Antimitochondrial antibody-associated myopathy with pulmonary hypertension due to left heart disease

Pulmonary hypertension caused by antimitochondrial antibody-associated cardiomyopathy contains therapeutic potential with prednisolone. Sir, AMA is a highly specific autoantibody to primary biliary cholangitis (PBC), a chronic immune-mediated liver disease resulting from progressive destruction of the bile ducts. PBC is often accompanied by another autoimmune condition including Sjögren’s syndrome, Hashimoto's thyroiditis and systemic sclerosis as extrahepatic manifestations; however, the association among AMA, myopathy and cardiopulmonary complications has not been well-recognized [1]. We here describe inflammatory myopathy and pulmonary hypertension (PH) due to left heart disease (LHD) in a patient with AMA and successful treatment with prednisolone (PSL) for the rare complications of PBC. A 45-year-old Japanese female visited our hospital complaining of dyspnoea and muscle weakness in her legs for several months. She had no medical history and was taking no chronic medications. She did not have dyspnoea at rest, but her daily activities were greatly limited by shortness of breath and fatigue. Manual muscle testing showed grade 3 knee extension and grade 4 shoulder abduction. Pitting-oedema was found on her legs. Laboratory examinations revealed high creatine kinase (CK) (2287 U/l, normal: <165 U/l), CK-MB (43 ng/ml, normal: <3 ng/ml) and brain natriuretic peptide (142 pg/ml, normal: <18 pg/ml) levels. A chest X-ray showed enlarged cardiac silhouette (Fig. 1A). Polymorphic ventricular premature beats were frequently found in an electrocardiogram (Fig. 1B). An echocardiography showed mild hypokinesis and left atrial enlargement as well as severe right heart enlargement and tricuspid regurgitation. Right heart catheterization indicated high mean pulmonary artery pressure (28 mmHg), high pulmonary artery wedge pressure (16 mmHg) and normal pulmonary vascular resistance (1.9 Wood unit), confirming PH-LHD. However, she was a middle-aged women without apparent cardiovascular risks and morbidity. MRI displayed abnormal high intensity on her quadriceps (Fig. 1C). The muscle biopsy showed myofibre degeneration and T cell (predominantly CD4+ T cell) infiltration around blood vessels, between muscle fascicles and in fibroadipose tissues (Fig. 1D), demonstrating inflammatory myopathy. We tested for AMA by fluorescence enzyme immunoassay on the suspicion of PBC because ALP level (1013 U/l, normal: <325 U/l) was elevated in her serum. She had positive AMA, but not antinuclear antibody, anti-Ro/SS-A antibody or myositis-specific autoantibodies including anti-ARS, MDA5, Mi-2 and TIF1-β antibodies. We considered that her inflammatory myopathy and LHD were associated with AMA and administered PSL at 60 mg/day concomitantly with furosemide at 40 mg/day and ursodeoxycholic acid (UDCA) at 600 mg/day. The serum CK, CK-MB and ALP levels were normalized and the results of manual muscle testing were recovered to grade 5 three months after initiation of the treatment. Polymorphic ventricular premature beats disappeared and echocardiographic systolic pulmonary artery pressure decreased from 55 to 24 mmHg. The remission has been maintained for over a year by tapered PSL at 10 mg/day with the same doses of furosemide and UDCA. Examination findings in the patient (A) Chest X-ray. (B) Electrocardiogram. (C) MRI of the leg, fat-suppressed T2-weighted image. The arrows indicate abnormal high intensity on the quadriceps. (D) Muscle biopsy specimen with haematoxylin-eosin staining. AMA can be detected in a group of idiopathic inflammatory myopathy [2]. The pathophysiology between AMA and myopathy has been unknown, although AMA-positive myopathy has been reported to be not only chronic skeletal muscle disorder but also to have severe cardiac complications, such as myocarditis, cardiomyopathy, conduction disorder and arrhythmias [3]. In the patient, the elevation of serum CK-MB levels and polymorphic ventricular premature beats suggested the presence of cardiomyopathy, and subsequent left heart dysfunction would lead to the development of PH. The PH-LHD was responsive to high dose of PSL synchronously with the improvement of skeletal myopathy. PH-LHD is a consequence of the underlying cardiac disorder, resulting in irreversible and poor prognostic situation in most cases [4]. Diuretics can alleviate the symptoms by reducing cardiac preload in patients with PH-LHD, but never improve their prognosis. We successfully treated her cardiomyopathy, as the cause of PH-LHD, with PSL. Our case is a valuable example of treatable PH-ILD. Generally, PBC does not require PSL therapy despite the autoimmune disease since UDCA satisfactorily can improve the liver prognosis [5]. PSL therapy is considered in patients with PBC only for coexisting other autoimmune condition. Clinicians should recognize inflammatory myopathy and cardiopulmonary involvement as important complications of PBC requiring PSL therapy. Based on our experience with this patient, we encourage clinicians to check the presence of AMA for patients with skeletal myopathy and/or unexplained cardiac dysfunction and to consider treating the manifestations with PSL in the case of positive AMA. Funding: No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: The authors have declared no conflicts of interest.