A critical review of the available evidence on the diagnosis and clinical features of CPPD: do we really need imaging?

Imaging has been playing an important role in the pathogenetic and clinical characterisation of many rheumatic diseases, especially in the most recent years with the advent of many new, highly technological and promising techniques. Calcium pyrophosphate deposition disease (CPPD) benefited also from these new techniques, most of which can readily identify calcium crystals. Nowadays, imaging is used mainly to identify crystals in joints but given the complexity of CPPD, imaging should be used with an "holistic" approach in order to gain insights in the pathogenesis, spectrum of clinical manifestations and natural history of the disease. Furthermore, overlap or association of CPPD with other prevalent diseases of the elderly makes the differential diagnosis challenging. In this review, we provide a critical review of the current knowledge on the use of imaging both for the identification of crystals and for its application in clinical practice as an aid for determining the impact of the disease on patients.Key Points• CPPD is a complex disease with a wide spectrum of clinical manifestations and understanding of pathogenetic mechanisms and clinical phenotypes is essential for correct characterisation• Imaging has made important advances regarding identification of CPPD in recent years, and new, more sophisticated techniques are under investigation• Imaging has the potential to improve our knowledge on pathogenesis and clinical phenotypes of CPPD• Imaging techniques have to be tested thoroughly for reliability, discrimination and sensitivity to change before they can be implemented in clinical trials.

Imaging in Gout and Other Crystal-Related Arthropathies.

In this article, the authors consider the manifestations of intraarticular and periarticular crystal deposits. Most cases of crystal deposits are asymptomatic and represent incidental findings at imaging. In symptomatic arthropathies, imaging can play an important role in the diagnosis and assessment of disease progression and the extent of crystal deposits. Conventional radiography is the most common imaging modality. But ultrasound, conventional computerized tomography (CT), dual-energy CT, and MRI play an increasing role. The authors review typical radiographic features of crystal-induced arthropathies and findings that help to differentiate them. The authors also emphasize the increasing role of complementary imaging techniques.

Ultrasound in crystal-related arthritis.

In the last decade, an increasing number of rheumatologists have been using ultrasound (US) for assessing patients with gout and calcium pyrophosphate deposition (CPPD) disease. The high reflectivity of the crystalline aggregates and the ability of US to detect even minimal crystal deposits explain the high sensitivity of this imaging technique. Furthermore, the peculiar distribution within the target tissues results in the generation of typical US patterns and explains the excellent specificity of some US findings. The large spectrum of US findings and their wide combination generate different scenarios in different patients and also in the same subject. Such a high variety impaired the standardisation of the definitions of each US finding. This review presents the main US findings indicative of crystal deposits, discusses the available evidence supporting the use of US in patients with gout and CPPD disease, and provides a research agenda to guide further investigations. The combined US examination of the target tissues and the clinically involved sites represents the key issue to obtain the best compromise between accuracy and feasibility, in the daily US assessment of patients with crystal-related arthropathies. Moreover, the US guided aspiration of synovial fluid may enhance the possibility to reach a crystal-proven diagnosis, making US a complementary tool, not in contrast, with microscopy, which rests the current gold standard. Finally, even if at moment other US findings are not included among the typical ones for crystal-related arthropathies, it is possible that in the future, thanks to continuous technological advances, we will be able to identify other specific patterns of pathology.

Tumoral calcium pyrophosphate dihydrate deposition disease of the ligamentum flavum.

OBJECTIVE: Calcium pyrophosphate dihydrate (CPPD) deposition disease (CPPDD), also known as pseudogout, is rarely known to affect the spine. The purpose of this article is to report our experience with six cases involving massive focal deposition of CPPD crystals in the ligamentum flavum. METHODS: Between January 1998 and June 2002, we treated six patients with CPPDD involving the ligamentum flavum of the cervical and thoracic spine. Their ages ranged from 45 to 70 years. There were five female patients and one male patient. The cervical spine was involved in two cases and the thoracic spine in four. All except one patient presented with an insidious onset of myelopathy. The remaining patient presented with paraplegia after trauma. None of the patients exhibited any systemic features of CPPDD or other metabolic conditions that can lead to CPPD deposition. Plain x-rays often yielded inconclusive results. Computed tomography and magnetic resonance imaging were useful in confirming the diagnoses. Decompressive laminectomy, with removal of the ossified ligamenta flava, was performed for all patients. Polarized-light microscopic examinations of the excised ligamenta flava revealed the characteristic rod-shaped, birefringent crystals. RESULTS: Five of the six patients experienced significant improvements in their myelopathic symptoms after surgery. The remaining patient experienced improvements in sensations but no appreciable improvement in motor power. During the follow-up periods, which ranged from 7 months to 3 years, none of the patients presented with a recurrence of CPPD crystal deposition at the previously treated level. However, one patient who exhibited improvement after surgery presented 2 years later with a recurrence of myelopathic features attributable to ossification of the ligamentum flavum at a new level. CONCLUSION: Tumoral CPPDD of the ligamentum flavum is rare. It commonly occurs among middle-age or elderly female patients and presents with progressive myelopathy. Computed tomography and magnetic resonance imaging are complementary in the diagnosis of this condition. Surgery, if performed early, leads to good improvement. However, long-term follow-up monitoring of these patients is necessary, because surgery provides only symptomatic relief and does not treat the underlying disease. With the increasing availability of magnetic resonance imaging, ossification of the ligamentum flavum is being more frequently recognized. In every case of ossified ligamentum flavum, the excised specimen should be examined with polarized-light microscopy. We think that this simple, inexpensive method will lead to the recognition of more cases of spinal CPPDD.

Cross-sectional study of 50 patients with calcium pyrophosphate dihydrate crystal arthropathy.

Calcium pyrophosphate dihydrate crystal arthropathy (CPPA) is a well known but heterogeneous disease with a variable presentation and course. We present a cross-sectional study undertaken in a Portuguese rheumatology unit with the aim of analysing clinical and radiological patterns of CPPA in our population. The study population included 50 patients, 34 (68%) women and 16 (32%) men. The mean age was 69.8 +/- 8.8 years. The onset features were acute arthritis in 19 (38%) patients and chronic joint complaints in 26 (52%); five (10%) patients were asymptomatic at the time of diagnosis, which was based only on radiological findings. The diagnosis was established in 37 (74%) cases by clinical and radiographic features, in eight (16%) by clinical, X-ray and synovial fluid analysis, and in five (10%) by clinical features and fluid analysis. The disease course was characterised by acute episodic arthritis in 16 (32%) patients and by persistent symptoms (with or without synovitis) in 34 (68%). The pattern of CPPA in 20 (40%) patients was pseudo-osteoarthritis with synovitis, pseudo-osteoarthritis without synovitis in nine (18%), pseudogout in nine (18%), monoarthropathy in eight (16%) and pseudorheumatoid arthritis in four (8%). The phosphocalcium balance was altered in nine (18%) cases: six patients had hypercalciuria two hyperphosphaturia, two hypocalciuria, one hypophosphaturia and one hypercalcemia. Five patients had abnormal thyroid hormone levels, but only one presented with clinical hypothyroidism. Four patients showed increased parathormone levels, but only one presented with clinical hyperparathyroidism. Radiographic findings showed that 43 (86%) patients had meniscus calcifications, 20 (40%) radiocarpal and 16 (32%) calcification of the symphysis pubis. The study confirms the clinical variability of the disease in a population of Portuguese patients. The knee meniscus calcifications were the most sensitive single finding for establishing the diagnosis of CPPA. Almost all our patients had sporadic idiopathic CPPA without associated pathological conditions.

Crystal deposition in normal and diseased articular cartilage: an extended report.

Particles observed on the surfaces of human articular cartilage following trauma and from chondromalacic, osteoarthritic and rheumatoid joints using the scanning electron microscope were analysed by x-ray diffraction technique. The particles contained calcium and phosphorus and they were identified only in structurally abnormal cartilage. These findings suggest that local abnormality of articular cartilage probably underlies crystal-deposition.

[Post-parathyroidectomy pseudogout in primary hyperparathyroidism]. / Seudogota posparatiroidectomía en el hiperparatiroidismo primario.

We report two cases of pseudogout after parathyroidectomy by primary hyperparathyroidism. The pseudogout in each instance developed within 48 hours after parathyroid adenoma resection. Calcium supplement therapy, nonsteroidal anti-inflammatory drugs and colchicine (1 mg/day) suppressed the acute attack. The chondrocalcinosis is often asymptomatic or undiagnosed, for that, preoperative radiological studies of the knees, wrists and pelvis are recommended to screen for chondrocalcinosis. We advocate also, therapy with colchicine (1 mg/day, oral) in the prophylaxis of postoperative pseudogout.

Familial hypokalemia/hypomagnesemia and chondrocalcinosis.

OBJECTIVE: Familial occurrence of Bartter's syndrome is well known, but the simultaneous occurrence of hypokalemia/hypomagnesemia and chondrocalcinosis in one family has not been described. We present the clinical, laboratory and radiological findings of a family, in which 7 members were affected by disease. METHODS: A total of 43 members of the family could be interviewed concerning their general health, past diseases and joint complaints. Serum potassium and magnesium were determined in all and radiographic studies were performed in those who had hypokalemia and hypomagnesemia or those with merely articular complaints. Urinary excretion of potassium, magnesium and calcium were determined in the affected persons. RESULTS: Seven patients were found with hypokalemia and hypomagnesemia. Urinary potassium and magnesium excretion was inappropriately high when compared to the serum levels of these electrolytes. All patients had hypocalciuria and extensive chondrocalcinosis, mainly in the knees, elbows and shoulders. In one patient, most probably as a result of magnesium supplementation, a striking reduction of chondrocalcinosis was observed during a followup of 10 years. CONCLUSION: A family with familial hypokalemia/hypomagnesemia and chondrocalcinosis is described. The reduction of chondrocalcinosis, after years of magnesium supplementation in one patient, suggests that hypomagnesemia is an important factor in the pathogenesis of chondrocalcinosis in these patients.

Pyrophosphate arthropathy in two Swedish families.

A clinical and radiographic survey of 110 members of 2 families with hereditary pyrophosphate arthropathy was performed. The mode of inheritance was autosomal, dominant with a variable penetrance. Twenty-two percent of the family members had joint involvement related to pyrophosphate arthropathy, 47% of those over 50 years of age had experienced acute attacks of arthritis and/or had joint calcifications. The majority of individuals with both arthritis and joint calcifications suffered from chronic pain that resulted in early retirement. A high frequency of back pain was observed, but no ankylosis or deformity. Surgery was performed for parathyroid hyperplasia on the propositus in 1 family, and several members of her family suffered from symptoms that suggested a disturbance of calcium phosphate metabolism. There were several differences between our patients and 50 cases of sporadic pyrophosphate arthropathy from the same area of Sweden. Familial cases had an earlier onset, a greater number of involved joints, and peripheral joint involvement more often. Back pain was more frequent, and calcifications of intervertebral discs were found only in the hereditary cases.

[Xeroradiography in the diagnosis of skeletal diseases (author's transl)]. / Xeroradiographie in der Diagnostik von Skeletterkrankungen.

The value of xeroradiography in the diagnosis of peripheral skeletal lesions is illustrated by some typical examples and compared with standard radiographic procedures. The advantages of xeroradiography depend on its convenient format, easy appreciation of structural changes and easy viewing. On the other hand, density gradations are flattened. Compared with a technically satisfactory film examination, there is no increase in diagnostic information. Xeroradiography can therefore only be regarded as complementary to conventional radiography for the diagnosis of skeletal conditions.