Chalky nodules suggest more tests are needed to rule out OA as a cause of pain.
Welcome to the latest edition of Rheumatology Reasoning.
My aim is to present a common case and work through the reasoning of why I order each test, what questions are most useful to help diagnose this condition and a simple approach to management. The approach is practical and based upon experience and evidence (where it exists). I hope you will find it useful in your daily practice.
A 62-year-old female presents with pain and difficulty using her hands. There has been a rapid increase in pain over the past four months and difficulty flexing her fingers, causing problems with daily activities. She has noticed nodules in several fingers. Her pain has become chronic but there were discrete episodes in the first months of pain, redness and swelling. There has not been lower-limb arthritis. Her medical background is notable for obesity with BMI of 34, hypertension requiring perindopril and hydrochlorothiazide, type 2 diabetes requiring Metformin and stage 3 chronic kidney disease with eGFR of 45. Renal impairment is presumed to be due to vascular disease.
She has pre-existing osteoarthritis of her fingers, and she had been advised that her pain is secondary to osteoarthritis.
Closer examination of her fingers show that the nodules appear chalky, raising suspicion that this is tophaceous gout. Examination does not reveal tophi elsewhere and there is no splenomegaly on examination. Serum uric acid is raised at 0.62mmol/L (N<0.40mmol/L).
It is unusual for gout to initially occur in the fingers without any preceding episodes of gout or evidence of tophi elsewhere in the body. There is a notable group of patients, often middle-aged to elderly females, who present with rapidly developing tophi in the fingers with no other evidence of gout. The tophi often lead to pain and functional impairment. It is more common in patients with metabolic syndrome and thiazide diuretics are often an implicating factor as well.
Given the slightly unusual presentation, I feel that investigations are required for a more definitive diagnosis. High serum uric acid levels do not diagnose gout, they merely confirm hyperuricaemia.
I order X-ray of her hands and feet (to assess for para-articular erosions that are typical of gout) and a dual energy CT scan of her hands. This is a specialised test available at select radiology practices and is usually Medicare rebatable. This test can detect the presence of crystals (both urate and CPPD). The sensitivity and specificity of this is around 80% in the presence of tophi, but much lower if trying to detect urate crystals in early gout or if there has only been a small number of isolated episodes of gout.
The other way for definitive diagnosis of gout is to aspirate a tophus and detect urate crystal under birefringent light microscopy. This is a far more invasive process and carries a risk of infection. I order RF and anti-CCP antibodies. Rheumatoid nodules could be an alternative explanation, and these nearly always occur in seropositive disease.
I negotiate with her GP to stop the thiazide component of her antihypertensive regime and start an alternative anti-hypertensive. The dual energy CT scan shows urate crystals in multiple fingers, confirming the diagnosis of tophaceous gout.
The treatment for chronic tophaceous gout is to commence urate lowering therapy, treating to a target serum uric acid level below 0.30mmol/L. Tophi will resolve faster the lower the serum urate level; however, rapid reduction of serum urate level carries the risk of more flares of gout.
First-line urate-lowering therapy is allopurinol. If eGFR is above 30, my usual routine is to start 100mg daily and increase by 100mg every two weeks until 300mg daily. Please note that other rheumatologists use slightly different protocols, but the general principle is to start at a low dose and slowly up-titrate. I always use colchicine prophylaxis to prevent acute flares when initiating allopurinol. I usually start colchicine 0.5mg BD if eGFR is above 30. I advise the patient to reduce this to one tablet daily if they get diarrhoea (the first sign of colchicine toxicity). The maximum allopurinol dose I use is 900mg daily.
I am contacted four weeks into treatment after she has presented to hospital with increasing severe myalgias and arthralgias, headaches and low-grade fevers. She did not improve with oral antibiotics. She is admitted with concerns over sepsis. Blood tests show C-reactive protein (CRP) is markedly raised at 212 (N<5). There is abnormal liver function test with ALT 195 (N<40) and AST 202 (N<40). CK is normal and renal function is unchanged. Septic screen is negative. I recognise this may be an allopurinol hypersensitivity reaction and ask her to stop this medication immediately. The allopurinol hypersensitivity reaction can occur at any time, but typically in the first two months of treatment. It often involves a rash but can present with more systemic features such as this case. Recognising this syndrome is important as it can be life-threatening if allopurinol is continued.
She improves rapidly in the first week after stopping allopurinol, although it takes six weeks for full resolution of all her symptoms and biochemical abnormalities.
She still requires urate-lowering therapy for her gout; however, allopurinol is now absolutely contraindicated. Second-line treatment is febuxostat (trade name: Adenuric). PBS indications for febuxostat include documented history of allopurinol hypersensitivity, medical contraindication to allopurinol (severe renal or hepatic impairment) or intolerance to allopurinol requiring permanent treatment discontinuation. Febuxostat can be considered first-line therapy if there is severe renal or hepatic impairment.
It is possible to use allopurinol in advanced renal or hepatic impairment, but this is best done with specialist consultation. In this situation, allopurinol needs to be initiated at a very low dose and with very cautious dose increases. The allopurinol hypersensitivity reaction occurs more frequently in patients with chronic kidney disease and with rapid dose escalation.
I start febuxostat 40mg daily (half a tablet). She still requires colchicine0.5 mg BD prophylaxis to prevent a flare. She tolerates febuxostat without side effects. After one month of treatment, her serum uric acid is 0.46mmol/L, still above the target. It is increased to 80mg daily and serum uric acid reduces to 0.28mmol/L. She will require life-long urate-lowering therapy to maintain uric acid below target (0.36mmol/L for all patients and below 0.30mmol/L until all tophi have resolved). Tophi typically resolve over the course of one or two years if the target serum uric acid level is attained. Joint damage may have occurred before initiating treatment and thus there may be some permanent functional impairment.
Gout is one of the few inflammatory rheumatic conditions that is completely treatable, as long as the dosing of urate therapy is adequate and there is good patient adherence.
Dr Andrew Jordan is a rheumatologist based in Parramatta, Sydney, with a special interest in inflammatory arthritis, gout and PRP injections.
