In the first two differential diagnoses there are often other features. In SLE photosensitive rashes, hair loss, serositis and oral ulceration are seen. Erythrovirus B₁₉ nearly always presents with flu-like symptoms and a widespread rash.

Post-streptococcal arthritis may be preceded by a sore throat but is rare. Psoriatic arthritis is usually asymmetrical but can occasionally present with a symmetrical pattern. Psoriatic nail changes and other evidence of psoriasis are usually present, although these might develop after the onset of arthritis.

Sjögren’s syndrome can be associated with intermittent parotid swelling and sicca symptoms: dry eyes (keratoconjuctivitis sicca) and dry mouth (xerostomia).

How would you manage this patient?

Remember

Rheumatoid arthritis is a multisystem disease so look carefully for pulmonary, cardiac or neurological involvement, although these are less common at presentation.

A full history and general medical examination is essential. Specific points:

• Look for nodules or vasculitis: uncommon at first presentation.

• A full musculoskeletal examination noting the symmetry of the joint involvement.

• Look for persistent inflammatory symmetrical arthritis (PISA). The most common cause of this is rheumatoid arthritis.

The most commonly involved joints at onset in rheumatoid arthritis are: wrists, MCPs, PIPs and MTP joints.

Admission is necessary if the patient is very unwell systemically and to exclude other pathology.

Initial management

• A short period of bed rest, ice packs if only a few joints involved.

• NSAIDS: ibuprofen is the safest; other NSAIDs have a higher risk of GI toxicity, although this patient is young.

• Disease-modifying anti-rheumatic drugs (DMARDs): these should be given at the earliest opportunity because RA is a systemic disease that leads rapidly to joint damage and disability. It is no longer acceptable to treat RA with NSAIDs alone. There is accumulating evidence to show that early DMARD use delays joint damage and functional disability.

Initial DMARDs commonly used include sulfasalazine, methotrexate or azathioprine. Others, such as IM gold and D-penicillamine, are less commonly used but still effective. Hydroxychloroquine and auranofin are the least effective but can be used in combination regimens. Combination therapies are showing good results.

Anti-TNFα agents, e.g. infliximab and etanercept, are effective when initial DMARD therapy has failed. Infectious complications such as tuberculosis are a concern with these agents.

Late manifestations of RA

Changes in the hand are shown in Figure 8.5. Other joints such as knees and hips become involved later in the disease course.

Figure 8.5 Rheumatoid arthritis (RA) – late manifestations.

All drugs need careful explanation to the patient and close monitoring for toxicity.

Prednisolone is not used in young patients but intramuscular methyl prednisolone 40–120 mg gives excellent short-term benefit.

The addition of prednisolone 7.5 mg to existing DMARD therapy might retard the progression of erosions, but studies in this area remain controversial and this is not recommended for general use at present.

Diagnosis.

This patient had a high ESR of 60 mm/h and a CRP of 90 mg/L, suggesting active disease. Her anti-CCP antibodies and rheumatoid factor were positive in the serum, typical of rheumatoid arthritis. The X-rays of her hands showed only soft tissue swelling. An MRI was therefore performed and showed early erosions, confirming the diagnosis.

Progress.

This patient was admitted and symptomatically treated with analgesics. She was started on prednisolone and methotrexate. The pain and swelling improved and she was discharged with still some remaining residual problems. She was given a follow-up in clinic for 2 weeks.

SLE and vasculitis

Case history

A 28-year-old woman is referred to you by her doctor. Six weeks ago she delivered her first baby and the pregnancy and delivery were uneventful. Two weeks after delivery she developed a widespread polyarthritis affecting her hands, feet and knees and a photosensitive rash on her face. In the last week or two she has become extremely unwell with weight loss and painful lesions on her hands and feet.

On examination she is clearly unwell with a facial rash and severe oral ulceration. Examination of her hands and feet shows extensive digital infarcts with necrotic ulceration on the palms, finger pulps and soles of the feet. There are splinter haemorrhages and nail-fold infarcts.

Discuss the differential diagnosis, investigation and management

The differential diagnosis includes an inflammatory autoimmune rheumatic disease such as systemic lupus erythematosus (SLE), which has developed after delivery of her baby. The lesions on her hands (Fig. 8.6) and feet are strongly suggestive of vasculitis, which is a serious prognostic factor that requires immediate therapy.

Figure 8.6 Vasculitic lesions seen in the fingers.

Investigations (Table 8.1) are performed to look for the possibility of major organ involvement, which might be vasculitic. Her urine must be tested immediately for blood and protein and sent for urine cytology looking for fragmented red cells and/or casts. The presence of an ‘active’ urine sediment with fragmented or dysmorphic red cells and granular casts has a > 90% specificity for glomerulonephritis.

Table 8.1 Investigations for SLE and vasculitis

Investigation	Typical finding
FBC	Immune cytopenias, especially neutropenia and thrombocytopenia, are common in SLE
	There may be anaemia of chronic disease or haemolytic anaemia – check Coombs’ test.
ESR and CRP	The pattern of a high ESR but normal CRP is characteristic of SLE
Renal function	U&E, 24-h urine protein/eGFR
Liver biochemistry	Hypoalbuminaemia is common
Lupus serology
ANA	Present in 95% of SLE patients
dsDNA	Specific marker for SLE. A negative dsDNA, however, does not exclude SLE
ENA	Ro/La photosensitivity/Sjogren’s RNP/Sm often seen in severe SLE
Complement	Low values indicate activation of complement or rarely congenital deficiency
ANCA	A marker of vasculitis: a systemic vasculitis is an alternative to SLE

Remember

The major risk of vasculitis is organ involvement including renal, cerebral and pulmonary disease, which can be life-threatening.

Diagnosis.

She was found to be anaemic with an Hb of 0.5 g/L, a raised ESR of 80 mm/h, normal CRP, a raised ANA and anti-ds DNA autoantibodies. A diagnosis of systemic lupus erythematosus.

Once the diagnosis of lupus and vasculitis is established on clinical and serological grounds, therapy is with prednisolone and IV pulse methyl prednisolone 500 mg on alternate days for three doses.

Immunosuppressive therapy is commonly used to treat vasculitis. One commonly used approach is intravenous 500 mg cyclophosphamide therapy given 2-weekly or monthly. The patient should be carefully counselled about the risks and benefits of cyclophosphamide; these include the adverse effects such as cytopenias, haemorrhagic cystitis, infections including herpes zoster and infertility. If the patient is breastfeeding she should discontinue this because cyclophosphamide and other immunosuppressives such as azathioprine are excreted in breast milk.

Remember

Specialist advice from a rheumatologist or immunologist should be sought.

Progress.

On treatment with steroids (see above) her symptoms settled and it was decided to delay immunosuppressive therapy until after she had stopped breastfeeding.

Acute autoimmune rheumatic disease

Case history

A 33-year-old woman of African origin is admitted through A&E complaining of breathlessness and swollen legs. Two years ago she was admitted with a psychotic illness that had features of schizophrenia and improved with anti-psychotic medication.

In the last 6 months she has developed a symmetrical small joint inflammatory arthritis, mouth ulcers and photosensitive facial rashes. Over the last 2 weeks she has become breathless and her legs have become severely swollen.

On examination she is anaemic and has a pulse rate of 120/min with pulsus paradoxus. Her BP is 90/60. She has bilateral pleural effusions, a raised jugular venous pressure with a sharp rise and y descent (Friedreich’s sign) and pitting oedema to her waist. There is synovitis of the small joints of her fingers and she has florid splinter haemorrhages. Her urine showed heavy proteinuria.

What is the likely diagnosis?

Diagnosis is likely to be SLE complicated by the nephrotic syndrome. In addition, she may have cardiac tamponade from a pericardial effusion.

SLE is nine times more common in females than in males, and is more common in people of African and Far Eastern ancestry; it is often more severe in these ethnic groups.

This patient has many characteristic features of SLE: inflammatory polyarthritis, mouth ulcers, photosensitive rashes, psychotic illness, serositis with pleural and probably pericardial effusions and renal disease with nephrotic syndrome (Fig. 8.7). The high JVP might indicate early tamponade.

Figure 8.7 Clinical features of systemic lupus erythematosus (SLE).

How would you manage this patient?

The most urgent priority is whether this patient has cardiac tamponade. The low BP and the presence of pulsus paradoxus, tachycardia and raised JVP with increased distension during inspiration and cardiomegaly on CXR are strong pointers to this. An echocardiogram is performed urgently, which shows an echo free region between the myocardium and the intense echo of the parietal pericardium. This confirms the effusion and the clinical signs confirm tamponade.

The overwhelming majority of patients with lupus who have cardiac tamponade associated with a pericardial effusion respond to high-dose oral corticosteroids and do not need pericardiocentesis. This, however, should be performed if the patient deteriorates despite corticosteroid therapy or if sepsis is present. A normal CRP makes infection less likely.

The next priority is to determine the extent and severity of the renal disease. Serum creatinine, eGFR, albumin, 24-h urine protein are essential. If there is an ‘active’ (p. 245) urine sediment, e.g. fragmented red cells and granular casts, indicating glomerulonephritis, renal biopsy is indicated.

Investigations

• FBC with reticulocyte count/Coombs’ (direct anti-globulin test) if positive: the anaemia is haemolytic

• U&Es (eGFR): renal impairment may be present

• Biochemistry: serum albumin will be low

• 24-h urine protein should be started

• Urine cytology for fragmented red cells and granular casts: a useful marker of glomerulonephritis

• CXR: to document pleural effusions and cardiomegaly (Fig. 8.8)

• Echocardiogram: to document pericardial effusion and possible valve lesions

• ECG

• Blood gases

• Blood cultures/urine cultures: to exclude sepsis, especially endocarditis, prior to corticosteroid and immunosuppressive therapy

• Full autoantibody screen: ANA, DNA, ENA, Rh factor, anti CCP, anti-cardiolipin antibodies, lupus anti-coagulant, ANCA

• Complement studies

• A diagnostic renal biopsy may be required later

Figure 8.8 Diagram of a CXR showing pleural effusions and cardiomegaly.

Other points

A normal protein diet is necessary with salt restriction and diuretic therapy with a thiazide, e.g. bendroflumethiazide 5 mg daily.

• Thrombosis prophylaxis: this patient is at high risk of deep vein thrombosis (DVT)/pulmonary embolus (PE). TED stockings and prophylactic low molecular weight heparin should be given.

• Is the anaemia haemolytic? If so, it should respond to corticosteroids.

• When the blood pressure has normalised as a result of treatment of the tamponade, start an ACE inhibitor. This is especially useful in proteinuric patients.

• If renal biopsy confirms proliferative glomerulonephritis: the treatment of choice is corticosteroid therapy and intermittent intravenous cyclophosphamide followed by azathioprine.

• This patient’s lipid profile might well be deranged, especially in the nephrotic syndrome. This will need to be assessed and managed actively. Measurement of serum lipids is performed and the patient started on a statin immediately if hypercholesterolaemia is present.

• Prophylaxis against corticosteroid-induced osteoporosis. A baseline dual energy X-ray absorptimetry (DXA) scan should be performed and calcium supplementation should be started.

Long-term prognosis

The majority of patients with SLE have a good prognosis, although clearly this patient has a serious disease with life-threatening complications. Mortality in SLE occurs at two peak periods: those patients who die from overwhelming disease, thrombosis or sepsis and those who die prematurely from accelerated atherosclerosis. Prognosis has been considerably improved by earlier recognition and effective therapy.

Progress.

This patient had several problems. Her cardiac effusion responded to high dose oral steroids gradually and her blood pressure improved. She had a haemolytic anaemia of 95 g/L. She was discharged on steroids and an ACE inhibitor after an inpatient stay of 2 weeks. She later had a renal biopsy which confirmed a proliferative glomerulonephritis and was seen by the neurologists for treatment. A DXA scan did not show osteoporosis.

Further reading

Tsokos GC. Systemic lupus erythematosus. New Eng J Med. 2011;365:2110–2121.

Thrombosis and the anti-phospholipid syndrome

Case history

A-25-year old woman presents with a 2-day history of left leg swelling and on the day of admission she notices breathlessness and chest pains that are worse on deep inspiration.

In her past medical history you find that she has had three miscarriages and one successful pregnancy. This pregnancy was complicated by hypertension and intrauterine growth retardation with a premature delivery at 31 weeks. On further questioning you note that she has had oral ulceration, rashes that are worse in the sunlight and has also been having headaches.

Drug history

She is on the oral contraceptive pill.

On examination

She has extensive splinter haemorrhages on most fingers. Her pulse is 100 and BP 110/70 but she is not cyanosed. Her heart sounds are normal but there is a soft murmur of mitral regurgitation. She also has a soft left pleural rub.

Abdominal examination and neurological examination are normal. The left calf is swollen and the calf circumference is 3 cm greater than on the right. You note extensive livedo reticularis on her arms, thighs and knees.

What is the differential diagnosis and your management?

This young woman (who is on the oral contraceptive pill) has a deep venous thrombosis (DVT) and a pulmonary embolus (PE) until proved otherwise.

A full blood count revealed thrombocytopenia, which is commonly seen in the anti-phospholipid syndrome.

Investigations

• An ECG: looking for the classic (but seldom seen) S1, Q3, T3 pattern of PE (Fig. 8.9)

• A CXR: but this is likely to be normal. However, it is useful to exclude other causes of pleuritic chest pain, including infective causes

• An ultrasound scan of the leg veins to document the extent of the left calf thrombosis

• A V/Q scan to show the extent of the pulmonary emboli is still useful if CT not available

• Plasma D-dimers: if undetectable the diagnosis of PE and DVT is excluded

• Multidetector CT with contrast: good specificity 96% and sensitivity 85% for medium-sized PEs

• Choose the imaging techniques according to local availability

Figure 8.9 Acute pulmonary embolism shown by a 12-lead ECG. There is an S wave in lead I, a Q wave in lead III and an inverted T wave in lead III (the S1, Q3, T3 pattern). There is sinus tachycardia (160 bpm) and an incomplete right bundle branch block pattern (an R wave in AVR and V₁ and an S wave in V₆).

An echocardiogram and blood cultures in women are essential because differential diagnosis includes Libman–Sacks endocarditis or infective endocarditis.

Differential diagnosis

In this case this includes the anti-phospholipid syndrome with a DVT and pulmonary emboli, along with an increased risk of thrombosis from the oral contraceptive pill. The history is rather suggestive of SLE, and this should be investigated further with autoantibodies to ANA, DNA and ENA with complement studies. The features favouring a diagnosis of the anti-phospholipid syndrome in this case would include the three previous miscarriages and one pregnancy complicated by intrauterine growth retardation and premature delivery. There is accumulating evidence in the literature to suggest that the intrauterine growth retardation is due to recurrent placental thrombosis and this is often manifested by reduced umbilical artery flow patterns on Doppler studies, with an increased resistance index, notching or even reversed flow in the umbilical vessels.

Information

• The anti-phospholipid syndrome is due to the presence of antibodies that bind phospholipids, leading to both venous and arterial occlusion

• The syndrome is most commonly seen in SLE but can occur in isolation: primary anti-phospholipid syndrome

The anti-phospholipid syndrome

Anti-cardiolipin antibodies and the lupus anti-coagulant should be performed. Both the anti-cardiolipin antibodies and the lupus anti-coagulant are anti-phospholipid antibodies and both should be requested because a small percentage of patients have either one or the other antibody but not both. A thrombophilia screen can exclude other factors, including the factor V Leiden mutation. Patients with the anti-phospholipid syndrome also have reduced protein C and S levels, which are associated with the lupus anticoagulant.

Libman–Sacks endocarditis

Splinter haemorrhages and a mitral murmur indicate Libman–Sacks endocarditis, which is a feature of the anti-phospholipid syndrome and SLE. These patients get a mucinous degeneration of the mitral valve leaflets and occasionally thrombus (which might embolise) is seen on the damaged valves. Similarly, the damaged valves might become secondarily infected, leading to infective endocarditis. The splinter haemorrhages could represent micro-emboli and are a feature of both anti-phospholipid syndrome and infective endocarditis.

How would you manage this patient?

Progress.

This woman should be admitted and commenced on heparin. The heparin can be given intravenously as a continuous infusion but many hospitals use once-daily low molecular weight heparin. Warfarin should be commenced and the eventual target INR should be 2.5.

The diagnosis of the anti-phospholipid syndrome was confirmed and therapy with life-long warfarin at the target INR was started. These patients are often resistant to warfarin and occasionally require high doses, e.g. 15–20 mg warfarin daily.

In terms of the mitral valve disease, this patient needed counselling about appropriate antibiotic therapy for any infection. Prophylactic antibiotics are not required. Infective endocarditis was excluded and she was monitored regularly because a small percentage of these patients require mitral valve replacement.

Further reading

Hughes GRV. Hughes’ syndrome: the anti-phospholipid syndrome. Journal of the Royal College of Physicians of London. 1998;32:260–264.

Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010;376:1498–1509.

Crystal arthritis

Two main types of crystal account for the majority of crystal-induced arthritis. They are sodium urate (gout) and calcium pyrophosphate (pseudogout) and are distinguished by their different shapes and refringence properties under polarized light with a red filter. Rarely, crystals of calcium apatite or cholesterol cause acute synovitis.

Case history

A 73-year-old woman was admitted a week ago to the Stroke Unit, having had a right hemiparesis. She has developed a hot, swollen right knee. You have been asked to see the patient for your advice on whether this might be a septic arthritis.

On further questioning, you discover that the patient has attended the hypertension clinic for many years and has been taking bendroflumethiazide. She has also complained of knee pain intermittently over the last 5 years but the joint has never previously swelled up. She is making a reasonable recovery from her stroke and there is no other relevant history.

Clinically, there is no evidence of tophi. The knee is hot and movement is restricted due to a large tense effusion. She is afebrile.

How would you manage this patient?

The X-ray showed chondrocalcinosis (Fig. 8.10) and patello-femoral and tibio-femoral osteoarthritis. The serum uric acid was elevated (520 µmol/L); she is taking a thiazide diuretic. The differential diagnosis thus includes gout or pseudo-gout, of which pseudo-gout is probably more likely in this clinical context. The uric acid level, although high, is usually > 600 µmol/L with gout.

Figure 8.10 Chondrocalcinosis of the knee. Note the linear calcification in the hyaline cartilage and calcification of the lateral meniscus (plus mild secondary OA).

Pseudo-gout

This patient has the typical presentation of pseudo-gout – an acute onset of a swollen joint in an elderly patient who has been admitted for other reasons – usually a stroke, MI or chest infection.

Calcium pyrophosphate is the most common crystal associated with pseudo-gout (Fig. 8.11). The crystals are diagnosed on synovial fluid analysis using polarised light microscopy. They are rhomboidal and positively birefringent and can be idiopathic or associated with osteoarthritis. A number of metabolic conditions are also associated with calcium pyrophosphate deposition; these include hypothyroidism, hyperparathyroidism, acromegaly, Wilson’s disease, haemochromatosis, hypophosphatasia and hypomagnesaemia.

Figure 8.11 Calcium pyrophosphate and urate crystals.

The differential diagnosis of gout is also confirmed on crystal examination. These urate crystals are negatively birefringent needle-shaped crystals.

Management

Septic arthritis, although unlikely, should be excluded and, providing joint aspiration and synovial fluid culture and blood cultures are all negative, the knee should be aspirated to dryness and injected with a steroid such as 40 mg of methylprednisolone. Risk factors should be minimised and, in particular, the thiazide diuretic (which can precipitate gout) should be switched to an alternative anti-hypertensive medication. Intensive physiotherapy is necessary, with particular attention to quadriceps exercises and maintaining mobility and hydration in the patient.

Progress.

She was started on diclofenac 50 g × 3 daily and was able to be gradually mobilised with the help of physiotherapy. Her speech improved over the first 2 weeks but she was left severely disabled by her right sided weakness. She was eventually transferred to long-term care.

Further reading

Neogi T. Gout. N Engl J Med. 2011;364:443–452.

Polymyalgia rheumatica/cranial arteritis

Polymyalgia rheumatica (PMR) and giant cell (cranial) arteritis are a systemic vasculitis affecting people over 50 years of age. Both are associated with the finding of a giant cell arteritis on temporal artery biopsy.

Case history

A 73-year-old woman presents to A&E feeling non-specifically unwell. On further questioning she has a headache and joint aches, particularly of her shoulders and hips, in addition to widespread aches and pains. She has marked joint stiffness particularly of the shoulders and hips, lasting for several hours each morning, and occasionally all day. The headache is predominantly right-sided and the patient says that it is painful when she brushes her hair. In addition, she has pains in the left jaw on talking or eating.

On examination the scalp is tender and it is difficult to palpate the temporal arteries. The rest of the examination is normal. Her shoulders and hips ache at the extremes of the range of movement but are otherwise normal.

Differential diagnosis and management

The most likely diagnosis in a patient over 50 years is temporal arteritis with PMR and there is therefore a significant risk of blindness from arteritis of the ophthalmic artery. A differential diagnosis includes malignancy of any cause and myeloma which can, rarely, mimic PMR. The ESR is nearly always significantly elevated but approximately 1–5% of patients with polymyalgia rheumatica have a normal ESR.

Investigations

The following investigations are essential:

• Temporal artery biopsy

This patient should be commenced on 60 mg of prednisolone immediately and a temporal artery biopsy should be arranged within the next 24 h. The clinical diagnosis is giant cell arteritis.

The histological features of GCA are:

Histological features of cranial arteritis

• Intimal hypertrophy

• Inflammation of the intima and sub-intima

• Breaking up of the internal elastic lamina

• Giant cells, lymphocytes and plasma cells in the internal elastic lamina

The response to steroids is usually dramatic in these patients and a response is often seen within 24–48 h. The steroid therapy can then be reduced reasonably quickly, over a few months, to 15–20 mg daily, and if this is not possible, then a steroid sparing agent such as azathioprine should be added to achieve this. The addition of low-dose aspirin may reduce the risk of blindness. This patient is also at high risk of osteoporosis and subsequent vertebral fractures, and calcium and vitamin D supplementation should be co-prescribed routinely. A baseline DXA should be requested. If there is already osteoporosis, bisphosphonates should be given.

Progress.

This patient’s headache quickly went on steroid therapy and in 6 months she was well on prednisolone 10 mg daily with a normal ESR. Her steroids will be continued for at least 1 year, with regular checks of her ESR.

Patients who fail to respond to steroids

Such patients should be investigated in detail for an underlying malignancy, especially multiple myeloma. Occasionally, other conditions such as severe hypothyroidism might also present with similar joint aches but the clinical picture of temporal arteritis with a good response to steroids is usually characteristic enough to establish the diagnosis.

Acute back pain

This is usually due to acute lumbar disc prolapse. The central disc gel may extrude into a fissure in the surrounding fibrous zone and cause acute pain and muscle spasm, which in turn leads to a forwards and sideways tilt when standing.

Case history

A 36-year-old publican presents to A&E having just lifted a barrel of beer. He experienced severe buttock and back pain. The pain radiated down the left leg to the sole of the foot with associated paraesthesiae. On further questioning he finds that it is extremely painful to move his back and that the pain is worse on coughing or sneezing. The pain is also worse in the leg than in the back. He says that he has not passed any urine for 6 h.

On examination

He is in severe pain and is lying flat on the examination couch. He finds it too painful to stand up but the hips, knees and other joints are all normal on examination. Straight leg raising on the right is 40° and on the left is only 10°, with a strongly positive sciatic stretch test. The femoral nerve stretch test is also strongly positive on the left and neurological examination reveals an absent left ankle jerk and sacral anaesthesia.

Discuss your further investigations, diagnosis and management

The history and clinical examination are almost diagnostic for a large L5/S1 disc protrusion with compromise of the cauda equina, which can lead to urinary retention. This is therefore a neurosurgical emergency.

The most urgent investigation is imaging of the lumbar spine and pelvis; magnetic resonance imaging (MRI; Fig. 8.12). The patient should be catheterised and analgesia given. This includes intramuscular non-steroidals such as IM diclofenac or opiate analgesics including morphine if needed. The patient should be referred immediately to a neurosurgeon or orthopaedic surgeon with an interest in acute spinal problems for urgent decompressive surgery with a laminectomy and discectomy. Any delay in diagnosis or decompression might lead to a permanent neurological deficit.

Figure 8.12 MRI of lumbar spine showing a central disc prolapse at the L4/L5 level (arrow). The signal from the L4/L5 and L5/S1 discs indicates dehydration, whereas the appearance of the L3/L4 signal is normal.

In patients without sacral anaesthesia or neurological deficit, the evidence-based advice is not to recommend bed rest but to mobilise the patient as soon as possible using adequate analgesia. Rapid access to physiotherapy can improve outcome, and procedures such as sacral or lumbar epidurals might be necessary to relieve pain while recovery occurs.

Progress.

This patient required urgent surgery as the MRI showed a large L5/S1 disc protrusion. He made a good recovery and had no permanent neurological deficit.

Severe back pain/osteoporosis

Osteoporosis is characterised by reduced bone density and micro-architectural deterioration of bone tissue, leading to increased bone fragility and the susceptibility to fracture.

Case history

A 71-year-old woman presents with severe thoracic spinal pain, which came on suddenly 6 h previously. The pain is severe and radiates around the thoracic spine and front of the chest and is worse on coughing or sneezing. In the past medical history she has had rheumatoid arthritis for the last 25 years and is currently taking 7.5 mg of prednisolone daily. Her rheumatoid arthritis has been in remission for 5 years on this therapy and she is on no other medication. Disease-modifying drugs used in the past have either induced toxicity or have been ineffective.

On examination there is evidence of quiescent rheumatoid arthritis with classic rheumatoid deformities, nodules and synovial thickening, but no active synovitis. On examination of the thoracic spine there is a marked kyphosis and she is exquisitely tender over T8. The thoracic spine is markedly restricted on rotation, reproducing her pain radiating around the chest to the anterior aspect of the chest.

Discuss your differential diagnosis and management in this case

The most likely diagnosis is steroid-associated osteoporosis with an acute vertebral fracture. The differential diagnosis should include myeloma and other malignancies because these can also present with vertebral fractures.

Imaging should include a chest X-ray and specific views of the dorsal spine, which are likely to show one or more vertebral crush fractures. Crush fractures have a fairly characteristic appearance and on the AP view of the thoracic spine all the pedicles should be visible. Should any pedicles be missing, this should immediately raise the suspicion of metastatic malignancy as a cause of the vertebral fracture.

Later, a myeloma screen including a protein electrophoresis strip, serum light chain assay and urine for Bence Jones protein should be done.

A DXA scan is performed to establish the degree of osteoporosis (Fig. 8.13). This gives an accurate index of bone mineral density in relation to the normal range for an age-, sex- and race-matched population. The World Health Organization definition of osteopenia is a T score of between –1.5 and 2.5. The definition of osteoporosis is a T score of greater than –2.5 standard deviations below the mean and established or severe osteoporosis is a T score of greater than –2.5 with an established fracture.

Figure 8.13 DXA scan. Graph showing BMD (vertical axis) against age. T score = number of standard deviations that patient’s BMD differs from population average for healthy young adult. Z score: as T score but BMD deviations from population average for patient’s age.

Initial management

In the acute setting of a recent vertebral fracture, strong analgesia, e.g. meptazinol 200 mg every 3–6 hours intramuscularly or intravenously if necessary. Salmon calcitonin 50 units daily, increasing to 100 units intramuscularly or 200 units daily by nasal spray for 6 weeks has a very good analgesic effect and works rapidly. Its main adverse effects include hypotension and flushing with nausea although most patients are able to tolerate 50 units daily. A single intravenous infusion of a bisphosphonate (pamidronate 60–90 mg) also gives some pain relief.

Progress.

This woman’s pain proved difficult to control and kyphoplasty was performed. This involves injecting methyl methacrylate through a needle placed directly into the damaged vertebra. This allowed mobilisation with physiotherapy help.

Later management

This patient should commence specific therapy for osteoporosis.

Therapies include cyclical etidronate with calcium or weekly alendronate or risedronate. These therapies are well tolerated in this age group but alendronate and risedronate are associated with a small but significant risk of oesophagitis. All the bisphosphonate drugs are poorly absorbed and should be taken at least 2 h before a meal with a full glass of water and, in particular with alendronate, the patient should not lie down for at least 2 h after taking the medication to reduce the risk of oesophagitis. Strontium ranelate is used in post-menopausal osteoporosis. These medications increase bone mineral density over a 3- to 5-year period and also reduce fracture risk.

Hormone replacement therapy (HRT) is not usually used in women of this age because of the adverse effects, which include breast tenderness and a return of menses. Raloxifene, a selective oestrogen-receptor modulator (SERM) has been shown to increase bone mineral density. The main adverse effects of raloxifene include a risk of thrombosis and possible endometrial/uterine malignancy. There is evidence that raloxifene protects against the risk of breast cancer.

Other factors used in the treatment of osteoporosis include stopping smoking, keeping alcohol intake to a moderate level and encouraging active weight-bearing exercise. Attention to diet is necessary, particularly in this age group, and a broad varied diet containing a reasonable calcium intake should be advised; if necessary a specific dietitian referral would be helpful. These patients should be monitored with DXA scan to check on progress.

Progress.

This woman had not been given prophylactic bisphonate therapy, which is usually necessary in addition to calcium for patients on long-term steroids. Nor did she have regular DXA scans to assess the development of osteoporosis.

Her prednisolone 7.5 mg daily was gradually tapered and stopped and her RA remained in remission, with some analgesia with an NSAID being required. She has continued on alendronate calcium and has regular DXA scans.

Osteomyelitis

Case history

A 56-year-old Asian woman presents with a 2-month history of upper back pain and weight loss. She has just arrived home after visiting relatives in Bangladesh for the last year.

There is no relevant past history and she is taking no medication.

On examination she is in pain and looks thin. Her pulse is 110 per minute and regular; her temperature is 38°C. Cardiovascular, respiratory and abdominal examinations are all normal and neurological examinations including power, tone and reflexes are within normal limits. There are no sensory signs.

All her joints are normal but she is tender over the thoracic spine, which is exquisitely painful on rotation of the thoracic spine.

Investigations

• Hb 106 g/L, MCV 83

• ESR 102 mm/hour, CRP 94

• U&Es normal

• Biochemistry – Serum Ca 2.3 mmol/L; phosphate 1.2 mmol/L; serum alkaline phosphatase 103 IU/L

A thoracic spine radiograph was normal. A chest X-ray showed no evidence of tuberculosis.

What is the differential diagnosis?

The differential diagnosis is spinal tuberculous osteomyelitis (Pott’s disease) despite the normal chest X-ray. A differential diagnosis would include Staphylococcus aureus discitis, although this tends to affect the lumbar spine whereas tuberculous spinal disease characteristically affects the thoracic spine or the thoraco-lumbar junction.

The most useful investigation is an MRI scan of the thoracic spine. This showed destruction of the vertebral body T4 with evidence of discitis T4/T5. A paravertebral abscess accompanied the bone destruction. These findings are typical of thoracic spine tuberculosis. There was no evidence of cord compression so a neurosurgical opinion was not required. Aspiration of the vertebral abscess was carried out to culture the tubercle bacillus and to obtain the sensitivities. She was commenced on isoniazid, pyrazinamide, rifampicin and ethanbutol, to be given for 9 months (reducing drugs when sensitivities known, p. 362). Other risk factors should always be considered, such as immunosuppression and HIV disease.

As vertebral collapse was not present, the prognosis is usually excellent in these patients if the organism is fully sensitive to therapy and compliance with therapy is maintained.

Progress.

This patient made an excellent recovery and was left with no sequelae from her spinal abscess.

Septic arthritis

Septic arthritis is due to haematogenous spread from skin or a respiratory tract infection. It is also seen occurring after surgery or sometimes following trauma to the joint.

Case history

A 21-year-old man presents with pain and swelling of his right knee. On further questioning he had no other symptoms. He had no relevant past medical history. Specifically, he has had no diarrhoea, urethritis, rashes or oral ulceration and has had no problems with inflammation of his eyes. His sexual history revealed many sexual contacts, including oral/anal sex with other men.

How would you investigate and manage this patient?

The most common diagnosis in a young man with a monoarthritis is a reactive arthritis associated either with diarrhoea or with urethritis, usually chlamydial in origin (Fig. 8.14). However, clinical questioning with this man has excluded any associated features that would point to reactive arthritis (a triad of urethritis, arthritis and conjunctivitis – Reiter’s disease)and septic arthritis should be considered as the most likely diagnosis, raising the possibility of HIV disease.

Figure 8.14 Clinical features of reactive arthritis.

Investigations

• Full blood count normal

• ESR 74 mm/1 hour

• Biochemistry, including a serum uric acid 420 µmol/L

The joint should be X-rayed and a series of blood cultures performed following admission to MAU.

Using sterile technique the joint should be aspirated and the fluid sent for microscopy, culture and crystals.

Information – knee aspiration

• Explain procedure and obtain consent

• Strict aseptic technique

• 2% lidocaine as local anaesthetic

• Medial or lateral approach 0.5–1 cm below the patella

• Use a white needle to ensure that even viscous or purulent fluid can be aspirated easily

• Caution in patients on warfarin

• Do not inject steroids if fluid is purulent

The most common organism is Staphylococcus aureus, which is seen in between 40% and 70% of patients. Gram-negative organisms are the next most common but a careful search for gonorrhoea should be conducted and the patient should be referred to the genitourinary medicine clinic for urethral swabs and other tests.

This man is at risk for HIV and should be counselled carefully before arranging an HIV test. Should HIV be proven then microbiology assessment of the synovial fluid is crucial, particularly for atypical organisms such as Mycobacterium avium intracellulare and other forms of tuberculosis.

Progress.

In this man, a septic arthritis was confirmed on blood and synovial fluid culture (Table 8.2) due to Staph. aureus infection. He required 6 weeks of intravenous antibiotics, flucloxacillin plus oral fucidic acid. Arthroscopic drainage and washout of the joint was performed at 48 hours, which minimised joint damage.

Table 8.2 Examination of synovial fluid