UNASSIGNED: Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome and one of the manifestations of pulmonary involvement in systemic lupus erythematosus (SLE), which is characterized by hemoptysis, diffuse pulmonary infiltrates, and respiratory failure. However, the treatment options for DAH remain limited, and DAH-related studies are needed to explore more effective therapeutic directions for better disease management and improved prognosis.
UNASSIGNED: This study utilized the pristane-induced DAH murine model to mimic the pathological process of DAH in patients with SLE. Proteomic analysis was conducted to detect differentially expressed proteins (DEPs) in the plasma of surviving and non-surviving mice, followed by an analysis of biological functions and pathways. The most significant DEP was then confirmed in the plasma of SLE patients with or without DAH and DAH murine model with or without fatal outcomes. Finally, the therapeutic value of haptoglobin (Hp) replacement was validated in a DAH murine model through lung histopathology, RT-qPCR, and survival analysis.
UNASSIGNED: This study identified 178 DEPs, with 118 upregulated and 60 downregulated DEPs in the non-survival group. Within a set of notable Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, complement and coagulation cascades emerged as the most prominent pathway associated with the process of DAH. Later, the most significant DEP, haptoglobin (Hp), was confirmed to exhibit a significant decrease in the plasma of individuals with SLE-DAH and DAH murine model with poor outcomes by the ELISA test. Finally, compared with the control group, the severity of DAH in the Hp treatment group was alleviated significantly, as manifested by the decreased levels of pro-inflammatory cytokines (IL-6 and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β), and decreased mortality.
UNASSIGNED: A reduction in plasma Hp levels was observed in SLE-DAH, and the replacement therapy with Hp could alleviate pulmonary hemorrhage and reduce mortality in DAH mice. This study identified Hp as a potential biomarker for its clinical diagnosis and a direction for treatment.

BACKGROUND:  Diffuse alveolar hemorrhage (DAH) is a rare complication with high mortality in patients with systemic lupus erythematosus (SLE). Early diagnosis and treatment are essential to improve patient prognosis. To determine the characteristics of patients with DAH and their mortality in a Spanish cohort of patients with SLE.
METHODS:  Patients from the RELESSER (Spanish Society of Rheumatology Lupus Register) who had had at least one confirmed episode of DAH were included. Epidemiological, clinical, and laboratory characteristics were analyzed.
RESULTS:  4024 patients were included in the RELESSER register, 37 (0.9%), had at least one recorded episode of DAH. Only further data for 14 patients could be analyzed. In total, 92.9% were women, and for 4 (28.6%) DAH coincided with the debut of SLE. More than 80% of patients had renal involvement and thrombocytopenia. The most frequent manifestations were dyspnea (85.7%) and hypoxemia (100%), with the classic triad of hemoptysis, anemia and pulmonary infiltrates, appearing in 6 (46.2%) patients. The most frequently used treatments were glucocorticoids (85.7%) and cyclophosphamide (69.2%); plasmapheresis was utilized in 5 patients (35.7%) and 8, (57.1%) received intravenous immunoglobulins; 12 (85.7%) patients required admission to the ICU and 5 (35.7%) died. Tobacco use, history of lupus nephritis (LN), concomitant infection, and treatment with cyclophosphamide were more frequent in patients who died.
CONCLUSIONS:  DAH is rare in patients with SLE; in up to one-third of patients, it may appear at the onset of the disease. Some factors, such as smoking, a history of LN, treatment with cyclophosphamide, or concomitant infection, are more prevalent in patients with an unfavorable outcome.

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis that affects blood vessels and presents with vague constitutional symptoms, but more serious manifestations can develop, including pulmonary complications and glomerulonephritis. Currently, there are no definitive treatment guidelines. We present a case of a 66-year-old male with no previous medical history who was admitted for generalized constitutional symptoms for the past month. Imaging of the patient\'s brain revealed dural enhancement. Bronchoalveolar lavage was done and revealed diffuse alveolar hemorrhage (DAH). A kidney biopsy revealed granulomatosis with polyangiitis. The patient\'s hospital course was complicated by acute renal failure and required hemodialysis. Due to the patient\'s multi-organ involvement, the patient was treated aggressively with cyclophosphamide, rituximab, plasma exchange (PE), and steroids. GPA is a systemic vasculitis that can present with multi-organ involvement. A prompt diagnosis is necessary to initiate treatment and preserve organ function. More research is needed to determine which combination therapies are the best treatment modalities in cases of severe multi-organ system involvement.

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We present a case report of diffuse alveolar hemorrhage (DAH), which presented with massive hemoptysis and impending airway compromise. A previously healthy 33-year-old female presented to the emergency department with dyspnea, chest pain, and massive hemoptysis. Due to impending respiratory failure, the patient was placed on mechanical ventilation and a bronchoscopy revealed a diagnosis of DAH. Throughout the hospital course, the patient received antibiotics, steroids, fresh frozen plasma (FFP), cryoprecipitate, tranexamic acid (TXA), and multiple blood transfusions. The patient was subsequently placed on extracorporeal membrane oxygenation (ECMO), but despite these life-saving measures, the patient died less than 48 hours after her initial presentation. This case serves as a harrowing reminder of DAH\'s destructive capabilities and the importance of rapid, aggressive management.

Microscopic polyangiitis (MPA) is a rare autoimmune disease characterized by the inflammation and necrosis of small vessels, primarily affecting kidneys and lungs. It is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) due to the presence of ANCA. MPA can manifest as diffuse alveolar hemorrhage (DAH) and rapidly progressive glomerulonephritis. In contrast, rheumatoid arthritis (RA) is an inflammatory disease that mainly targets the synovial joints. The coexistence of these two conditions presents significant diagnostic challenges, highlighting the need for further research and understanding. We report a case of a 58-year-old male with a past medical history of RA, chronic bronchitis, tobacco use, and recent Legionella pneumonia who presented with acute dyspnea. The patient was intubated for acute hypoxemic respiratory failure. Laboratory workup revealed anemia, hyponatremia, and acute kidney injury. Urinalysis showed hematuria and proteinuria. A CT scan of the chest exhibited bilateral extensive patchy infiltrates. He was transfused with one packed red blood cell (PRBC) unit. Hemoglobin decreased below 6 g/dL after transfusion. A bronchoscopy revealed erythema throughout the tracheobronchial tree, and blood on bronchial alveolar lavage suggested DAH. High-dose steroids were started. Subsequent laboratory results were positive for rheumatoid factor (RF), perinuclear ANCA (p-ANCA), anti-myeloperoxidase (anti-MPO), and antinuclear antibody (ANA). The kidney biopsy demonstrated focal crescentic necrotizing glomerulonephritis pauci-immune type, confirming MPA. RA pathogenesis involves immune dysregulation and activation of various cells, leading to the release of cytokines. Antibodies such as RF and anti-cyclic citrullinated peptide (anti-CCP) can be detected up to 10 years before the clinical manifestation of RA. Recent studies have revealed a predominance of MPA in AAV while coexisting with RA. The underlying mechanism of its occurrence remains unclear. Our patient had recurrent respiratory symptoms and renal dysfunction before hospitalization. MPA-RA overlap syndrome is potentially treatable and clinicians should maintain a high index of suspicion when encountering patients with preexisting RA. Timely initiation of immunosuppressive therapy at early stages is essential to prevent renal and pulmonary complications. ANCA serology should be assessed in these cases.

Diffuse alveolar hemorrhage (DAH) can be caused by various conditions, categorized as autoimmune and non-autoimmune. Immunofactor-mediated vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, and antiphospholipid antibody syndrome, are common autoimmune causes. Non-autoimmune factors include infectious or toxic exposures and neoplastic conditions. The diagnosis of DAH, resulting from excessive catecholamine release from an adrenal pheochromocytoma or extra-adrenal paraganglioma, can present diagnostic challenges and necessitate prompt treatment. In this report, we present a case of pheochromocytoma that manifested as an adrenal incidentaloma (diagnosed during the management of sudden-onset DAH after cholecystectomy). Case report: A 39-year-old female patient with adrenal incidentaloma developed DAH following a cholecystectomy procedure, presenting with sudden-onset hemoptysis and dyspnea. Administration of glucocorticoids, known to precipitate pheochromocytoma crisis (PCC), was required before the cause was determined. Intubation and mechanical ventilation were necessary due to persistent hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). The patient in this case experienced two epidoses of PCC while she was on mechanical ventilation. Subsequent work-up revealed a 26 × 25 mm left adrenal adenoma with hormonal confirmation of catecholamine hypersecretion. A laparoscopic adrenalectomy was done eight months later to excise the left adrenal gland. Subsequent examination of the tissue revealed pheochromocytoma, thereby validating the initial diagnosis. Conclusion: Adrenal incidentalomas may be pheochromocytomas (adrenal incidentalomas can manifest as pheochromocytomas), even without adrenergic symptoms. It is recommended that adrenal incidentalomas undergo evaluation for pheochromocytoma before undergoing invasive surgery or receiving corticosteroid treatment. When considering potential causes of DAH without further elucidation, including a pheochromocytoma or paraganglioma (PPGLs) in the differential diagnosis is important.

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk factors and outcomes are not well understood owing to a sparsity of cases spread across multiple centers. The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplantation-related risk factors and comorbid critical care diagnoses associated with post-HCT DAH. Retrospective analysis was performed in a multicenter cohort of 6995 patients age ≤21 years who underwent allogeneic HCT between 2008 and 2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox regression, with DAH as a time-varying covariate. DAH occurred in 81 patients at a median of 54 days post-HCT (interquartile range, 23 to 160 days), with a 1-year post-transplantation cumulative incidence probability of 1.0% (95% confidence interval [CI], .81% to 1.3%) and was noted in 7.6% of all pediatric intensive care unit patients. Risk factors included receipt of transplantation for nonmalignant hematologic disease (reference: malignant hematologic disease; hazard ratio [HR], 1.98; 95% CI, 1.22 to 3.22; P = .006), use of a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis (referent: CNI plus methotrexate; HR, 1.89; 95% CI, 1.07 to 3.34; P = .029), and grade III-IV acute GVHD (HR, 2.67; 95% CI, 1.53-4.66; P < .001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (P < .05) than those without DAH. From the time of DAH, median survival was 2.2 months, and 1-year overall survival was 26% (95% CI, 17% to 36%). Among all HCT recipients, the development of DAH when considered was associated with a 7-fold increase in unadjusted all-cause post-HCT mortality (HR, 6.96; 95% CI, 5.42 to 8.94; P < .001). In a landmark analysis of patients alive at 2 months post-HCT, patients who developed DAH had a 1-year overall survival of 33% (95% CI, 18% to 49%), compared to 82% (95% CI, 81% to 83%) for patients without DAH (P < .001). Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of nonmalignant hematologic indication for HCT, use of CNI + MMF as GVHD prophylaxis, and severe acute GVHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes.

UNASSIGNED: After quarantine-related measures were completely lifted in China, the respiratory infection rate of children caused by Mycoplasma pneumoniae (MP) increased significantly, and MP infection may lead to rare severe intra- and extrapulmonary manifestation. Hemophagocytic lymphohistiocytosis (HLH) and diffuse alveolar hemorrhage (DAH) are life-threatening clinical syndromes. Timely recognition may contribute to timely treatment and an improved prognosis. Currently there are no reports of children with DAH secondary to MP infection complicated with HLH.
UNASSIGNED: We successfully treated a previously healthy school-aged child who was admitted to the pediatric intensive care unit with fever, cough, drowsiness, and progressive dyspnea. HLH was confirmed by clinical and testing criteria, DAH was indicated by computed tomography scan of the chest, and Mycoplasma antibody detection and endotracheal aspirates pathogen metagenomic next-generation sequencing (mNGS) confirmed MP infection. After invasive mechanical ventilation, antibiotics, and glucocorticoid treatment, the patient recovered well and was discharged. At follow-up, she did not experience any more initial symptoms. For the fourth consecutive month, all indexes remained normal.
UNASSIGNED: mNGS can be considered for identifying the causative agent of infection in patients with DAH and/or HLH. The clinical manifestations of DAH in children may only present as acute hypoxic respiratory failure, significantly decreased hemoglobin without bleeding elsewhere, and chest imaging findings may assist in the diagnosis of DAH. When MP infection is associated with hemocytopenia, HLH should be considered.

Kampo medicine, a traditional Japanese herbal medicine, is covered by the Japanese National Health Insurance and prescribed for various purposes. While relatively safe with few adverse effects, it may potentially cause severe adverse effects, such as lung injury. Herein, we describe the case of a 61-year-old Japanese woman with choreito-induced lung injury that manifested as organizing pneumonia (OP) with diffuse alveolar hemorrhage (DAH). She was referred to our department due to multiple abnormal opacities detected on annual chest radiography. Chest computed tomography (CT) revealed multiple nodules in bilateral lungs. Bloody bronchoalveolar lavage fluid was obtained from the left lingular lobe, appearing nearly normal, while a transbronchial lung biopsy from a subpleural nodule in the left lower lobe was pathologically consistent with OP. The drug lymphocyte stimulation test result was positive for choreito, which the patient had regularly consumed for 6 - 7 months to treat hematuria. Consequently, a diagnosis of choreito-induced OP and DAH was made. Owing to the discontinuation of choreito alone and without the introduction of systemic steroid therapy, the multiple nodules shrank and eventually disappeared on follow-up chest CT. Regardless of the type of crude drug used in Kampo medicine, clinicians must always be careful for potential lung injury, which may present as OP with DAH.