Prognosis and outcome of 26 patients with systemic necrotizing vasculitis admitted to the intensive care unit

B. A. Cruz1,3, J. Ramanoelina1, A. Mahr1, P. Cohen1, L. Mouthon1, Y. Cohen2, P. Hoang2 and L. Guillevin1

1Department of Internal Medicine, UPRES EA-3409 Recherche Clinique et Thérapeutique and 2Intensive Care Unit, Hôpital Avicenne, Assistance Publique des Hôpitaux de Paris, Université Paris-Nord, Bobigny, France. 3Present address: Department of Rheumatology, Hospital Biocor, Belo Horizonte, Brazil.

Correspondence to: L. Guillevin, Service de Médecine Interne, Hôpital Avicenne, 125, route de Stalingrad, 93009 Bobigny Cedex, France. E-mail: loic.guillevin{at}avc.ap-hop-paris.fr


    Abstract
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 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conflict of interest
 References
 
Objectives. To investigate presenting features, prognostic factors and outcomes of patients with systemic necrotizing vasculitis (SNV) admitted to the intensive care unit (ICU).

Methods. We retrospectively reviewed the medical records of all 210 SNV patients followed in our university hospital and admitted to the ICU between 1982 and 2001, with respect to clinical features, ICU disease severity scores (APACHE II and SAPS II), the Birmingham vasculitis activity score (BVAS), the five-factors score (FFS) and outcomes.

Results. Twenty-six patients (16 men, 10 women) with a mean age of 46.3±16.5 yr were included. The reasons for ICU admission were: active SNV, 20 (77%); infection, 3 (12%); others, 3 (12%). SNV was diagnosed in 11 (42%) patients in the ICU. The mean APACHE II and SAPS II scores were significantly higher for patients who died in the ICU (P = 0.01 and P = 0.01 respectively). After a mean follow-up of 31.4±29.2 months, the overall mortality rate was 39% (10 patients). Among patients admitted to the ICU with active SNV, BVAS calculated at ICU admission was significantly higher for non-survivors at the end of follow-up (26.9±13.0 vs 14.7±4.6, P = 0.02).

Conclusion. The main reason for admitting SNV patients to the ICU was active vasculitis, which was often the first manifestation of SNV and led to its diagnosis. ICU disease severity scores at admission were associated with mortality in the ICU but did not predict long-term outcome, unlike BVAS, which accurately predicted long-term outcome but not ICU prognosis for patients admitted to the ICU with active SNV.

KEY WORDS: Systemic vasculitis, Intensive care unit, Outcome, Prognosis.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conflict of interest
 References
 
The systemic necrotizing vasculitides (SNV) are a group of diseases defined by vessel wall inflammation that, although heterogeneous, share some common clinical characteristics. When severe, SNV require a combination of corticosteroids and cytotoxic drugs [1]; in this feature they are like Wegener’s granulomatosis (WG), which should be treated with this combination systematically [2]. Whether for severe organ dysfunction related to active disease or for complication(s) of immunosuppressive therapy, e.g. infection, these patients can develop life-threatening conditions requiring admission to the intensive care unit (ICU) [3, 4].

Upon ICU admission, the accurate prediction of outcome is reported to be helpful for non-selected patients [3] and for patients with rheumatic diseases [4, 5]. The underlying disease is considered to be one of the most important prognostic factors in intensive care [6, 7].

We conducted this study to investigate presenting features (including specific disease severity scores), prognostic factors and outcomes, of SNV patients admitted to the ICU. We also evaluated the scores commonly used to predict the prognosis of vasculitis and to follow their evolution [8, 9].


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conflict of interest
 References
 
Patients
The medical records of all 210 of the SNV patients regularly followed in our department were reviewed retrospectively, and the 26 who had been admitted to the ICU between January 1982 and December 2001 were retained for further analysis. Patients who had been referred for a second opinion and those who consulted at another hospital during the acute phase of vasculitis were not included in the study. The diagnoses were established according to the American College of Rheumatology classification criteria for WG [10] and Churg–Strauss syndrome (CSS) [11], and the Chapel Hill Consensus Conference Nomenclature [12] for the other vasculitides. The following data were recorded: age at ICU admission; sex; duration of illness before ICU admission; previous immunosuppressive treatments, defined as prednisone >=20 mg/day and/or cytotoxic drugs during the 3 months preceding admission; in-ICU mortality; and overall mortality using the closing date of 1 November 2001.

Methods
Reasons for ICU admission were classified as follows: (i) active vasculitis, defined as non-infectious manifestation(s) directly attributable to the SNV; (ii) infection, microbiologically documented or clinically suspected; and (iii) all other diseases, for situations not associated with SNV or caused by an infectious agent. For patients admitted to the ICU more than once, only the first admission was considered for this study.

The Acute Physiology and Chronic Health Evaluation II (APACHE II) [13] score and Simplified Acute Physiology Score II (SAPS II) [14] were applied in the ICU to assess disease severity. These scores include age and physiology variables specifically selected to evaluate the majority of systemic failures encountered in ICU patients (i.e. Glasgow coma score, body temperature, blood pressure, heart rate, respiratory rate, ventilation, arterial pH or serum HCO3, blood urea or creatininaemia, serum sodium, serum potassium, haematocrit, white blood cell count, glycaemia and urinary output for SAPS II). In addition, APACHE II includes previous health status based on five underlying diseases [cirrhosis, congestive heart failure (CHF), chronic respiratory insufficiency, chronic haemodialysis and immunodeficiency].

The Birmingham Vasculitis Activity Score (BVAS) [8] was used only at the time of ICU admission, to assess vasculitis activity specifically. This clinical index is based on symptoms and signs in nine categories: systemic signs; skin; mucous membranes and eyes; ear, nose and throat (ENT); chest; heart and vessels; gastrointestinal tract; kidney; and nervous system. The five-factors score (FFS) [9] was calculated for patients with microscopic polyangiitis (MPA), CSS or polyarteritis nodosa (PAN) related or not to hepatitis B virus (HBV) infection. FFS comprises the following items: classes of serum creatinine levels (<=1.58 and >1.58 mg/dl) and proteinuria (<=1 and >1 g/day), presence of severe gastrointestinal tract involvement, cardiomyopathy, and/or central nervous system involvement. The FFS was calculated retrospectively from data recorded in the patients’ files during the first 24 h in the ICU. All scores were computed by the same person (B.A.C.) to ensure interscore reliability and equal bias.

Statistical analysis
Survivors and non-survivors were compared according to the clinical data, APACHE II, SAPS II, BVAS and FFS. Quantitative variables were compared using a non-parametric test (the Kruskal–Wallis test) and qualitative variables with the {chi}2 test or, when appropriate, analysed using Fisher’s exact test. FFS was analysed as a categorical nominal variable. For all statistical analyses, P <= 0.05 was considered to be significant. Statistical analyses were computed using the SAS statistical package, version 8.12 (SAS Institute, Cary, NC, USA).


    Results
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 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conflict of interest
 References
 
Twenty-six patients (16 men and 10 women; mean±S.D. age, 46.3±16.5 yr) were included in the study (Table 1). The mean (S.D.) duration of their SNV before ICU admission was 33.4±76.2 months (range 0–332 months). For 11 (42%) patients, SNV was diagnosed in the ICU. The vasculitides included WG (n = 5), MPA (n = 4), CSS (n = 7), PAN without HBV infection (n = 2), HBV-related PAN (n = 3), cryoglobulinaemic vasculitis (n = 2), and one of each of HIV-related vasculitis, Henoch–Schönlein purpura or Goodpas-ture’s syndrome.


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TABLE 1. Characteristics of the 26 SNV patients admitted to the ICU

 
The main reason for ICU admission was active SNV (20 patients, 77%), including acute renal insufficiency due to rapidly progressive glomerulonephritis (n = 6) or to bilateral ureteral stenoses (n = 1), severe asthma attack with pulmonary infiltrates related to CSS (n = 5), CHF (n = 5), and acute respiratory distress syndrome due to alveolar haemorrhage (n = 3) (Table 1). Three (12%) patients were admitted to the ICU for infections, including pneumonia (Legionella pneumophila, n = 1; Staphylococcus aureus, n = 1) and sepsis (Escherichia coli, n = 1), after 1 month of immunosuppressive treatment for newly diagnosed HBV-related PAN treated with plasma exchanges (PE) and corticosteroids. Three (12%) patients were admitted for other reasons: pulmonary embolism (n = 1), thrombotic thrombocytopenic purpura attributed to uterine cancer radiotherapy (n = 1), and haemorrhagic shock following cardiac catheterization (n = 1).

Four (15%) patients died in the ICU, three of septic shock caused by Pseudomonas aeruginosa (n = 1), S. aureus (n = 1) pneumonia or urinary tract infection (E. coli, n = 1). Patient 22 died following refractory septic shock associated with CHF related to cryoglobulinaemic vasculitis. After a mean follow-up of 31.4±29.2 months, the overall mortality rate was 39% (10 patients). Six patients died after discharge: two from CHF attributable to the SNV; one of pneumonia without bacteriological proof; and three of other causes, including lymphoma (n = 1), sudden death, probably reflecting underlying ischaemic heart disease (n = 1), and sudden death during a haemodialysis session (n = 1).

The analysis of factors associated with outcome showed that the patients admitted to the ICU for an infectious complication tended to have a higher in-ICU mortality (67 vs 9%, P = 0.05). The four (15%) patients who died in the ICU had higher mean APACHE II (28.0±9.3 vs 15.9±6.4, P = 0.01) and SAPS II (50.0±22.0 vs 25.7±10.5, P = 0.01) than surviving SNV patients. These scores were not associated with survival at the end of follow-up (Table 2). Conversely, long-term survival was influenced by age at ICU admission (41.3±12.7 yr for survivors vs 54.4±19.3 yr for non-survivors, P = 0.048), but not by sex (P = 0.22), previous immunosuppressive therapy (P = 1.0) or FFS (P = 0.37). The mean BVAS at entry to the ICU was 16.3±11.7. For the subgroup of 20 patients admitted to the ICU with active SNV, the mean BVAS calculated at ICU admission was significantly higher for non-survivors than survivors at the end of follow-up (26.9±13.0 vs 14.7±4.6, P = 0.02) (Table 2).


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TABLE 2. APACHE II, SAPS II and BVAS (mean±S.D.) determined retrospectively at admission to ICU according to early (in-ICU) and late (end of follow-up) survival

 

    Discussion
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 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conflict of interest
 References
 
SNV can be severe and responsible for death because of visceral involvement, infections and malignancies. Survival can be predicted by organ involvement, as assessed by the FFS [9] for PAN, CSS and MPA, and the BVAS [8] for others. Visceral involvement often occurs initially or later because of relapses. Infections mainly reflect the use of steroids and cytotoxic agents prescribed to treat the disease. They occur at different times during the disease. Malignancies are the third main cause of death. They were not related to the SNV and were not the reasons for ICU admission. ICU admission reflects the severity of clinical manifestations and/or treatment side-effects that can be life-threatening.

For patients with systemic rheumatic diseases, the reported data [5, 15] suggest that hospitalization occurs several years after diagnosis, mainly for infections facilitated by immunosuppressant therapy, but it might be different for the subgroup of patients with SNV. In our study, SNV exacerbation was the most frequent cause of ICU admission, and was often the first manifestation of the disease leading to its diagnosis. This is especially important for intensive care physicians, who should include SNV in the differential diagnosis for patients admitted to the ICU with as yet unexplained severe systemic manifestations, mainly renal or pulmonary. In the present series, many patients with rapidly progressive glomerulonephritis, a manifestation of SNV, were hospitalized, but they were admitted to the ICU but for the acute renal failure that it engendered.

Although SNV are recognized as severe diseases, our in-ICU mortality was lower than the mortality rates of 30–45% reported for patients with systemic rheumatic diseases admitted to the ICU [4, 5]. This observation could be explained by the potentially reversible diseases of most of our patients, which were diagnosed and treated promptly. When infection was the reason for ICU admission, the mortality rate was high (2/3 patients) but remains uninterpretable in the light of the small number of patients.

In this series, MPA and WG (two patients each) were diagnosed in the ICU among 10 patients admitted for renal insufficiency due to rapidly progressive glomerulonephritis or acute respiratory distress syndrome due to alveolar haemorrhage. CSS was diagnosed in the ICU in three of the seven patients admitted for severe asthma attacks with pulmonary infiltrates or CHF. The latter can also occur later, even when CSS is in remission and can be responsible for death (two deaths 6 months after discharge). Concerning PAN with or without HBV infection, no uniform cause was observed for ICU admission.

The relatively lower infection rate could also have influenced ICU survival, as infection is considered to be a factor of poor prognosis for patients with systemic rheumatic disease admitted to the ICU [5, 16]. In this study, infection tended to be associated with higher in-ICU mortality but, as reported for an unselected population [17], it did not influence survival after ICU discharge. However, infection remains a major cause of in-ICU death, even for patients admitted for active vasculitis, and after discharge, as described for other systemic rheumatic diseases [1820]. Concerning the entire cohort of patients followed in our department, only one patient developed Pneumocystis carinii pneumonia, complicating vasculitis associated with leukaemia, and he died immediately after its diagnosis and before ICU admission. One other patient developed cytomegalovirus retinitis but did not require ICU admission.

Published data support the use of ICU disease activity scores to predict outcome for patients with systemic rheumatic diseases [4, 5]. In a study on non-selected patients, disease severity at admission was the most crucial indicator of long-term survival [17]. Our results show that APACHE II and SAPS II, but not BVAS, are good predictors of in-ICU mortality. On the other hand, APACHE II and SAPS II were not able to predict long-term outcome after discharge, but BVAS was. The long-term outcome of SNV should be evaluated with different assessment scores, such as FFS and BVAS, because the usual ICU disease activity scores might underestimate the severity of underlying SNV by not including variables that have been shown to be significantly associated with prognosis (e.g. gastrointestinal tract and cardiac involvement) [12]. Our results suggest that BVAS, a tool specifically designed to assess vasculitis activity, can be used to predict the long-term survival of patients admitted to the ICU because of active vasculitis. In a large prospective study, FFS was significantly associated with outcome [9]. In the present study, it probably did not predict survival because of the small number of patients with diseases for which it has been validated. BVAS was calculated retrospectively, which can lead to its underestimation because of the numerous parameters it takes into consideration, but this did not affect the results, as any oversight would merely have increased the score. On the basis of published reports [1, 8, 9], we think that the two vasculitis activity scores, BVAS and FFS, are complementary and can help in decision-making for patients with SNV, but they do not predict ICU mortality adequately.


    Conflict of interest
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conflict of interest
 References
 
The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conflict of interest
 References
 

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Submitted 30 November 2002; Accepted 17 February 2003





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