isotope bone scan; an inconvenient truth? Clin Radiol ; 63 : 108 \200\223 10. 9 CASE 2 Case 2 A 60-year-old woman was referred to the lymphoma clinic in view of a 2 month history of nig ht sweats, fatigue, and general malaise. There was no past medical or travel history of not e, but significant weight loss had been noted by her husband. She denied any gas- trointest inal symptoms but had been experiencing recurrent generalized headaches over the last 6 wee ks. She was a lifelong non-smoker and drank alcohol only occasionally. On examination she had a temperature of 38.2 C, but other vital signs were normal. She a ppeared thin with no lymphadenopathy. Full systemic examination, including urinalysis, was otherwise normal. Investigations revealed elevated inflammatory markers (erythrocyte sedimentation rate (ESR) 85 mm/h, CRP 44 mg/L) but no evidence of hematological abnormality, infection, or malignan cy. The results of diagnostic and staging investigations are shown in Figs 2.1 and 2.2 , re spectively. Fig. 2.1 (See also Plate 1) Diagnostic investigation. 10 CASE HISTORIES IN RHEUMATOLOGY Fig. 2.2 Staging investigation . 11 CASE 2 Questions 1. What is the diagnosis? What is the diagnostic investigation that was performed and what abnormalities are shown in Fig. 2.1? 2. Which investigation results are shown in Fig. 2.2 ? When should this investigation be considered? 3. What is the most worrying complication of this condition? 4. What features should be sought on examination? 5. What immediate action should be taken when this condition is suspected? 6. Which other imaging modality may be helpful in the investigation of this condition? 12 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What is the diagnosis? What is the diagnostic investigation that was performed and what abnormalities are shown in Fig. 2.1? The diagnosis is giant cell arteritis (GCA), also known as temporal arteritis or Horton \200\231s headache. It is a primary large vessel vasculitis with a mean age at onset of 70 years. It is rare before the age of 50 years and is more common in Caucasian than African C aribbean people. It has a significant female preponderance. Headache is the most common com plaint; it occurs in 90 % of patients and is the presenting feature in 48 % of cases. Heada ches can be quite variable in quality and nature, and can mimic tension headache, migraine, and cluster headaches. Other common features include scalp tenderness and jaw or tongue cl audication. Systemic features including fever, weight loss, and malaise occur in 50 % of pa tients. Rarely, it can present with systemic features alone or limb claudication. The diagnostic investigation is a temporal artery biopsy (Figs 2.1 and 2.3). This investiga tion should be considered in all cases of suspected temporal arteritis. Ideally, a temporal artery biopsy should be obtained within a week of commencing steroids in order to maximize its diagnostic and prognostic value. However, there is evidence to suggest that temporal a rtery biopsy may remain positive up to 28 days after commencing steroid therapy. Contralate ral biopsy does not provide any additional information and is not routinely recommended. In order to maximize the diagnostic potential, a biopsy at least 1 cm long is suggested. This example (Fig. 2.3) demonstrates the classical histological features of GCA which include: \227\206 disruption of the internal elastic membrane (1) \227\206 multinucleate giant cells (2) \227\206 occlusion of the lumen (3) \227\206 intimal hyperplasia (4). 1 4 2 3 Fig. 2.3 (See also Plate 2) Temporal artery biopsy. 13 CASE 2 The severity of intimal hyperplasia on temporal artery biopsy is associated with increased risk of neuro-ophthalmic complications. 2. Which investigation results are shown in Fig. 2.2 ? When should this investigation be considered? Figure 2.2 shows the results of a whole-body FDG PET scan. The use of FDG, a glucose analog , enables the visualization of inflamed vessels, which are glucose- consuming, provided tha t they are greater than 4 mm in diameter. This size limita- tion and proximity to the high glucose consumption of the brain explains why the temporal arteries themselves are not visi ble using this imaging modality. Large- vessel vasculitis can be demonstrated and is partic ularly specific to large-vessel vasculitis when seen in the larger thoracic vessels, as is seen here with marked aortitis. This type of imaging should be considered in patients demonstrating systemic features, limb claudication, or persistent symptoms despite adequate steroid therapy. MRI can also be use d to assess for large-vessel involvement and does not expose the patient to radiation. 3. What is the most worrying complication of this condition? Visual loss is the most serious complication of GCA, and occurs in 15 % of patients. If one eye is affected, there is high risk (20 \200\22350 % ) of bilateral loss of vision if ther e is any delay or cessation of treatment. Blindness is most commonly the result of optic is chae- mic neuropathy and is associated with a positive temporal artery biopsy. Retinal and ophthalmic artery thromboses are rare causes of blindness in GCA. 4. What features should be sought on examination? Examination findings include the following: \227\206 Cranial : tender, thickened, or beaded superficial temporal artery with reduced or absent pulsation, scalp tenderness, and upper cranial nerve palsies. \227\206 Visual : transient or permanent reduction in acuity, relative afferent pupillary defect, and pale swollen optic disc. \227\206 Systemic : asymmetrical pulses and blood pressure, presence of bruits. The presence of temporal artery prominence, beading, and tenderness all increase the likeli hood of obtaining a positive temporal artery biopsy. 5. What immediate action should be taken when this condition is suspected? All patients with suspected GCA should be commenced on high-dose steroids imme- diately. Th e dose and administration of steroids depends on the clinical scenario. \227\206 Uncomplicated GCA with no claudication or visual symptoms: 40 \200\22360 mg daily . \227\206 Evolving visual loss or amaurosis fugax: intravenous methylprednisolone 500 mg for 3 days before commencing oral steroids. \227\206 Established visual loss: 60 mg prednisolone daily, to protect the contralateral e ye. 14 CASE HISTORIES IN RHEUMATOLOGY All patients should receive bone protection with calcium and vitamin D supple- ments and a bisphosphonate (see p. 7). Gastric protection with a proton pump inhibitor should also be c onsidered. Once the diagnosis has been confirmed, aspirin is recommended if no contraindica tion exists, and statin therapy can also be con- sidered. Steroid-sparing agents, such as m ethotrexate or azathioprine, may be indicated if there is evidence of recurrent relapse or difficulty weaning steroids. Essential investigations include full blood count, liver function tests, urea and electroly tes, ESR, CRP, and urgent temporal artery biopsy. These investigations should not delay ini tiation of appropriate treatment. 6. Which other imaging modality may be helpful in the investigation of this condition? The diagnostic use of ultrasound in GCA is currently under investigation. It is widely avai lable, relatively inexpensive, repeatable, non-invasive, and lacks radiation expo- sure. It can provide information regarding the vessel wall, lumen, pulsatility, and blood flow char acteristics. The main potential drawback of ultrasound is operator dependency, although rec ent studies of temporal artery ultrasound have shown inter-observer agreement of more than 90 % . The features shown on ultrasound include the following: \227\206 Oedema : a dark hypoechoic thickening or halo around the vessel wall. \227\206 Stenosis : manifests as disrupted turbulent blood flow on color Doppler. \227\206 Occlusion : color signals are absent. A recent meta-analysis showed that temporal artery ultrasonography has a pooled sensitivity of 80 % and specificity of 96 % compared with the clinical diagnosis. Further studies are under way to explore this further and determine the pragmatic utility of ultrasound in the diagnosis of GCA. Further reading Blockmans D , Bley T , Schmidt W ( 2009 ). Imaging for large-vessel vasculitis . Curr Opin Rheumatol ; 21 : 19 \200\223 28 . Mukhtyar C , Guillevin L , Cid MC , et al . ( 2009 ). EULAR recommendations for the management of large vessel vasculitis . Ann Rheum Dis ; 68 : 318 \200\223 23 . 15 CASE 3 Case 3 A 19-year-old Brazilian woman, who was previously well, presented with a 10-day history of sudden-onset polyarthritis and a diffuse necrotizing rash. Since moving to England 4 years previously, she had noticed nasal congestion and clear discharge during the winter months. Examination revealed fever (37.9 C), tachycardia (110 beats/min), tender axillary and in guinal lymphadenopathy, and a symmetrical synovitis of elbows, wrists, ankles, and MCP join ts. She had widespread tender erythematous nodules over her face, arms, and legs with trunc al sparing (Fig. 3.1 ). Investigations showed the following: \227\206 CRP 191 mg/L \227\206 Routine biochemistry, FBC, RF, ANA, ANCA, complement levels, CPK, throat swab, AS OT, Epstein \200\223Barr virus (EBV), and cytomegalovirus (CMV) serology, urine microscopy, and three sets of blood cultures were all normal \227\206 ECG showed sinus tachycardia \227\206 CXR normal \227\206 Skin biopsy initially showed granulomatous and perivascular inflammation (Fig. 3. 2 ). By day 5 of admission, the patient became increasingly unwell with persistent pyrexia, and worsening periorbital inflammation. She also developed numbness in a stocking distribution with preserved reflexes and power. In response to the clinical deterioration empirical trea tment with intravenous methylprednisolone was administered. 16 CASE HISTORIES IN RHEUMATOLOGY Fig. 3.1 (See also Plate 3) Erythematous nodules on elbow. Large granuloma Perivascular inflammation Fig. 3.2 (See also Plate 4) Skin biopsy with haematoxylin and eosin staining. 17 CASE 3 Questions 1. What is the differential diagnosis based on the clinical features? 2. The initial skin biopsy (Fig. 3.2 ) shows granulomatous inflammation. How does this alter the differential diagnosis? 18 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What is the differential diagnosis based on the clinical features? The presence of a rash and small-joint polyarthritis raises a broad differential. Primary r heumatological conditions would include systemic lupus erythematosis, which would be suppor ted by the malar distribution of the rash, dermatomyositis, which can cause severe periorbi tal oedema, and vasculitis, with the nasal discharge. Wegener \200\231s granulomatosis (WG) should be considered (see p. 131). In addition, the history should be explored for feature s of a possible reactive arthritis (see p. 249) or a drug reaction. The presence of fever and tender nodules on the face raise the possibility of acute febrile neutrophilic dermatosis or Sweet \200\231s syndrome. This is characterized by tender red-t o-purple papules, and nodules that coalesce to form plaques usually on the upper extremitie s, face, and neck. It is due to a hypersensitivity reaction in response to systemic factors such as hematological disease, infection, inflammation, vaccina- tion, or drug exposure. H owever, the condition is mediated by neutrophils and there- fore is not supported in the cu rrent case by the normal peripheral white cell count. 2. The initial skin biopsy (Fig. 3.2 ) shows granulomatous inflammation. How does this alte r the differential diagnosis? The skin biopsy with haematoxylin and eosin staining shows evidence of perivascular necroti zing granulomatous inflammation. Larger magnification also revealed perineural inflammation . The presence of granulomatous inflammation on the skin biopsy is still in keep- ing with va sculitis, in particular WG. Lymphomatoid granulomatosis, an angio- destructive lymphoprolif erative systemic disease associated with EBV which is known to mimic WG, should also be con sidered but is less likely in the context of the negative serology. Granulomatous disease i n the context of musculoskeletal symptoms should always raise the possibility of sarcoidosi s (see p. 20) and its coun- terpart tuberculosis. A normal chest X-ray (CXR) does not exclu de either of these diagnoses. Alongside tuberculosis, another granulomatous infectious etio logy is leprosy. The absence of a neutrophilic inflammatory response, in addition to the normal peripheral white cell count, excludes the diagnosis of Sweet \200\231s syndrome. Further staining revealed the presence of acid-fast bacilli on Wade \200\223Fite staining, diagnostic of leprosy (Fig. 3.3 ). 3. What are the musculoskeletal manifestations of leprosy? Musculoskeletal complications are common and include arthralgia, arthritis, and Charcot joi nts. A symmetrical small-joint polyarthritis, mimicking rheumatoid arthritis, is common, an d the combination of arthritis, neurological involvement, and skin lesions can easily be mi sdiagnosed as primary vasculitis. The subsequent 19 CASE 3 Acid-fast bacilli visible with Wade \200\223Fite staining Fig. 3.3 (See also Plate 5) Skin biopsy with Wade \200\223Fite staining. delay in diagnosis can be a number of years, even in countries with endemic leprosy such as India. Untreated leprosy results in severely reduced quality of life, mainly due to diffus e irreversible nerve damage. Moreover, the use of systemic immuno- suppressive agents for a presumed non-infective condition can impact on the disease activity and progression to the more severe lepromatous form of leprosy. Further reading Cossermelli-Messina W , Festa , Neto C , Cossermelli W ( 1998 ). Articular inflammatory man ifestations in patients with different forms of leprosy . J Rheumatol ; 25 : 111 \200\223 19 . Haroon N , Agarwal V , Aggarwal A , Kumari N , Krishnani N , Misra R ( 2007 ). Arthrit is as presenting manifestation of pure neuritic leprosy \200\224 a rheumatologist \200\231 s dilemma . Rheumatology ; 46 : 653 \200\223 6 . 20 CASE HISTORIES IN RHEUMATOLOGY Case 4 A 32-year-old Caucasian primary school teacher was seen in the rheumatology clinic. Eight w eeks previously she had developed generalized malaise and a sore throat. These symptoms res olved within a week, but 3 weeks later she developed a rash over the dorsum of her feet and shins. The rash comprised multiple red tender lumps. She also developed pain and swelling of both ankles, alongside mild aching of the limb girdle. The joint symptoms improved sligh tly with naproxen, prescribed by her general practitioner. She had no significant travel hi story. On examination she appeared systemically well, with mild swelling and tenderness of both an kles. The rash had resolved apart from a single yellowish tender lesion on her right shin. The rest of her examination was normal. Investigations showed the following: \227\206 FBC, U&Es, LFTs, calcium, CPK, TSH all normal \227\206 CRP 36 mg/L, ESR 24 mm/h \227\206 ASOT 20 U/ml. The CXR is shown in Fig. 4.1 . Fig. 4.1 Chest X-ray. 21 CASE 4 Questions 1. What is the rash likely to be and what is the differential diagnosis, based on the history and examination findings alone? 2. What is the most likely diagnosis, taking the CXR findings into account? 3. What is a likely explanation for this patient \200\231s muscle aches and what are the systemic manifestations of this condition? 4. How would you manage this patient and what is her prognosis? 22 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What is the rash likely to be and what is the differential diagnosis, based on the history and examination findings alone? The rash is most likely to be due to erythema nodosum. It characteristically develops as an acute nodular erythematous eruption. It is most commonly found on the extensor aspect of t he legs and is particularly painful during the first week. As it heals, it changes from red to blue and ultimately resembles a bruise. Individual lesions tend to last for about 2 wee ks, but individual crops usually develop in a staggered fashion. The presence of a sore throat prior to the onset of the joint symptoms raises the possibili ty of rheumatic fever or a post-streptococcal reactive arthritis (see p. 249). The arthriti s of rheumatic fever does usually affect large joints, including the knees and ankles, and usually settles within 1 \200\2232 weeks. However, the absence of the typical migratory pol yarthritis, whereby several joints are affected in quick succession, each for a brief perio d of time, makes it unlikely. It would also usually be accompanied by an acute febrile illn ess. Although it is possible that the nodular rash represents the subcutaneous nodules foun d in rheumatic fever, these tend to be painless and resolve within a few days. The presenta tion is not typical for post-streptococcal reactive arthritis either, as it usually develop s 2 weeks after the initial throat infec- tion and is often associated with a non-migratory large-joint oligoarthritis which persists for longer than 2 weeks. Reactive arthritis does commonly affect the ankles and many of the causative organisms, inc luding Mycoplasma , Campylobacter , and Salmonella , are also associ- ated with erythema no dosum. However, there is nothing in this patient \200\231s history to suggest a preceding i nfective illness with these organisms. Viral arthritis (see p. 246), for example following human parvovirus B19 infec- tion, is an other possibility: particularly given that the patient is a primary school teacher. However , the viral arthritides tend to develop during the viral prodrome itself and are usually as sociated with a symmetrical small-joint polyarthritis, with a predilection for the upper li mbs. Other causes of arthritis or arthralgia in the context of erythema nodosum include enteropa thic arthritis (see p. 31), Beh et \200\231s disease (BD), lymphoma, tuber- culosis, and a cute sarcoidosis. Although enteropathic arthritis does usually result in a large-joint olig oarthritis affecting the knees and ankles, this woman does not have any symptoms suggestive of underlying inflammatory bowel disease (IBD). BD (see p. 223) would be uncommon in a Cau casian female, and it is usually associated with orogenital ulceration. Arthritis as the pr esenting feature of lymphoma in adults is rare, and has been reported more in children. Tub erculosis can spread to affect joints by haematogenous or lymphatic routes, or via contiguo us spread from an infected area. This tends to affect the spine and large weight-bearing jo ints. Alternatively, pulmonary or other organ tuberculosis can cause a reactive polyarthri- tis known as Poncet \200\231s disease. This can affect any joint areas, but knees, ankles, and elbows are the most common. This patient does not have any known risk factors or 23 CASE 4 symptoms suggestive of tuberculosis. Patients with acute sarcoidosis commonly have joint co mplaints (50 % ), with symmetrical ankle involvement being a strong diagnostic indicator. 2. What is the most likely diagnosis, taking the CXR findings into account? The CXR shows right paratracheal lymphadenopathy with symmetrical bilateral hilar lymphaden opathy. These radiographic findings comprise Garland \200\231s triad, which is a commonly s een in sarcoidosis with pulmonary involvement. Chest radiograph findings are staged as foll ows. \227\206 Stage 0: Normal \227\206 Stage 1: Bilateral hilar lymphadenopathy \227\206 Stage 2: Bilateral hilar lymphadenopathy with parenchymal involvement \227\206 Stage 3: Parenchymal involvement with shrinking adenopathy \227\206 Stage 4: Parenchymal involvement evolves to show volume loss. As there is no parenchymal involvement, this would be consistent with stage 1 disease. Lymp homa is an important differential diagnosis in the context of bilateral hilar lymphadenopat hy, and can only be definitively excluded on biopsy. Therefore the most likely diagnosis is acute sarcoidosis with stage 1 pulmonary involvement. 3. What is a likely explanation for this patient \200\231s muscle aches and what are the systemic manifestations of this condition? Muscle involvement in sarcoidosis is relatively common, occurring in 50 \200\22380 % of cas es. It is usually asymptomatic and so is often undetected. Granulomatous mus- cle involveme nt can lead to weakness, proximal pain, and tenderness. This may be focal or diffuse, in wh ich case it is symmetrical and causes progressive weakness and atrophy. Electromyography (E MG) studies show similar findings to polymyositis. Sarcoidosis is a multisystemic condition of unknown etiology, characterized by the presence of non-caseating granuloma in affected tissues. The various manifes- tations are summarized below: \227\206 Lungs (90 % ): lymphadenopathy parenchymal involvement pleural involvement may manifest as pneumothorax or pleural effusion (rare). \227\206 Skin (25 % ): erythema nodosum subcutaneous nodules papules 24 CASE HISTORIES IN RHEUMATOLOGY plaques lupus pernio. \227\206 Joints (50 % ): transient flitting arthralgia can precede fever symmetrical periarthritis knees, ankles. \227\206 Bone (30 % ): cysts, hands, and feet lytic lesions (rare) in the vertebral bodies, and occasionally in skull, long bones. \227\206 Eyes (25 % ): keratoconjunctivitis uveitis retinal vasculitis. \227\206 Neurological (5 % ): unilateral facial nerve palsy hypothalamic \200\223pituitary axis basal granulomatous infiltration peripheral neuropathy. \227\206 Abdominal (50 % ): hepatosplenomegaly nephrolithiasis due to hypercalcaemia. \227\206 Cardiac (5 % ): cor pulmonale due to lung disease arrhythmia left ventricular failure pericarditis. 4. How would you manage this patient and what is her prognosis? The joint symptoms usually improve with a combination of rest and non-steroidal anti-inflam matory drug (NSAID) treatment. In severe cases, steroids or colchicine may be used, but the re is little evidence base for this. Pulmonary involvement is treated according to disease and symptom severity. Steroid therapy is first line in symptomatic disease. Although stage 4 disease repre- sents pulmonary fibr osis, patients usually still derive symptomatic benefit which may be due to suppression of ongoing inflammation. In resistant cases, immuno- suppressive agents have been used with va riable benefit, but lung transplantation should be considered in those with progressive tre atment-resistant disease. The erythema nodosum usually self-resolves within a few weeks, but topical steroid therapy can be used as required. 25 CASE 4 Further reading Visser H , Vos K , Zanelli E , et al . ( 2002 ). Sarcoid arthritis: clinical characteristic s, diagnostic aspects, and risk factors . Ann Rheum Dis ; 61 : 499 \200\223 504 . 26 CASE HISTORIES IN RHEUMATOLOGY Case 5 A 76-year-old retired general practitioner presented to the rheumatology department with po lyarthritis which had developed insidiously over the previous 18 months. He was a lifelong asthmatic with a 10-year history of hypertension, a heavy smoker, and a heavy social drinke r. He took diclofenac, enalapril, and prednisolone 5 mg daily, and used salbutamol and becl ometasone inhalers. He admitted to self-medicating with oral steroids for most of his life to control his chest symptoms. On examination, he was in atrial fibrillation and had a barrel-shaped chest. He had bilater al swelling of his MCP joints, a left knee effusion, a right olecranon bursa, Dupuytren \200\231s contractures, and signs consistent with right carpal tunnel syndrome. Investigations showed the following: \227\206 Hb 16 g/L; WCC 7 \227 10 9 /L; platelets 232 \227 10 9 /L \227\206 Liver function normal; creatinine 135 mol/L; glomerular filtration rate (GFR) 55; fasting glucose 5.5 mmol/L; urate 642 mmol/L \227\206 CRP 10; RF latex screen positive; ELISA equivocal; anticitrullinated C-peptide (ACCP) negative. 27 CASE 5 Questions 1. What is the likely diagnosis and why? 2. Aspirate from the knee helped confirm the diagnosis. What are the likely findings? 3. What is the significance of the rheumatoid factor and uric acid levels? 4. What are the clinical manifestations of hyperuricaemia? 5. What management strategies will you suggest? Fig. 5.1 X-ray of patient s hands. 28 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What is the likely diagnosis and why? The most likely diagnosis is chronic gout. The differential diagnosis is between an acute inflammatory arthritis such as rheumatoid ar thritis and chronic gout. The radiograph (Fig. 5.1 ) shows asymmetri- cal swelling with \200\230punched-out \200\231 erosions away from the joint surface with no osteo- penia. The long-term steroid use is likely to have masked early episodic attacks of gout. Gout often affects osteoarthritic joints. Tophi over Heberden \200\231s or Bouchard \200\231s nodes ca n ulcerate and discharge, mimicking septic arthritis. This patient could have developed an acute inflammatory arthritis in addition to long-stand ing chronic gout which had been masked by long-term steroid use. This is an important diffe rential diagnosis to make as the management of the two condi- tions is very different. 2. Aspirate from the knee helped confirm the diagnosis. What are the likely findings? Knee aspirate revealed negatively birefringent monosodium urate crystals. A diagno- sis of gout is confirmed by the presence of uric acid crystals in a joint bursa or tophus. Aspirat e from his olecranon bursa was thick, chalky, and rich in urate crystals. Ideally, affected joints should be aspirated. However, if there are no actively inflamed jo ints, aspirate and washout from unaffected joints can aid diagnosis. The most common joint used in this situation is the knee. Diagnosis is confirmed if uric acid crystals are presen t in macrophages. 3. What is the significance of the rheumatoid factor and uric acid levels? The rheumatoid factor is positive in approximately 10 % of patients over the age of 60, and the percentage increases with age. The ACCP antibody is more specific for RA, and can help to differentiate between the two conditions. However, negative ACCP antibodies do not help to differentiate between gout and rheumatoid arthritis. Hyperuricaemia does not equate to a diagnosis of gout. Furthermore, serum urate levels fall , and may be misleadingly low during attacks of gout. However, hyperuricaemia is the most i mportant risk factor for developing acute gout, with a 5-year cumulative risk of one-third for patients with serum urate > 0.6 mmol/L. 4. What are the clinical manifestations of hyperuricaemia? The clinical manifestations of hyperuricaemia are: \227\206 asymptomatic hyperuricaemia \227\206 acute gout \227\206 recurrent gout \227\206 chronic tophaceous gout 29 CASE 5 \227\206 renal stone \227\206 rarely urate nephropathy. 5. What management strategies will you suggest? Gout is associated with hypertension, metabolic syndrome, insulin resistance, diabetes, and chronic renal failure. Once a diagnosis of gout is established, the aims of management are to control symp- toms, prevent future attacks, and prevent structural damage of joints and kidneys. This patient p resents a number of management problems because of his long-term steroid use and comorbidit ies, including hypertension and borderline renal function. NSAIDs should be stopped as they can exacerbate hypertension and decrease renal perfusion. In addition, the combination with oral corticosteroids puts this patient at high risk of a gastrointestinal bleed. Cyclo-oxgenase-2 (COX-2) selective NSAIDs such as etoricoxib and ce lecoxib have better gastrointestinal profiles, but should not be used in patients with pre- existing cardiovascular disease. Oral colchicine at a dose of 500 g twice to four times daily is an alternative treatment for inflammatory joint symptoms. Higher doses can cause diarrhea. Simple analgesics should be used for pain relief. Intra-articular or intramuscular steroids can help settle the acu te inflammatory symptoms. For long-term control of joint symptoms, the serum urate needs to be lowered and maintained below the saturation point for monosodium urate (<0.38 mmol/L). Target levels for serum ur ate are <0.30 mmol/L (BSR) and < 0.36 mmol/L (European League Against Rheumatism (EULAR)). Patients with gout are either under-excretors or over-producers of uric acid. This patient, as with 90 % of patients, is likely to be an under-excretor of uric acid. Long-term treatm ent using uricostatic or uricosuric therapies is needed if patients are unable lower their serum urate sufficiently to prevent attacks of gout with life- style modification. This is especially so in renal failure patients with symptomatic gout. The long-term treatment of c hoice is prevention of urate production using allopurinol is a xanthine oxidase inhibitor w hich inhibits production of urate from hypoxanthine and xanthine. Allopurinol should be sta rted once the acute symp- toms have been settled for 2 \200\2236 weeks using colchicines (o r NSAIDs if the patient is not in renal failure), otherwise there is a significant risk of acute gouty flare. The starting dose depends on the GFR ( > 80 mL/min, 300 mg daily; 15 mL/ min, 50 mg on alternate days) This patient (GFR 60) should start at 100 mg daily and increa se by 50 mg doses at fortnightly intervals until his serum urate is <0.030 mmol/L. Transien t rashes (2 % ) are uncommon but usually settle with dose reduction. Rarely, a life-threate ning allergic reaction with high fever, exfoliative dermatitis, acute hepatitis, interstiti al nephritis, and vasculitis can occur. Desensitization regimes are possible, but are rarel y used in practice. Patients who are intolerant or allergic to allopurinol can use a uricosuric agent to enhanc e urate renal clearance. These drugs inhibit the urate anion exchange in the proximal nephr on (URAT-1). Sulfinpyrazone (200 \200\223800 mg/day in divided doses) is the only drug read ily available in the UK, but requires normal renal function. It is effective in diuretic-in duced gout. Probenecid (0.5 \200\2232.0 g/day) can be used in 30 CASE HISTORIES IN RHEUMATOLOGY mild renal failure (creatinine <200 mol/L) and is available on a named patient only basis i n UK. Benzbromarone (50 \200\223200 mg/day) is effective in mild renal failure (eGFR 30 \200\22360) but is unlicensed in the UK (available on named patient basis). All three drugs have a significantly worse side-effect profile than allopurinol and are used as second-lin e agents in the UK. Benzbromarone can be used in combination with allopurinol. Febuxostat (40 \200\22380 mg/day) is a recently developed non-purine selective xan- thine o xidase inhibitor which is available to patients who are allergic to allopurinol and have fa iled uricosuric therapy. Enzyme therapy with urate oxidase is now licensed for intravenous infusion treatment for al lopurinol-intolerant patients. As a new therapy, the use will be limited by antibody format ion and cost. Lifestyle advice is important. Patients with early or mild gout can prevent future attacks by altering their lifestyle. \227\206 Fluid intake depends on cardiovascular and renal function. In general, patients a re advised to drink plenty of water to prevent renal stones. Over-producers of uric acid an d those taking uricosuric agents are particularly prone to renal stones. \227\206 Sweetened soft drinks and drinks high in fructose are associated with increased risk of gout in men. \227\206 Dietary advice is the same as the general advice given for the associated meta- b olic syndrome. In addition, patients should avoid foods rich in purines such as red meat, g ame, offal, and shellfish. \227\206 Alcohol enhances urate production, decreases renal urate clearance, decreases sol ubility of urate crystals, and can be relatively dehydrating. Beer, even non- alcoholic bee r, is purine rich. Avoid beer and binge drinking. Limit alcohol intake per week to <21 unit s (men) and <14 units (women). It is important to monitor renal function and general metabolic state. The patient \200\231 s metabolic syndrome may be a much more serious cause of mortality and morbid- ity than the ir gout. The lipid-lowering drugs atorvostatin and fenofibrate, and the antihypertensives l osartan and amlodipine, have mild uricosuric effects. This may be helpful when treating the comorbid conditions associated with gout. Further reading Jordan KM , Cameron JS , Snaith M, et al . ( 2007 ). British Society for Rheumatology and B ritish Health Professionals in Rheumatology guideline for the management of chronic gout . Rheumatology ; 46 : 1372 \200\223 4. Rider T , Jordan K ( 2010 ). The modern management of gout . Rheumatology ; 49 : 5 \200 \223 14. Zhang W , Doherty M , Bardin T , et al . ( 2006 ). EULAR evidence based recommenda tions for gout . Ann Rheum Dis ; 65 : 1301 \200\223 11. 31 CASE 6 Case 6 A 17-year-old Caucasian male was seen urgently in outpatients with a 3-week history of inte rmittent pain and swelling of his right knee. He had a past history of heel pain when he wa s 12 years old which had settled spontaneously. He was otherwise healthy, with no recent tr auma and no significant past medical history. A paternal uncle had psoriasis. On examination his height and weight were on the 60th centile and he was apyrexial with nor mal pulse and blood pressure. Examination of skin and musculoskeletal system was normal apa rt from a tense effusion of his right knee: 150 mL of straw- colored fluid was aspirated fr om his knee and 80 mg of Depo-Medrone was injected. Investigations showed the following: \227\206 Hb 12.4 g/dL; MCV 74 fL; WCC 12.4 \227 10 9 /L; neutrophils 6.9 \227 10 9 /L; p latelets 488 \227 10 9 / L; CRP 89.2 mg/L \227\206 Renal and liver functions were normal \227\206 Synovial fluid: no organisms; no crystals; 2 + WCC; 0 RBC; no growth. Questions \200\224Part 1 1. What is the differential diagnosis? 2. What further information is needed to make the diagnosis? 32 CASE HISTORIES IN RHEUMATOLOGY Answers 1. What is the differential diagnosis? In a young person, the most important differential diagnoses to consider are septic arthrit is (see p. 208), trauma, and reactive arthritis. A travel history and sexual his- tory are essential. With teenagers, it may be important to interview the patient without their paren ts to obtain an accurate history. The differential diagnosis is wide and includes enthesiti s-related juvenile idiopathic arthritis (JIA), early seron- egative inflammatory arthritis (psoriatic or enteropathic), undifferentiated spond- ylarthritis with peripheral joint invo lvement, atypical presentation of rheumatoid arthritis, and rarer conditions such as BD and acute sarcoidosis. In older patients a crystal arthritis should be considered. Enthesitis-related JIA would fit with the previous history of heel pain and knee swelling, more common in human leucocyte antigen (HLA) B27-positive patients (his first rheumatologic al presentation was at age 12). The heel pain may represent an enthesopathy; these are freq uently associated with spondyloarthritis but, as their symptoms are short-lived, they are o ften forgotten by patients and therefore need direct enquiry and examination. The MCV of 74 fL is significant. Blood loss due to NSAID use, iron-deficiency anae- mia due to malabsorption, inadequate diet, and blood loss should be considered. This patient had n ormal growth and was on the 60th centile for height and weight, which would not support a d iagnosis of long-standing malabsorption. However, undiag- nosed coeliac disease is known to be present in 0.5 % of the population, and should be screened for. There is an association with muscle pain, probably related to low-grade vitamin D insufficiency. There is no assoc iation with inflammatory arthritis. His low MCV might suggest a diagnosis of asymptomatic enteropathic arthritis. A careful GI history, particularly noting mouth ulcers, weight loss, and systemic malaise should be obtained. A history of psoriasis in a second-degree relative is of borderline significance, given the background population frequency of psoriasis; however, it does lend weight to a diagnosis of psoriatic arthritis. In younger children, a history of psoria- sis in a first-degree rel ative (psoriatic diathesis) may be enough for a diagnosis of psoriatic arthritis, as the ar thritis may precede the skin disease by many years, par- ticularly in children. 2. What further information is needed to make the diagnosis? A personal or family history of iritis, psoriasis, or colitis should be established. Clinic al examination should include all joints, especially the spine and sacroiliac joints. Skin, nail, and eye examination should be documented. This patient \200\231s diagnosis was enteropathic arthritis, with microcytosis due to gas- trointestinal blood loss. Six weeks later he was admitted with a 3-day history of severe abdominal pain associated wi th vomiting. He underwent laparotomy where he was found to have a 50cm segment of inflamed ileum proximal to the ileocaecal junction. Histology confirmed Crohn \200\231s disease (Fig s 6.1 \200\223 6.3 ). 33 CASE 6 Fig. 6.1 (See also Plate 6) Linear fissuring ulcer formed by granulation tissue on either s ide, and containing neutrophils. Fig. 6.2 (See also Plate 7) Granulomatous inflammation and giant cells. 34 CASE HISTORIES IN RHEUMATOLOGY Fig. 6.3 (See also Plate 8) Distorted acutely inflamed colonic crypts (crypt abscesses). 35 CASE 6 Questions \200\224Part 2 3. What are the treatment options? 4. How are his joint symptoms related to his Crohn \200\231s disease? 36 CASE HISTORIES IN RHEUMATOLOGY Answers 3. What are the treatment options? First-line treatment for the joint disease is aspiration and intra-articular steroid inject ion to the affected joint(s). The effect of drugs on the bowel needs to be considered in any treatment regime. Many patie nts are intolerant of NSAIDs, which can precipitate a flare of inflamma- tory GI symptoms. If joint symptoms do not settle with local steroid injections, sulfasalazine, methotrexate, or azathioprine are options. Anti-TNF treatments such as infliximab or adalimumab are curr ently used for severe Crohn \200\231s disease and enteropathic arthritis. 4. How are his joint symptoms related to his Crohn s disease? The peripheral arthritis may be mono-, oligo-, or polyarticular. Some authorities suggest a classification into two groups. Type I is a large joint oligoarticular pattern, primarily affecting the knees and ankles, with self-limiting episodes often mirroring bowel activity. Type II is a symmetrical peripheral polyarthritis, involv- ing both upper and lower limb. The clinical course of arthritis may run independ- ently of the IBD, although in some patie nts a flare of arthritis can signal a flare of IBD. The prevalence and pattern of arthritis is similar in Crohn \200\231s disease and ulcer- ative colitis. Approximately 20 % of patients with IBD have inflammatory joint disease during the course o f their illness. Symptoms are often episodic and variable, with 9 % suf- fering inflammator y back pain, 2 % having classical ankylosing spondyloarthritis (AS), and 5 % having asympto matic radiographic sacroiliitis.