Rheumatology Case: The Morning After Toe

The patient presented with acute onset of symptoms involving a single joint. Acute inflammation of the left first MTP joint with erythema, swelling, and extreme tenderness is known as podagra (derived from the Greek words “pous” meaning foot, and “agra” meaning attack or seizure). Acute inflammation of the first MTP is sometimes mistakenly assumed to be gout, but a similar presentation may be seen with other crystal-induced forms of arthritis , such as calcium pyrophosphate dihydrate crystal-deposition disease or hydroxyapatite crystal disease.
Trauma is also a potential cause of podagra. In this patient, trauma should be high on the list of differential diagnoses, given his history of excessive ethanol ingestion.
Whenever seeing a patient with acute monarticular arthritis, an infectious etiology must be considered. This is further suggested by the patient’s fever.
Sometimes the clinical picture of gout mimics cellulitis, with diffuse erythema, tenderness, fever, and swelling of periarticular tissues so intense as to obscure the articular origin of the findings.
Rheumatoid arthritis is unlikely, given the lack of other joint involvement. Although the presence of nodules at the olecranon bursa and extensor areas of the hand suggests rheumatoid nodules, this patient’s overall presentation is atypical for RA, and these nodules may be tophaceous deposits. Some patients with rheumatoid arthritis present with monarticular disease, but usually not with inflammation as acute as is described in the present case.
Osteoarthritis is a potential cause of podagra, but is not likely in this patient, given the rapidity of onset of symptoms and the presence of acute inflammation. Reiter’s syndrome or psoriatic arthritis may be present in a patient with podagra, monarthritis elsewhere, or oligoarthritis and would be a consideration, but these possibilities are not among the top four for this patient, given the lack of other associated findings (such as enthesopathy or rash) or historical features.

The CBC and differential can provide evidence of acute infection or inflammation. Studies in the chemistry profile that would be helpful include the uric acid, liver enzymes, and tests of renal function. However, uric acid levels are sometimes depressed during an acute attack, occasionally even into the normal range. Aspiration of the acutely inflamed MTP joint should be performed to look for crystals and to identify the presence of bacteria. Intracellular crystals are the sine qua non in the diagnosis of acute crystal-induced arthritis. Bacteria seen on a Gram stain would suggest septic arthritis.

X-rays of the feet should be done to determine whether a fracture might be responsible for the acute symptoms and inflammatory response. Additionally, such films may demonstrate abnormalities characteristic of one or another form of arthritis in patients who have been chronically symptomatic. X-ray revealed erosion but no fracture in this patient. With no abnormalities in the hands, hand x-rays are not indicated.

Blood culture can be helpful in identifying bacteremia in patients with septic arthritis (and in suspected cellulitis) when the organism cannot be identified in synovial fluid. However, blood cultures are not a substitute for arthrocentesis in the diagnosis of septic arthritis.

Arthroscopy is not indicated in this patient. Even in a more easily accessible joint it is unlikely to yield any information additional to that obtained from synovial fluid analysis. Serologic testing, including ANA and RF , has extremely limited utility in evaluating acute monarticular arthritis. Rheumatoid arthritis is considered in the differential diagnosis because of the nodules, but RF may also be positive in liver disease, which is a possibility in this patient.

X-ray of the knees might show cartilage calcification (chondrocalcinosis) in patients with CPPD, but would not directly answer the question of the cause of the MTP inflammation. Similarly, aspiration of a knee with no effusion is difficult and unlikely to yield useful information.

The crystals described in this case report have the typical needle-shaped morphology of monosodium urate crystals. When viewed under polarized light with a first-order red plate compensator, they are yellow when parallel to the slow axis of the compensator. Crystals that are aligned perpendicular to the axis are blue. These are “negatively birefringent” crystals and are a hallmark of gout.

CPPD crystals are found in patients with a similar clinical presentation that is often referred to as “pseudogout” . The terms pseudogout and CPPD are sometimes used interchangeably with chondrocalcinosis. Chondrocalcinosis is a radiographic finding, meaning cartilage calcification. Pseudogout is a clinical presentation that can be caused by several diseases, although CPPD crystal deposition is the one most commonly associated with this presentation. CPPD crystals are typically rhomboid. When viewed under polarized light with a first-order red compensator, the coloration of the crystal is the opposite of urate crystals -- that is, CPPD crystals are blue when parallel to the slow axis of the compensator and yellow when perpendicular to the axis. These are “positively birefringent” crystals. Another distinguishing characteristic between urate and CPPD crystals is the intensity of color. Urate crystals are typically brightly colored, almost neon-like; in contrast, CPPD crystals have a washed-out appearance and are sometimes more difficult to see under polarizing light microscopy, requiring patience when examining the specimens.

Apatite crystals are also associated with acute arthritis. Hydroxyapatite is an amorphous substance that is not seen under polarized light microscopy. Apatite can be detected in synovial fluid with alizarin red S, a calcium stain, although the stain does not differentiate between different kinds of calcium crystals.

Cholesterol crystals are found in rheumatoid arthritis , as well as in other diseases in which there is chronic synovitis . These crystals are typically square, often with a notch cut out of one corner (shaped like the state of Utah). However, this patient clearly has acute synovitis.

Crystals from intra-articularly injected corticosteroids may be found in synovial fluid. The crystals are birefringent and can be confused with sodium urate and calcium pyrophosphate crystals.

Septic arthritis is always a consideration in patients with acute monarticular arthritis. The lack of organisms on Gram stain is somewhat reassuring, but does not entirely exclude infection. If sufficient fluid is obtained, cultures should be done. Even a very small amount of fluid sent for culture may yield results. Crystals and bacteria may coexist in a joint. Although cellulitis and gout may present in a similar fashion, this patient’s findings are more typical of gout.

A. IV antibiotic.
B. IV colchicine.
C. Oral colchicine.
D. Short-acting NSAID (not ASA).
E. Intraarticular steroid injection.
F. Oral prednisone.
G. Allopurinol.
H. ACTH.

Short-acting NSAIDs are the treatment of choice for acute gout. Oral colchicine may be beneficial if started within the first 12 hours of an acute attack. It can be given in a dose of 0.5 or 0.6 mg hourly, to a maximum of 10 tablets or until joint symptoms are relieved or GI symptoms develop, but its use in acute gout has been largely supplanted by other alternatives. Intraarticular steroid injection is effective for alleviating acute gouty arthritis. Injection into a small joint can be difficult, however, and a flare can occur when the antiinflammatory effect subsides. IM or oral steroids are also effective, as is IM or IV ACTH.

Acetaminophen with codeine can be useful as an adjunct for pain control, but this is not effective in treating the inflammation. Allopurinol and probenecid are used for managing chronic hyperuricemia and do not have a place in treating acute gouty arthritis, and, in fact, may exacerbate the symptoms. Without better evidence of infection, empiric use of a broad-spectrum antibioticis not indicated. IV colchicine has extremely limited utility because of its high potential for serious, sometimes fatal, adverse events. Corticosteroid injections or ACTH are better alternatives for patients unable to take medications orally.

Obesity is probably simply associated with hyperuricemia and not a causative factor. The role of hypertension is not entirely understood, but it is present in 25-50% of patients with gout, and 2-14% of patients with hypertension have gout.

Hyperuricemia can be due to overproduction of uric acid and/or underexcretion of uric acid by the kidneys. The use of diuretics and/or low-dose aspirin , as well as cyclosporin, can result in underexcretion of uric acid. In contrast, high-dose aspirin is associated with low levels of serum uric acid.

Hyperuricemia associated with ethanol use is due to both overproduction and underexcretion of uric acid. Gout associated with lead exposure , known as “saturnine gout,” is due to underexcretion of uric acid caused by lead nephropathy.

Smoking and angiotensin-converting enzyme inhibitor use do not increase serum uric acid.

If left untreated , this patient would continue to have episodes of acute gouty arthritis. In patients with untreated hyperuricemia, the interval between attacks typically shortens and the severity of the attacks worsen, they last longer, and frequently they are polyarticular rather than monarticular. This patient has already had multiple and increasingly frequent attacks of gout and has nodules, which likely represent tophi. To document that they are tophi, one of the nodules could be aspirated and the material examined under polarizing light.

Colchicine has been shown to prevent flares associated with changes in uric acid. This treatment should continue for one month prior to initiating hypouricemic therapy.

In general, the decision of whether to use allopurinol or probenecid is predicated on identifying whether a patient is an overproducer or an underexcretor of uric acid. For patients who are underexcretors, treatment with probenecid is the most reasonable approach because the drug enhances uric acid excretion. However, probenecid is not a good choice for those who have renal disease. In the patient with renal insufficiency and a glomular filtration rate of less than approximately 50 ml/min, probenecid is not effective because uric acid must first be filtered before the drug has a chance to act within the renal tubule. In patients with a history of kidney stones, probenecid may encourage stone formation by increasing uric acid secretion.
However, there are still other considerations in choosing which drug to prescribe. Although laboratory test results seem to indicate that this patient is an underexcretor, his use of low-dose aspirin is a contraindication to probenecid because at any dose, low or high, aspirin inhibits the uricosuric effect of probenecid. Since he should probably continue taking aspirin because of the risk of cardiovascular disease, allopurinol in a dose sufficient to lower the serum uric acid to 6.0 mg/dl or less is the treatment of choice.

It is essential that this patient receive counseling. He needs to understand the importance of taking the medications as prescribed, including the appropriate use of colchicine for acute attacks. He should be advised that limiting (or better yet, stopping) alcohol consumption and losing weight will help to lower his uric acid levels. Finally, he should be advised to avoid a purine-rich diet (e.g., more than 200 g/day of meat, poultry, or fish) and foods with a high purine content (e.g., organ meats, asparagus, spinach, peas, and beans).

The patient’s brother has asymptomatic hyperuricemia. In this circumstance, the most reasonable approach is to not treat the hyperuricemia, but to follow him and see what happens. The vast majority of patients with hyperuricemia (over 75%) do not develop any clinical consequences. When illness does occur from hyperuricemia, it is usually gouty arthritis or kidney stones, neither of which is life threatening. There is no need to consider treating him with allopurinol or probenecid to lower the serum uric acid level until one or the other of these conditions has developed. Likewise, colchicine prophylaxis is not indicated.
Counseling to provide reassurance, advice on avoiding unnecessary use of diuretics or excessive use of alcohol, and education to assist him in recognizing symptoms are all that are needed.