Pulmonary infection due to Acrophialophora fusispora in a patient with underlying mixed connective tissue disease and chronic pulmonary aspergillosis: A case report and review of literature.

Acrophialophora fusispora is a soil-borne fungus rarely implicated in human infections. Here, we report a case of pulmonary infection due to A. fusispora in a 59-year-old male who presented with productive cough and gradually progressive dyspnoea for 20 days. He had a past history of pulmonary tuberculosis and was a known case of chronic obstructive pulmonary disease for past five years. He was diagnosed with mixed connective tissue disease and had been receiving oral azathioprine and prednisolone for three months. CECT thorax revealed an aspergilloma and serum Aspergillus fumigatus-specific IgG levels were raised, suggestive of chronic pulmonary aspergillosis. He was also tested positive for influenza A (H1N1) and received treatment with oral oseltamivir without any clinical benefit. Culture of sputum and bronchoalveolar lavage fluid showed growth of a fungus which was identified as Acrophialophora fusispora based on characteristic microscopic morphology and internal transcribed spacer sequencing of the ribosomal DNA. Antifungal susceptibility testing for six antifungal drugs showed itraconazole to have the most potent in vitro activity (MIC=0.25µg/mL) against A. fusispora in comparison to the other drugs tested. Treatment with itraconazole capsule 200mg twice daily was initiated and favourable clinical response was observed after 10 days of therapy. Follow-up visit after three months showed marked clinical and radiological improvement. A. fusispora is an emerging opportunistic fungus capable of causing invasive infections in immunocompromised hosts. Lack of knowledge about this fungus and confusion with morphologically similar opportunistic fungi have led to its misidentification and hence its prevalence remains largely underestimated. Accurate identification is crucial as it can help initiate early effective antifungal therapy and improve patient outcomes. To our knowledge, this is the first case of pulmonary infection due to A. fusispora reported from India.

Mixed connective tissue disease.

A defining feature of mixed connective tissue disease (MCTD) is the presence of antibodies against the U1-ribonucleoprotein (RNP) complex, but other autoantibodies in MCTD have recently been described. Research has also further elucidated the immune responses directed against U1-RNP in humans and in murine models of disease. Hypotheses implicating modified self-antigens and/or infectious agents in the pathogenesis of MCTD have been advanced. Links between the immunologic and clinical phenomena in MCTD are emerging. Longitudinal study of patients with MCTD highlights the impact of pulmonary hypertension on disease outcome.

Mycobacterium tuberculosis infection in a corticosteroid-treated rheumatic disease patient population.

OBJECTIVE: To investigate the incidence and risk factors of Mycobacterium tuberculosis infection in longterm corticosteroid treated rheumatic disease patients. METHODS: We assessed retrospectively the incidence of active tuberculosis and its risk factors in 269 rheumatic disease patients treated with moderate to high doses of corticosteroid for an evaluation period representing 1,035 corticosteroid years of therapy. RESULTS: The mean daily dose of steroid was 18.7 mg prednisolone and the mean daily dose during the first year of treatment was 20.4 mg prednisolone. 21 of these patients developed active tuberculosis resulting in an incidence rate of 20/1,000 patient-years. Cumulative and mean daily steroid doses during the follow-up period and during the first year of treatment, and a history of steroid pulse therapy were significantly correlated with the development of tuberculosis. A past history of tuberculosis, initial chest P-A abnormality, the starting dose of steroid, a history of more than 30 mg/day of prednisolone for more than one month, and a history of cytotoxic therapy were not related to the development of tuberculosis. CONCLUSION: The incidence of active tuberculosis is increased in rheumatic patients on moderate-to-high dose steroid treatment. Its risk factors are the cumulative and mean daily steroid doses during the follow-up period and during the first year of steroid treatment, and a history of steroid pulse therapy.

Seroprevalence of Helicobacter pylori infection in patients with connective tissue diseases.

To assess the possibility that Helicobacter pylori might be an etiologic agent, titers of anti-H. pylori IgG in sera of patients with connective tissue diseases [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyositis or dermatomyositis (PM/DM), progressive systemic sclerosis (PSS), mixed connective tissue disease (MCTD) and Sjögren's syndrome (SjS)] were compared with those of non-patient (healthy) volunteers and of patients with chronic pulmonary diseases (CPD) by ELISA using an extract of sonicated H. pylori as the antigen. Among patients with connective tissue diseases, those with SLE and RA had anti-H. pylori titers as low as healthy volunteers. Patients with SjS had much higher average titers than patients with CPD (P < 0.05). We previously reported that levels of myeloid calcium-binding protein (MRP8 and MRP14) were elevated in the serum of patients with connective tissue diseases. No correlation was found between serum levels of anti-H. pylori IgG and of MRP, a novel marker of inflammation. Furthermore, sera with high IgG titers were selected, and their reactivity with the H. pylori antigen were analyzed by Western blotting. H. pylori antigens with a variety of molecular masses were immunostained with sera from patients and from healthy volunteers, but a 16-kDa antigen was only immunostained by reaction with the sera of patients with MCTD and SjS, although the number of test samples was small.

Antibodies against polypeptides of purified Epstein-Barr virus in sera from patients with connective tissue diseases.

Antibodies to Epstein-Barr virus (EBV) were investigated in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) by immunoblotting using purified virus. Compared with sera from Epstein-Barr virus seropositive healthy individuals who served as control, sera from patients less frequently recognized several polypeptides. In particular, a 100 kDa envelope polypeptide was recognized by 92% of healthy subjects and only 11% of patients (P less than 0.001). On the other hand, 62% of the patient sera had antibodies to the 42 kDa envelope polypeptide, whereas these antibodies were only present in 4% of the sera from the control subjects (P less than 0.001). These results could reflect either perturbations of the immune response associated with connective tissue disorders or a possible pathogenic role of EBV.

Isolation of human herpesvirus-6 (HHV-6) from patients with collagen vascular diseases.

The prevalence and activity of human herpesvirus-6 in patients with collagen vascular diseases (CVD) was determined. One hundred and fifty patients with CVD (56 with systemic lupus erythematosus-SLE, 92 with rheumatoid arthritis-RA, 1 with Sharp's syndrome and 1 with atypical polyclonal lymphoproliferation-APL and rheumatoid features) were screened serologically (IFA and ELISA) for antibodies against human herpesvirus-6 (HHV-6), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Virus isolation was attempted from peripheral blood lymphocytes (PBL) of 25 persons with various disorders. PBL were grown in tissue culture and tested with standard HHV-6-positive antisera for viral antigen expression. Supernatants of the patient's lymphocyte cultures were used to infect HSB2 cells, and virus infection in these cells was proven by IFA, in situ hybridization and by electron microscopy. Fifty-five percent of the SLE patients, 6.5% of the RA patients and both patients with Sharp's syndrome or with APL had antibody titers indicative of active HHV-6 infection. Virus cultures were positive in 9 of the 25 attempts with establishment of stable virus lines. These patients were 5 with SLE or UCVD, and one each with RA, CFS, APL as well as one healthy control. Reactivated and chronic active HHV-6 infections are frequent in SLE like EBV in RA. The role of these viruses in the pathogenesis of the diseases or in their reactivation still needs further investigation.