Pulmonary-renal syndrome in systemic sclerosis: a report of three cases and review of the literature

We describe three cases of acute renal failure with diffuse alveolar hemorrhage, which is designated pulmonary-renal syndrome (PRS), in systemic sclerosis (SSc) and review the literature to better define this rare but severe complication of SSc. The clinical course of three SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage are reported, and the literature published between 1967 and 2005 is reviewed following a PubMed search. Including our cases, a total of 19 SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage have been reported. Pulmonary-renal syndrome developing in SSc patients can be categorized clinicopathologically into three entities: PRS with thrombotic microangiopathy, PRS with small vessel vasculitides accompanied with SSc, and d-penicillamine-induced Goodpasture-like syndrome. Patients with scleroderma PRS with thrombotic microangiopathy, to which group our all patients belong, often developed diffuse alveolar hemorrhage after receiving high-dose corticosteroid therapy. Pulmonary-renal syndrome is a fatal complication of SSc and results from different pathogenic processes. Prompt differential diagnosis between the subsets is critical, because therapeutic strategy may differ in the use of high-dose corticosteroid and plasma exchange between the subsets of PRS. Clinical courses of the patients with PRS with thrombotic microangiopathy suggest that high-dose corticosteroid therapy is a trigger of diffuse alveolar hemorrhage in patients with diffuse SSc with signs of thrombotic microangiopathy.     

Leptospirosis presenting as diffuse alveolar hemorrhage: case report and literature review

The literature on diffuse alveolar hemorrhage heavily emphasizes the causal role of vasculitides. We present a patient with diffuse alveolar hemorrhage caused by leptospirosis. Although the pathology in leptospirosis occurs secondary to a vasculitic process, this disease is not listed as a cause of diffuse alveolar hemorrhage in the review literature. In the right clinical scenario, the disease should be considered in a patient presenting with diffuse alveolar hemorrhage.     

Takayasu arteritis presenting as a pulmonary-renal syndrome

Takayasu arteritis is an uncommon disease with a variety of presentations. We report a case of Takayasu arteritis with a presentation of a pulmonary-renal syndrome in a 22-year-old woman. She presented in acute respiratory failure with hemoptysis and acute renal failure; interestingly, however, the renal biopsy was normal. Magnetic resonance angiography (MRA) showed significant narrowing in the distal abdominal aorta with bilateral renal and common iliac artery occlusions. Thoracic and abdominal angiogram confirmed MRA findings of type IV Takayasu arteritis. Percutaneous transluminal angioplasty of the left renal artery normalized kidney function. The initial presentation of Takayasu arteritis as a pulmonary-renal syndrome with severe acute renal failure and diffuse pulmonary hemorrhage is unusual; to our knowledge, this has not been described previously in the literature. We provide a clinical review of Takayasu arteritis and a discussion of systemic manifestations pertinent to the case.     

Leptospirosis in the tropics and in travelers

Leptospirosis, caused by spirochetes of the genus Leptospira, has increasingly been recognized to affect travelers and residents in tropical settings. A zoonotic disease, leptospirosis is transmitted to humans through environmental surface waters contaminated by the urine of chronically infected mammals. Outcome of infection varies, ranging from acute febrile illness (including selfresolving undifferentiated fever) to aseptic meningitis to a fulminant syndrome of jaundice, oliguric renal failure, pulmonary hemorrhage, and refractory shock. Hospitalized cases have mortality rates as high as 25%. A recent clinical trial showed that third-generation cephalosporin is as effective as doxycycline and penicillin in the treatment of acute disease. Doxycycline is effective in preventing leptospirosis in travelers. No protective vaccine is currently available.     

Pulmonary-renal syndrome, diffuse pulmonary hemorrhage and glomerulonephritis, associated with Wegener's granulomatosis effectively treated with early plasma exchange therapy

We present a case of a 38-year-old Japanese man with Wegener's granulomatosis complicated with pulmonary-renal syndrome, i.e., diffuse pulmonary hemorrhage and rapidly progressive renal glomerulonephritis. As this is a life-threatening condition, we promptly initiated plasma exchange with intravenous methylprednisolone therapy. Diffuse pulmonary hemorrhage and renal failure were markedly improved. This case merits presentation because there are few clinical studies of the treatment of Wegener's granulomatosis with pulmonary-renal syndrome, particularly with pulmonary hemorrhage.     

Syndrome pneumo-rénal : une urgence diagnostique et thérapeutique pour le réanimateur et l’interniste

The pulmonary-renal syndrome is a rare and life-threatening condition. It is defined as the association of a diffuse alveolar hemorrhage and a rapidly progressive glomerulonephritis. The characteristic histological lesion common to all underlying diseases is a necrotizing and crescentic glomerulonephritis. The pulmonary-renal syndrome is a diagnostic and therapeutic emergency: any delay in its management will lead to death or serious functional damage as pulmonary and renal impairment. ANCA-associated vasculitis and Goodpasture's disease are the main disorders associated to pulmonary-renal syndrome. More rarely systemic lupus, cryoglobulinaemia, Henoch-Schonlein purpura or subacute endocarditis may induce a pulmonary-renal syndrome. Differential diagnosis can sometimes be difficult, highlighting some ambiguity in the definition of the syndrome. Initial treatment usually associates systemic corticosteroid, cyclophosphamide and plasma exchange. The role of biotherapy as first line therapy remains to be determined.     

Das pulmorenale Syndrom

Pulmonary-renal syndrome is a potentially life-threatening disorder, characterised by diffuse alveolar hemorrhage on the basis of pulmonary capillaritis in association with rapidly progressive glomerulonephritis. It can originate from various systemic autoimmune diseases. ANCA-associated vasculitides account for approximately 60% and Goodpasture's syndrome for approximately 20% of the cases. Fulminant pulmonary capillaritis can result in acute respiratory failure with the more subtle forms only being detectable by bronchoalveolar lavage. Kidney biopsy displays extracapillary proliferating glomerulonephritis and renal immunohistology facilitates detection of the underlying systemic disease. By accelerating the diagnosis of the specific underlying disease, auto-antibody testing fosters rapid initiation of treatment and thereby strongly improves the prognosis of pulmonary-renal syndrome. Intense immunosuppression with cyclophosphamide and glucocorticoids, augmented by plasmapheresis in the event of Goodpastures's syndrome, is the mainstay of therapy. Supportive measures such as temporary ventilation and hemodialysis have further reduced mortality.     

Pulmonary-renal syndrome

Pulmonary-renal syndrome is a potentially life-threatening disorder, characterized by diffuse alveolar hemorrhage on the basis of pulmonary capillaritis in conjunction with rapidly progressive glomerulonephritis. Pulmonary-renal syndrome can originate from various systemic autoimmune diseases. ANCA-associated vasculitides account for approximately 60%, Goodpasture's Syndrome for approximately 20% of the cases. Fulminant pulmonary capillaritis can result in acute respiratory failure, more subtle courses are only detected by bronchoalveolar lavage. Renal biopsy displays extracapillary proliferating glomerulonephritis and renal immunohistology facilitates detection of the underlying systemic disease. By accelerating the diagnosis of the specific underlying disease, autoantibody testing fosters rapid initiation of treatment and thereby significantly improved the prognosis of pulmonary-renal syndrome. Intense immunosuppression with cyclophosphamide and glucocorticoids, augmented by plasmapheresis in the event of Goodpastures' syndrome, is the mainstay of therapy. Supportive measures as temporary ventilation and hemodialysis have further reduced mortality.     

Clinical and Imaging Manifestations of Hemorrhagic Pulmonary Leptospirosis: A State-of-the-Art Review

Leptospirosis, a spirochetal zoonosis, is frequently unrecognized due to its manifestation as an undifferentiated fever. It is an emerging infectious disease that has changed from an occupational disease of veterinarians, farmers, butchers, and other animal handlers to a cause of epidemics in poor and decayed urban communities in developing countries. Humans are infected when mucous membranes or abraded skin come into direct contact with the urine of infected animals, especially rats and dogs. Mortality from severe leptospirosis is high, even when optimal treatment is provided. The diagnosis of leptospirosis is based on clinical findings, history of direct or indirect exposure to infected animals in endemic areas, and positive serological tests. It should be considered in the differential diagnosis of patients with febrile illnesses associated with pneumonitis and respiratory failure, especially when hemoptysis is present. Severe pulmonary involvement in leptospirosis consists primarily of hemorrhagic pneumonitis. In advanced cases, adult respiratory distress syndrome and massive pulmonary hemorrhage may occur. Chest radiographs show bilateral alveolar infiltrates and/or resemble viral pneumonia, bronchopneumonia, tuberculosis, adult respiratory distress syndrome, and other causes of pulmonary hemorrhage such as Goodpasture syndrome. High-resolution computed tomography scans may show nodular infiltrates, areas of consolidation, ground-glass attenuation, and crazy-paving patterns. Bronchoalveolar lavage and autopsy studies have suggested that ground-glass opacities and air-space consolidations are secondary to pulmonary hemorrhage. Although not specific, the presence of these computed tomography findings in a febrile patient with an appropriate history should suggest a diagnosis of leptospirosis.     

Pulmonary renal syndrome

Pulmonary-renal syndrome is a potentially life-threatening disorder, characterised by diffuse alveolar hemorrhage on the basis of pulmonary capillaritis in association with rapidly progressive glomerulonephritis. It can originate from various systemic autoimmune diseases. ANCA-associated vasculitides account for approximately 60% and Goodpasture's syndrome for approximately 20% of the cases. Fulminant pulmonary capillaritis can result in acute respiratory failure with the more subtle forms only being detectable by bronchoalveolar lavage. Kidney biopsy displays extracapillary proliferating glomerulonephritis and renal immunohistology facilitates detection of the underlying systemic disease. By accelerating the diagnosis of the specific underlying disease, auto-antibody testing fosters rapid initiation of treatment and thereby strongly improves the prognosis of pulmonary-renal syndrome. Intense immunosuppression with cyclophosphamide and glucocorticoids, augmented by plasmapheresis in the event of Goodpastures's syndrome, is the mainstay of therapy. Supportive measures such as temporary ventilation and hemodialysis have further reduced mortality.     

Das pulmorenale Syndrom

Pulmonary-renal syndrome is a potentially life-threatening disorder, characterized by diffuse alveolar hemorrhage on the basis of pulmonary capillaritis in conjunction with rapidly progressive glomerulonephritis. Pulmonary-renal syndrome can originate from various systemic autoimmune diseases. ANCA-associated vasculitides account for approximately 60%, Goodpasture’s Syndrome for approximately 20% of the cases. Fulminant pulmonary capillaritis can result in acute respiratory failure, more subtle courses are only detected by bronchoalveolar lavage. Renal biopsy displays extracapillary proliferating glomerulonephritis and renal immunohistology facilitates detection of the underlying systemic disease. By accelerating the diagnosis of the specific underlying disease, autoantibody testing fosters rapid intiation of treatment and thereby significantly improved the prognosis of pulmonary-renal syndrome. Intense immunosuppression with cyclophosphamide and glucocorticoids, augmented by plasmapheresis in the event of Goodpastures’s syndrome, is the mainstay of therapy. Supportive measures as temporary ventilation and hemodialysis have further reduced mortality.     

Pulmonary-renal syndrome in systemic sclerosis

BACKGROUND AND OBJECTIVE: Renal failure, pulmonary hypertension, and interstitial lung disease are major causes of morbidity and mortality in systemic sclerosis (SSc). However, the concomitant occurrence of pulmonary hemorrhage associated with acute renal failure in SSc has been rarely described. The present study is the first analysis of pulmonary-renal syndrome in SSc. PATIENT AND METHODS: We present a 44-year-old woman with SSc who died of a fulminant course of acute renal failure associated with diffuse alveolar hemorrhage. We termed this uncommon and fatal complication of SSc scleroderma-pulmonary-renal syndrome (SPRS). A search of the English-written literature yielded reports of 10 additional similar cases. These patients, together with our present case, form the basis of the present analysis. RESULTS: The average age of the patients with SPRS was 46 years. The majority of the patients (80%) were women, and most had diffuse SSc. SPRS occurred an average of 6.4 years after disease onset and was associated with prior fibrosing alveolitis and/or D-penicillamine treatment. Interestingly, normotensive renal failure seems to characterize the scleroderma patients, because 9 of 11 (82%) had normal blood pressure. SPRS bears a poor prognosis: all of the 11 patients (100%) died within 12 months of admission. However, only 60% of the 5 patients for whom we have treatment data received corticosteroids. CONCLUSIONS: Pulmonary-renal syndrome is a rare but fatal complication of SSc. Because the treatment data are scarce and the prognosis is poor, aggressive treatment with pulse corticosteroids, cyclophosphamide, and possibly plasmapheresis is suggested.     

Leptospirosis presenting as ascending progressive leg weakness and complicating with acute pancreatitis

Leptospirosis is a spirochetal bacterial infection of great public health importance. It has a broad spectrum of clinical manifestations which goes from subclinical infection and self-limited anicteric febrile illness (80-90% of all cases) to icteric leptospiropirosis known as Weil's disease. This is a severe disease characterized by hemorrhage, acute renal failure and jaundice. It is uncommon for leptospirosis to present itself as a primary neurological disease. Additionally, acute pancreatitis is an unusual gastrointestinal manifestation. We report a case of leptospirosis presenting as ascending progressive leg weakness and complicating with acute pancreatitis in an adult patient treated at Hospital Universitário, Universidade Federal de Santa Catarina. The diagnosis was confirmed through ELISA-IgM antibody testing positive for leptospirosis. After antibiotic therapy and support treatment for a few weeks, total resolution of severe manifestations was achieved. Rare and unusual presentations of leptospirosis should be kept in mind in relevant epidemiological scenario.     

Cardiogenic shock due to acute myocarditis complicating leptospirosis

A 48 year old man was admitted to the intensive care unit with septicaemic shock associated with febrile jaundice and anuric renal failure. Within hours, he developed cardiogenic shock with multi-organ failure due to an acute myocarditis refractory to catecholamines and requiring intra-aortic balloon pumping. The diagnosis was an ictero-haemorrhagic leptospirosis, the outcome of which was finally favourable. Myocarditis is an underestimated complication of leptospirosis because it is often symptomless. The main signs are arrhythmias, conduction defects and ST-T wave abnormalities which have little clinical expression. The disease may progress and is sometimes fatal. Leptospirosis myocarditis should therefore be carefully considered because of its potential severity and its reversibility with appropriate antibiotic therapy and also the necessity of initial management in a specific infrastructure.     

Diffuse alveolar hemorrhage

Diffuse alveolar hemorrhage represents a medical emergency, and clinicians must have an expedient approach to its identification. There are many causes of diffuse alveolar hemorrhage, including vasculitides, immunologic conditions such as Goodpasture's syndrome, collagen vascular disease, and idiopathic conditions. Careful attention to the medical history, physical examination, and targeted laboratory evaluation often suggests the underlying cause. Patients in whom the diagnosis of diffuse alveolar hemorrhage remains uncertain should undergo diagnostic bronchoscopy. In patients with evidence of diffuse alveolar hemorrhage and renal involvement, kidney biopsy should be considered to identify the underlying cause and help direct therapy.     

Prompt plasmapheresis successfully rescue pulmonary-renal syndrome caused by ANCA-negative microscopic polyangiitis

Pulmonary-renal syndrome (PRS) associated with antineutrophil cytoplasmic antibodies (ANCA)-negative microscopic polyangiitis (MPA) is relatively rare, and the effects of plasmapheresis on these patients remain unclear. Here, we report the case of a 66-year-old man who presented with fever, acute renal failure, thrombocytopenia, and sudden onset of diffuse pulmonary hemorrhage. Prompt plasmapheresis and concurrent pulse therapy with methylprednisolone effectively rescued his pulmonary-renal syndrome. The patient was then diagnosed with MPA on the basis of typical histological findings and the absence of surrogate markers of Wegener's granulomatosis and Churg–Strauss syndrome. This case demonstrates the therapeutic effects of plasmapheresis on ANCA-negative MPA and highlights the necessity of prompt plasmapheresis for not only resolving pulmonary hemorrhage but also increasing the likelihood of renal function restoration in patients with PRS.     

Hyperamylasemia and Pancreatitis in Leptospirosis

Hyperamylasemia has been documented in up to 65% of our patients with leptospirosis and jaundice. However, pancreatitis is an uncommon complication of leptospirosis. Three patients with leptospirosis and pancreatitis are described and compared with two leptospirosis patients who had hyperamylasemia but in whom the diagnosis of pancreatitis could not be substantiated. The cause of the hyperamylasemia in the latter patients was nonpancreatic. The elevation of the amylase in these latter two patients could not be explained by renal insufficiency, because the level of the amylase was greater than three to four times the normal value, the upper limit to which amylase rises in renal failure. Thus, hyperamylasemia in patients with leptospirosis can be from pancreatic and nonpancreatic sources. Leptospirosis should be considered in the differential diagnosis of hyperamylasemia and pancreatitis.     

Pulmonary-renal syndromes

Pulmonary-renal syndromes or lung-kidney syndromes are clinical syndromes defined by a combination of diffuse alveolar haemorrhage (DAH) and glomerulonephritis. Pulmonary-renal syndromes are not a single entity, but are caused by a wide variety of diseases, including various forms of primary systemic vasculitis (especially Wegener's granulomatosis and microscopic polyangiitis), Goodpasture's syndrome (associated with autoantibodies to the alveolar and glomerular basement membrane) and systemic lupus erythematosus. The diagnosis rests on the identification of particular patterns of clinical, radiologic, pathologic and laboratory features. Serologic testing is important in the diagnostic work-up of patients presenting with a pulmonary-renal syndrome. The majority of cases of pulmonary-renal syndrome are associated with ANCAs, either c-ANCA or p-ANCA, due to autoantibodies against the target antigens proteinase-3 and myeloperoxidase respectively. The antigen target in Goodpasture's syndrome is type IV collagen, the major component of basement membranes. Diffuse alveolar haemorrhage is characterized by the presence of a haemorrhagic bronchoalveolar lavage (BAL) in serial BAL samples. In the clinical setting of an acute nephritis syndrome, percutaneous renal biopsy is commonly performed for histopathology and immunofluorescence studies. Treatment of generalized ANCA-associated vasculitis consists of corticosteroids and immunosuppressive agents such as cyclophosphamide (as induction therapy) or azathioprine (as maintenance therapy once remission has been achieved). The combination of plasmapheresis with these cytotoxic agents and steroids is effective in patients with Goodpasture's syndrome, especially if instituted early in the course of the disease. Recent evidence suggests that patients with severe ANCA-associated vasculitis, defined by the presence of diffuse alveolar haemorrhage and/or severe renal involvement (creatinine concentration > 5.7 mg/dl), might benefit from plasma exchange in combination with cyclophosphamide and corticosteroids.     

Acute kidney injury in leptospirosis: Overview and perspectives

Leptospirosis is a bacterial disease disseminated through the centuries in the whole world which causes symptoms that go from self-limited diseases to hemorrhagic manifestations and organ failure, including acute kidney injury(AKI), composing the severe disease known as the Weil's syndrome. Mortality rates varies according to the clinical presentation and usually increases when kidney injury is present, and is even higher in the setting of pulmonary hemorrhage. There are recent advances in the search for novel biomarkers of renal involvement and early detection of AKI in leptospirosis, as well as in its pathophysiology. We review in this article the clinical aspects of leptospirosis-associated AKI and the perspectives for future research.     

Irreversible sequels of leptospirosis

Leptospirosis is a zoonotic feral nidal disease (synonyms: Weil-Vasilyev disease, waterborne fever) running as an acute febrile disease with evident intoxication, renal, hepatic, and central nervous system involvements, evolving hemorrhagic syndrome mainly with its severe complicated course and high mortality rates. The clinical features of leptospirosis have been little studied in patients with comorbidities. Its poor outcomes are generally due to the development of serious complications, such as infection-toxic shock, acute renal and hepatic failure, massive hemorrhagic syndrome, infectious myocarditis, etc. This communication describes a case of the disease with developed irreversible complications: involvement of the kidney and heart in 1 case and that of the kidney with a fatal outcome. Leptospirosis mortality is frequently associated with delayed diagnosis due to the misunderstanding of the clinical picture of this disease (particularly in its similarity to hemorrhagic fever with renal syndrome). The severer acute course of the infectious process in leptospirosis is burdened with the activation of the infection foci existing in the body or the exacerbation of somatic comorbidity, which substantiates the necessity of goal-oriented early individual, background pathology-depended correction of diagnostic, etiotropic, and pathogenetic therapy, rehabilitative measures. Comorbidities in patients with leptospirosis exert a significant impact on the development of its clinical form and the course of the infectious process manifesting itself as its worsening, the more frequent and more prolonged signs ofendogenous intoxication and multiple organ dysfunction, and a larger number of nonspecific complications in the structure of causes of deaths.