Cryptogenic organizing pneumonia (ORPHA:1302)
A rare form of idiopathic interstitial pneumonia characterized pathologically by organizing pneumonia (OP) that presents with nonspecific flu-like symptoms, as well as cough and dyspnea, and where no etiological agent is found.
Epidemiology
Cryptogenic organizing pneumonia (COP) represents 5-10% of interstitial lung diseases. The annual incidence in Iceland has been estimated at 1/90,900.
Clinical description
Mean age of onset is 50-60 years of age and patients present with nonspecific features of mild fever, non-productive cough, malaise, anorexia, weight loss and progressive but mild-to-moderate dyspnea. At auscultation, focal and sparse crackles are often found over the involved areas with clinical features of consolidation in some. There is no sign of finger clubbing. There is often a delay of 3 months or more between the onset of first symptoms and diagnosis. In rapidly progressive cases, dyspnea can be severe. Rare manifestations include chest pain, night sweats, and hemoptysis. Pneumothorax and pneumomediastinum have been reported. COP usually resolves with treatment but relapses occur in up to half of the cases. Though most diagnosed cases are now treated, spontaneous improvement occurring over 3-6 months has also been reported.
Etiology
Etiology is unknown. The stages of COP pathogenesis include the injury phase (permeability edema and fibrin deposits in response to alveolar cell injury), the proliferating phase (formation of fibroinflammatory buds), the mature phase (presence of ''mature'' fibrotic buds in the alveolar space) and the resolution phase (reversibility of lesions).
Diagnostic methods
Diagnosis is based on clinical picture, imaging, histopathology of the lung and the exclusion of all causes of secondary OP. High resolution computed tomographic scan reveals 3 main imaging patterns: multiple patchy alveolar opacities that may migrate (in the majority of cases; typical COP), a solitary focal nodule or mass (focal COP), or diffuse infiltrative opacities (infiltrative or progressive fibrotic COP). Video-assisted thoracoscopy is the method of choice in obtaining lung tissue but transbronchial biopsies, core needle biopsies, and recently transbronchial cryobiopsies are alternate methods. Hallmark histological findings of OP are patchy filling of the lung alveoli and respiratory bronchioles by buds of granulation tissue composed of fibroblasts and myofibroblasts (Masson bodies). Fiberoptic bronchoscopy with bronchoalveolar lavage reveals a mixed inflammatory profile with marked increase in lymphocytes and slight increase in neutrophils and eosinophils. Elevated C-reactive protein serum level and peripheral blood neutrophil count are reported.
Differential diagnosis
The main differential diagnosis is idiopathic chronic eosinophilic pneumonia. Secondary OP must also be excluded by elimination of its possible causes, including primary biliary cirrhosis, ulcerative colitis, Crohn disease, Sweet syndrome, sarcoidosis, Behçet disease, primary pulmonary lymphoma, drugs, inhalation exposure, infections, all connective tissue diseases, especially rheumatoid arthritis and idiopathic inflammatory myopathies, and other specific contexts like solid organ transplantation, bone marrow transplantation, etc.
Management and treatment
Standard therapy for COP is corticosteroids, usually with prednisone doses of 0.75 mg/kg/day for 4 weeks that gradually decreases over a period of 24 weeks. In those with rapidly progressing COP, high-dose intravenous methylprednisolone can be given. Focal COP is often diagnosed by the removal of lesions initially thought to be neoplastic, with further therapy often not needed. Relapses should be treated with a starting dose of 20 mg/day of prednisone then tapered over a period of 12 weeks. Relapses that occur too often or while undergoing corticosteroid therapy should prompt a reappraisal of the diagnosis. Immunosuppressive therapy may rarely be used in severe infiltrative COP.
Prognosis
The prognosis is usually good with most cases resolving after corticosteroid treatment. Morbidity is mostly related to prolonged corticosteroid treatment. However, relapses are seen in 13-58% of patients and can have an effect on quality of life if they are frequent.

                            Last update: 
                            October 2022


                            - Expert reviewer(s): 
                            Pr Vincent COTTIN | ERN-LUNG*


                                * European Reference Network