Rheumatology Advance Access originally published online on June 28, 2008
Rheumatology 2008 47(9):1431-1432; doi:10.1093/rheumatology/ken241
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Pulmonary artery hypertension as the presenting feature of systemic sclerosis sine scleroderma
1Royal National Hospital for Rheumatic Diseases, Bath, 2Department of Cardiology, Royal Free Hospital, London, 3Department of Cardiology and 4Department of Respiratory Medicine, Royal United Hospital, Bath, UK
Correspondence to: N. J. McHugh, Royal National Hospital for Rheumatic Diseases, Bath, BA1 1RL, UK. E-mail: neil.mchugh{at}rnhrd.nhs.uk
SIR, Pulmonary artery hypertension (PAH) is now the leading cause of mortality in patients with lcSSc. Effective treatments for PAH such as prostenoid analogues, endothelin receptor antagonists and phosphodiesterase inhibitors are currently available, and screening for pulmonary vascular disease is recommended for all patients with lcSSc. Major organ involvement as part of SSc without the characteristic skin changes of scleroderma, defined as SSc sine scleroderma (ssSSc), was first described in 1954 [1]. Here we report the case of a 29-yr-old woman with severe PAH as the presenting feature of ssSSc.
The patient first presented in March 2004 with a history of RP. There were no additional clinical features of CTD, in particular SSc. Digital thermography confirmed RP and nail-fold capillaroscopy demonstrated some elongated capillaries with punctate haemorrhages. Routine haematological and biochemical investigations were normal. She had a positive ANA, 1/2560 titre with nucleolar staining pattern on indirect IF. Further characterization of the ANA specificity was negative by routine methods, which at that stage did not include immunoprecipitation. A diagnosis of auto-immune RP was made and she was seen annually over the next 3 yrs with stable RP and no new symptoms or signs to suggest CTD.
In March 2007, she presented to hospital with worsening exertional dyspnoea, a dry cough and right-sided pleuritic chest pain. Her exercise tolerance subsequently declined significantly and she became breathless at rest (New York Heart Association, NYHA Grade 4). She had signs of right-sided heart failure with a raised jugular venous pressure and peripheral oedema. ECG revealed right bundle branch block and P-wave pulmonale suggestive of right atrial hypertrophy. A CT pulmonary angiogram (CTPA) was reported as showing some minor consolidation in the right middle lobe and hypertrophy of her right heart chambers but there was no evidence of pulmonary embolus or interstitial lung disease (ILD) (Fig. 1). Trans-thoracic echocardiography demonstrated high estimated right ventricular pressures with a tricuspid regurgitation gradient of 75 mmHg. On right heart catheterization, the patient had evidence of significant pulmonary hypertension, with a mean pulmonary artery pressure of 57 mmHg, cardiac index of 2.4 l/min/m2 and a pulmonary vascular resistance of 11.9 WU.
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On reassessment, there were no other clinical features of CTD, including no skin thickening. Her autoimmune serology was repeated, and a high-titre nucleolar ANA was demonstrated as previously. The specificity was further characterized using immunoprecipitation as being anti-U3RNP (fibrillarin) autoantibodies. Based on the finding of an SSc-specific-autoantibody, and her clinical features, a diagnosis of ssSSc with isolated PAH was made. She was treated with diuretics, anticoagulants, and intra-venous epoprostenol. She responded well to treatment and her exercise tolerance improved to Grade 2 NYHA symptoms (walking >200 yards at normal pace).
The first case report of clinical features of SSc in the absence of cutaneous manifestations described a patient with isolated gastrointestinal disease and subsequently the term ssSSc was defined [1,2]. In a study by Poormoghim et al. [3] of 48 patients with ssSSc, 98% had RP. Severe dyspnoea was more prevalent in the ssSSc cohort (P < 0.0004) compared with their lcSSc cohort, but it was not clear if this was due to ILD, ILD associated with PAH or primary PAH. However, primary PAH that they defined either clinically or by cardiac catheterization was more frequent in the ssSSc cohort (23%) compared with lcSSc cohort (13%) (P = NS). PAH was the leading cause of mortality in both groups but this was more frequent in the ssSSc patients (52% compared with 24%, P = 0.009). In addition, the most common autoantibody specificity in the ssSSc group was ACA and this is a recognized risk factor for PAH in SSc. Patients with ssSSc can present in other ways and there are reports of ssSSc renal crisis and ssSSc-associated ILD associated with other nucleolar ANAs such as anti-RNAP-III and anti-Th/To [4–7].
To our knowledge this is the first published case of ssSSc presenting with isolated PAH associated with anti-U3 RNP autoantibodies. This autoantibody specificity has been previously reported in patients with dcSSc, lcSSc, overlap myositis, ILD, PAH and renal disease [8, 9]. Our case highlights the importance of close monitoring of patients who present with RP and a strongly positive nucleolar ANA pattern, for further organ involvement such as PAH that can now be effectively treated if detected early enough. More widespread use of specialist techniques to further characterize such ANA patterns would help to identify those patients at particular risk. In addition, the presence of abnormal nail-fold capillaries at presentation can be another indicator of future risk. A strong case can be made for such patients having annual pulmonary function tests and echocardiography to estimate pulmonary artery pressures as is currently recommended for patients with lcSSc [10].
Disclosure statement: H.G. is supported by the Arthritis Research Campaign. J.G.C. received research grants from GlaxoSmithKline. J.S. received travel grants from Encysive and Actelion. All other authors have declared no conflicts of interest.
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