INTRODUCTION: We report the simultaneous occurrence of lymphocytic interstitial pneumonitis (LIP) and pulmonary embolism (PE) in a patient with tetralogy of Fallot. A possible explanation based on the pathogenesis of these diseases is proposed.
CASE PRESENTATION: A 45-year-old Caucasian woman with tetralogy of Fallot surgically corrected at age 6, presented with severe dyspnea and an acute episode of pleuritic right-sided chest pain, associated with fevers of 102 °F and chills. She was treated as an outpatient with antibiotics and steroids for presumptive pneumonia twice in the previous 12 weeks, without improvement. On admission her medications included albuterol and prednisone 30 mg/day. She had a 20-pack-year smoking history, denied the use of illegal drugs or alcohol. She was afebrile, hemodynamically stable with a pulse oximetry of 78% on room air. Neck exam was negative for carotid bruits, JVD, lymphadenopathy or palpable thyroid. The lungs exhibited diffuse expiratory ronchi and wheezes. A grade 2 systolic ejection murmur and a grade 2 early diastolic murmur were noted at the upper left sternal border. Extremities revealed distal cyanosis, but no clubbing or edema. WBC 20,000/mm3 with 96% neutrophils and 3% lymphocytes. β-natriuretic peptide 256 pg/ml. CT angiogram of the chest showed right middle lobe acute pulmonary embolus, with extensive bilateral ground glass opacities. Transthoracic echocardiography showed small residual VSD; right to left shunt at the atrial level and RVSP of 64 mmHg. Treatment with heparin was instituted. A bronchoalveolar lavage performed 3 days later showed 45% neutrophils, but no organisms. Cultures were negative. A VATS lung biopsy was consistent with LIP. HIV testing was negative. ANA and RF were negative. Antiphospholipid antibodies were positive. Serum immunoglobulins were all significantly reduced. Total IgG 510 mg/dl, IgG2 75 mg/dl, IgG3 19.7 mg/dl, and IgG4 4.6 mg/dl. Pulmonary function tests showed obstruction, restriction and a reduction in diffusing capacity of moderate degree. Subsequently she was treated with prednisone 60 mg/day for 3 months, with significant radiological and lung function improvement, she remains on oral anticoagulation.
DISCUSSIONS: LIP, an infrequent cause of interstitial lung disease, has been associated with abnormalities of the immune system. Thus it has been described in cases of hypogammaglobulinemia, monoclonal and polyclonal gammopathy, Sjögren's syndrome, SLE, primary biliary cirrhosis, autoimmune thyroiditis and HIV infection among others. Significant disproteinemia is reported in 50% to 70% of the patients with LIP and it may preceed, occur during or follow the onset of the pulmonary disease. In this patient the gammaglobulins reach their nadir during the acute episode. The occurrence of hypogammaglobulinemia, low levels of T-lymphocytes and complement has been described in patients with Tetralogy of Fallot with chromosome 22q11.2 deletion. Embryologically the thymus and the cardiac outflow structures develop at the same time and all receive migrating cells from the neural crest. Despite these immunological abnormalities the association of LIP with Tetralogy of Fallot has not been reported. The occurrence of PE in this setting could be explained by the presence of antiphospholipid antibodies (aPL) and the severe limitation of the patient's physical activity. Interestingly aPL are present in patients with pulmonary hypertension (PH), irrespective of its cause and severity. The RVSP of 64 mmHg made us suspect that the patient had a certain degree of PH before the acute event. In patients with PH, endothelial dysfunction plays a key factor in the development of in situ thrombosis. This process was supported by the presence of intra-arterial thrombosis in the patient's lung biopsy.
CONCLUSION: The occurrence of LIP in this case can be explained by the underlying immunologic abnormalities described in patients with Tetralogy of Fallot, the occurrence of PE could have originated as a complication of the these two diseases.
DISCLOSURE: Martin Valdivia-Arenas, None.