Singular Crystal Points the Way to a Pseudogout Diagnosis

BOSTON— To differentiate definitively between acute gout and pseudogout, look at the crystals.

On UV light microscopy, fluid aspirated from the inflamed joint of a patient with pseudogout will be teeming with rhomboid-shaped calcium pyrophosphate dihydrate (CPPD) crystals, which are morphologically different from the needle-shaped monosodium urate (MSU) crystals implicated in the pain and swelling of acute gout, Dr. Dwight R. Robinson said at a meeting on rheumatology sponsored by Harvard Medical School. “Calcium pyrophosphate dihydrate crystals are less well formed and show more variation in size and shape than monosodium urate crystals. In that way, they are a little more difficult to identify.”

Like MSU crystals in the joints of gout patients, the deposition of CPPD crystals in pseudogout causes acute pain and swelling in one or multiple joints. The acute attacks can last anywhere from 1 day to 4 weeks and sometimes are accompanied by fever, leukocytosis, and elevated acute-phase reactants said Dr. Robinson, a rheumatologist and professor of medicine at Harvard Medical School, Boston. Because the latter signs also may be indicative of septic arthritis, sepsis first must be excluded by gram stain and culture of synovial fluid.

In general, CPPD crystals have a predilection for depositing in articular and fibrocartilage, said Dr. Robinson. In pseudogout, this process commonly involves the knee or wrist joint but also may involve the first metatarsophalangeal joint, as occurs in gout, or almost any other joint, he said. Radiographically, the diagnosis of pseudogout often can be confirmed by evidence of chondrocalcinosis in the affected joint space.

In addition to mimicking the clinical patterns of gout, the symptoms of CPPD joint disease may overlap with other inflammatory conditions. “The disease may present as pseudorheumatoid arthritis, pseudo-osteoarthritis with or without pseudogout, or pseudoneuropathic arthritis,” said Dr. Robinson. “In many patients, the condition is actually asymptomatic.”

CPPD disease develops idiopathically in individuals older than age 50. In younger patients, “it's more likely to be a complication of osteoarthritis, a late consequence of joint trauma or knee meniscectomy, or related to an underlying metabolic disease, such as hyperparathyroidism, dialysis-dependent renal failure, hemochromatosis, and hypomagnesemia,” said Dr. Robinson, noting that there also may be a familial component.

Although the exact mechanism for the development of CPPD deposition disease is uncertain, an overactivity of enzymes that break down nucleoside triphosphates has been implicated, as have genetic defects, specifically mutations in the human homologue of the murine ANK gene. “Several mutations in the [human homologue] may be responsible for human disease, including CPPD arthropath,” said Dr. Robinson.

There currently are no proven prophylactic therapies for pseudogout, but acute attacks can be treated effectively with, primarily, nonsteroidal anti-inflammatory drugs, said Dr. Robinson. Given the risks of gastrointestinal and renal toxicities associated with NSAIDs, particularly in elderly patients, intra-articular corticosteroid injection into the affected joint is a reasonable treatment option, he said, as is a short course of systemic corticosteroids for polyarticular pseudogout attacks. Oral or intravenous colchicine should be considered only as a treatment of last resort because of the associated risks of gastrointestinal and other toxicities.

BOSTON— To differentiate definitively between acute gout and pseudogout, look at the crystals.

On UV light microscopy, fluid aspirated from the inflamed joint of a patient with pseudogout will be teeming with rhomboid-shaped calcium pyrophosphate dihydrate (CPPD) crystals, which are morphologically different from the needle-shaped monosodium urate (MSU) crystals implicated in the pain and swelling of acute gout, Dr. Dwight R. Robinson said at a meeting on rheumatology sponsored by Harvard Medical School. “Calcium pyrophosphate dihydrate crystals are less well formed and show more variation in size and shape than monosodium urate crystals. In that way, they are a little more difficult to identify.”

Like MSU crystals in the joints of gout patients, the deposition of CPPD crystals in pseudogout causes acute pain and swelling in one or multiple joints. The acute attacks can last anywhere from 1 day to 4 weeks and sometimes are accompanied by fever, leukocytosis, and elevated acute-phase reactants said Dr. Robinson, a rheumatologist and professor of medicine at Harvard Medical School, Boston. Because the latter signs also may be indicative of septic arthritis, sepsis first must be excluded by gram stain and culture of synovial fluid.

In general, CPPD crystals have a predilection for depositing in articular and fibrocartilage, said Dr. Robinson. In pseudogout, this process commonly involves the knee or wrist joint but also may involve the first metatarsophalangeal joint, as occurs in gout, or almost any other joint, he said. Radiographically, the diagnosis of pseudogout often can be confirmed by evidence of chondrocalcinosis in the affected joint space.

In addition to mimicking the clinical patterns of gout, the symptoms of CPPD joint disease may overlap with other inflammatory conditions. “The disease may present as pseudorheumatoid arthritis, pseudo-osteoarthritis with or without pseudogout, or pseudoneuropathic arthritis,” said Dr. Robinson. “In many patients, the condition is actually asymptomatic.”

CPPD disease develops idiopathically in individuals older than age 50. In younger patients, “it's more likely to be a complication of osteoarthritis, a late consequence of joint trauma or knee meniscectomy, or related to an underlying metabolic disease, such as hyperparathyroidism, dialysis-dependent renal failure, hemochromatosis, and hypomagnesemia,” said Dr. Robinson, noting that there also may be a familial component.

Although the exact mechanism for the development of CPPD deposition disease is uncertain, an overactivity of enzymes that break down nucleoside triphosphates has been implicated, as have genetic defects, specifically mutations in the human homologue of the murine ANK gene. “Several mutations in the [human homologue] may be responsible for human disease, including CPPD arthropath,” said Dr. Robinson.

There currently are no proven prophylactic therapies for pseudogout, but acute attacks can be treated effectively with, primarily, nonsteroidal anti-inflammatory drugs, said Dr. Robinson. Given the risks of gastrointestinal and renal toxicities associated with NSAIDs, particularly in elderly patients, intra-articular corticosteroid injection into the affected joint is a reasonable treatment option, he said, as is a short course of systemic corticosteroids for polyarticular pseudogout attacks. Oral or intravenous colchicine should be considered only as a treatment of last resort because of the associated risks of gastrointestinal and other toxicities.

BOSTON— To differentiate definitively between acute gout and pseudogout, look at the crystals.

On UV light microscopy, fluid aspirated from the inflamed joint of a patient with pseudogout will be teeming with rhomboid-shaped calcium pyrophosphate dihydrate (CPPD) crystals, which are morphologically different from the needle-shaped monosodium urate (MSU) crystals implicated in the pain and swelling of acute gout, Dr. Dwight R. Robinson said at a meeting on rheumatology sponsored by Harvard Medical School. “Calcium pyrophosphate dihydrate crystals are less well formed and show more variation in size and shape than monosodium urate crystals. In that way, they are a little more difficult to identify.”

Like MSU crystals in the joints of gout patients, the deposition of CPPD crystals in pseudogout causes acute pain and swelling in one or multiple joints. The acute attacks can last anywhere from 1 day to 4 weeks and sometimes are accompanied by fever, leukocytosis, and elevated acute-phase reactants said Dr. Robinson, a rheumatologist and professor of medicine at Harvard Medical School, Boston. Because the latter signs also may be indicative of septic arthritis, sepsis first must be excluded by gram stain and culture of synovial fluid.

In general, CPPD crystals have a predilection for depositing in articular and fibrocartilage, said Dr. Robinson. In pseudogout, this process commonly involves the knee or wrist joint but also may involve the first metatarsophalangeal joint, as occurs in gout, or almost any other joint, he said. Radiographically, the diagnosis of pseudogout often can be confirmed by evidence of chondrocalcinosis in the affected joint space.

In addition to mimicking the clinical patterns of gout, the symptoms of CPPD joint disease may overlap with other inflammatory conditions. “The disease may present as pseudorheumatoid arthritis, pseudo-osteoarthritis with or without pseudogout, or pseudoneuropathic arthritis,” said Dr. Robinson. “In many patients, the condition is actually asymptomatic.”

CPPD disease develops idiopathically in individuals older than age 50. In younger patients, “it's more likely to be a complication of osteoarthritis, a late consequence of joint trauma or knee meniscectomy, or related to an underlying metabolic disease, such as hyperparathyroidism, dialysis-dependent renal failure, hemochromatosis, and hypomagnesemia,” said Dr. Robinson, noting that there also may be a familial component.

Although the exact mechanism for the development of CPPD deposition disease is uncertain, an overactivity of enzymes that break down nucleoside triphosphates has been implicated, as have genetic defects, specifically mutations in the human homologue of the murine ANK gene. “Several mutations in the [human homologue] may be responsible for human disease, including CPPD arthropath,” said Dr. Robinson.

There currently are no proven prophylactic therapies for pseudogout, but acute attacks can be treated effectively with, primarily, nonsteroidal anti-inflammatory drugs, said Dr. Robinson. Given the risks of gastrointestinal and renal toxicities associated with NSAIDs, particularly in elderly patients, intra-articular corticosteroid injection into the affected joint is a reasonable treatment option, he said, as is a short course of systemic corticosteroids for polyarticular pseudogout attacks. Oral or intravenous colchicine should be considered only as a treatment of last resort because of the associated risks of gastrointestinal and other toxicities.