Cryptogenic organizing pneumonia is one of the variants of interstitial lung disease, which is characterized by damage to the bronchioles, alveolar passages and alveoli. The reasons for its development are unknown. The disease is manifested by an unproductive cough, chest pain, shortness of breath and asthenic syndrome. The diagnosis of the disease is carried out according to the results of radiography and CT of the lungs, bronchoscopy, examination of washing waters obtained during bronchoalveolar lavage. Conservative treatment: long-term therapy with glucocorticosteroids until complete regression of signs of the disease.
ICD 10
J84.1 Other interstitial pulmonary diseases with mention of fibrosis
Meaning
Cryptogenic organizing pneumonia (OP) is from 2 to 13% among all interstitial lesions of the bronchopulmonary system. The frequency of this disease reaches 10 cases per 100 thousand adults, although the true prevalence may be higher due to the complexity of diagnosis. The peak of diagnosis occurs at the age of 50-60 years, men and women get sick equally often. Pathology does not lose relevance for practical pulmonology, since its frequency is constantly increasing, diagnostic and treatment protocols require further improvement.
Causes of cryptogenic organizing pneumonia
The prefix “cryptogenic” when determining the diagnosis of organizing pneumonia indicates an unknown origin of the disease. Unlike secondary forms of OP, which have clear etiological factors – they occur after bacterial pneumonia, radiation therapy, exposure to drugs and toxins – the cryptogenic form is not associated with any of these factors and is established only after their exclusion.
Pathomorphology
Macroscopically, the foci of cryptogenic pneumonia are represented by dense gray-red tissue with a yellowish tinge. Their size ranges from 2-3 mm to a segment and even a whole fraction of a lung. Microscopic examination reveals an organized exudate, which consists of fibrin, lymphocytes, plasma cells and macrophages with foamy cytoplasm. The basis of foci in bronchioles and alveoli is granulation tissue.
With a long-existing process, fibroblasts are present in the pathological focus, which are located parallel to each other. A large amount of mucopolysaccharides is determined in the intercellular matrix. For foci of organized cryptogenic pneumonia, the presence of thin-walled vessels is also characteristic. Pulmonary alveoli have thickened walls due to lymphocytic-histiocytic infiltration.
Classification
According to the generally accepted systematization, cryptogenic organizing pneumonia is attributed to one of the 7 variants of idiopathic interstitial pneumonia. Some authors propose to exclude it from this classification, since the restrictions of air flow in the bronchial tree in this variant of OP prevail over fibrous changes in the lungs. There is an X-ray classification of the disease, according to which there are 4 forms:
- Classic. Pathology is represented by multiple alveolar infiltrates, which mainly affect the peripheral parts of the lungs. Diffuse nodular-mesh changes in the pulmonary parenchyma are possible in 20% of patients.
- Nodular (focal). It is manifested by a single nodular formation, which is most often located in the upper lobe of the lung. This is a difficult form of OP to diagnose, so the final diagnosis is often made after surgery for the removal of an atypical tumor formation.
- Infiltrative. This form is characterized by numerous mesh changes in the lung tissue, which are accompanied by small areas of compaction and fibrosis.
- Atypical. The rarest variant of cryptogenic OP, which is represented by isolated infiltrates around the bronchi and pulmonary vessels, micronodular changes in the lung parenchyma.
Symptoms of cryptogenic organizing pneumonia
The disease manifests itself as a flu-like syndrome. The most common symptom is dry cough, which occurs in 70% of patients. Typical manifestations include fever (occurs in 50% of cases), shortness of breath (50%), chest pain (30%). The detailed clinical picture of the disease resembles bacterial pneumonia, so such patients may receive ineffective antibiotic treatment for a long time.
For organizing pneumonia, a prolonged course is typical. Symptoms of varying intensity last longer than 3 months. In addition to respiratory disorders, patients complain of weight loss, constant weakness, deterioration of performance. Due to respiratory disorders and hypoxia, dizziness, memory and concentration disorders occur.
Complications
The disease has a relatively favorable course. In 20% of patients, spontaneous resolution of pathological foci occurs, after which the lung tissue restores its normal structure. In symptomatic forms of the disease, proper and timely therapy allows to achieve regression of pathology. Complications in the form of respiratory failure and pulmonary fibrosis are extremely rare, although relapses of cryptogenic OP are not excluded.
Diagnostics
Patients with typical bronchopulmonary symptoms are referred for consultation by a pulmonologist. In most patients, the clinical picture of infectious pneumonia is determined during the initial examination and physical examination. To exclude this form of lung inflammation and to make a final diagnosis, a number of instrumental and laboratory diagnostic methods are carried out, such as:
- Lung x-ray. When studying the radiograph, lesions in the lung tissue are noted by the type of infiltrates, mesh changes, limited compaction and fibrosis. Radiological findings correspond to the above-mentioned forms of cryptogenic pneumonia.
- CT of the lungs. A more sensitive diagnostic method is necessary to identify small infiltrates that are not visible on radiographs. In 20% of cases, the reverse halo sign is determined – a focus of “frosted glass surrounded by a corolla of peripheral consolidation. Occasionally, bronchiectasia is detected on CT.
- Bronchoalveolar lavage. Microscopy of bronchial flushing waters reveals an increase in the number of cellular elements, among which lymphocytes (20-40%), neutrophils (10-20%) and eosinophils (5-10%) predominate. A characteristic feature of organizing pneumonia is called “foamy” macrophages.
- Bronchoscopy. Endoscopic visualization of the bronchial tree is necessary for differentiation with other pathologies. On examination, no local inflammatory changes or increased mucus formation are detected, which makes it possible to exclude a classic infectious lesion. The study is often supplemented with a biopsy with a histological examination of the lung tissue.
- Functional tests. Restrictive respiratory disorders are observed in 50% of patients. It is characterized by a decrease in the diffusion capacity of the lungs and its relation to the alveolar volume, an increase in respiratory disorders during physical exertion. Unfavorable results of the study are revealed in smokers with experience who have cryptogenic OP.
- Laboratory methods. The hemogram shows signs of a systemic inflammatory reaction: leukocytosis, an increase in ESR. In a biochemical study, 80% of patients have an elevated level of C-reactive protein. To exclude the infectious nature of the disease, microscopy and sputum culture are shown.
Differential diagnosis
The classic variant of OP is differentiated with eosinophilic pneumonia, multiple lung infarctions, Wegener’s granulomatosis and allergic angiitis-Charge-Strauss granulomatosis. With limited nodular infiltrates, bronchoalveolar cancer and lung lymphoma are excluded. Migrating infiltrates require differential diagnosis with aspergillosis, parasitic infestations. When verifying the diagnosis, secondary OP is excluded: post-infectious, post-radiation, post-transplant.
Cryptogenic organizing pneumonia treatment
The main method of treatment is long-term use of glucocorticosteroids (GCS). The cryptogenic form of OP shows high sensitivity to these drugs, therefore, clinical and laboratory improvement in the form of corticosteroid therapy is an additional criterion for confirming the diagnosis. The use of GCS is necessary for the rapid and complete disappearance of fibrous tissue from the lungs and bronchioles.
The generally accepted protocol of therapy involves the administration of drugs for 24 weeks with a gradual reduction of the dose to the maintenance. With insufficient effectiveness, treatment is extended to 12 months. In severe cases, pulse therapy of GCS is used in the form of intravenous bolus injection. According to indications, the therapeutic regimen is enhanced with immunosuppressants. With a mild course of cryptogenic OP, the appointment of macrolides is possible.
Given the high risk of relapse, patients with cryptogenic organizing pneumonia are on the dispensary register with a pulmonologist. With the recurrence of symptoms, high doses of corticosteroids are required for up to 12 weeks, after which the dosages are gradually reduced and the drugs are canceled. Relapses occur in the first year after the diagnosis of the disease, later exacerbations may indicate an alternative diagnosis (for example, Wegener’s granulomatosis).
Prognosis and prevention
Although cryptogenic OP is successfully amenable to corticosteroid therapy, relapses are possible within 2-6 months after drug withdrawal. Repeated exacerbations occur in 58% of patients. They are successfully stopped by pharmacotherapy, so the prognosis for health and life is favorable. In most patients, it is possible to completely restore respiratory function and lung function. Disease prevention measures are not provided.
Literature
- Clinical manifestations of organizing pneumonia. Hunter M, Ludueña A, Telias I, Aruj P, Rausch S, Suárez JP. Medicina (B Aires). 2016;76(6):338-342. link
- Clinical analysis of 25 cases of biopsy-proven cryptogenic organizing pneumonia. Li HP, Fan F, Li QH, Zhao L, Li X, Yu H, 2007 Apr;30(4):259-64. link
- Comparison between cryptogenic organizing pneumonia and connective tissue disease-related organizing pneumonia. Yoo JW, Song JW, Rheumatology (Oxford). 2011 May;50(5):932-8. link
- Organizing pneumonia: diagnosis and treatment. [No authors listed] Ter Arkh. 2012;84(3):38-44. link
- Cryptogenic organizing pneumonia. A report of 25 cases and a review of the literature. Alasaly K, Muller N, Ostrow DN, Champion P, FitzGerald JM. Medicine (Baltimore). 1995 Jul;74(4):201-11. link