206 Malignancy such as acute lymphoblastic leukemia \227\206 IBD, \227\206 Systemic-onset juvenile idiopathic arthritis (SOJIA), \227\206 Connective tissue disease such as SLE \227\206 Vasculitis such as Kawasaki disease, \227\206 Castleman \200\231s disease (giant lymph node hyperplasia) \227\206 Periodic fever such as FMF. Fever is a common sign of illness in children and when prolonged beyond 2 weeks is termed p yrexia of unknown origin (PUO). Investigation includes a full infection screen, echocardiog raphy, bone marrow examination, serum lactate dehydrogenase (LDH), urate, and urinalysis fo r catecholamines. Recurrent bouts of fever may be associated with a number of rheumatological disorders, incl uding BD and SLE, as well as the hereditary periodic fever syndromes. Leukemia may present with musculoskeletal pain and arthritis; typically there is diffuse pain and tenderness in the long bones, migratory joint pain and swelling, and systemic features including low-grad e fever and weight loss. The full blood count may be normal or demonstrate abnormal white c ell or platelet counts. There may be increased inflammatory markers and LDH and urate level s. A neuroblastoma may present with bone metastases and fever, and high urinary vanillylman delic acid and homovanillic acid support the diagnosis. Recurrent fever may occur in IBD, a ssociated with diarrhea, anemia, and growth delay. Kawasaki disease is one of the most comm on vasculitides of childhood and is an important differential. It generally presents under the age of 5 years with fever, bilateral conjunctival injection, oropharyngeal mucous membr ane changes (fis- sured lips and strawberry tongue), a polymorphous rash, cervical lymphade nopa- thy, and erythema and oedema of the hands and feet, resulting in periungual desquamat ion. Castleman \200\231s disease is rare in children and presents with diffuse lymphadenopa thy and systemic symptoms. The hereditary periodic fever syn- dromes are autoinflammatory d iseases affecting the innate immune system. Episodes of pyrexia generally last days and may be associated with rash, abdominal pain, headache, and joint symptoms. There may be a fami ly history and immunol- ogy is negative. This child presented with evidence of systemic inflammation, rash, and a spiking temperatur e lasting for weeks. The development of arthritis supported the diagnosis of SOJIA. It is i ncluded in the classification of JIA and is defined as arthritis in one or more joints prec eded by at least 2 weeks by a quotidian fever and accompanied by a non-fixed evanescent ery thematous macular rash, generalized lymphadenopathy, 91 CASE 15 hepatomegaly or splenomegaly, and serositis. It is characterized by marked extra- articular features. The quotidian fever associated with SOJIA differs from that due to sepsis by a r eturn to normal at least once during each 24 hours and it must be present for 2 weeks. It c haracteristically occurs in association with the development of a discrete, pink, non-pruri tic macular rash occurring in crops over the trunk and limbs which may exhibit Koebner \200 \231s phenomenon. Laboratory features include a hypochromic normocytic anemia, leucocytosis , and thrombocytosis. The ESR, CRP, and ferritin levels are usually high. The etiology of SOJIA is unclear but it resembles the autoinflammatory syn- dromes and appe ars to be related to an abnormal genetic coding for proinflammatory proteins. High serum le vels of tumor necrosis factor (TNF) and interleukins 6 and 1 (IL-6 and IL-1) have been demo nstrated in the sera of patients with the condition. 2. What does the CT scan show? The CT scan (Fig. 15.1 ) shows a small pericardial effusion. Pericardial effusions occur in 3 \200\2239 % of SOJIA cases and are usually asymptomatic, although some children have dys pnoea or precordial pain. It may be evident on examination by diminished heart sounds, tach ycardia, cardiomegaly, and a pericardial friction rub at the left lower sternal border. 3. What is the management of the initial condition? Depending on severity, the management of SOJIA may include the following: \227\206 NSAIDS (e.g. ibuprofen 10 mg/kg three times daily). \227\206 high-dose oral steroids (prednisolone 2 mg/kg/day). \227\206 intravenous methylprednisolone 10 \200\22330 mg/kg/day for 1 \200\2233 days, foll owed by oral prednisolone. \227\206 methotrexate 15 \200\22320 mg/m2 weekly for long-term control of articular diseas e, although it may be less effective in controlling systemic symptoms. Biological agents against IL-6 and IL-1 have been used with some success when the systemic features are marked. 4. What is the likely cause of his deterioration and what is the management of this complication? The deterioration in his condition with the development of persistent fever raised concerns that he was developing macrophage activation syndrome (MAS). This is a severe and potentia lly life-threatening syndrome characterized by fever, pancyto- penia, hepatosplenomegaly, l ymphadenopathy, elevated liver transaminases, intra- vascular coagulation, and CNS dysfunct ion. Triglycerides and ferritin are raised, PT and PTT are prolonged, and ESR is paradoxica lly low in association with hypofibrinoginaemia. MAS is associated with SOJIA, SLE, and pol yarticular JIA. It may be triggered by infection with members of the herpesvirus family, in cluding EBV, or drugs including gold, NSAIDs, hydroxychloroquine, and d -penicillamine. 92 CASE HISTORIES IN RHEUMATOLOGY MAS is a form of secondary haemophagocytic lymphohistiocytosis, but differs from the classi cal form of this disease in a number of ways, presenting with a rela- tive rather than abso lute decrease in white cell count, platelets, or fibrinogen. Bone marrow aspirate may not d emonstrate haemophagocytosis early in the disease. In this case, the WCC count remained hig h but MAS was indicated by the low ESR, raised triglycerides, and falling hemoglobin and pl atelets. The treatment of MAS is with: \227\206 high-dose parenteral corticosteroids \227\206 ciclosporin 4 mg/kg/day. Biological agents such as etanercept, anakinra, and tocilizumab have also been used with va riable results. This patient had an incomplete response to intravenous corticosteroids and was treated with anakinra. He made a good recovery and was managed in the longer term with subcutaneous wee kly injections of methotrexate 20 mg/m 2 . Further reading Hull RG on behalf of the British Pediatric Rheumatology Group ( 2001 ). Guidelines for management of childhood arthritis. Rheumatology ; 40 : 1309 \200\223 12. Petty RE , Southwood TR , Manners P , et al . ( 2004 ). International League of Association s for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmont on, 2001. J Rheumatol ; 31 : 390 \200\223 2 . Ravelli A ( 2002 ). Macrophage activation syndrome . Curr Opin Rheumatol ; 14 : 548 \200 \223 52. Ravelli A , Magni-Manzoni S , Pistorio A , et al . ( 2005 ). Preliminary diagnosti c guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic a rthritis . J Paediatr ; 146 : 598 \200\223 604 . Woo P ( 2006 ). Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome . Nature Clinical Practice ; 2 , 28 \200\223 34 . 93 CASE 16 Case 16 A 67-year-old man with a 26-year history of AS presented to the rheumatology clinic with in creased pain in his back. Four months previously he had been admitted under the general med ical team after collapsing at home. A diagnosis of pulmonary embo- lism was made and confir med on a computed tomography pulmonary angiogram (CTPA). The patient was discharged home on wafarin, but continued to have severe pain in his back. The pain was not alleviated by exe rcise, prevented sleep, and was very debilitating. There was no history of weight loss or systemic features of infection, and the patient had no prior treatment with immunosuppressive therapy. His analgesia included diclofenac 50 mg three times daily and morphine sulfate tablets 10 mg twice daily, with breakthough Oramorph as required. Examination revealed a moderate kyphosis. He was tender to palpation over T12 \200\223L3 wi th restricted hip movement and no evidence of peripheral synovitis. The patient was afebril e and systems examination was unremarkable, including intact neurology. His Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was 6/10 and his spinal pain Visual Anal og Score (VAS) was 9/10 cm. Investigations showed the following: \227\206 Hb 13.5 g/dL; WCC 7.7 \227 109/L; platelets 192 \227 109/L; creatinine 110 m ol/L \227\206 CRP 8 mg/L, ESR 4 mm/h. MRI of the spine is shown in Fig. 16.1 . 94 CASE HISTORIES IN RHEUMATOLOGY Fig. 16.1 T 2 -weighted sagittal MRI of spine. 95 CASE 16 Questions 1. What is your differential diagnosis of the back pain? 2. What does the MR scan show? 3. How would you manage this patient? 4. Would you consider this patient for biological therapy? 5. What are the current NICE guidelines for the treatment of AS with biological therapy? 96 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What is your differential diagnosis of the back pain? The patient has a raised BASDAI and spinal VAS which could indicate a flare in his inflamma tory back pain. However, the pain is more mechanical in nature, i.e. it does not settle wit h exercise and there is point tenderness over the spine. A recent pulmonary embolism may su ggest an undiagnosed malignancy with secondary metastases in the spine. Other differentials include an acute discitis or osteomyeli- tis, although the normal CRP and lack of fever wo uld argue against this. Finally, the patient sustained a fall when he collapsed at home, so he should be investigated for a fracture. 2. What does the MR scan show? The MRI of the spine demonstrates high signal in the vertebral bodies of T11 and T12 extend ing into the posterior elements, with collapse of the superior endplate of T12 and the infe rior endplate of T11. The findings would be in keeping with a traumatic Andersson lesion, o r pseudo-arthrosis, involving the posterior elements. The lack of high signal in the disc s pace itself makes infection unlikely. There is extrusion of the disc material anteriorly an d the anterior longitudinal ligament is displaced. There is no evidence of spinal canal ste nosis and the cord signal is normal. The diagnosis of AS is confirmed by the partial fusion of the lumbar and thoracic vertebrae. Standard CT allows better evaluation of fractures an d destructive verte- bral lesions than MRI of the spine and was subsequently performed in t his case (Fig. 16.2 ). This confirmed AS with a T11/12 Andersson lesion as the cause of the sudden-onset back pain in this patient. Fig. 16.2 Sagittal CT image of spine showing Andersson lesion (arrow). 97 CASE 16 Fig. 16.3 X-ray of whole spine showing extensive spinal instrumentation with pedicle screws from the upper thoracic to the lower lumbar region. The rods bridge the pseudo-arthrosis i n the upper lumbar spine. 3. How would you manage this patient? This patient \200\231s spine is unstable with an increased risk of spinal cord compression if left untreated. Surgical fixation is the treatment of choice, and the outcome is shown i n Fig. 16.3 . The possible complications of spinal surgery include damage to the spinal cor d or spinal nerves in addition to general risks including anesthetic complications, bleedin g, thrombosis, dural tear, infection, and persistent pain. 4. Would you consider this patient for biological therapy? Although this patient has raised BASDAI and spinal VAS scores, these can be attributed to t he pseudo-arthrosis rather than reflecting inflammatory disease activity. This patient woul d be unlikely to benefit from biological therapy and treatment should focus on surgical cor rection, appropriate analgesia, and physiotherapy postoperatively. 5. What are the current NICE guidelines for the treatment of AS with biological therapy? NICE guidance recommends the use of the TNF inhibitors adalimumab and etanercept as treatme nt options in adults with severe active AS. There are three elements that should be satisfi ed before a patient is eligible for anti-TNF therapy. First, the Modified New York Criteria for the diagnosis of AS must be satisfied, including the radiological criterion and at least one clinical criterion. 98 CASE HISTORIES IN RHEUMATOLOGY \227\206 Clinical criteria: low back pain present for > 3 months, improved by exercise but not relieved by rest limitation of lumbar spine motion in sagittal and frontal planes limitation of chest expansion relative to normal values for age and sex. \227\206 Radiological criterion: sacroiliitis on radiographs . Further, there must be evidence of sustained active spinal disease, which is confirmed by: \227\206 score of \211 4 units on BASDAI \227\206 score of \211 4 cm on the 0 \200 \22310 cm spinal pain VAS. These scores must be measured twice, at least 12 weeks apart, on stable treatment. Lastly, patients should have failed treatment with at least two different conven- tional NS AIDs taken at maximum tolerated or recommended dosages for 4 weeks respectively. Exclusion criteria for the use of anti-TNF agents include patients with active significant infection, a septic arthritis of a native joint within the last 12 months, prosthetic joint infection within the last 12 months or indefinitely if the prosthesis if not removed, New York Heart Association (NYHA) grade 3 or 4 congestive cardiac failure (CCF), history of dem yelinating disease, women who are pregnant or breastfeeding, and malignancy. Patients who are started on anti-TNF therapy must be assessed 12 weeks after starting treat ment. An adequate response is defined as a 50 % reduction or a reduc- tion by \211 2 unit s in BASDAI, and a reduction in the spinal pain VAS by \211 2 cm. Patients who reach this response are eligible to continue treatment with anti-TNF therapy. If patients are intolerant to a specific anti-TNF therapy, for example due to injection sit e reactions, then they are eligible to switch to another, but under NICE they cannot switch because of lack of efficacy alone. At present, the published NICE guidance does not recommend the use of inflixi- mab in the t reatment of AS, although if patients are already receiving the treatment they have the opti on to continue. This is in contrast to the British Society for Rheumatology (BSR) guideline s (2006) which recommend the use of infliximab as an option for treating patients with AS. Further reading Keat A , Barkham N , Bhalla A, et al . on behalf of the BSR Standards, Guidelines, and Audi t Working Group ( 2005 ). BSR guideline for prescribing TNF- blockers in adults with ank ylosing spondylitis. Report of a working party of the British Society for Rheumatology . Rh eumatology ; 44 : 939 \200\223 47 . Kim KT , Lee SH , Suk KS , Lee JH , Im YJ ( 2007 ). Spinal pseudoarthrosis in advanced anky losing spondylitis with sagittal plane deformity . Spine ; 32 : 1641 \200\223 7 . NICE ( 2008 ). Adalimumab, etanercept and infliximab for ankylosing spondylitis . NICE Technology Appraisal Guidance 143 . Available from : http://guidance.nice.org.uk/TA143. 99 CASE 17 Case 17 A 24-year-old male competitive 800 m runner presented with a 6-week history of left posteri or heel pain and swelling. The pain had started insidiously with no specific injury. The pa in was now constant at mild to moderate intensity but significantly worse during and for a few hours after running. He had changed coaches 2 months previously and had modified his tr aining program to include more speed work. He had tried ice massage to his heel and oral NSAIDs with limited benefit. His past medical history included a motor vehicle accident 2 years previously. This had resulted in chronic lower back pain and morning stiffness. Examination revealed over-pronation of his hindfoot during walking and running. There was m ild swelling and moderate tenderness over the insertion of the left Achilles tendon into th e calcaneus. Lower back movement was restricted in all planes. A modi- fied Sch ber \200 \231s test gave a result of + 3 cm. There was no discomfort on stressing the sacroiliac joi nts. A few red scaly patches were noted on the back of his scalp. Investigations showed the following: \227\206 CRP 7 mg/L \227\206 Ultrasound of left Achilles tendon: irregular fusiform swelling of the distal por tion of the tendon at the inserted into the calcaneus with mild hypoechoic echotexture and loss of fibrillar pattern associated small bony heel spur \227\206 His HLA B27 status was negative. Questions 1. What is the differential diagnosis? 2. What further information might be helpful in making a diagnosis? 3. Are there any other investigations you would like to perform? How would these help? 4. How would you manage this patient? 100 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What is the differential diagnosis? He has an insertional Achilles tendinopathy. The two most likely differential diag- noses a re: \227\206 mechanical overuse tendinopathy \227\206 enthesitis related to a spondyloarthropathy (e.g. psoriatic arthropathy). Mechanical overuse tendinopathy is a degenerative condition thought to be the result of rep etitive strain which causes chronic micro-tears to the tendon. Tendons continuously slowly remodel to adapt to the loads placed upon them. If they are unable to adapt, tendinopathy c an develop. The histological features are hypertro- phy of fibroblasts, abundant disorganiz ed collagen, and vascular hyperplasia. This does not involve inflammatory cells and therefo re the term tendonitis is mislead- ing. The mechanism of the pain is poorly understood. Running is one of the most common causes of a mechanical overuse tendinopa- thy of the Achi lles tendon. Excessive motion of the hindfoot due to lateral heel strike and over-pronation can cause a whipping action of the Achilles tendon and predispose it to injury. Recent cha nges to running technique, increased training intensity, and new or worn footwear can be pr ecipitating factors. The most com- mon area for Achilles tendinopathy to develop in an athl ete is in the mid-portion (2 \200\2236 cm proximal to the tuber calcanei). Only about 20 % of mechanical Achilles tendinopathies are insertional. Insertional tendinopathies are often associated with retro-calcaneal bursitis and/or Haglund \200\231s deformity (bony enlargem ent of the back of the calcaneus). Tendinopathy is also common in the non-athletic populati on, particularly in people who are overweight and have biomechanical lower-limb problems. In this patient an enthesitis related to an inflammatory spondyloarthropathy needs to be co nsidered in view of his chronic low back pain and morning stiffness. Less than 30% of patie nts with psoriatic arthritis are positive for HLA B27. 2. What further information might be helpful in making a diagnosis? It is important to ascertain whether he had back symptoms prior to his motor vehicle accide nt. It is also pertinent to ask about other symptoms which might sug- gest spondyloarthriti s such as peripheral arthritis, dactylitis, psoriasis, palmar plantar pustulosis, balanitis , nail changes, other recurrent tendon problems, iritis, or inflammatory bowel symptoms. En quiries should be made about a family his- tory of psoriasis and inflammatory arthritis. 3. Are there any other investigations you would like to perform? How would these help? Consider imaging the sacroiliac joints and lumbar/thoracic spine with an MRI scan. Features of sacroiliitis (bone oedema, synovitis, erosion, and sclerosis) may 101 CASE 17 be visible on MRI if the underlying etiology is psoriatic arthritis or ankylosing spondylit is. Romanus lesions at the corners of the vertebral body may be present in the lumbar or th oracic spine. These appear as bright signal on STIR MRI sequences and indicate enthesitis o f the spinal ligament insertion to the vertebral body. Ultrasound of the tendon is useful t o monitor improvement over time, but is unlikely to differentiate between insertional mecha nical overuse tendinopathy and enthesitis from a spondyloarthropathy. Thickening of the ten don insertion, calcific deposits, periosteal changes, and vascularization (seen by Doppler ultrasound) can be found in both settings. 4. How would you manage this patient? Treatment will be guided by whether or not the insertional tendinopathy is thought to be me chanical or inflammatory in etiology: Mechanical overuse i) Relative rest from activities causing the problem (in this case time off from running). ii) Eccentric calf raises. This is a well-established therapy for mid-portion Achilles tend inopathy but has not been very successful in insertional tendinopathies. In the original st udies with eccentric training the patient did the exercise on a step and the heel went lowe r than the rest of the foot, causing dorsiflexion at the ankle. It is now thought that dors iflexion causes impingement between ten- don, bursa, and bone at the insertion, resulting i n a compressive force, and hence is the reason for treatment failure in those with insertio nal tendinon- opathy. It has been demonstrated that eccentric calf raises done on flat grou nd with no dorsiflexion at the ankle improves insertional tendinopathy. Three sets of 15 re petitions with knee straight and three sets of 15 repetitions with knee bent twice a day fo r 12 weeks are the minimum treatment course. iii) Correct any biomechanical abnormality. In this patient, correction of over- pronation is important, either by using support shoes or by referral for orthotics to have medial arc h supports made to fit his running shoes. iv) A variety of \200\230novel \200\231 treatments are currently used but they have little or no evidence base at present. Sclerotherapy has been used to reduce the \200\230neovasc u- larization \200\231 which is thought to contribute to the pain. Dry needling, autologous blood, and platelet-rich plasma (PRP) injections are also in use. The rationale is that th e trauma and blood/PRP provides the growth factors necessary for tendon repair. Extracorpor eal shock wave therapy and high-volume tenotomy are also occasionally offered, but the reco mmendation for these second-line therapies is anecdotal rather than evidence-based. Inflammatory spondyloarthropathy i) Education about disease and symptomatic treatment. ii) Physiotherapy to maintain range of back flexibility. iii) Anti-inflammatories. 102 CASE HISTORIES IN RHEUMATOLOGY iv) Consider corticosteroid injection into sacroiliac joint if there is sacroiliitis on MRI. v) Anti-TNF therapy for refractory disease. There is no proven benefit of traditional DMARD therapy in the setting of spinal inflammation or enthesitis. DMARDs can be used if there i s an associated peripheral arthritis. Further reading Alfredson H ( 2005 ). The chronic painful Achilles and patellar tendon: research on basic biology and treatment . Scand J Med Sci Sports ; 15 : 252 \200\223 9 . Antoni CE , Kavanaugh A , Kirkham B , et al . ( 2005 ). Sustained benefits of infliximab th erapy for dermatologic and articular manifestations of psoriatic arthritis: results from th e Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) . Arthritis Rheum ; 52 : 1227 \200\223 36 . Jonsson P , Alfredson H , Sunding K , et al . ( 2008 ). New regimen for eccentric calf-musc le training in patients with chronic insertional Achilles tendinopathy: results of a pilot stu dy . Br J Sports Med ; 42 : 746 \200\223 9 . 103 CASE 18 Case 18 A 26-year-old healthy landscape gardener attended the rheumatology clinic com- plaining of a year \200\231s history of intermittent wrist discomfort, numbness, and pins and needles i n his hands. His symptoms had started during a period of heavy gardening. His past medical history included an injury to his upper spine 6 years previously, which ha d occurred while using a sledgehammer. These symptoms resolved over a 6-month period. He ha d a more recent 2-year history of stiffness across his shoulders and upper back. On examination he had a forward protruding neck at the cervico-thoracic junction, with some restriction of thoracic and scapular mobility. He had a full range of pain- free movement at the wrists and fingers with no swollen or tender joints. Power, tone, reflexes, and sens ation in the upper and lower limbs were normal. Tapping the palmar aspect of the wrist over the carpal tunnel to elicit paraesthesia in the distribution of the median nerve (Tinel \200\231s test) was negative. However, he reported mild paraesthesia 1.5 minutes into Phale n \200\231s test where the wrist is held in a fully flexed position for 2 minutes. The physiotherapist was able to reproduce his symptoms by stressing the brachial plexus on both sides. The upper thoracic joints were described as hypomobile. Questions 1. What are the possible causes of the symptoms in his hands? 2. What clinical tests are useful in confirming the diagnosis? 3. How would you manage this patient? 104 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What are the possible causes of the symptoms in his hands? \227\206 Musculoskeletal soft tissue symptoms related to adverse neural dynamics (AND) are the most likely cause of his symptoms in view of his age, neck posture, the intermittent n ature of his symptoms, and the absence of other neurological signs. \227\206 Central cervical disc prolapse at C5 \200\2236 or C6 \200\2237 should be consider ed in view of his previous history of injury and his symptoms during a period of heavy gard ening. \227\206 Bilateral median nerve entrapment is a possible diagnosis in view of his occupa- tion and use of heavy equipment. \227\206 CNS disorders such as demyelination are less likely. 2. What clinical tests are useful in confirming the diagnosis?