Pulmonary-renal syndrome in systemic sclerosis

doi:10.1053/sarh.2001.21904

Seminars in Arthritis and Rheumatism

Volume 30, Issue 6, June 2001, Pages 403-410

https://doi.org/10.1053/sarh.2001.21904 Get rights and content

Abstract

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. Semin Arthritis Rheum 30:403-410. Copyright © 2001 by W.B. Saunders Company

Section snippets

Methods

In addition to the case reported here, we performed a MEDLINE search of all English-written reports, articles, and reviews that had been published during the period of 1966 to 2000, using “pulmonary hemorrhage” or “alveolar hemorrhage” and “scleroderma” or “systemic sclerosis” as search words. All relevant articles were carefully reviewed, and the data were summarized. SSc was defined according to the classification criteria of the American Rheumatism Association ⁽¹⁰⁾. We looked for concomitant

Case report

A 44-year-old woman with limited cutaneous SSc of 8 years' duration was admitted with fever and dyspnea. During the last years she had been functionally quite stable, despite mild reduction of lung volumes on spirometry. During that period she had been treated with D-penicillamine. Her blood pressure and renal and hepatic functions had been normal. Two months before the last admission she was hospitalized because of pulmonary edema and hypertension of 220/110 mm Hg. The serum creatinine level

Literature review

The literature search revealed 10 additional cases of pulmonary hemorrhage with concomitant acute renal failure that fulfilled our definition of SPRS 12, 13, 14, 15. The reports of these patients, together with our present case, form the basis of the present analysis (Table 1).The data for the 6 cases with normotensive renal failure associated with pulmonary hemorrhage reported by Helfrich et al are limited ⁽¹²⁾.

Discussion

Our patient, who had a 7-year history of slowly progressive but functionally stable limited cutaneous SSc, succumbed to SPRS, which was manifested by acute respiratory insufficiency with pulmonary hemorrhage, together with rapidly progressive renal failure caused by scleroderma kidney disease.

This ominous combination of rapidly progressive renal failure and alveolar hemorrhage has been designated pulmonary-renal syndrome and has been previously reported in systemic lupus erythematosus, mixed

Acknowledgements

We thank Dr Eran Segal and the staff of the General Intensive Care Unit, Tel Hashomer, for the devoted care of the patient reported.

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Alveolar hemorrhage occurs relatively rarely and is a therapeutic emergency because it can quickly lead to acute respiratory failure, which can be fatal. Hemoptysis associated with anemia and pulmonary infiltrates suggest the diagnosis of alveolar hemorrhage, but may be absent in one third of cases including patients in respiratory distress. The diagnosis of alveolar hemorrhage is based on the findings of a bronchoalveolar lavage. The causes are numerous. It is important to identify alveolar hemorrhage due to sepsis, then separate an autoimmune cause (vasculitis associated with antineutrophil cytoplasmic antibody, connective tissue disease and Goodpasture's syndrome) with the search for autoantibodies and biopsies from readily accessible organs, from a non-immune cause, performing echocardiography. Lung biopsy should be necessary only in exceptional cases. If the hemorrhage has an immune cause, treatment with steroids and cyclophosphamide may be started. The indications for treatment with rituximab are beginning to be established (forms that are not severe and refractory forms). The benefit of plasma exchange is unquestionable in Goodpasture's syndrome. In patients with an immune disease that can lead to an alveolar hemorrhage, removing any source of infection is the first priority.
Alveolar Hemorrhage and Rare Infiltrative Diseases
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Kidney involvement in systemic sclerosis
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Normotensive renal crisis requires the presence of other features, primarily rapidly progressive unexplained azotemia and/or microangiopathic hemolytic anemia with thrombocytopenia. Pulmonary hemorrhagic is a rare life-threatening problem, which has occurred in several of these patients [20,55]. It complicates the diagnosis and is a poor prognostic sign.
Kidney involvement in systemic sclerosis (SSc) is primarily manifested by scleroderma renal crisis (SRC). Formerly, it was the most severe complication in scleroderma and was the most frequent cause of death in these patients. More than 30 years ago, with the development of angiotensin converting enzyme (ACE) inhibitors, SRC became a very treatable complication of scleroderma. Although there are still many patients who do not survive and have poor outcomes, early diagnosis of renal crisis and prompt therapeutic intervention can achieve excellent outcomes. Renal abnormalities independent of renal crisis have been noted, but can usually be attributed to other problems. Further understanding of the pathogenesis of renal disease in scleroderma may lead to additional improvement in the therapy of renal crisis and perhaps the disease in general. This chapter reviews the pathogenesis, clinical setting, and therapy of this serious complication of SSc.
Alveolar hemorrhage
2013, Revue de Medecine Interne
L’hémorragie intra-alvéolaire (HIA) est définie par la présence dans les espaces alvéolaires d’hématies provenant des capillaires ou des veinules pulmonaires. Le diagnostic repose sur des arguments cliniques, d’imagerie, et surtout le lavage broncho-alvéolaire. Les causes d’HIA, multiples, sont regroupées selon leur origine auto-immune ou non. L’HIA de cause immune regroupe les vascularites, les connectivites, en particulier le lupus érythémateux systémique, et la maladie des anticorps antimembrane basale glomérulaire (anti-MBG). La prise en charge associe un traitement symptomatique et étiologique avec une corticothérapie à dose élevée souvent complétée d’un traitement immunosuppresseur (cyclophosphamide intraveineux). Des échanges plasmatiques sont réalisés dans la maladie des anticorps anti-MBG et dans le lupus érythémateux systémique, et sont discutés en cas de vascularite systémique. Les causes d’HIA non immune comprennent les cardiopathies gauches, les troubles de l’hémostase, les infections, les toxicités médicamenteuses ou l’HIA idiopathique. La prise en charge repose alors sur le traitement de la cause. Dans tous les cas, l’HIA est une urgence nécessitant un bilan diagnostique et une prise en charge rapides.
Diffuse alveolar hemorrhage (DAH) is defined by the presence of red blood cells originating from the lung capillaries or venules within the alveoli. The diagnosis is established on clinical features, radiological pattern, and especially bronchoalveolar lavage. Diffuse alveolar hemorrhage may have many immune or non-immune causes. Immune causes of DAH include vasculitides, connective tissue diseases, especially systemic lupus erythematosus, and antiglomerular basement membrane antibody disease (Goodpasture's syndrome). Treatment is both supportive and causal, often based on high dose corticosteroids and immunosuppressive therapy (especially intravenous cyclophosphamide). Plasma exchanges are performed in antiglomerular basement membrane antibody disease and systemic lupus erythematosus, and are considered in systemic vasculitis. Non-immune causes of DAH mainly include heart diseases, coagulation disorders, infections, drug toxicities and idiopathic DAH. Treatment of non-immune DAH is that of its cause. Whatever the cause, DAH is an emergency requiring prompt assessment and early treatment.
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Diffuse alveolar hemorrhage (DAH) is often a catastrophic clinical syndrome causing respiratory failure. Recognition of DAH often requires BAL as symptoms are nonspecific, hemoptysis is absent in up to one-third of patients, and radiographic imaging is also nonspecific and similar to other acute alveolar filling processes. Once the diagnosis is established, the underlying cause must be established in order to initiate treatment. This review discusses the diagnosis of the underlying histologies and the clinical entities that are responsible for DAH as well as treatment options.
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The association of SSc with pulmonary haemorrhage is well-recognized. Pulmonary renal syndrome is a rare complication of SSc, consisting of diffuse pulmonary haemorrhage associated with acute renal failure and has a poor prognosis.24 Several drugs used in the management of SSc are capable of causing infiltrative lung disease, but there are no data on the incidence of drug-related disease in SSc.
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^*: Address reprint requests to Dr. Hanan Gur, Department of Medicine C, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel. E-mail: [email protected]

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Pulmonary-renal syndrome in systemic sclerosis*

Abstract

Section snippets

Methods

Case report

Literature review

Discussion

Acknowledgements

Clin Chest Med

Am J Med

Chest

Respir Med

Am J Kidney Dis

Clin Immunol Immunopathol

Scleroderma

Systemic sclerosis and related syndromes B. Clinical features. :

Systemic sclerosis, localized forms of scleroderma and calcinosis.

Systemic sclerosis and related syndromes A, epidemiology, pathology, and pathogenesis.:

The relationship of hypertension and renal failure in scleroderma (progressive systemic sclerosis) to structural and functional abnormalities of the renal cortical circulation

Medicine (Baltimore)

Predictors of survival in systemic sclerosis (scleroderma)

Arthritis Rheum

Organ involvement: pulmonary.

Preliminary criteria for the classification of systemic sclerosis (scleroderma)

Arthritis Rheum

Pathological observations concerning renal involvement in progressive systemic sclerosis (PSS)

Arch Pathol

Normotensive renal failure in systemic sclerosis

Arthritis Rheum

Diffuse alveolar haemorrhage associated with progressive systemic sclerosis

Thorax