Age: 50.0
Sex: F
Vaccine: HEP
Symptoms: Allergic sinusitis, Angiotensin converting enzyme, Antineutrophil cytoplasmic antibody negative, Antinuclear antibody negative, Arteriosclerosis
Clinical narrative: This female subject was enrolled in a non-GSK study. On 27 April 2010, 25 May 2010 and 12 October 2010, the subject received a 1st, 2nd and 3rd dose of investigational product. The subject received ENGERIX-B. The subject's past medical history included allergic reaction to sulfa drugs (rash). Medical conditions at the time of the event included chronic sinusitis, intermittent environmental allergies and upper respiratory tract infection. Concomitant medications included XOPENEX, Steroids, PREDNISONE, Augmentin, Antibiotics and Amoxicilline. On 23 November 2010, 42 days after the 3rd dose of Blinded vaccine, this 50-year-old subject developed reactive airway disease. The subject was hospitalised. The subject was treated with salbutamol sulphate, oxygen, methylprednisolone sodium succinate, ipratropium bromide, ADVAIR, proton pump inhibitors, prednisone, AUGMENTIN and mometasone furoate. The event resolved on 25 November 2010. The investigator considered that there was a reasonable possibility that the reactive airway disease may have been caused by investigational product and that the event was possibly due to the subject's medical condition of chronic sinusitis. Relevant risk factors: On 08-Apr-2011, a family history was reported by the subject. Her father had hypertension. There were thyroid problems among family members, but the exact family members affected and the exact diagnosis was unknown. The subject was not taking any other medication at the time of the event. Investigator comments: This reactive airway disease concerns a 50-year-old female subject. The subject received her first injection of study vaccine on 27-Apr-2010. Additional injection of study vaccine occurred on 25-May-201 and 12-Oct-2010. Since 20-Jul-2010, the subject had been dealing with cough and associated symptoms of congestion, shortness of breath, wheezing, chest tightness, chest pain and vomiting secondary to cough. She had been seen by her primary care physician, and a pulmonologist who had told her that she did not have asthma. The subject had gone through four courses of oral antibiotics and oral steroids in six months which helped initially but symptoms resumed quickly thereafter. On 01-Nov-2010, the subject had been diagnosed with an upper respiratory tract infection. She was treated with amoxicillin 500 mg BID from 05-NOV-2010 until 15-NOV-2010 and with prednisone dose pack 1 tab since daily from 05-NOV-2010 until 11-NOV-2010. On 16-Nov-2010, she was seen by an ENT whose differential diagnoses included adult onset asthma versus pertussis versus other infectious process. A sinus CT scan was ordered and showed sinusitis. She was started on a prolonged course of Augmentin. It was felt by the ENT specialist that the subject's chronic sinusitis may have been causing her to have reactive airway disease. Per subject, she usually treated her wheezing and shortness of breath successfully with a XOPONEX inhaler. On 22-Nov-2010, the subject was unable after several attempts to relieve her symptoms with the inhaler and woke at 1:15 am and had difficulty breathing. She then tried her albuterol nebulizer and still had difficulty breathing. On 23-NOV-2010 at 2:00 in the morning, 42 days after the most recent dose of study vaccine, the subject went to the emergency room for acute exacerbation of shortness of breath, wheezing, and cough. Vital signs included blood pressure of 138/80 mmHg, pulse of 105 bpm, respiration of 24, temperature of 97.2 degrees Fahrenheit, and oxygen saturation on room air of 88%. An arterial blood gas showed a PH of 7.38, PCO2 of 42, a PO of 56 and oxygen saturation of 89% on room air. She was found to be hypoxic and was placed on 4 litres continuous oxygen via nasal cannula to bring her up to 96% oxygen saturation. An EKG performed was normal. She was admitted on 24-Nov-201 for further evaluation. A CT scan of the chest with contrast showed no evidence of pulmonary embolism or aortic dissection. Mild atherosclerotic vascular disease was suspected. A 4 mm non-specific pulmonary nodule in the right middle lobe was noted and a follow-up CT scan in three months was recommended. The subject was started on intravenous SOLU-MEDROL, albuterol, and ATROVENT nebulizer. She had immediate improvement in her symptoms after the SULO-MEDROL was initiated and she was weaned off oxygen within a few hours. The subject was seen by a pulmonologist who recommended treatment with SOLU-MEDROL and ADVAIR. He also recommended starting the subject on a protein pump inhibitor and treating her with a prednisone taper after discharge. Cardiac enzymes were negative. Anti-proteinase-3 antibody (anti-PR3), antinuclear cytoplasmic antibody (ANCA), antinuclear antibody (ANA) and angiotensin converting enzyme (ACE) were tested separately and were all negative. The investigator assessed that the subject's continued upper respiratory tract infection that worsened on medication had become a pansinusitis which created reactive airway disease. On 25-Nov-2010, the subject had remained off oxygen and had good oxygen saturations on room air without further recurrence of shortness of breath, cough or wheezing and was discharged in good condition. The reactive airway disease and hypoxia where  considered resolved on the same date. The subject continued to be treated for pansinusitis upon discharge. She was started on augmentin 875 mg BID, prednisone taper starting with 40 mg daily for three days, ADVAIR 250/50 1 puff BID, and NASONEX (once daily). Prednisone treatment was stopped on 06-Dec-2010. The subject was followed up by her ENT specialist on 16-NOV-2010, 29-NOV-2010, 13-DEC-2010 and on 07-FEB-2011 she was recommended for sinus surgery. On 17-Feb-2011, the subject underwent functional endoscopic sinus surgery for chronic rhinosinusitis with Medtronic fusion image guided assistance in an outpatient setting. The procedure included bilateral endoscopic total ethmoidectomy, bilateral endoscopic maxillary antrostomy with tissue removal, bilateral endoscopic sphenoid sinusotomy with tissue removal, and bilateral endoscopic frontal sinusotomy. Additional procedures were sinonasal endoscopy with excision of lateral lamina left concha bullosa, intraoperative culture left sphenoid (fungal smear and culture) as well as left maxillary sinuses (gram stain, aerobic and anerobic culture and sensitivity). The pathology report showed chronically inflamed respiratory mucosa and portions of bone, necroinflammatory debris and mucus with entrapped eosinophils and neutrophils compatible with allergic sinusitis. Negative for fungi on GMS and PAS stains with appropriate controls. Although special stains were negative for fungal organisms, the background necroinflammatory debris and mucus was highly suspicious for allergic fungal sinusitis. After receipt of additional clinical information from the ENG specialist, the case was re-reviewed, with the following findings: (sic) "No active vasculitis nor granulomatous inflammation is present in the tissue fragments for evaluation, though numerous eosinophils are present in the tissue and in the surrounding mucin. Overall, the findings are non-specific but consistent with an allergic rhinitis. As upper airway disease in Churg-Strauss can present as allergic rhinitis with rhinorrhea rather than an ulcerating, destructive process, the above findings could potentially be seen in Churg-Strauss disease. However, additional clinical studies including p-ANCA, could be helpful for further characterization." The subject was seen by her ENT specialist, who described the subject as "doing well from a sinonasal standpoint, with some asthma symptoms." As of 24-May-2011, a CT scan to follow up on the pulmonary nodule had not been performed. The subject had plans to follow-up with both her primary care physician and her ENT specialist. Because of the ENT specialist's concern about the low possibility of Churg-Strauss syndrome, the sponsor submitted documentation of this case to a rheumatologist who is an expert on Churg-Strauss syndrome on 18-May-2011. Based on a review of the available records, the rheumatologist gave the opinion that there is currently no evidence for Churg-Strauss syndrome. In the absence of asthma, peripheral eosinophilia, evidence of vasculitis, chest radiographic abnormalities, this subject does not fulfill any existing definition of Churg-Strauss syndrome. No action was taken with regard to study vaccine administration. The investigator reported that the event of reactive airway disease was severe in intensity. Per investigator the relationship to study vaccine administration was uncertain but possible with no test results available. On 24-Jul-2011, unblinding information was received. The subject was found to have been randomized to ENGERIX-B. Relevant tests: The subject's laboratory results throughout the study were unremarkable except for an elevated eosinophil fraction of 9% (below or equal to 5%) and a normal absolute eosinophil count of 0.52x103/uL on 24-Nov-2010.