MAUDE Adverse Event Report: GENZYME BIOSURGERY (RIDGEFIELD) HYLAN G-F 20; INTRA-ARTICULAR HYALURONIC ACID

Device Problem Insufficient Information (3190)

Patient Problems Arthritis (1723); Hemorrhage/Bleeding (1888); Inflammation (1932); Pain (1994); Synovitis (2094); Discomfort (2330)

Event Date 01/01/2016

Event Type  Injury  

Event Description

Upon internal review on 07-dec-2016, suspect drug was updated from hyaluronic acid to synvisc (hylan g-f 20).Also, the modifier was updated from unknown to injection.This unsolicited literature case from united states was received on 02-dec-2016 from health care professional via full article: korsh jm, bassett wp, polakoff dr.Late hemorrhagic pseudoseptic arthritis encountered during total knee arthroplasty due to hyaluronic acid viscosupplementation.Arthroplast.Today.2016 dec 01; 2(4):165-69.Doi: 10.1016/j.Artd.2016.08.006 this case concerns a (b)(6)female who received treatment with synvisc (hylan g-f 20) and later after unknown latency experienced hemorrhagic pseudoseptic arthritis.Patient reported having tried acetaminophen, various nonsteroidal anti-inflammatory drugs, narcotics, and topical medications over the past 8 months.All failed to provide any relief.Patient related constant, debilitating pain when walking, kneeling, and going up or down the stairs that has acutely worsened.Patient's past medical history included asthma and hyperlipidemia.Patient only medication was simvastatin.Patient has no known medical allergies.Patient social history included infrequent alcohol use, and was a nonsmoker.On an unknown date in 2016, patient initiated treatment with synvisc injections (orthovisc), weekly (dose, form, route, lot number and expiry date: not provided) for osteoarthritis.It was reported that there was no effusion or acute inflammatory reaction after these initial hyaluronic acid (ha) injections.Patient's physical examination revealed an overweight female with a body mass index of 29 kg/m2.Patient had an antalgic gait.The dermis overlying her right knee was intact without erythema or warmth.Patient knee examination revealed a moderate effusion, diffuse tenderness to palpation, and palpable crepitation during passive range of motion.Goniometer assessment exhibited a 20 degree flexion contracture, and maximal flexion was limited to 90 degree.Strength testing limited by pain but discernibly intact for age.Mechanical alignment showed a valgus deformity.Weight bearing radiographs were obtained, which showed severe tricompartmental arthritis.Taking into consideration patient's history of knee injections and the severity of her symptoms, inflammatory markers were obtained to rule out infectious or other inflammatory etiology.Patient's white blood cell (wbc) count and c-reactive protein (crp) were within normal limits at 5.9 x 109 per liter and <0.5 mg/dl, respectively; erythrocyte sedimentation rate (esr) was found to be slightly elevated at 38 mm/h.The decision was made to proceed with total knee arthroplasty (tka).It was reported that in the operating room, the knee was prepped and draped in the usual sterile fashion.Preoperative antibiotics consisting of 2 grams cefazolin were administered before skin incision.A 12-cm longitudinal incision was made through the skin centered over the patella.A medial parapatellar arthrotomy was performed, which revealed a significant effusion of purulent fluid.On an unknown date, after unknown latency, patient experienced hemorrhagic pseudoseptic arthritis during tka due to hyaluronic acid viscosupplementation.It was reported that marked synovitis was noted.Eversion of the patella reveled large areas of blackened articular cartilage on both the femoral condyles and underside of the patella.An intraoperative pathology consult was obtained.Frozen section histopathology showed greater than 5 neutrophils per high-powered field.Specimens were obtained, and the decision was made to abort the knee replacement and instead perform an irrigation, synovectomy, and closure.Postoperatively, the patient was placed on cefazolin for 3 days pending tissue and fluid cultures.All final cultures were negative, and antibiotics were discontinued before discharge.Postoperative inflammatory markers were obtained: wbc count was 8.1 x 109 per liter, esr was 53 mm/h, crp was 14.1 mg/dl.Permanent histopathology showed synovial tissue with marked chronic inflammation, focal acute inflammation, and old hemorrhage.There were also abundant histiocytes containing foreign material.Following the initial procedure, 2 months later, the patient's inflammatory markers had normalized: wbc was 6.3 x 109 per liter, esr was 25 mm/h, and crp was <0.5 mg/dl.On an unknown date, arthrocentesis was done, and the synovasure (zimmer) panel for native septic arthritis was negative.The patient was taken for an uncomplicated tka 3 months postoperative.It was reported that synovium, cartilage, and bone were sent to pathology for special consideration.The specimens showed proliferative synovium with brown pigment (hemosiderin) in the stroma and inflammation around foreign material.Prussian blue stain showed hemosiderin (iron deposition) in the synovium and cartilage.Foreign body material was seen in synovial giant cells at the various foci of inflammation.This foreign body material was shown to be hyaluronate on alcian blue staining.It was stated that patient was seen 2 weeks after tka for staple removal.The incision was clean, dry, and non-erythematous.Patient's pain was well controlled.Patient was fully weight bearing and advancing well with outpatient physical therapy with improved range of motion.At the time of manuscript, the patient was doing well 6 months after tka.Triad of findings included acute and chronic inflammatory cells on frozen section, synovitis with hemosiderin deposition and blackened cartilage with iron deposition on permanent histopathology.Histopathology revealed foreign body granulomatous inflammation consistent with previous reports of acute, adverse inflammatory reactions to ha.Corrective treatment: irrigation; synovectomy.Outcome: unknown.Reporter causality description: late hemorrhagic pseudoseptic arthritis due to ha viscosupplementation seriousness criteria: important medical event additional information was received on 07-dec-2016.Patient age and gender was added.Product start date and frequency was added.Synovitis and effusion were added as symptom of hemorrhagic pseudoseptic arthritis.Medical history, past drugs and concomitant medication was added.Clinical course updated and text amended accordingly.Upon internal review on 07-dec-2016, suspect drug was updated from hyaluronic acid to synvisc (hylan g-f 20).Also, the modifier was updated from unknown to injection.

Event Description

Upon internal review on 07-dec-2016, suspect drug was updated from hyaluronic acid to synvisc (hylan g-f 20).Also, the modifier was updated from unknown to injection.This unsolicited literature case from united states was received on 02-dec-2016 from health care professional via full article: korsh jm, bassett wp, polakoff dr.Late hemorrhagic pseudoseptic arthritis encountered during total knee arthroplasty due to hyaluronic acid viscosupplementation.Arthroplast.Today.2016 dec 01; 2(4):165-69.Doi: 10.1016/j.Artd.2016.08.006 this case concerns a (b)(6) female who received treatment with synvisc (hylan g-f 20) and later after unknown latency experienced hemorrhagic pseudoseptic arthritis.Patient reported having tried acetaminophen, various nonsteroidal anti-inflammatory drugs, narcotics, and topical medications over the past 8 months.All failed to provide any relief.Patient related constant, debilitating pain when walking, kneeling, and going up or down the stairs that has acutely worsened.Patient's past medical history included asthma and hyperlipidemia.Patient only medication was simvastatin.Patient has no known medical allergies.Patient social history included infrequent alcohol use, and was a non-smoker.On an unknown date in 2016, patient initiated treatment with synvisc injections (orthovisc), weekly (dose, form, route, lot number and expiry date: not provided) for osteoarthritis.It was reported that there was no effusion or acute inflammatory reaction after these initial hyaluronic acid (ha) injections.Patient's physical examination revealed an overweight female with a body mass index of 29 kg/m2.Patient had an antalgic gait.The dermis overlying her right knee was intact without erythema or warmth.Patient knee examination revealed a moderate effusion, diffuse tenderness to palpation, and palpable crepitation during passive range of motion.Goniometer assessment exhibited a 20 degree flexion contracture, and maximal flexion was limited to 90 degree.Strength testing limited by pain but discernibly intact for age.Mechanical alignment showed a valgus deformity.Weight bearing radiographs were obtained, which showed severe tricompartmental arthritis.Taking into consideration patient's history of knee injections and the severity of her symptoms, inflammatory markers were obtained to rule out infectious or other inflammatory etiology.Patient's white blood cell (wbc) count and c-reactive protein (crp) were within normal limits at 5.9 x 109 per liter and <0.5 mg/dl, respectively; erythrocyte sedimentation rate (esr) was found to be slightly elevated at 38 mm/h.The decision was made to proceed with total knee arthroplasty (tka).It was reported that in the operating room, the knee was prepped and draped in the usual sterile fashion.Preoperative antibiotics consisting of 2 grams cefazolin were administered before skin incision.A 12-cm longitudinal incision was made through the skin centered over the patella.A medial parapatellar arthrotomy was performed, which revealed a significant effusion of purulent fluid.On an unknown date, after unknown latency, patient experienced hemorrhagic pseudoseptic arthritis during tka due to hyaluronic acid viscosupplementation.It was reported that marked synovitis was noted.Eversion of the patella reveled large areas of blackened articular cartilage on both the femoral condyles and underside of the patella.An intraoperative pathology consult was obtained.Frozen section histopathology showed greater than 5 neutrophils per high-powered field.Specimens were obtained, and the decision was made to abort the knee replacement and instead perform an irrigation, synovectomy, and closure.Postoperatively, the patient was placed on cefazolin for 3 days pending tissue and fluid cultures.All final cultures were negative, and antibiotics were discontinued before discharge.Postoperative inflammatory markers were obtained: wbc count was 8.1 x 109 per liter, esr was 53 mm/h, crp was 14.1 mg/dl.Permanent histopathology showed synovial tissue with marked chronic inflammation, focal acute inflammation, and old hemorrhage.There were also abundant histiocytes containing foreign material.Following the initial procedure, 2 months later, the patient's inflammatory markers had normalized: wbc was 6.3 x 109 per liter, esr was 25 mm/h, and crp was <0.5 mg/dl.On an unknown date, arthrocentesis was done, and the synovasure (zimmer) panel for native septic arthritis was negative.The patient was taken for an uncomplicated tka 3 months postoperative.It was reported that synovium, cartilage, and bone were sent to pathology for special consideration.The specimens showed proliferative synovium with brown pigment (hemosiderin) in the stroma and inflammation around foreign material.Prussian blue stain showed hemosiderin (iron deposition) in the synovium and cartilage.Foreign body material was seen in synovial giant cells at the various foci of inflammation.This foreign body material was shown to be hyaluronate on alcian blue staining.It was stated that patient was seen 2 weeks after tka for staple removal.The incision was clean, dry, and non-erythematous.Patient's pain was well controlled.Patient was fully weight bearing and advancing well with outpatient physical therapy with improved range of motion.At the time of manuscript, the patient was doing well 6 months after tka.Triad of findings included acute and chronic inflammatory cells on frozen section, synovitis with hemosiderin deposition and blackened cartilage with iron deposition on permanent histopathology.Histopathology revealed foreign body granulomatous inflammation consistent with previous reports of acute, adverse inflammatory reactions to ha.Corrective treatment: irrigation; synovectomy outcome: unknown a pharmaceutical technical complaint was initiated with global ptc number: 45866 the product lot number was not provided; therefore, a batch record review was not possible.Based on the lack of information provided, no capa was required.It was the requirement to review all finished batch records for specification conformance prior to release.Any out of specification result was identified and mitigated through the ncr process.Sanofi global pharmacovigilance and epidemiology continuously monitored adverse event reports with or without lot numbers, and assessed possible associations with their corresponding product lot, as part of routine safety surveillance effort to detect safety signals.This review had not indicated any safety issue.Sanofi will continue to monitor adverse events to determine if a capa is required.Reporter causality description: late hemorrhagic pseudoseptic arthritis due to ha viscosupplementation seriousness criteria: important medical event.Additional information was received on 07-dec-2016.Patient age and gender was added.Product start date and frequency was added.Synovitis and effusion were added as symptom of hemorrhagic pseudoseptic arthritis.Medical history, past drugs and concomitant medication was added.Clinical course updated and text amended accordingly.Upon internal review on 07-dec-2016, suspect drug was updated from hyaluronic acid to synvisc (hylan g-f 20).Also, the modifier was updated from unknown to injection.Additional information was received on 19-dec-2016.Global ptc number and results were added.Text was amended accordingly.

• Brand Name: HYLAN G-F 20
• Type of Device: INTRA-ARTICULAR HYALURONIC ACID
• Manufacturer (Section D): GENZYME BIOSURGERY (RIDGEFIELD); 1125 pleadantview terrace; ridgefield NJ 07657
• Manufacturer Contact: heather schiappacasse ; 55 corporate drive; 55b-220a; bridgewater, NJ 08807 ; 9089817289
• MDR Report Key: 6201962
• MDR Text Key: 63189197
• Report Number: 2246315-2016-00184
• Device Sequence Number: 1
• Product Code: MOZ
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: P940015
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: health professional,literatur
• Reporter Occupation: Health Professional
• Type of Report: Initial,Followup
• Report Date: 12/02/2016

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 12/23/2016
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Other
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 12/19/2016
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Is the Device Single Use?: Yes
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Treatment: ACETAMINOPHEN(CON.); CEFAZOLIN(CON.); SIMVASTATIN(PREV.)
• Patient Outcome(s): Required Intervention
• Patient Age: 70 YR