The clinical spectrum of connective tissue diseases – a single intensive care experience
*Danuta Gierek1, Marcin Jezienicki1, Tomasz Cyzowski1, Henryka Chmurzewska1, Eugeniusz Kucharz2, Anna Kotulska2, Józefa Dąbek3
1Department of Anaesthesiology and Intensive Therapy, Teaching Hospital no. 7, Medical University of Silesia, Upper Silesia Medical Centre in Katowice
2Department of Internal Diseases and Rheumatology, Teaching Hospital no. 7, Medical University of Silesia, Upper Silesia Medical Centre in Katowice
3Department of Cardiology, Teaching Hospital no. 7, Medical University of Silesia, Upper Silesia Medical Centre in Katowice
Background. Systemic connective tissue diseases are relatively rare disorders of unknown origin, possibly related to autoimmunity. In the retrospective study, we analysed the records of nine patients suffering from connective tissue disorders who were treated during a two-year period in an intensive therapy unit.
Methods. Hospital medical records, observational charts and all other available medical documents were analysed.
Results. The clinical courses of 9 patients were studied. They included 4 with scleroderma, 3 with systemic lupus erythematosus, and 2 with inflammatory myopathy. They were admitted to the ITU because of sepsis and/or pneumonia, pulmonary haemorrhage, or cardiovascular failure. Three patients (2 with systemic sclerosis, 1 with systemic lupus erythematosus) died.
Conclusions. A multidisciplinary approach to treatment is a key factor in the successful management of patients with rare diseases, such as connective tissue pathologies. Frequent infections with respiratory and/or circulatory complications are the most common causes of severe morbidity in these patients.
Until 1983, systemic connective tissue diseases (or systemic inflammatory connective tissue diseases) were known as ‘collagenoses’ or ‘collagen diseases’ and although the term is incorrect it is still occasionally used. Systemic connective tissue diseases include a variety of ailments of unknown causes and unclear pathogenesis . According to the American College of Rheumatology classification, they constitute the first group of rheumatic diseases [1, 2], i.e. affecting the connective tissue of multiple organs and related to autoimmunity.
Despite their common pathogenesis, individual systemic diseases differ in the clinical characteristics. Their wide range of symptoms depends on the type of organ injuries accompanying a given disease. The symptoms can be mild (skin lesions, joint pain) or severe, often life-threatening, requiring emergent therapy. Their clinical features are likely to be characteristic of the majority of known urgent cardiac, renal, pulmonary, gastric, neurological or haematological conditions, in which ITU treatment is necessary.
The treatment of the affected patients is extremely difficult due to unclear and significantly different pathogenesis, compared to other conditions [3, 4]. In general, their management involves immunosuppressive drugs, immunoglobulins, glucocorticosteroids and plasmapheresis [1, 2]. The symptomatic treatment depends on the type and severity of organ failure. Due to immunodeficiency, the patients are at risk of various infections; therefore, their prevention improves outcomes.
The aim of the present study was to analyse the cases of systemic connective tissues diseases in patients treated in the intensive therapy unit, the problems encountered and differences in therapeutic management, in particular.
The retrospective analysis was conducted involving medical records and observation charts of patients hospitalised in the ITU due to systemic connective tissue diseases during a two-year period. Age, gender, mortality, types of systemic connective tissue diseases, number and duration of hospitalisation in ITU, causes of ITU admissions, treatment used, APACHE II, and TISS 28 scores were analysed.
The statistical analysis was abandoned due to a small size of the sample. The results were presented as absolute values.
Between 01.01.2008 and 12.31.2009, nine patients with the diagnosis of systemic connective tissues disease were hospitalised in the ITU of the Upper Silesia Medical Centre, which constituted 2.3% of patients treated in this unit during the study period. Four patients were diagnosed with systemic sclerosis (SSc), three with systemic lupus erythematosus (SLE) and two with inflammatory myopathy (IM) (1 with polymyositis and 1 with dermatomyositis). The duration of hospitalisation was comparable in all groups of patients (Table 1).
The major cause of ITU admission was cardiovascular insufficiency.
Sepsis was the most common infective complication observed (5 cases). In 3 cases sepsis was diagnosed on admission (2 in patients with SSC and 1 with SLE); in the remaining 2 cases, sepsis developed during hospitalisation. In 1 patient sepsis was caused with the methicillin-sensitive Staphylococcus aureus (MSS) - infected catheter, in another 1 – with urinary infection caused by extended-spectrum beta lactamase producing (ESBL) Klebsiella pneumoniae. Pneumonia was diagnosed in 4 patients whereas urinary infections developed during hospitalisation in 2 patients.
Pulmonary complications included hypodynamic respiratory insufficiency, alveolar haemorrhage, pulmonary hypertension and pleural effusion. Among the patients with SLE, there were 2 cases of pulmonary hypertension, 1 of pleural effusion, and 2 of alveolar haemorrhage. In the SSc group, 2 patients were diagnosed with pleural effusion, 1 with alveolar haemorrhage and 1 with hypodynamic respiratory insufficiency. The patient with dermatomyositis had hypodynamic respiratory insufficiency.
The pulmonary-renal syndrome was recognised in 2 out of 3 SLE patients; 1 was admitted due to airway haemorrhage; both required renal replacement therapy and in both, the treatment was complicated with sepsis.
Renal failure requiring renal replacement therapy was noted during 6 hospitalisations. In the SLE group, 4 patients were administered intermittent haemodialysis and 1 – continuous veno-venous haemofiltration (for 14 days). Moreover, intermittent haemodialysis was used in 1 SSc patient.
The cardiovascular complications observed in SLE patients included: pulmonary oedema in 1 case, pericarditis with fluid in the pericardial sac in 2 and aseptic endocarditis in 1. All patients with SSc had reduced ejection fraction; 1 developed myocardial infarction without ST segment elevation and required coronary angioplasty.
All patients were mechanically ventilated. The total time of ventilation was 169 days. Furthermore, almost all patients required vasoconstricting drugs. Heparin (non-fractionated or low molecular) was used in all cases. All patients with SLE and IM received hydrocortisone. Four patients were administered immunosuppressants: 2 – methylprednisolone, 1 – cyclophosphamide and 1 – mycophenolate mofetil and mycophenolic acid.
The severity of patient’s condition on admission, assessed according to APACHE II score, was 22-28, and the range of mean 24 h values according to TISS-28 was 27-34. The highest score was observed in SLE patients.
The SLE morbidity is estimated at 40-50 cases per 100000, with young females affected 10 times more frequently [1, 5], which is confirmed in our material. The treatment of this disease has been constantly improved and the majority of patients survive the period of 10 years. The commonest cause of death in these patients is the pulmonary-renal syndrome and infections due to reduced immunity during immunosuppressive treatment.
According to literature data, the mortality in pulmonary-renal syndrome is 50-90% [4, 5, 6]. At present, the mortality rates are slightly lower thanks to implementation of appropriate diagnostic procedures and intensive therapy . In our material, 2 patients were diagnosed with pulmonary-renal syndrome; despite intensive pharmacotherapy, artificial ventilation and renal replacement therapy administered, 1 patient did not survive.
Likewise, the incidence of systemic sclerosis is higher in females compared to males (7:1), yet the course is more severe in males [8, 9], which is consistent with our observations: all patients hospitalised in ITU were males and half of them died.
In the period analysed, 1 patient was treated due to dermatomyositis and another 1 because of polymyositis. In this group, no deaths were noted.
Vast advances in the treatment of SSc were associated with the introduction of angiotensin convertase inhibitors, which significantly reduced the incidence of acute renal failure [7, 10], the main cause of ITU admissions. At present, in the medical centres, which treat this disease, the key causes of ITU hospitalisation are fibrotic lesions of the heart and lungs, with or without pulmonary hypertension, leading to circulatory-respiratory failure.
Among 4 patients with SSc, 3 were diagnosed with pulmonary fibrosis, which is the commonest cause of death of such patients [7, 9, 10]. The disease course in them was aggressive, often with severe multiple organ failure on admission. Chronic renal failure in SSc was observed in 1 patient, who required chronic haemodialysis throughout the hospitalisation. Moreover, cardiovascular complications were recognised. All systemic sclerosis patients had impaired myocardial function of various severity reflected in reduced ejection fraction of the left ventricle, which is consistent with the data reported by other authors .
Furthermore, the complications in SSc include disorders of gastrointestinal motor activity with all their consequences (dysphagia, retained gastric contents, impaired intestinal passage, obstruction, dysfunction of sphincters) . In our material, gastrointestinal symptoms of various severities were observed in all patients treated due to SSc.
One of the severe complications of SLE is the pulmonary-renal syndrome, whose clinical picture includes diffuse haemorrhagic inflammation of small vessels and capillaries of pulmonary alveoli manifesting as variously intensive airway haemorrhage and rapidly progressing glomerulitis, not infrequently complicated with acute renal failure [11, 12, 13]. Prognosis in acute haemorrhagic lesions in the lungs combined with deteriorating renal function is poor [4, 5].
In the group of patients with the diagnosis of IM, the commonest cause of ITU admission was circulatory failure accompanied by pneumonia. Additionally, complications of the underlying disease included weakened respiratory muscles, inducing hypodynamic respiratory insufficiency. Impaired cough and swallowing reflexes were also observed. This led to difficulties in coughing up the airway secretion and thus to increased risk of pneumonia [14, 15, 16]. Due to difficult swallowing, long-term tube feeding was required and oral feeding subsequently instituted had to be continuously controlled by the medical staff.
The modern medicine lacks the effective, causal therapy for systemic connective tissue diseases. In the majority of cases, the therapy only inhibits or modifies the disease course [1, 17]. In the therapy of patients with SSc, there are no drugs inhibiting or delaying the development of fibrosis of the skin and internal organs. This differentiates SSc from other systemic connective tissue diseases, in which the autoimmune mechanism dominates. Although causal treatment of such diseases is not available, proper use of immunosuppression (most commonly cyclophosphamide or mycophenolate mofetil) substantially alleviates the symptoms, significantly prolongs survival and improves the quality of life . Cyclophosphamide does not affect the existing fibrotic lesions [10, 17], but some studies indicate that the process of fibrosis is slowed down after this treatment. During the ITU stay, 1 of our patients with SSc received cyclophosphamide. It should be remembered, however, that the institution of that immunosuppress
ive therapy is associated with increased risk of infection.
The use of glucocorticosteroids in SSc patients is limited [7, 10, 17]. The drugs are likely to accelerate the development of renal failure; moreover, their beneficial effects on fibrosis, similarly to those of non-steroidal anti-inflammatory drugs, have not been demonstrated. In our study, none of the patients with SSc received glucocorticosteroids during hospitalisation.
In recent years, autologous stem cell transplantation was used in patients with SSc [17, 18]. In almost 50% of cases, autologous transplantation improves the condition of the skin and internal organs even for several years. However, not all patients qualify for such a therapy due to infections and advanced failure of internal organs.
The treatment of SLE depends on the activity of disease. In severe cases, glucocorticosteroids and immunosuppressants are recommended; in some cases plasmapheresis is necessary [1, 2, 19]. One of our patients with aggressive SLE, treated with mechanical ventilation, renal replacement therapy, and activated protein C,
underwent 4 courses of plasmapheresis. Moreover, immunosuppressants and immunomodulators were administered, which resulted in stable improvement of the clinical condition. Therefore, the improved survival rates of these patients depend on early diagnosis, immediate aggressive immunosuppressive therapy, sometimes supported by plasmapheresis. The intensive treatment of complications, including septic conditions, is equally important to limit the risk of multiple organ failure [5, 19].
Systemic connective tissue diseases are frequently accompanied by immunological deficiencies, of IgA, in particular . In our study, infections developed in 11 out of 15 hospitalised patients. Such a high number of complications may be explained by markedly reduced resistance due to long-term and intensive treatment of the underlying disease with high doses of glucocorticosteroids and immunosuppressants. Similar findings were reported in literature; infections were considered the major complication and the main cause of death in this group of patients [5, 13, 19].
The severity of patients` conditions was reflected in the APACHE II score on ITU admission. Their relatively low TISS scores, however, were disproportionate to the high treatment costs incurred.
1. In patients hospitalised in ITUs due to systemic connective tissue diseases the circulatory-respiratory disturbances are the dominating multi-organ lesions.
2. Infections developing in these patients result from impaired immunity and chronic immunosuppressive therapy. The priority of therapeutic management is to minimise the risk of infections.
3. A multidisciplinary approach is required to treat multiple organ lesions in patients with systemic connective tissue diseases.
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Oddział Anestezjologii i Intensywnej Terapii
Samodzielny Publiczny Szpital Kliniczny Nr 7
Śląskiego Uniwersytetu Medycznego
Górnośląskie Centrum Medyczne
ul. Ziołowa 45/47, 40-635 Katowice-Ochojec
tel.: +48 32 359 81 00
received: 08.03.2011 r.
accepted: 25.05.2011 r.