It was approved as a treatment for gastroparesis by the US Food and Drug Administration (FDA) in 1979 and remains the first-line drug. It acts as a prokinetic by its antagonistic effect on dopamine 2 (D2) receptors promoting gastric emptying and, in addition, binds to the 5-hydroxytryptamine 4 receptor (serotonin 5-HT4) to stimulate cholinergic nerve pathways in the stomach. Physiologically, it accelerates intestinal transit by increasing the tone and amplitude of gastric contractions, increases lower esophageal sphincter pressure and improves antropyloroduodenal coordination. In addition, this antiemetic agent provides relief through antagonism of central and peripheral dopamine receptors.

55-year-old woman with type 1 diabetes diagnosed at age 15 years who refers nausea and abdominal distention, especially after meals. Evaluation is consistent with diabetic gastroparesis. Which of the following medications would be the most appropriate treatment to improve her symptoms:

Gastroparesis in Adolescent Patient with Type 1 Diabetes: Severe Presentation of a Rare Pediatric Complication.

Gastroparesis is a long-term complication of diabetes related to autonomic neuropathy. It is clinically characterized by delayed gastric emptying and upper gastrointestinal symptoms including early satiety, postprandial fullness, nausea, vomiting, and abdominal pain. Gastric emptying scintigraphy is the gold standard for the diagnosis as it reveals delayed gastric emptying. Therapeutic strategies include dietary modifications, improvement of glycemic control, and prokinetic drugs. Case descriptions of diabetic gastroparesis in pediatric age are very scarce. We hereby report the case of a 16-year-old adolescent with severe presentation of diabetic gastroparesis. She presented with recurrent episodes of nausea, vomiting and abdominal pain which led progressively to reduced oral intake and weight loss. Her past glycemic control had been quite brittle as demonstrated by several hospitalizations due to diabetic ketoacidosis and recurrent episodes of severe hypoglycemia. After the exclusion of infectious, mechanical, metabolic, and neurological causes of vomiting, a gastric emptying scintigraphy was performed, leading to the diagnosis of gastroparesis. Treatment with metoclopramide was started with progressive relief of symptoms. To improve glycemic control, insulin therapy with advanced hybrid closed loop system was successfully practiced. Pediatricians should seriously consider diabetic gastroparesis in children and adolescents with long-standing, poorly controlled diabetes.

Comparison of metoclopramide and erythromycin in the treatment of diabetic gastroparesis.

To compare the effects of erythromycin and metoclopramide on gastric emptying and symptoms of gastroparesis in diabetic patients with delayed gastric emptying. The study group consisted of 13 patients with symptoms of severe gastroparesis and delayed gastric emptying. Gastric emptying was evaluated using a radionuclide method, and gastrointestinal symptoms were scored. The patients were given either erythromycin (250 mg 3 times/day) or metoclopramide (10 mg 3 times/day) in random order for 3 wk, and after a washout period of 3 wk they were crossed-over to the other medication for another 3 wk. Parameters of gastric emptying were assessed before treatment and after both erythromycin and metoclopramide administration. The half-time of gastric emptying in diabetic subjects was 110 (77-120) min before treatment. At 60 and 90 min, the median value of residual isotope activity was 66.5 (55-83.5) and 55% (43-74.3), respectively. The half-time decreased to 55 min (28.6-115) after 3 wk of treatment with erythromycin and percentages of meal retention in the stomach at 60 and 90 min were 49.9 (38.4-70) and 40.5% (29.7-60), respectively. After taking metoclopramide, the median value of half-time was 67 min (15-115) and percentages of meal retention at 60 and 90 min were 51 (34.5-93.9) and 42% (24-71.2), respectively. When compared with baseline values a significant difference in gastric emptying parameters was found after both erythromycin and metoclopramide. A significant improvement of the total score for gastrointestinal symptoms was observed with both drugs, but this improvement was more pronounced with erythromycin. Erythromycin, a macrolide antibiotic and a motilin receptor agonist, appears to stimulate intestinal motility and seems to be an alternative agent for the treatment of gastroparesis caused by diabetic autonomic neuropathy.

Effect of metoclopramide in diabetic gastroparesis.

The aims of our study were to: determine the effect of metoclopramide parenterally and orally on delayed gastric emptying of a radionuclide test meal in symptomatic patients with diabetic gastroparesis not explained by ulceration or other mechanical problems; and evaluate in a double-blind crossover fashion the efficacy of metoclopramide in relieving the symptoms of diabetic gastroparesis. Thirteen patients with subjective evidence of gastric stasis had delayed gastric emptying of an isotope-labeled semisolid meal which was significantly accelerated (p less than 0.05) after 10 mg of metoclopramide parenterally. Patients then received metoclopramide 10 mg and placebo before meals and prior to retiring for 3 weeks in a randomized double-blind crossover design. During metoclopramide therapy nausea, vomiting, anorexia, fullness, and bloating were significantly (p less than 0.05) ameliorated compared to placebo with an overall mean symptom reduction of 52.6%. Gastric emptying studies after completion of the trial is seven patients, subjectively improved and receiving open-labeled metoclopramide, showed significantly less gastric retention. Individual improvements in gastric emptying after parenteral or oral metoclopramide, however, could not be correlated with symptom change during the treatment trial. We conclude that metoclopramide is an important therapeutic adjunct in the management of diabetic gastroparesis and its therapeutic effects are mediated through its prokinetic properties as well as centrally mediated antiemetic actions.

Management of diabetic gastroparesis.

Symptoms suggestive of gastroparesis occur in 5% to 12% of patients with diabetes. Such a complication can affect both prognosis and management of the diabetes; therefore, practicing clinicians are challenged by the complex management of such cases. Gastroparesis is a disorder characterized by a delay in gastric emptying after a meal in the absence of a mechanical gastric outlet obstruction. This article is an evidence-based overview of current management strategies for diabetic gastroparesis. The cardinal symptoms of diabetic gastroparesis are nausea and vomiting. Gastroesophageal scintiscanning at 15-minute intervals for 4 hours after food intake is considered the gold standard for measuring gastric emptying. Retention of more than 10% of the meal after 4 hours is considered an abnormal result, for which a multidisciplinary management approach is required. Treatment should be tailored according to the severity of gastroparesis, and 25% to 68% of symptoms are controlled by prokinetic agents. Commonly prescribed prokinetics include metoclopramide, domperidone, and erythromycin. In addition, gastric electrical stimulation has been shown to improve symptoms, reduce hospitalizations, reduce the need for nutritional support, and improve quality of life in several open-label studies.

Metoclopramide Nasal Spray Reduces Symptoms of Gastroparesis in Women, but not Men, With Diabetes: Results of a Phase 2B Randomized Study.

Metoclopramide nasal spray, unlike oral tablets, is absorbed even when patients have delayed gastric emptying or nausea and vomiting. We performed a randomized phase 2b study to evaluate the efficacy and safety of 10-mg and 14-mg metoclopramide nasal spray vs placebo in patients with diabetes and gastroparesis. We performed a multicenter, double-blind study of 285 subjects (71% female) with type 1 or type 2 diabetes and a previous diagnosis of gastroparesis. Subjects were assigned randomly to groups given metoclopramide nasal spray (10 or 14 mg) or placebo 30 minutes before meals and bedtime for 28 days. The primary end point was the change in total symptom score from baseline to week 4, based on symptom items (nausea, bloating, early satiety, and upper abdominal pain) reported in daily diaries. We performed a prespecified subgroup analysis of male vs female subjects. Subjects given metoclopramide nasal spray had an overall reduction in symptom scores, although there was no statistically significant difference in reduction between the metoclopramide groups and the placebo group. Gastroparesis symptom scores were reduced significantly in female subjects given either dose of metoclopramide compared with placebo (mean reduction from 10-mg dose, 1.2 ± 1.18; P = .0247; mean reduction from 14-mg dose, 1.3 ± 0.94; P = .0215). In men, symptom scores decreased more in the placebo group than the metoclopramide groups. The most common treatment-emergent adverse effects were dysgeusia, headache, and fatigue. Metoclopramide nasal spray reduces symptoms of gastroparesis in women, but not in men, with diabetes. Patient sex therefore might be considered in the selection of treatment for diabetic gastroparesis. ClinicalTrials.gov no: NCT00845858.

A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis.

A double-blind, multicenter, randomized trial was conducted to compare the side effects and efficacy of domperidone and metoclopramide in symptomatic diabetic gastroparesis. Ninety-three insulin-dependent diabetes patients with a > or = 3-month history of gastroparesis symptoms were recruited; 48 received domperidone 2 x 10-mg tablets 4 times daily, and 45 received metoclopramide 1 x 10-mg tablet + 1 placebo tablet 4 times daily. Nausea, vomiting, bloating/distension, and early satiety were evaluated for severity after 2 and 4 wk. Adverse central nervous system (CNS) effects of somnolence, akathisia, asthenia, anxiety, depression, and reduced mental acuity were elicited and graded for severity at 2 and 4 wk. Domperidone and metoclopramide were equally effective in alleviating symptoms of diabetic gastroparesis. Elicited adverse CNS effects were more severe and more common with metoclopramide. Somnolence was acknowledged by 49% of patients (mean severity score, 1.03) after 4 wk of metoclopramide compared with 29% of patients (mean severity score, 0.49) after 4 wk of domperidone (incidence, p = 0.02; severity; p = 0.03). A reduction in mental acuity was acknowledged by 33% of patients (mean severity score, 0.62) after 4 wk of metoclopramide, compared with 20% of patients (mean severity score, 0.27) after 4 wk of domperidone (incidence, p = 0.04; severity, p = 0.04). Akathisia, asthenia, anxiety, and depression were also acknowledged less often, and at a lower severity, after 4 wk of domperidone, although these differences were not statistically significant. Domperidone and metoclopramide effectively reduce the symptoms of diabetic gastroparesis; CNS side effects are more pronounced with metoclopramide.

Delayed gastric emptying: whom to test, how to test, and what to do.

Gastroparesis, or delayed gastric emptying, is a common cause of chronic nausea and vomiting as seen in a gastroenterology practice. Diabetic, postsurgical, and idiopathic causes remain the three most common forms of gastroparesis. In addition to nausea and vomiting, symptoms of gastroparesis may include early satiety, postprandial fullness, and abdominal pain. Physiologic changes that may explain symptoms in patients with gastroparesis, in addition to delayed gastric emptying, include impaired fundic accommodation, antral hypomotility, gastric dysrhythmias, pylorospasm, and perhaps visceral hypersensitivity. Diagnosis of gastroparesis is best determined using a radioisotope-labeled solid meal with scintigraphic imaging for at least 2 hours, and preferably 4 hours, postprandially. Most commonly, a 99mTc sulfur colloid-labeled egg sandwich with imaging at 0, 1, 2, and 4 hours is used. Extension of the gastric emptying test to 4 hours improves the accuracy of the test, but unfortunately, this is not commonly performed at many centers. Emptying of liquids remains normal until the late stages of gastroparesis and is less useful. The aims of treatment should be to control symptoms and maintain adequate nutrition and hydration. Patients should be advised to eat small meals and to limit their intake of fat and fiber. Additional dietary recommendations may include increasing caloric intake in the form of liquids. For diabetic patients, control of blood glucose levels is important, as symptom exacerbation is frequently associated with poor glycemic control. Specific treatment often begins with metoclopramide, 10 mg, up to four times daily, after a discussion of possible side effects with the patient. An antiemetic agent, such as prochlorperazine, 5 to 10 mg orally or 25 mg by suppository, can be added on an as-needed basis every 4 to 6 hours to control nausea. If these antiemetic medications are not effective, or if side effects develop, orally dissolving ondansetron, 8 mg every 8 to 12 hours, can be tried on an as-needed basis. If this regimen is unsuccessful, then alternative prokinetic agents--erythromycin, 125 mg, or tegaserod, 6 mg, prior to meals--can be tried. For cases refractory to these treatments, referral to a center with US Food and Drug Administration permission to use domperidone should be considered. Alternatively, symptom modulators such as low-dose tricyclic antidepressants can be tried to reduce symptoms, but these do not improve gastric emptying. In patients for whom all medical therapy fails, other options that are tried at experienced centers include the injection of botulinum toxin into the pylorus, placement of a feeding jejunostomy, and/or placement of a gastric electrical stimulator.

A multicenter placebo-controlled clinical trial of oral metoclopramide in diabetic gastroparesis.

Metoclopramide tablets were compared with placebo in the treatment of gastrointestinal symptoms in 40 patients with diabetic gastroparesis. Results of a 3-wk double-blind study indicate that metoclopramide at a dosage of one 10-mg tablet four times daily reduced nausea, vomiting, fullness, and early satiety and improved meal tolerance better than placebo. Statistically significant differences were noted for nausea and postprandial fullness. Mean gastric emptying assessed by radionuclide scintigraphy was significantly improved in the metoclopramide-treated group when compared with their baseline result. Metoclopramide is an effective agent for improving the upper gastrointestinal motor function in diabetic patients with gastroparesis.

A case of nausea and vomiting to remember.

Nausea and vomiting are the most common overlooked debilitating symptoms that significantly impact the quality of life and acute care we provide as physicians. The duo has an extensive aetiology ranging from common known causes to uncommon idiopathic reasons. Our case illustrates the fact that identifying the aetiology of nausea and vomiting can be lifesaving, given the characteristics of the patient. This case is about a 31-year-old Caucasian woman, with history significant for insulin-dependent diabetes mellitus on insulin pump since the age 2, Hypothyroidism, diabetic peripheral neuropathy with no significant known family history, who was admitted with intractable nausea and vomiting. She was discharged twice from hospital after temporary symptom control with presumed diagnosis of diabetic gastroparesis. Her third hospital visit enabled us to identify the cause of her symptoms being Addison's crisis rather than gastroparesis.

Domperidone

Nausea and vomiting There is some evidence that domperidone has antiemetic activity. It is recommended by the Canadian Headache Society for treatment of nausea associated with acute migraine. Gastroparesis Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting, fullness after eating, early satiety (feeling full before the meal is finished), abdominal pain and bloating. Domperidone may be useful in diabetic and idiopathic gastroparesis. However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate (equate) well with relief of symptoms.

Gastroparesis

Metoclopramide, a dopamine D2 receptor antagonist, increases contractility and resting tone within the GI tract to improve gastric emptying. In addition, dopamine antagonist action in the central nervous system prevents nausea and vomiting. Similarly, the dopamine receptor antagonist domperidone is used to treat gastroparesis. Erythromycin is known to improve emptying of the stomach but its effects are temporary due to tachyphylaxis and wane after a few weeks of consistent use. Sildenafil citrate, which increases blood flow to the genital area in men, is being used by some practitioners to stimulate the gastrointestinal tract in cases of diabetic gastroparesis. The antidepressant mirtazapine has proven effective in the treatment of gastroparesis unresponsive to conventional treatment. This is due to its antiemetic and appetite stimulant properties. Mirtazapine acts on the same serotonin receptor (5-HT3) as does the popular anti-emetic ondansetron. Camicinal is a motilin agonist for

Diabetic gastroparesis. A critical reappraisal of new treatment strategies.

Delayed gastric emptying, gastroparesis, is one of the sequelae of diabetes mellitus. Symptoms may include postprandial nausea, epigastric pain, bloating, vomiting, early satiety and unpredictable blood sugar fluctuations. Nowadays diagnosis is made by the measurement of gastric emptying with a radionuclide test meal. Using this technique some 50% of diabetic patients show signs of disordered gastric emptying. Relief is best delivered by agents promoting gastric emptying. In phase II single-dose studies metoclopramide, domperidone, cisapride, erythromycin and renzapride were all able to enhance gastric evacuation of solid and liquid meals in patients with diabetic gastroparesis. A few short term studies support the efficacy of domperidone and renzapride, but long term trials are lacking. Erythromycin, mimicking the potent gastrokinetic effect of motilin, may hold considerable promise for the future. Experience with erythromycin in diabetic gastroparesis is nonetheless very limited. To some extent the therapeutic effectiveness of metoclopramide and cisapride has been established in placebo-controlled trials. In trials with a placebo-controlled crossover design, however, only metoclopramide showed a sustained positive effect. Metoclopramide, which combines gastrokinetic and antiemetic properties seems, so far, the best therapeutic option in diabetic gastroparesis. Cisapride may be considered as a good alternative in cases where limited efficacy or side effects preclude the use of metoclopramide.

[New therapeutic approaches to diabetic gastroparesis].

CASE HISTORY AND PHYSICAL EXAMINATION: A 24-year-old man with type 1 diabetes, nonresponding to standard treatment for severe gastroparesis, was admitted to hospital due to persisting nausea and vomiting. Further known complications included diabetic retinopathy, diabetic nephropathy with mild renal impairment, diabetic peripheral and cardiac autonomic neuropathy, and arterial hypertension. Gastric motility parameters were evaluated by functional scintigraphy. Gastric emptying was severely delayed showing first appearance of food in duodenum after 25 min. After 60 min, technetium activity in the stomach was still detected in considerable amounts. The 50% emptying time was 58 min (normal time 10-20 min). A detailed symptom score for gastroparesis, prospectively investigated by a standardized patient diary, showed a severe and complex clinical disturbance: the frequency of daily attacks of impulsive vomiting ranged from 2 to 21 and the mean daily duration of nausea was 7.5 h. A value of 3.4 on the scale for a premature feeling of satiety (range 0-4, normal=0) was determined, as well as scores of 2.5 for symptoms of abdominal bloating (range 0-3, normal=0) and 3.7 for general well-being (range 0-4, normal=0). Pharmacological interventions with antibiotics, prokinetics, antiemetics and, as a second step, percutaneous gastrostomy (first intervention) and jejunostomy (second intervention) were not long-term effective in reducing the clinical symptoms described above. Therefore, a single intrapyloric injection with 100 U of botulinum toxin was performed leading to a prompt and significant improvement of symptoms and an adequate oral nutrient intake the day after the procedure. Determined by gastric scintigraphy 1 week later, this led to a significant reduction of the 50% emptying time (36 min) and to an improvement of the symptom score for gastroparesis as determined 4 weeks later: frequency of daily attacks of impulsive vomiting ranged from 0 to 1, mean daily duration of nausea was 1 h, premature feeling of satiety (score 1.9), symptoms of abdominal bloating (1.1), and general well-being (2.1). The beneficial effect of the botulinum toxin injection was unchanged over 3 months, slightly diminishing by 4.5 months. After a second round of botulinum toxin injection, again, prompt relief of most of the symptoms was achieved. Percutaneous jejunostomy was then revised. Intrapyloric injection of botulinum toxin is effective in improving the complex symptoms and clinical syndrome associated with diabetic gastroparesis resistant to conventional treatment. Upon waning of the therapeutic effect over time, the procedure can be repeated with success.

Cyclic vomiting: association with multiple homeostatic abnormalities and response to ketorolac.

Cyclic vomiting is a rare syndrome that over the years has variously been ascribed to psychogenic causes, sensory seizures, abdominal migraine, and more recently, to mechanical or electrical disturbances in gastric physiology. We describe the case of a 65-year-old white diabetic female with a 10-yr history of recurrent episodes of nausea and vomiting, occurring every 10-12 days and lasting approximately 1-3 days at a time. These episodes were accompanied by edema, mild temperature elevations, and remarkable elevations in blood pressure. In between these episodes, the patient remained asymptomatic. Initial screening tests were also negative except for moderate gastroparesis. However, antral motility was found to be normal, as was an electrogastrogram. Detailed neurological and psychiatric evaluations were negative. Trials of erythromycin, metoclopramide, naloxone, ondansetron, and amitryptiline were unsuccessful. Serial endocrinological testing revealed that an episode of vomiting was always preceded by an abnormal elevation in at least one of the following: serum adrenocorticotropic hormone, serum cortisol, or urinary cortisol. In the midst of an episode, all three values were exceedingly high (e.g., > 10-fold increases in 24-hr urinary cortisol levels). Fluctuations of a milder degree, though still abnormally high, were also noted in between cycles at times when the patient was completely asymptomatic. High-dose dexamethasone suppressed these hormonal surges completely but not the clinical symptoms, which continued undisturbed. The patient was finally given a trial of intramuscular ketorolac during one of her episodes, which produced prompt and sustained relief. During the next few weeks, she was given this drug each time her symptoms commenced, and each time it appeared that her cycle had been aborted. She has since been able to terminate her episodes promptly and completely by self-administration of ketorolac. We speculate that her syndrome is caused by a poorly characterized disorder of endogenous prostaglandin release, resulting not only in derangements in the hypothalamic pituitary system but also in nausea and vomiting.

Use of metoclopramide, domperidone, and cisapride in the management of diabetic gastroparesis.

The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy.

Current concepts in diabetic gastroparesis.

Diabetic gastroparesis is a common and debilitating condition affecting millions of patients with diabetes mellitus worldwide. Although gastroparesis in diabetes has been known clinically for more than 50 years, treatment options remain very limited. Until recently, the scientific literature has offered few clues regarding the precise aetiology of gastric dysfunction in diabetes.Up to 50% of patients with diabetes may experience postprandial abdominal pain, nausea, vomiting and bloating secondary to gastric dysfunction. There is no clear association between length of disease and the onset of delayed gastric emptying. Gastroparesis affects both type 1 (insulin dependent) and type 2 (non- insulin dependent) forms of diabetes. Diagnosis requires identifying the proper symptom complex, while excluding other entities (peptic ulcer disease, rheumatological diseases, medication effects). The diagnosis of gastroparesis may be confirmed by demonstrating gastric emptying delay during a 4-hour scintigraphic study. Treatment options are limited and rely on dietary modifications, judicious use of available pharmacological agents, and occasionally surgical or endoscopic placement of gastrostomies or jejunostomies. Gastric pacing offers promise for patients with medically refractory gastroparesis but awaits further investigation. Current pharmacological agents for treating gastroparesis include metoclopramide, erythromycin, cisapride (only available via a company-sponsored programme) and domperidone (not US FDA approved). All of these drugs act as promotility agents that increase the number or the intensity of gastric contractions. These medications are not uniformly effective and all have adverse effects that limit their use. Cisapride has been removed from the open market as a result of over 200 reported cases of cardiac toxicity attributed to its use. Unfortunately, there is a paucity of clinical studies that clearly define the efficacy of these agents in diabetic gastroparesis and there are no studies that compare these drugs to each other. The molecular pathophysiology of diabetic gastroparesis is unknown, limiting the development of rational therapies. New studies, primarily in animals, point to a defect in the enteric nervous system as a major molecular cause of abnormal gastric motility in diabetes. This defect is characterised by a loss of nitric oxide signals from nerves to muscles in the gut resulting in delayed gastric emptying. Novel therapies designed to augment nitric oxide signalling are being studied.

A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant.

A 31-year-old woman with an 11-year history of poorly controlled type 1 diabetes mellitus was admitted with severe vomiting and ketoacidosis. The patient had been admitted to hospital on 14 occasions in the past 3 years for diabetic ketoacidosis precipitated by intractable vomiting, and she had been diagnosed with gastroparesis 2 years previously. Assessment of the patient's response to standard treatments for diabetic gastroparesis. These approaches involved tight glycemic control that included subcutaneous insulin infusion via a pump, correction of electrolyte disturbances, use of standard antiemetic and promotility agents, somatostatin-analog treatment, intrapyloric injection of botulinum toxin, and insertion of a percutaneous jejunal feeding tube. Severe diabetic gastroparesis refractory to standard treatments. The neurokinin-receptor antagonist aprepitant was started and her vomiting stopped within 24 h. This treatment was successfully continued for 4 months until a gastric electrical stimulation device was inserted, which enabled aprepitant treatment to be withdrawn and the percutaneous jejunostomy feeding tube to be removed. This successful treatment led to a substantial improvement in the patient's quality of life and overall glycemic control.

Metoclopramide as a prokinetic agent for diabetic gastroparesis: revisiting the risk of Parkinsonism.

Metoclopramide is used to relieve gastrointestinal symptoms, however, it could cause adverse reactions of motor disorders. The aim of this study was to investigate whether metoclopramide treatment has a duration-response or dose-response effect and to estimate the risk of developing Parkinsonism following different and specific durations of treatment. A cohort study of newly diagnosed type 2 diabetes mellitus in 45- to 79-year-old patients, between 1999 and 2008, was selected using the Longitudinal Health Insurance Database 2005. A nested case-control study was conducted in the diabetes cohort in which all incident cases of Parkinsonism were identified. We randomly matched each case with up to 10 controls from the risk set. Conditional logistic regression was utilized to estimate odds ratio of Parkinsonism associated with metoclopramide use. A total of 34,685 patients with diabetes were assembled as the cohort, and 541 incident Parkinsonism cases were identified. There were duration-response and dose-response effects on the risk of developing Parkinsonism. Compared with never-use patients, the adjusted odds ratios (ORs) of continuing therapy for 0-1 month, 1-2 months, 2-3 months, 3-5 months, and more than 5 months were 1.17 [95% confidence interval (CI) 0.93-1.45], 1.44 (95% CI 1.04-2.00), 1.74 (95% CI 1.14-2.65), 1.90 (95% CI 1.23-2.93), and 2.17 (95% CI 1.50-3.12), respectively. With metoclopramide treatment, regardless of less or more than 3 months of use, the risk of developing Parkinsonism in patients with newly diagnosed diabetes escalated with the duration of therapy. Therefore, we recommend close monitoring for the development of Parkinsonism in patients treated with metoclopramide, particularly (but not limited to) those with prolonged exposure.

Metoclopramide nasal spray is effective in symptoms of gastroparesis in diabetics compared to conventional oral tablet.

Delayed gastric emptying symptoms interfere with the absorption of oral medications. Intranasal metoclopramide is being developed as an alternative to oral metoclopramide for patients with diabetic gastroparesis. To compare the efficacy and safety of metoclopramide nasal spray to oral tablets in diabetic patients with symptoms of gastroparesis, this randomized, open-label, parallel design study randomized subjects to 10 or 20 mg nasal spray or 10 mg tablet four times a day for 6 weeks. Efficacy was evaluated using a total symptom score (TSS). Eighty-nine subjects were enrolled. For the intention to treat population, both nasal dose groups (10 and 20 mg) had lower TSS with treatment compared to the oral 10 mg group. The change from baseline in TSS for nasal 20 mg was greater than the oral 10 mg at Week 6 (p = 0.026). For the per-protocol population, there was a significant difference in the TSS between baseline and Week 6 for both the nasal 10 mg (p = 0.026) and the nasal 20 mg (p = 0.008) cohorts compared to the oral 10 mg group. Based on the definition of a responder, 88.9% of subjects who received oral 10 mg, 91.2% who received nasal 10 mg, and 97.1% who received nasal 20 metoclopramide were classified as responders. The side-effect profile of the metoclopramide nasal spray was favorable. More side effects, especially nausea, occurred with the oral tablets. Metoclopramide nasal spray offers better symptom control than metoclopramide oral tablet in diabetic patients with symptoms of gastroparesis.

Gastroparesis

Gastroparesis present similar symptoms to slow gastric emptying caused by certain opioid medications, antidepressants, and allergy medications, along with high blood pressure. For patients already with gastroparesis, these can make the condition worse. More than 50% of all gastroparesis cases are idiopathic in nature, with unknown causes. It is, however, frequently caused by autonomic neuropathy. This may occur in people with type 1 or type 2 diabetes, about 30-50% among long-standing diabetics. In fact, diabetes mellitus has been named as the most common cause of gastroparesis, as high levels of blood glucose may effect chemical changes in the nerves. The vagus nerve becomes damaged by years of high blood glucose or insufficient transport of glucose into cells resulting in gastroparesis. Adrenal and thyroid gland problems could also be a cause.

Glossary of medicine

Coeliac disease – Coeliac disease or celiac disease is a long-term autoimmune disorder that primarily affects the small intestine. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite and among children failure to grow normally. This often begins between six months and two years of age. Non-classic symptoms are more common, especially in people older than two years. There may be mild or absent gastrointestinal symptoms, a wide number of symptoms involving any part of the body or no obvious symptoms. Coeliac disease was first described in childhood; however, it may develop at any age. It is associated with other autoimmune diseases, such as diabetes mellitus type 1 and thyroiditis, among others. Colorectal surgery – is a field in medicine dealing with disorders of the rectum, anus, and colon.

Velusetrag

Velusetrag showed accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing in healthy volunteer subjects. In addition, velusetrag showed accelerated gastric emptying in patients with diabetic or idiopathic gastroparesis. The proportion of patients who experienced at least a 20% improvement is gastric emptying ranged from 20% to 52% for velusetrag dosed patients and 5% for placebo patients. On December 6, 2016, Theravance Biopharma announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to velusetrag for the treatment of symptoms associated with diabetic and idiopathic Gastroparesis. As of May 10, 2017, Velusetrag is being studied, at doses of 5, 15 and 30 mg over a 12-week treatment period, for symptomatic improvement in patients with diabetic or idiopathic gastroparesis in the DIGEST study. See also Prucalopride Naronapride References

Stomach disease

Gastroparesis Another very common long term problem which is now more appreciated is gastroparesis. Gastroparesis affects millions of individuals and is often never suspected and most patients have a delay in diagnosis. Basically in gastroparesis, the stomach motility disappears and food remains stagnant in the stomach. The most common cause of gastroparesis is diabetes but it can also occur from a blockage at the distal end of stomach, a cancer or a stroke. Symptoms of gastroparesis includes abdominal pain, fullness, bloating, nausea, vomiting after eating food, loss of appetite and feeling of fullness after eating small amounts of food.

Gastroparesis and Severity of Delayed Gastric Emptying: Comparison of Patient Characteristics, Treatments and Medication Adverse Events.

Gastroparesis is a heterogeneous disorder. Patient characteristics and treatment responsiveness may differ based on the extent of delay in gastric emptying. Characterize gastroparesis patients based on the degree of delay in gastric emptying, and assess the relationship of patient demographics, symptoms and response to therapy based on the extent of delay. 1333 solid-phase 4-h scintigraphic gastric emptying scans were reviewed. Delayed emptying was categorized on percent retention at 4 h: mild (10-19%), moderate (20-29%), and severe (≥ 30%). Analyses were performed with regard to demographics, symptoms, esophagogastroduodenoscopy findings, medication use, and emergency department (ED) visits/hospitalizations. 284 patients had delayed gastric emptying: mild (42.6%), moderate (19.3%), and severe (37.3%). 79.5% were women, the mean age was 45 years (± 15), and mean symptom duration was 4.6 years (± 6.5). The main categories of gastroparesis were idiopathic and diabetes mellitus. The most commonly prescribed medications were metoclopramide, domperidone and erythromycin. Opiate use (n = 69) was associated with an increased degree of delayed gastric emptying (p = 0.03) with 50% of opiate users having very delayed gastric emptying. One-way analysis revealed that severely delayed gastric emptying correlated with both increased hospitalizations and ED visits. Severe delay in gastric emptying is a risk factor for increased hospitalizations and ED visits. Opiate use correlates with increased severity of gastric emptying. Identifying at-risk patients, stopping opioids, and instituting a programmatic care plan for patients with severely delayed gastric emptying may reduce ED visits, hospitalizations, and healthcare costs.

Efficacy of Pro-Kinetic Agents in Type 2 Diabetes Mellitus Patients With Gastroparesis Using Lactulose Hydrogen Breath Testing: A Randomized Trial.

Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.

Metoclopramide for gastroparesis diabeticorum.

Three patients with uncontrolled diabetes mellitus and with symptoms due to gastric retention proved to have gastroparesis diabeticorum. The diagnosis was established by the beefsteak-barium meal. After the administration of metoclopramide, gastric emptying improved and the diabetes was easily controlled. Gastroparesis diabeticorum is one cause of uncontrolled diabetes mellitus and may be helped by the administration of metoclopramide.

Mirtazapine treatment of diabetic gastroparesis as a novel method to reduce tube-feed residual: a case report.

Gastroparesis is a common motility disorder that is characterized by delayed gastric emptying in the absence of mechanical obstruction. Diabetes, along with other neuromuscular and infiltrating disorders, can predispose individuals to an increased risk of developing gastroparesis. Gastroparesis can be easily diagnosed through gastric emptying studies but is usually difficult to successfully treat. Therapy usually begins with pro-kinetic and anti-emetic agents. Our patient was an 87-year-old African-American woman who was a nursing home resident, with a history of diabetes mellitus type 2 and subarachnoid hemorrhage leading to aphasia, hemiplegia, seizures and dysphagia requiring percutaneous gastric feeds. While at the nursing home, she had recurrent aspiration pneumonia and large tube-feed residuals consistent with a diagnosis of underlying gastroparesis. Her management included metoclopramide and reduced tube-feeding rates, which improved her symptoms. However, within months the aspiration and increased residuals returned. After trials of different medication therapies without success, she started mirtazapine and her residual volume and aspirations decreased with a dose of 15mg nightly. In patients with gastroparesis recalcitrant to first line therapies such as metoclopramide, off-label use of mirtazapine may provide adequate non-invasive management of gastroparetic symptoms.

Diabetic Gastroparesis -- Treatment / Management

Domperidone is a dopamine (D2) agonist with effects similar to metoclopramide but is much less likely to cause extrapyramidal side effects as it does not cause the blood-brain barrier. Symptomatic patients with diabetes have reported improved domperidone therapy, but again, the effect could be lost in about six weeks. [26] [27] [28] Domperidone was associated with cardiac arrhythmias in the past and is not FDA approved in the United States. Cisapride is a 5-HT4 agonist that might have effects that last up to 1 year, but unfortunately, it was also associated with ventricular arrhythmias, including torsades de pointes, and has been withdrawn from the US market. Both these drugs are available through select investigators as part of clinical trials with strict patient monitoring. In patients who do not respond well to the above therapies alone, combination prokinetic therapies can be tried. Symptomatic control of nausea using antiemetics is another option. Several studies have evaluated pyloric botulinum toxin injection, but these studies were often unblinded and had small numbers of patients. [16]

Gastroparesis-associated refractory nausea treated with aprepitant.

To report a case of refractory nausea in a patient with idiopathic gastroparesis successfully treated with aprepitant. A 41-year-old female with idiopathic gastroparesis demonstrated by a delayed gastric emptying time experienced significant nausea, vomiting, and abdominal pain. This resulted in numerous hospital admissions and regular outpatient intravenous fluid administration. Over a 3-year period the patient had been treated with numerous agents for nausea and vomiting, including metoclopramide 10 mg 3 times daily, ondansetron 8 mg 2 times daily, and promethazine (various doses from 12.5 to 25 mg orally up to 3 times daily). No treatment tried was either tolerated or effective. As a last option before considering gastric pacing the patient was started on aprepitant 40 mg daily. The patient had a dramatic response to aprepitant and reported that her nausea had decreased significantly after 48 hours of starting the medication (2 doses). She was able to tolerate oral feeding and her need for outpatient intravenous hydration abated. Over the course of 2 months while using aprepitant her gastroparesis symptoms continued to improve. She reported no adverse effects attributable to aprepitant. After the first 2 months of aprepitant treatment, the patient was unable to continue the medication due to cost. Although her symptoms did worsen after discontinuation, they did not return to their initial severity. At 4 months after the trial of aprepitant, she continued to have improved symptoms. She claimed not to have daily nausea or vomiting, but still required high-dose promethazine and occasional outpatient intravenous fluids. At that point, she had gained 7.2 kg from the time that she had started aprepitant. Aprepitant, a neurokinin-1 receptor antagonist, is approved in the US for nausea and vomiting associated with surgery and cancer chemotherapy. To our knowledge, this is the second reported case of its use in gastroparesis-induced nausea. Our patient reported relief of nausea and vomiting despite existing evidence showing that aprepitant has no significant effect on accelerating gastric emptying. Despite its acquisition cost, our patient avoided hospital admission and the administration of intravenous hydration, suggesting aprepitant may be cost-effective in this case. Aprepitant may have some utility in treating refractory nausea caused by gastroparesis. This case suggests that the drug's antiemetic effect may be successfully used in areas not approved by the Food and Drug Administration. A controlled trial examining aprepitant in patients with such challenging clinical conditions may be warranted.

Metoclopramide therapy in fifty-five patients with delayed gastric emptying.

Fifty-five patients with delayed gastric emptying and the symptoms of nausea, vomiting, postprandial bloating and early satiety were treated with metoclopramide. Obstruction was excluded by upper endoscopy and standard upper gastrointestinal series. None were on medication known to retard gastric emptying. All patients had an abnormal barium burger radiologic study. Twenty-one patients had had previous vagotomy and drainage procedure, five had diabetic gastroparesis and 29 had idiopathic delayed gastric emptying. Metoclopramide significantly decreased the symptom scores of the surgical and idiopathic patients. When all patients were analyzed together, there was a significant improvement in both the metoclopramide and placebo treated patients. When, however, the improvement on metoclopramide was compared to the improvement on placebo, there was a significant metoclopramide effect beyond the placebo effect. Thus, metoclopramide is an effective agent in treating the symptom-complex of patients with delayed gastric emptying.

Diabetic Gastroparesis -- Enhancing Healthcare Team Outcomes

Treatment of diabetic gastroparesis aims to alleviate the associated symptoms and replenish electrolytes, nutrition, and hydration. Frequently used medications include erythromycin (macrolide antibiotic-associated with increased gastrointestinal motility) and metoclopramide (antiemetic and prokinetic), and polyethylene glycol 3350 may additionally be used to provide relief from severe constipation. Patients who continue to experience gastroparesis symptoms despite medical therapy may be candidates for gastric electrical stimulation (GES), wherein an electrical device is implanted into the abdomen. Unfortunately, no treatment works reliably or consistently. Once the condition has been diagnosed, it is progressive and imparts a very poor quality of life. [32] [33]

[Comparative data of prokinetics in treatment of gastroesophageal reflux disease in patients with diabetes].

The purpose is to evaluate the effectiveness of itopride (IP) and domperidone (DP) in the treatment of patients with gastroesophageal reflux disease (GERD), in combination with diabetes mellitus (DM) type 1 and 2. 40 patients were examined with GERD and type 1 diabetes and 50 patients with GERD and type 2 diabetes. Each group of patients with GERD, DM 1 and 2 has been divided into: the basic subgroup receiving IG 50 mg 3 tid and control--DP 10 mg tid. Patients were also administered omeprazole. Both subgroups were strictly randomized to key indicators, except for therapy. Baseline and after 2 and 4 weeks, all patients were examined to identify complaints, endoscopy and pH-metric changes, gastric motility was studied by electrogastroenterographic method (PEGEG). In the subgroups of patients with GERD + DM 1 and GERD + DM 2, received treatment with IG complaints on heartburn, regurgitation, odynophagia relieved significantly earlier then in the subgroups treated with DP. After 4 weeks of therapy, decreasing in the number of gastroesophageal refluxes, number of patients with erosive esophagitis B level, and normalization of the motility of the stomach were significantly higher in the groups of GERD + DM 1 and GERD + DM 2 received treatment with IG when compared with the subgroup of PD. There were no side effects of prokinetics. IG was more effective then DP in the treatment of GERD in patients with diabetes, and may be recommended for inclusion in the scheme of treatment of this comorbidity.


It is a chondrocalcinosis. There is no treatment for this disease, only treatment for flare-ups (colchicine, NSAIDs or corticosteroids), although sometimes if the flare-ups are habitual the colchicine is maintained. Allopurinol has not shown any efficacy in this microcrystal arthropathy, but it has shown efficacy in gout.

A 40-year-old man, with no history of interest, presents with acute arthritis of the right knee of 5 days of evolution as well as fever up to 37.7°C. He has no history of trauma. He presented with joint effusion, warmth on palpation and functional limitation due to pain. Diagnostic arthrocentesis was performed and showed 30000 cels/microliter with predominance of neutrophils. Polarized light examination revealed rhomboidal and cylindrical crystals with weakly positive birefringence. On plain radiograph of the knee, radiodense deposits are found in the external meniscus of the knee. Mark the FALSE answer:

Initial treatment will consist of non-steroidal anti-inflammatory drugs, as well as aspiration of synovial fluid.

It is advisable to perform a synovial fluid culture to rule out infectious synovitis.

Once the acute flare-up has passed, treatment with allopurinol should be started to reduce the incidence of new arthritis flare-ups in the future.

The most likely diagnosis is acute arthritis due to calcium pyrophosphate crystal deposition (pseudogout).

Gout

Diagnosis Gout may be diagnosed and treated without further investigations in someone with hyperuricemia and the classic acute arthritis of the base of the great toe (known as podagra). Synovial fluid analysis should be done if the diagnosis is in doubt. Plain X-rays are usually normal and are not useful for confirming a diagnosis of early gout. They may show signs of chronic gout such as bone erosion. Synovial fluid A definitive diagnosis of gout is based upon the identification of monosodium urate crystals in synovial fluid or a tophus. All synovial fluid samples obtained from undiagnosed inflamed joints by arthrocentesis should be examined for these crystals. Under polarized light microscopy, they have a needle-like morphology and strong negative birefringence. This test is difficult to perform and requires a trained observer. The fluid must be examined relatively soon after aspiration, as temperature and pH affect solubility.

Acute Monoarthritis: Diagnosis in Adults.

Acute monoarthritis can be the initial manifestation of many joint disorders. The most common diagnoses in the primary care setting are osteoarthritis, gout, and trauma. It is important to understand the prevalence of specific etiologies and to use the appropriate diagnostic modalities. A delay in diagnosis and treatment, particularly in septic arthritis, can have catastrophic results including sepsis, bacteremia, joint destruction, or death. The history and physical examination can help guide the use of laboratory and imaging studies. The presence of focal bone pain or recent trauma requires radiography of the affected joint to rule out metabolic bone disease, tumor, or fracture. If there is a joint effusion in the absence of trauma or recent surgery, and signs of infection (e.g., fever, erythema, warmth) are present, subsequent arthrocentesis should be performed. Inflammatory synovial fluid containing monosodium urate crystals indicates a high probability of gout. Noninflammatory synovial fluid suggests osteoarthritis or internal derangement. Pitfalls in the diagnosis and early treatment of acute monoarthritis include failure to perform arthrocentesis, administering antibiotics before aspirating the joint when septic arthritis is suspected (or failing to start antibiotics after aspiration), and starting treatment based solely on laboratory data, such as an elevated uric acid level.

[Arthrocentesis in the Emergency Department].

Arthrocentesis in the Emergency Department <bAbstract.</b Acute joint swelling is a common presentation to the emergency department. Although routine investigations like clinical exam, labs and eventually x-ray are usually obtained, definitive diagnosis must be established since timely recognition of septic arthritis in particular is crucial. Definitive diagnosis is achieved by performing an arthrocentesis of the affected joint. While arthrocentesis of larger joints and large effusions (e. g. knee) are relatively easy to perform using the landmark-technique, smaller and less accessible joints (shoulder, elbow, hip) are more difficult to access and it is therefore recommended to use ultrasound guidance. Compared with the landmark-technique, ultrasound-guided arthrocentesis is more successful and less painful. Synovial fluid should be analyzed for cell count with differential, crystals as well as for microbiological analysis such as Gram-stain and culture. Once the diagnosis of septic arthritis has been established, irrigation of the joint should be performed by orthopedic surgery. Antibiotic therapy should be withheld until the sampling of synovial fluid has been completed. After exclusion of septic arthritis, acute arthritis due to crystal arthropathy (CPPD or gout) is treated with either glucocorticoid-infiltration of the joint or with nonsteroidal anti-inflammatory drugs. In this article, the different technical aspects of arthrocentesis are discussed, including asepsis, landmark- and ultrasound-guided access, preanalytics and interpretation of the laboratory results.

Knee Arthrocentesis in Adults.

Arthrocentesis of the knee is a procedure in which a needle is inserted into the knee joint, and synovial fluid is aspirated. An arthrocentesis can be diagnostic or therapeutic. Synovial fluid may be removed for testing to determine the nature of the knee effusion. If septic arthritis is suspected, urgent arthrocentesis before initiation of antibiotic treatment is indicated. Moreover, arthrocentesis can also aid in diagnosing crystal-induced arthritis such as gout or pseudogout, or non-inflammatory arthritis such as osteoarthritis. Identifying the cause of the knee effusion can guide treatment. Furthermore, removing fluid from a knee can reduce intraarticular pressure to decrease pain and improve range of motion. There is no absolute contraindication to performing this procedure, but in selecting the needle entry site, an area of skin that is infected should be avoided. Therefore, caution should be exercised when a patient presents with suspected cellulitis over the knee joint to avoid the potential risk of causing iatrogenic septic arthritis. A knee that has undergone arthroplasty should be assessed for arthrocentesis by an orthopedic surgeon. Arthrocentesis of the knee is typically performed with the patient supine. The site for needle insertion is marked, and then the skin is disinfected. After a local anesthetic is administered, a needle is inserted along the pathway that was anesthetized. Synovial fluid is aspirated, and then the needle is withdrawn. Pressure is applied until any bleeding stops. The synovial fluid can be analyzed for infection and inflammation but cannot directly confirm a diagnosis of internal derangement or autoimmune causes of arthritis. In addition to the history and physical examination, laboratory findings and imaging can clarify the etiology of a knee effusion.

Knee effusion

In overweight or obese individuals the body places more weight on the knee joint. This causes more wear in the joint. Over time, the body may produce excess joint fluid. Diagnosis Diagnostic tests include: Joint aspiration Also known as arthrocentesis, this procedure includes withdrawal of fluid from inside the knee for analysis such as cell count, culture for bacteria, and examination for crystals, such as uric acid or calcium pyrophosphate dihydrate ram crystals found in gout or pseudogout. Imaging An X-ray is useful to verify that there is no break or dislocation when there is a history of trauma. May show signs of osteoarthritis. MRI Magnetic Resonance Imaging detects abnormalities of the bone or knee joint, such as a tear in the ligaments, tendons or cartilage.

Arthrocentesis

Gross Appearance: Opaque-appearing synovial fluid may indicate the presence of white blood cells, red blood cells, or acellular material such as lipids. Yellow-green appearing synovial fluid may indicate the presence of inflammation or infection. In the case of an infection or septic arthritis, the synovial fluid may contain pus and be more viscous. Crystal Analysis: Using a microscope and polarizing light filter, birefringence of crystals can be detected in a sample of synovial fluid. This is essential to distinguish monosodium urate crystals in gout from calcium pyrophosphate dihydrate crystals in pseudogout. Cell Count and Differential: In cases of bacterial joint infections, synovial fluid will typically show white blood cell counts of 50,000 to 150,000 cells/mm3. Cases of inflammatory arthritis are also likely to have an elevated white blood cell count in the synovial fluid, although the count will typically be lower than that seen in septic arthritis.

Monarthritis: differential diagnosis.

Acute monarthritis should be regarded as infectious until proved otherwise. Early evaluation is crucial because of the capacity of some infectious agents to destroy cartilage rapidly. The history and physical examination can provide highly suggestive clues, but a definitive diagnosis may depend on arthrocentesis and analysis of synovial fluid. The diagnosis of acute monarthritis is rarely established by radiography. The most common cause of bacterial arthritis is Neisseria gonorrhoeae. Staphylococcus aureus and streptococci are the organisms most frequently implicated in nongonococcal bacterial arthritis, although the possibility of Gram-negative bacteria or anaerobes should not be overlooked in intravenous drug users or immunocompromised patients. Inflammation in a large joint, particularly the knee, might arouse suspicion of Lyme disease. Other, less frequently encountered infectious causes of acute monarthritis include tuberculosis and other mycobacteria, fungi, and viruses. Arthroscopic examination and synovial tissue biopsy may be necessary to diagnose such processes. Microscopic examination of the synovial fluid may reveal a crystalline etiology for monarthritis. Monosodium urate crystals induce gout, usually in the toe, ankle, or midfoot, while calcium pyrophosphate crystals cause pseudogout, most often in the knee or wrist. Acute monarthritis is sometimes a manifestation of osteoarthritis or an early sign of a systemic arthritis such as rheumatoid or reactive arthritis. Processes underlying acute monarthritis can also evolve into a more chronic clinical picture as exemplified by the spondyloarthropathies.

Acute pseudoseptic arthritis after viscosupplementation of the knee: a case report.

Intra-articular injections of hyaluronan are generally well tolerated; the most common adverse event associated with their use is an inflammatory reaction or a flare at the injection site. Naturally derived sodium hyaluronates have not been associated with pseudosepsis; we describe a case of severe arthritis mimicking acute septic arthritis after naturally hyaluronan. A 70-year-old woman had a medial femorotibial and patellofemoral compartment knee osteoarthritis. Hyaluronic acid injection was indicated because of the persistence of a pain while walking and restricted ability to walk 100 m, as well as the installation of a flessum. She was admitted for an evaluation of a joint effusion occurring within 48 h after the first hyaluronic acid intra-articular injection (first course), with no fever or chills. Joint fluid was found to be cloudy and contained 24,000 cells per mm(3). A knee aspiration was performed to evaluate the possibility of a joint infection. The examination of synovial fluid under phase contrast and polarizing microscopes showed no crystals, and culture on standard media was negative. Acute septic arthritis was considered to be the most likely diagnosis, and probabilistic antibiotic therapy was started. The result of the bacteriological examinations also returned negative. The absence of general signs, particularly fever and chills, with fast effusion regression in less than 4 days did not plead in favor of a septic origin. In front of this beam of arguments, antibiotic therapy was stopped after 4 days. The nonsteroidal anti-inflammatory drug (Nimésulide) was given. The clinical and laboratory test abnormalities were normalized within 2 weeks. Our case has the particularity to occur after using Curavisc, which is known as producing no allergenic reactions. Moreover, the described reaction occurred with the very first infiltration within the very first course.

Induction of an acute attack of calcium pyrophosphate dihydrate arthritis by intra-articular injection of hylan G-F 20 (Synvisc).

Little is known about the induction of acute calcium pyrophosphate dihydrate arthritis after the intra-articular injection of hylan G-F 20 (Synvisc). Two reports have documented this adverse effect after the intra-articular injection of hyaluronan. Our patient, a 60-year-old man with osteoarthritis in both knees, presented with a history of an arthroscopy with meniscus shaving 7 years previously. He was given an injection of hylan G-F 20 in the right knee joint. Two days after the second injection, pain and swelling of the knee occurred. There was a severe loss of physical function. Systemic inflammatory reactions such as fever were not observed. A microscopic investigation of the synovial fluid showed evidence of calcium pyrophosphate dihydrate crystals. Bacterial contamination was not detected. There was no indication for calcium pyrophosphate dihydrate in the history of the patient. Some days after receiving nonsteroidal anti-inflammatory drugs and an intra-articular injection of steroids, the symptoms disappeared.

[Diff-Quik(R) staining method for detection and identification of monosodium urate and calcium pyrophosphate crystals in synovial fluids]

The aim of this study was to evaluate whether DQ could prove useful to identify monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals on permanent mounted stained slides. To this end, we studied 27 synovial fluid (SF) samples obtained from the knees of patients with the pseudogout (n=21) and acute gouty arthritis (n=6). Wet analysis for crystal detection and identification was performed within one hour of joint aspiration. In addition, we studied 16 inflammatory synovial effusions obtained from patients with knee arthritis not induced by crystals. For each SF, DQ stained slides were analyzed by 2 experienced doctors in SF analysis. The observers were blinded to the type of crystal present in the SF. Each slide was analyzed by compensated polarized and transmitted light microscopy. SF was considered positive if intracellular and/or extracellular crystals were clearly identified. In addition, the observers were asked to identify the type of the crystals using compensated polarized light microscopy. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the DQ staining method were determined. 51 true positive and 28 true negative specimens were correctly classified (39 CPPD samples, 12 MSU samples, and 28 samples of crystals-unrelated arthropathies). All MSU specimens were correctly diagnosed.

Serum-synovial gradient data of normouricemic patients with history of gout and acute knee effusion.

The etiology of arthritis episodes in normouricemic patients with gout is still unclear. We propose that the fluctuation in synovial urate level, as well as pH, ion strength, albumin, and globulin values relative to serum levels, could be involved in crystal formation. To assess serum-synovial gradient (SSG), the sera and synovial fluid (SF) of six normouricemic patients (men, age 48-79) with a history of gout (American College of Rheumatology criteria) and acute knee effusion were screened for uric acid, pH, osmolality (Osm), P/Ca, albumin, globulin, and SSG. Monosodium urate monohydrate (MSUM) crystals were determined by polarized light (PL). Infectious arthritis was ruled out via Gram staining and synovial fluid culture. Negative X-ray and PL microscopy results excluded chondrocalcinosis. Five patients (1-5) had inflammatory knee effusion (WBC >2,000/mm(3)), and one (patient 6) had noninflammatory knee effusion (600 WBC/mm(3)). MSUM crystals were found in the WBC of patient 1 only. He had tophaceous gout with normal serum uric acid levels and showed significant negative Osm and P and positive Ca SSG. Two crystal negative patients had severe negative pH SSG with alkaline synovial fluid, significant P/Ca SSG, and high positive globulin SSG, while one of them had supersaturated SF uric acid content. The other patients displayed an increased Osm and P/Ca SSG. All SSG values were five to ten times higher than the coefficient of variance for used methods. Noninflammatory SF of patient 6 does not appear to be related to active gout. The data on SSG for MSUM, pH, Osm, Alb/Glob, and P/Ca in normouricemic patients with gout history and acute knee effusion was not homogeneous. We propose that acid-base and ionic-protein gradient may lead to instability of subsaturated urate solution, thereby predisposing to MSUM deposits within synovial membrane and inducing inflammation.

A case of calcium pyrophosphate dihydrate crystal deposition disease presenting as an acute polyarthritis.

We report a case of calcium pyrophosphate dihydrate crystal deposition disease (CPDD) presenting as an acute polyarthritis. A 66-yr-old woman was admitted with a 5-day history of fever and multiple joint pain including wrists, elbows, shoulders, knees, and ankles developed 5 days before admission. Her plain radiographs of wrists, elbows, shoulders, knees, and ankles showed chondrocalcinosis. The pubic symphysis, lumbar intervertebral discs, and both hip joints, which were asymptomatic, also had calcium deposits. The compensated polarized microscopic examination of the joint fluid, aspirated from the right knee revealed intracellular and extracellular weakly positive birefringent crystals, confirming the CPDD. This case showed that CPDD may manifest as an acute polyarthritis mimicking acute onset rheumatoid arthritis.

Acute pseudogout mimicking septic arthritis following urologic manipulation.

An 80-year-old man presented with an acute, rapidly worsening synovitis with a hot effusion of the right knee approximately 48 hours following a urologic procedure. Initial aspirates failed to reveal crystals and suggested an acute infectious arthritis. Because his course continued to deteriorate despite adequate antibiotic treatment, the patient underwent arthroscopy in order to place tubes and to effect adequate irrigation and debridement. The preoperative diagnosis was septic arthritis. At the time of arthroscopy, there was gross evidence of crystals that were subsequently diagnosed as calcium pyrophosphate. This case illustrates the importance of an adequate differential diagnosis and the usefulness of the arthroscope in obtaining adequate tissue and aspirate under confusing circumstances.

Arthrocentesis

Synovial Fluid Analysis Patients with a fever, suspected flare of existing arthritis, or unknown cause of joint effusion should undergo arthrocentesis with synovial fluid analysis. Samples of synovial fluid can be analyzed for gross appearance, presence of crystals, white blood cell count with differential, red blood cell count, and bacterial culture. Normal synovial fluid should not have any cells or crystals present and should appear colorless and clear.

Advanced erosive gout as a cause of Fever of unknown origin.

A 61-year-old man was referred to our hospital due to a 3-month history of fever of unknown origin, and with right knee and ankle joint pains. At another hospital, extensive investigations had produced negative results, including multiple sterile cultures of blood and joint fluids, and negative autoantibodies. His serum uric acid level was not elevated. However, after admission to our hospital, we performed right knee arthrocentesis, which revealed uric acid crystals. These findings, combined with the results of imaging tests, which showed joint degeneration, led to a diagnosis of advanced erosive gout. After receiving a therapeutic non-steroidal anti-inflammatory drug and a maintenance dose of colchicine for prophylaxis against recurrence, the patient's symptoms subsided and did not return. Advanced erosive gout should be considered a possible cause of fever of unknown origin and diagnostic arthrocentesis should be performed in patients with unexplained arthritis.

Painful knee locking caused by gouty tophi successfully treated with allopurinol.

A 67-year-old man presented to a rheumatology clinic with a 1-week history of severe pain and swelling of his right knee. He had been receiving allopurinol for about 5 months for the treatment of chronic gouty arthropathy of more than 30 years' duration. On examination, his right knee was warm and swollen. The aspirated fluid contained intracellular and extracellular monosodium urate crystals, but Gram staining and culture were negative. The affected knee was injected with triamcinolone, but the patient continued to experience severe pain and complained of locking of the knee 3 weeks after the onset of his initial symptoms. Physical examination at this time showed no sign of inflammation, but the knee had a very limited range of motion. Physical examination; routine laboratory investigations, including CBC, complete metabolic panel, measurement of serum uric acid levels, and synovial fluid analysis; radiological investigations, including radiography of the right knee and CT of the right knee with intra-articular contrast. CT showed no internal derangement, but revealed extensive intra-articular and extra-articular amorphous soft tissue calcifications, compatible with gouty tophi. The patient declined an arthroscopic procedure to remove the gouty tophi. Treatment consisted of continuous allopurinol therapy and narcotics for symptomatic pain relief. Over the next 12 months, the patient's serum uric acid levels, and presumably his total-body urate pool, were substantially reduced. The knee unlocked and the pain subsided. Follow-up CT about 3 years after the initial examination showed complete resolution of the calcified intra-articular and extra-articular tophi.

20 Years of Radiographic Imaging: Crystalline Deposits Causing Severe Arthropathy and Erosions.

Urate crystal gout arthritis and calcium pyrophosphate deposition disease (CPPD) are crystalline arthropathies seen in middle age to elderly patients, but are also seen in the active duty military population. Flares of either can be identified by acute joint pain, associated swelling, tenderness, and warmth. Definitive diagnosis involves synovial analysis from arthrocentesis. Gout and CPPD are common inflammatory joint diseases. Both arthropathies presenting themselves in the same joint are rather rare. An elderly female with a history of gout presented to the hospital with severe hip pain. She was on urate-lowering therapy at the time, and uric acid levels on admission were not significantly elevated. Radiographic imaging of her hip demonstrated periarticular cartilage calcifications. A review of radiographic imaging over the last 20 years found significant erosive arthropathy in multiple joints and radiographic evidence of chondrocalcinosis, suggesting CPPD. Synovial analysis was not obtained during this admission as the patient declined procedures due to her elderly age. Her condition improved with oral steroids. Few literatures have demonstrated that gout and CPPD are common crystal arthropathies that can occur concomitantly in the same joint. A 20-year review of imaging in an elderly female with known gout arthropathy found that she had radiographic evidence of concomitant CPPD-associated damage to many of her joints. Clinicians should be aware of the different erosive arthropathies, their corresponding imaging findings, evaluation for underlying metabolic disorders if appropriate, and the possibility that they may occur in the same joint. Early prevention can reduce joint destruction later in life.

Diagnosing acute monoarthritis in adults: a practical approach for the family physician.

Acute monoarthritis can be the initial manifestation of many joint disorders. The first step in diagnosis is to verify that the source of pain is the joint, not the surrounding soft tissues. The most common causes of monoarthritis are crystals (i.e., gout and pseudogout), trauma, and infection. A careful history and physical examination are important because diagnostic studies frequently are only supportive. Examination of joint fluid often is essential in making a definitive diagnosis. Leukocyte counts vary widely in septic and sterile synovial fluids and should be interpreted cautiously. If the history and diagnostic studies suggest an infection, aggressive treatment can prevent rapid joint destruction. When an infection is suspected, culture and Gram staining should be performed and antibiotics should be started. Light microscopy may be useful to identify gout crystals, but polarized microscopy is preferred. Blood tests alone never confirm a diagnosis, and radiographic studies are diagnostic only in selected conditions. Referral is indicated when patients have septic arthritis or when the initial evaluation does not determine the etiology.

Markedly elevated intra-articular white cell count caused by gout alone.

Joint pain accompanied by erythema, swelling, and decreased range of motion is concerning for septic arthritis and typically warrants joint aspiration. The synovial fluid white blood cell count plays a central role in the decision-making process regarding these patients. Traditional teaching holds that a cell count greater than 50,000 white blood cells/µL is likely caused by infection and therefore warrants either operative intervention or serial aspiration. This report describes 2 patients with extremely high synovial fluid white blood cell counts in the absence of infection. Case 1 involved a 59-year-old man who presented to the emergency department with sudden onset of atraumatic left elbow pain and was found to have a white blood cell count of 168,500 white blood cells/µL on joint aspiration and innumerable monosodium urate crystals. The patient ultimately improved with treatment with oral prednisone, avoiding operative intervention. Case 2 involved a 69-year-old man who presented to the emergency department with acute onset of atraumatic left knee pain. On arthrocentesis, the patient had a cell count of 500,000 white blood cells/µL and was therefore taken to the operating room for arthroscopic irrigation and debridement. Final analysis of the synovial fluid showed monosodium urate crystals and negative culture findings. These cases illustrate the highest synovial fluid white blood cell count reported in patients with gout and highlight the potential difficulty in differentiating between acute gout and septic arthritis in the setting of markedly elevated white blood cell count.

[Fever of unknown origin as a sign of calcium pyrophosphate deposition disease].

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease may manifest clinically as septic fever (40 degrees C), acute pseudogout attack of knee, wrist and shoulders, or as a variety of patterns of chronic inflammatory or degenerative joint disease. The association of pseudogout with fever is less widely recognised and may lead to over-investigation, delay in appropriate treatment and disproportionate costs. We report on a 67-year-old woman with a history of recurrent episodes of fever and polyarthritis every 2 months for the last 3 years. Because of this she was hospitalised several times, finally with suspected culture-negative endocarditis, and was treated for 6 weeks with gentamicin, rifampicin and vancomycin. During this therapy the patient again developed septic fever and acute arthritis of the right wrist. Radiographs of the wrist, knee and symphysis pubis revealed prominent chondrocalcinosis and destructive arthropathy.

Arthrocentesis

Arthrocentesis, or joint aspiration, is the clinical procedure performed to diagnose and, in some cases, treat musculoskeletal conditions. The procedure entails using a syringe to collect synovial fluid from or inject medication into the joint capsule. Laboratory analysis of synovial fluid can further help characterize the diseased joint and distinguish between gout, arthritis, and synovial infections such as septic arthritis. Uses In general, arthrocentesis should be strongly considered if there is suspected trauma, infection, or effusion of the joint. Diagnostic Arthrocentesis can be used to diagnose septic arthritis or crystal arthropathy. In the case of a septic joint, arthrocentesis should preferably be performed prior to starting treatment with antibiotics, in order to ensure a proper sample of synovial fluid is obtained.

A 3-day delay in synovial fluid crystal identification did not hinder the reliable detection of monosodium urate and calcium pyrophosphate crystals.

Arthrocentesis is an essential emergency step in managing patients with acute arthritis. To identify a bacterial infection, Gram staining is performed promptly. However, crystal analysis may not be immediately performed in many facilities. Being considered not to be stable over time, synovial fluid (SF) is sometimes discarded instead of being stored for crystal identification. The aim of this study was to assess the detectability of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in SF over a period of 3 days. Consecutive SF samples from 75 joints were analyzed for MSU, CPP crystals, and pH. Two independent observers evaluated the samples by regular light and polarization microscopy immediately after arthrocentesis and after 1, 2, and 3 days at room temperature or at 4°C. Of 75 samples, 27 contained crystals (16 MSU, 6 CPP, 5 both); semiquantitative counts of both MSU and CPP crystals did not change significantly after 3 days. There was no new formation of crystals in any of the crystal-negative samples, which was independent of the storage temperature. Synovial fluid pH was not predictive of crystals and did not change over time. Although immediate workup for microbiology, including Gram stain and culture, is indispensable and well established, crystal analysis may at times not be immediately performed. Our study suggests that when crystal identification cannot be done immediately, it can be safely performed up to 3 days after arthrocentesis when SF is stored at 4°C or even at stable room temperature (20°C).

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.

Knee Arthrocentesis -- Clinical Significance

Crystal analysis is usually an important result of a successful knee aspiration. The clinician commonly differentiates gout (negatively birefringent urate crystals), pseudogout (weakly positive birefringent crystals), and an infectious process. [7] Synovial fluid associated with septic or infectious joint effusion is as follows:

Gout-induced arthropathy after total knee arthroplasty: a report of two cases.

Gout, although relatively rare in joint replacements, can present as an acute or chronic painful knee or hip arthroplasty. Gout and acute infection of a joint replacement can be difficult to differentiate, with the physical examination and laboratory study results frequently being similar. Both conditions can present with a rapid onset of joint pain, swelling, erythema, and constitutional symptoms, including fevers and malaise. Laboratory findings in both conditions often include an elevated leukocyte count, erythrocyte sedimentation rate, and C-reactive protein level. Negatively birefringent, needle-shaped crystals in the synovial fluid confirm the diagnosis of gout. The mistaken diagnosis of septic arthritis in a joint replacement with crystal-induced synovitis can lead to inappropriate open debridement or component removal. The current study includes a review of the literature and presents two cases of gout after total knee arthroplasty. These cases suggest that in situations of suspected sepsis without synovial fluid crystals, operative intervention is indicated with a presumed diagnosis of septic arthritis. The identification of chalky white or yellow deposits in the synovium or bone is highly suggestive of gout. The definitive diagnosis is made by polarized light histologic evaluation of these tissues. If these deposits are present in the absence of a positive preoperative culture, positive Gram stain for bacteria, or component loosening, component retention is indicated.

InternalMed_Harrison

attacks, needle-shaped MSU crystals typically are seen both intracellularly and extracellularly (Fig. 395-1). With compensated polarized light, thesecrystalsarebrightlybirefringentwithnegativeelongation.Synovial fluid leukocyte counts are elevated from 2000 to 60,000/μL. Effusions appear cloudy due to the increased numbers of leukocytes. Large amounts of crystals occasionally produce a thick pasty or chalky joint fluid. Bacterial infection can coexist with urate crystals in synovial fluid; if there is any suspicion of septic arthritis, joint fluid must be cultured. MSU crystals also can often be demonstrated in the first metatarsophalangeal joint and in knees not acutely involved with gout. Arthrocentesis of these joints is a useful technique to establish the diagnosis of gout between attacks.

Pseudogout - a rare manifestation of hungry bone syndrome after focused parathyroidectomy.

Pseudogout, also known as calcium pyrophosphate deposition disease, is a rheumatological condition arising from accumulation of calcium pyrophosphate dihydrate crystals in connective tissues. We present a case of a 56-year-old Bangladeshi woman who underwent focused right inferior parathyroidectomy for primary hyperparathyroidism from a right inferior parathyroid adenoma. On the first post-operative day, she complained of left elbow painful swelling with redness and warmth. Arthrocentesis of left elbow was done due to suspicion of septic arthritis. Two weeks prior to this surgery, she had sudden bilateral knee swelling was diagnosed in her home country of bilateral knee osteoarthritis with effusion and arthrocentesis showed no crystals. Aspiration of left elbow showed calcium pyrophosphate crystals, associated with post parathyroidectomy hypocalcemia, hypomagnesemia confirming pseudogout. Her uric acid level was normal. Bilateral wrist x-rays showed triangular fibrocartilage complex chondrocalcinosis. The patient's condition improved with colchicine and naproxen, as well as calcium and magnesium replacement. Her left elbow swelling and pain resolved. Pseudogout flare is a rare but known sequelae after parathyroidectomy. Early recognition and expeditious treatment is essential.

Synovial fluid

Monosodium urate crystals are seen in gout or gouty arthritis and appear as needle-shaped negatively birefringent crystals varying in length from 2 to 20 μm. With negative birefringence, the crystals appear yellow in parallel light and blue with perpendicular light. Calcium pyrophosphate crystals are seen in pseudogout (also known as calcium pyrophosphate deposition disease or, CPPD). These crystals are rod-shaped or rhomboids varying in length from 2 to 20 μm and with positive birefringence (blue with parallel light, yellow with perpendicular light). Hydroxyapatite crystals are small and negatively birefringent. They are usually only detectable with an Alizarin Red S stain. Corticosteroid crystals may be seen following therapeutic corticosteroid injection into the joint space. They appear blunt, jagged, and show variable birefringence. Cracking joints

Inflammatory Arthritis -- Evaluation -- Synovial Fluid Analysis

Aspiration of the synovial fluid and detailed analysis is critical in the evaluation of inflammatory arthritis. Synovial fluid shall be analyzed for total cell counts and differential, polarized light microscopy, Gram stain and cultures, and fungal/AFB cultures when appropriate. Total cell counts are usually less than 2000 cells/mm3 in non-inflammatory arthritis and more than 5000 cells/mm^3 in inflammatory arthritis. A total cell count of more than 50,000 cells/mm^3 cells and/or more than 90% neutrophils have a strongly positive likelihood ratio of being associated with septic arthritis, although it can present in acute gout or pseudogout as well. Septic arthritis and crystalline arthropathies usually have neutrophilic predominance, while rheumatoid arthritis usually has lymphocytic predominance in the synovial fluid.  Monosodium urate crystals on polarized light microscopy are needle-shaped and strongly negatively birefringent. Calcium pyrophosphate crystals on polarized light microscopy or rhomboid-shaped and weakly positively birefringent. Basic calcium phosphate crystals are not visible on polarized light microscopy and need special staining for visualization.

Crystal-induced arthritis after arthroplasty: 7 cases.

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

Calcium pyrophosphate dihydrate crystal deposition disease

Arthrocentesis, or removing synovial fluid from the affected joint, is performed to test the synovial fluid for the calcium pyrophosphate crystals that are present in CPPD. When stained with H&E stain, calcium pyrophosphate crystals appears deeply blue ("basophilic"). However, CPP crystals are much better known for their rhomboid shape and weak positive birefringence on polarized light microscopy, and this method remains the most reliable method of identifying the crystals under the microscope. However, even this method suffers from poor sensitivity, specificity, and inter-operator agreement. These two modalities currently define CPPD disease, but lack diagnostic accuracy. Thus, the diagnosis of CPPD disease is potentially epiphenomenological.

Joint aspiration and injection and synovial fluid analysis.

Joint aspiration/injection and synovial fluid (SF) analysis are both invaluable procedures for the diagnosis and treatment of joint disease. This chapter addresses: (1) the indications, the technical principles and the expected benefits and risks of aspiration and injection of intra-articular corticosteroid; and (2) practical aspects relating to SF analysis, especially in relation to crystal identification. Intra-articular injection of long-acting insoluble corticosteroids is a well-established procedure that produces rapid pain relief and resolution of inflammation in most injected joints. The knee is the most common site to require aspiration, although any non-axial joint is accessible for obtaining SF. The technique requires a knowledge of basic anatomy and should not be unduly painful for the patient. Provided sterile equipment and a sensible, aseptic approach are used, it is very safe. Analysis of aspirated SF is helpful in the differential diagnosis of arthritis and is the definitive method for diagnosis of septic arthritis and crystal arthritis. The gross appearance of SF can provide useful diagnostic information in terms of the degree of joint inflammation and presence of haemarthrosis. Microbiological studies of SF are the key to the confirmation of infectious conditions. Increasing joint inflammation is associated with increased SF volume, reduced viscosity, increasing turbidity and cell count, and increasing ratio of polymorphonuclear: mononuclear cells, but such changes are non-specific and must be interpreted in the clinical setting. However, detection of SF monosodium urate and calcium pyrophosphate dihydrate crystals, even from un-inflamed joints during intercritical periods, allow a precise diagnosis of gout and of calcium pyrophosphate crystal-related arthritis.