Calcium Pyrophosphate Disease Research Articles

A case report of rare form of calcium pyrophosphate disease: sacroiliitis with soft tissue involvement mimicking an infectious disease

A case report of rare form of calcium pyrophosphate disease: sacroiliitis with soft tissue involvement mimicking an infectious disease

The Association of Diuretics and Proton Pump Inhibitors With Chondrocalcinosis

ObjectiveHypomagnesemia increases the risk of chondrocalcinosis and calcium pyrophosphate disease. We examined whether the use of drugs that can cause hypomagnesemia, diuretics and proton pump inhibitors (PPIs), increases the risk of chondrocalcinosis.MethodsParticipants in the Multicenter Osteoarthritis (MOST) Study obtained weight‐bearing knee radiographs, and their medication use was recorded at baseline and 30‐, 60‐, 84‐, and 144‐month examinations. We read radiographs serially for chondrocalcinosis and characterized incident chondrocalcinosis when it first appeared. We classified diuretic use as thiazide, loop, and other. To test drug effects on incident chondrocalcinosis at each interval (eg, 30‐60 months), we excluded persons with chondrocalcinosis at the interval’s beginning. For each drug, we evaluated exposure at the beginning and end of the interval. We conducted knee‐based analyses using Bayesian mixed‐effects discrete time survival models adjusted for age, sex, body mass index, radiographic osteoarthritis, race, and clinic site.ResultsOf 5272 knees, 196 developed chondrocalcinosis. Thiazide use (21.7% of examinations) and PPI use (13.7%) were common. Neither loop nor other diuretic use was associated with incident chondrocalcinosis. Thiazide use at the beginning and end of the interval of incidence conferred a high risk (hazard ratio [HR] = 2.18; 95% confidence interval [CI] 1.23‐3.89), but use at the beginning of the interval was not associated with risk (HR = 1.04). PPI use at the interval’s beginning increased risk of chondrocalcinosis (HR = 2.29; 95% CI 1.37‐3.79).ConclusionThiazide diuretics, but not other diuretics, and PPI use probably increase the risk of chondrocalcinosis. These findings may have important clinical implications.

P116 Hypophosphatasia presenting as musculoskeletal pain: a case series of 12 adults presenting to general rheumatology clinic

Abstract Background/Aims Hypophosphatasia is a metabolic bone disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphate (TNSALP). Adults present with a variety of manifestations including musculoskeletal pain, calcium pyrophosphate disease (CPPD), dental problems and low trauma fractures. The characteristic finding in hypophosphatasia is a persistently low ALP. Due to the non-specific presentation, hypophosphatasia diagnoses are often delayed and this can result in misdiagnosis and incorrect treatment decisions. This is particularly significant in patients presenting with musculoskeletal pain. Methods Here we present 12 adults diagnosed with hypophosphatasia after referral to our general rheumatology clinic with musculoskeletal pain over the past decade. A persistently low ALP was established in all patients. Hypophosphatasia was diagnosed by an elevated fasting vitamin B6 and/or a positive genetic test. All patients had a normal DEXA scan. Results 11 patients were female and 1 was male.The average age at presentation to rheumatology clinic was 42 years. All patients had a consistently low ALP. This was first documented at the mean age of 39 years. Mean ALP across all patients was 24 U/L (normal range 60-35). ALP range for all patients was <5 to 58 U/L. Descriptions of pain were diverse. Common features included lower limb pain (92%) and pain with flare ups (42%). The average age of pain onset was 26 years. When considering the mean age at diagnosis of 45 years, this gives a mean diagnostic delay of 19 years. Other features of hypophosphatasia were dental symptoms (83%), CPPD (58%), family history (92%) and fractures (42%). P116 Table 1:No.SexAge at diagnosis of HPP (years)Mean ALPu/L[60-350]Age at first documented low ALP (years)Fasted vitamin B6 result µg[5-50]Urine PEA (phospho ethanol amine)ALPL gene mutationsDEXAMSK featuresCPPDFracturesDentalRelevant family history1F5118.539228NegativeHeterozygousNormalTrochanteric bursitis, leg and buttock pain_____________Left ankleRemoved since early 20sLoss of teeth early in life2F5512.542243Not doneHeterozygousNormalBurning in shoulders, knees, arm pain worse on activity with flare upsConfirmed on x ray___________Dentures since early adulthoodFamily history of hypophosphatasia3F324327196Not doneNot doneNormalJoint pain in lower limbs with flare ups, aching in hands, swelling of fingersClinical diagnosis___________Few fillingsGum disease, multiple tooth removals, history of hypophosphatasia4M543050176NegativeHeterozygousNormalTrochanteric bursitis, pain in ankles and wristsClinical diagnosis______________________Dentures5F2516.523415Small peakHeterozygousNormalUpper back pain, pain in knuckles and left wristChondrocalcinosis on US of hand3 toes, 2 fingersfillingsLost teeth, joint pains, osteoporosis6F323521155Not doneNegativeNormalPain in neck, shoulder, lower back, weakness________________________Decay in primary dentitionDental problems, fractures, joint pains7F542152268Small peakheterozygousNormalEarly morning stiffness, skeletal pain in upper arms and lateral thighs_____________Elbow, lower legDecay since age 10Dentures, osteoarthritis, osteoporosis8F6024.555163Not doneheterozygousNormalWeakness, pain in left side worse with activity_____________Vertebral__________Dentures, arthritis, hypermobility9F4517.541287NegativeheterozygousNormalPain in hands, kneesClinical diagnosisLoose teeth in adulthoodOsteoporosis, dentures, gout, joint/muscle pain10F5113.538359Not doneheterozygousNormalPain in legs, backache, leg stiffness________________________Poor teeth since teenage yearsRheumatoid arthritis11F142721126Marginal increaseVariant of uncertain significanceNormalWrist pain worse on use with flare upsClinical diagnosis___________6 teeth removed in childhood_______________12F7037.561195Not doneNot donenormalTrochanteric bursitis, night pain in right knee, back painChondrocalcinosis on x rayL ankle, rib fractures_________________________Mean age at diagnosis - 45 yearsMean ALP - 24 U/LMean age at first documented low ALP - 39 yearsMean fasting vitamin B6 - 235 µg Conclusion Our patients experienced a significant diagnostic delay even after the establishment of a persistently low ALP. Various musculoskeletal symptoms were seen and a diagnosis of CPPD was common, affecting 7 of 12 patients (58%). Patients with hypophosphatasia, presenting to rheumatology clinic with musculoskeletal pain, experience significant diagnostic delay. This can be shortened by considering their pain in conjunction with a persistently low ALP, a history of pain earlier in life, dental problems, fractures, CPPD and a positive family history of dental problems, fractures or arthritis. Disclosure A. Rauf: None. K.E. Moss: None.

Synovial fluid analysis for the enhanced clinical diagnosis of crystal arthropathies in a tertiary care institution.

Few studies have addressed the detection and clinical impact of different crystals in patients with diverse rheumatologic diagnoses in Latin America. The aim of this study was to assess the consistency between the clinical referring diagnosis and the identification of crystals, such as monosodium urate (MSU) and calcium pyrophosphate (CPP), in the synovial fluid (SF) of patients from a Mexican tertiary care institution. We reviewed the results of 264 SF analyses to identify any changes in diagnosis upon SF analysis. We reported patient medical file data on sex, age, diagnosis, and microscopic SF analysis results. We performed consistency analyses between referring diagnoses and SF findings with McNemar's test. The prevalence of MSU crystals in SF was noted in 89.1% of gout cases and 9.09% of cases of calcium pyrophosphate disease (CPPD). CPP crystals were present in 54.5% of CPPD cases, 42.9% of osteoarthritis (OA) cases, and 7.27% of gout cases. Calcium hydroxyapatite (HA) crystals were identified in 5.45% of gout cases, 33.3% of rheumatoid arthritis (RA) cases, 57.1% of OA cases, and 63.6% of CPPD cases. Cholesterol and lipid crystals were present in small proportions in RA cases. Glucocorticoid crystals were observed in 1.85% of gout cases, 44.4% of RA cases, and 42.9% of OA cases. We observed an association of MSU identification with clinical suspicion of gout (P = 0.08), CPP with OA (P = 0.26) and CPPD (P = 0.50). An association was noted between HA and the diagnosis of CPPD (P = 0.84) and OA (P > 0.99). The number of initial diagnoses that changed upon SF analysis was 14.3%. SF analysis has major diagnostic value regarding MSU crystals and gout. Our findings underscore the importance of SF crystal analysis in identifying the prevalence of crystals in the Mexican population. SF analysis provides for better diagnosis of crystal arthropathies and improves the quality of the medical care that the patient receives. Key Points • Synovial fluid analysis in laboratories from developing countries has been scarce. • In some cases, the initial diagnosis is modified after of synovial fluid analysis. • This study confirmed that synovial fluid analysis exhibits major diagnostic value for urate crystals and gout.

Reply to: Calcium pyrophosphate disease and polymyalgia rheumatica: association or coincidence?

Reply to: Calcium pyrophosphate disease and polymyalgia rheumatica: association or coincidence?

Calcium pyrophosphate disease and polymyalgia reumatica: association or coincidence? Comment on "Ultrasound shoulder assessment of calcium pyrophosphate disease with suspected polymyalgia rheumatica" Ottaviani et al.

Calcium pyrophosphate disease and polymyalgia reumatica: association or coincidence? Comment on "Ultrasound shoulder assessment of calcium pyrophosphate disease with suspected polymyalgia rheumatica" Ottaviani et al.

Diagnostic challenges in a case of reactive arthritis with concurrent calcium pyrophosphate disease

Diagnostic challenges in a case of reactive arthritis with concurrent calcium pyrophosphate disease

Cervical CT-Dependent Diagnosis of Crowned Dens Syndrome in Calcium Pyrophosphate Dihydrate Crystal Deposition Disease

PurposeThe purpose of this study is to assess the presence of crowned dens syndrome in patients with calcium pyrophosphate disease. We report 34 patients with crowned dens syndrome in one of the largest series from a single tertiary medical center in North America. MethodsA retrospective chart review was conducted at the University of Kansas Medical Center from November 1, 2005-November 1, 2017. A total of 191 patients with calcium pyrophosphate disease were identified. The available cervical computed tomography scans were analyzed by a musculoskeletal radiologist for the presence of periodontoid calcifications and erosions. ResultsOf the 191 patients with calcium pyrophosphate disease, 57 had cervical computed tomography scans; 34 of them (34/57, 59.64%) had periodontoid calcifications. Only 12/34 patients were formally evaluated and diagnosed by rheumatologists with crowned dens syndrome. Twenty-two of 34 were either not seen by a rheumatologist or were not diagnosed with crowned dens syndrome. The median age was 78.5 years, with 73.52% over 70 years old; 24/34 (70.58%) were female; 17/34 patients (50%) were symptomatic; 28/34 (82.35%) had additional sites of chondrocalcinosis on available radiographs; 8 (28.57%) had 3 or more sites of chondrocalcinosis in typical calcium pyrophosphate disease locations. Six patients did not have any radiographs. ConclusionCrowned dens syndrome is an under-recognized entity that should be considered in elderly patients with neck pain in the setting of calcium pyrophosphate disease. Our data demonstrated a high percentage (about 60%) of patients with calcium pyrophosphate disease who had cervical computed tomography findings consistent with crowned dens syndrome. This underscores the importance of performing cervical computed tomography when evaluating patients with neck pain and calcium pyrophosphate disease.

Updated Treatment for Calcium Pyrophosphate Deposition Disease: An Insight.

Calcium pyrophosphate disease (CPPD) is caused by the deposition of calcium pyrophosphate (CPP) crystals in the joint tissues, particularly fibrocartilage and hyaline cartilage. CPP crystals trigger inflammation, causing local articular tissue damage. Our review article below covers different aspects of CPPD. It discusses how CPPD can manifest as different kinds of arthritis, which may be symptomatic or asymptomatic. The metabolic and endocrine disease associations and routine investigations used in the diagnostic workup are briefly reviewed. Conventional and newer therapies for the treatment of CPPD are outlined. Overall, this extensive review would provide an updated insight to clinicians for evidence-based treatment of CPPD.

Current advances in therapies for calcium pyrophosphate crystal arthritis.

Calcium pyrophosphate (CPP) crystal disease is a common rheumatologic disorder that has received limited attention from the scientific community. This review is aimed at summarizing current evidence for managing CPP disease (CPPD), focusing on recently reported advances. New data from case series indicate that interleukin-1β inhibitors can help patients with refractory forms of CPPD. Methotrexate, formerly a promising agent, failed to demonstrate benefits in a recent trial, but still merits consideration for some patients. No significant advances on crystal dissolution have been achieved to date. Proper characterization of the CPP crystal disease picture is needed, ruling out the possible coexistence of another persistent arthritis unrelated to the CPP deposition. Advances on CPP crystal dissolution and establishing definitions of the clinical spectrum of CPPD remain the main challenges for CPP crystal disease management.

Value of tomosynthesis for lesion evaluation of small joints in osteoarthritic hands using the OARSI score

To determine the diagnostic performance of tomosynthesis in depicting osteoarthritic lesions in comparison to conventional radiographs, with use of computed tomography (CT) as standard-of-reference. Imaging of 12 cadaveric hands was performed with tomosynthesis in dorso-palmar (dp) projection, conventional radiographs (dp) and multi-detector CT. Distal interphalangeal joint (DIP)II, DIPIII, proximal interphalangeal joint (PIP)II, PIPIII, first carpometacarpal (CMC) and scaphotrapezotrapezoidal joint (STT) were graded by two independent readers using the Osteoarthritis Research Society International (OARSI) score. The mean score for each feature was calculated for all modalities. Additional wrists were evaluated for presence of calcium pyrophosphate disease (CPPD). CT served as reference-standard. Inter-reader agreement (ICC) was calculated. Comparing tomosynthesis and conventional radiographs to CT, the sensitivity for the presence of osteophytes was 95,7% vs 65,2%; for joint space narrowing 95,8% vs 52,1%; for subchondral sclerosis 61,5% vs 51,3%; for lateral deformity 83.3% vs 83,3%; and for subchondral cysts 45,8% vs 29,2%. Erosions were not present. While tomosynthesis showed no significant difference in OARSI score grading to CT (mean OARSI-score CT: 16.8, SD=10.6; mean OARSI-score Tomosynthesis: 16.3, SD=9.6; P=0.84), conventional radiographs had significant lower mean OARSI scores (mean OARSI-score X-ray: 11.1, SD=8.3; P=0.04). Inter-reader agreement for OARSI scoring was excellent (ICC=0.99). CPPD calcifications present in CT, were also visible with tomosynthesis, but not with conventional radiography. In conclusion, tomosynthesis depicts more osteoarthritic changes in the small joints of the hand than conventional radiography using the OARSI scoring system and CT as the standard of reference.

Native Joint Septic Arthritis: Epidemiology, Clinical Features, and Microbiological Causes in a New Zealand Population.

To determine the epidemiology, clinical features, and microbiology of adult native joint septic arthritis in Canterbury, New Zealand, over a 5-year period in individuals with and without an underlying rheumatic disorder. Patients with native joint septic arthritis were identified retrospectively and classified by Newman's criteria. The clinical characteristics were described and comparisons made between those with and without underlying rheumatic disease. Two hundred forty-eight cases of native joint septic arthritis (mean age 60, range 16-97 yrs) were identified with an overall incidence rate of 12.0/100,000/year (95% CI 10.6-13.6). Yearly incidence increased with age to a maximum of 73.4/100,000 in those > 90 years of age. Septic arthritis was iatrogenic in 16.9% of cases while 27% had an underlying inflammatory arthritis including gout (14.9%), calcium pyrophosphate disease (8.5%), and rheumatoid arthritis (4%). Few patients were taking immunosuppressant therapy, with just 1 taking a biological agent. Staphylococcus aureus was the most commonly identified organism. Those with underlying inflammatory arthritis were significantly older (73.6 yrs vs 55.6 yrs; p < 0.001), more likely to be female (55.2% vs 26.0%; p < 0.001), and to have septic polyarthritis (16.4% vs 4.4%; p = 0.002). The 30-day mortality was 2%, increasing to 6% at 90 days. The incidence of septic arthritis in Canterbury, New Zealand, is higher than in previous studies. Crystal arthropathy commonly coexisted with infection although autoimmune arthritis and immunosuppression was less of a factor than anticipated.

Distinguishing gouty arthritis from calcium pyrophosphate disease and other arthritides.

Differentiating gout, calcium pyrophosphate deposition disease (CPPD), and non-crystal-related inflammatory arthropathies (non-CRA) is essential but often clinically impossible. The sonographic double contour (DC) sign may have good specificity for gout in highly specialized centers, but it can be challenging to use it to distinguish gout from cartilage hyperenhancements in CPPD. We evaluated the diagnostic value of the DC sign alone and in combination with Doppler signals and uric acid (UA) levels in patients with acute arthritis. We retrospectively investigated 225 acutely inflamed joints and documented the presence of DC, Doppler hypervascularization, and serum UA (SUA) levels. All patients underwent synovial fluid (SF) analysis. Sensitivity, specificity, and positive predictive values were calculated, and correlation analyses and a binary regression model were used to investigate their diagnostic values. The sensitivity of DC sign for crystalline arthritides was 85% and specificity 80%. Its specificity for gout was 64%, for CPPD 52%. In contrast to non-CRA hypervascularization, degree 2 and 3 Doppler signals were highly associated with gout and less with CPPD (p < 0.01). The combination of DC sign with hypervascularization and elevated UA levels increased specificity for gout to more than 90% and resulted in a 7-fold increase of the likelihood of diagnosis of gout (p < 0.01), but with a loss of sensitivity (42%). The DC sign alone is suitable for predicting crystal-related arthropathies, but it cannot reliably distinguish gout from CPPD in everyday clinical routine. Combining hypervascularization and SUA levels increases the diagnostic value, leading us to propose a diagnostic algorithm.

AB1118 Retrospective Study of the Causes of Hospitalizations and Mortality of Rheumatological Inpatients in Singapore General Hospital over 10 Years

BackgroundCauses of death and hospitalizations are well studied in developed countries, but studies are lacking in Asian countries. The Department of Rheumatology and Immunology in Singapore General Hospital was founded...

Novel ANKH Amino Terminus Mutation (Pro5Ser) Associated With Early-Onset Calcium Pyrophosphate Disease With Associated Phosphaturia

This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father.

Calcium pyrophosphate deposition—nothing 'pseudo' about it!

Calcium pyrophosphate disease remains—50 years after its initial description—a challenging disease to diagnose and manage. Newly-reached consensus among European experts suggests standard nomenclature, some recommendations for diagnosis and treatment, and an ambitious future research agenda based on these decisions.

Tratamiento de la enfermedad por cristales de pirofosfato cálcico

Although major advances have been made in the understanding of the pathogenesis, physiopathology and treatment of many rheumatic diseases, calcium pyrophosphate disease (CPPD) is a glaring omission, despite its high prevalence in rheumatology clinics. Current treatment schemes have not been tested in high quality trials and consequently clinicians’ decisions are based on clinical practice results. Non-steroidal anti-inflammatory drugs, colchicine and corticosteroids are the most widely used drugs, usually with success. However, in some patients, these drugs are ineffective, contraindicated or cannot be used because of side effects. In these patients, other drugs, such as methotrexate or antimalarials, may be useful.

The Etiology of Osteoarthritis of the Hip

More than 90% of patients with so-called primary or idiopathic osteoarthritis of the hips in whom sufficient data were available to make an assessment of the normality of the hip joint at the cessation of growth clearly showed demonstrable abnormalities in the hip joint. The most common are mild acetabular dysplasia and/or pistol grip deformity. This latter deformity is associated with mild slipped capital femoral epiphysis (recognized or unrecognized at the time), Legg-Perthes' disease (recognized or unrecognized at the time), multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, and/or the presence of an intraacetabular labrum, as well as, in certain instances, acetabular dysplasia. When these abnormalities are taken in conjunction with the detection of other metabolic abnormalities that can lead to osteoarthritis of the hip and which may not be recognized readily, such as hemochromatosis, ochronosis, calcium pyrophosphate disease, and monarticular rheumatoid arthritis, it seems clear that either osteoarthritis of the hip does not exist at all as a primary disease entity or, if it does, is extraordinarily rare.

Acute carpal tunnel syndrome a rare complication of chondrocalcinosis

Acute carpal tunnel syndrome is rare and usually is secondary to trauma, burns, infection or acute rheumatoid arthritis. A case is presented in which the acute syndrome was produced by Chondrocalcinosis (pseudogout or calcium pyrophosphate disease) of the wrist.