Sarcoidosis: a state of the art review from the Thoracic Society of Australia and New Zealand.

Sarcoidosis is a systemic disease of unknown aetiology, characterised by non-caseating granulomatous inflammation. It most commonly manifests in the lungs and intrathoracic lymph nodes but can affect any organ. This summary of an educational resource provided by the Thoracic Society of Australia and New Zealand outlines the current understanding of sarcoidosis and highlights the need for further research. Our knowledge of the aetiology and immunopathogenesis of sarcoidosis remains incomplete. The enigma of sarcoidosis lies in its immunological paradox of type 1 T helper cell-dominated local inflammation co-existing with T regulatory-induced peripheral anergy. Although specific aetiological agents have not been identified, mounting evidence suggests that environmental and microbial antigens may trigger sarcoidosis. Genome-wide association studies have identified candidate genes conferring susceptibility and gene expression analyses have provided insights into cytokine dysregulation leading to inflammation. Sarcoidosis remains a diagnosis of exclusion based on histological evidence of non-caseating granulomas with compatible clinical and radiological findings. In recent years, endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated the diagnosis, and whole body positron emission tomography scanning has improved localisation of disease. No single biomarker is adequately sensitive and specific for detecting and monitoring disease activity. Most patients do not require treatment; when indicated, corticosteroids remain the initial standard of care, despite their adverse side effect profile. Other drugs with fewer side effects may be a better long term choice (eg, methotrexate, hydroxychloroquine, azathioprine, mycophenolate), while tumour necrosis factor-α inhibitors are a treatment option for patients with refractory disease.

Enhanced LPS-induced activation of IL-27 signalling in sarcoidosis.

RATIONALE: Granulomas in sarcoidosis have recently been described as containing Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits were hypothesised to differ between patients with sarcoidosis compared to healthy controls in peripheral blood. METHODS: Using a cross-sectional study design, plasma and peripheral blood mononuclear cells (PBMC) were collected from patients and control subjects. Protein and mRNA (in PBMC) levels for IL-27 and IL-35 (IL27, EBI3, IL12A subunits) as well as IL-27 receptor (IL6ST and IL27RA subunits) were assessed spontaneously and following direct (LPS) and indirect (anti-CD3/28 activation beads) macrophage stimulation using RT- PCR, ELISA and flow cytometry. RESULTS: Following stimulation with LPS, PBMC of patients with sarcoidosis displayed significantly enhanced expression of IL27 and EBI3 mRNA (p = 0.020 and p = 0.037 respectively) compared to PBMCs from healthy controls. There was also significantly enhanced production of IL-27 by PBMC from patients with sarcoidosis compared to healthy controls in response to LPS stimulation (p = 0.027). IL6ST mRNA and IL6ST protein were significantly lower in patients with sarcoidosis (mRNA p = 0.0002; MFI p = 0.0015) whilst IL27RA protein levels were significantly higher in patients with sarcoidosis compared to healthy controls (MFI p < 0.0001). Plasma IL-35 protein levels did not differ between control and sarcoidosis subjects (p = 0.23). CONCLUSION: These results suggest there may be exaggerated activation of IL-27 signalling in response to LPS in sarcoidosis.

An unusual case of spinal cord compression from concomitant spinal epidural lipomatosis and Hodgkin's lymphoma.

Spinal epidural lipomatosis (SEL) results from an abnormal accumulation of unencapsulated fat within the epidural space and is a rare cause of spinal cord compression, which needs to be considered with a high index of suspicion. It most commonly occurs secondary to chronic corticosteroid use and endocrinopathies. Idiopathic cases are highly associated with obesity. We report an unusual case of idiopathic thoracic SEL in a 69-year-old male, with an adjacent infiltrative Hodgkin's lymphoma and associated vertebral crush fracture, which resulted in ataxia and sensory loss. Magnetic resonance imaging scans displayed extensive SEL and an infiltrative disease process causing thoracic cord compression. Surgical decompression confirmed the presence of extensive epidural lipomatosis and Hodgkin's lymphoma and subsequently led to improvement in neurological symptoms. To our knowledge, this is the first reported case of concomitant SEL with an adjacent Hodgkin's lymphoma resulting in cord compression.

Measurement of neopterin, TGF-ß1 and ACE in the exhaled breath condensate of patients with sarcoidosis.

Exhaled breath condensate (EBC) is a non-invasive method of sampling airway lining fluids in respiratory diseases. This may be useful in identifying exhaled biomarkers of granulomatous inflammation and pulmonary fibrosis in patients with sarcoidosis. The aim of this pilot study was to identify markers of granulomatous airway inflammation and disease activity including neopterin, transforming growth factor-ß1 (TGF-ß1) and angiotensin converting enzyme (ACE) in EBC. EBC was collected from 16 patients with sarcoidosis and 22 healthy control subjects. EBC neopterin, and active-TGF-ß1 were measured by ELISA. EBC-ACE activity was measured using a colorimetric assay. EBC neopterin was detectable in 3/20 controls and 7/16 patients with sarcoidosis. Patients with sarcoidosis had greater mean neopterin levels compared to control subjects (0.57 ± 0.45 nmol l(-1) versus 0.41 ± 0.22 nmol l(-1), p = 0.04). TGF-ß1 was detectable in the EBC of all subjects and concentrations were higher in patients with sarcoidosis compared with controls (115.5 ± 79.6 pg mol(-1) versus 82.3 ± 16.2 pg mol(-1), p = 0.048). There was no difference in EBC ACE activity, which was only detectable in 3/20 healthy controls and 2/16 patients (p = 0.91). EBC markers of granulomatous inflammation are detectable at greater levels in patients with sarcoidosis compared to healthy controls subjects. Larger studies and development of sensitive assays are warranted to examine the disease correlates and predictive utility of these markers.

An unusual case of a pituitary fossa aspergilloma in an immunocompetent patient mimicking infiltrative tumour.

Sellar aspergillosis is a rare infection commonly mistaken for a pituitary tumour. We present a rare case of pituitary fossa Aspergillus fumigatus mycetoma in an immunocompetent 90-year-old female, who presented with headaches. Magnetic resonance imaging scans demonstrated an enhancing pituitary fossa mass that appeared to infiltrate the sphenoid sinus, suggestive of an invasive tumour. Stereotactic trans-sphenoidal resection confirmed localized A. fumigatus infection. The abscess was debrided and the dura was left intact. Her headaches resolved post-operatively and she was treated with voriconazole. This indicates that aspergilloma should be considered as a differential for an unexplained pituitary lesion even in elderly immunocompetent patients.

The potential of the immunological markers of sarcoidosis in exhaled breath and peripheral blood as future diagnostic and monitoring techniques.

Sarcoidosis is characterised by non-caseating granulomatous inflammation, with exaggerated immune responses at sites of disease and derangements of normal tissue architecture. The lungs are most commonly involved and progressive inflammation may result in pulmonary fibrosis. The immunopathogenesis and aetiology remain uncertain, which has made it difficult to identify a single sufficiently sensitive or specific diagnostic marker. Further investigation is needed to identify sensitive and specific markers of disease, such as in peripheral blood and exhaled breath condensate (EBC). Identification of disease markers may also be useful for investigating disease activity and predicting progression to fibrosis. This review explores the literature on the cytokine profiles of blood and bronchoalveolar lavage lymphocytes following ex vivo stimulation, as well as disease markers measured using the medium of EBC.

Liver abscess or neoplasm? A diagnostic and surgical dilemma.

Hepatocellular carcinoma can is often associated with hepatitis B infection. With localised tumours, liver resection can result in a cure. This case presents an unusual finding of concurrent hepatitis B and liver fluke infection with hepatocellular carcinoma in a 50 year old man from Thailand. The discussion illustrates difficulties of arriving at a diagnosis and ensuring appropriate surgical management.