a history of antisynthetase syndrome (mechanic's hands, arthritis, interstitial lung ... 4, April 2011, pp 633â634. © 2011, American College of Rheumatology.
Arthritis Care & Research Vol. 63, No. 4, April 2011, pp 633– 634 © 2011, American College of Rheumatology
LETTERS DOI 10.1002/acr.20392
Pulmonary arterial hypertension in antisynthetase syndrome: comment on the article by Chatterjee and Farver To the Editors: We read the case report by Chatterjee and Farver published recently in Arthritis Care & Research (1), which described a patient affected by antisynthetase syndrome who developed fatal pulmonary arterial hypertension (PAH). Of the 18 cases of antisynthetase syndrome referred to our unit, we observed 2 cases of PAH. These patients had a history of antisynthetase syndrome (mechanic’s hands, arthritis, interstitial lung disease [ILD], myositis, and anti– Jo-1 positivity) that started in 2001 and in 2003, respectively; prednisone and cyclosporine led to disease control (Table 1). After 7 and 6 years, respectively, from the onset of antisynthetase syndrome, ILD was stable according to the Kazerooni score (2) and pulmonary function tests; dyspnea worsened and estimated pulmonary arterial pressures (PAPs) were increased. Right heart catheterization confirmed a precapillary–PAH. Sildenafil led to clinical improvement in both patients (from New York Heart Association categorization class IV to class II) and to hemodynamic improvement in the second patient (mean PAPs normalization).
Unfortunately, the first patient was lost to followup 8 months after PAH diagnosis. Also, in our patients it is difficult to hypothesize that PAH was secondary to ILD; in fact, interstitial involvement was stable over time and forced vital capacity/diffusing capacity for carbon monoxide was ⬎1.4. In general, this ratio is ⬍1.4 in ILD-related pulmonary hypertension (3). Moreover, in our patients, PAH was a late finding that appeared when the disease was in remission. In contrast, the patient in the case report by Chatterjee and Farver experienced PAH that appeared early and progressed together with disease activity. Finally, sildenafil was effective in our patients, whereas the patient in the case report was unresponsive to sildenafil, trepostinil, high-dose corticosteroids, and cyclophosphamide. Taken together, these data suggest that associated PAH appearance should be taken into account also in antisynthetase syndrome patients, independently of ILD extension, disease activity, and duration. Lorenzo Cavagna, MD Elena Prisco, MD Carlomaurizio Montecucco, MD Roberto Caporali, MD University of Pavia and Foundation IRCCS Policlinico S. Matteo Pavia, Italy
Table 1. General characteristics and clinical findings of AS at the onset of the disease and at the development of PAH*
Sex Anti–extractable nuclear antigen Age (AS/PAH), years Active findings (AS) Active findings (PAH) Pulmonary function tests FVC (AS/PAH), % predicted DLCO (AS/PAH), % predicted FVC:DLCO (PAH), % predicted Chest HRCT Total Kazerooni score (AS/PAH) Fibrosis Kazerooni score (AS/PAH) Right heart catheterization Mean PAP, mm Hg Systolic PAP, mm Hg Diastolic PAP, mm Hg Cardiac index, liters/minute/m2 Right atrial pressure, mm Hg Pulmonary capillary wedge pressure, mm Hg Pulmonary vascular resistance, dynes/second/cm5
Patient 1
Patient 2
Male Jo–1-Ro 49/56 Myositis, ILD, arthritis, mechanic’s hands None
Female Jo–1-Ro 72/78 Myositis, ILD, arthritis, mechanic’s hands None
61/58 33/31 1.87
85/87 55/51 1.7
22/15 22/16
15/15 16/16
25 55 35 1.8 11 7 210
25 53 34 3.28 12 8 240
* AS ⫽ antisynthetase syndrome; PAH ⫽ pulmonary arterial hypertension; ILD ⫽ interstitial lung disease; FVC ⫽ forced vital capacity; DLCO ⫽ diffusing capacity for carbon monoxide; HRCT ⫽ high-resolution computed tomography; PAP ⫽ pulmonary arterial pressure.
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Letters
1. Chatterjee S, Farver C. Severe pulmonary hypertension in anti– Jo-1 patients. Arthritis Care Res (Hoboken) 2010;62:425–9. 2. Kazerooni EA, Martinez FJ, Flint A, Jamadar DA, Gross BH, Spizarny DL, et al. Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. Am J Roentgenol 1997;169:977– 83. 3. Steen V, Graham G, Conte C, Owens G, Medsger TA Jr. Isolated diffusing capacity reduction in systemic sclerosis. Arthritis Rheum 1992;35:765–70.
DOI 10.1002/acr.20391
Reply To the Editors: We thank Dr. Cavagna and colleagues for their comments regarding our recently published article on PAH in antisynthetase syndrome. We do agree that the appearance of associated PAH should be taken into account in patients with antisynthetase syndrome, independent of the duration, disease activity, and extension of ILD. At the time of submission of our case report, we were aware of only 1 other reported case of antisynthetase syndrome that developed severe PAH and concomitant ILD (1). That patient’s disease was associated with anti–PL-12 (anti–alanyl–transfer RNA synthetase) antibody production (1). Since our case report was published, more reports highlighting this association have been described. A series of 3 cases by Minai (2), from our institution, includes the case that we had described in our case report. The other 2 cases, both women with polymyositis, also had anti–Jo-1 antibodies, significant but stable ILD, and severe and progressive PAH. Like our patient, 1 other patient eventually died from progressive respiratory failure despite being on a combination regimen of epoprostenol and sildenafil. Taniguchi et al also reported another case of severe pulmonary hypertension in a 62-year-old woman with anti–Jo-1 syndrome (3). Therefore, if we include the 2 cases reported by Cavagna et al, it seems likely that at least in a subset of patients with polymyositis (and specifically in patients with antisynthetase syndrome), PAH tends to develop and
progress independent of the occurrence and progression of ILD. The exact prevalence of this complication is not known at this time. The pathophysiologic pathways and pathogenesis of this complication in antisynthetase syndrome need exploration, and the effectiveness of the novel pharmacologic agents used for idiopathic PAH and for scleroderma-associated PAH needs evaluation in this subset of patients as well. It would seem logical that if PAH contributes to dyspnea in patients with antisynthetase syndrome, it would be appropriate to offer pharmacologic therapy for the same, with the hope of providing additional symptomatic relief and disease modification, besides the benefit derived from immunosuppressive treatment of ILD. We are currently studying this association more systematically among patients with polymyositis/dermatomyositis (and specifically in patients with antisynthetase syndrome). If this association is found to be more common than realized, it may be worthwhile to routinely evaluate patients with antisynthetase syndrome for PAH, early in the course of their presentation, which is similar to what is recommended in patients with systemic sclerosis. Whether early intervention will halt or delay the progression of PAH in antisynthetase syndrome remains to be seen and may be the subject of another debate. Soumya Chatterjee, MD, MS, FRCP Ashwini Mhatre, MD, MS Carol Farver, MD Cleveland Clinic Cleveland, OH 1. Handa T, Nagai S, Kawabata D, Nagao T, Takemura M, Kitaichi M, et al. Long-term clinical course of a patient with anti PL-12 antibody accompanied by interstitial pneumonia and severe pulmonary hypertension. Intern Med 2005;44:319 –25. 2. Minai OA. Pulmonary hypertension in polymyositisdermatomyositis: clinical and hemodynamic characteristics and response to vasoactive therapy. Lupus 2009;18:1006 –10. 3. Taniguchi Y, Horino T, Kato T, Terada Y. Acute pulmonary arterial hypertension associated with anti-synthetase syndrome [letter]. Scand J Rheumatol 2010;39:179 – 80.
DOI 10.1002/acr.20472 New Manuscript Submissions to Go to Dr. Hannan Starting April 1
Dr. Marian Hannan of Harvard Medical School and the Institute for Aging Research, Hebrew SeniorLife becomes Editor of Arthritis Care & Research on July 1, 2011. A transition period will take place April 1– June 30, 2011. During this transition, review of new manuscript submissions will be handled by Dr. Hannan and her team, and pending manuscripts will continue to be handled by Drs. Katz and Yelin and their team. There will be no change in the process for submitting manuscripts, i.e., via Manuscript Central at http:// mc.manuscriptcentral.com/acr.
