New paleopathological findings from the Quaternary of the Brazilian Intertropical Region expand the distribution of joint diseases for the South American megafauna.

OBJECTIVE: To evaluate pathological changes in fossils from the Brazilian Intertropical Region (BIR), expanding the records of previously reported diseases for representatives of the Quaternary South American megafauna, including taxa not studied in previous works. MATERIALS AND METHODS: We carried out a thorough macroscopic analysis of fifteen unpublished specimens belonging to representatives of the Quaternary megafauna of BIR to identify evidence of pathological alterations. RESULTS: Alterations included: osteophytes in Toxodontidae, Megatheridae and E. laurillardi; rough subchondral bone, bone overgrowth and bone erosion in E. laurillardi; slit-shaped subchondral depressions in Equidae and E. laurillardi; and a triangular-shaped porous lesion in Mylodontidae. CONCLUSIONS: The alterations found allowed the recognition of the first cases of osteoarthritis for Toxodontidae and articular depressions for Equidae, and new cases of both diseases in Eremotherium laurillardi; a new case of osteochondritis dissecans for Mylodontidae; potential new cases of calcium pyrophosphate deposition and spondyloarthropathy for E. laurillardi SIGNIFICANCE: Our results provide additional evidence that calcium pyrophosphate deposition disease was widely spread among species of the South American megafauna and suggest that osteochondritis dissecans may have been relatively common among ground sloths. LIMITATIONS: The identification of calcium pyrophosphate deposition and spondyloarthropathy in E. laurillardi are quite tentative because the evidence found is ambiguous and the number of examined specimens is limited.

[Acute monoarthritis in a third level hospital]. / Estudio de los pacientes con monoartritis aguda en un hospital de tercer nivel.

INTRODUCTION: Acute monoarthritis (AM) represents a relevant cause of morbidity that requires prompt medical care. The study of synovial fluid becomes relevant to allow a rapid diagnostic approach. The main objective of the study was to determine the frequency and clinical-analytical characteristics of episodes of AM and acute bursitis evaluated in a hospital during a period of 6 years. METHODS: Cross-sectional retrospective analytical study in a hospital at Córdoba, Argentina. All episodes of acute monoarthritis and bursitis that occurred in patients aged 18 years or older between 2012 and 2017 were included. AM in pregnant women and chronic monoarthritis were excluded. RESULTS: One hundred and eighty episodes of AM and 12 of acute bursitis were included. Among the AM, 120 (66.7%) occurred in male patients and the average age was 62.1±16.9 years. The main cause of AM was septic, identifying 70 (36%) cases, followed by microcrystalline AM identify 54 (28%) cases, which corresponded to gout and calcium pyrophosphate dihydrate (CPPD) with 27 (14%) cases each one. Monosodium urate crystals were identified in 26 (14.3%) patients, CPPD in 28 (15.6%) and cholesterol in 1 (0.6%). DISCUSSION: The main cause of AM was septic arthritis, followed by microcrystalline AM (gout and secondary to CPPD). The main affected joint was the knee, followed by the shoulder. Synovial fluid analysis was a key element when making the differential diagnosis between the different causes of acute monoarthritis and bursitis.

Introducción: La monoartritis aguda (MA) representa una causa relevante de morbilidad que requiere de atención médica oportuna: El estudio del líquido sinovial constituye un elemento clave para su diagnóstico. El objetivo del estudio fue determinar la frecuencia y características clínicas-analíticas de los episodios de MA y bursitis agudas valoradas en un hospital durante un período de 6 años. Métodos: Estudio analítico retrospectivo de corte transversal en un hospital de Córdoba, Argentina. Se identificaron todos los episodios de monoartritis y bursitis agudas que ocurrieron en pacientes de =18 años entre 2012 y 2017. Se excluyeron los cuadros de MA en embarazadas y las monoartritis crónicas. Resultados: Se incluyeron 180 episodios de MA y 12 de bursitis aguda. Entre las MA, 120 (66.7%) ocurrieron en hombres, la edad promedio fue 62.1±16.9 años. La principal causa de MA fue séptica, identificándose 70 (36%) casos, seguida la secundaria a microcristales con 54 episodios (28%) que correspondieron 27 (14%) a MA por gota y 27 (14%) a MA por depósitos de pirofosfato de calcio dihidratado (CPPD). Se identificaron cristales de urato monosódico en 26 (14.3%) pacientes, CPPD en 28 (15.6%) y de colesterol en 1 (0.6%). Discusión: La principal causa de MA fue séptica, seguida de la secundaria a microcristales (gota y secundaria a CPPD). La principal articulación afectada fue la rodilla, seguida del hombro. El análisis del líquido sinovial fue un elemento clave a la hora de poder realizar el diagnóstico diferencial entre las distintas causas de monoartritis aguda y bursitis.

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

INTRODUCTION/OBJECTIVES: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

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.

Knee effusion: ultrasound as a useful tool for the detection of calcium pyrophosphate crystals.

The objective of this study was to evaluate the sensitivity and specificity of ultrasound (US) and conventional radiography (CR) for the detection of calcium pyrophosphate (CPP) crystals in patients with knee effusion. Consecutive patients ≥50 years old with knee effusion were included. All patients underwent arthrocentesis with aspiration of synovial fluid (SF) and subsequent analysis of CPP crystals using plain light and polarizing light microscopy. US and CR of the involved knee were performed immediately after arthrocentesis. CR results were read by an experienced rheumatologist, searching for chondrocalcinosis. US examinations were carried out by an experienced rheumatologist blinded to all clinical and imaging data. The following US abnormal findings were considered indicative of CPP crystals deposition (CPPD): (1) hyperechoic bands within the femoral hyaline cartilage layer, and (2) hyperechoic sparkling spots in meniscal fibrocartilage. A total of 75 knees were evaluated in the same number of patients. Analysis of SF revealed CPP crystals in 15 out of 75 (20 %) knees: all (10) patients with previous diagnosis of CPPD, 3 patients with previous diagnosis of primary knee osteoarthritis (OA) and 2 patients without previous definitive diagnosis of a rheumatic condition. Using SF analysis as reference method, sensitivity and specificity for US findings was 60 and 96.7 %, respectively, while CR showed a sensitivity of 40 % and a specificity of 83.3 %. US results showed high specificity with acceptable sensitivity to detect CPP crystals in patients with knee effusion. Compared with CR, US results had better specificity and sensitivity. US may be used in daily rheumatologic practice when CPPD is suspected.

[Calcium pyrophosphate dihydrate crystal deposition disease as an example of illness presentation in the elderly]. / Enfermedad por depósito de cristales de pirofosfato de calcio como ejemplo de forma de manifestación de la enfermedad en el adulto mayor.

Illness presentation in the elderly may be entirely non-specific, with fatigue, loss of function or the presence of geriatric syndromes. We report a 90 years old male consulting in the emergency room for delirium that persisted throughout hospitalization without finding a cause. During the course of hospitalization mild fever appeared and a left knee swelling became apparent. A synovial fluid aspiration showed a leukocyte count of 360 per field with 60% polymorphonuclear cells. The culture was negative. With a presumptive diagnosis of pseudogout, cochicine and celecoxib were started with remission of the confusional state. The patient was discharged 13 days after admission in good conditions.

Enfermedad por depósito de cristales de pirofosfato de calcio como ejemplo de forma de manifestación de la enfermedad en el adulto mayor / Calcium pyrophosphate dihydrate crystal deposition disease as an example of illness presentation in the elderly

Illness presentation in the elderly may be entirely non-specific, with fatigue, loss of function or the presence of geriatric syndromes. We report a 90 years old male consulting in the emergency room for delirium that persisted throughout hospitalization without finding a cause. During the course of hospitalization mild fever appeared and a left knee swelling became apparent. A synovial fluid aspiration showed a leukocyte count of 360 per field with 60% polymorphonuclear cells. The culture was negative. With a presumptive diagnosis of pseudogout, cochicine and celecoxib were started with remission of the confusional state. The patient was discharged 13 days after admission in good conditions.

Síndrome de la corona / Crowned dens syndrome

El dolor de cuello inducido por cristales a veces ocurre en pacientes con enfermedades por depósitos de hidroxiapatita o pirofosfato de calcio deshidratado. Los depósitos de hidroxiapatita comprometen el ligamento longitudinal cervical, los discos intervertebrales, y los depósitos de CPPD, el ligamento amarillo, las articulaciones interapofisarias y probablemente el ligamento transverso. Esto sugiere que la enfermedad por depósito de CPPD compromete frecuentemente la columna cervical. Aunque pueden ser asintomáticos, estos depósitos se asocian a ataques agudos de cervicalgias con rigidez, fiebre y aumento de la VSG, simulando PMR y/o arteritis de células gigantes o síntomas neurológicos. Nosotros describiremos 2 casos con síndromes de la corona de presentación atípica simulando PMR.(AU)

Síndrome de la corona / Crowned dens syndrome

El dolor de cuello inducido por cristales a veces ocurre en pacientes con enfermedades por depósitos de hidroxiapatita o pirofosfato de calcio deshidratado. Los depósitos de hidroxiapatita comprometen el ligamento longitudinal cervical, los discos intervertebrales, y los depósitos de CPPD, el ligamento amarillo, las articulaciones interapofisarias y probablemente el ligamento transverso. Esto sugiere que la enfermedad por depósito de CPPD compromete frecuentemente la columna cervical. Aunque pueden ser asintomáticos, estos depósitos se asocian a ataques agudos de cervicalgias con rigidez, fiebre y aumento de la VSG, simulando PMR y/o arteritis de células gigantes o síntomas neurológicos. Nosotros describiremos 2 casos con síndromes de la corona de presentación atípica simulando PMR.

Helium-neon laser reduces the inflammatory process of arthritis.

OBJECTIVE: A histological study of the anti-inflammatory effect of helium-neon laser in models of arthropathies induced by hydroxyapatite and calcium pyrophosphate in rats. BACKGROUND: Crystal deposition diseases are inflammatory pathologies induced by cellular reaction to the deposit of crystals in the joints. METHODS: Fifty-six Suquia strain rats were distributed in seven groups. Two mg of each crystal diluted in 0.05 ml physiologic solution were injected six times in each back limb joint, during two weeks on alternate days. Eight J/cm(2) were applied daily to the crystal-injected joints on five consecutive days. The joints were cut and put in 10% formaldehyde, stained with hematoxylin-eosin and observed by light microscopy. The percentage of area with inflammatory infiltrates was determined in five optical microscopy photographs (100X) for each group and analyzed using the Axionvision 4.6 program. A Pearson's Chi Squared test was applied, with significance level set at p < 0.05. RESULTS: Both crystals produced an inflammatory process in the osteoarticular structures, consisting of predominantly mononuclear infiltration, fibrosis, and granulomas of foreign body-type giant cells containing phagocytosed remains of crystals. In the arthritic joints treated with laser, a marked decrease (p < 0.0001) was found in the percentage of area with inflammatory infiltrates, although the granulomas remained in a less ostensible form, with adipose tissue cells, fibrosis bands with light residual inflammation, and an absence of or very few crystals. Laser alone or physiologic solution injection did not produce histological changes. CONCLUSIONS: Helium-neon laser reduced the intensity of the inflammatory process in the arthritis model induced by hydroxyapatite and calcium pyrophosphate crystals.

Inflammatory and oxidative stress markers in experimental crystalopathy: their modification by photostimulation.

Crystalopathies are inflammatory pathologies caused by cellular reactions to the deposition of crystals in the joints. The anti-inflammatory effect of the helium-neon (He-Ne) laser and that of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, meloxicam, celecoxib, and rofecoxib was studied in acute and chronic arthritis produced by hydroxyapatite and calcium pyrophosphate in rats. The presence of the markers fibrinogen, L-citrulline, nitric oxide, and nitrotyrosine was determined. Crystals were injected into the posterior limb joints of the rats. A dose of 8 J/cm(2) of energy from an He-Ne laser was applied for 3 d in some groups and for 5 d in other groups. The levels of some of the biomarkers were determined by spectrophotometry, and that of nitrotyrosine was determined by ELISA. For statistical analysis, Fisher's exact test was used, and p +/- 0.05 was considered significant. In arthritic rats, the fibrinogen, L-citrulline, nitric oxide, and nitrotyrosine levels increased in comparison to controls and to the laser-treated arthritic groups (p +/- 0.001), (p +/- 0.001), (p +/- 0.02), and (p +/- 0.01), respectively. When comparing fibrinogen from arthritic rats with disease induced by hydroxyapatite with undiseased and arthritic rats treated with NSAIDs, the He-Ne laser decreased levels to values similar to those seen in controls (p +/- 0.01). Inflammatory and oxidative stress markers in experimental crystalopathy are positively modified by photobiostimulation.

Condrocalcinose articular difusa / Diffuse articular chondrocalcinosis

Condrocalcinose é uma doença causada por depósitos intrarticularesde pirofosfato de cálcio, o que pode levar à diversas apresentaçõesclínicas. Esta fascinante enfermidade pode apresentar-se como artriteinfl amatória recorrente (Pseudogota), como outras formas de artritecrônica (por exemplo, pseudo AR) ou mesmo, como assintomática.A forma primária ocorre, principalmente, em adultos jovens, e asecundária é predominante nos idosos, além de ser, quase sempre,associada à osteoartrite. O diagnóstico é feito por meio do achadode cristais birrefringentes de pirofosfato de cálcio no líquido sinovial.Alterações em raio X também podem ajudar no diagnóstico, revelandoimagens hiperdensas (lineares ou puntiformes) na cartilagem.O prognóstico depende da causa (se secundária), número de articulaçõesacometidas e gravidade. O tratamento é baseado no uso deantiinfl amatórios não esteróides e corticoterapia sistêmica.

Photobiomodulation of pain and inflammation in microcrystalline arthropathies: experimental and clinical results.

OBJECTIVE: This article presents the results of laser therapy in crystal (hydroxyapatite, calcium pyrophosphate, and urates) deposition-induced arthritis in rats and the clinical applications in humans. BACKGROUND DATA: Microcrystalline arthropathies are prevalent among geriatric patients, who are more vulnerable to the side effects of drugs. The effectiveness of laser therapy for pain relief, free of side effects, has been reported in painful conditions. METHODS: Two milligrams of each of the above-mentioned crystals was injected in both joints of the back limbs in three groups of rats; these groups were then treated with laser irradiation. Three other groups received no treatment after the injections. We determined the plasmatic levels of inflammatory markers (fibrinogen, prostaglandin E2, and TNF(alpha)), tissues (prostaglandin E(2)) and conducted anatomopathological studies. Twenty-five patients with acute gout arthritis were randomized into two groups and treated over 5 days: group A, diclofenac 75 mg orally, twice a day; and group B, laser irradiation once a day. Forty-nine patients with knee chronic pyrophosphate arthropathy were randomized into two groups and treated over 21 days; group A, diclofenac 50 mg orally, twice a day; and group B, laser irradiation once a day. Thirty patients with shoulder chronic hydroxyapatite arthropathy were randomized into two groups and treated over 21 days; group A, diclofenac 50 mg orally, twice a day; and group B, laser irradiation once a day. RESULTS: Fibrinogen, prostaglandin E(2), and TNF(alpha) concentrations in the rats injected with crystals and treated with laser decreased significantly as compared with the groups injected with crystals without treatment. Both laser therapy and diclofenac achieved rapid pain relief in patients with acute gouty arthritis without significant differences in efficacy. Laser therapy was more effective than diclofenac in patients with chronic pyrophosphate arthropathy and in patients with chronic apatite deposition disease. CONCLUSION: Laser therapy represents an effective treatment in the therapeutic arsenal of microcrystalline arthropathies.

Condrocalcinose articular familiar / Familial articular chondrocalcinosis

Condrocalcinose articular familiar é uma condição clínica caracterizada pela deposição de cristais de pirofosfato de cálcio no líquido sinovial e cartilagens articulares levando à artrite. Descrevemos três membros de uma família com condrocalcinose cujo quadro clínico era caracterizado por artrite intermitente em dois e artrite crônica lembrando artrite reumatóide em um. A avaliação radiológica mostrou calcificações em cartilagens de diversas articulações, particularmente de joelhos. A utilização de colchicina foi suficiente para prevenir as crises de artrite em dois pacientes e o paciente com a forma crônica necessitou uso contínuo de antiinflamatórios não-hormonais. Embora aparentemente rara no Brasil, não afastamos a possibilidade desse dado estar subestimado e sugerimos que seja realizada uma avaliação radiológica articular dos familiares de todo paciente com diagnóstico de condrocalcinose esporádica.

Familial osteoarthritis and Milwaukee shoulder associated with calcium pyrophosphate and apatite crystal deposition.

OBJECTIVE: To characterize and define the phenotypes observed in a large Italo-Argentinean kindred with osteoarthritis, chondrocalcinosis, and Milwaukee shoulder (MS). METHODS: Seventy-five members were evaluated with a history, examination, and radiographs of shoulders, spine, hands, and knees. Superior subluxation of the glenohumeral joint was graded using shoulder radiographs and tomography and nuclear magnetic resonance imaging and 3 dimensional computed tomography was performed on selected members. In 31 family members peripheral blood DNA was utilized for genetic linkage analysis of several candidate gene loci previously linked to chondrocalcinosis phenotypes, as well as those implicated in the proper patterning of skeletal elements and cartilage differentiation. In addition, direct sequence analysis of type II collagen gene (COL2A1), the gene that codes for the major structural protein of cartilage, was undertaken in 3 affected and 3 unaffected members of the family. RESULTS: MS was seen in one member of the first generation and 6 members of the 2nd generation, while 8 members of the 3rd generation showed an incomplete form of MS. Isolated superior subluxation of the shoulder was seen in 16 other family members of the 3rd and 4th generations. Osteoarthritis of the spine and peripheral joints was seen in 31 affected members, while chondrocalcinosis was observed in 6 members of the first generation. Shoulder synovial fluid from 2 patients showed the presence of both apatite and calcium pyrophosphate dihydrate crystals. Direct analysis of the COL2A1 gene indicated no known disease determining mutations in affected members, thus excluding this gene as a candidate gene in this family. Genetic linkage to several candidate loci, including the chondrocalcinosis loci on chromosomes 5p and 8q, as well as loci for HOX A and C were also excluded. Linkage analyses of other loci for the HOX B and D genes and the PAX 1 and 9 genes were uninformative in this kindred. CONCLUSION: This kindred illustrates an unusual type of osteoarthritis with secondary intraarticular and periarticular calcification and MS in the most severely affected elderly members. A search for linkage to some potential candidate genes was either excluded or uninformative. Further linkage analysis to identify potential candidate genes is in progress.

Artropatía por depósito de cristales de dihidrato de pirofosfato de calcio / Calcium pyrophosfate dihydrate crystal deposition disease: review

Los autores estudiaron las características radiológicas en 67 pacientes con artropatía por depósito de cristales de dihidrato de pirofosfato de calcio encontrados en un total de 2.565 pacientes con articulaciones dolorosas no traumáticas; 2 por ciento de los casos presentaron artropatía por pirofosfato. La radiología convencional fue generalmente diagnóstica en todos los casos cuando se analizaron signos específicos para diferenciar la artropatía por pitofosfato de otras artropatías como la osteoartritis, considerando: a) condocalcinosis (94 por ciento), b) articulación no afectada usualmente en la osteoartritis primaria (22 por ciento) y c) compartimientos no comúnmente comprometidos en la osteoartritis (29 por ciento). Todos los pacientes presentaron además signos de artropatía degenerativa (AU)

Artropatía por depósito de cristales de dihidrato de pirofosfato de calcio / Calcium pyrophosfate dihydrate crystal deposition disease: review

Los autores estudiaron las características radiológicas en 67 pacientes con artropatía por depósito de cristales de dihidrato de pirofosfato de calcio encontrados en un total de 2.565 pacientes con articulaciones dolorosas no traumáticas; 2 por ciento de los casos presentaron artropatía por pirofosfato. La radiología convencional fue generalmente diagnóstica en todos los casos cuando se analizaron signos específicos para diferenciar la artropatía por pitofosfato de otras artropatías como la osteoartritis, considerando: a) condocalcinosis (94 por ciento), b) articulación no afectada usualmente en la osteoartritis primaria (22 por ciento) y c) compartimientos no comúnmente comprometidos en la osteoartritis (29 por ciento). Todos los pacientes presentaron además signos de artropatía degenerativa

Myelopathy due to calcification of the cervical ligamenta flava: a report of two cases in West Indian patients.

Two cases of cervical myelopathy due to calcification of the ligamenta flava (CLF) are described for the first time in black patients from the French West Indies. A pre-operative CT scan differentiated the diagnosis from one of ossification of the ligamenta flava. Microanalysis on the operatively excised specimen in one patient revealed a mixture of calcium pyrophosphate dihydrate crystals and hydroxypatite crystals. Poor outcome in one patient contrasting with excellent recovery in the other one, who had undergone posterior decompressive laminectomy, emphasizes the importance of surgery in the management of CLF.