Acute fibrinous and organizing pneumonia (AFOP) was first described by Beasley et al1 in 2002. This term indicates one of the histologic patterns of lung injury, and AFOP is considered as a variant of diffuse alveolar damage (DAD).
This rare condition has an acute or subacute presentation and has been associated with multiple infectious, inflammatory, and malignant processes. The mortality for patients requiring mechanical ventilation is significant and usually due to the associated condition or acute respiratory distress syndrome (ARDS); shock has not been described as part of the presentation of AFOP.
We present a patient with AFOP presenting with ARDS and shock who improved with corticosteroids.
A 38-year-old African American man presented with cough, fever, and shortness of breath of 1-week duration. He complained of fatigue, decreased appetite, and weight loss of 2 to 3-week duration. He denied any medical history or exposure to tuberculosis. Social history included tobacco smoking (more than 15 pack-years); he denied use of alcohol or drugs. He had moved to USA from Ivory Coast, Africa 9 years ago and presently worked in a shipping warehouse. His sister was treated for tuberculosis.
On physical examination, he seemed cachectic and in moderate distress with the following vital signs: temperature, 98.8°F; blood pressure, 130/70 mm Hg; heart rate, 110/min; respiratory rate, 25/min; and oxygen saturation of 90% on 2 L/min oxygen. Chest examination revealed bilateral mild crackles in the lower lung fields.
Laboratory testing showed a positive enzyme-linked immunosorbent assay test for human immunodeficiency virus (HIV). Initial arterial blood gas on ambient air revealed severe hypoxemia with a PaO2/FiO2 ratio of <200. Blood cell count and basic metabolic panel were remarkable for a hematocrit of 42%, white blood cells 2.7 K/uL, and platelet 294 K/uL, serum creatinine 1.1 mg/dL, albumin 2.9 g/dL, lactate dehydrogenase 1874 U/L, alanine transaminase 41 U/L, aspartate transaminase 142 U/L, creatine kinase 605 U/L, Sodium 130 meq/L, and potassium 5.4 meq/L.
Chest radiograph (CXR) showed bilateral alveolar infiltrates (Fig. 1).
His clinical condition deteriorated rapidly with development of respiratory failure and shock, and he required intubation and mechanical ventilation. Management included broad-spectrum antibiotics for presumptive community-acquired pneumonia (ceftriaxone and azithromycin) and Pneumocystis Carinii pneumonia (PCP) (sulfamethoxazole-trimethoprim and systemic corticosteroids). ARDS protocol with lung protective strategies and vasopressors were started. Central venous pressure was maintained at 12 to 14 mm Hg and mixed venous saturation was 72%.
A chest computed tomographic scan revealed diffuse ground-glass opacities, bilateral ill-defined nodular infiltration of the lungs, and a focal mass-like consolidation in right lung apex (Fig. 2).
The CD4 lymphocyte count was <20/mL, with a HIV RNA titer of 22,000 IU/mL. Hepatitis B surface antigen was positive. Tuberculin skin test, nasal swab for influenza, and blood, urine, stool, and respiratory cultures were all negative. On the second day of admission, the patient underwent flexible bronchoscopy with bronchoalveolar lavage. Cultures for bacterial, fungal, mycobacterial, and viral organisms were all negative. No Pneumocystis organisms were identified. Echocardiogram and autoimmune workup were noncontributory.
By the third day of admission, the patient's clinical condition started to improve; he was weaned off vasopressors and the PaO2/FiO2 ratio increased to 320.
On the fifth day, the patient underwent repeated flexible bronchoscopy with bronchoalveolar lavage and transbronchial biopsy (TBBx) from the right upper lobe. Again, all cultures and cytology were negative. The TBBx revealed intra-alveolar fibrin deposit, interstitial inflammation, and organizing intra-alveolar focus suggestive of AFOP (Fig. 3). The patient was continued on systemic corticosteroids, and all antibiotics were discontinued by day 7 after admission. He was successfully weaned off the ventilator and he was discharged home on 40 mg prednisone daily for 3 months. In subsequent follow-up at the pulmonary clinic, he remains asymptomatic and no pulmonary symptoms were noticed; repeated CXR is shown in Figure 4.
AFOP is an extremely rare pathologic entity that was first described by Beasley et al1 in 2002. To our knowledge, there is no case of shock associated with AFOP reported in the literature.
AFOP has been reported to occur in idiopathic context or in association with a wide range of clinical conditions that include collagen-vascular diseases (polymyositis/dermatomyositis and ankylosing spondylitis), inhalation-related diseases, lymphoma and acute lymphocytic leukemia, bacterial infections caused by Haemophilus influenzae and Acinetobacter baumannii, and secondary to drugs, including abacavir, amiodarone, and busulfan.1–4
Diffuse lung disease in HIV-infected patients carries an extensive clinical differential, with the most common etiologies being infectious processes and malignancies such as Kaposi sarcoma and lymphomas. Idiopathic interstitial lung diseases are uncommon in HIV patients; there are cases of cryptogenic organizing pneumonia (COP) and nonspecific interstitial pneumonia reported in the literature. To date, we were able to find only 1 HIV-infected patient with AFOP, which was associated with PCP.1,5,6
AFOP presents with a clinical picture of acute lung injury that differs from the classic histologic patterns of DAD, bronchiolitis obliterans with organizing pneumonia, or eosinophilic pneumonia (EP).
The symptoms are nonspecific, with cough, shortness of breath, and hemoptysis being most commonly reported. In few cases, chest, pleural, or abdominal pain, and constitutional flu-like symptoms have been mentioned. There is no age predilection associated with AFOP; the average reported age is 62 years (range, 33 to 78 y).
Patients with AFOP may have an acute or subacute clinical presentation. The acute form presents as a fulminant illness often overlapping with ARDS, both clinically and pathologically. On the other hand, the subacute presentation resembles COP. In terms of prognosis and recovery, the subacute form of AFOP carries a better prognosis than the acute form, and mechanical ventilation is rarely required. Those patients with acute AFOP, similar to that of our patient, have a clinical course similar to those with DAD. In the larger review of AFOP published by Beasley et al1, 30% of the patients with AFOP required mechanical ventilation; all those patients died.
The radiologic features of AFOP are still not well defined. The CXR findings are almost identical to COP, with multiple, migratory, patchy diffuse alveolar opacities with peripheral and bilateral basilar distribution. Bilateral reticulonodular infiltrates and infiltrates consistent with pulmonary edema and interstitial pneumonia have been reported. Multiple patchy consolidations and peribronchial changes that include air bronchograms, bronchial wall thickening, and centrilobular small nodules can be found on chest computed tomographic scans. Rare cases of AFOP presenting as solitary or multiple nodule have been reported.1,6,7
The histologic hallmarks of AFOP are the fibrin deposits forming fibrin balls within the alveolar spaces in a patchy distribution involving predominantly the lower lobes. The alveolar walls adjacent to areas of fibrin deposition demonstrate a variety of associated changes, such as acute or chronic inflammatory cell infiltrate and interstitial widening and hyperplasia of type 2 pneumocyte. However, the intervening lung shows only minimal histologic changes. The main differential diagnoses include DAD, COP, and EP. DAD is distinguished from AFOP by the disease distribution; DAD is characterized by diffuse pathology affecting all aspects of lung parenchyma whereas AFOP is in a patchy distribution, typically involving the alveoli and terminal bronchioles. Hyaline membranes classically seen in DAD are not observed in AFOP. AFOP is distinguished from COP and EP by the lack of fibrosis typically seen in COP and lack of eosinophilic infiltrates seen in EP.1,6
There are no standard treatment guidelines for patients with AFOP. Long-term corticosteroid therapy is associated with good clinical outcomes, especially in those patients with subacute presentation. The overall prognosis is poor for patients with pathologic findings of AFOP with a mortality rate of >50%. The outcome for patients requiring mechanical ventilation is dismal with a mortality of 100%.
COP shows some clinical and radiologic similarities with AFOP. The response to corticosteroid therapy in COP is far superior to the response in AFOP.
The rare, rapidly progressive form of COP has an extremely poor prognosis.
This form can occur in a previously healthy individual or can be associated with other systemic illness. Patients can develop acute respiratory failure. Most fatal cases have a secondary form of COP. The rapidly progressive primary form of COP seems to have a better prognosis and can be indistinguishable from acute interstitial pneumonitis on clinical grounds. Focal lung nodules in the idiopathic form of COP are clinically important as they may mimic lung cancer.
In HIV-infected patients presenting with acute respiratory failure and hyperdynamic shock associated with nonspecific radiologic findings, the differential diagnosis is extensive and includes mainly infectious and cardiovascular etiologies. PCP and bacterial pneumonias are the most common pulmonary complications, and the initial evaluation should focus on the diagnosis and management of those pathologies. However, noninfectious, rare etiologies, such as acute manifestations of interstitial lung diseases, should be rapidly considered if there is no identifiable cause or clinical improvement. Shock should be included as part of the presentation of AFOP.
The rapid clinical-radiologic improvement seen in our patient was remarkable. Taking into consideration that open lung biopsy was not performed in our patient, we cannot exclude the possibility that he had a variant of COP with histologic resemblance to AFOP.
To the best of our knowledge, this is the first case of idiopathic AFOP with ARDS and shock in an HIV-infected patient. Flexible bronchoscopy with TBBx can assist in establishing the diagnosis.
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Keywords:© 2011 Lippincott Williams & Wilkins, Inc.
acute fibrinous and organizing pneumonia; acute respiratory distress syndrome; transbronchial biopsy; shock