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Introduction We describe a case of a 40-year-old male with recurrent episodes of fever, polyarthralgia, myalgia and pharyngitis. Investigations revealed intermittent transaminitis and high serum ferritin, but also positive streptococcal serology, despite negative microbiology. This case illustrates the challenges faced when diagnosing adult-onset Still’s disease (AOSD) and distinguishing between alternative diagnoses, such as post streptococcal reactive arthritis (PSRA). It is important to differentiate between these conditions as they have different organ involvement, monitoring requirements, treatments and prognoses. This case has prompted a review of studies where the frequencies of clinical and serological features are noted in these two conditions. Case description A 40-year-old male was referred to acute medicine with 3 months of headache, fatigue, polyarthralgia, myalgia, night sweats, lymphadenopathy and otalgia. He reported a severe pharyngitis at symptom onset, 12 weeks earlier, for which he was given 20 days of phenoxymethylpenicillin by his GP. His sore throat improved, but his other symptoms persisted. His GP then suspected sinusitis, so prescribed doxycycline. He had no significant past medical history other than a tonsillectomy in his 20s and had been on no regular medication. On admission, he reported fever, headache, sweats, myalgia and arthralgia of the elbows and wrists. He had no meningism and denied any rashes, nasal discharge, joint swelling, neurological symptoms, weight loss or symptoms to suggest underlying malignancy. An ENT specialist felt sinusitis to be unlikely.  On examination, the initial positive findings included tenderness of the right mastoid process, low grade cervical lymphadenopathy, tender wrists, erythematous pharynx and myalgia of the thighs. There was no rash, clinical synovitis, or organomegaly.  Investigations included: Throat cultures: negative; Urine dip: trace blood; Anti-Streptolysin O Titres (ASOT): 1600 units/ml; Anti-DNAse B titres: 800; WCC: 16, neutrophils: 73%; ESR: 62; CRP: 120; Ferritin: 1322 (5x upper limit of normal); Transaminitis: ALT: 234, AST: 123; LDH: 428; CK: 47; ANCA, ANA, rheumatoid factor, anti-CCP, CMV, EBV, hepatitis A, B & C, HIV: negative; Echocardiogram: normal; CT head, chest, abdomen, pelvis: normal Our patient was referred to rheumatology and treatment for presumed AOSD was commenced with 30mg prednisolone (weaning dose) and methotrexate. His arthralgia and systemic symptoms vastly improved within one month. At that stage his ASOT was noted to have risen further to 3200 units/ml. He has stopped all medications after one year of treatment. Two months after cessation of methotrexate he remains asymptomatic, with marginally elevated ferritin but otherwise normal routine bloods. Discussion This case illustrates the difficulties involved in establishing an AOSD diagnosis. Despite meeting the Yamaguchi criteria, serositis, maculopapular rash and documented quotidian fever were absent. ASOT levels were elevated and rose after presentation, whilst pharyngitis had been evident at symptom onset, which could imply an alternative differential of PSRA.  Identification of AOSD is important as it necessitates monitoring for cardiopulmonary manifestations and rarely macrophage activation syndrome. In AOSD, IL6-IL1 blockade is used for recalcitrant disease. For PSRA, it is important to ensure there are no features of acute rheumatic fever, renal disease, or cardiac disease. PSRA was less likely due to liver and ferritin abnormalities, which persisted long after CRP normalisation, persistent lymphadenopathy and negative throat swabs. The rise in ASOT was considered a false positive. The table compares clinical and serological features for the conditions. Table: Clinical and laboratory features in AOSD and PSRA AOSDPSRACLINICALJointsMild, oligoarticular and transientMay evolve into severe, destructive polyarticular formNon-migratory symmetrical polyarthritisUsually resolves in weeks but can last for monthsPredominantly affects knees, ankles and wristsRashEvanescent salmon pink macular/maculopapularOccurs with feverKoebner phenomenon (73%)Scarlatine rash at disease onsetGuttate psoriasisErythema nodosum/multiformeLeukocytoclastic vasculitisFeverDaily/twice daily lasting less than 4 hoursMay be present at initial point of infectionPharyngitisFrequently (70%)Usually precedes joint symptoms by 14 daysLiver50%No dataSpleen50%No dataCardiacPericarditis, myocarditis (30-40%)No increased risk in adultsPulmonaryPleuritis, transient pulmonary infiltrates (30-40%)No dataHaematologicalTTP/HUS/MAS (rare)No dataSEROLOGICALPositive Rheumatoid Factor0-7%0%Positive ASOTNo data82-100%ComplementNo dataNormal in 100%Deranged LFTs35-76%17%Hyperferritinaemia86-100%No dataRaised ESR100%76-100%Raised CRP100%100%Leucocytosis67-81%12-47%Anaemia62%No data Key learning points There can be diagnostic uncertainty regarding the diagnosis of AOSD, particularly as other conditions may share clinical features, such as recurrent pharyngitis with polyarthralgia/arthritis. PSRA is an important condition to keep in mind when investigating and managing these patients. Both conditions can present with polyarthralgia, but the chronic arthritis of AOSD can progress to destructive arthropathy.  The rashes in both conditions generally differ, helping to distinguish between the two. Persistent pyrexia and pharyngitis would be rare in PSRA unless the patient is having recurrent streptococcal infections. Therefore, it is important to perform ENT examination with bacterial throat swabs and for the patient to keep a fever diary. Similarly, cervical lymphadenopathy should only be present during the acute phase of the streptococcal infection rather than persistently, as in the case of AOSD. Hepatosplenomegaly and haematological manifestations are more strongly associated with AOSD, so if these features are present there is greater diagnostic certainty, as long as infection and malignancy can be ruled out. ASOT can be falsely positive due to cross reactivity with myeloma, liver disease, hypergammaglobulinaemia, and autoimmune disease associated with increased rheumatoid factor. ASOT levels peak at 3 weeks and decrease at 8 weeks, and only decreases to pre-infectious levels at 8 months. Anti-DNAse B peaks at 6-8 weeks, decreases at 12 weeks and returns to pre-infectious levels at 12 months. Therefore, the timeline of possible streptococcal infection is important, as even if the infection was months prior, ASOT may be elevated. Repeating both titres is useful, as a disproportionate rise in anti-DNASe B compared with ASOT suggests an acute infection. ASOT may remain elevated for many months in the pharyngeal carrier state. It would be interesting to clarify the experience of other centres in the identification of raised ASOT in AOSD. Conflicts of interest The authors have declared no conflicts of interest.

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.

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