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Contributor: Santhanam Lakshminarayanan, MD
A 78 year old man is seen in the clinic for a painful swelling of the left elbow. Over the past year, he has had a few episodes of pain and swelling in his right knee and left foot, for which he received ibuprofen and once was treated with an antibiotic. His elbow is shown in the picture. He also has hypercholesterolemia and hypertension and is on simvastatin, hydrochlorothiazide and metoprolol.
He drinks several beers a day but does not smoke.
His exam is remarkable only for the appearance of his hands, similar to the picture shown.
What is the most appropriate next step, respectively?
Aspiration of the olecranon bursa was performed. Findings under polarized microscopy showed the presence of intracellular negatively birefringent crystals. Treatment consists of injection of steroids (in the absence of an obvious infection) into the olecranon bursa. In addition to intra-articular injections, other treatments for acute gout include NSAIDs, colchicine, and oral glucocorticoids. Urate-lowering therapy should not be initiated during an acute attack. If a patient is already on urate-lowering therapy or it was briefly interrupted, it should be continued or restarted.
Having established the diagnosis and provided relief for the acute problem what are the next steps in the management of this patient?
You are asked to see an elderly lady admitted to the hospital for pneumonia 4 days ago. She has a painful swollen wrist with no antecedent history of a fall. The hospitalist team did an x-ray of the wrist and hand. The wrist is minimally warm and tender with some decreased range of motion secondary to pain. The pneumonia is improving and she was looking forward to being discharged on oral antibiotics. She mentioned that she had bumped her knee on the dresser on the day of admission and had an x-ray.
What is your diagnosis?
What is the most appropriate intervention?
Aspiration of the synovial fluid from the wrist for analysis, and intra-articular Injection of steroids (in the absence of any obvious infection). The fluid may show weakly positively bi-refringent crystals.
What chronic management is indicated?
CPPD is common in older individuals, especially with osteoarthritis. In younger people, a work-up for secondary causes of CPPD is indicated. Therefore, screening for hemochromatosis, hypothyroidism, hyperparathyroidism and disorders of magnesium and phosphatase are indicated. In the absence of a secondary cause, chronic intervention is usually not needed, or very effective.
(Answer questions 1 – 5 on a piece a paper. The Answer Key is at the bottom of the page.)
1. An 80 year old man presents with an acutely swollen R ankle and with erythema and pain. He has a known history of gout with previous attacks in both the first MTP of the R foot and the L ankle. He has Chronic kidney disease, atrial fibrillation and hyper- cholesterolemia and is on Furosemide, Lisinopril , Metoprolol, coumadin and a statin. He continues to drink alcohol liberally. His laboratory tests reveal WBC 3200/µL, platelets 100,000/µL, Hb 9.8g/dL, creatinine 3.6mg/dL, uric acid 9.0mg/dL and INR 4.0. The most appropriate management step in this patient is:
2. A previously healthy 70 year old lady is admitted with pneumonia and on the 2nd day of hospitalization develops a painful swollen R knee with tenderness and warmth. She is afebrile. The rest of her articular exam is normal except for nodular osteoarthritis of her hands and crepitus in the L knee. The most appropriate first step in her management is:
3. You are asked to evaluate a currently asymptomatic 67 year-old man who has a long history of gout. During the past six months, he has had multiple acute gouty flares involving the left wrist, the right knee, and the first metatarsophalangeal joints. A year ago, he underwent heart transplantation because of viral cardiomyopathy. At that time, his regimen of allopurinol, 300 mg daily, and colchicine, as needed for acute flares, was discontinued. He has taken no regular medication for gout since then, except for indomethacin during the recent flares.
Current medications are cyclosporine, 400 mg; azathioprine, 100 mg daily, and prednisone, 10 mg daily. Physical examination reveals a tophus in the left olecranon bursa. No joint tenderness or swelling is present. Leukocyte count is 7500/cu mm with a normal differential. Serum creatinine level is 1.8 mg/dL. Serum uric acid level is 10.6 mg/dL. The best treatment plan for this patient is:
4. A 46-year-old man is evaluated because of a three-month history of progressive generalized weakness without pain and the recent onset of numbness in the hands and toes. For the past three weeks, the patient has required support while walking and assistance in rising from a chair. Medical history includes hypertension and two attacks of gout. He has taken colchicine, 0.6 mg twice daily, for the past four years, and he currently takes hydrochlorothiazide, 50 mg daily. He drinks 2 to 3 cans of beer daily. At the time of physical examination, the patient cannot stand or walk without assistance. Blood pressure is 160/100 mm Hg. There is marked symmetric proximal muscle weakness which is more severe in the legs. Sensation to pinprick and vibration is decreased in the toes. Deep tendon reflexes are absent.
Hemoglobin 12.5 g/dL
Mean corpuscular volume 99 fL
Erythrocyte sedimentation rate 32 mm/hr
Serum aspartate aminotransferase 125 U/L (AST)
Serum creatinine 1.9 mg/dl
Serum creatine kinase 2010 U/L
Serum uric acid 8.0 mg/dL
Which of the following is the most likely diagnosis?
Which of the following findings on synovial fluid analysis is consistent with an asymptomatic lady with a minimal knee effusion that was aspirated after obtaining the X- ray below?
(Answer questions 1 – 5 on a piece a paper. Find Answer Key at the bottom on the page.)
The correct answer is D.
Acute gout can be treated with colchicine, NSAID’s such as indomethacin, intra-articular injections of corticosteroids or oral or parenteral corticosteroids. In this patient on Coumadin with a supra-therapeutic INR injecting the ankle poses the risk of intra-articular bleeding. The impaired renal function precludes the use of NSAID’s and colchicine. Colchicine is also relatively contraindicated in the setting of the patient’s impaired marrow function (likely the result of ETOH). Initiating allopurinol in the setting of an acute attack of gout will only exacerbate the patient’s symptoms. Systemic corticosteroid therapy affords the best risk-benefit profile for this patient.
The correct answer is B.
This lady has no comorbid conditions. Both acute gout and acute pseudo-gout can happen in the setting of an inter-current illness/hospitalization. Given the mono articular presentation it would be best to attempt a synovial aspiration and treat with intra-articular steroids. There is nothing in the history or examination to suggest a septic joint. While systemic corticosteroids and colchicine may help they are not indicated as first-line treatments given the mono articular presentation. Furthermore obtaining the synovial fluid will help clarify the exact cause of the crystalline arthropathy.
The correct answer is C.
This question is designed to highlight the interaction between allopurinol and azathioprine. Allopurinol and azathioprine should not be co-prescribed unless the combination cannot be avoided. Allopurinol interferes with the metabolism of azathioprine, increasing plasma levels of 6-mercaptopurine which may result in potentially fatal blood dyscrasias. Concomitant use requires special precautions: the dose of azathioprine should be reduced to 25% of the recommended dose and the patient’s blood count should be monitored carefully and frequently. After oral administration and absorption, approximately 90% of azathioprine is converted to 6-mercaptopurine (6-MP). At this point, 6-MP can undergo metabolism by 1 of 3 different pathways; 2 of these pathways serve to inactivate 6-MP and produce metabolites that are largely inactive, while the third pathway results in the production of active metabolites. The 2 inactivating pathways are carried out separately by the enzymes thiopurine methyltransferase (TPMT) and XO. The inactivation pathway catalyzed by TMPT is straight forward, but unfortunately, is subject to the influence of genetic polymorphism. The inactivating XO pathway is also straight forward in terms of converting 6-MP to the inactive metabolite 6-thiouracil. However, anything that inhibits XO will shunt 6-MP down the pathway that results in the formation of the active 6-thioguanine (TGN) and 6-methyl-MP (MMP) metabolites. This is where allopurinol, and likely febuxostat, interact with azathioprine. There have been rare case reports of allopurinol increasing the serum levels of cyclosporine and cyclosporine itself can cause/worsen hyperuricemia.
The correct answer is A.
Certain drugs produce painless, largely proximal; myopathy .These drugs include the amiodarone, chloroquine, hydroxychloroquine and the antimicrotubular drug colchicine. Muscle biopsy can be useful in the identification of toxicity since autophagic vacuoles are prominent pathologic features of these toxins. Colchicine can also cause a neuropathy in the setting of impaired renal function. Myotoxicity is a potential consequence of addiction to alcohol. Toxicity usually occurs in the setting of poor nutrition and possible contributing factors such as hypokalemia and hypophosphatemia. Acute muscle weakness with myoglobinuria may occur with prolonged severe hypokalemia, hypophosphatemia, or hypomagnesaemia that is seen in chronic alcoholics. Low vitamin D levels are related to muscle atrophy while changes in muscle antioxidant enzymes may play a role in alcoholic myopathy. Chronic alcoholics may develop painful myopathy with myoglobinuria after a bout of heavy drinking or present with a painless, acute hypokalemic myopathy that is completely reversible with replacement therapy.
Synovial fluid analysis includes initial inspection at bedside. Normal synovial fluid is clear and viscous. In inflammatory conditions the fluid becomes turbid due to the presence of cells and it loses its viscosity since the inflammatory process breaks down the hyaluronate content of the synovial fluid. Pseudogout is an acute inflammatory arthropathy triggered by calcium pyrophosphate crystals. These may be seen on radiographs as chondrocalcinosis. However both osteoarthritis and chondrocalcinosis can coexist without necessarily presenting as pseudogout. The patient in this question was asymptomatic. Hence the correct answer is D with the non-inflammatory synovial fluid and incidental finding of calcium pyrophosphate crystals.
Last updated February 2015.