A 15-day follow up report received 8/7/2003 adds: Report A0344264A (formerly 2001005626-1) describes rheumatoid arthritis in a 65-year-old male who received Lyme disease vaccine recombitant OspA (Lymerix). This report was received from the pt. Additional info was received as part of litigation proceedings, with forwarding of medical records. The pt reported that he had been active in playing golf, hunting, fishing, camping, traveling and gardening, along with caring for his 4 grandchildren, ages 4 to 9 until April 2000. Until April 2000 he had reportedly been in "excellent health". He had no known allergies. Medical records indicated that his medical history included tinea versicolor, diet-controlled hyperglycemia, hypercholesterolemia, hypertriglyceridemia, hemorrhoids, Dupuytren's contracture of the hands (1997), hand stiffness, osteoarthritis of the lower back and flat feet. The pt sustained a skull fracture during a motor vehicle accident in the 1950's. HLA-DR analysis by polymerase chain reaction (PCR) on 11/01/2000 was negative for HLA-DR4 and HLA-DR2. There were no known drug allergies. Surgical history included Dupuytren's contracture surgery "years ago", hemorrhoidectomy (1955), radical excision of plantar fibromatosis of the right foot (02/18/1998) and arthroplasty of a deformed 5th digit on the right foot (02/18/1998). Concurrent medications included vitamin E, metoprolol tartrate (Lopressor), nitroglycerine (Nitropaste), atorvastatin calcium (Lipitor), diltiazem hydrochloride (Tiazac), acetylsalicylic acid, isosorbide mononitrate (Imdur) and magnesium. The pt was a former smoker for 20 years (quit approx 1966). He had asbestos exposure in the past. He drank 3 to 4 beers and "2 cocktails" a week on average. A 15-day follow up report received 10/15/2003 adds: Following the reported onset of rheumatoid arthritis, the pt experienced hypertension, atypical chest pain, coronary artery disease, mitral annular calcification, "mild" aortic sclerosis without stenosis, "1+" mitral regurgitation, "1+" aortic regurgitation, paroxysmal supraventricular tachycardia, atypical pneumonia, and a tear of the left achilles tendon. These were not reported as adverse events due to vaccine administration, but were found during the course of review of the pt's medical records. Theyfore, they are not listed as adverse events. The pt reported that he received his 1st and 2nd injections of Lymerix in April 1999 and May 1999, respectively. He stated that he had no adverse events following receipt of these injections. He reported that he received his 3rd injection of Lymerix on 04/18/2000. He claimed that within a few days, he developed progressive fatigue, weakness, and gradually increasing shortness of breath. The pt also noted that one week after the 3rd injection, he "couldn't get out of bed" with stiffness in his hips, neck ankle and knees. He reportedly could not close his hands to make a fist. His stiffness had improved "slightly over the months", but he still had "stiff joints, mainly in (his) knees, ankles and hands." The pt stated, "My latest blood work has shown no inflammation in my system now." On 02/11/2002, in a Statement of Injuries, the pt's attorney alleged that the pt "suffers from joint pain and fatigue. He also suffers from fibromyalgia." The following info was obtained from medical records. Laboratory analyses performed on 05/03/2000 revealed Lyme total antibodies to total immunoglobulins index, measured by EIA, 7.96; rheumatoid arthritis (RA) factor 108.9 IU/mL, erythrocyte sedimentation rate (ESR) 43 mm/hr, and rapid plasma reagin (RPR) non-reactive. On 05/22/2000, Lyme total antibodies to total immunoglobulins index, measured by EIA, was 10.31. Western blot analyses for Lyme IgG and IgM were negative. The pt was seen by a rheumatologist on 06/08/2000 to be evaluated for a "relatively acute onset of articular pain that happened in April. He seems to correlate the onset of this articular involvement with a 3rd dose of Lyme vaccine. Since then he has been presenting morning stiffness. swelling and pain in the small and large articulations. He has also been having difficulty sleeping, tossing and turning, and waking up during the night secondary to pain. He mainly refers that the shoulder area and the muscles in the proximal portion of the arms is what hurts. Although, in the past he has also had problems with the elbows, hands, knees and feet. The pt refers that at times the swelling is severe and the stiffness is more prevalent in the morning that lasts between one and two hours, but lately all of the symptoms have become a little bit better since he started on Celebrex (celecoxib)." The rheumatologist noted that the medical history was "Remarkable for contraction of the hands. Foot surgery on the right foot in the past and has a history of flat feet." Medications at the time of the evaluation included Celebrex 100 mg twice daily and vitamin E. Under review of systems, the rheumatologist wrote, "The only problem he is actually having is the diffuse arthralgias and myalgias and morning stiffness as described above. Also, he has sleep disturbances and some degree of fatigue associated with the discomfort that he is experiencing." On physical examination, blood pressure was 138/96 mmHg. "He has some stiffness and decrease in range of motion, mainly related to stiffness in the upper extremities - shoulders and elbows. In the hands he has some decrease of range of motion. There is no active or overwhelming synovitis of the wrists, MCPs (metacarpophalangeals), PIPs (proximal interphalangeals), or DIPs (distal interphalageals). In the lower extremities he had good range of motion of the lumbosacral spine, and knees and hips, though he has some elements of osteoarthritis in both knees. There is no evidence of synovitis in the knees, ankles, or feet. There is also some wasting of the muscles of the quadriceps muscles bilaterally. The muscle mass seems to have decreased recently. Impression: 1. Articular pain of unclear etiology, rule out rheumatoid arthritis. Certainly the possibility that this may be related to Lyme disease is raised by the correlation of the injections with the onset of symptoms." The rheumatologist prescribed a short, tapered course of prednisone and cyclobenzeprine (Flexeril) at bedtime. Laboratory analyses performed 06/08/2000 were significant for reduced red blood cell (RBC) count, hemoglobin and hematocrit (please see Laboratory Data section). C-reactive protein concentration was elevated. Total protein concentration was within the reference range, but gamma globulin was elevated. Protein electrophoresis indicated that "Gamma increased appears polyclonal on agarose gel". The pt returned to the rheumatologist on 06/29/2000. "Overall he is doing better on low doses of Prednisone. There is a decrease in the amount of articular pain. His inflammatory markers are still slightly elevated, but not as before. He has been noticed in the past to have positive rheumatoid factor as well. His Hemoglobin is 12 and Hematrocrit 35. C-reactive protein is 19." Medications at the time of this office visit included Celebrex 100 mg twice daily, Flexeril, prednisone 5 mg daily, and vitamin E. On physical examination, blood pressure was 150/80 mmHg. "Extremities were symmetrical without significant evidence of synovitis. Pt has good range of motion of articulations. There is some tightness in the lower extremities especially when squatting. IMPRESSION: 1) Articular pain probably RA." On 07/14/2000, RBC, hemoglobin, and hematocrit remained reduced. RA factor was elevated. Antinuclear antibody (ANA) titer was 1:80 (reported as "Borderline") with a speckled pattern. The pt was seen by the rheumatologist on 07/19/2000. "He had improved since the last visit but recently he had plateaued. He remains with significant articular discomfort. C-reactive protein is slightly elevated. Overall he is not feeling well. He is very frustrated and angry about the onset of symptoms. He blames this on the vaccines for Lyme's (sic) disease." On physical examination, blood pressure was 132.80 mmKg. "Extremities were symmetrical without significant evidence of synovitis. Pt has some fullness on the MCPs and wrists bilaterally. IMPRESSION: 1) Articular pain probably RA, secondary to inflammatory characteristics and positive rheumatoid factor." The rheumatologist added hydroxychlorouine (Plaquenil) 200 mg twice daily to the pt's medication regimen. The pt was seen by the rheumatologist on 09/06/2000. "He is doing better at this time. He is taking low doses of Prednisone and, secondary to a mild degree of inflammation, we'll start (him) on Plaquenil as well. He remains with some discomfort in the articulations, but, clearly, it is less than what he experienced in the past." Medications included Celebrex 100 mg twice daily, prednisone 5 mg daily, Plaquenil 200 mg twice daily, and vitamin E. On physical examination, blood pressure was 128/72 mmHg. "The extremities were symmetrical without evidence of synovitis. There was good range of motion and no significant problems were noticed today on exam. Impression: 1. Rheumatoid arthritis. 2. High risk medications." On 09/11/2000, the pt was seen by his primary care physician for a routine visit at which time he was found to be slightly short of breath and very tachycardic. The pt reported that he while golfing earlier that morning, he felt a little short of breath and felt chest discomfort which he thought was "indigestion". Physical exam revealed a pulse of 153 and a grade II/VI systolic ejection murmur. His lungs were clear. He was also noted to have good range of motion, pain in the right Achilles tendon, which was tendonitis, but no warmth or effusion at these joints. Some mild synovitis in the left knee was noted. Impression and Plan: Pt admitted to rule out possible myocardial infarction or unstable angina. He was treated (Nitro paste) and metoprolol (Lopressor) intravenously. Hydroxychloroquine sulfate (Plaquenil) and celecoxib (Celebrex) were held until there was no moreo evidence of arrhythmia. An electrocardiogram (ECG) ruled out a myocardial infarction and subsequent ECG's were normal. A Persantine Cardiolite stress test revealed anterior ischemia. Chest X-ray revealed "marked vascular congestion with possible inflammation at the left base. This could, however, simply represent a manifestation of the vascular congestion". The pt was discharged on 09/13/2000. Discharge diagnoses were supraventricular tachycardia converted to sinus rhythm, hypertension, rheumatoid arthritis, and coronary artery disease. Discharge medications included diltiazem HCl (Tiazac), enteric coated aspirin (Ecotrin) and isosorbide mononitrate (Imdur). The pt was seen by a cardiologist on 09/20/2000, for evaluation of the abnormal nuclear stress test. The cardiologist noted, "He is very active including fishing, hunting and walking the golf course without problems." Medications at that time included Celebrex 200 mg twice daily, hydroxychloroquine 200 mg twice daily, prednisone 5 mg daily, isosorbide mononitrate (Imdur) 30 mg daily, extended-release diltiazem (Tiazac) 120 mg daily, enteric-coated aspirin 500 mg daily, and vitamin E 800 units daily. On physical examination, blood pressure was 125/99 mmHg. On 11/01/2000, HLA-DR analysis by PCR did not demonstrate HLF-DR4 or HLA-DR2. On 11/20/2000, RBC, hemoglobin, and hematocrit remained reduced. C-reactive protein concentration was within the reference range. The pt returned to the cardiologist on 11/13/2000. The cardiologist noted, "He has been able to walk 18 holes of golf". Medications included atorvastatin (Lipitor) 10 mg daily, Celebrex 200 mg twice daily, hydroxychloroquine 200 mg twice daily, prednisone 5 mg daily, Tiazac 120 mg daily, aspirin 325 mg daily and vitamin E 800 units daily. Blood pressure was 134/84 mmHg. The pt returned to the rheumatologist on 12/06/2000. "Most recently the pt has had no elevation in inflammatory markers, but he remains with significant discomfort in the shoulders and soft tissues. He is getting increasingly frustrated by the amount of discomfort he is experiencing. He feels that the Lyme vaccine is the etiology for all these problems and is something that he could have avoided...He seems to be bothered also by the fact that despite our interventions and now that the inflammations are under control, he is not feeling better. On the contrary, he is hurting all over and feeling very tired." Medications at that time included Celebrex 200 mg twice daily, prednisone 5 mg daily, Plaquenil 200 mg twice daily, Lipitor 10 mg daily, Tiazac 120 mg daily, acetylsalicylic acid daily, and vitamin E. On physical examination, blood pressure was 170/100 mmHg. "The extremities were symmetrical without significant synovitis. There was soft tissue tenderness noted today on examination. Impression: 1. Rheumatoid arthritis. 2. Early stages of fibromyalgia. The pt seems to be very frustrated by the fact that he is not feeling better despite the amount of medications that he is taking. I am concerned that he seems to have a worsening of soft tissue tenderness and the fact that having negative inflammatory markers he remains with significant pain." The rheumatologist prescribed Flexeril at night. The pt was seen by the rheumatologist on 01/23/2001. The pt "comes for evalulation with a history of a positive rheumatoid factor associated with inflammation and was treated with Plaquenil and Prednisone initially with control of symptoms. Subsequently, he has developed persistent arthralgias and myalgias and significant fatigue. At this time, he refers that his articulations are "killing him". The amount of pain he's having is very dramatic. He is not comfortable with the current medications. He is growing increasingly frustrated due to the amount of pain and discomfort he experiences daily." On physical examination, blood pressure was 156/100 mmHg. "The extremities revealed no evidence of synovitis, no significant decrease in the range of motion although stiffness is noticed in the articulations. Impression: 1. Rheumatoid arthritis. 2. Early stages of fibromyalgia. 3. It is not clear how this correlates with the Lyme vaccine that he received in April 2000. Secondary to the fact that I have controlled the inflammation, I have treated him with tricyclics in an attempt to control what seems to be early stages of fibromyalgia. Since he is not doing better, I have discussed the possibility of referring him to the University Center for further treatment and for a second opinion." The pt was referred to the tertiary care center on 01/31/2001. The pt was evaluated by a physician at the tertiary care center on 03/22/2001. At that time, he reported that his symptoms began "several weeks" after his 3rd injection of Lymerix. On physical examination, the physician noted "tenderness and swelling of multiple large and small joints" and knee effusions. He noted no subcutaneous nodules or evidence of cutaneous vasculitis. The physician write, "I fee (the pt) definitely has rheumatoid arthritis and although he has been on low dose Prednisone, Plaquenil and Celebrex his disease remains very active and he has a high probability for the development of erosions, deformity and disability...I have recommended that he consider Remicade (infliximab) infusions. I also advised him about participating in a clinical trial currently being conducted using Remicade in early rheumatoid arthritis in Methotrexate naive individuals...of course treatment with more standard agent such as Methotraxate or Arava (leflunomide) remain a viable option." On 03/22/2001, rheumatoid factor and erythrocyte sedimentation rate were elevated. Hand x-rays revealed abnormalities. Analysis of synovial fluid aspirated from the left knee revealed an increased concentration of polymorphonuclear lymphocytes. Please see Laboratoy Data section. The vaccine provider made a telephone call to the pt on 04/02/2001, regarding a recent chest x-ray. In the office notes, the physician wrote, "Pt has increased intersitial markings on chest x-ray and will need follow-up with pulmonary consult...Also pt tells me he'll be in a research trial of MTX (methotrexate) and Remicade (infliximab) with ...rheumatologist at (the tertiary care center) for his R.A. Currently just taken off Plaquenil." On 04/17/2001, the pt presented to the ER complaints of "severe" shortness of breath that had progressively worsened since 04/16/2001, non-productive cough, and chills. The pt reported that he was "discharged from (another hospital) on 4/11 with diagnosis of rheumatoid arthritis/scar tissue on lung suspect secondary to Lyme vaccine". His nail beds were blue and his color was pale. While receiving 3 liters/minute of oxygen via nasal canula, oxygen saturation was 97%. The physician's impression was acute dyspnea and pulmonary fibrosis. The pt was given a single intravenous injection of methylprednisolone (SoluMedrol). He was discharged with portable oxygen and his daily dosage of prednisone was increased. The pt returned to the ER via ambulance on 04/23/2001 with a chief complaint of shortness of breath. The paramedic report stated that the pt was examined in his home for a chief complaint of shortness of breath. Paramedics administered nebulized albuterol and ipratropium as well as oxygen. During transport to the hospital, the pt's breathing became easier. At the hospital, the pt stated he was "recently to have fibrosis" in March of this year. He underwent a week long evaluation at (a tertiary care center). He was referred to see a pulmonologist. When he arrived for his outpatient evaluation he was tachycardic. He was hospitalized for "one week" at (the tertiary care center). The pt states that he had no bronchoscopic or thoracic lung biopsies. He did have a CT scan of the chest. He was due to be reevaluated for a "rheumatoid lung protocol at (another tertiary care center)." Since discharge from (the first tertiary care center), the pt has had progressive relentless dyspnea. This has been primarily breathlessness and not associated with cough, sputum production, or wheezing. He was seen (in the ER) approx 5 days ago and started on oxygen. Despite the initiation of oxygen, his dyspnea has continued to worsen. I carefully questioned the pt, his wife, and his daughter. They all feel this is a progressive process without any dramatic intercurrent deterioration. He is basically, "going downhill every day". The pt relates that his lung problem began following Lyme vaccination. Except for the pt's claim there is nothing to substantiate the relationship at this juncture." One of the consulting physicians noted that the pt "was felt, at least by (the 2nd tertiary care center) to have a rheumatoid lung as well back sometime late last year." On physical exam, the pt was dyspneic and his head, eyes, ears, nose and throat revealed mild cushingoid facies. Ascultation of the lungs revealed "diffuse velcro type rales" that did not clear with deep cough. Chest x-ray performed in the ER revealed "diffuse pulmonary fibrosis with a near, "white out," to the left lung." White blood cell count, eosinophil count, and platelet count were elevated. The physician's assessments were "1. Severe hypoexemia. 2. Diffuse lung disease. A) Possible rapidly progressive interstitial pneumonitis (Hammond-Rich type syndrome). B) Pulmonary fibrosis, plus intercurrent lung process. C) Rule out eosinophilic pneumonia. D) Rule out optimistic (sic) pneumonia, on corticosyteroids. E) Rule out viral pneumonitis. 3. Esonophilia on corticosteroids. 4. Hypertension. 5. Hyperlipidemia. 6. Rheumatoid arthritis." The pt was admitted to the hospital and with intravenous SoluMedrol, intravenous ceftriaxone, and intravenous azithromycin. "The pt's condition on admission is critical and his prognosis is poor." CT of the chest revealed "Extensive air space and ground glass density in the lungs." The pt underwent thorascopic left lung wedge biopsy on 04/24/2001. The pathologist's diagnoses were "1. Acute and organizing pneumonia with bronchiolitis and occlusion, consistent with BOOP (bronciolitis obliterans with organizing pneumonia). Negative for identifiable fungal elements and Pneumocystitis (sic) carinii organisms. 3. No evidence of malignancy. 4. Microbiology cultures - negative to date." Testing for Legionella was negative, and no eosinophils were seen in a sputum sample. A 2nd pathology opinion was obtained, "which revised the diagnosed to diffuse alveolar damage of some elements of bronchiolitis. The exact etiologic diagnosis was never ascertained." The lung biopsy was complicated by pneumothorax that required the placement of multiple chest tubes. The pt was dependent on mechanical ventilation and required permissive hypercarbia throughout his hospital stay to avoid plateau pressure exceeding 35 mmHg. The pt became febrile approx 13 days after intubation, and had purulent, tan sputum. He was seen by an infectious disease specialist who noted a primary problem of "Diffuse alveolar damage - ARDS (adult respiratory distress syndrome) like syndrome. The entire process present for over the past year appears to have newly worsened over the past 3 weeks. This is incompatible with any infectious disease process." He also noted that a secondary infection as the reason for the present hospital admission had been ruled out by the open lung biopsy. However, based on examination of sputum, a diagnosis of Enterobacter cloacae nosocomial ventilator-associated pneumonia was made. The pneumonia was treated with the following intravenous antiobiotics: vancomycin, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, and ciprofloxacin. The hospital course was further complicated by right pneumothorax, acute gastrointestinal bleed with anemia felt to be secondary to gastritis (required blood transfusions), prolonged ileus, acute renal insufficiency felt to be a toxic reaction to trimethoprim and sulfamethoxazole, steroid-induced diabetes mellitus, atrial fibrillation, thrombocytopenia, and hypersmolar state with components of hypernatremia, azotemia, and hyperglycemia. Other medications administered during the hospitalization included heparin, salbutamol, ipratropium, digoxin, famotidine, acetazolamide, sodium bicarbonate, and insulin. He was also treated with total parenteral nutrition. The pt developed tachycardia, then torsade de pointe. He underwent initial cardiopulmonary resuscitation, then designated "comfort only care". He subsequently expired on 05/27/2001. Cause of death was recorded as "Cardiac arrhythmias complicating chronic respiratory failure". No autopsy was performed. Info received on 08/16/2002 indicated that respiratory failure, possibly as a complication of rheumatoid arthritis, was fatal. Therefore, this report has been reclassified as serious, unlabelled. The most recent info received on 09/23/2003, provided details on treatment received from paramedics prior to the hospitalization on 04/23/2001. A 15-day follow up report received 10/31 /2003 adds: The most recent info received on 10/17/2003, provided chest x-ray results from 02/26/2001 and 03/26/2001. Follow up on 12/12/03: "The most recent information received on 11/26/2003, a hospital discharge summary, provided additional details regarding the vaccinee's hospital tx from 04/23/2001-05/27/2001."