Safety and efficacy of colchicine in crystal-induced arthritis flare in 54 patients with severe chronic kidney disease.

INTRODUCTION: Colchicine, commonly used in gout flare, is contraindicated in severe chronic kidney disease (CKD) (estimated glomerular filtration rate <30 mL/min). However, in this context, there are few alternatives, and colchicine use persists. We evaluated the tolerance of colchicine and its efficacy in patients with severe CKD. PATIENTS AND METHODS: All prescriptions of colchicine for managing crystal-induced arthritis flare (gout or calcium pyrophosphate deposition (CPPD) disease) in a hospitalised patient with severe CKD were screened from September 2020 to September 2021. After patient consent and treatment information, clinical and biological safety and efficacy data were prospectively collected from day 1 (D1) to D11. RESULTS: We included 54 patients (median age 75 years (IQR 67-83)) with 62 colchicine prescriptions (cases). Twelve (22%) patients were on dialysis. The main reason for hospitalisation was heart failure (31.5%), acute renal failure (22.2%), infection (18.5%) or an acute joint episode (9.3%). In total, 59.3% of patients had diabetes. The prescriptions concerned 58 cases of gout flares, 1 case of CPPD and 3 cases of both. Initial colchicine dosages were ≤0.5 mg/day in 47/62 (75.8%) cases; no dosage exceeded 1 mg/day (median duration of 6 days (IQR 3-11)). Colchicine was well tolerated in 47/61 (77%) cases. No serious adverse event was reported. Colchicine was considered completely effective by the medical team in 48/58 (83%) of cases. CONCLUSION: The use of colchicine, at reduced doses, was mostly effective to treat crystal-induced arthritis flare in 54 patients with severe CKD and was well tolerated, without any serious adverse events.

[Diastolic dysfunction of ventricles in patients with calcium pyrophosphate crystal deposition disease while receiving anti-inflammatory therapy].

BACKGROUND: Calcium pyrophosphate crystal deposition disease (CPPD) may be associated with developing of diastolic dysfunction (DD). AIM: To determine the variability of echocardiographic parameters in patients with CPPD receiving anti-inflammatory therapy. MATERIALS AND METHODS: Twenty six patients with CPPD and osteoarthritis (OA) from 18 to 65 years old were included in the case-control study. All patients underwent echocardiography, laboratory parameters at baseline and after 6 months. Patients with CPPD received methotrexate 15 mg per week or hydroxychloroquine 200 mg once a day, or colchicine 1 mg per day. Diastolic function according to echocardiography was assessed. RESULTS: Diastolic dysfunction was detected in 19 patients: in 11 (42%) patients with CPPD and 8 (31%) patients with OA (p=0.39). The baseline serum CRP level was higher in the CPPD group (p=0.03), no differences were found for other indicators. Twenty-two patients with CPPD and 19 patients with OA completed the study. In patients with OA, there were no significant changes in indicators reflecting the diastolic function of ventricles. CONCLUSION: CPPD therapy with colchicine, hydroxychloroquine and methotrexate has a positive effect on indicators of diastolic ventricular function.

Acute monoarticular hip joint pseudogout masquerading as septic arthritis.

Monoarticular pseudogout of the hip joint is rare and to the best of our knowledge only four other cases exist in the literature. We present a case of primary monoarticular pseudogout affecting the right hip in a patient in his 50s. The diagnosis was confirmed through ultrasound-guided synovial fluid aspiration and crystal analysis. The patient was treated conservatively with analgesia and after hip joint aspiration resulted in dramatic symptomatic resolution. Acute attack of pseudogout is a rare cause of acute hip pain. The clinical features may mimic hip joint septic arthritis and should be considered in the differential diagnosis of any presentation of acute joint pain. Diagnosis is important to avoid unnecessary medical and surgical intervention reducing hospital stay.

Case report: crowned dens syndrome in a patient with seronegative rheumatoid arthritis.

Chondrocalcinosis (CC) is the one of the most common crystal pyrophosphate disease associated arthritis in the elderly. It has been shown to coexist with seronegative and seropositive rheumatoid arthritis (RA), yet mostly with seronegative RA. Among the localisation of CC, the deposition in the ligaments surrounding the odontoid process may remain asymptomatic for years or may lead to and acute severe symptomatology, which may mimic several clinical illnesses among which meningitis (fever, severe pain, acute phase reactants). This is called the 'crowned dens syndrome (CDS)', which has been reported to represent an important percentage of acute neck pain needing hospital admission in neurosurgery units. In this case, the rapid demonstration of 'crowned dens' through CT scan may allow to avoid lumbar puncture and cerebrospinal fluid examination. The coexistence of RA and CDS is very rare, and rarely reported in the literature, yet it may represent a clinical challenge. We describe here one case that while on therapy with methotrexate (MTX) and naproxen (NPX) had an acute neck pain, and peripheral arthritis flare, that responded well to colchicine given along with MTX and NPX.

A single-centre retrospective case series of Anakinra for incident calcium pyrophosphate deposition disease.

In this 2-year retrospective case series, we characterise the calcium pyrophosphate deposition disease (CPPD) inpatient cohort at a single centre and assess the efficacy and safety of anakinra in its treatment. Adult inpatients with CPPD between 1st September 2020 and 30th September 2022 were identified by ICD-10 codes and confirmed based on clinical diagnosis and either CPP crystals on aspirate or chondrocalcinosis on imaging. Charts were reviewed for demographic, clinical, biochemical data, treatment choice, and response. Response to treatment was determined from chart documentation and calculated from time of first CPPD treatment. Daily responses to anakinra were recorded if anakinra was used. Seventy patients accounting for 79 cases of CPPD were identified. Twelve cases received anakinra, whilst 67 cases received conventional therapy only. Patient receiving anakinra were predominantly male, had multiple comorbidities, and had higher CRPs and serum creatinine when compared to the non-anakinra group. Anakinra was rapidly effective with the mean time to substantial and complete response being 1.7 and 3.6 days respectively. Anakinra was well tolerated. This study adds to the small amount of retrospective data present about the use of anakinra in CPPD. We observed a rapid response to anakinra in our cohort with minimal adverse drug reactions. Key Points • Treatment of CPPD with anakinra appears to be rapidly efficacious without safety concerns.

Confirming Prior and Identifying Novel Correlates of Acute Calcium Pyrophosphate Crystal Arthritis.

OBJECTIVE: To investigate previously identified and novel correlates of acute calcium pyrophosphate (CPP) crystal arthritis among well-characterized cases. METHODS: In this case-control study, we identified cases of acute CPP crystal arthritis using a validated algorithm (positive predictive value 81%) applied in the Partners HealthCare electronic health record (EHR). Cases were matched to general patient controls on the year of first EHR encounter and index date. Prespecified potential correlates included sex, race, and comorbidities and medications previously associated with CPP deposition/acute CPP crystal arthritis in the literature. We estimated odds ratios (ORs) and 95% confidence intervals using conditional logistic regression models adjusted for demographic characteristics, comorbidities, medications prescribed in the past 90 days, health care utilization, and multimorbidity score. RESULTS: We identified 1,697 cases matched to 6,503 controls. Mean ± SD age was 73.7 ± 11.8 years, 56.7% were female, 80.8% were White, and 10.3% were Black. All prespecified covariates were more common in cases than controls. Osteoarthritis (OR 3.08), male sex (OR 1.35), rheumatoid arthritis (OR 2.09), gout (OR 2.83), proton pump inhibitors (OR 1.94), loop diuretics (OR 1.60), and thiazides (OR 1.46) were significantly associated with acute CPP crystal arthritis after full adjustment. Black race was associated with lower odds for acute CPP crystal arthritis compared to White race (OR 0.47). CONCLUSION: Using a validated algorithm to identify nearly 1,700 patients with acute CPP crystal arthritis, we confirmed important correlates of this acute manifestation of CPP deposition. This is the first study to report higher odds for acute CPP crystal arthritis among males.

Histone Deacetylase Inhibitors Downregulate Calcium Pyrophosphate Crystal Formation in Human Articular Chondrocytes.

Calcium pyrophosphate (CPP) deposition disease (CPPD) is a form of CPP crystal-induced arthritis. A high concentration of extracellular pyrophosphate (ePPi) in synovial fluid is positively correlated with the formation of CPP crystals, and ePPi can be upregulated by ankylosis human (ANKH) and ectonucleotide pyrophosphatase 1 (ENPP1) and downregulated by tissue non-specific alkaline phosphatase (TNAP). However, there is currently no drug that eliminates CPP crystals. We explored the effects of the histone deacetylase (HDAC) inhibitors (HDACis) trichostatin A (TSA) and vorinostat (SAHA) on CPP formation. Transforming growth factor (TGF)-ß1-treated human primary cultured articular chondrocytes (HC-a cells) were used to increase ePPi and CPP formation, which were determined by pyrophosphate assay and CPP crystal staining assay, respectively. Artificial substrates thymidine 5'-monophosphate p-nitrophenyl ester (p-NpTMP) and p-nitrophenyl phosphate (p-NPP) were used to estimate ENPP1 and TNAP activities, respectively. The HDACis TSA and SAHA significantly reduced mRNA and protein expressions of ANKH and ENPP1 but increased TNAP expression in a dose-dependent manner in HC-a cells. Further results demonstrated that TSA and SAHA decreased ENPP1 activity, increased TNAP activity, and limited levels of ePPi and CPP. As expected, both TSA and SAHA significantly increased the acetylation of histones 3 and 4 but failed to block Smad-2 phosphorylation induced by TGF-ß1. These results suggest that HDACis prevented the formation of CPP by regulating ANKH, ENPP1, and TNAP expressions and can possibly be developed as a potential drug to treat or prevent CPPD.

Acute Calcium Pyrophosphate Crystal Arthritis of the Wrist Elicited by Anti-COVID-19 Vaccination After Carpal Tunnel Release.

BACKGROUND Calcium pyrophosphate dihydrate deposition disease includes a variety of clinical syndromes, including acute calcium pyrophosphate (CPP) crystal arthritis. Most patients with CPP crystal arthritis have a primary/idiopathic form presenting with severe pain, swelling, and stiffness. COVID-19 infection, which originated in China in December 2019, required extraordinary efforts to develop and test new vaccines to halt the pandemic. The Vaxzervria vaccine has shown excellent safety and efficacy in phase 3 trials with a mechanism based on the expression of the SARS-CoV-2 spike protein gene coding for the S-antigen, which stimulates the immune response. CASE REPORT We describe an acute event of crystal arthritis after a carpal tunnel syndrome release followed by administration of the second dose of anti-COVID-19 Vaccine Oxford-AstraZeneca (ChAdOx1 nCoV-19). Medical treatment resulted in full resolution of the symptoms in 2 weeks. CONCLUSIONS Although most episodes of acute arthritis happen spontaneously, certain factors may trigger the acute CPP crystal arthritis such as intercurrent illnesses or surgeries. Although the association between carpal tunnel syndrome and CPP arthritis has been known for over 40 years, surgical release of the carpal ligament has always been associated with full resolution of symptoms. This is the first case report describing an exacerbation after carpal canal release, concomitant with the administration of the vaccine. According to our opinion, the vaccination associated with a prior surgery in the same anatomical site could have synergically triggered the arthritis flare-up, in a predisposed patient, with a mechanism still unknown.

Calcium pyrophosphate deposition (CPPD) disease - Treatment options.

In contrast to gout, no disease-modifying therapies currently exist that reduce articular crystal deposition of calcium pyrophosphate crystals (CPPs). Treatment is aimed at ameliorating the inflammatory response and reducing the frequency and severity of clinical symptoms due to CPP deposition (CPPD). Despite being one of the most common forms of inflammatory arthritis, CPPD remains under-studied and evidence-based treatment guidelines remain lacking. Commonly used treatments for clinical manifestations of CPPD (non-steroidal anti-inflammatory drugs [NSAIDs], colchicine and corticosteroids [CSs]) are extrapolated from use in gout. Anakinra and tocilizumab can be used in refractory cases. Though no current crystal-targeted treatments exist, studies suggest that nucleoside analogues and phosphocitrate can attenuate calcification of human cartilage ex-vivo. Hindering research, is the lack of a well-defined description of CPPD. However, international working groups have convened to establish classification criteria and validated outcome domains for CPPD. This should help facilitate the setting up of large multicentre studies, with well-defined cohorts, which can evaluate suitable therapies, providing high levels of evidence to guide clinicians. Here, we summarise and discuss the currently available anti-inflammatory treatment options for CPPD and discuss potential future crystal-targeted approaches.

The role of Interleukin-1 receptor antagonist as a treatment option in calcium pyrophosphate crystal deposition disease.

Calcium Pyrophosphate Crystal Deposition (CPPD) disease is characterized by the deposition of calcium pyrophosphate crystals in the cartilage. In most cases, it can manifest as a subclinical condition named chondrocalcinosis, often revealed by joint x-ray examination. In other cases, deposition can cause flares of arthritis, known as acute CPP crystal arthritis. In the last few years, many pathogenic pathways have been discovered. Interleukin-1 (IL-1) plays a key role in the pathogenesis of CPPD disease, both as a mediator of inflammatory response to crystals and as a promoter of damage to articular cartilage. In this review, we investigated the role of IL-1R inhibitor, such as Anakinra, as an alternative to the various therapeutic strategies for CPPD disease, especially among patients resistant to traditional treatment with NSAIDs, corticosteroids and colchicine.

Classifying Pseudogout Using Machine Learning Approaches With Electronic Health Record Data.

OBJECTIVE: Identifying pseudogout in large data sets is difficult due to its episodic nature and a lack of billing codes specific to this acute subtype of calcium pyrophosphate (CPP) deposition disease. The objective of this study was to evaluate a novel machine learning approach for classifying pseudogout using electronic health record (EHR) data. METHODS: We created an EHR data mart of patients with ≥1 relevant billing code or ≥2 natural language processing (NLP) mentions of pseudogout or chondrocalcinosis, 1991-2017. We selected 900 subjects for gold standard chart review for definite pseudogout (synovitis + synovial fluid CPP crystals), probable pseudogout (synovitis + chondrocalcinosis), or not pseudogout. We applied a topic modeling approach to identify definite/probable pseudogout. A combined algorithm included topic modeling plus manually reviewed CPP crystal results. We compared algorithm performance and cohorts identified by billing codes, the presence of CPP crystals, topic modeling, and a combined algorithm. RESULTS: Among 900 subjects, 123 (13.7%) had pseudogout by chart review (68 definite, 55 probable). Billing codes had a sensitivity of 65% and a positive predictive value (PPV) of 22% for pseudogout. The presence of CPP crystals had a sensitivity of 29% and a PPV of 92%. Without using CPP crystal results, topic modeling had a sensitivity of 29% and a PPV of 79%. The combined algorithm yielded a sensitivity of 42% and a PPV of 81%. The combined algorithm identified 50% more patients than the presence of CPP crystals; the latter captured a portion of definite pseudogout and missed probable pseudogout. CONCLUSION: For pseudogout, an episodic disease with no specific billing code, combining NLP, machine learning methods, and synovial fluid laboratory results yielded an algorithm that significantly boosted the PPV compared to billing codes.

Management of calcium pyrophosphate crystal deposition disease: A systematic review.

OBJECTIVE: Calcium pyrophosphate crystal deposition disease (CPPD) is a common cause of acute and chronic arthritis, especially in the elderly population. There is a paucity of data regarding the management of CPPD disease, which is currently based on expert opinion and evidence derived from the treatment of gout. We conducted a systematic literature review in order to identify the available treatment options for CPPD, and describe their efficacy and safety. MATERIAL AND METHODS: Online databases were searched from inception to May of 2020 using the search terms: (CPPD [Title/Abstract] OR CPDD [Title/Abstract] OR calcium pyrophosphate [Title/Abstract] OR chondrocalcinosis [Title/Abstract]) AND (treatment [Title/Abstract] OR management [Title/Abstract] OR therapy [Title/Abstract]). Articles evaluating the use of specific treatment agents for CPPD were eligible for inclusion. Case reports were excluded. RESULTS: A total of 22 eligible studies and 403 unique patients were selected. We identified only 3 randomized, double-blind, controlled trials (RCTs) evaluating the use of methotrexate, hydroxychloroquine, and magnesium carbonate in CPPD, and these therapeutic options, with the exception of methotrexate, have shown efficacy and reduction of pain intensity. Further, 10 case series and 9 cohort studies were included. Intramuscular and intra-articular glucocorticoids, ACTH, as well as the biologic agents anakinra and tocilizumab appear to be efficacious in CPPD. Intra-articular injections of glycosaminoglycan polysulphate, hyaluronic acid and yttrium, as well as synovial membrane destruction by laser irradiation were associated with symptomatic improvement. Due to significant study heterogenicity, direct comparison between studies was not possible. CONCLUSION: There are a limited number of studies evaluating the treatment of CPPD. High quality evidence is rather limited, while commonly administered agents such as NSAIDs, colchicine and corticosteroids have not been evaluated by RCTs. The need for high quality evidence supporting specific treatment modalities is urgent for this common yet neglected form of arthritis.

Síndrome constitucional y fiebre prolongada en relación con enfermedad por depósito de pirofosfato cálcico de presentación atípica / Constitutional syndrome and fever in a patient with atypical presentation of calcium pyrophosphate deposition disease

No disponible

Arthroscopic diagnosis and medical management of calcium pyrophosphate deposition disease in the temporomandibular joint.

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthropathy that can involve the temporomandibular joint. It is known to accelerate the osteoarthritic process, often initially presenting with advanced level of disease. The management of CPPD in the rheumatology and orthopedic literature is one of early diagnosis and medical management of acute attacks. The cases of three patients who presented with initial complaints of joint pain and limited mouth opening are presented. Preoperative imaging identified calcifications in two of these patients. Definitive diagnosis was achieved through arthroscopic-assisted biopsy. Rheumatology referrals revealed chondrocalcinosis of the knee in one patient. All patients had improved mouth opening and pain.

Biologics in the treatment of calcium pyrophosphate deposition disease: a systematic literature review.

The main aim of this systematic literature review (SLR) was to summarise the evidence in the use of biological therapies in calcium pyrophosphate deposition disease (CPPD). We performed a SLR using PubMed, Embase and Cochrane databases. Only studies reporting the efficacy of biologics in CPPD were selected. The search resulted in 83 articles; 11 were further evaluated in the SLR. Seventy-six patients were included: 2 received infliximab, whereas 74 anakinra. Anakinra was used in refractory disease (85.1%) or in patients with contraindications to standard treatments (23.0%). Clinical response to anakinra was observed in 80.6% of patients with acute and 42.9% of those with chronic CPPD. Short-term treatment was well tolerated and adverse events were reported in 4.1% of the cases. This review provides evidence in favour of the use of anakinra as a therapeutic option in patients with CPPD, especially in acute refractory CPPD or when standard treatments are contraindicated.

Bilateral hamstring origin calcification: rare presentation of Gitelman syndrome.

This case report is the first case to our knowledge of intratendinous or peritendinous calcification reported in Gitelman syndrome (GS) patients. GS represents the clinical manifestations of inactivation of the Slc12a3 genes encoding the thiazide-sensitive sodium chloride cotransporter and the Trpm6-Mg genes encoding the magnesium transporters in the distal convoluted tubule. Hence, the biochemical findings resemble those with thiazide diuretics such as hypokalaemia, hypomagnesaemia, hypocalciuria, metabolic alkalosis and low normal blood pressure. Serum calcium and phosphate levels are usually unaffected in GS unless associated with hyperparathyroidism or other hypercalcaemic aetiologies. We report a 69-year-old male patient with a history of GS who presented with bilateral ischial tuberosity tenderness. Further investigations confirmed the calcification of bilateral hamstring origin. Chondrocalcinosis is a known association of GS; however, extra-articular calcification is rare. Literature review illustrates sclerochoroidal calcification as the only reported soft tissue calcification apart from chondrocalcinosis.

Calcium Pyrophosphate Deposition Disease Involving a Lumbar Facet Joint Following Urinary Tract Infection.

A 75-year-old woman was admitted with urosepsis due to Escherichia coli infection. After improvement with a ureteral stent and antimicrobial agent, she complained of back pain and showed elevated inflammation marker levels. Arthralgia and arthritis of multiple peripheral joints were noted, and radiography indicated cartilage calcification. Magnetic resonance imaging revealed lumbar facet joint effusion. Her symptoms improved with nonsteroidal anti-inflammatory drug administration. Thus, she was diagnosed with calcium pyrophosphate deposition (CPPD)-related facet joint arthritis (FJA) rather than infectious FJA. CPPD-related FJA is an important differential diagnosis in elderly individuals with a risk of CPPD disease who complain of back pain.