The Relentless Recurrence of Diffuse Alveolar Hemorrhage in Catastrophic Antiphospholipid Syndrome and Lupus: A Therapeutic Challenge.

Diffuse alveolar hemorrhage (DAH), a rare complication of coexisting antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE), poses significant diagnostic and therapeutic challenges, especially with recurrent episodes. We present a 27-year-old male with catastrophic APS and SLE who experienced acute respiratory failure and hemoptysis due to DAH. Despite aggressive therapy with immunosuppressants, plasma exchange, and anticoagulation, he had recurrent DAH episodes requiring repeated admissions. Early recognition, multidisciplinary management, and utilization of effective targeted therapies, such as intravenous immunoglobulin, in refractory cases are crucial for improving outcomes in this challenging complication.

A Case of Dupilumab-Induced Diffuse Alveolar Hemorrhage.

Eosinophilic pneumonia is a known side effect of dupilumab; however, diffuse alveolar hemorrhage has not yet been reported in association with dupilumab. We herein report a case of diffuse alveolar hemorrhage caused by dupilumab. A 57-year-old man with severe asthma was unable to discontinue oral steroids and thus was prescribed dupilumab. The patient was admitted to the hospital four weeks after treatment because of suspected eosinophilic pneumonia. Bronchoscopy revealed diffuse alveolar hemorrhage characterized by hemosiderin-phagocytic macrophages in the bronchoalveolar lavage fluid without eosinophils. The steroid dosage improved the respiratory status and resolved the infiltrate shadow. Dupilumab may thus cause diffuse alveolar hemorrhage, which can be differentiated using bronchoscopy.

Recurrent diffuse alveolar hemorrhage and extracorporeal membrane oxygenation utilization in a hematopoietic stem cell transplant patient with Hunter's syndrome.

We describe the natural history of a three-month-old patient with Hunter Syndrome with hematopoietic stem cell transplant (HSCT) who developed recurrent diffuse alveolar hemorrhage (DAH) requiring extracorporeal membrane oxygenation (ECMO). The patient underwent HSCT with several complications, including veno-occlusive disease and DAH. He was managed with ECMO. Unfortunately, despite initial success he developed recurrent DAH and ultimately died. This is a novel report of this severe adverse event requiring ECMO following the use of HSCT in this rare patient population. We share the clinical strategies employed to address the complications associated with HSCT and the progression of his disease over his hospitalization.

Pulmonary Manifestation of Granulomatosis With Polyangiitis: A Challenging Case Presentation.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare and potentially life-threatening autoimmune disease characterized by antineutrophil cytoplasmic antibody (ANCA)-associated vasculature inflammation. It presents as a systemic autoimmune disease with necrotizing granulomatous inflammation and pauci-immune small vessel vasculitis. This case initially posed a diagnostic challenge due to its atypical presentation and was misdiagnosed as hypersensitivity pneumonitis. The avian precipitin screening assay was positive in our patient, which may be consistent with bird breeder's lung disease or a non-specific reactivity of the chicken antigen test. However, the presence of positive c-ANCA was pivotal for the GPA diagnosis. Here, we describe in detail the clinical manifestations, diagnostic approach, and treatment of GPA in a 54-year-old female who presented with alveolar hemorrhage, but no renal involvement. Treatment involved the use of high-dose corticosteroids to suppress the autoimmune response. Finally, we discuss the striking response of this unique form of granulomatosis with polyangiitis to corticosteroid treatment and emphasize the importance of early initiation of treatment.

A Fatal Case of Drug-Induced Lung Injury Potentially Related to Olanzapine.

Drug-induced lung injury (DILI) occurs when exposure to a drug leads to inflammation and, eventually, fibrosis of the lung interstitium. While DILI is a rare side effect of antipsychotic medication, once it manifests, it requires detailed investigation and prompt treatment. Diagnosing DILI can be challenging at times due to its similarity to conditions such as infectious diseases or interstitial pneumonia induced by other causes. We hereby report a fatal case of suspected DILI associated with olanzapine. A 61-year-old female with a history of delusional disorder was admitted to our hospital due to worsened psychiatric symptoms. Ten milligrams of olanzapine had been initiated a week prior to admission by a psychiatrist at the local clinic to control these symptoms. After admission, although the patient claimed no respiratory symptoms, she developed a slight fever and deterioration of chest radiologic findings. Bronchoalveolar lavage revealed a progressively bloody return of fluid, suggesting pulmonary alveolar hemorrhage. Since no respiratory disorders have been noted, and considering the exclusion of other potential diagnoses, DILI was strongly suspected. Although olanzapine was promptly discontinued, the patient's condition rapidly deteriorated. Despite high-dose steroid therapy, the patient's response to treatment was inadequate, and she finally succumbed to the illness. This case highlights that olanzapine may induce lung injury similar to other psychiatric drugs. Furthermore, early diagnosis and treatment are essential for patients with psychiatric disorders who may sometimes present with fewer symptoms.

Clinical characteristics, radiological features and outcomes in pulmonary involvement of cryoglobulinemia.

BACKGROUND: Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood. METHODS: Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia. RESULTS: The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001). CONCLUSIONS: A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome.

Intrapulmonary administration of recombinant activated factor VII in pediatric, adolescent, and young adult oncology and hematopoietic cell transplant patients with pulmonary hemorrhage.

Introduction: Diffuse alveolar hemorrhage (DAH) is a devastating disease process with 50-100% mortality in oncology and hematopoietic cell transplant (HCT) recipients. High concentrations of tissue factors have been demonstrated in the alveolar wall in acute respiratory distress syndrome and DAH, along with elevated levels of tissue factor pathway inhibitors. Activated recombinant factor VII (rFVIIa) activates the tissue factor pathway, successfully overcoming the tissue factor pathway inhibitor (TFPI) inhibition of activation of Factor X. Intrapulmonary administration (IP) of rFVIIa in DAH is described in small case series with successful hemostasis and minimal complications. Methods: We completed a single center retrospective descriptive study of treatment with rFVIIa and outcomes in pediatric oncology and HCT patients with pulmonary hemorrhage at a quaternary hematology/oncology hospital between 2011 and 2019. We aimed to assess the safety and survival of patients with pulmonary hemorrhage who received of IP rFVIIa. Results: We identified 31 patients with pulmonary hemorrhage requiring ICU care. Thirteen patients received intrapulmonary rFVIIa, while eighteen patients did not. Overall, 13 of 31 patients (41.9%) survived ICU discharge. ICU survival (n=6) amongst those in the IP rFVIIa group was 46.2% compared to 38.9% (n=7) in those who did not receive IP therapy (p=0.69). Hospital survival was 46.2% in the IP group and 27.8% in the non-IP group (p=0.45). There were no adverse events noted from use of IP FVIIa. Conclusions: Intrapulmonary rFVIIa can be safely administered in pediatric oncology patients with pulmonary hemorrhage and should be considered a viable treatment option for these patients.

A Rare Presentation of Late-Onset Idiopathic Pulmonary Hemosiderosis: A Case Report.

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage (DAH). It is associated with a high mortality rate and recurrent episodes of widespread alveolar hemorrhage and most commonly affects children. Here, we present a rare occurrence of late-onset idiopathic pulmonary hemosiderosis in a 74-year-old male. He was admitted for non-resolving pneumonia, hemoptysis, and type 1 respiratory failure, along with sideropenic anemia. Chest imaging showed bilateral upper lobe and right middle lobe alveolar opacities. Infective and autoimmune etiologies of diffuse alveolar hemorrhage were ruled out during the evaluation. Transbronchial lung biopsy showed patchy alveolar hemorrhage and abundant hemosiderin pigment deposition, revealing idiopathic pulmonary hemosiderosis. The patient was successfully treated with oral steroids, followed by complete radiological resolution without clinical relapse at one-year follow-up.

Massive hemoptysis with end stage renal disease (ESRD): An initial symptom of rare disease.

Microscopic polyangiitis is a rare autoimmune vasculitis, that could present with renal-pulmonary symptoms, posing diagnostic challenges in patients with preexisting kidney disease. Timely diagnosis is crucial to improve patient outcomes.

Diffuse Alveolar Hemorrhage Caused by Disseminated Cryptococcosis in a Patient With Systemic Lupus Erythematosus.

A teenage girl with systemic lupus erythematosus (SLE) was admitted with fever, dry cough, and dyspnea on exertion. Chest computed tomography revealed bilateral diffuse infiltration and swelling of the mediastinal lymph nodes. The bronchoalveolar lavage (BAL) fluid was light red, suggesting diffuse alveolar hemorrhage (DAH). Therefore, glucocorticoid pulse therapy was initiated. However, blood and BAL fluid cultures showed the growth of Cryptococcus neoformans. The patient was diagnosed with disseminated cryptococcosis. The patient was treated with liposomal amphotericin B and flucytosine; the prednisolone dose was rapidly tapered. Infections should be thoroughly ruled out in patients with SLE and DAH.

Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS).

Rationale: Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The PEXIVAS (Plasma Exchange and Glucocorticoids in Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis) (NCT00987389) trial was the largest in AAV and the first to enroll participants with DAH requiring mechanical ventilation. Objectives: Evaluate characteristics, treatment effects, and outcomes for patients with AAV with and without DAH. Methods: PEXIVAS randomized 704 participants to plasma exchange (PLEX) or no-PLEX and reduced or standard-dose glucocorticoids (GC). DAH status was defined at enrollment as no-DAH, nonsevere, or severe (room air oxygen saturation of ⩽ 85% as measured by pulse oximetry, or use of mechanical ventilation). Measurements and Main Results: At enrollment, 191 (27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3 (proteinase 3)-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH (n = 513; 72.9%). Among those with DAH, 8/95 (8.4%) receiving PLEX died within 1 year versus 15/96 (15.6%) with no-PLEX (hazard ratio, 0.52; confidence interval [CI], 0.21-1.24), whereas 13/96 (13.5%) receiving reduced GC died versus 10/95 (10.5%) with standard GC (hazard ratio, 1.33; CI, 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX versus no-PLEX (medians, 25; interquartile range [IQR], 22-26 vs. 22-27) and fewer with reduced GC (median, 23; IQR, 20-25) versus standard GC (median, 26; IQR, 25-28). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within 1 year versus 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Conclusions: Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Original clinical trial registered with www.clinicaltrials.gov (NCT00987389).

Diffuse Alveolar Hemorrhage Occurring Suddenly in a Diabetic Patient With Asthma Exacerbation.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially life-threatening condition characterized by bleeding into the alveolar spaces of the lungs. DAH can occur due to a wide range of etiologies including autoimmune diseases, infections, drugs, and malignancies. The clinical presentation is variable and may include cough, dyspnea, fever, and hemoptysis. Diagnosis is often challenging due to the nonspecific symptoms and a lack of definitive diagnostic criteria. Treatment is primarily aimed at addressing the underlying cause and providing supportive care.

Pulmonary Renal Syndrome in ANCA-Negative Vasculitis.

Below we highlight a rare case of anti-neutrophil cytoplasmic antibody (ANCA)-negative vasculitis, unique in its own right, as the diagnosis was hard to make and the respiratory decline rapid, with the patient going from a 23% fraction of inspired oxygen (FiO2) on admission to 100% FiO2 within four days for what was initially presumed to be community-acquired pneumonia. Precise data on the incidence or prevalence of ANCA-associated vasculitis are lacking. However, a 20-year population-based study in the United States found that, of 58 incident cases, 9% were ANCA-negative. We present the case of a 69-year-old Egyptian male with worsening shortness of breath who was found to have elevated inflammatory markers and an ANCA-negative panel and was later diagnosed with ANCA-negative vasculitis. By highlighting this case, we aim to increase awareness and point out the need to keep the disease high on the list of differential diagnoses in order to allow for timely intervention. Though there isn't a lot of data available on definitive treatment or the disease itself, there are studies that point to rituximab, cyclophosphamide, plasmapheresis, and hemodialysis as useful interventions for treatment.

Rare case of cardiac angiosarcoma and alveolar hemorrhage in an adolescent patient initially suspected COVID19 infection: A case report and literature review.

Primary cardiac tumors are a rarity, and sarcomas emerge as the prevailing form of primary malignant cardiac tumors across age groups, encompassing both children and adults. Within this category, angiosarcoma stands out, constituting around 31% of all primary malignant cardiac tumors. Primary cardiac angiosarcoma displays a notably aggressive nature, characterized by early systemic metastasis, and is accompanied by a generally unfavorable prognosis. We describe a case concerning a previously healthy teenage girl who displayed persistent constitutional symptoms and hemoptysis for 15 days. Subsequent investigation uncovered alveolar hemorrhage, ultimately linked to a cardiac angiosarcoma. The difficulty in this instance arose from the vague nature of the initial symptoms, posing a challenge to promptly and accurately diagnose the condition. This case highlights the aggressive nature of primary cardiac angiosarcoma. The vague initial symptoms underscore the need for early detection and optimized treatment to improve the generally unfavorable prognosis associated with this condition. Increased awareness and a multidisciplinary approach are crucial in addressing the diagnostic and therapeutic challenges posed by primary cardiac angiosarcoma.

Algorithms Identifying Patients With Acute Exacerbation of Interstitial Pneumonia and Acute Interstitial Lung Diseases Developed Using Japanese Administrative Data.

BACKGROUND: We aimed to develop algorithms to identify patients with acute exacerbation of interstitial pneumonia and acute interstitial lung diseases using Japanese administrative data. METHODS: This single-center validation study examined diagnostic algorithm accuracies. We included patients >18 years old with at least one claim that was a candidate for acute exacerbation of interstitial pneumonia, acute interstitial lung diseases, and pulmonary alveolar hemorrhage who were admitted to our hospital between January 2016 and December 2021. Diagnoses of these conditions were confirmed by at least two respiratory physicians through a chart review. The positive predictive value was calculated for the created algorithms. RESULTS: Of the 1,109 hospitalizations analyzed, 285 and 243 were for acute exacerbation of interstitial pneumonia and acute interstitial lung diseases, respectively. As there were only five cases of pulmonary alveolar hemorrhage, we decided not to develop an algorithm for it. For acute exacerbation of interstitial pneumonia, acute interstitial lung diseases, and acute exacerbation of interstitial pneumonia or acute interstitial lung diseases, algorithms with high positive predictive value (0.82, 95% confidence interval: 0.76-0.86; 0.82, 0.74-0.88; and 0.89, 0.85-0.92, respectively) and algorithms with slightly inferior positive predictive value but more true positives (0.81, 0.75-0.85; 0.77, 0.71-0.83; and 0.85, 0.82-0.88, respectively) were developed. CONCLUSION: We developed algorithms with high positive predictive value for identifying patients with acute exacerbation of interstitial pneumonia and acute interstitial lung diseases, useful for future database studies on such patients using Japanese administrative data.

Successful rituximab therapy in adult-onset IgA vasculitis with diffuse alveolar hemorrhage and renal failure: a case report.

Background: Immunoglobulin A vasculitis (IgAV) is a rare condition that most commonly presents during childhood. Patients with adult-onset IgAV are more likely to exhibit severe symptoms at presentation with worse renal outcomes. Pulmonary manifestations of adult-onset IgAV have been described rarely in the literature and often indicate higher morbidity and mortality. Given the rarity of alveolar hemorrhage in IgAV, the literature describing the clinical entity and offering management recommendations is insufficient. Case Description: We describe a patient with known adult-onset IgAV who presented with one month of abdominal pain, bloody stools, new skin lesions, and progressive shortness of breath. She developed rapidly worsening hypoxic respiratory failure associated with a hemoglobin drop and diffuse pulmonary infiltrates on imaging. Bronchoscopy demonstrated progressively hemorrhagic effluent on bronchoalveolar lavage (BAL) consistent with a diagnosis of diffuse alveolar hemorrhage (DAH). She developed acute renal failure requiring the initiation of emergent renal replacement therapy. Given concomitant DAH and acute renal failure, methylprednisolone and rituximab (RTX) therapy were initiated. With this treatment regimen, she exhibited marked improvement in respiratory function and complete renal recovery. Conclusions: This case highlights the importance of considering DAH as a rare and life-threatening pulmonary manifestation of adult-onset IgAV. Our case demonstrates the novel and successful use of RTX in combination with steroids to treat a patient with adult-onset IgAV presenting with concomitant DAH and renal failure.

An Adult Case of Idiopathic Pulmonary Hemosiderosis Associated with Pulmonary Fibrosis and Emphysematous Change.

A 48-year-old woman was admitted to our hospital with acute respiratory failure. Chest computed tomography showed ground-glass opacity and patchy emphysematous lesions in both lungs. Corticosteroid therapy was effective; however, the disease worsened with the tapering of corticosteroids. Bronchoalveolar lavage revealed hemosiderin-laden macrophages, and video-assisted thoracic surgery showed diffuse interstitial fibrosis with diffuse alveolar hemorrhage (DAH). There was no evidence of vasculitis nor autoimmune diseases. This patient was diagnosed with idiopathic pulmonary hemosiderosis (IPH) that progressed to end-stage pulmonary fibrosis despite treatment. Autopsy demonstrated DAH with pulmonary fibrosis and emphysematous change, suggesting IPH-related pulmonary lesions.

[Lung involvement in autoinflammatory diseases]. / Atteinte pulmonaire dans les maladies auto-inflammatoires.

Genetic autoinflammatory diseases are now a recognized and rapidly expanding group. The lung involvement historically associated with autoinflammatory diseases is inflammatory seritis, primarily seen in familial Mediterranean fever and other interleukin-1 mediated diseases. Over the last ten years, pulmonary involvement has been the core presentation of two autoinflammatory diseases associated with constitutive type I interferon activation, i.e. SAVI and COPA syndrome. Most patients with these diseases usually develop early progression to pulmonary fibrosis, which is responsible for high rates of morbidity and mortality. Other rare autoinflammatory diseases are associated with alveolar proteinosis, particularly when related to MARS mutations. Additionally, in adults, VEXAS is frequently associated with pulmonary involvement, albeit without prognosis effect. A molecular approach to autoinflammatory diseases enables not only the definition of biomarkers for diagnosis, but also the identification of targeted treatments. Examples include JAK inhibitors in SAVI and COPA syndrome, even though this therapy does not prevent progression to pulmonary fibrosis. Another illustrative example is the efficacy of methionine supplementation in alveolar proteinosis linked to MARS mutations. Overall, in autoinflammatory diseases the lung is now emerging as a possible affected organ. Continuing discovery of new autoinflammatory diseases is likely to uncover further pathologies involving the lung. Such advances are expected to lead to the development of novel therapeutic perspectives.

An Atypical Case of Microscopic Polyangiitis Associated With Myelodysplastic Syndrome and Complete Atrioventricular Block Mistaken for Infectious Pneumonia.

The association between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and hematologic malignancy has been previously described and remains a rare phenomenon (although potentially underdiagnosed). We report the case of an 81-year-old patient with myelodysplastic syndrome who was managed for an infectious-appearing pneumonia, which subsequently complicated into complete heart block and severe acute respiratory distress syndrome with a fatal outcome. The final diagnosis is severe hemorrhagic alveolitis due to ANCA-associated vasculitis meeting the criteria for microscopic polyangiitis. This article provides an opportunity to discuss the association between ANCA-associated vasculitis and hematologic malignancies and the adverse prognosis associated with it.

Neumonía por Pneumocystis jirovecii asociada a hemorragia alveolar difusa en un paciente con trasplante renal / Pneumocystis jirovecii pneumonia associated with diffuse alveolar hemorrhage in a renal transplant patient. Case report

La neumonía por Pneumocystis jirovecii es una enfermedad fúngica oportunista descrita principalmente en pacientes con VIH, sin embargo, tras la introducción de la TARV, ha incrementado su incidencia en pacientes con inmunosupresión no asociada a VIH, como neoplasias hematológicas y trasplantes de órganos sólidos. Presentamos el caso de un varón de 17 años, receptor de un trasplante renal, con inmunosupresión prolongada con corticoesteroides, con cuadro clínico de tos, disnea y fiebre. La TC mostró micronódulos pulmonares centrolobulillares y vidrio esmerilado. El LBA fue compatible con hemorragia alveolar difusa (HAD), con RPC positiva para P. jirovecii. Se descartaron otras infecciones y enfermedades autoinmunes. Recibió tratamiento con cotrimoxazol con buena evolución clínica y mejoría radiológica. Si bien las causas más frecuentes de HAD son etiologías autoinmunes como enfermedades reumatológicas o vasculitis, es prioritario descartar causas infecciosas, incluyendo P. jirovecii, ya que el tratamiento dirigido puede tener un impacto significativo en la mortalidad en este grupo de pacientes.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection, described mainly in HIV patients, however, after the introduction of ART, its presentation has increased in patients with non-HIV immunosuppression, such as hematological cancers, solid or hematopoietic stem cell transplantation. We report the case of a 17-year-old male, kidney transplant patient, with prolonged immunosuppression with corticoesteroids, with history of cough, dyspnea, and fever. Chest CT evidences centrilobular pulmonary micronodules with ground glass. BAL was performed compatible with diffuse alveolar hemorrhage, with positive PCR for P. jirovecii. Other infections and autoimmune disease were ruled out. He received treatment with cotrimoxazole with clinical improvement of the patient, and follow up chest CT at the end of treatment showed decrease of pulmonary infiltrates. Although the most frequent causes of DAH are autoimmune etiologies such as rheumatic diseases or vasculitis, it is a priority to rule out infectious causes, including P. jirovecii, since targeted treatment could have a significant impact on mortality outcomes in this group of patients.