Respiratory failure due to muscle weakness in inflammatory myopathies: maintenance therapy with home mechanical ventilation

A. Selva-O'Callaghan, L. Sanchez-Sitjes, X. Muñoz-Gall1, T. Mijares-Boeckh-Behrens, R. Solans-Laque, J. Angel Bosch-Gil, F. Morell-Brotad1 and Miguel Vilardell-Tarrés

Department of Internal Medicine and
1 Pneumology Service, Vall D'Hebron General Hospital, Barcelona, Spain


    Abstract
 Top
 Abstract
 Introduction
 Case reports
 Discussion
 References
 
Polymyositis and dermatomyositis are idiopathic inflammatory myopathies. Respiratory complications are a common feature, but ventilatory insufficiency is rare in these patients. We describe here three patients diagnosed with inflammatory myopathy (polymyositis) with respiratory failure due to muscle weakness who did not respond to immunosuppressive therapy. Mechanical ventilation at home with nasal or tracheal intermittent positive pressure resulted in improved chronic hypoventilation. This treatment improves the quality of life of patients with inflammatory myopathies and can be lifesaving in some cases.

KEY WORDS: Pulmonary, Polymyositis/dermatomyositis, Evaluation of new systems of care.


    Introduction
 Top
 Abstract
 Introduction
 Case reports
 Discussion
 References
 
The inflammatory diseases of muscle are a heterogeneous group of disorders characterized by proximal muscle weakness resulting from idiopathic chronic inflammation. Most cases fall into three major diagnostic categories: polymyositis (PM), dermatomyositis (DM) and the recently described inclusion body myositis [13].

Although PM (a cell-mediated autoimmune disorder) and DM (an antibody-mediated disease) may differ in their pathogenesis, both produce proximal symmetrical muscle weakness and, in severe cases, pharyngeal and respiratory weakness that may result in respiratory failure [4]. Patients with fulminant inflammatory myopathy with respiratory or bulbar involvement may require intensive care. Corticoids are the mainstay of treatment, while other forms of immunosuppressive and immunomodulatory therapy are reserved for patients who fail to respond adequately to corticoids [5].

Respiratory complications are a common feature of inflammatory myopathies. The incidence of this manifestation is reported to be as high as 45% [68]. Different forms of pulmonary involvement have been identified, interstitial lung disease being the most frequent [9, 10]. Chronic respiratory failure due to respiratory muscle weakness, which is more often seen in other types of muscle diseases, such as muscular dystrophies, has also been described [11]. When treatment with corticoids and immunosuppressive therapy is not effective for this clinical condition, maintenance therapy with home mechanical ventilators can be lifesaving.

We present our experience with respiratory failure due to muscle weakness in PM and in the treatment of this condition by home mechanical ventilation.


    Case reports
 Top
 Abstract
 Introduction
 Case reports
 Discussion
 References
 
Case 1
A 61-yr-old patient presented with a 1-month history of progressive, proximal, symmetrical muscle weakness of the limb girdles and neck. He experienced paradoxical dysphagia, which was secondary to oesophageal dysfunction, as demonstrated by manometry. Laboratory analyses showed elevated serum transaminase, creatinine phosphokinase (1494 IU/l; normal value <195 IU/l) and aldolase (132 IU/l; normal value <9 IU/l), along with increased values of inflammatory signs (erythrocyte sedimentation rate 48 mm/h, fibrinogen 6 g/dl). Abnormal findings consistent with PM were found on electromyogram and muscle biopsy. Treatment with prednisone 1 mg/kg per day was initiated, with a moderate clinical response. There were no immunological alterations. Screening for neoplasm included a chest X-ray and a computed tomography scan of the chest and abdomen, which appeared normal. On the third day of hospitalization, during the diagnostic work-up, the patient presented with severe ventilatory failure and was admitted to the intensive care unit (ICU). Peak flow was <100 ml/min and carbon dioxide partial pressure (PCO2) was 86 mmHg; the patient was intubated and assisted ventilation was started. An accurate assessment of muscle strength could not be made at that time because of severe respiratory impairment. Treatment with intravenous immunoglobulins (0.4 g/kg per day for 5 days) and cyclosporin (150 mg/12 h, cyclosporinaemia 225 ng/ml) was added to prednisone. The patient improved and was extubated 20 days later. One week after leaving the ICU, the patient's state worsened suddenly and he died.

The autopsy showed diffuse muscle disease consistent with the diagnosis of PM. The cricopharyngeal muscles were mildly affected and there was severe involvement of the diaphragm, which could explain the patient's clinical course. A laryngeal carcinoma that had not been noticed before was also discovered.

Case 2
This 43-yr-old woman had been diagnosed with PM at the age of 18 yr. She presented with proximal muscle weakness that caused important functional disability. Analytical and electrophysiological studies suggested inflammatory myopathy. The antinuclear antibody titre was 1/640 and anti-Jo-1 (antisynthetase) antibody was negative; other myositis-specific autoantibodies [12], such as signal-recognition particle (SRP), were not determined. Muscle biopsy of the deltoids, performed at the Mayo Clinic (Rochester, Minnesota, USA), showed pathological changes that were consistent with PM. Although the patient had received treatment with corticoids and azathioprine, she had been in a wheelchair since the age of 34 yr with chronic hypercapnic respiratory failure. The pulmonary function test (PFT) showed the following results: forced vital capacity (FVC) = 0.528 l (13.4%); forced expiratory volume in one second (FEV1) = 0.528 l (17.3%); and FEV1% 100% (respiratory time <1 s). In May 1996, during the course of an acute infection of the respiratory tract, the patient developed acute respiratory failure, arterial blood gases while the patient was breathing air room showed hypoxaemia (PO2 = 40 mmHg) and hypercapnia (PCO2 = 68 mmHg), and she required intubation and mechanical ventilation by tracheostomy. After a stay in the ICU, the patient was discharged with overnight home mechanical ventilation, connected to a fenestrated tracheostomy cannula (Shiley no. 8). The ventilation parameters included the following: respiratory frequency 12/min, tidal volume 600 ml; and inspiratory/expiratory ratio 1/1. Arterial blood gas values after 3 months were nearly normal (PO2 = 83 mmHg; PCO2 = 45 mmHg), and there was no significant change at 6, 12 and 24 months.

Case 3
A 46-yr-old woman was admitted to our hospital in 1985 with progressive loss of strength in the proximal muscles of both legs and arms. The electromyogram at that time was consistent with inflammatory myopathy. The creatine phosphokinase concentration was elevated to 450 IU/l (normal value <195 IU/l), the antinuclear antibody titre was 1/320 in a homogeneous pattern, anti-Jo-1 antibody was negative, and other myositis-specific autoantibodies [12], such as SRP, were not determined. Muscle biopsy of the deltoids was consistent with PM; the patient was treated with prednisone 1 mg/kg per day and azathioprine 1.5 mg per day, with moderate improvement. In 1994 she presented with ventricular arrhythmia and congestive heart failure. She was diagnosed as having dilated myocardiopathy, probably related to PM, and a permanent pacemaker was implanted (type VVI). Repeated chest X-rays were normal. The PFT results were as follows: FVC = 1.02 l (30.9%); FEV1 = 0.91 l (37.4%); FEV1% = 88%, maximum inspiratory pressure (MIP) = 2.32 kPa; and maximum expiratory pressure (MEP) = 4.43 kPa. In 1995 she was admitted with respiratory failure to another hospital, where she was treated with large doses of prednisone (1 g per day for 3 days) without improvement; arterial blood gases, tested while the patient was breathing room air, showed hypoxaemia (PO2 = 42 mmHg) and hypercapnia (PCO2 = 75 mmHg), and mechanical ventilation was applied.

The patient was discharged with invasive home mechanical ventilation. Arterial blood gases values after 3 months were nearly normal (PO2 = 86 mmHg; PCO2 = 44 mmHg), and there was no significant change at months 6, 12 and 24. After 6 months, the tracheostomy was closed and non-invasive ventilation with a nasal mask (10 h per night, respiratory frequency 17/min, tidal volume 700 ml, inspiratory/expiratory ratio 1/1.3) was started. Since then the patient has been well, largely independent in her daily activities, has not required new admittances and has adapted well to the ventilation.


    Discussion
 Top
 Abstract
 Introduction
 Case reports
 Discussion
 References
 
Inflammatory myopathies are systemic diseases; thus they can affect structures other than the muscles. Pulmonary involvement is an important cause of morbidity and mortality in polymyositis/dermatomyositis. The three main types of pulmonary involvement are interstitial lung disease (the most frequent pathological pulmonary finding associated with PM/DM), aspiration pneumonia and ventilatory insufficiency, and alveolar hypoventilation due to muscle weakness, three new cases of which are presented in this report.

There are a small number of reported cases of hypercapnic respiratory failure due to muscle weakness [1315], a recognized complication of inflammatory myopathies, including inclusion body myositis [16]. Loss of respiratory muscle strength is a common occurrence in this heterogeneous group of diseases, but it rarely leads to chronic respiratory failure. The typical alterations in pulmonary function test in patients with alveolar hypoventilation are low total lung capacity and vital capacity, high residual volume, and very low MIP and MEP [4, 17]. Blood gas analysis in these patients shows chronically diminished oxygen partial pressure, with important decreases during exertion, and increased carbon dioxide partial pressure. These features are more often observed in hereditary and congenital myopathies, including nemaline myopathy and neonatal myotonic dystrophy and other muscular dystrophies. In the three cases presented here, the absence of a family history of myopathies or similar illness, the sex and age of presentation, the fact that symptoms were not related to exercise, and the characteristic electromyogram and pathology of inflammatory muscle disease leave little doubt that the diagnosis is correct. Although support measures with mechanical ventilation are a recognized treatment for chronic respiratory failure in muscular dystrophies [18,19], respiratory involvement in PM is extremely rare and, to our knowledge, there are no reported cases in which mechanical ventilation has been used in patients with inflammatory myopathy.

The first of our three patients had a paraneoplastic inflammatory myopathy in which the diaphragm was severely affected, an unusual occurrence. Our literature search turned up only one other case with similar findings [15]. In the other two patients, nocturnal home mechanical ventilation was lifesaving, and resulted in improved chronic hypoventilation during daytime spontaneous ventilation. This might be attributed to improved respiratory muscle strength, as occurs in patients with chronic obstructive pulmonary disease. More probably, nocturnal intermittent positive pressure ventilation resulted in a reduction in exposure of the central chemoreceptors to profound hypercapnia during sleep, and relief from sleep deprivation, both of which would increase the carbon dioxide sensitivity [20].

In conclusion, home ventilation with nasal or tracheal intermittent positive pressure only at night resulted in improved chronic hypoventilation during daytime spontaneous ventilation in patients with inflammatory myopathies. This treatment improves the quality of life of these patients and can be lifesaving.


    Notes
 
Correspondence to: A. Selva-O'Callaghan, C/ Siracusa No. 12 bis A, Barcelona 08012, Spain. Back


    References
 Top
 Abstract
 Introduction
 Case reports
 Discussion
 References
 

  1. Bohan A, Peter JB. Polymyositis and dermatomyositis (parts 1 and 2). N Engl J Med1975;292:344–7.[ISI][Medline]
  2. Miller FW. Classification and prognosis of inflammatory muscle disease. Rheum Dis Clin North Am1994;20:811–23.[ISI][Medline]
  3. Griggs RC, Askanas V, DiMauro S, Engel A, Karpati G, Mendell JR et al. Inclusion body myositis and myopathies. Ann Neurol1995;38:705–12.[ISI][Medline]
  4. Teener JW, Raps EC. Life-threatening complications of autoimmune disease. Evaluation and treatment of respiratory failure in neuromuscular disease. Rheum Dis Clin North Am1997;23:277–92.[ISI][Medline]
  5. Mastaglia FL, Philipps BA, Zilko P. Treatment of inflammatory myopathies. Muscle Nerve1997;20:651–64.[ISI][Medline]
  6. Dickey BF, Myers AR. Pulmonary disease in polymyositis/dermatomyositis. Semin Arthritis Rheum1984;14:60–76.[ISI][Medline]
  7. Lakhanpal S, Lie JT, Conn DL, Martin II WJ. Pulmonary disease in polymyositis/dermatomyositis: a clinicopathological analysis of 65 autopsy cases. Ann Rheum Dis1987;46:23–9.[Abstract]
  8. Selva A, Cuenca R, San José A, Navarro C, Bosch JA, Vilardell M. Pulmonary involvement in PM/DM [abstract]. Br J Rheumatol1990;29:111.[ISI][Medline]
  9. Tazelaar HD, Viggiano RW, Pickersgill J, Colby TV. Interstitial lung disease in polymyositis and dermatomyositis. Clinical features and prognosis as correlated with histologic findings. Am Rev Respir Dis1990;141:727–33.[ISI][Medline]
  10. Grau JM, Miró O, Pedrol E, Casademont J, Masanés F, Herrero C et al. Interstitial lung disease related to dermatomyositis. Comparative study with patients without lung involvement. J Rheumatol1996;23:1921–6.[ISI][Medline]
  11. Marie I, Hatron PY, Hachulla E, Wallaert B, Michon-Pasturel U, Devulder B. Pulmonary involvement in polymyositis and in dermatomyositis. J Rheumatol1998;25:1336–43.[ISI][Medline]
  12. Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH et al. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define a useful homogeneous patient group. Medicine (Baltimore)1991;70:360–74.[ISI][Medline]
  13. Mahler DA. Dyspnea and muscle weakness in a 65-year-old woman. Chest1992;102:1875–6.[ISI][Medline]
  14. Sano M, Suzuki M, Sato M, Sakamoto T, Uchigata M. Fatal respiratory failure due to polymyositis. Intern Med1994;33:185–7.[ISI][Medline]
  15. Blumbergs PC, Byrne E, Kakulas BA. Polymyositis presenting with respiratory failure. J Neurol Sci1984;65:221–9.[ISI][Medline]
  16. Cohen R, Lipper S, Dantzker DR. Inclusion body myositis as a cause of respiratory failure. Chest1993; 104:975–7.[Abstract]
  17. Martin L, Chalmers IM, Dhingra S, McArthy D, Hunter T. Measurements of maximum respiratory pressures in polymyositis and dermatomyositis. J Rheumatol1985;12:104–7.[ISI][Medline]
  18. Hillberg RE, Johnson DC. Current concepts: noninvasive ventilation. N Engl J Med1997;337:1746–52.[Free Full Text]
  19. Kingston WJ, Moxley III RT. Treatment of muscular dystrophies and inflammatory myopathies. Clin Neuropharmacol1986;4:361–72.
  20. Annane D, Quera-Salva MA, Lofaso F, Vercken JB, Lesieur O, Fromageot C et al. Mechanisms underlying effects of nocturnal ventilation on daytime blood gases in neuromuscular diseases. Eur Respir J1999;13:157–62.[Abstract/Free Full Text]
Submitted 12 November 1999; revised version accepted 15 February 2000.