Interstitial pneumonitis in myasthenia gravis

Br.

INTERSTITIAL PNEUMONITIS MYASTHENIA GRAVIS R. G. MCFADDEN, *Departments

I. D. CRAIG

AND N. A.M.

of Medicine and Pathology, South University of Western Ontario, London,

Street Ontario

J. Dis.

Chest

78,

187

IN

PATERSON* Campus, 3 75 South N6A

(1984)

4G5,

Street,

Canada

Summary both myasthenia gravis and interstitial pneumonitis are associated with various autoimmune phenomena and can coexist with other immune disorders, but the two have not been described together. We present a woman with such a concurrence whose clinical picture improved following plasmapheresis and thymectomy . Introduction In 1968 Montes et al. described a woman with myasthenia gravis who was found to have features of a lymphocytic or plasmacytic interstitial pneumonia on open lung biopsy. The patient also had a monoclonal gammopathy, and certain features of the biopsy specimen suggested pseudolymphoma. Myasthenia gravis has been reported in association with systemic lupus erythematosus, rheumatoid arthritis, scleroderma and Sjogren’s syndrome (Adner et al. 1964; Downes et al. 1966; Wolf et al. 1966; Mitchell et al. 1975; Chan & Britton 1980; Killian & Hoffman 1980), and fibrosing alveolitis is a well recognized complication of these disorders (Hunninghake & Fauci 1979). Sarcoidosis and myasthenia have coexisted (Simpson 1960; Wolf et al. 1966; Saper & Fry 1977) but these patients have presented with hilar lymphadenopathy rather than parenchymal infiltrates. We present here a woman with myasthenia gravis and interstitial pneumonitis whose pulmonary function improved with therapy directed against her neurological disorder.

Case Report A 45-yearold female first complained of diplopia and left-sided ptosis in March 1980 and this progressed to almost complete ophthalmoplegia. She subsequently developed proximal muscle weakness such that it was difficult for her to climb stairs, and mild dysphagia. The diagnosis of myasthenia gravis was established in June 1980 on the basis of-her response to edrophonium chloride and electromyography. A chest radiograph was normal and a CT body scan revealed no evidence of thymoma. She was maintained on the anticholinesterase drug pyridostigmine bromide until October 1980 when clinical worsening necessitated therapy with prednisone, eventually on an alternate day basis. At this time she had mild proximal muscle weakness and occasional diplopia. *Reprint requests to: Dr N. A. M. Paterson, Westminster Campus, Victoria Hospital Corporation, 777 Baseline Rd East, London, Ontario, Canada N6A 4S2.

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R. G. McFadden,

I. D. Craig and N. A. M. Paterson

She had no respiratory symptoms until January 1981 when she developed a dry cough and dyspnoea on exertion, which increased over a 3-month period. She had smoked for about 5 years some 20 years previously and had no significant occupational exposures. Past medical history included hypertension for which she had been taking propranolol 40 mg twice daily until 3 months before admission. In January 1980 she was diagnosed as having thyrotoxicosis and she was treated with radioactive iodine. She received thyroid replacement for a short time but this was subsequently discontinued and she remained euthyroid. Physical examination in January 1981 revealed a woman with cushingoid body habitus, a blood pressure of 130/90 mmHg and a pulse of 84 per minute. Her respiratory rate was 24 per minute and there was no enlargement of the thyroid. Chest auscultation revealed bilateral paninspiratory crackles most pronounced at the bases. Cardiovascular and abdominal examinations were normal and there was no peripheral lymphadenopathy. Her extraocular muscles were normal but she had reduced power in hip flexors and quadriceps. Repetitive movements induced excessive muscle fatigue. Routine chest radiographs were normal but a magnification view of the right lung showed a fine micronodular pattern with air bronchiolograms consistent with diffuse parenchymal disease. There was no evidence of an anterior mediastinal mass. Pulmonary function testing revealed a reduction of all static lung volumes and a markedly reduced transfer factor (Table I). Flow rates were normal. Capillary blood gases showed mild hypoxaemia (Pa02 9.6 kPa or 72 mmHg) along with mild alveolar hyperventilation (PC02 4.4 kPa or 33 mmHg). An electrocardiogram was normal. Table I. Pulmonary

TLC (litres) RV (litres) FRC (litres) FVC (litres) FEVt /FVC PEFR (litreslsec) TLCO, (ml/min/mmHg) Thymectomy

28 Jan 1981

31 March

2.37 0.52 1.24 1.85 76% 5.42 5.2

3.51 1.06 1.46 2.45 71% 6.24 9.1

function 1981

tests 29 Se#t 1981

Predicted

4.16 1.33 1.67 2.83 71% 7.92 9.9

4.90 1.70 2.77 3.20 72-92% 7.80 15.1

Feb 17,1982

She had a normal haemoglobin and mild leucocytosis at 11400 with a shift to the left. She had persistent mild hyperglycaemia but serum electrolytes, liver enzymes and CPK were normal. Serum thyroxine, resin Ts uptake and TSH were normal. Serum immunoglobulins and complement levels were normal and antinuclear antibody, rheumatoid factor and Clq binding assay for immune complexes were negative. Antithyroglobulin and antimicrosomal antibodies were present at titres of 1:16 and 1:64 respectively but there was no antimitochondrial, antismooth muscle or antiskeletal muscle and antibodies. Previously, HL-A typing had shown an HL-A 1,2; B 8,44 pattern. Because of the incomplete response to anticholinesterases and steroids she underwent plasmapheresis followed on the same day by transthoracic thymectomy (17 February 1982). Her perioperative course was entirely uncomplicated. A lung biopsy was obtained at the time of thymectomy from an area of lung that appeared most severely involved radiologically. This revealed chronic inflammatory cell infiltration of the alveolar septae (Fig. 1). There was focal proliferation of alveolar type II lining cells but only minimal desquamation and no evidence of either acute inflammation or interstitial fibrosis. There was no significant staining on immunofluorescent examination. Electron microscopy failed to show evidence of increased collagen production or disruption of elastic tissue. No viral inclusions could be identified. Overall, the morphological picture was that of a non-specific chronic interstitial pneumonitis.

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Her muscle strength improved considerably after surgery and since discharge she has been maintained without steroids. Repeat examination 1 month later revealed fewer inspiratory crackles and repeat pulmonary function studies showed improvement in all lung volumes and transfer factor (Table I). Capillary blood gases showed a Pa02 of 10.8 kPa (81 mmHg) and a PaCOa of 5.0 kPa (37 mmHg). In October 1981 the chest radiograph was normal, the previous abnormality no longer being apparent. Upon review in December 1981 she had no respiratory symptoms and her physical examination was normal.

1. Lung, H & E X ZOO. Portion tial pneumonitis with lymphocytic were seen

Fig.

of open lung biopsy showing chronic non-specific interstiinfiltration of the alveolar septae. No lymphoid aggregates

Discussion Interstitial pneumonitis has been described in many of the collagen vascular diseases and has been associated with other disorders of suspected autoimmune pathogenesis, including chronic liver disease and thyroiditis (Turner-Warwick 1968; Fulmer & Crystal 1979). Autoantibodies and circulating immune complexes have been demonstrated in some of these patients (Dreisin et al. 1978; Thomas 1978). The serum of patients with myasthenia gravis may contain circulating antibodies to skeletal muscle and the acetylcholine receptor as well as other organ-specific antibodies (Adner et al. 1964; Downes et al. 1966; Wolf et al. 1966; Sagar et al. 1980). Myasthenia has also been reported in association with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren’s syndrome, Graves’ disease, Hashimoto’s thyroiditis and pernicious anaemia (Adner

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et a1.1964; Downes et al. 1966; Wolf et al. 1966; Mitchell et al. 1975; Chan & Britton 1980; Killian & Hoffman 1980; Kiessling et al. 1981). There has also been a controversial overlap between the myopathy seen late in the course of myasthenia and polymyositis (Wolf et al. 1966; Namba et al. 1973). Respiratory failure is a common form of death in myasthenia gravis, related to poor respiratory muscle function and corresponding inability to clear airway secretions. These patients are also prone to aspiration. Two autopsy studies (Rowland et al. 1956; Genkins et al. 1959) revealed a high prevalence of focal or generalized pulmonary infection, atelectasis and pulmonary congestion, the latter often associated with a degree of myocarditis. Neither interstitial pneumonitis nor fibrosis was reported. Recently, Chisholm and Gilson (1980) reported a case of pulmonary hypertension secondary to chronic respiratory muscle weakness in myasthenia gravis. This patient’s right ventricular dysfunction and pulmonary hypertension improved with successful therapy of her myasthenia. Studies of pulmonary function in myasthenia gravis have shown that most patients have some impairment of flow rates and other effort-dependent tests such as minute ventilation and inspiratory flow (Osserman & Genkins 1971; Newball et al. 1976). Although a reduction in transfer factor has occasionally been noted, a reduction in lung volumes has either not been seen or not measured. None of the recorded patients has had clinical or radiological evidence of interstitial lung disease. Improvement in pulmonary function has been noted following anticholinesterase and steroid therapy (Newball & Braham 1976; Magyar et al. 1979) and respiratory failure in severe myasthenia has been dramatically reversed with plasmapheresis (Gerlag et al. 1981). Swick et al. (1976) employed 67gallium-citrate scanning to localize thymic tumours in 24 patients with myasthenia gravis. They did not recognize any uptake in the lung fields (personal communication) as can be seen with various interstitial lung diseases (Line et al. 1978, 1981). The patient described herein had no evidence of hypoventilation, and respiratory muscle weakness could not account for all the changes in her pulmonary function tests or the histological findings seen on open lung biopsy. It is premature to assume that this patient’s intersitial lung disease will continue to improve as her myasthenia remains in remission, or to attribute the improvement to either the plasmapheresis or the thymectomy. This case report demonstrates the interstitial pneumonitis can occur in patients with myasthenia gravis, and the frequency of this association should now be determined by careful prospective study. References Adner,

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