Myositis

Inclusion body myositis (IBM) is a slowly progressive myopathy that has not been reported to affect respiratory muscles. It is often refractory to treatment and a muscle biopsy specimen is necessary for the diagnosis. This is a report of a patient with IBM who quickly progressed to respiratory muscle failure requiring intubation.

Inclusion body myositis (IBM) is a form of inflammatory myopathy that is characterized by a protracted course, involvement of distal muscles, and unresponsiveness to steroid therapy. The most severely affected muscles are those of the limbs and, to our knowledge, there are no reports of respiratory muscle involvement. Extramuscular involvement of this disease has been described infrequently and usually involves the cardiovascular and the gastrointestinal systems. We describe a patient with respiratory failure secondary to IBM.

CASE REPORT

A 69-year-old woman was admitted to the ICU with respiratory failure. She had a 10-day history of progressive shortness of breath, cough, lethargy, and weakness. There was no history of fever, sweats, or chills. The patient was hospitalized in 1987 with a similar presentation. At that time, she had complained of a 2-week history of progressive dyspnea and slowly worsening limb weakness for the preceeding five years. The electromyogram (EMG) at that time was compatible with a myopathy; however, the creatine kinase (CK) and liver function test results were normal. She was found to have an elevated partial thromboplastin time (PTT) that was shown to be due to a lupus anticoagulant. Her antinuclear antibody (ANA) titer was 1:320. Her platelet count was normal as were the results of her thyroid function tests. A Tensilon test was negative. The chest radiograph was normal. She required mechanical ventilation and was treated as having mixed connective tissue disease and received large doses of intravenous methylprednisolone sodium succinate (Solu-Medrol). Her hospital course was complicated by multiple infections that were, in part, attributed to the large doses of steroids. As there was no clinical improvement, the steroid therapy was discontinued. The patient underwent a muscle biopsy from the left quadricep that showed isolated myofiber degeneration, atrophic fibers, and no inflammatory infiltrates. She was discharged from the hospital 1 year later with a diagnosis of idiopathic myopathy. She remained well until the present hospital admission without worsening of the myopathy or further respiratory problems.

The physical examination showed the patient to be in moderate respiratory distress. She had petechiae on both calves and poor air entry in the lungs, which were otherwise clear. The neurologic examination showed her to be alert and oriented, with distal muscle atrophy and strength that was rated as 1/5. There was also proximal muscle weakness rated as 3/5. Findings from the sensory examination were normal. Deep tendon reflexes were rated as 1/3 in the lower extremities and 2/3 in the upper. The plantar reflexes were downgoing. Laboratory tests showed a platelet count of 19,000/[mu]l and a hemoglobin of 12 g/dl. The white blood cell count and differential cell count were normal; she had a PTT of 51.7 s with a normal prothrombin time. The ANA titer was 1:640, anti dsDNA was normal. The arterial blood gases revealed a pH of 7.40, a [PCO.sub.2] of 49 mm Hg, and a [PO.sub.2] of 55 mm Hg on room air. The CK, lactate dehydrogenase, and liver function test results were normal. The chest radiograph was normal. She refused to perform a tidal volume maneuver. The negative inspiratory force was -- 12 cm [H.sub.2]O. The EMG was again consistent with myopathy.

Her respiratory status quickly deteriorated requiring intubation. The low platelet count was thought to be secondary to immune thrombocytopenia and responded to intravenous immunoglobulin therapy with normalization of the count. A muscle biopsy specimen revealed occasional fibers containing small round or angular vacuoles situated centrally or peripherally. Vacuoles showed granular rimming with the modified Gomori stain (Fig 1). Electron microscopy showed the vacuoles to contain membranous whorls and rare tubulofilaments (Fig 2). The features were those of IBM. The patient's course worsened after she developed an upper gastrointestinal tract bleed and sepsis; she died due to complications of the sepsis.

DISCUSSION

Inclusion body myositis is an inflammatory muscle disorder that was initially thought to be due to a viral etiology although that remains unproven.[1] There is a 2:1 male preponderance, and the onset is usually after age 50 years. The average duration from onset of symptoms to diagnosis has ranged from 5 to 19 years.[2] This disease is usually characterized by a slow but progressive course, distal muscle weakness, and resistance to immunosuppressive therapy. The weakness and atrophy can be asymmetric, with selective involvement of the quadriceps, iliopsoas, triceps, and biceps muscles. Early loss of the patellar reflex can occur due to the quadricep weakness and a neurogenic disease is often suspected.[2,3] This disorder can clinically mimic idiopathic polymyositis and in one report accounted for almost one third of the adults with "polymyositis unresponsive to therapy."[3] The occurrence of respiratory failure due to IBM is distinctly unusual.

While dysphagia has been noted to occur in 40 percent of those affected, our patient did not complain of any swallowing difficulties and there was no clinical or radiologic evidence of aspiration. Lotz et al[2] reported a 55 percent incidence of cardiovascular signs and symptoms such as hypertension, ECG changes compatible with ischemia, and rhythm disturbances in their 40 patients. Other diseases such as malignancy and diabetes have been associated with IBM,[2] but to our knowledge, respiratory muscle weakness had not been reported. The positive ANA, immune thrombocytopenia, and antiphospholipid antibody present in our patient give evidence of disturbed immune regulation. Both elevated ANA titers and thrombocytopenia were reported in patients with IBM;[2,3] we have found no reported association with lupus anticoagulant. Serum CK levels can be up to 10-fold elevated or normal.[3] Electromyographic findings are those of a myopathy, although there is occasionally evidence of a neuropathy.[1,2,4] A muscle biopsy specimen is important in excluding primary neuropathic disease and in diagnosing IBM and distinguishing it from other myopathies that may cause respiratory failure such as polymyositis and systemic lupus erythematosus. Not only is the natural history of IBM different, but since it is refractory to treatment with corticosteroids and cytotoxic agents, the correct diagnosis can spare the patient the side effects associated with these medications. It is important to obtain the biopsy specimen from muscles where the inflammation is active and the biopsy site should be correlated with activity on the EMG.[4,5] The inflammation may be distributed in a patchy fashion as likely was the case in our patient and occasionally multiple or repeated biopsy specimens are needed to establish the diagnosis. Review of first biopsy specimen did not show any evidence of IBM. It is likely that the patient had IBM when she was first admitted to the hospital in 1987. However, for the above-mentioned reasons, the diagnosis was not made on the initial muscle biopsy specimen. A low index of suspicion, as IBM is thought to evolve slowly, and the lack of reported respiratory muscle involvement contributed to the lack of earlier recognition in the present case.

REFERENCES

[1] Chou S. Inclusion body myositis: a chronic persistent mumps myositis? Hum Pathol 1986; 17:765-77

[2] Lotz BP, Engel AG, Nishino H, Stevens JC, Litchy WJ. Inclusion body myositis: observation in 40 patients. Brain 1989; 112:727-47

[3] Dalakas M. Polymyositis, dermatomyositis and inclusion body myositis. N Engl J Med 1991; 21:1487-98

[4] Carpenter S, Karpati G, Heller I, Eisen A. Inclusion body myositis: a distinct variety of idiopathic inflammatory myopathy. Neurology 1978; 28:8-17

[5] Purvis J, Fam AG, Lewis A. Clinically unsuspected inclusion body myositis. J Rheumatol 1991; 18:289-92

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