P. J. Roberts-Thomson

Risk of cancer in patients with scleroderma: a population based cohort study

Background: Previous studies have suggested an increased risk of cancer among patients with scleroderma. Objective: To study a population based cohort of patients with scleroderma in South Australia. Methods: Subjects with scleroderma were identified from the South Australian Scleroderma Registry established in 1993. All subjects on the scleroderma registry were linked to the South Australian Cancer Registry to identify all cases of cancer until 31 December 2000. Standardised incidence ratios (SIRs) for cancer for subjects with scleroderma were determined using the age- and sex-specific rates for South Australia. Results: In 441 patients with scleroderma, 90 cases of cancer were identified, 47 of which developed after inclusion on the scleroderma registry. The SIRs for all cancers among these patients were significantly increased (SIR=1.99; 95% confidence interval (95% CI) 1.46 to 2.65) compared with the cancer incidence rates for South Australia. The SIRs for lung cancer (SIR=5.9; 95% CI 3.05 to 10.31) were also significantly increased. The SIRs for all cancers among the subgroups with diffuse scleroderma (SIR=2.73; 95% CI 1.31 to 5.02) and limited scleroderma (SIR=1.85; 95% CI 1.23 to 2.68) were significantly increased. Conclusions: This population based cohort study provides evidence that scleroderma is associated with cancer, and in particular, lung cancer. In addition, both diffuse and limited forms of scleroderma are associated with a similarly increased risk of cancer.

Diurnal variation of lymphocyte subsets identified by monoclonal antibodies.

Monoclonal antibodies specific for lymphocyte subsets were used to examine circulating lymphocytes obtained at frequent intervals from healthy subjects. A diurnal rhythm was found in the total numbers of lymphocytes, T cells, inducer/helper cells, suppressor/cytotoxic cells, Ia positive cells, and B cells. The lowest levels of all subsets were seen at 0900 hours and the highest levels at 2100. In some subjects the ratio of helper to suppressor cells varied considerably during the sample period, though the ratio was relatively constant for the group as a whole.

Scleroderma in South Australia: epidemiological observations of possible pathogenic significance

Background: Scleroderma is an autoimmune disorder of unknown cause. Previous epidemiological studies have suggested some regional clustering and associations with occupations involving exposure to silica dusts and hydrocarbons.

Isolated pulmonary hypertension in scleroderma

Background: Isolated pulmonary hypertension (PHT) is now the most frequent cause of disease‐related death in limited cutaneous scleroderma, the commonest disease variant of this disabling connective tissue disorder. Endothelin‐1 receptor antagonists provide symptomatic benefit but to date have not been shown to prolong survival.

New insights into disease pathogenesis in crusted (Norwegian) scabies: the skin immune response in crusted scabies

Background  Crusted scabies is a rare and severely debilitating disease characterized by infestation of the skin with up to millions of Sarcoptes scabiei mites, high total IgG levels, extremely high total IgE levels, and the development of hyperkeratotic skin crusts that may be loose, scaly and flaky or thick and adherent.

Scleroderma renal crisis: poor outcome despite aggressive antihypertensive treatment

Background:  Scleroderma renal crisis (SRC) is a rare but feared complication of scleroderma. Angiotensin‐converting enzyme (ACE) inhibition has significantly improved survival, but it is unknown whether prophylactic ACE inhibitors will prevent this complication.

South Australian Scleroderma Register: autoantibodies as predictive biomarkers of phenotype and outcome

Aim:  To investigate the relationship between scleroderma‐specific autoantibodies and clinical phenotype and survival in South Australian patients with scleroderma.

Clinical heterogeneity and prognostic features of South Australian patients with anti‐synthetase autoantibodies

Aim:  To determine the clinical, serological and prognostic features of patients with autoantibodies against three aminoacyl‐transfer RNA synthetases (ARS), namely Jo‐1 (histidyl‐tRNA synthetase), PL‐7 (threonyl‐tRNA synthetase) and PL‐12 (alanyl‐tRNA synthetase) in South Australia.

Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis

Objectives: To characterise the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active rheumatoid arthritis (RA). Methods: Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies to detect dendritic cell subsets, including activation markers and cytokines relevant to dendritic cell function. Co-localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy. Results: The dendritic cells identified in RA synovial tissue that strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid- and plasmacytoid-type dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL12 as well as interferon α and γ. Conclusions: The close correlation of these dendritic cells with the presence of serum rheumatoid factor, a prognostic factor for worse disease outcome, and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.

Risk factors for lung cancer in patients with scleroderma: A nested case-control study

Objectives: To study potential risk factors for the development of lung cancer in patients with scleroderma and explore the chronological relationship between onset of scleroderma symptoms and subtypes of lung cancer. Method: Linkage of two population-based registers to identify lung cancer cases and gender-matched controls with scleroderma, followed by retrospective case note review for clinical details. Results: Patients with scleroderma who smoke are seven times more likely to develop lung cancer than non-smokers (p = 0.008). Smokers with scleroderma and cancer smoke more than smokers with scleroderma without cancer (p = 0.019). Pulmonary fibrosis and anti-topoisomerase antibody do not increase the risk of lung cancer. Peripheral lung tumours occur earlier after the onset of scleroderma symptoms than bronchogenic tumours (p = 0.05). Conclusions: Smokers with scleroderma should be monitored for the presence of lung cancer and counselled to quit smoking. The earlier development of peripheral lung tumours is not consistent, with pulmonary fibrosis being an aetiological factor.