How I diagnose and treat organizing pneumonia in hematopoietic cell transplant recipients.

ABSTRACT: Organizing pneumonia (OP) is a known noninfectious pulmonary complication following allogeneic hematopoietic cell transplant (HCT) and represents a significant risk factor for nonrelapse mortality in HCT recipients. Unlike bronchiolitis obliterans syndrome, it is not universally acknowledged as a distinctive pulmonary manifestation of chronic graft-versus-host disease (cGVHD) and, therefore, its diagnostic criteria and management approach are lacking. Given its shared similar clinical features and radiological and histologic findings to OP in the non-HCT population, the diagnostic approach and treatment strategy for OP in HCT recipients is largely adapted from the non-HCT population. In this article, we aim to enhance the understanding of OP within the context of cGVHD following HCT and distinguish its clinical features and treatment strategy from non-HCT counterparts, thereby reinforcing its recognition as a pulmonary manifestation of graft-versus-host disease. We will propose the diagnostic criteria and outline our approach in diagnosis and treatment strategy, highlighting the potential challenges that may arise in each process. Finally, we will discuss knowledge gaps in this field and identify the area of need for future research.

¿Enfermedad o reacción pulmonar intersticial? Investigar hasta encontrar el origen / Interstitial lung disease or reaction? Investigate until you find the source

La neumonía organizativa es un patrón histológico que puede observarse asociado o reactivo en diferentes patologías.Presentamos el caso de una mujer de 67 años con diagnóstico inicial de neumonía organizada criptogénica, sin respuestaa los glucocorticoides y autoinmunidad negativa. Finalmente, la neumonía organizada resultó ser secundaria a neoplasiahematológica. En estos casos es importante insistir en la anamnesis y realizar los procedimientos necesarios para conseguirel diagnóstico definitivo.(AU)

Organizational pneumonia is a histological pattern that can be observed associated or reactive in different pathologies. Wepresent the case of a 67-year-old woman with an initial diagnosis of organized pneumonia, no response to glucocorticoidsand negative autoimmunity. Finally, organized pneumonia was found to be secondary to hematologic malignancy. In thesecases, it is important to insist on the anamnesis and perform the necessary procedures to achieve the definitive diagnosis.(AU)

Mujer de 66 años con nódulos cutáneos recurrentes, esplenomegalia, anemia hemolítica y neumonía organizada / A 66-year-old woman with recurrent skin nodules, splenomegaly, hemolytic anemia, and organizing pneumonia

We present the case of a women previously diagnosed with nodularpanniculitis (biopsy compatible with neutrophilic dermatosis) andmultifactorial anemia with signs of hemolysis and splenomegaly,who refers reappearance of painful nodules in extremities and general syndrome. The differential diagnosis of the coexistence of these alterations is proposed, with the subsequent solution of the case. (AU)

Presentamos el caso de una mujer con diagnóstico previo de paniculitis nodular con biopsia compatible con dermatosis neutrofílicay anemia multifactorial con componente hemolítico asociada a esplenomegalia, que consulta por reaparición de nódulos dolorososen extremidades y síndrome general. Se plantea el diagnóstico diferencial de la aparición conjunta de estas alteraciones y posteriorresolución del caso clínico. (AU)

[Update 2021: Pulmonary Sequelae of COVID-19 Pneumonia]. / Update 2021: Pulmonale Folgen nach COVID-19-Pneumonie.

Acute COVID-19 pneumonia may result in persistent changes with various imaging and histopathological patterns, including organizing pneumonia and pulmonary fibrosis. In addition, SARS-CoV-2 infection is associated with increased risk of pulmonary vascular endothelialitis and thrombosis. Herein, current findings on pulmonary consequences of COVID-19 with implications for clinical management are summarized based on a selective literature review.

Organizing pneumonia in ALK+ lung adenocarcinoma treated with ceritinib: A case report and literature review.

RATIONALE: Anaplastic lymphoma kinase (ALK) inhibitors have been approved for patients with ALK-rearrangement lung cancer. The effect is superior to the standard first-line therapy of pemetrexed plus platinum-based chemotherapy. However, ALK inhibitors are associated with rare and sometimes fatal adverse events. Organizing pneumonitis (OP) is a rare and serious adverse event usually caused by ceritinib, and it is easily misdiagnosed as infectious pneumonia, metastasis, or cancer progression. PATIENT CONCERNS: A 56-year-old female presented with chest tightness and dyspnea for more than 10 days. She was previously healthy with no significant medical history. Workup including chest computed tomography (CT), pathological examination of a biopsy specimen, and next-generation sequencing was consistent with a diagnosis of IVA ALK-rearrangement lung adenocarcinoma. She was treated with pemetrexed plus platinum-based chemotherapy and crizotinib concurrently, followed by maintenance therapy with crizotinib alone and she had an almost complete response. However, about 26 months after beginning treatment she developed multiple brain metastases. Crizotinib was discontinued and she was begun on ceritinib. After about 3 months the brain metastases had almost complete response. After 5 months of ceritinib, however, multiple patchy lesions appeared in the bilateral upper lungs. DIAGNOSES: Treatment with antibiotics had no effect and blood and sputum cultures are negative. A CT-guided biopsy of the upper lung was performed, and pathological hematoxylin-eosin staining and immunohistochemical studies were consistent with OP. INTERVENTIONS: Ceritinib was discontinued, she was begun on prednisone 0.5 mg/kg orally every day, and regular follow-up is necessary. OUTCOMES: CT of the chest 2 and 4 weeks after beginning prednisone showed the lung lesions to be gradually resolving, and she was continued on prednisone for 2 months and gradually reduced the dose of prednisone every 2 weeks. No related adverse events were occurred in patient. LESSONS: OP must be differentiated from infectious pneumonia, metastasis, or cancer progression. The mechanism of OP is still unknown and needs further research. Biopsy plays a role in making a diagnosis of OP. In our patient, discontinuing ceritinib and treating her with prednisone resulted in a good outcome.

A 69-Year-Old Woman With Ulcerative Colitis and Pulmonary Nodules.

CASE PRESENTATION: A 69-year-old woman with a medical history significant for COPD, ulcerative colitis (UC), and tobacco dependence was referred to a pulmonologist for lung nodules found on routine annual low-dose CT scan for lung cancer screening. Her review of systems was negative for dyspnea, angina, hemoptysis, fever, night sweats, anorexia, and weight loss. She had a successful total proctocolectomy with ileal pouch-anal anastomosis performed 5 years ago because of acute fulminant UC refractory to corticosteroids and biologic agents. Her home medications were albuterol inhaler, umeclidinium, and vilanterol inhalation powder. She denied any history of lung cancers in her family. She was an active smoker and had a 35-pack-year smoking history. She worked as a cashier in a local supermarket and had been doing so for the past 25 years.

[Medical prevention and treatment of radiation-induced pulmonary complications]. / Prévention médicale et traitement des complications pulmonaires secondaires à la radiothérapie.

Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury.

A Cryptogenic Case of Fulminant Fibrosing Organizing Pneumonia.

Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. Rare cases of organizing pneumonia are rapidly progressive. Yousem et al. studied pathologic predictors of idiopathic bronchiolitis obliterans organizing pneumonia/COP with an unfavorable prognosis. Beardsley and Rassl proposed the name fibrosing organizing pneumonia (FOP). A 74-year-old female non-smoker presented with a 2-week history of dry cough followed by dyspnea and a fever. The clinical course was fulminant, but we successfully performed bronchoscopy. After the diagnosis of FOP, we treated the patient with mechanical ventilation and high-doses of steroids/immunosuppressants, which improved the disease.

[Radiation-induced bronchiolitis obliterans with organizing pneumonia]. / Complications pulmonaires de la radiothérapie après cancer du sein : penser à la BOOP.

Bronchiolitis obliterans with organizing pneumonia is an inflammatory reaction that can occur as a consequence of various pulmonary affections. Radiotherapy is not the sole and systematic cause of bronchiolitis obliterans with organizing pneumonia. Radiation-induced should not be confused with post-radiation, dose-dependent, inflammatory pulmonary fibrosis, which is non-immunological and located within the irradiation field. The role of immunity, local inflammation and individual radiosensitivity in bronchiolitis obliterans with organizing pneumonia is not well defined. Bronchiolitis obliterans with organizing pneumonia represents 1% of irradiated patients with breast cancer. It results in fever (flu-like symptoms), a rather dry cough and dyspnea. In the post-radiation context, bronchiolitis obliterans with organizing pneumonia may be diagnosed several months and up to a year after breast irradiation. The treatment consists of prolonged steroids or immunosuppressants, which do not prevent chronicity in 15% of patients and death in up to 5% of cases, the remaining 80% of patients healing without sequelae.

[Cryptogenic organizing pneumonia]. / Pneumopathie organisée cryptogénique.

INTRODUCTION: Organizing pneumonia is a particular type of inflammatory reaction of the lung which gives rise to a clinico-pathological syndrome. It is called "secondary" when a cause such as an infection, a drug toxicity, or a connective tissue disease can be identified, or "cryptogenic" when no cause is identified. The clinical picture is usually characterized by the subacute onset of fever, fatigue, cough and dyspnea, with multiple subpleural areas of consolidation on thoracic imaging. STATE OF THE ART: Organizing pneumonia is characterised by the presence of buds of endoalveolar connective tissue. These result from an injury to the alveolar epithelium, followed by the deposition of fibrin in the alveolar spaces, and the migration of fibroblasts which produce a myxoid endoalveolar matrix. A remarkable feature of organizing pneumonia is the complete disappearance of these endoalveolar buds with corticosteroid treatment, in sharp contrast with what is seen in pulmonary fibrosis. The clinical response to corticosteroids is usually prompt and excellent. Relapses are frequent but usually benign. PERSPECTIVES AND CONCLUSION: As the clinical, imaging and pathological characteristics of organizing pneumonia are now well established, many questions remain unanswered, such as the mechanisms involved in the complete reversibility of the pulmonary lesions, and the role of steroid-sparing treatments such as immunomodulatory macrolides.

Azacitidine-induced cryptogenic organizing pneumonia: a case report and review of the literature.

BACKGROUND: Myelodysplasia syndrome is a heterogeneous group of hematological disorders that are characterized by abnormal morphology and cytopenias of bone marrow elements. Azacitidine is a hypomethylating agent that is commonly used in treatment of myelodysplasia syndrome. We present an extremely rare case of cryptogenic organizing pneumonia following therapy with azacitidine and a review of the relevant literature. This is the fifth case of azacitidine-induced interstitial lung disease and the sixth one due to hypomethylating drugs; of interest, this is the first reported case that has occurred after the second cycle. Our case report highlights an important, potentially treatable and rare side effect of azacitidine and hypomethylating agents in general that might be overlooked by oncologists. Furthermore, our review of the literature showed heterogeneity in the clinical outcome which might, in part, be due to delay in initiating corticosteroids treatment. CASE PRESENTATION: A 67-year-old white man presented with worsening shortness of breath and mild productive cough that started 1 week prior to his presentation. An initial chest X-ray showed infiltration of both lung fields. Radiographic findings of computed axial tomography, results of bronchoscopy and a lung biopsy were consistent with cryptogenic organizing pneumonia. The patient showed variable clinical response to steroids and he remained dependent on home oxygen. CONCLUSIONS: We concluded that there is a recognizable potentially life-threatening toxicity due to organizing pneumonia secondary to azacitidine in the setting of myelodysplasia syndrome treatment. This toxicity is not limited to the first cycle as in previous cases; furthermore, pleural effusion can be associated with this toxicity. Health care professionals should be aware of this recognizable side effect. Early recognition and timely management are critical to prevent permanent lung fibrosis.

Bronchiolitis obliterans organizing pneumonia in patients with autoimmune rheumatic diseases.

Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by buds of granulation tissue within lung distal airspaces. The diagnosis requires the histopathologic evidence of organizing pneumonia along with a suggestive clinical and radiographic pattern. This disorder is characterized by a good response to corticosteroids and an excellent prognosis. It can occur in association with a broad spectrum of clinical conditions or can be isolated, in this last case named cryptogenic organizing pneumonia. We searched for BOOP in patients with autoimmune rheumatic diseases (ARD) in the literature, and we found 32 well-documented cases. We reported here demographic features, manifestations, treatment and outcome of patients with BOOP associated with ARD. Notably, BOOP can be the presenting feature in some patients with ARD; thus, a close follow-up of patients with BOOP is recommended.

The diagnostic utility of chest computed tomography scoring for the assessment of amiodarone-induced pulmonary toxicity.

BACKGROUND/AIMS: Amiodarone is one of the most widely used antiarrhythmic agents; however, amiodarone-induced pulmonary toxicity (APT) can be irreversible and sometimes fatal. The aim of this study was to evaluate the feasibility of chest computed tomography (CT) as a diagnostic tool for APT and to assess the utility of the CT APT score as an index for predicting the severity of APT. METHODS: Patients underwent amiodarone treatment for various reasons, most often atrial fibrillation, for more than 2 years, and those that received a cumulative dose > 100 g were enrolled. A total of 34 patients who underwent chest CT between December 2011 and June 2012 were enrolled, whether or not they had clinical symptoms. The APT CT score was defined as the number of involved regions in the lung, which was divided into 18 regions (right and left, upper, middle, and lower, and central, middle, and peripheral). The CT findings were evaluated according to the total dose and duration of amiodarone treatment and the results of a pulmonary function test. Clinical symptoms and outcomes were also evaluated according to APT CT scores. RESULTS: Seven patients had positive APT CT scores (interstitial fibrosis in five, organizing pneumonia in one, and mixed interstitial fibrosis and organizing pneumonia in one), and these patients exhibited significantly lower diffusion capacity for carbon monoxide in the lungs compared with patients without an increased APT CT score (70.2% ± 6.9% vs. 89.7% ± 19.4%; p = 0.011). Three of the seven patients experienced overt APT that required hospital admission. CONCLUSIONS: Chest CT is a useful diagnostic tool for APT, and the APT CT score might be a useful index for assessing the severity of APT.

Radiographic patterns in the diagnostic approach to organizing pneumonia.

A 56-year-old woman, non-smoker, who complained of dry cough and dyspnea during the last month came to the emergency department due to increased dyspnea. The chest X-ray showed areas of poorly defined, bilateral alveolar opacities, leading to the diagnosis of bronchopneumonia with partial respiratory failure. During admission, she experienced an exacerbation of the dyspnea. A high-resolution computed tomography scan was performed, showing areas of ground glass opacities with interlobular septal thickening ("crazy-paving" pattern), predominantly in lower lobes. She required mechanical ventilation and she was admitted to the intensive care unit. Subsequently, an open lung biopsy was performed. The following questions should be proposed:

[Cryptogenic organizing pneumonia]. / La pneumonie organisée cryptogénique.

Cryptogenic organizing pneumonia (COP) is a distinct clinico-pathologic entity described for the first time by Davison in 1983 and 2 years later by Epler under the name of idiopathic Bronchiolitis Obliterans Organizing Pneumonia (BOOP). It most often presents with the clinical and radiological features of an infectious pneumonia which fails to respond to antibiotic therapy. In this article, we will review the clinical and radiographic features, diagnostic assessment, and the treatment of COP.

Is acute fibrinous and organizing pneumonia the expression of immune dysregulation?

INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a recently described histologic pattern of diffuse pulmonary disease. In children, all cases reported to date have been fatal. In this study, we describe the first nonfatal AFOP in a child and review the literature. DESCRIPTION: A 10-year-old boy developed very severe aplastic anemia (VSAA) after being admitted to our hospital with a fulminant hepatic failure of unknown origin. A chest computed tomography scan revealed multiple lung nodules and a biopsy of a pulmonary lesion showed all the signs of AFOP. Infectious workup remained negative. We started immunosuppressive therapy with antithymocyte globulin and cyclosporine to treat VSAA. Subsequent chest computed tomography scans showed a considerable diminution of the lung lesions but the VSAA did not improve until we performed hematopoietic stem cell transplantation 5 months later. CONCLUSIONS: Aplastic anemia is associated with a variety of autoimmune syndromes. The sequence of events in our patient suggests that the hepatic failure, AFOP, and the VSAA may all have been part of an autoimmune syndrome. AFOP could be the result of immune dysregulation in this pediatric case with favorable outcome after immunosuppressive therapy and hematopoietic stem cell transplantation.