[Update on Gout and Calcium pyrophosphate deposition (CPPD)]. / Gicht und Calciumpyrophosphat-Dihydrat-Arthropathie ("Pseudogicht") ­ ein Update.

The metabolic diseases gout and calciumpyrophosphate deposition (CPPD) (formerly: chondrocalcinosis/pseudogout) are crystal arthropathies which are caused by crystals in synovial fluid and in the case of gout also in periarticular structures. Today, in particular gout is considered as an auto-inflammatory process since phagocytosis of monosodium urate crystals by monocytes/macrophages results in the activation of the innate immune system by activation of the NRLP3-Inflammasome and consecutive secretion of the key cytokine interleukin-1ß and other pro-inflammatory cytokines. The prevalence of both crystal arthropathies rises with increasing age of patients. Most often they present clinically as an acute monarthritis of different locations. Beside typical clinical presentation, performance of ultrasonography, conventional X-Ray of joints and under special circumstances dual-energy-computer tomography could be also helpful diagnostic tools. There are EULAR guidelines describing the diagnostic algorithm for making right diagnosis. The arthrocentesis with microscopic detection of crystals is established diagnostic gold standard. Whereas crystals of monosodium urate could be very clearly be seen as relatively large intra- and extracellular needles with a strong birefringence in polarized light microscopy the detection of CPPD-crystals is more difficult. Those crystals are much smaller, showing weaker birefringence and are sometimes only seen with ordinary light microscopy. As both crystal diseases are mediated by IL-1 driven processes, the therapeutic intervention first target the acute inflammation consisting in colchicine, NSAIDs and glucocorticoids. Secondarily, in gout there are well established causal therapies to lower effectively serum urate levels below the target of 6 mg/dL (360 µmol/l). Unfortunately, those causal therapeutic options are still lacking in CPPD.

Emergent nanotherapies in microcrystal-induced arthritis.

The anti-inflammatory and immunomodulatory effects of nanoparticles in several chronic diseases have been extensively researched. The aim of this review is to examine how nanoparticles modulate the inflammatory pathways that characterize the most prevalent forms of microcrystal-induced arthritis, including gout, pseudogout, and BCP-induced arthritis. The nanoparticles of chitosan-coated calcium phosphate, uricase, aceclofenac, and gold have been investigated in crystal-inducedarthritis. The most important results of the studies outlined in this review show that nanoparticles can inhibit the expression and the release of some pro-inflammatory mediators and proteolytic enzymes, and the activity of different transcriptional factors in vitro, as well as decrease the uric acid levels in several studies of in vitro and in vivo models of gout, which show interesting results in terms of decreasing the amount of crystals and tissue damage, respectively. In view of their multiple beneficial effects, nanoparticles can be considered a valuable therapy that contributes to the pharmacological treatment in crystalinduced arthritis.

Diagnosis and Treatment of Gout and Pseudogout for Everyday Practice.

Gout and pseudogout are crystalline arthropathies commonly seen in primary care. It is important to understand their pathophysiology to facilitate recognition and appropriate treatment. Prompt gouty arthritis treatment relieves short-term suffering. Long-term treatment with urate-lowering therapy prevents recurrent attacks and is generally well-tolerated though flare risk is increased during treatment initiation. When anti-inflammatory medications are prescribed, the flare risk is low. Pseudogout acute treatment is similar to acute gouty arthritis treatment. There is no standard regimen for long-term chronic therapies of pseudogout. This article enhances the recognition and treatment of these diseases in the primary care setting.

Crowned dens syndrome.

Crowned dens syndrome is a rare presentation of calcium pyrophosphate deposition disease. It is characterised by severe occipital pain and neck stiffness. Acute presentations are typically accompanied by fever and an inflammatory response and hence can be misdiagnosed as polymyalgia rheumatica or meningitis. Chronic relapsing presentations may be misdiagnosed as cervicogenic neck pain or occipital neuralgia. We present a patient who presented with a chronic relapsing form of crowned dens syndrome and discuss the epidemiology, typical presentation and management of this eminently treatable condition.

Condrocalcinosis axial: reporte de un caso / Axial chondrocalcinosis: a case report

La artropatía por pirofosfato de calcio (CPPD) se caracteriza por la acumulación de cristales de pirofosfato de calcio en el tejido articular y periarticular. La localización más frecuente son rodillas, muñecas y pelvis. Sin embargo, también existen reportes aislados de compromiso de columna. Se presenta el caso de un paciente varón de 52 años, con antecedentes de doble prótesis de caderas por coxartrosis diagnosticada a los 20 años de edad. Es evaluado en reumatología en febrero de 2017, por cuadro de poliartralgias de grandes articula-ciones, asociada a dolor de columna cervical, dorsal y lumbar. Se realizan exámenes imagenológicos que demuestran la presencia de calcificaciones interdiscales con sobrecrecimiento óseo, secundario a artrosis severa y discreta este-nosis raquídea solo en segmentos lumbares bajos.

The Calcium pyrophosphate dihydrate (CPPD) deposition disease is characterised by the deposition of crystals of CPPD in the articular as well as in periarticular structures. The most frequent location are knees, wrist and pelvis. However, also there are iso-lated cases involving the spine. It presents the case of a 52 years male patient, with history of bone arthrosis dou-ble hips prosthesis by bone arthrosis diagnosed 30 years ago. He is evaluated in feb-ruary 2017 by pain of large joints associated cervical spine pain dorsal and lumbar. Imagenological tests are prerfomed and confirms the presence of intervertebral discs calcifications and bone overgrowth secundary to severe osteoarthrosis and spinal ste-nosis in lower lumbar segments.

[From chondrocalcinosis to rheumatism with calcium pyrophosphate dehydrate]. / De la chondrocalcinose au rhumatisme à cristaux de pyrophosphate de calcium.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is a joint pathology that affects joints, fibrocartilages and periarticular structures. Chondrocalcinosis refers to CPPD deposits on the X-ray that does not summarize the disease. It willingly affects the knees and the wrists, but all the joints can be affected. There are primitive and secondary forms of the disease to particularly look for in patients less than 50 years. The diagnosis is usually easy with standard radiography, ultrasound and synovial fluid analysis that shows the microcrystals. The therapeutics of the acute attacks are nonspecific and close to those used for acute attacks of gout.

Destructive pseudo-neuroarthropathy associated with calcium pyrophosphate deposition.

BACKGROUND: Calcium pyrophosphate deposition (CPPD) disease is a metabolic disorder characterized by soft tissue calcific deposits formed primarily in articular cartilage. What can result is a crystal-induced arthropathy often referred to as pseudogout, which is variable in both presentation and severity. A particularly destructive and deforming arthritis is an uncommon but well-recognized subtype of this disease. Radiologically resembling the neuroarthropathy described by Charcot, a pattern of joint fragmentation and structural collapse occurs in the absence of peripheral neuropathy. This pseudo-neuroarthropathy is rarely reported in the foot and ankle. METHODS: A total of 15 cases of pseudo-neuroarthropathy involving some previously unreported joints within the foot and ankle are described in this case series of 9 patients. RESULTS: All patients presented with disease involving multiple joints. Clinical deformity was apparent in each case, and extensive joint destruction was seen on plain radiographs. In 6 patients, histopathological CPPD disease was confirmed on tissue biopsy of the affected joints. In the remaining 3 patients a clinical diagnosis was made on the basis of the classic appearance of pseudo-neuroarthropathy in the foot, with additional recognized features of CPPD. Operative management with deformity correction using joint arthrodesis produced satisfactory clinical and radiological results. CONCLUSIONS: In the absence of peripheral neuropathy and systemic disease, the pseudo-neuroarthropathy of CPPD should be considered when a progressively deforming and destructive arthritis is seen in the foot and ankle. LEVEL OF EVIDENCE: Level IV, case series.

Nonpharmacologic and pharmacologic management of CPP crystal arthritis and BCP arthropathy and periarticular syndromes.

Calcium crystal arthritis is often unrecognized, poorly managed, and few effective therapies are available. The most common types of calcium crystals causing musculoskeletal syndromes are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP). Associated syndromes have different clinical presentations and divergent management strategies. Acute CPP arthritis is treated similarly to acute gouty arthritis, whereas chronic CPP and BCP arthropathy may respond to strategies used for osteoarthritis. Calcific tendonitis is treated with a variety of interventions designed to dissolve BCP crystals. A better understanding of the causes and larger well-planned trials of current therapies will lead to improved care.

The forgotten crystal arthritis: calcium pyrophosphate deposition.

Calcium pyrophosphate crystals are related to a variety of articular manifestations known as calcium pyrophosphate deposition (CPPD) arthritis. Acute CPPD arthritis is commonly known as pseudogout, but there are many other presentations. Diverse endocrine and metabolic diseases may be related to CPPD arthritis. Septic arthritis is in the differential diagnosis of acute CPPD arthritis. The treatment options for CPPD arthritis include non-steroidal anti-inflammatories and steroids.

Presentation and conservative management of acute calcific tendinopathy: a case study and literature review.

BACKGROUND: The efficacy of a variety of noninvasive, conservative management techniques for calcific tendinopathy has been investigated and established for improving pain and function and/or facilitating a decrease in the size or presence of calcium deposits. Surprisingly, few have reported on the use of traditional therapeutic exercise and rehabilitation alone in the management of this condition, given the often spontaneous resorptive nature of calcium deposits. The purpose of this case is to present the results of a conservative approach, including therapeutic exercise, for the management of calcific tendinopathy of the supraspinatus, with an emphasis on patient outcomes. CASE DESCRIPTION: The patient was a self-referred 41-y-old man with complaints of acute right-shoulder pain and difficulty sleeping. Imaging studies revealed liquefied calcium deposits in the right supraspinatus. The patient reported constant pain at rest (9/10) and tenderness in the area of the greater tuberosity. He exhibited a decrease in all shoulder motions and had reduced strength. The simple shoulder test (SST) revealed limited function (0/12). Conservative management included superficial modalities and medication for pain and a regimen of scapulothoracic and glenohumeral range-of-motion (ROM) and strengthening exercises. OUTCOMES: At discharge, pain levels decreased to 0/10 and SST scores increased to 12/12. ROM was full in all planes, and resisted motion was strong and pain free. The patient was able to engage in endurance activities and continue practicing as a health care provider. DISCUSSION: The outcomes with respect to pain, function, and patient satisfaction provide evidence to support the use of conservative therapeutic interventions when managing patients with acute cases of calcific tendinopathy. Successful management of calcific tendinopathy requires attention to outcomes and an understanding of the pathophysiology, prognostic factors, and physical interventions based on the current stage of the calcium deposits and the patient's status in the healing continuum.

Treatment of hyperuricemia, gout and other crystalline arthritidies.

Gout is a very common joint disease which is due to chronic hyperuricemia and its related articular involvements. Yet it can be cured when appropriately managed. Comprehensive management of gout involves correct identification and addressing all causes of hyperuricemia, treating and preventing attacks of gouty inflammation (using colchicine NSAIDs, and/or steroids), and lowering serum urate (SUA) to an appropriate target level indefinitely. The ideal SUA target is, at a minimum, less than 6 mg/dL (60 mg/L or 360 µmol/L), or even less than 5 mg/dL in patients with tophi. The SUA target should remain at less than 6 mg/dL for long in all gout patients, especially until tophi have resolved. Patient education and adherence to therapy are key point to the optimal management of gout, aspects which are often neglected. Adherence can be monitored in part by continuing, regular assessment of the SUA level. More difficult cases of gout often need a combination of urate lowering therapy (ULT) for both refractory hyperuricemia and chronic tophaceous arthritis. Chronic tophaceous gouty arthropathy which do not respond adequately to optimized oral ULT might benefit from the use of pegloticase, when this is available in, for example, Italy and other European countries. By contrast, in calcium pyrophosphate (CPP) crystal deposition disease (CPPD), as evidenced by pseudo gout attacks or chronic polyarthritis, similar anti-inflammatory strategies have been recommended, but there have as yet been no controlled trials. Of note, there is no treatment for the underlying metabolic disorders able to control the CPPD. Management of crystal-induced arthropathies (CIA) depends not only on clinical expression, namely acute attacks or chronic arthropathy, but also on the underlying metabolic disorder. We will mainly focus on gout as an archetype of CIA.

Role of Newman's classification in predicting outcomes in patients with crystal arthritis.

PURPOSE: The aim of the study was to evaluate the utility of Newman's classification in predicting outcomes in patients presenting with crystal arthritis. METHODS: Between January and December 2009, all patients who presented to our institution with acute crystal arthritis and were investigated with microbiological assessment of their synovial fluid were included in the study. Patients were divided into two groups depending on the fulfilment of Newman's criteria for culture-negative septic arthritis. Group 1 included patients that fulfilled Newman's B criteria. Group 2 included patients that fulfilled Newman's C criteria. A database looking at the demographics, mode of presentation, investigations, treatment and outcomes was then established and the results compared between the two groups. RESULTS: A total of 58 patients were identified (group 1: n = 13; group 2: n = 45). The average age was 71 years (range 33-96). The joint most commonly involved was the knee followed by the wrist. Clinical findings at presentation were comparable in both groups; however, WBC and C-reactive protein (CRP) were more likely to be raised in group 1. Although most patients in group 1 were treated with antibiotics (62%) there was still a higher rate of morbidity, greater use of supportive therapy and a longer hospital stay (22.3 days, SD 17.4) in comparison with group 2, where most patients were treated by observation only (76%, mean hospital stay 3.5 days, SD ± 4.4). The difference in length of hospital stay was statistically significant (p < 0.0001). CONCLUSIONS: Newman's criteria are a good indicator for prognosis in patients with crystal arthritis. However, the presence of crystals in an acutely inflamed joint does not exclude the need for supportive therapy and long hospital stay even in the absence of positive synovial fluid culture.