Distinguishing Periprosthetic Crystalline Arthropathy from Infection in Total Knee Arthroplasty: A Systematic Review.

Distinguishing periprosthetic crystalline arthropathy from periprosthetic joint infection (PJI) remains a diagnostic challenge as both symptom presentation and diagnostic tests overlap. Accurate differentiation is important as treatment plans vary significantly. We sought to systematically review all cases of total knee arthroplasty (TKA) periprosthetic crystalline arthropathy reported in the literature and summarize clinical, diagnostic, and operative findings in the context of guidelines for diagnosing PJI. The goal of this systematic review is to determine the amount of diagnostic overlap and to identify best practices for differentiating between these two diagnoses. MEDLINE and Google Scholar were searched to identify cases of crystalline arthropathy following TKA. Case reports were reviewed for patient characteristics, clinical symptoms, physical exam, laboratory results, and treatment outcomes. These findings were summarized across patients and dichotomized based on current thresholds for diagnosing PJI according to Musculoskeletal Infection Society criteria. Twenty-six articles were identified which included 42 cases of periprosthetic crystalline arthropathy (17 gout, 16 pseudogout, one both, and eight not specified). Of these cases, 25 presented over 1 year after their index arthroplasty and 15 had no prior history of crystalline arthropathy. Only six cases had a superimposed infection based on aspiration or intraoperative cultures. For cases without a culture-positive infection, several diagnostic tests overlap with PJI thresholds: 95% of patients had C-reactive protein greater than 1 mg/dL, 76% had an erythrocyte sedimentation rate greater than 30 mm/hour, 91% had a synovial white blood cell greater than 3,000 cells, and 76% had a synovial polymorphonuclear cells percent greater than 80%. Patients without co-infection were managed with non-steroidal anti-inflammatory drugs, colchicine, allopurinol, steroids, or a combination of these treatments and most had complete resolution of symptoms within 1 week. Commonly used markers of PJI fail to reliably distinguish periprosthetic crystalline arthropathy from infection. Though clinical judgement and consideration of the implications of delayed treatment for acute PJI remain paramount, in the setting of synovial crystals, surgeons may wish to consider this alternate etiology as the source of the patient's clinical symptoms.

Radiological features of crystal-induced arthropathy associated with hereditary hemochromatosis with homozygous C282Y mutation. / Características radiológicas de la artropatía microcristalina asociada a hemocromatosis hereditaria con mutación homocigota C282Y.

I present a clinical case of a 64-year-old male patient with hemochromatosis (homozygous C282Y) and crystal induced arthropathy showing the most common radiological features found in this metabolic disorder and the differences that may exist when compared to other primary degenerative processes or other inflammatory pathologies.

Efficacy of anakinra in acute hydroxyapatite calcification-induced joint pain: A retrospective study of 23 cases.

OBJECTIVE: Hydroxyapatite (HA) crystal calcifications in or around the joint can induce acute flares with severe pain. A previous pilot study suggested that the interleukin-1ß (IL-1ß) inhibitor anakinra was effective. The goal of this observational study was to confirm these results in a larger set of patients and to report on the long-term follow-up. METHODS: Flare was defined as acute pain for<10 days. Calcification in or around a joint (rotator cuff: 15/23 patients) was confirmed by conventional radiography and/or ultrasonography (US). Anakinra 100mg daily was administered subcutaneously for 1 to 3 consecutive days. Clinical data collected before the injection and on days 3 and 21 included pain score on a visual analog scale (VAS, 0-10cm) and C-reactive protein (CRP) level. When available, US baseline and follow-up findings were compared. Long-term follow-up data were collected from patient charts and/or after a phone call. RESULTS: 23 patients (15 males, mean [SD] age 58 [11] years) were included. Baseline mean (SD) VAS pain was 7.7 (1) cm and CRP level was elevated in half of the patients. After therapy, mean (SD) VAS pain score decreased rapidly in the first 3 days to 1.6 (1.4) cm (P<0.001) and remained stable for 3 weeks at 1.8 (2.1) cm. US assessment revealed decreased Doppler intensity but no significant change in size of calcifications. No significant side effects were noted. After long-term follow-up (median duration 24 months), half of the patients still had some chronic pain, but only 4 experienced acute relapse. CONCLUSION: This study suggests that IL-1ß inhibition may be an efficient therapeutic approach for acute HA flare, with a good safety profile.

Disease-Associated Particulates and Joint Inflammation; Mechanistic Insights and Potential Therapeutic Targets.

It is now well established that intra-articular deposition of endogenous particulates, such as osteoarthritis-associated basic calcium phosphate crystals, gout-associated monosodium urate crystals, and calcium deposition disease-associated calcium pyrophosphate crystals, contributes to joint destruction through the production of cartilage-degrading enzymes and pro-inflammatory cytokines. Furthermore, exogenous wear-debris particles, generated from prosthetic implants, drive periprosthetic osteolysis which impacts on the longevity of total joint replacements. Over the last few years, significant insight has been gained into the mechanisms through which these particulates exert their effects. Not only has this increased our understanding of the pathological processes associated with crystal deposition but it has also led to the identification of a number of therapeutic targets to treat particulate-associated disease. In this review, we discuss recent developments regarding the cellular events triggered by joint-associated particulates, as well as future directions in therapy for particulate-related arthropathies.

Basic calcium phosphate crystal-associated musculoskeletal syndromes: an update.

PURPOSE OF REVIEW: Basic calcium phosphate (BCP) crystals are associated with two important musculoskeletal syndromes. Deposition of BCP crystals in tendons, bursae, and other soft tissues around joints causes calcific periarthritis, whereas intra-articular BCP crystals contribute to osteoarthritis and cause the highly destructive arthritis known as Milwaukee Shoulder Syndrome. The epidemiology and natural history of these syndromes are poorly understood, and because the pathogenesis remains unclear, few targeted therapies are available. I will review new developments in this field. RECENT FINDINGS: I will discuss a case collection of calcific periarthritis of the hip, and evidence-based management strategies for shoulder calcific periarthritis that might be applied to calcific periarthritis at other locations. I will summarize several recent articles addressing mechanisms of crystal formation and identifying pathways through which BCP crystals produce tissue damage and explore some newly identified risk factors for pathologic mineralization. SUMMARY: We are making slow, but steady progress in understanding the clinical presentation of calcific periarthritis in sites other than the shoulder. A growing appreciation of the mechanisms through which BCP crystals mediate tissue damage should lead to the development of novel management strategies for these common musculoskeletal syndromes.

Crystal-Induced Arthropathy in Elderly Patients Hospitalized for Acute Conditions.

BACKGROUND: Arthritis and arthralgia are painful symptoms experienced by many elderly patients during hospitalization. Crystal-induced arthritis (CIA) is one of the most common causes of arthritis worldwide and represents the most common cause of acute arthritis in the elderly. OBJECTIVES: To determine the incidence of both acute new onset or acute exacerbation of CIA among elderly patients hospitalized due to an acute medical illness. METHODS: This study comprised 85 patients. Patients aged 70 years and older who complained of any articular pain were included in the study. Exclusion criteria were signs of septic arthritis, chronic use of steroids or non-steroidal anti-inflammatory drugs, or admission to the hospital due to an acute attack of CIA. RESULTS: RSynovial aspiration was performed in 76 patients (89%). Joint aspiration yielded a diagnosis in 67 of them (79%). The predominant type of crystal was calcium pyrophosphate dehydrate (68%) followed by monosodium urate (20%). The main causes of hospitalization were acute infectious disease (57%) followed by neurologic and cardiac diseases, 14% and 9% respectively, and orthopedic problems (6%). Among patients with acute infectious disease, the main causes were pulmonary (57%) and gastrointestinal (22%) infections. In 9 patients (12%) who underwent synovial aspiration, visible crystals were identified without a definite diagnosis. CONCLUSIONS: Our study showed that hospitalization could be a risk factor for the development of CIA, and the time to diagnose CIA is during hospitalization for other acute illnesses.

Update on calcium pyrophosphate deposition.

Calcium pyrophosphate crystal deposition (CPPD) associates with ageing, osteoarthritis (OA), uncommon metabolic diseases, mutations and polymorphisms in the ankylosis human gene (ANKH). CPPD is frequently polyarticular, occurs due to a generalised articular predisposition, and the association between CPPD and OA is joint specific, for example CPPD associates with knee OA, but not with hip OA. Other recently identified associations include knee malalignment (knee CC), low cortical BMD and soft-tissue calcification. CPPD is generally asymptomatic. A recent study reported that knees with OA plus CC at the index joint, or at distant joints (in absence of index joint CC), were more likely to have attrition. CPPD can cause acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and is frequently present in joints with OA. Joint aspiration remains the gold standard for diagnosing CPPD, although other promising techniques are emerging. Patients with polyarticular or young onset CPPD should be screened for underlying metabolic abnormalities, however, such testing can be unrewarding. The treatment of CPPD is symptomatic. Acute CPP crystal arthritis is treated with rest, local application of ice-packs, joint aspiration, colchicine and/or intra-articular corticosteroid injection (once infection is excluded). Colchicine, low-dose corticosteroids, hydroxychloroquine and radiosynovectomy are recommended for the treatment of chronic or recurrent acute CPP crystal arthritis. Recent RCTs did not confirm any benefit from methotrexate, and although there is increasing interest in the use of anti-IL1 agents for acute or chronic CPP crystal arthritis, their efficacy has not been formally examined. Unlike gout, currently there are no treatments to eliminate CPP crystal deposits.

Crystal-induced arthritis after arthroplasty: 7 cases.

OBJECTIVES: To describe the occurrence in prosthetic joints of crystal-induced arthritis (CIA) defined as the deposition within the synovial membrane and/or joint cavity of calcium pyrophosphate dehydrate (CPPD) (chondrocalcinosis), sodium urate (gout), or hydroxyapatite. METHODS: We retrospectively reviewed the 7 cases of prosthetic-joint CIA seen between 1993 and 2013 at a medical-surgical center specialized in the management of osteoarticular infections. RESULTS: The 4 females and 3 males ranged in age from 67 to 79 years. Acute CIA occurred at the knee in 6 patients (5 with total knee arthroplasty and 1 with unicompartmental knee arthroplasty) and at the hip in 1 patient (with total hip arthroplasty). Time from arthroplasty to CIA varied from 7 days to 9 years. An abrupt onset was a consistent feature, with pain, complete loss of function, and local evidence of inflammation. A single patient had a fever and 6 patients had laboratory evidence of systemic inflammation. Joint aspiration showed hemarthrosis in 3 patients and inflammatory joint fluid with 20,000 to 79,000neutrophils/mm(3) in 6 patients. Joint fluid cultures were negative in 6 patients. CPPD crystals were evidenced in 5 patients, including 1 who also had hydroxyapatite crystals detected by electron microscopy after alizarin red staining. Monosodium urate crystals were found in 1 patient. The remaining patient had both CPPD crystals and positive cultures for Campylobacter fetus. In 5 patients, treatment with colchicine or a nonsteroidal antiinflammatory drug ensured prompt control of the symptoms and systemic inflammation. The patient with total hip arthroplasty underwent joint aspiration for hemarthrosis. In 1 patient, an intraarticular injection of triamcinolone hexacetonide improved the symptoms and systemic inflammation. The patient with Campylobacter fetus infection was treated with antibiotics, excision of the abscess, and synovectomy. CONCLUSION: CIA may occur after arthroplasty, within synovial membrane remains or neosynovium developed around the prosthetic joint. CIA is a manifestation of a metabolic disease that persists and can reactivate after surgery. Routine testing for crystals is rarely performed in patients with sterile arthritis of a prosthetic joint, and crystals are difficult to detect in joints with hemarthrosis; consequently, the frequency of prosthetic-joint CIA may be underestimated. Although rare, CIA should be considered routinely when symptoms suggesting septic arthritis develop in a prosthetic joint, in order to avoid unnecessary prolonged antibiotic therapy and, in some cases, surgery. The treatment is usually simple.