Calcium Pyrophosphate Dihydrate Research Articles

Systematic literature review to inform the EULAR recommendations for the use of imaging in crystal-induced arthropathies in clinical practice

ObjectiveTo summarise current data regarding the use of imaging in crystal-induced arthropathies (CiAs) informing a European Alliance of Associations for Rheumatology task force.MethodsWe performed four systematic searches in Embase, Medline...

CT imaging features of calcium pyrophosphate dihydrate crystal deposition involving spine

PurposeTo explore the computed tomography (CT) imaging features of the spine involved by calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) in order to improve the understanding of this disease. Materials and methodsAmong 79 patients diagnosed with CPPD-CDD in our hospital, 51 patients with spinal involvement were selected, 9 patients without CT examination were excluded, and 42 patients were finally included as research objects. The CT images of the 42 patients were retrospectively analyzed. The analysis contents mainly included the distribution of lesions and the characteristic imaging findings of intervertebral disc, posterior ligament complex, sacroiliac joint and atlantoaxial joint. ResultsIn this paper, 42 patients with 11 males and 31 females were studied. The onset age ranged from 62 to 95 years. There were 264 lesions in 42 patients with spinal involvement, including 177 lumbar vertebrae, 43 cervical vertebrae, 27 thoracic vertebrae and 17 sacroiliac joints (14 bilateral and 3 unilateral). Characteristic imaging findings include: disc calcification (129 cases), posterior ligament complex calcification (107 cases), sacroiliac articular cartilage calcification (17 cases), and ligaments around the odontoid process calcification (11 cases). ConclusionsThe characteristic images of CPPD-CDD involving the spine are calcification of intervertebral disc, posterior ligament complex, sacroiliac joint surface and ligaments around odontoid process, and the lesions are frequent and coexisting, so it should be differentiated from gout, rheumatoid arthritis, ankylosing spondylitis, ossification of ligamentum flavum, basic calcium phosphate and infectious spondylodiscitis.

Crystal induced arthropathies-a comparative study of 40 patients with apatite rheumatism, chondrocalcinosis and primary synovial chondromatosis.

Introduction: Apatite rheumatism (AR), chondrocalcinosis (Ch-C), and primary synovial chondromatosis (prSynCh) are regarded as distinct clinical entities. The introduction of the non-staining technique by Bély and Apáthy (2013) opened a new era in the microscopic diagnosis of crystal induced diseases, allowing the analysis of MSU (monosodium urate monohydrate) HA (calcium hydroxyapatite), CPPD (calcium pyrophosphate dihydrate) crystals, cholesterol, crystalline liquid lipid droplets, and other crystals in unstained sections of conventionally proceeded (aqueous formaldehyde fixed, paraffin-embedded) tissue samples. The aim of this study was to describe the characteristic histology of crystal deposits in AR, Ch-C, and prSynCh with traditional stains and histochemical reactions comparing with unstained tissue sections according to Bély and Apáthy (2013). Patients and methods: Tissue samples of 4 with apatite rheumatism (Milwaukee syndrome), 16 with chondrocalcinosis, and 20 with clinically diagnosed primary synovial chondromatosis were analyzed. Results and conclusion: Apatite rheumatism, chondrocalcinosis, and primary synovial chondromatosis are related metabolic disorders with HA and CPPD depositions. The authors assume that AR and Ch-C are different stages of the same metabolic disorder, which differ from prSynCh in amorphous mineral production, furthermore in the production of chondroid, osteoid and/or bone. prSynCh is a defective variant of HA and CPPD induced metabolic disorders with reduced mineralization capabilities, where the deficient mineralization is replaced by chondroid and/or bone formation. The non-staining technique of Bély and Apáthy proved to be a much more effective method for the demonstration of crystals in metabolic diseases than conventional stains and histochemical reactions.

Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression.

Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1β maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107-111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5'-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1β and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-α (TNF-α) were also decreased due to the reduced activation of the NF-κB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-κB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis.

CPPD and Associated Crystals in Clinically Diagnosed Chondrocalcinosis: A Clinicopathological Study of 20 Patients

Introduction: Chondrocalcinosis (Ch-C), induced by calcium pyrophosphate dihydrate crystals (CPPD) [Ca2P2O7.2H2O] is considered as a distinct metabolic disease and a well-defined clinical entity, with characteristic clinical manifestations and symptoms. This study used previously found method by the author .i.e, non-staining approach to discover crystal deposits in patients with clinically diagnosed Ch-C, to find a possible correlation between coexisting crystals, and to assess the role of coexistent crystals in inflammatory cellular processes of joints. Patients and methods: There were forty (40) surgical specimens that had been traditionally processed from 16 patients who had been clinically diagnosed with Ch-C. Results: In unstained tissue sections CPPD crystals were found in 22 of 40 samples of all 16 patients. Beside the CPPD crystals calcium hydroxyapatite (HA) [Ca5(PO4)3(OH)] crystals were found in 26 tissue samples of all 16 patients, cholesterol (CC) [C27H46O] in 23 tissue samples of 12 patients, and crystalline liquid lipid droplets (CL) in 11 tissue samples of 5 patients. More or less amorphous deposits of calcium carbonate [CaCO3] and/or calcium phosphate [Ca3(PO4)2] were present alongside CPPD and the contemporaneous crystals. There was a significant and positive correlation between prevalence of CPPD and HA. The connection between inflammatory cellular infiltration and CPPD, HA, CC or CL crystals surrounded by mineral deposits was not significant. Conclusions: The non-staining approach is a practical, low-tech way to find CPPD, HA, CC, and other crystals (with or without CL). The positive and significant correlation between CPPD and HA support the earlier premise that CPPD and HA represent basically an identical metabolic disorder). CPPD and/or HA crystals can provoke inflammatory processes responsible for the clinical symptoms, but the variable amounts of amorphous minerals enclose (isolate) the crystals, and can reduce or eliminate the inflammatory reaction. The authors assume that CC (with or without CL) is an associated phenomenon (concomitant fat metabolic malady) without direct cause of inflammation, and is not responsible for clinical symptoms of crystal induced arthropathies.

Crowned Dens Syndrome: A Rare Cause of Sudden Onset Neck Pain

Objective: To report a case of Crowned Dens Syndrome (CDS), which is a rare disorder caused by crystal deposition by calcium pyrophosphate dihydrate in the peridontoid soft tissues surrounding the C1 and C2 vertebrae that presents in elderly with sudden onset neck pain, neck stiffness, fever, and elevated inflammatory markers, with periodontal calcification in a halo or crown configuration on radiography considered diagnostic.Methods: A 64-year-old diabetic and hypertensive female patient presented with a 6-day history of sudden onset posterior neck pain and stiffness. Movements of the cervical spine were equally limited in all directions, causing marked aggravation of pain. There was no focal neurologic loss. Her inflammatory markers were markedly raised.Results: Based on radiography, she was diagnosed with Crowned Dens syndrome and started on oral prednisolone, paracetamol, and tizanidine along with topical diclofenac. Oral NSAIDs were contraindicated due to her renal insufficiency.Conclusion: Crowned Dens Syndrome (CDS) is a rare cause of neck pain. Clinicians should consider this syndrome in their differential diagnosis. Timely diagnosis and treatment of CDS will lead to avoidance of unnecessary investigations and medications in such patients, along with a reduction in the length of stay.

Lateral meniscus with tears or with histologic calcification does not increase the risk of lateral osteoarthritis after medial unicompartmental arthroplasty.

Meniscal tears or histological meniscal calcifications (in the absence of radiological chondrocalcinosis) are frequent in osteoarthritis. Whether lateral meniscal lesions influence clinical outcomes after medial unicompartmental knee arthroplasty (UKA) is unknown. We analyzed 130 patients (130 knees) with medial unicompartmental knee arthroplasties between 2005 and 2015. These 130 knees had full articular cartilage thickness in the lateral compartment and no radiological chondrocalcinosis on preoperative radiographs. The lateral meniscus was analyzed with preoperative MRI and a biopsy of the anterior horn at the time of surgery. Synovial fluid was collected and analyzed for calcium pyrophosphate dihydrate crystal deposition (CPPD crystals). Lateral meniscal tears were untreated when detected on MRI or during surgery, with the hypothesis that these tears on the opposite compartment would remain asymptomatic in medial UKA. At average 10-year follow-up, patients were evaluated with clinical and radiographic outcome, with a focus on the risk of joint space narrowing of the lateral femorotibial compartment. CPPD crystals were present in the synovial fluid of 70 knees. Lateral meniscal tears were seen on MRI in 34 (49%) normal meniscuses of the 60 knees without CPPD crystals and in six other knees without histological meniscal calcification despite CPPD crystals. Histological calcification was present on 61 lateral meniscuses with 53 meniscal tears. The results showed no significant differences in the clinical outcomes between knees with lateral meniscal tears or lateral meniscal histological chondrocalcinosis or both lesions and those without these conditions. Additionally, radiographic progression of osteoarthritis in the opposite femorotibial compartment of the knee was not more frequent in patients with these meniscal issues. The tenyear cumulative survival rates, measured by the need for total knee arthroplasty, were 91% for knees without meniscal lesions and 92% for knees with these lesions. On this basis, treatment of meniscal tears of the lateral compartment and routine aspiration of the knee to assess for birefringent crystals in the planning of medial UKA do not appear necessary.

E062 Calcium pyrophosphate dihydrate crystal in operated rheumatoid arthritis of the knee

Abstract Background/Aims Calcium pyrophosphate dihydrate (CPPD) crystals are also one of the common types of crystals causing crystal-induced inflammatory arthritis. Several studies have elucidated important aspects of the molecular and cellular mechanisms of CPPD crystal formation. CPPD crystal deposition disease is a common arthritic disorder in mainly elderly patients. CPPD crystals are found in multiple joints (e.g. knee, wrist joints) in association with severe cartilage degeneration in osteoarthritis. However, there are few reports concerning about CPPD crystals in patients with rheumatoid arthritis (RA). In this study, I investigated the relationship between CPPD crystal and operated RA of the knee. Methods Seventy-seven total knee arthroplasties were performed for RA knees from January 2016 to September 2021. I defined the lower extremity alignment (LEA) base on the femorotibial angle (FTA) as valgus (FTA<170°), neutral (170°≤FTA<180°), and varus (FTA≥180°). I also defined the osteophyte formation degree (OFD) in the knee (grade 0-3). At the operation, joint fluids were collected from 70 knees (average age 71.6; male 8; female 72 body mass index (BMI) 24.4kg/m2,; C-reactive protein (CRP) 1.20mg/dL; erythrocyte sedimentation rate (ESR) 49.5mm/h; matrix metalloprotease (MMP)-3 289.5ng/dL; OFD (0/1/2/3) 0/38/25/7; FTA 177.9°; LEA: varus 35; neutral 22; valgus 13). We evaluated the relationship between CPPD crystals and age, gender, FTA, BMI, CRP, ESR, MMP-3, OFD and LEA. When I analyzed the risk factors using the logistic regression method, LEA were defined as valgus (FTA<175°) and varus (FTA≥176°). Results CPPD crystals were detected from 19 RA knees (27.1%). There were no significant differences between CPPD(+) and (-) groups about age, gender, FTA, BMI, CRP, ESR and MMP-3. The more severe osteophyte formation showed higher CPPD(+) rate tendency; however, there was no significance. CPPD(+) rates were 34.2% in varus knees, 23.1% in valgus knees and 18.2% in neutral knees, respectively. We reported that age, valgus knee, severe osteophyte and low BMI were the risk factors of CPPD(+) in operated osteoarthritis (OA) knees, previously. In this study, there was no difference between CPPD(+) and (-) groups about these factors. Especially, CPPD(+) rate in RA valgus knees was one third of that of OA valgus knees. Conclusion It may be suggested that CPPD production mechanism in RA knees is different from that in OA knees. Disclosure M. Nishikawa: None.

CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE OF ELBOW WITH ULNAR NERVE NEUROPATHY: A CASE REPORT

Crystal deposition disorders are one of the causes of inflammatory arthropathy. A rare variety of this disorder is Calcium Pyrophosphate Dihydrate deposition disease. It is usually seen in the elderly and progresses as calcifications in and around the joint i.e. Chondrocalcinosis with repeated synovitis leading to degenerative changes of large and unusual or non-weight-bearing joints. It is a case report of 43 years housewife with a gradually enlarging mass at posteromedial aspect of the left elbow with ulnar nerve weakness for 1 year. Radiographs revealed degenerative joint with periarticular calcifications. The electrodiagnostic test showed ulnar nerve demyelination and axonal neuropathy. Surgical excision with decompression of ulnar nerve was done. Histopathology revealed features consistent with Pseudogout. Subsequent follow-up resulted in improvement of nerve function with no clinicoradiological evidence of recurrence. So, degenerative changes with periarticular calcifications in non-weight-bearing joints should be suspected for pseudogout. It may be associated with compressive neuropathy.

Diagnosis and Treatment of Calcium Pyrophosphate Deposition (CPPD) Disease: A Review.

Calcium Pyrophosphate Dihydrate (CPPD) crystal-related arthropathies are a common cause of acute and chronic arthritis caused by the deposition of calcium pyrophosphate crystals in joints and soft tissues, resulting in inflammation and joint damage. They present with a wide spectrum of clinical manifestations and often present challenges to diagnosis and management as they commonly affect older co-morbid patients. The challenges are compounded by a lack of a well-defined description of CPPD. However, an international expert-driven process is underway to develop CPPD classification criteria. Treatment is also problematic as unlike gout, there are no agents available that decrease the crystal burden. Treatment options have often been extrapolated from gout treatment pathways without having extensive trials or a solid evidence base. It is hoped the new CPPD classification guidelines will contribute to large multicentre studies, with well-defined patient cohorts, which will facilitate the production of high-quality evidence to guide the management of this condition. Here, we discuss the barriers and facilitators in diagnosing and treating CPPD-related arthropathy.

Incidental findings involving the temporomandibular joint on computed tomography and magnetic resonance imaging.

The temporomandibular joint (TMJ) is frequently imaged in head and neck computed tomography (CT) and magnetic resonance imaging (MRI) studies. Depending on the indication for the study, an abnormality of the TMJ may be an incidental finding. These findings encompass both intra- and extra-articular disorders. They may also be related to local, regional or systemic conditions. Familiarity with these findings along with pertinent clinical information helps narrow the list of differential diagnoses. While definitive diagnosis may not be immediately apparent, a systematic approach contributes to improved discussions between clinicians and radiologists and better patient management.

Management of temporomandibular joint diseases: a rare case report of coexisting calcium pyrophosphate crystal deposition and synovial chondromatosis

BackgroundThe coexistence of calcium pyrophosphate dihydrate crystal deposition (CPP) and synovial chondromatosis (SC) in the temporomandibular joint (TMJ) is rarely reported. CPP disease (CPPD) is complex arthritis synonymous with excessive pyrophosphate production and variable aberrations in mineral and organic phase metabolism of the joint cartilage, leading to local inundated CPP and crystal deposition of partially deciphered predispositions. Meanwhile, SC is a rare benign synovial joint proliferative disease of unclear etiology and has a low risk of malignant transformation. However, SC manifests severe joint disability and dysfunction because of connective tissue metaplasia of the synovial membrane, which forms cartilaginous nodules with or without calcifications or ossifications. These nodules often detach and form intra-articular loose bodies and very rarely within extraarticular spaces.Case presentationWe report the case of a 61-year-old man to expand the body of literature on these unusual coexisting arthropathies of the TMJ. The patient presented to our hospital in 2020 with complaints of pain in the right TMJ and trismus for over 6 months. Radiographic assessments of the TMJ provided a preoperative provisional diagnosis of SC. However, the histopathology of the open biopsy revealed tumor-like lesions comprising several deposits of rhomboid and rod-shaped crystals that displayed positive birefringence in polarized light, confirming a coexistence of CPPD. A second-stage operation was performed for the complete removal of the loose bodies and chalk-like lesions including synovectomy. No evidence of recurrence was recorded after a follow-up of nearly 1.5 years.ConclusionsIsolated CPPD and SC of the TMJ are prevalent in the literature however, monoarticular coexistence of these diseases is rare, due to the lack of consistency in the diagnostic criteria in clinical practice. Moreover, optimal treatment depends on several considerations. This report delineated the molecular etiopathology and underscored the need for continued deciphering of the causal mechanisms of coexisting CPPD and SC of the TMJ. In addition, the importance of confirmatory testing for accurate diagnosis, and appropriate management of these diseases were discussed.

Extensive concomitant optic nerve sheath and sclerochoroidal calcifications

Computed tomography revealed tram track–like calcifications within bilateral optic nerve sheaths and large, amorphous calcific plaques on the sclera of a 91-year-old man (Fig. 1). His past medical history was significant for calcium pyrophosphate dihydrate deposition disease, chronic renal failure, and hypothyroidism. To the best of our knowledge, there is only 1 reported case describing concomitant optic nerve sheath and sclerochoroidal calcifications that were idiopathic.1 Disorders of calcium-phosphorus homeostasis are another known etiology of these calcifications.

Cartilage calcification in osteoarthritis: mechanisms and clinical relevance.

Pathological calcification of cartilage is a hallmark of osteoarthritis (OA). Calcification can be observed both at the cartilage surface and in its deeper layers. The formation of calcium-containing crystals, typically basic calcium phosphate(BCP) and calcium pyrophosphate dihydrate (CPP)crystals, is an active, highly regulated and complex biological process that is initiated by chondrocytes and modified by genetic factors, dysregulated mitophagy or apoptosis, inflammation and the activation of specific cellular-signalling pathways. The links between OA and BCP deposition are stronger than those observed between OA and CPP deposition. Here, we review the molecular processes involved in cartilage calcification in OA and summarize the effects of calcium crystals on chondrocytes, synovial fibroblasts, macrophages and bone cells. Finally, we highlight therapeutic pathways leading to decreased joint calcification and potential new drugs that could treat not only OA but also other diseases associated with pathological calcification.

Agreement Among Multiple Observers on Crystal Identification by Synovial Fluid Microscopy.

Despite the fact that polarized microscopy remains the gold standard for diagnosing crystal arthritis, some uncertainties hamper full implementation in clinical practice. We undertook this study to analyze the agreement among multiple observers in crystal identification using compensated polarized microscopy, as well as to assess potential outcome modifiers. This was a cross-sectional, observational study with consecutive synovial fluid sampling. Samples were immediately analyzed when possible or kept refrigerated at 4°C. Five observers analyzed them separately, blinded to clinical data, using a compensated polarized optical microscope (400×), through 3 stages (ordinary, simple polarized, and compensated polarized light) to detect and identify crystals. They recorded the presence and type of crystal (no crystals, monosodium urate [MSU], and calcium pyrophosphate dihydrate [CPP]). Interrater agreement was measured by Cohen's kappa. Subanalyses were performed on visualization delay and cumulative expertise. Discrepancies between each stage of the microscopy and the final decision were also examined. A total of 250 observations from 50 samples completed full assessment. Overall, κ=0.74 (95% confidence interval [95% CI] 0.64-0.84), indicating good agreement. Agreement for crystal detection was κ=0.71 (95% CI 0.59-0.82), for MSU was κ=0.88 (95% CI 0.75-1.0), and for CPP was κ=0.69 (95% CI 0.56-0.82). Most of the crystal identifications were already made by ordinary light. No differences between observations made before or after 24 hours (P=0.859) or in expertise on crystal analysis (P=0.989) were found. Observations performed under ordinary light matched the final diagnosis in 96.8% of cases (242 of 250). Compensated polarized microscopy remained consistent in detecting and identifying crystals in synovial fluid, even when examined among multiple observers, confirming its high utility for clinical practice.

Calcium pyrophosphate dihydrate of the ligamentum flavum in the cervical spine - A review of the literature.

Calcium pyrophosphate dihydrate (CPPD) deposition, also known as pseudogout, in the cervical ligamentum flavum (CLF), is a rare disease which can cause spinal cord signaling changes leading to rapid deterioration in function. The natural history of cervical myelopathy as a result of CPPD deposition within the CLF is not well understood. Our objective is to describe the presentation, imaging findings, and treatment options of CPPD deposition or pseudogout of the cervical spine. Using PubMed, we analyzed studies published from 1978 to 2022. Key words used were "pseudogout," "CPPD deposit disease," "cervical yellow ligament," "CLF," and "cervical spine." We excluded "crowned dense syndrome" and "ossification of ligament flavum." Using a department database, we queried for patients treated for CPPD of the cervical spine. Twenty clinical studies on CPPD of the cervical spine with 69 patients aged between 15 and 92 years (mean = 72) were identified. Neck pain and numbness of the hands were the most common symptoms. Diabetes mellitus and hypertension were the most common comorbidities. Males and females were affected at equal rates. C4-C5 and C5-C6 were the most affected segments. Earlier surgical treatment produced better outcomes. A laminectomy and fusion or laminoplasty were the most common procedures performed with most patients experiencing some return of neurologic function. Although rare, CPPD deposit disease in the CLF should be readily considered as a differential diagnosis due to the continuously aging population. CPPD's progressively worsening nature makes an early diagnosis and treatment important in improving the patient's overall quality of life.

Lumbar Spinal Involvement in Calcium Pyrophosphate Dihydrate Disease: A Systematic Literature Review.

BackgroundCalcium-pyrophosphate-dihydrate-disease (CPPD) is a crystal-induced arthropathy. The lumbar-spinal involvement is rare and often under-diagnosed. This study aimed to report the case of a lumbar spine CPPD involvement and to perform a systematic review of clinical, imaging features of lumbar involvement in CPPD patients, and treatments that have been implemented.MethodsThis systematic review was conducted in accordance with the Preferred-Reporting-Items-for-Systematic-Reviews and Meta-Analyses (PRISMA) guidelines.ResultsOne hundred and sixty-seven articles met the search criteria using electronic databases searches. We retained 28 articles (20 case reports, 2 case series, 1 family survey, 4 retrospective studies, and 1 prospective study) involving a total of 62 patients. The age ranged between 39 and 89 years old. Among patients with lumbar spine CPPD, 32 were women. The duration of symptoms varied between one day and 8 years. The affection has been discovered during back pain in most cases. In 5 studies, the diagnosis was made on histological specimens of patients operated on for another pathology. X-ray showed calcifications in 2 cases. CT-scan detected calcium deposit in 7 cases. MRI showed lesions going from the increased signal of the disk, to calcified or not-cystic lesion of the facet joints, an intramedullary mass mimicking a schwannoma. Histological examination established the diagnosis of CPPD in 21 patients in all studies. Medical treatment included NSAIDs, Colchicine, Interleukin-1-receptor-antagonist, and antibiotics. Surgery was performed on 13 patients and allowed to establish the histological diagnosis.ConclusionIn the case of inflammatory back pain in elderly subjects, without an infectious gateway, diagnosis of CPPD should be considered, especially for patients with a history of spinal surgery or degenerative radiography changes. CT scan is more sensitive than conventional radiographs. The discovertebral biopsy is the Gold-Standard and should be performed whenever the diagnosis was uncertain. Treatment includes the medical and surgical components.

Drugs Recommended in Adult Rheumatic Diseases, But Considered for Off-Label Use in Argentina

BackgroundOff-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. MethodsA list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. ResultsOne hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. ConclusionsAlmost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.

Drugs Recommended in Adult Rheumatic Diseases, But Considered for Off-Label Use in Argentina.

Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.

Case Report: Posterolateral Epidural Supra-C2-Root Approach (PESCA) for Biopsy of a Retro-Odontoid Lesions in Same Sitting After Occipitocervical Fixation and Decompression in a Case of Crowned Dens Syndrome With Brainstem Compression and Displacement

Background‘Crowned dens syndrome' (CDS) is a special form of calcium pyrophosphate dihydrate deposition disease which is characterized radiologically by a halo-like or crown-like distribution in the periodontoid region and clinically by cervical pain. Herein, we will describe our experience of posterolateral epidural supra-C2-root approach (PESCA) for biopsy of retro-odontoid lesions in one surgical session after occipitocervical fixation and decompression in a patient with CDS and massive brainstem compression.Case PresentationA 70-year-old woman presented to our department with a 4-week history of progressive walking impairment, neck pain, neck rigidity, fever, dizziness, slight palsy of the left hand, and multiple fall episodes. Magnetic resonance imaging (MRI) of the craniovertebral junction (CVJ) and cervical spine revealed a lesion of the odontoid process and the retro-odontoid region with mainly solid components, as well as small cystic components, and brainstem compression and displacement. In first step, fusion surgery of the CVJ C0–C4 was performed with occiptocervical decompression. After fusion and decompression the lower lateral part of the C1 arc and the lateral superior part of the left side of the C2 arc were removed. The entry point was located directly above the superior part of the C2 root. A biopsy of the lateral portions of the lesions was obtained by bioptic forceps under microscope guidance. Pathologic examination of the mass revealed deposition of birefringent crystals compatible with calcium pyrophosphate. In addition to the clinical symptoms (especially neck pain), the diagnosis of CDS was made. Non-steroidal inflammatory drugs (NSAIDs) and colchicine (and later magnesium) were started. At follow-up examination 6 months after surgery, an MRI scan of the cervical spine revealed regression of the pannus and the cyst with replacement of the brainstem, clinical improvement of walking, and increased strength of the left hand.ConclusionsThis study demonstrates that PESCA can be used to obtain tissue for pathological analysis in one surgical sitting after fusion and decompression and that fusion, decompression, and PESCA (in the same session) together with subsequent conservative management could be a good alternative for the treatment of CDS.