Episodes Of Diffuse Alveolar Hemorrhage Research Articles

Lung transplant to manage end-stage lung disease due to idiopathic pulmonary hemosiderosis: A review of the literature.

Idiopathic pulmonary hemosiderosis (IPH) is a rare immunological disease with a genetic predisposition. It is characterized by recurrent episodes of diffuse alveolar hemorrhage (DAH). Timely use of immunosuppressive medications has significantly improved overall outcomes, including mortality. Still, uncontrolled and frequent episodes of DAH can eventually cause pulmonary fibrosis, leading to end-stage lung disease (ESLD). The objective of the present project was to scrutinize the literature and summarize the demographic, clinical, radiological, and histopathological features, as well as the overall outcomes, in this patient population following lung transplant. The Medline database was searched using the PubMed platform. Articles published in English between 1960 and 2020 were included in the search. Different search terms were used to identify all patients who underwent lung transplantation to manage ESLD due to IPH. Only four cases of lung transplantation have been reported in the literature in patients with IPH. All but one of these underwent deceased donor lung transplant; recurrence was reported in two of these patients and suspected in the third. One patient received living donor lung transplant and had no recurrence during a five-year follow-up. Patients with IPH should not be excluded from lung transplantation because the disease may not recur in all patients, and even when it does recur it can be promptly treated by increasing immunosuppression.

IDIOPATHIC PULMONARY HEMOSIDEROSIS IN A DOWN SYNDROME PATIENT

SESSION TITLE: Fellows Diffuse Lung Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Idiopathic Pulmonary Hemosiderosis (IPH) is a rare disease found primarily in children characterized by recurrent episodes of diffuse alveolar hemorrhage. The exact etiology and pathogenesis of IPH is unknown. Patients with Down Syndrome have a higher risk of developing pulmonary hemosiderosis. Additionally, in this population IPH manifests more severely. CASE PRESENTATION: Patient is 25 months old ex 36-week female with history of Trisomy 21, Atrial septal defect (ASDs) who has had a history of recurrent hemoptysis, anemia, and pulmonary infiltrates. Patient underwent extensive work-up including bronchoscopy and lung biopsy with the final diagnosis of Idiopathic Pulmonary Hemosiderosis (IPH). The patient presented to our PICU with acute alveolar hemorrhage and severe anemia secondary to RSV pneumonia and IPH recurrence despite being on maintenance therapy of prednisone and hydroxychloroquine. Patient required advanced respiratory support and was treated with a short course of pulse steroids. Patient eventually was placed on Azathioprine instead of Hydroxychloroquine with an increased Prednisone maintenance dose. DISCUSSION: IPH generally occurs in children below the age of 10 years, most commonly from 1 to 7 years. The classical triad of anemia, hemoptysis, and pulmonary infiltrates is a distinguishing characteristic of this disease; however, any one of them could be the initial manifestation. The estimated prevalence of IPH reaches 1.85 per 1,000,000 children, compared to 138.5 per 1,000,000 children with Down Syndrome. Patients with Down Syndrome tend to present earlier and more severely; they experience more dyspnea at diagnosis, more frequent secondary pulmonary hypertension (PAH), and an increased risk of fatal evolution. Systemic glucocorticoids are the mainstay of therapy for acute alveolar hemorrhage due to IPH. In a prior series of 23 children with IPH, low-dose oral prednisone was associated with prolonged survival compared with historical controls. In another series of 17 patients, long-term glucocorticoid therapy was associated with a five-year survival of 86 percent. The duration of corticosteroid treatment was variable among the patients based on clinical, radiological (alveolar infiltrates), and biological (hemoglobin, reticulocytes) evolution. Currently, there are no definitive guidelines directing use or choice of steroid-sparing medications in IPH; however, a few case reports describe the use of an immunosuppressant (cyclophosphamide, hydroxychloroquine, mycophenolate mofetil, azathioprine) in conjunction with oral glucocorticoids in the setting of respiratory failure. CONCLUSIONS: Additional studies investigating different therapeutic options are critical in order to reduce overall morbidity & mortality, particularly in children with Down Syndrome who are more predisposed to IPH relapse. Reference #1: Dr. Inderpal Randhawa Reference #2: Dr. Bugsu Ovunc Reference #3: Dr. Cyrus Shahriary DISCLOSURES: No relevant relationships by Yaron Fireizen, source=Web Response No relevant relationships by Nastasia Nianiaris, source=Web Response No relevant relationships by Inderpal Randhawa, source=Web Response No relevant relationships by Cyrus Shahriary, source=Web Response No relevant relationships by Dibanni Vasquez, source=Web Response

IT CAN'T BE LUPUS...UNTIL IT IS: A CASE OF DIFFUSE ALVEOLAR HEMORRHAGE IN SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Diffuse Alveolar Hemorrhage (DAH) is a rare, but well-documented phenomenon in systemic lupus erythematosus (SLE). DAH affects only 4% of patients with SLE but has a 50% mortality. CASE PRESENTATION: A 67 year-old female with SLE complicated by lupus nephritis requiring four renal transplants (last in 2015), but currently in remission on maintenance tacrolimus and mycophenolate mofetil with recurrent episodes of hemoptysis and hypoxic respiratory failure. In October 2018 she was admitted with dry cough, scant hemoptysis and developed rapidly progressive respiratory failure requiring intubation. Workup showed normal immunosuppressive levels, elevated white blood count and inflammatory markers. CT revealed diffuse ground glass opacities. Antinuclear antibody (ANA) and anti-double stranded DNA were negative with normal complement levels. Bronchoscopy showed mononuclear predominance with unrevealing microbiology and cytology and no active bleeding despite sequential BAL. She rapidly improved with antibiotics and steroids. In January 2019 she was admitted with similar symptoms of cough, scant hemoptysis, multilobar infiltrates. Again, serologic and bronchoscopic workup were unrevealing, without classical evidence of DAH leading to a broad differential and needing to determine the etiology for the recurrent episodes of hemoptysis. An open lung biopsy was performed and results returned from Mayo Clinic showing acute alveolar hemorrhage, secondary to SLE. Patient was started on high dose steroids. However, 24 hours later she had frank hemoptysis, this time with bronchoalveolar lavage confirming DAH. Unfortunately, despite steroids, dialysis and plasmapheresis, hospital course was complicated by multi-organ dysfunction and she ultimately expired. DISCUSSION: DAH due to SLE is usually in the setting of a flare with thrombocytopenia, hypocomplementemia as well as elevated lupus antibodies. It is often seen within the first 5 years of diagnosis. Our patient had well-controlled disease on immunosuppressive therapy and had consistently negative antibodies and normal complement levels. Her only known risk factor was recurrent lupus nephritis, which is the most associated extrapulmonary manifestation in patients with SLE and DAH. This patient was given high-dose steroids and plasmapheresis; in reviews of DAH in SLE nearly 100% were given steroids, 55% cyclophosphamide and 31% plasmapheresis. Utilizing recombinant factor VII during the massive hemoptysis was considered, but the data to support it was not well-supported. CONCLUSIONS: This may be the first documented patient with well-controlled Lupus, without evidence of a flare, who developed recurrent episodes of DAH from SLE without classical symptoms highlighting need for broad differentials and exact diagnosis. Given the high mortality associated with DAH, it must be recognized that this can occur and recur despite ongoing immunosuppressive therapy. Reference #1: Kusunoki et al. Severe Progressive Diffuse Alveolar Hemorrhage in a Patient with Systemic Lupus Erythematosus. Case Reports in Critical Care. 2018 Reference #2: Kazzaz NM, Coit P, Lewis EE, McCune WJ, Sawalha AH, Knight JS. Systemic lupus erythematosus complicated by diffuse alveolar haemorrhage: risk factors, therapy and survival. Lupus Sci Med. 2015;2(1):e000117. Published 2015 Sep 23. https://doi.org/10.1136/lupus-2015-000117 Reference #3: Ednalino, Christina & Yip, Julie & Carsons, Steven. (2015). Systematic Review of Diffuse Alveolar Hemorrhage in Systemic Lupus Erythematosus: Focus on Outcome and Therapy. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases. 21. 305-10. 10.1097/RHU.0000000000000291. DISCLOSURES: No relevant relationships by Achal Dhupa, source=Web Response No relevant relationships by Jamie Felzer, source=Web Response No relevant relationships by Shazia Jamil, source=Web Response No relevant relationships by Lakshmi Koripella, source=Web Response

Alveolar hemorrhage in systemic lupus erythematosus: a cohort review.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%.

Systematic Review of Diffuse Alveolar Hemorrhage in Systemic Lupus Erythematosus: Focus on Outcome and Therapy.

Diffuse alveolar hemorrhage (DAH) is an uncommon but potentially life-threatening manifestation of systemic lupus erythematosus (SLE) associated with high mortality. Although survival and its associated clinical, laboratory, and therapeutic features have been reported for case reports and series, they have not been systematically reviewed. The purpose of this systematic review was to assess survival of episodes of DAH in SLE over 3 decades and to categorize trends in therapies, commonly utilized to treat this disorder. Overall, SLE patients survived 61% of 174 DAH episodes representing 140 patients. Episode survival was 67% in the time period from 2000 to 2013. Corticosteroids were nearly universally used therapeutically, and cyclophosphamide was used in 55%. Plasmapheresis was used in 31% and did not appear to be associated with survival. Diffuse alveolar hemorrhage in SLE still carries a high risk of mortality; however, survival trends appear to demonstrate an increase from approximately 25% in the 1980s to 67% in the current decade. Increased use of cyclophosphamide appears to be associated with better survival, whereas plasmapheresis does not appear to influence outcome. Although these results need to be interpreted with caution because they are not derived from randomized controlled trials, we believe this represents the largest reported compilation of survival data in DAH associated with SLE.

Diffuse Alveolar Hemorrhage in Coumarin Users: A Fibrosing Interstitial Pneumonia Trigger?

Fibrosing interstitial pneumonias (IPs) include idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). It has been suggested that oxidative damage plays a role in the pathophysiology of idiopathic interstitial pneumonias. Diffuse alveolar hemorrhage (DAH) can cause oxidative stress. Accordingly, we hypothesized that episodes of DAH might trigger fibrosing IP development. Patients using coumarins with confirmed DAH were retrospectively gathered during a 9 year period and reviewed for the development of IPF or fibrosing NSIP. A total of 65 patients with DAH could finally be included, 31 (48 %) of whom subsequently developed a fibrosing IP. The majority of these 31 patients developed the fibrosing IP within 3 years after DAH confirmation. A total of 41 (63 %) patients died within 3.0 ± 0.9 (range 1.3-4.7) years after the DAH diagnosis had been confirmed. Twenty-two of the deceased (54 %) had finally developed fibrosing IP. Almost half of the patients with established episodes of DAH developed fibrosing IP; therefore it seems that DAH might be a trigger for the development of fibrosing IP. This observation warrants prospective studies to further evaluate the clinical impact of these findings.

Recurrent diffuse alveolar haemorrhage in a patient with systemic lupus erythematosus: long-term benefit of rituximab

Diffuse alveolar haemorrhage (DAH) is an uncommon complication of systemic lupus erythematosus (SLE), and recurrences of DAH with remission periods are unusual. We describe a young woman with cachexia as the initial manifestation of SLE who presented posterior reversible encephalopathy syndrome (PRES), intestinal vasculitis and four episodes of DAH even though she was receiving combined immune suppressive therapy. After treatment with rituximab (RTX) the patient has not presented further episodes of DAH.

Idiopathic Pulmonary Hemosiderosis in Adults: A Case Report and Review of the Literature

Idiopathic pulmonary hemosiderosis is a very rare condition rarely affecting adults and causing recurrent episodes of diffuse alveolar haemorrhage that may lead to lung fibrosis. Due to lack of pathognomonic findings, IPH diagnosis is established upon exclusion of all other possible causes of DAH in combination with specific pathologic findings revealing bland alveolar haemorrhage with absence of vasculitis and/or accumulation of immune complexes within lung parenchyma. Here we describe a rare case of idiopathic pulmonary hemosiderosis in an otherwise healthy 27-year-old Greek male patient with relapsing episodes of fever accompanied by general fatigue and discomfort. He was at this time point a light smoker and had been hospitalised once in the past for similar symptoms. His iron deficiency anemia coupled with chest high-resolution computed tomography and bronchoalveolar lavage revealed findings compatible with diffuse alveolar hemorrhage. After excluding all other sources of bleeding through extensive gastrointestinal workup and thorough immunologic profile, video-assisted thoracic lung biopsy was performed and the diagnosis of Idiopathic Pulmonary Hemosiderosis was established. Patient was treated with high doses of oral corticosteroids, leading to clinical response. We highlight the need for vigilance by the respiratory physician for the presence of DAH, a challenging, acute condition requiring early recognition along with identification of the underlying syndrome and appropriate treatment to achieve optimal results.

Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome

Diffuse alveolar hemorrhage (DAH) is a rare manifestation of primary antiphospholipid antibody syndrome (APS). We describe a patient with primary APS and refractory recurrent episodes of DAH. The patient was admitted 15 times due to recurrent episodes of DAH in a period of 18 months. Multiple immunosuppressive drugs did not improve his condition. Two years after his presentation, he was treated with rituximab (two doses of 1 g, 2 weeks apart). Six months later, the attacks of DAH have gradually disappeared. In a follow-up of more than 2 years after he received rituximab, the patient has had no further admissions due to DAH. Levels of antiphospholipid antibodies were measured during follow-up of 4 years. Anti-β2 glycoprotein IgG titer decreased to normal 6 months after therapy but anticardiolipin (aCL) antibody titer increased. We conclude that rituximab caused a dramatic clinical response in this patient. Anti-β2 glycoprotein IgG correlated better with the clinical response in this patient than aCL.

Predictors of mortality in diffuse alveolar haemorrhage associated with systemic lupus erythematosus

The objective of this study was the evaluation of clinical, demographic and treatment-associated mortality factors in patients with diffuse alveolar haemorrhage (DAH) associated with systemic lupus erythematosus (SLE). Clinical, laboratory test, SLEDAI-2K, predictors of mortality (APACHE II) and different treatments including cyclophosphamide, methylprednisolone and rituximab were evaluated in SLE patients who were diagnosed with DAH, to determine potential association with mortality. Twenty-nine episodes of DAH in 22 SLE patients were included (one patient with four episodes, four patients with two episodes (seven recurrences)), 15 died. Mean age was 25.1 years and 1.5 years of SLE evolution with haemoglobin drop 3.4 g/dl. In 4 of 22 patients, the DAH diagnosis was confirmed by autopsy. Six episodes were in patients under 18 years of age (2 patients with recurrence). DAH was the initial manifestation of SLE in 10 patients. Of the 22 patients, 17 were women and 22/29 had DAH episodes. Dyspnoea and nephritis occurred in all patients, less common were arthritis (75.9%) and fever (65.5%); haemoptysis was present only in 44.8%. Through evaluation of all included factors, only thrombocytopenia, renal failure, requirement for mechanical ventilation and high APACHE II were associated with higher mortality. Cyclophosphamide use was associated with less mortality (not statistically significant).

Intrapulmonary Hemorrhage in Collagen-Vascular Diseases Includes a Spectrum of Underlying Conditions

To elucidate the background and clinical features of intrapulmonary hemorrhage in collagen-vascular diseases (CVD) patients. The charts of collagen-vascular diseases patients who were hospitalized and had intrapulmonary hemorrhages between 1981 and 2006 were retrospectively examined for underlying diseases, clinical and laboratory features, and treatments and outcomes. Of 4,017 patients, 11 females aged 52.1+/-12 had total of 17 episodes of diffuse or non-diffuse intrapulmonary hemorrhage. Fourteen episodes of diffuse alveolar hemorrhage (DAH) developed in 4 microscopic polyangiitis (MPA) patients having a high MPO-ANCA level, 4 systemic lupus erythematosus (SLE) patients having a high SLEDAI score, and 1 SLE/MPA patient having a high MPO-ANCA level. Among the 9 DAH patients, 2 had complicated Goodpasture syndrome, 3 had thrombotic thrombocytopenic purpura (TTP), and 1 had disseminated intravascular coagulation. In DAH the peripheral blood hemoglobin level decreased from 9.3+/-2.2 (n=13) to 6.8+/-1.5 g/dL (n=14, p<0.0001) at 0.5+/-0.7 g/dL/day, and the lymphocyte count decreased from 854+/-424 to 462+/-376 /microL. No patient died of DAH, including 1 who spontaneously remitted. The 3 episodes of non-DAH included 2 pulmonary aneurysm ruptures in 1 SLE patient, and 1 thromboembolism that developed in 1 SLE patient who had anti-phospholipid antibody; their SLEDAI scores were low and these remitted spontaneously. Of intrapulmonary hemorrhage in CVD patients, DAH developed with active MPA or SLE, upon which Goodpasture syndrome or TTP was occasionally superimposed. With DAH, the magnitude of peripheral blood Hb level decrease was approximately 0.5 g/dL/day, and the lymphocyte count decreased. No patient died of DAH.

A NOVEL TREATMENT FOR RECURRENT DIFFUSE ALVEOLAR HEMORRHAGE ASSOCIATED WITH NON-MYELOABLATIVE ALLOGENIC STEM CELL TRANSPLANTATION

INTRODUCTION: Diffuse alveolar hemorrhage (DAH) occurs in about 5% of hematopoietic stem cell transplant (HSCT) recipients with a mortality rate of 30 – 70% (1Afessa B Tefferi A Litzow MR et al.Diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients.Am J Respir Crit Care Med. 2002; 166: 641-645Crossref PubMed Scopus (153) Google Scholar). We describe a patient with recurrent episodes of DAH occurring late in the post-HSCT course.

Radiological aspects of diffuse alveolar haemorrhage

This paper describes chest X-ray (CXR) and computed tomography (CT) findings of diffuse alveolar haemorrhage (DAH). We retrospectively reviewed 23 episodes of DAH in 20 patients, 17 of known aetiology and three of unknown aetiology. All cases were studied by CXR and 15 also by CT. Parenchymal consolidations and ground-glass opacities were evaluated after dividing each lung into three regions (upper, middle, lower) for a total of six zones. Consolidations or ground-glass opacities were identified on CXR in 16/20 patients, mainly in the middle fields (73%). In 4/20 patients, all with Wegener's granulomatosis, CXR was negative or demonstrated only nodular opacities; in two of these cases, CT revealed ground-glass opacities. A complete follow-up was available for ten patients: initially, they showed consolidation opacities in 36/60 zones, which persisted in 16/60 after 7 days and in 11/60 after 15 days. Conversely, ground-glass opacities increased after 7 days owing to the partial regression of consolidation opacities, and they markedly diminished after 15 days. DAH is radiologically characterised by a nonspecific alveolar-filling pattern. Diagnosis or suspicion of DAH needs to be supported by the evidence of haemoptysis and/or rapid-onset anaemia. CT is superior in detecting ground-glass opacities and is required in cases of suspected DAH with normal CXR findings.

Diffuse Alveolar Hemorrhage: Retrospective Review of Clinical Outcome in Allogeneic Transplant Recipients Treated With Aminocaproic Acid

Diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (HSCT) is often fatal. Standard therapy with high-dose corticosteroid is not always effective. There is paucity of data in the literature about other potentially useful agents, such as aminocaproic acid (Amicar) in the post-transplantation setting. We retrospectively reviewed our data on 115 consecutive patients who underwent HSCT and had pulmonary complications, with the aim of determining the overall clinical outcome in recipients of allogeneic transplants and in the subgroup of these patients who were treated with concomitant Solu-Medrol and aminocaproic acid. Aminocaproic acid was added at the discretion of the attending physician. We identified 14 allogeneic transplant recipients (median age, 41 years) with 15 episodes of DAH who were treated with Solu-Medrol (250 mg to 1 g intravenously per day). Of these, 8 patients also received concomitant aminocaproic acid at 1000 mg intravenously every 6 hours. Failure to improve was the most common reason for adding aminocaproic acid. The incidence of DAH was 12.2% (10.3% in myeloablative versus 1.9% in nonmyeloablative recipients). The overall 100-day DAH mortality and median transplantation survival were 60% and 99 days, respectively. Among the subset of patients treated with the combination of Solu-Medrol and aminocaproic acid, we observed a 100-day DAH mortality and median transplantation survival of 44% and 167 days, respectively, compared with 83% and 96.5 days in those treated with Solu-Medrol alone. The median time to DAH was 40.5 days, and the median time to death was 53 days in the combined treatment group compared with 29.5 days in those treated with steroid alone. There were no significant differences in coagulation parameters between subsets. Infections (yeast, respiratory syncytial virus, herpes simplex virus, and parainfluenza) were isolated and treated from 6 diagnostic bronchial alveolar lavage samples and were more common in the subgroup treated with Solu-Medrol only. Respiratory failure was the documented cause of death in 89% of patients. There were no clinically significant side effects from aminocaproic acid. Although these historically lower DAH outcomes are intriguing, prospective studies are needed to confirm the role of aminocaproic acid in DAH occurring in the allogeneic transplantation setting.

Treatment of Diffuse Alveolar Hemorrhage with Recombinant Factor VIIa in Patients with Hematologic Malignancies.

Diffuse alveolar hemorrhage (DAH) is a potentially life-threatening pulmonary complication in patients following hematopoietic stem-cell transplantation (HSCT) or acute leukemia induction therapy. This syndrome is associated with a high mortality rate. Current management strategies include high-dose steroids, platelet transfusions and mechanical ventilatory support to treat acute respiratory failure. Recombinant factor VIIa (rFVIIa) is approved for treatment of bleeding in patients with hemophilia A/B with inhibitors. A greater understanding of the mechanism by which rFVIIa restores hemostasis has become available; with the in-vitro evidence supporting that the thrombin burst achieved by rFVIIa is independent of the presence or binding to tissue factor. This insight has suggested a range of other potential clinical uses for the drug. We report our experience of using rFVIIa for the treatment of DAH in the setting of HSCT and acute leukemia induction therapy. We treated 5 episodes of DAH in 4 adult patients with hematologic malignancies. Two patients had undergone matched unrelated donor HSCT. Clinically, DAH was suspected because of progressive respiratory failure. DAH was confirmed by radiologic and bronchoscopic exams. All patients received high-dose steroids, broad-spectrum antibiotics and respiratory support, as indicated. Packed red cells and platelets were transfused to keep the hemoglobin above 8gm/dL and platelets above 50,000/μL. Patients received boluses of rFVIIa at 90mcg/kg, every 3-12 hrs. The dose of rFVIIa ranged from 7,200–28,000 mcg/day. All five episodes of DAH achieved clinicoradiologic improvement. No toxicity or adverse events were observed with rFVIIa use. Our experience indicates that rFVIIa might be an effective treatment option for patients with DAH, post-HSCT or acute leukemia induction therapy. The optimal dosing schedule in this clinical situation needs to be studied.Patient demographics and outcomesPatientDiagnosisPre-interventionrFVIIa used (microgms)PRBC/Platelet transfused (units)Clinical outcomeOWALL-MUD, BMT, day +758.8/12,00024000/d X 4days3/10100 Non-rebreather to 6L nasal cannula O2OWALL-MUD, BMT, day +808/8,00028000/d X 4 days6/14Ventilatory support to successful weaningCSRelapsed AML, S/P induction8.8/19,0008400/d X 2 days2/4O2 requirement decreasedLWCML blast crisis, S/P induction8.6/101,00010800/d X 2 days4/1Clinically no bleeding, decreased O2 requirementRBRelapsed ALL8.7/7,0007200/d X 1 day2/4Ventilatory support to successful weaning

Idiopathic pulmonary haemosiderosis revisited

Idiopathic pulmonary haemosiderosis is a rare cause of diffuse alveolar haemorrhage of unknown aetiology. It occurs most frequently in children, has a variable natural history with repetitive episodes of diffuse alveolar haemorrhage, and has been reported to have a high mortality. Many patients develop iron deficiency anaemia secondary to deposition of haemosiderin iron in the alveoli. Examination of sputum and bronchoalveolar lavage fluid can disclose haemosiderin-laden alveolar macrophages (siderophages), and the lung biopsy shows numerous siderophages in the alveoli, without any evidence of pulmonary vasculitis, nonspecific/granulomatous inflammation, or deposition of immunoglobulins. Contrary to earlier reports, corticosteroids alone or in combination with other immunosuppressive agents may be effective for either exacerbations or maintenance therapy of idiopathic pulmonary haemosiderosis.

Isolated Pulmonary Capillaritis and Diffuse Alveolar Hemorrhage in Rheumatoid Arthritis and Mixed Connective Tissue Disease

To demonstrate that pulmonary capillaritis and diffuse alveolar hemorrhage (DAH) occur and are isolated to the lung and therefore not part of systemic vasculitis at the time of the DAH episode in rheumatoid arthritis (RA) and mixed connective tissue disease (MCTD). Lung biopsy specimens from patients with DAH were reviewed and those with the histologic features of pulmonary capillaritis were identified. The patients were selected from seven Denver-area general hospitals. Fifty-eight patients with biopsy specimen proved pulmonary capillaritis (1991 to 1997) were identified and classified according to disease. Three patients met the American Rheumatism Association criteria for RA and one patient fulfilled clinical and serologic criteria for MCTD. All clinical, laboratory, and radiographic data on initial presentation and at follow-up periods were extracted from the charts of the four study patients. Histologic slides were reviewed and immunofluorescent studies of lung tissue were performed. All four patients had a connective tissue disease diagnosis prior to the DAH episode. Symptoms referable to pulmonary capillaritis were of short duration (2 to 14 days) and there was no clinical or serologic evidence for an accompanying systemic vasculitis, in particular glomeronephritis. Three patients, two with RA and one with MCTD, demonstrated pulmonary immune complex deposition. Three resolved their illness following IV methylprednisilone and cyclophosphamide therapy. One RA patient died following a myocardial infarction. In the three survivors, no further episodes of DAH have occurred after a mean of 24 months (range, 10 to 48 months). To our knowledge, these are the first cases of DAH due to pulmonary capillaritis documented to complicate RA and MCTD. The capillaritis was not part of a systemic vasculitis at the time of the DAH episode, but rather represented an isolated small-vessel vasculitis of the lungs in this group of patients. Immune complex deposition may be involved in the pathogenesis.

Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival, and outcome.

Diffuse alveolar hemorrhage (DAH) complicating systemic lupus erythematosus (SLE) remains a devastating pulmonary complication of this systemic disease. We conducted this study to review the clinicopathologic presentation and the effects of prior treatment, presence of infection, and current treatment on the survival and outcome of patients with DAH and SLE. We reviewed the records of 15 SLE patients who experienced 19 episodes of DAH over a 10-year period in a single tertiary care hospital. These patients were compared with 57 previously reported cases. The 19 episodes of DAH represented 3.7% of the 510 admissions occasioned by various complications of SLE. As previously reported, the majority (66%) were women with a median age of 27 years. The onset was often abrupt: < 3 days in 12 of the episodes. In 3 patients (20%), DAH was the initial manifestation of SLE, compared with 11% in the literature series. In the other patients in the present series, DAH appeared a median of 31 months following the diagnosis of SLE, versus 35 months in the literature series. In only 42% of the episodes in the present series, compared with 66% in the literature series, was hemoptysis present at the time of admission. However, hemoptysis eventually appeared in all 19 episodes. Temperature elevation (> 38 degrees C) was another inconsistent finding, found in only 5 episodes (26%) in the present series. The most constant concurrent systemic finding was lupus nephritis (14/15 patients). This represents a significant increase when compared with the literature series (29/48 patients). In 8 of 10 patients in whom lung tissue was available, pulmonary capillaritis accompanied the DAH. This represents a marked difference in the underlying histologic pattern when compared with the literature series. In those patients, 72% (31/43 patients) had bland pulmonary hemorrhage, and capillaritis was described in only 6 patients. The overall patient mortality rate was 53% in the current series and 50% in the literature series. Factors associated with an increased mortality in the present series include the following: mechanical ventilation (62%) versus no mechanical ventilation (0%); infection (78%) versus no infection (20%); and cyclophosphamide therapy for the acute DAH episode (70%) versus no cyclophosphamide therapy (20%). The incidence of infection in DAH and SLE (9/19 episodes) is far greater than previously reported (7/ 57 episodes). One possible explanation for this difference is the increased use of outpatient immunosuppressive therapy with monthly intravenous cyclophosphamide therapy for lupus nephritis. Eighteen DAH episodes in the present series were treated with intravenous methylprednisolone. When one combines both the current and literature series experience (16 episodes), the use of plasmapheresis does not improve survival. Of the 7 patients in the present series who survived all episodes of DAH, 6 remain alive a median of 50 months post episode and without recurrence of DAH. Diffuse alveolar hemorrhage is an uncommon but lethal complication of SLE. The survival rate remains unchanged from previous reports. The absence of hemoptysis should not exclude this diagnosis, particularly in those patients who experience an acute pulmonary syndrome with new radiographic infiltrates accompanied by falling hematocrit and the presence of a hemorrhagic bronchoalveolar lavage. Evidence for lupus nephritis is present in the great majority of cases. Most cases demonstrate the histologic pattern of pulmonary capillaritis. The mortality is adversely affected by the need for mechanical ventilation, either the presence of infection at the time of admission or the development of infection in the hospital, and the use of cyclophosphamide for treatment of the acute event.

Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation

background: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation and is associated with very high mortality. This disorder's association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pulmonary hemorrhage syndromes provided the rationale for this study. methods: We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that had occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. results: Overall survival at the end of the follow-up period was significantly higher for the high-dose corticosteroid group compared with the supportive therapy group ( P = 0.005); however; treatment with low-dose steroids did not increase survival over supportive therapy alone ( P = 0.198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups ( P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections ( P >0.4, all comparisons). conclusions: In this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, and further prospective studies are warranted to verify the effectiveness of the treatment.

Pulmonary Capillaritis: The Association with Progressive Irreversible Airflow Limitation and Hyperinflation

We report two patients with systemic necrotizing vasculitis (microscopic polyarteritis) and associated recurrent pulmonary capillaritis, in whom progressive irreversible airway dysfunction began approximately 10 yr after disease onset. Their course was characterized by repeated episodes of diffuse alveolar hemorrhage, glomerulonephritis, palpable purpura, and splinter hemorrhages. The lung revealed intraalveolar hemorrhage, neutrophilic infiltration and cellular fragmentation, fibrinoid necrosis of the alveolar interstitium, and parenchymal hemosiderin deposits. No medium-sized vessel involvement, granulomatous inflammation, or bronchiolar obliteration were seen. Renal biopsies revealed focal segmental necrotizing glomerulonephritis, and a cutaneous biopsy in one case showed a leukocytoclastic vasculitis. Immunofluorescent studies of lung and kidney showed minimal or no immunoreactivity. The clinical course and serologic tests did not support another systemic vasculitis, connective tissue disease, or antiglomerular basement membrane antibody disease. The acute episodes responded to antiinflammatory and immunosuppressive therapy. Symptoms, serial pulmonary function tests, and chest imaging documented the development of a progressive irreversible obstructive airway disease. No other predisposing factors were identified. These cases demonstrate the unexpected appearance of an irreversible obstructive airway disease with lung parenchymal hyperinflation after systemic necrotizing vasculitis associated with recurrent pulmonary capillaritis and diffuse alveolar hemorrhage.