28. Acute pulmonary arterial hypertension in primary Sjögren’s syndrome with known cryptogenic organising pneumonia
Authors: Wittner Liora , Joy Mareen , Ellis Spencer 
Published: September 2019

Abstract

Introduction
We describe the case of a 58-year-old female with a background of primary Sjögren’s syndrome (PSS) and cryptogenic organising pneumonia (COP), who recently presented with worsening of her breathlessness and reduced exercise tolerance. CT pulmonary angiogram (CTPA) ruled out pulmonary embolism (PE) and indicated an improvement in the radiological appearance of her COP. However, an echocardiogram suggested the development of significant pulmonary arterial hypertension (PAH), requiring specialist input for vasodilators, phosphodiesterase inhibitors, endothelin receptor antagonists and diuretics. This case highlights the importance of thoroughly investigating breathlessness in connective tissue disease (CTD) patients and the need to consider dual pathology.

Case description
We report a case from 2019 involving a 58-year-old female who was already known to rheumatology with PSS, diagnosed in 2012. She was known to be ANA positive with anti-Ro and anti-La antibodies and had a history of anxiety. She was referred to the respiratory team in 2017, due to 6 months of progressive exertional breathlessness. A CT scan showed features consistent with COP, although lung function was considered to be stable, so no treatment was initiated.
Prednisolone was commenced in November 2018, due to worsening breathlessness. Despite this she continued to deteriorate, and in February 2019 her exercise tolerance reduced significantly, with new ankle swelling and postural dizziness. Clinical examination demonstrated a raised JVP. CTPA was negative for pulmonary thromboembolism. An urgent echocardiogram showed a severely dilated right ventricle with impaired systolic function, severe tricuspid regurgitation and an estimated PASP of 81mmgHg, suggestive of significant PAH.
The patient was admitted but developed type 1 respiratory failure and was transferred to a specialist centre for right heart catheterisation, confirming PAH. The patient received intravenous epoprostenol, dopamine and furosemide. The admission was complicated by pyrexia of unknown origin despite prolonged antibiotics, with no microorganisms grown on blood or bronchoscopic cultures. CT chest showed new widespread ground glass changes. Her fevers settled after withdrawal of antimicrobials and she was discharged on oral selexipag, tadalafil, macitentan, furosemide and spironolactone.
Her post discharge exercise tolerance is improved, and she has even been able to return to horse riding. Symptoms remain less severe than prior to her hospital admission, although worse than they had been as an inpatient on intravenous therapy; however, her oral medications are still being titrated. Right heart catheterisation, echocardiography and lung function tests will be repeated 4 months post discharge.

Discussion
PSS is not as strongly associated with severe organ involvement compared with other CTDs. At clinic reviews, clinicians tend to focus on dealing with sicca and joint symptoms and lymphoma monitoring. This case emphasises the importance of screening for and investigating respiratory symptoms, and the importance of considering PAH even when other lung diagnoses are present.
The case demonstrated several potential causes for breathlessness: worsening COP, PAH and PE. She was diagnosed with COP 6 months after the onset of her sicca symptoms and had been stable until 3 months before presentation. She had regular pulmonary function tests to monitor progress under respiratory follow up.
COP is a form of interstitial lung disease (ILD) which is thought to occur when alveolar epithelial injury ultimately results in intra-alveolar fibrosis. Radiological appearances include multiple patchy alveolar opacities which tend to be distributed peripherally and bilaterally. Opacities may appear like typical infective consolidation or have more of a ground glass appearance and may spontaneously migrate during the disease course, meaning severity may be difficult to assess. Air bronchograms are often present.
When she was reviewed in clinic with worsening breathlessness, there was no evidence that her COP was worsening radiologically, and her breathlessness had not improved with prednisolone. CTPA had excluded chronic thromboembolic pulmonary hypertension; however, studies have shown that CTD patients with antiphospholipid antibodies are more likely to develop PAH, even in absence of thrombosis. Our patient was positive for cardiolipin IgG and IgM. Nonetheless, clinical suspicion was sufficient for the patient to have echocardiography which indicated new onset PAH.
Her PAH was severe and symptomatic resulting in urgent admission to a specialist unit. This case highlights the key symptoms and signs which may make clinicians suspect PAH including reduced exercise tolerance and features of right heart failure.

Key learning points
Pulmonary involvement in PSS is common and 10-20% of patients develop significant respiratory disease. COP, although a rare ILD in the context of PSS (more common in rheumatoid arthritis), should be suspected in Sjögren’s patients with radiological consolidation who do not respond to antibiotic treatment.
The most common subtype of ILD in Sjögren’s is non-specific interstitial pneumonia (fibrosing variant). Along with COP, other less common manifestations include usual interstitial pneumonia and lymphocytic interstitial pneumonitis. These rarer manifestations of ILD are not as clearly identifiable radiologically and may require lung biopsies.
Studies suggest that the main risk factors for lung involvement include smoking, late onset and long evolution of disease. As in this case, pulmonary involvement is commonly associated with hypergammaglobulinaemia and anti-SSA, anti-SSB, ANA and rheumatoid factor positivity. We are not aware of many clinical or serological parameters which could be used to risk stratify which PSS patients are likely to develop ILD.
PAH should be suspected in patients with underlying CTD even in the context of pre-existing lung disease such as ILD or COP. Studies suggest that up to 20% of primary Sjögren’s patients may have asymptomatic PAH, therefore PAH should be considered in patients who respond poorly to steroid treatment for suspected ILD. PAH is challenging, as by the time it progresses to symptoms it can be severe and even life threatening. Early diagnosis and appropriate referral to a specialist unit may be critical. Guidance regarding echocardiogram as a tool for detecting PAH in PSS patients would be helpful. Our case illustrates the value of full clinical examination in CTD patients as a raised JVP led to early detection of PAH.

Conflicts of interest
The authors have declared no conflicts of interest.