Acute Fibrinous and Organizing Pneumonia
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Waleed, M.B.B.S. [2]
Overview
Acute fibrinous and organizing pneumonia (AFOP) is an uncommon form of lung injury, either acute or subacute, marked by the presence of fibrin deposits within the alveoli. Unlike diffuse alveolar damage (DAD), AFOP is characterized by the absence of hyaline membranes. Instead, AFOP shows intra-alveolar fibrin deposition and organizing pneumonia. These unique features often lead to challenges in diagnosing AFOP, as its clinical symptoms, including cough, fever, and shortness of breath, are nonspecific and can be mistaken for more common respiratory diseases like bacterial pneumonia or tuberculosis [1]
Historical Perspective
The term AFOP was first introduced in 2002 by Beasley and colleagues, who reported a distinct histological pattern in a group of 17 patients. This condition was differentiated from other forms of lung injury such as DAD and bronchiolitis obliterans with organizing pneumonia (BOOP) by its unique lack of hyaline membranes and presence of intra-alveolar fibrin balls. This initial study provided the basis for further exploration into AFOP, enhancing the understanding of its clinical and pathological characteristics. Since then, AFOP has been identified in various clinical situations, often linked to infections, drug reactions, and autoimmune disorders. [2]
Classification
AFOP can be categorized into two main types based on its cause and clinical presentation:
Idiopathic AFOP: Occurs without any identifiable cause.
Secondary AFOP: Associated with known conditions such as bacterial, viral, or fungal infections, autoimmune diseases (like systemic lupus erythematosus or rheumatoid arthritis), reactions to drugs (such as amiodarone or abacavir), and exposure to environmental toxins (such as asbestos or coal dust). In these cases, the AFOP is considered secondary because it arises due to these underlying factors.[1]
Pathophysiology
AFOP’s pathophysiology involves the formation of fibrin within the alveoli, which then organizes into fibrin balls. This process is distinct from DAD, which typically shows hyaline membranes lining the alveoli. The exact cause of fibrin deposition in AFOP is not fully understood but is believed to involve an abnormal inflammatory response to lung injury. This response results in fibrinogen leaking into the alveolar spaces, where it converts to fibrin. Subsequently, fibroblasts and myofibroblasts organize this fibrin, creating the characteristic fibrin balls.[1] [2]
In AFOP, the intra-alveolar fibrin appears in a patchy distribution, involving 25% to 90% of the alveolar spaces in the lung tissue, with an average of 50% involvement. These fibrin deposits are not confined to the areas around the bronchioles but are dispersed throughout the lung parenchyma. This pattern is accompanied by organizing pneumonia, characterized by loose connective tissue in the alveolar ducts and bronchioles.
The lung tissue surrounding the fibrin deposits shows various changes. There is usually a mild to moderate infiltration of lymphocytes and plasma cells in the interstitium, with occasional cases exhibiting more severe inflammation. Neutrophils are present but are generally sparse and located within the alveolar walls rather than the airspaces, distinguishing AFOP from typical acute bacterial pneumonia. Eosinophils are rare, and their presence does not dominate the histological picture.
Other notable histological features include type 2 pneumocyte hyperplasia, which is an increase in these cells as they proliferate to repair the alveolar lining. Additionally, there may be interstitial widening due to edema and the presence of myxoid fibroblastic tissue in the alveolar walls. Unlike DAD, AFOP does not show dense collagen deposition or extensive interstitial fibrosis. Some cases may display vascular thrombi and alveolar edema, but these features are not consistently prominent.
A key distinguishing feature of AFOP is the absence of hyaline membranes, which are a hallmark of DAD. Instead, the fibrin deposition and organizing pneumonia are the dominant findings, making AFOP unique. This pattern can pose diagnostic challenges, especially in small biopsy samples, due to its patchy and focal nature.
Histological examinations often include special stains, such as Grocott methenamine silver, Ziehl-Neelsen, Brown-Brenn, or Brown-Hopps, to rule out infectious organisms. In AFOP cases, these stains typically do not reveal any microorganisms, supporting the non-infectious nature of the condition.[2]
Causes
Various factors can lead to AFOP, including:
Infections: Caused by bacteria, viruses, and fungi, such as Staphylococcus aureus, Streptococcus pneumoniae, and viruses like influenza or SARS-CoV-2.[3]
Autoimmune diseases: Conditions such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome.
Drugs: Medications like amiodarone, abacavir, bleomycin, and certain chemotherapy agents.
Environmental exposures: Inhalation of asbestos, coal dust, and other toxic substances.
Transplantation: Observed in patients who have undergone hematopoietic stem cell or lung transplants, possibly due to immune suppression and chronic inflammation associated with transplantation.[1]
Epidemiology and Demographics
AFOP is rare, with only a small number of cases reported globally. It affects people of all ages and genders, although it seems to be more common in older adults. Due to its rarity and potential for underdiagnosis, the precise prevalence and incidence rates of AFOP are not well-documented. Many cases might be misdiagnosed as other, more common forms of pneumonia or lung injury.[1]
Risk Factors
Several factors increase the risk of developing AFOP, including:
Autoimmune conditions: Diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome.
Certain medications: Drugs known to cause lung injury, including amiodarone, abacavir, and some chemotherapy agents.
Exposure to environmental toxins: Chronic exposure to inhaled toxins like asbestos and coal dust.
Recent infections: Particularly severe or atypical respiratory infections.
History of organ transplantation: Especially hematopoietic stem cell or lung transplants, due to immunosuppressive therapy and chronic inflammation.[1]
Screening
No established screening protocols exist for AFOP due to its rarity and nonspecific presentation. Diagnosis is typically made after a clinical suspicion arises, followed by histopathological confirmation through lung biopsy. Clinicians should consider AFOP in patients with persistent or worsening pneumonia unresponsive to standard antibiotic therapy, particularly those with known risk factors.
Natural History, Complications and Prognosis
AFOP can present acutely or subacutely:
Acute AFOP: Rapid onset and progression to respiratory failure, often requiring mechanical ventilation. The prognosis is generally poor, with a high mortality rate.
Subacute AFOP: More gradual onset of symptoms and slower progression. Often responds well to corticosteroid therapy and has a better prognosis than the acute form. Complications can include chronic respiratory impairment and fibrosis if treatment is delayed.[1]
Diagnosis
Diagnosis of AFOP is confirmed through histopathological examination of lung tissue obtained by biopsy. Key histological features include:
Intra-alveolar fibrin balls: Clumps of fibrin within the alveoli.
Organizing pneumonia: Proliferation of fibroblasts and myofibroblasts within the alveoli and alveolar ducts.
Lack of hyaline membranes: Unlike DAD, AFOP does not show hyaline membranes lining the alveoli.
Imaging studies such as high-resolution computed tomography (HRCT) can support the diagnosis by showing diffuse ground-glass opacities, consolidation, and other nonspecific changes. Laboratory tests may reveal elevated inflammatory markers, but these findings are not specific to AFOP. [1]
Treatment
The mainstay of treatment for AFOP is corticosteroids, although there is no standardized regimen. The following treatment options are commonly used:
Corticosteroids: High-dose corticosteroids, such as prednisone or methylprednisolone, are typically administered to reduce inflammation and promote resolution of lung injury.
Immunosuppressants: In refractory cases, additional immunosuppressive agents such as mycophenolate mofetil, azathioprine, or cyclophosphamide may be used.
Supportive care: Oxygen therapy and mechanical ventilation may be required for patients with severe respiratory distress.
Prompt initiation of treatment can lead to significant improvement in symptoms and lung function. The duration of therapy varies depending on the severity of the disease and response to treatment.[1][3]
Case Studies
A 70-year-old man presented with a two-day history of cough and fever. His initial vital signs were stable, with a blood pressure of 120/74 mmHg, heart rate of 72 beats per minute, respiratory rate of 20 breaths per minute, temperature of 38.2°C, and oxygen saturation of 98% on 2 liters per minute of supplemental oxygen delivered via nasal cannula. Initial laboratory tests showed a white blood cell count of 7.41 x 10^9/L, hemoglobin level of 132.0 g/L, platelet count of 387.0 x 10^9/L, red blood cell count of 4.27 x 10^12/L, erythrocyte sedimentation rate (ESR) of 72 mm/H, C-reactive protein (CRP) level of over 150 mg/L, interleukin-6 (IL-6) level of 88.19 pg/ml, and procalcitonin (PCT) level of 0.244 ng/ml. Further evaluations, including arterial blood gas analysis, liver and kidney function tests, electrolytes, respiratory virus tests, and fungi tests, were normal. Blood cultures did not grow any pathogens, and sputum cultures showed normal respiratory flora. Tests for acid-fast bacilli in three consecutive samples were negative. There was no other identifiable source of infection. Autoimmune tests, including anti-neutrophil antibody, anti-neutrophil cytoplasmic antibody, and rheumatoid factor, were all negative.
Imaging studies, including an electrocardiogram, abdominal ultrasound, thyroid ultrasound, and lower limb vascular ultrasound, showed no abnormalities. A chest computed tomography (CT) scan revealed consolidation in the right upper lobe, patchy infiltrates, and a ground-glass appearance in the right lower lobes. The patient was initially treated with empirical antibiotics for community-acquired pneumonia, but his condition did not improve. A follow-up CT scan performed 10 days after starting antibiotics showed that the lung lesions had become denser and more extensive.
To obtain a definitive diagnosis, endobronchial ultrasonography with a guide sheath (EBUS-GS) was performed, retrieving about eight tissue samples from the B2a segment of the right upper lobe. Histological examination revealed significant fibrinous exudation and the presence of “fibrin balls” within the alveolar spaces. Next-generation sequencing (NGS) of lung tissue and bronchoalveolar lavage fluid (BALF) did not detect any bacteria, fungi, DNA viruses, or parasites.
Based on these findings, a diagnosis of acute fibrinous and organizing pneumonia (AFOP) was made. The patient was started on intravenous methylprednisolone at a dose of 40 mg twice daily. His fever subsided, and his cough improved. The patient was discharged with a tapering dose of methylprednisolone, starting at 24 mg once daily. A follow-up CT scan 1.5 months later showed significant resolution of the bilateral lung lesions, with only a few fibrous strands remaining. His dose was then reduced to 20 mg, and he remains in stable condition with regular outpatient follow-up.[1]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Lu J, Yin Q, Zha Y, Deng S, Huang J, Guo Z; et al. (2019). "Acute fibrinous and organizing pneumonia: two case reports and literature review". BMC Pulm Med. 19 (1): 141. doi:10.1186/s12890-019-0861-3. PMC 6683570 Check
|pmc=value (help). PMID 31382933. - ↑ 2.0 2.1 2.2 Beasley MB, Franks TJ, Galvin JR, Gochuico B, Travis WD (2002). "Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage". Arch Pathol Lab Med. 126 (9): 1064–70. doi:10.5858/2002-126-1064-AFAOP. PMID 12204055.
- ↑ 3.0 3.1 García-Huertas D, López-Fernández A, De Dios-Chacón I (2022). "Acute fibrinous and organizing pneumonia". Med Clin (Engl Ed). 158 (3): 144–145. doi:10.1016/j.medcle.2021.04.017. PMC 8767989 Check
|pmc=value (help). PMID https://pubmed.ncbi.nlm.nih.gov/35071765 Check|pmid=value (help).