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Q1: What are the common causes of pleuropericardial effusion?
The combination of fever and pleuropericardial effusion is an unusual presenting feature and raises the possibility of infectious, neoplastic and connective tissue disorders. The most frequent causes are listed in table 1.
Q2: What further investigations are necessary in this patient's case?
Investigations should be directed at determining the cause and will initially involve haematological tests including: full blood count, urea and electrolytes, liver and thyroid function, inflammatory markers (ESR or C reactive protein), antinuclear antibody (with DNA and extractable nuclear antigen screen if positive), antineutrophil cytoplasmic antibody (ANCA), rheumatoid factor, and serology for viruses and other infective causes. Analysis of the pericardial and/or pleural fluid will nearly always be necessary and should include culture for bacteria and mycobacteria, protein and glucose concentrations, differential cell count, and cytology. Pleural or pericardial biopsy might be indicated if malignancy or tuberculosis is suspected. Specific tumour markers might be helpful in detecting occult malignancy. In this patient's case thyroid function and other liver function tests were normal, rheumatoid factor, antinuclear factor, and ANCA were negative and serology did not suggest recent bacterial or viral infection by any of the common respiratory pathogens. Cytological and microbiological analysis of the pericardial and pleural fluid did not show any evidence of infection or malignancy. The pleural fluid contained small lymphocytes and neutrophils with total protein 41 g/l. Abdominal ultrasound was used to exclude ovarian carcinoma and other malignancies.
Q3: The patient's symptoms and radiology returned to normal after treatment with aspirin 3.6 g daily. What is the likely diagnosis?
Pleuropericardial effusion in the context of a history of joint symptoms together with fever and negative investigations for connective tissue disorders, malignancy, and infection suggested a diagnosis of adult onset Still's disease (AOSD). This is a diagnosis of exclusion and in clinical practice care should be taken to continue to look for signs of the more common causes such as rheumatoid arthritis or systemic lupus erythematosus.
Once AOSD was suspected the patient was started on 3.6 g of aspirin daily in divided doses. Within three days systemic symptoms and pyrexia were beginning to settle and she was discharged. At review three weeks later her cough had disappeared, joint pains had settled, and chest radiography showed partial resolution of the effusions. Eight weeks later the effusions were no longer seen, ESR was 13 mm/hour, and haemoglobin 133 g/l. She remained well for five months when she experienced aching and swelling of both wrists despite continued aspirin and was started on hydroxychloroquine 200 mg twice daily. Reassessment one year after diagnosis showed no serological or clinical evidence of an evolving connective tissue disease, supporting the diagnosis of AOSD.
AOSD is a rare disorder typically affecting young adults between the ages of 16 and 35 with equal sex distribution. The diagnosis rests on the combination of typical clinical and laboratory findings and diagnostic criteria have been developed by Cush (table2).1 Three features (fever, rash, and arthralgia) are common at presentation.2 A daily spiking fever of 39°C or more is seen in 97% of cases. Eighty eight per cent of cases have a characteristic rash, the so-called “Still's” rash, which is pink, macular or maculopapular, and evanescent. It usually occurs on the trunk and proximal extremities and may coincide with a fever spike. Arthralgia is universal and most develop a predominantly distal polyarthritis. Pharyngitis, splenomegaly, lymphadenopathy, cardiopulmonary involvement, and hepatomegaly are sometimes seen. Not all the eventual symptoms and signs may be apparent at presentation and the condition can evolve over a period of weeks or months.
The consistent laboratory findings are anaemia, high ESR, leucocytosis, and deranged liver function tests. A negative rheumatoid factor and antinuclear antibody are required for the diagnosis to be made. Infection, malignancy, and other connective tissue diseases may give a similar clinical picture and investigations should be directed at excluding these as possible causes. Additionally when there are any atypical features, such as the age of this patient, it is essential to review the diagnosis after some months to rule out evolving connective tissue disorders.
Pulmonary involvement in AOSD is reported in the largest series to occur in 20%–30% of cases.2-6 Pleuritis leading to pleurisy and/or pleural effusions is the commonest pulmonary manifestation. Effusions are usually bilateral and the pleural fluid is an exudate with increased numbers of inflammatory cells particularly neutrophils. Pneumonitis occurs in about 10% of cases giving rise to chest radiograph opacities. Pulmonary function tests generally show a mild restrictive picture and gas transfer may be reduced. The commonest cardiac manifestation of AOSD is pericarditis and pericardial effusion, seen in 26%–28% of cases7 and usually occurs with pleural effusion. Tamponade occurs in 1%–2% of cases. Rarer cardiac findings are myocarditis (5%) and endocarditis.
The treatment of choice is a salicylate, usually aspirin, in high dose and this may be combined with another non-steroidal anti-inflammatory drug (NSAID) if there is no response to a single agent. Altogether 20%–25% of patients respond to NSAIDs alone. Systemic corticosteroids can be used if symptoms fail to improve with these measures and prompt remission is typical. Disease modifying antirheumatic drugs may be required particularly if joint symptoms persist as was the case in this instance and intramuscular gold, penicillamine, sulfasalazine, and hydroxychloroquine have been used. Methotrexate may be useful if systemic features are present.7 The majority of patients can expect prolonged or permanent remission, however, intermittent relapses or chronic disease course does occur in 30%–50% of cases. During follow up it is necessary to check rheumatoid factor and antinuclear antibodies regularly to ensure that the presenting illness is not an early presentation of another connective tissue disorder.
This case fulfils the diagnostic criteria for AOSD except for the finding that the leucocytosis was slightly below that stipulated by Cush. As alternative diagnoses were sought thoroughly but not found and the patient responded completely to NSAIDs we feel this is the likely diagnosis. She was unusual in her late age of presentation and this increased the importance of excluding malignancy. The absence of a Still's rash and the relatively minor articular involvement are associated with a better prognosis.3 Response to NSAID treatment is also associated with a favourable outcome. Awareness of the condition is important when investigating patients with pleural and pericardial effusions particularly when these occur together.
Pleuropericardial effusion caused by adult onset Still's disease.