Given the challenges of diagnosing gout, this author provides four case studies that convey pertinent keys to the diagnostic workup and evaluation of this patient population, and offers salient insights on treatment as well.

More commonly known as gout, monosodium urate crystal deposition (MSU) induced arthritis is a disorder characterized by the deposition of MSU crystals in joints and subcutaneous tissue. The metabolic disorder underlying gout is hyperuricemia.

Hyperuricemia can be caused by increased uric acid production or a diminution in uric acid clearance. The latter commonly results from impaired renal function. Gout passes through three distinct stages — asymptomatic hyperurecemia, acute intermittent gout and chronic, often tophaceous gout. It has a variety of clinical patterns.

The following case studies illustrate the spectrum of gout.

Case One: When A Patient Presents With An Acutely Swollen Right Knee
Peter is a 50-year-old African-American male who presented to the emergency room (ER) with an acutely swollen right knee. He noted that he woke up and experienced a sudden onset of pain and warmth in that joint. Over the next two days, the pain and swelling increased to the point where he could no longer bear weight. He had called in sick to his job in the post office and had consumed so much Advil in the last two days that he was also complaining of a queasy stomach.

While his job kept him on his feet for long periods of the day, he had no prior episodes of similar symptoms. Peter had not sustained any trauma in the immediate past and had no recent febrile illness.

Peter’s past medical history includes mild hypertension. For this condition, he takes lisinopril 10 mg daily and 325 mg of aspirin daily. In regard to the patient’s social history, he is a non-smoker who drinks several beers daily after work and is married with two teenaged daughters. He played softball most weekends.

Photo courtesy of N. Lawrence Edwards, MD Here is a typical case of acute gout involving the distal interphalangeal joint. All patients with suspected septic arthritis or crystal-induced arthritis should undergo joint aspiration and appropriate studies.

Peter is a slender man in mild to moderate distress. His vital signs appear to be normal except for a slightly elevated temperature of 100.6ºF. With the exception of his right knee, the musculoskeletal exam was not remarkable. Upon examination, Peter’s right knee was swollen, red and warm. He had a large effusion and could not flex his knee without pain.

The emergency room (ER) team ordered a plain film of his knee. However, it was not a weightbearing view as the patient could not stand. The film showed a small degree of medial joint space narrowing and apparent soft tissue swelling from a large effusion. The patient had a 60 mm erythrocyte sedimentation rate (ESR), a serum uric acid level of 7.0 mg and creatinine of 1.0 mg. The complete blood count (CBC) was normal with a slightly elevated white blood cell count (WBC) of 13,000. His rheumatoid factor (RF) was negative.

The differential diagnosis includes severe, inflammatory osteoarthritis, a septic joint and gout.

What The Arthrocentesis Revealed
It was important to perform an arthrocentesis to sort this out. His knee was so tender that Peter was extremely reluctant to consider the procedure. He feared that the procedure would cause more pain and simply wanted something more than Advil for the pain.

Peter finally consented to aspiration of the joint. After administering anesthesia with 10 mg of 2 percent lidocaine intraarticularly, we aspirated 90 cc of cloudy, yellow fluid. We proceeded to inject a mixture of 30 mg of Depo Medrol (Pfizer) and 5 cc of marcaine. The patient felt immediate relief and could finally bear weight.

We sent the aspirate to the lab for cell count and culture. This analysis found numerous intracellular MSU crystals. The culture was negative and the patient’s white cell count of the synovial fluid was 15,000.

Given the analysis of the aspirate, we were able to diagnose acute gout. However, we could not rule out infection until the culture results came back. The negative gram stain and low cell count made the ER team feel comfortable in initiating the following therapy.

Key Treatment Considerations
While in the ER, Peter received an injection of Acthar gel (ACTH 80 units subcutaneously) and we initiated 0.6 mg BID of colchicine.

At the follow-up office visit three weeks later, we reassessed the patient’s serum uric acid level. Be aware that this can be “falsely normal” during a gout flare. This was the patient’s first attack of gout. Unless his serum urate was very high, one may not initiate urate lowering therapy at the follow-up visit. However, clinicians can introduce the possibility that this may be necessary should future gout attacks occur.

We emphasized that the patient reduce his intake of beer or hard liquor. Treating clinicians also instructed him to lower his aspirin dose to 81 mg per day. These lifestyle and medication changes may be sufficient therapy. Coupled with some underlying osteoarthritis, aspirin use and heavy beer intake were the likely triggers of his acute gout attack.

Photo courtesy of N. Lawrence Edwards, MD Here we see sheets of needle-shaped, negatively birefringent crystals that are common in cases of acute gout.

When patients present with symptoms that suggest septic arthritis or gout, one should perform joint aspiration and obtain appropriate studies. In regard to acute gout, the goals are decreasing pain and inflammation. Many approaches work. At my practice, we favor ACTH 80 units subcutaneously. We have come to appreciate the rapid onset of the medication in relieving acute symptoms.

One may reserve urate lowering therapy for follow-up visits. However, not all people with acute gout will need urate lowering therapy. Never start or stop allopurinol during a gout flare as it will prolong the flare. It is important to wait three to six weeks after an acute attack before instituting urate lowering therapy. However, keep the patient on BID dosing of colchicine.

Case Two: When An Elderly Man Has Acute Wrist Pain
Michael is a 73-year-old, recently widowed man who came to the ER complaining of 24 hours of acute pain in his right wrist. The pain had come on suddenly and he could not comfortably move the joint. The joint was quite warm with a dorsal effusion. He was a healthy appearing adult male who presented with his right wrist wrapped in a cool cloth.

One of his previous hobbies was gardening but the patient noted he was no longer as avid with gardening since his wife’s death. However, he had been trimming trees the morning prior to the onset of his pain. He said he was doing most of the cutting with his right wrist in constant motion.

Michael’s past medical history consists of type 2 diabetes, which was well controlled by the use of metformin. He lives alone in an adult retirement community, is a non-smoker and has the occasional social drink. However, Michael admitted to drinking more alcohol now than in recent years. He also has been sexually active.

The patient’s vital signs were normal except for his temperature of 101.6ºF. His CBC was slightly abnormal. His WBC was 12,500 with a normal differential. His screening labs were normal except for creatitine, which was 1.4 mg. He also had an A1C of 7.5 mg and an ESR of 90 mm. In a plain film view of the wrist, there were no bony abnormalities and only soft tissue swelling.

Upon performing a focused, musculoskeletal exam, it was clear that Michael did not appear to be ill but did seem uncomfortable. He had no tophi or joint deformities. There was a diffuse effusion over the dorsum and his range of motion was reduced to 10 degrees of flexion due to pain.

Our differential diagnosis was crystal arthropathy versus joint infection, perhaps gonococcus. The symptoms were a bit severe for an overuse injury and the lab findings suggested more acute inflammation than one would typically see in overuse cases.

What The Joint Aspiration Revealed
It also took some reassurance for Michael to agree to joint aspiration. After obtaining consent, we aspirated less than 1 cc of cloudy synovial fluid. Since we had a high index of suspicion for septic arthritis, perhaps gonococci, we sent the fluid out for crystal analysis, cell count and culture. The analysis of the aspirate fluid revealed many intracellular, needle-shaped, negatively birefringent crystals.

The presence of MSU crystals in the aspirate confirmed gout. However, there was real concern for concomitant infection. Accordingly, Michael was admitted to the hospital and clinicians initiated broad-spectrum antibiotics and narcotic analgesia. The synovial fluid cell count was 40,000 WBC. Both the synovial fluid and blood cultures failed to confirm infection. He was diagnosed with MSU crystal-induced arthropathy.

Treating clinicians had withheld corticosteroids pending the culture report but once that report ruled out infection, they proceeded with corticosteroid therapy and discontinued his antibiotic coverage. Michael’s wrist improved within 48 hours and he was discharged on colchicine 0.6 mg BID.

What You Should Know About Gout Recurrence And Urate Lowering Therapy
At a follow-up appointment three weeks later, we reassessed his serum urate and symptoms. In this case, the patient’s uric acid was 8.9 mg/dl. He was clearly hyperuricemic with one episode of crystal-proven gout. Untreated gout attacks are typically self-limiting. However, about 80 percent of patients have a recurrence within two years.³ This man elected not to begin urate lowering therapy (ULT) at the time. He was amenable to remaining on colchicine.

Urate lowering therapy is always indicated in patients with frequent gout attacks, with renal disease, with deforming arthritis, renal stones or tophi. There is a growing trend to begin ULT as well as lifestyle changes in those who are at a high risk for recurrence or who have established comorbidities such as metabolic syndrome. Links between hyperuricemia and/or gout and cardiovascular events continue to emerge. Clinicians should inform patients of these associations.⁴ While clinicians commonly and successfully use corticosteroids and ACTH to treat acute gout, no randomized controlled trial (RCT) data is available to support this clinical experience.⁵

Case Three: Is The Longstanding Inflammation In The Hands And Feet RA Or Gout?
Chris is a 67-year-old Caucasian man who was referred to a rheumatologist for ongoing care of presumed rheumatoid arthritis (RA). His primary care physician made the RA diagnosis approximately five years ago when he presented to her with longstanding inflammatory arthritis in his hands and feet.

Chris had been treating himself with various over-the-counter (OTC) pain and antiinflammatory therapies for 10 years prior to the diagnosis. Over the next five years of medical care, he used nonsteroidal antiinflammatory drugs (NSAIDs) that helped somewhat. Three years ago, the primary care physician prescribed low-dose methotrexate. In spite of several years of both NSAID and methotrexate therapy, Chris continued to have “flares” of his “RA.” These flares were becoming more frequent but they responded to oral Medrol dose packs.

Nonetheless, Chris was developing subcutaneous nodules of the elbows and finger deformities that were progressing to the point where he could not keep up with his golf game. This was an important activity for him and his limitations with this sport prompted self-referral to an arthritis specialist.

Photo courtesy of N. Lawrence Edwards, MD Here is a case of chronic tophaceous gout involving both hands. Be aware that chronic tophaceous gout may resemble RA but the erosive changes and serologies associated with gout are quite different than those of RA.

The patient’s past medical history consisted of significant hypertension and obesity as well as hyperlipidemia. His hypertension was controlled by daily doses of 25 mgs of hydrochlorothiazide (HCTZ) and clinicians treated the patient’s lipid abnormalities by prescribing 40 mg simvastatin (Zocor, Merck) daily. In regard to the patient’s RA, Chris was taking 25 mg of methotrexate a week and a rotating array of NSAIDs with the occasional Medrol dose pack.

Chris did not smoke, use illicit drugs or drink alcohol. The retired salesman was married with grown children. His relevant labs included a serum urate of 10.0 mg/dl and a serum creatinine of 1.2 mg/dl. The patient’s rheumatoid factor (RF) and anti-CCP antibody were negative. His ESR was 35 mm/hr and the CBC was normal. While the patient had normal blood pressure, his body mass index (BMI) was 32. His pain index was 6/10 at this visit but surged to 9/10 when his arthritis was “in flare.”

A Closer Look At Pertinent Findings From The Diagnostic Workup
We obtained radiographs of his hands and feet. The X-rays revealed erosive changes in both the distal and proximal interphangeal joints of his hands, and in both large toes. These erosions had a classic “overhanging edge” feature.

The directed musculoskeletal exam revealed several pertinent findings. Chris had bony enlargements and poor alignment of his distal interphalangeal (DIP) and posterior interphalangeal (PIP) joints bilaterally. This was most significant in fingers two to four. He had several firm nodules over several of his PIPs with one as large as 1 cm. It was draining a chalky colored material. He had a large (egg-sized), firm nodule in his right olecranon bursa. Chris had bony enlargement in both metacarpophalangeal (MCP) joints. He also had bland, chronic synovitis in both wrists and restricted range of motion in the right elbow.

The previous diagnosis of RA was questionable. His RF and anti-CCP antibody were negative. While Chris had hyperuricemia, hypertension and was obese, he was not anemic.

Anemia of chronic disease is common in people with RA. His X-rays are more consistent with gout than RA.

We made a touch prep of the draining material from Chris’ finger. The analysis of the draining material revealed sheets of needle-shaped crystals, which were strongly and negatively birefringent. This examination established the diagnosis of gout. The culture of the same material was negative.

Essential Treatment Considerations
This is a case of chronic tophaceous gout misdiagnosed as RA. We started Chris on allopurinol and urate lowering therapy that reduced his serum urate to the point where he no longer had flares of gout and some of his tophi resorbed. When treating gout, one of the goals is to get the serum urate to 6.0 mg/dl or lower. One can slowly titrate the allopurinol to achieve that level.

Advanced polyarticular, deforming gout occurs in the setting of longstanding, untreated gout. Tophi and joint deformities occur. It may resemble RA but the erosive changes and serologies associated with gout are quite different than those of RA. Hyperuricemia is the metabolic underpinning of gout. Positive RF and anti-citrullinated peptide (+CCP) antibodies typically occur with RA.

Chris was not responding to the therapy used for the presumed RA diagnosis. That was the red flag that prompted a referral to rheumatology. Unfortunately, it was too late in the disease process to reverse most of the deformities.

Case Four: When A Patient Complains Of ‘Water On Both Knees’
Jane is a 59-year-old Caucasian woman. Over the last year, she noted a slow accumulation of “water on both of her knees.” These joints ache but are not very warm. The knee effusions had recently begun to impede lower extremity function. She was no longer able to go to her swim classes.

Her past medical history was only significant for hypothyroidism, which was controlled with thyroid supplementation. Synthroid was her only daily medication and she took Tylenol for her knee pain three to four times a week. The patient works as a banker. She is married with two adult children. She is a non-smoker and social drinker.

The physical exam revealed a middle-aged woman with normal vital signs and a BMI of 28. The serum thyroid-stimulating hormone (TSH), basic metabolic profile and CBC were also within normal limits. However, the patient’s serum uric acid was 4.0 mg/dl and her ESR was 30 mm/dl.

Plain bilateral films of her standing knees revealed chondrocalcinosis in the meniscal cartilage. There was no evidence of coexisting osteoarthritis (OA). Upon performing the physical exam, we noted that both knees were mildly effused. They were not very warm but she did have a reduced range of motion, especially in flexion. There were no other significant findings during the musculoskeletal exam.

We aspirated both knees, obtaining approximately 40 cc of clear, yellow synovial fluid from each knee. Analysis of the fluid revealed rhomboid-shaped crystals, which were weakly and positively birefringent. The synovial fluid cell count was 16,000 WBC and the culture was negative. After reviewing the diagnostic workup/tests, we diagnosed Jane with calcium pyrophosphate dehydrate deposition disease (CPPD) in both knees.

What You Should Know About Treating CPPD
The knee is the most frequent site of CPPD with calcification in both the meniscal and hyaline cartilage. As with gout, CPPD may be idiopathic or familial, or occur in association with other diseases such as OA and metabolic disorders. This woman was recently diagnosed and is now under treatment for hypothyroidism.

Keep in mind that NSAIDs are effective in controlling the inflammation of CPPD-induced synovitis. Previous clinicians had not prescribed NSAIDs and Jane had no contraindications. She had synovitis for several months so we initiated 200 mg BID of celecoxib (Celebrex, Pfizer). If that is effective, she could, in time, go to QD dosing. If the drug failed to control her knee effusions or if the patient could not tolerate the drug, clinicians could consider the use of colchicine or intra-articular corticosteroids.

No good current epidemiologic data exists for this disorder but most patient series reveal a female preponderance.6 In many cases, aspiration and intra-articular steroids greatly relieve symptoms and may be all that are necessary to settle the synovitis. There is no metabolic underpinning to CPPD but clinicians often see it in association with metabolic disorders.