Age: 52.0
Sex: M
Vaccine: FLU3, HEPAB, HIBV, IPV, MEN, PNC13, TDAP, DTAP, FLUX, HEPAB, HIBV, IPV, MEN, PNC13
Symptoms: Cough, Dyspnoea, Endotracheal intubation, Hypoxia, Intensive care
Clinical narrative: This case was reported in a literature article and described the occurrence of acute fibrinous organizing pneumonia in a 52-year-old male patient who received DTaP vaccine. Co-suspect products included HAB (Hepatitis A and Hepatitis B vaccine), Haemophilus influenzae type b vaccine, Influenza vaccine, Meningococcal vaccine, PCV 13 vaccine and Inactivated Polio vaccine. The patient's past medical history included angioimmunoblastic T-cell lymphoma stage IV (with bone marrow involvement), stem cell transplant and graft versus host disease (mild classic chronic GvHD of skin and eyes treated with topical hydrocortisone and REFRESH eye drops). Previously administered products included cyclophosphamide, doxorubicin, vincristine, prednisone, ifosfamide, carboplatin, etoposide, cyclosporine with an associated reaction of seizure, romidepsin, tacrolimus, mycophenolate and rabbit anti-thymocyte globulin. On an unknown date, the patient received DTaP vaccine at an unknown dose, Hepatitis A and Hepatitis B vaccine at an unknown dose, Haemophilus influenzae type b at an unknown dose, Influenza vaccine at an unknown dose, Meningococcal vaccine at an unknown dose, PCV 13 vaccine at an unknown dose and Inactivated Polio vaccine at an unknown dose. On an unknown date, 85 days after receiving DTaP vaccine, Hepatitis A and Hepatitis B vaccine, Haemophilus influenza type b vaccine and Influenza vaccine, the patient experienced acute fibrinous organizing pneumonia (serious criteria hospitalization and GSK medically significant), hypoxemia (serious criteria hospitalization and GSK medically significant), respiratory failure (serious criteria hospitalization and GSK medically significant), cough (serious criteria hospitalization), dyspnea (serious criteria hospitalization), lung infiltration (serious criteria hospitalization), pneumothorax (serious criteria hospitalization and GSK medically significant) and pneumomediastinum (serious criteria hospitalization and GSK medically significant). The patient was treated with methylprednisolone, tacrolimus, etanercept and prednisone. On an unknown date, the outcome of the acute fibrinous organizing pneumonia, hypoxemia, respiratory failure, cough, dyspnea, lung infiltration, pneumothorax and pneumomediastinum were recovering/resolving. The reporter considered the acute fibrinous organizing pneumonia, hypoxemia, respiratory failure, cough, dyspnea, and lung infiltration to be related to DTaP vaccine, Hepatitis A and Hepatitis B vaccine, Haemophilus influenza type b vaccine and Influenza vaccine. It was unknown if the reporter considered the pneumothorax and pneumomediastinum to be related to DTaP vaccine, Hepatitis A and Hepatitis B vaccine, Haemophilus influenza type b vaccine and Influenza vaccine. Additional information was provided. This case was reported in a literature article and describe the occurrence of acute organizing fibrinous pneumonia (AFOP) in a 52-year-old male who was vaccinated with unspecified DTaP, haemophilus influenza type B, Hepatitis A and B, influenza, meningococcal, pneumococcal 13 and inactivated polio vaccines (manufacture unknown for all). In 2011, the patient was diagnosed with stage IV angioimmunoblastic T-cell lymphoma with bone marrow involvement. He was originally treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) x6. Owing to refractory lymphoma, the patient received salvage ifosfamide, carboplatin, etoposide x2, a clinical trial with high-dose cyclosporine discontinued due to seizures, and reached a partial response with seven cycles of romidepsin before matched unrelated donor haematopoietic cell transplant (HCT). His conditioning regimen was reduced intensity with rabbit anti-thymocyte globulin, 2.5mg/kg from day 9 to 7 followed by total body irradiation (TBI) to a total dose of 4.5 Gy, delivered in three 1.5 Gy fractions on day 1 to 0. For graft versus host disease (GvHD), he received tacrolimus and mycophenolate. His days +60 and +100 bone marrow, blood and T cells were 100% donor and no evidence of disease recurrence was found on radiographic imaging. Pulmonary function testing day +100 revealed a forced expiratory volume (FEV)1 of 93% and diffusing capacity of the lungs for carbon monoxide (DLCO) of 78%; pre-transplant FEV1 and DLCO were 93% and 80%, respectively. The patient had mild classic chronic GvHD of skin and eyes treated with topical hydrocortisone and REFRESH eye drops. The patient was off immunosuppression by day +168. His post-transplant course was uncomplicated by day +180. No information on patient's family history was provided. On an unspecified date, on day +240 post-transplant, the patient received unspecified DTaP, haemophilus influenza type B, hepatitis A and B, influenza, meningococcal, pneumococcal 13 and inactivated polio vaccines (administration route and site unspecified; dosages unknown; batch number not provided for all) as part of starting his vaccination protocol. On an unspecified date, on day +325 post-transplant, 85 days after vaccinations, the patient presented to the outpatient bone marrow transplant clinic with sub-acute cough, dyspnoea, hypoxemia and no other clinical symptoms of GvHD. Pulse oximetry showed oxygen saturations of 68% on room air. Computed tomography (CT) of the chest showed rapidly progressive pulmonary infiltrates. He was admitted to the inpatient bone marrow transplant floor. The patient was started on broad spectrum antimicrobials and subsequently underwent bronchoscopy that was non-diagnostic. Over the next 2 days he developed worsening hypoxemia requiring transfer to the medical intensive care unit for hypoxemic respiratory failure. High-dose methylprednisolone 125 mg every 6 h was initiated. On day +328, he underwent video-assisted thoracoscopic surgery (VATS) and left upper lobe/left lower lobe wedge resection. He was extubated on day +329, but remained hypoxic, requiring non-invasive ventilation. On day +331, the pathology from the wedge resections showed AFOP. Given the lack of clinical improvement, methylprednisolone was increased from 125 to 250 mg every 6 h, tacrolimus was continued (goal trough level 10) and started etanercept 25 mg subcutaneously (SC) twice weekly for a total of 8 doses. After the initiation of etanercept, the patient had significant improvement in respiratory status. His hypoxemia improved, he was off non-invasive ventilation after 2 days and supplemental oxygen and was rapidly weaned. He completed 8 doses of etanercept; continued tacrolimus and steroids were tapered off over 2 weeks. His VATS was complicated by pneumothorax and pneumomediastinum, which required small bore thoracostomy placement and eventually mechanical pleurodesis due to persistent air leak. On day +364, he was discharged home off supplemental oxygen with significant clinical and radiographic improvement. His post-hospitalisation (FEV)1 was 72% and DLCO was 58%. At the time of reporting, the patient was 2.5 years from HCT and remained in remission from his lymphoma. He was on tacrolimus and twice weekly every other week extracorporeal photopheresis for GVHD as a steroid sparing agent that was started after day +364 upon discharge from the hospital. Prednisone was discontinued at day +393. The patient had no other symptoms of GVHD except for an erythematous rash on day +519. He was started on 20 mg of prednisone, which was tapered off by day +756. He was off supplemental oxygen and recent CT scans revealed mild air trapping, however, a significant improvement from prior CT scans and his spirometry was normal (FEV1: 96% and DLCO: 89). This case has been considered serious due to hospitalisation. The authors did not comment on the relationship between the event of acute organizing fibrinous pneumonia (AFOP) and unspecified DTaP, haemophilus influenza type B, hepatitis A and B, influenza, meningococcal, pneumococcal 13 and inactivate polio vaccines. The authors concluded that "The pathogenesis of AFOP is unknown, but our patient's response to etanercept suggest a role of TNF-alpha as part of a cytokine-modulated immune response causing inflammation and fibrosis. To our knowledge this is the first case AFOP after HCT, successfully treated with etanercept. Although, there is a lack of clinical evidence to support the use of etanercept in patients with AFOP. Our rationale for the use of etanercept in this critically ill patient with a non-infectious lung injury was that AFOP may be driven by oxidative stress, which may be modulated by TNF-a. Interestingly, the lung biopsy was positive for both HO-1 and TNF-a. This supports our hypotheses that AFOP may be driven by oxidative stress induced by TNF-a. Therefore, we propose that etanercept may be responsible for the marked clinical improvement in the patient because with high-dose steroids, and tacrolimus the patient was requiring non-invasive ventilation and high-flow oxygen 15 L nasal cannula until the addition of etanercept. We speculate that AFOP is a manifestation of GvHD, and that TNF-a is implicated in its pathogenesis. Until more information is available on the pathogenesis of AFOP after HCT, we recommend early use of etanercept in patients with AFOP post HCT because of rapidly progressive respiratory failure and high mortality".