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Inclusion body myositis masquerading as cardiac dyspnea.

INTRODUCTION

While respiratory failure is a frequent complication from advanced and longstanding IBM, it is unusual for dyspnea to be a presenting symptom of the disease. The literature on IBM has commonly focused on neurological symptoms, such as proximal weakness, as the cardinal presenting features of IBM. We present a case of dyspnea due to IBM initially thought to be cardiogenic in nature. Our case demonstrates the importance of performing a complete history and physical examination in evaluation of dyspnea, and, to maintain a broad differential diagnosis, considering other less common causes when more frequent cardiovascular and pulmonary etiologies have been excluded.

CASE PRESENTATION

An 81-year-old gentleman was seen by his primary care provider over four months in early 2012 at Mayo Clinic in Rochester, Minnesota for persistent dyspnea on exertion. His past medical history was notable for coronary artery disease, status post-coronary artery bypass grafting with multiple percutaneous interventions, a permanent pacemaker, congestive heart failure, restrictive lung disease, and obstructive sleep apnea. The dyspnea he complained of was distinct from his previous episodes of angina, with his last percutaneous coronary intervention with a drug eluting stent having occurred approximately one year prior to presentation.

Echocardiography demonstrated an ejection fraction of 55% with a right ventricular systolic pressure of 55 mmHg. Decreased inspiratory collapse of his inferior vena cava was noted. Trials of aggressive diuretic therapy failed to improve his dyspnea. Pulmonary embolism was ruled out with chest computed tomograpy angiography. Right-sided heart cath eterization was performed, which confirmed the presence of pulmonary hypertension. A trial of phosphodiesterase inhibitor therapy failed to improve his symptoms. Pulmonary function tests demonstrated little change from previous studies, with a vital capacity of 1.32 L (37% predicted), FEV1 0.88 L (32% predicted), FEV1/FVC 73.7%, and DLCO 8.0 mL CO/min/mmHg (36% predicted). His permanent pacemaker, which had been placed 15 years prior for carotid hypersensitivity and intermittent pacemaker dependency, was interrogated and found to be functioning appropriately.

Subsequent to the development of his dyspnea, a left foot drop was noted. He was evaluated by a physiatrist who believed the etiology to be either a peroneal neuropathy or S-1 radiculopathy. The patient believed the foot drop was improving and an electromyogram was deferred. Generalized gait impairment was attributed to deconditioning from decreased mobility due to exercise intolerance and exertional dyspnea, and a walker was prescribed.

This patient then presented to the emergency department with acute progression of dyspnea that was significantly impacting completion of his daily activities. While the patient had a good cough reflex, he had a paradoxical breathing pattern and substantial accessory muscle use, concerning for diaphragmatic dysfunction. Strength testing demonstrated neck flexor weakness, as well as bilateral deltoid and iliopsoas weakness. Distal muscle strength was preserved. Toes were downgoing on Babinski's examination.

Laboratory investigation was significant for anemia (hemoglobin 10.7 g/dL, normal 13.5-17.5) and a creatinine of 1.5 mg/dL (normal 0.8-1.3). Initial troponin T was 0.24 ng/ mL (normal <0.01) and remained unchanged after three and six hours. NT-pro-BNP was 1,900 pg/mL (normal <131), and arterial blood gas showed a pH of 7.35, PCO2 of 54 mmHg, and PO2 of 85 mmHg. Creatine kinase was normal, and aldolase was found to be 9.5 U/L (normal <7.7).

Radiographs of the chest demonstrated no evidence of pulmonary edema or infectious pneumonia. Transthoracic echocardiogram showed no wall motion abnormalities, and left ventricular ejection fraction, as well as right ventricular systolic pressure, was unchanged from six months prior. Ventilation perfusion scan of the lungs was performed, which demonstrated low probability for chronic pulmonary embolism.

Despite empiric treatment in the hospital with diuretics, antibiotics, and noninvasive positivepressure ventilation, the patient's dyspnea progressed. Based on his physical exam and the chest radiograph demonstrating bilateral elevation of the hemidiaphragms. Neurology was consulted to evaluate for a neuromuscular etiology of dyspnea. Electromyogram of the finger flexors, quadriceps, and right hemidiaphragm showed reduced recruitment of muscle fibers and small motor unit potentials. The electromyogram was an abnormal study and demonstrated electrophysiological evidence of a proximal and distal myopathy, as well as fibrillation potentials suggestive of myonecrosis, fiber splitting, and vacuolization consistent with inclusion body myositis. Muscle biopsy of the left vastus medialis muscle revealed rimmed vacuoles in muscle fibers with necrosis, regeneration, and congophilic staining inclusions, consistent with a diagnosis of inclusion body myositis (IBM) (Figures 1 and 2).

Unfortunately, the patient developed worsening respiratory failure necessitating intubation and mechanical ventilation. In concordance with the patient's wishes and advanced directives, ventilatory support was withdrawn.

DISCUSSION

Dyspnea is an extremely common complaint, particularly in the elderly. While the most common causes of dyspnea involve the respiratory and cardiovascular systems, it is essential to maintain a broad differential diagnosis, as there are a myriad of etiologies for dyspnea, spanning every organ system. Dyspnea reflects inadequate oxygen delivery to systemic organs, resulting in a sensation of breathing discomfort. Inadequate respiratory drive and oxygen intake, impaired gas exchange, shunt physiology, reduced oxygen carrying capacity, inadequate pumping of the oxygen-rich blood, and poor oxygen exchange at peripheral tissues may all contribute to the sensation of dyspnea.

There are many neuromuscular conditions that may result in dyspnea. Guillain Barre Syndrome is a progressive inflammatory demyelinating polyneuropathy that often results in symmetric distal weakness and can progress to severe respiratory muscle weakness. Amyotrophic lateral sclerosis is a progressive, incurable neurodegenerative condition that causes combined upper- and lower-motor neuron patterns of weakness that inevitably lead to respiratory failure and death. Myasthenia gravis is an autoimmune disorder of neuromuscular signal transmission, resulting in fatigable weakness that commonly involves the ocular muscles and can also involve the respiratory muscles. Inflammatory myopathies arise from immune-mediated muscle injury and can progress from proximal muscle weakness to respiratory involvement. Differentiating these neuromuscular conditions requires a high clinical suspicion, recognition of the pattern of weakness, and laboratory shidies including electromyography and/or muscle biopsies.

Sporadic IBM is a devastating rheumatologic disease in the class of inflammatory myopathies. Prevalence varies from 1 to 15 per million people and appears to be linked to the HLA-DR3 autoimmune allele cluster. (1) IBM is more common among the elderly population, rarely occurring in those below age 50, and tends to afflict men more than women. (2) Unlike polymyositis and dermatomyositis, IBM tends to be associated with insidious onset of muscle weakness, most notably involving the quadriceps, finger flexors, and ankle dorsiflexors. (3) While most cases of IBM include weakness that is usually symmetric and in the proximal muscles, there is an important subgroup of patients that have predominantly asymmetric or distal involvement at various locations, and this proportion is greater than in polymyositis. Dysphagia is also common. While respiratory muscle weakness leading to respiratory failure is a common cause of death among those with IBM, it is considered extremely rare and unusual as a presenting symptom of the disease. (4)

While a good clinical history is essential in detecting IBM, electrodiagnostic and pathologic confirmation is necessary. Unlike polymyositis, laboratory studies are generally unremarkable in IBM, with muscle enzymes generally normal or only mildly elevated. (5) Electromyography is revealing of a neurogenic and myopathic pattern, but it is generally nonspecific among the inflammatory myopathies. (6) The most definitive diagnostic test is a biopsy of an affected muscle. Pathologically unique to IBM are the presence of intramuscular vacuoles and amyloid deposits. (7) The pathophysiology of IBM is believed to be related to the accumulation of injurious molecules and proteins in the muscle fibers. (8) Cells thought to be associated with muscle fiber injury include T-cells, dendritic-cells, and plasma-cells that infiltrate the fascicular myofibers. (9) One possible antigen involved in the immune response leading to muscle fiber damage is alphaB crystallin. (10) Furthermore, deposition of proteins such as beta-amyloid and phosphorylated microtubule-associated protein tau (MAPT) may contribute to muscle injury. (11,12)

IBM is unique among the inflammatory myopathies because of its relative resistance to standard immunotherapy (prednisone, methotrexate, and azathioprine), with continued gradual deterioration of muscle strength. Physical and occupational therapy may play a role in patient rehabilitation and palliation. The most common cause of death among patients with IBM is respiratory infection, while direct respiratory failure from muscle weakness is also possible but rarer.

We present a case of IBM presenting primarily with symptoms of dyspnea in an individual with impaired cardiopulmonary reserve due to his underlying cardiopulmonary comorbidities. In retrospect, even though the patient's major complaint was dyspnea, his foot drop and gait impairment were subtle clues to an underlying neuromuscular disorder. The restrictive respiratory pattern demonstrated on his pulmonary function tests also hinted at a neuromuscular abnormality. While intrinsic lung diseases such as interstitial lung disease may cause these findings on pulmonary function testing, extrinsic factors such as obesity and neuromuscular disorders can also contribute to a restrictive pulmonary pattern. The patient expired approximately two weeks after his diagnosis of inclusion body myositis. This case highlights the importance of early diagnosis of IBM, which would allow for the patient and family to discuss treatment options and plan for end-of-life care.

CONCLUSIONS

Our patient's presenting symptom was progressive dyspnea that failed to respond to aggressive management of multiple cardiac comorbidities. The diagnosis of IBM was eventually made as respiratory failure progressed. IBM uncommonly presents as respiratory failure from diaphragmatic weakness. A high suspicion from a detailed history and physical exam was required to make the correct diagnosis in our patient after the more common cardiovascular and pulmonary causes of dyspnea were ruled out.

ACKNOWLEDGEMENTS

We would like to acknowledge Dr. Andrew Engel, Professor of Neurology at the Mayo Clinic in Rochester, for his contribution of the muscle biopsy pathology images. REFERENCES

(1.) Mastaglia FL. Sporadic inclusion body myositis: variability in prevalence and phenotype and influence of the MHC. Acta Myol 2009;28:66-71.

(2.) Wilson FC, Ytterberg SR, St Sauver JL, Reed AM. Epidemiology of sporadic inclusion body myositis and polymyositis in Olmsted County, Minnesota. J Rheumatol 2008;35:445-7.

(3.) Greenberg SA. Inclusion body myositis. Curr Opin Rheumatol 2011;23:574-8.

(4.) Voermans NC, Vaneker M, Hengstman GJ, et al. Primary respiratory failure in inclusion body myositis. Neurology 2004;63:2191-2.

(5.) Lotz BP, Engel AG, Nishino H, Stevens JC, Litchy WJ. Inclusion body myositis. Observations in 40 patients. Brain 1989;112 (Pt 3):727-47.

(6.) Solorzano GE, Phillips LH, 2nd. Inclusion body myositis: diagnosis, pathogenesis, and tieatinent options. Rheum Dis Clin North Am 2011;37:173-83, v.

(7.) Engel WK, Askanas V. Inclusion-body myositis: clinical, diagnostic, and pathologic aspects. Neurology.

(8.) Dalakas MC. Pathophysiology of inflammatory and autoimmune myopathies. Presse Med 2011;40:e237-47.

(9.) Greenberg SA. Proposed immunologic models of the inflammatory myopathies and potential therapeutic implications. Neurology 2007;69:2008-19.

(10.) Banwell BL, Engel AG. AlphaB-crystallin immunolocalization yields new insights into inclusion body myositis. Neurology 2000;54:1033-41.

(11.) Fukuchi K, Pham D, Hart M, Li L, Lindsey JR. Amyloid-beta deposition in skeletal muscle of transgenic mice: possible model of inclusion body myopathy. Am J Pathol 1998;153:1687-93.

(12.) Salajegheh M, Pinkus JL, Nazareno R, Amato AA, Parker KC, Greenberg SA. Nature of "Tau" immunoreactivity in normal myonuclei and inclusion body myositis. Muscle Nerve.

Drs. Wan, Liang, and Greenlund are with the Department of Internal Medicine in the Mayo Clinic in Rochester, Minnesota.

Siu-Hin Wan, MD; Jackson J. Liang, DO; Andrew C. Greenlund, MD, PhD
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Author:Wan, Siu-Hin; Liang, Jackson J.; Greenlund, Andrew C.
Publication:The Journal of the Louisiana State Medical Society
Date:Nov 1, 2014
Words:1893
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