Rapidly Progressive Respiratory Failure in Mixed Connective Tissue Disease: Report of an Autopsy Case

Abstract

A 64-year-old woman presented with exertional dyspnea. The case was diagnosed as mixed connective tissue disease (MCTD) due to presence of swollen fingers, Raynaud's phenomenon, muscle weakness, positive anti-U1RNP antibody, pericarditis and interstitial pneumonia. Although the histology from a transbronchial lung biopsy (TBLB) indicated organizing pneumonia, corticosteroid therapy was postponed for two months at the patient's request. She died 8 weeks later from acute progressive interstitial pneumonia in spite of the administration of intravenous cyclophosphamide combined with prednisolone. The autopsy revealed exudative and organizing diffuse alveolar damage (DAD). Previous reports have shown that DAD is an extremely rare pulmonary complication in MCTD. This report presents a case of MCTD with acute respiratory failure. This case thus suggests that this therapy should be administered as soon as possible.

Auto-antigenic Properties of the Spliceosome as a Molecular Tool for Diagnosing Systemic Lupus Erythematosus and Mixed Connective Tissue Disease Patients

“…The initial, but not always reliable, description of MCTD as a benign disease that transforms into other well known autoimmune disorders has limited its recognition during the study of SLE and other cohorts of autoimmune patients (Sharp et al, 1972;Tan et al, 1982;Hochberg et al, 1997;Lundberg, 2005;Petri et al, 2012;Shi et al, 2012). Recent studies have shown lung disease seems to be specifically associated with MCTD but not SLE patients (Shirai et al, 2012;Watanabe et al, 2012;Gunnarsson et al, 2013). By contrast, renal disorders have long been a characteristic prevalent in SLE but not the MCTD population (Everett and Harrell, 1956;Natali et al, 1972;Cavagna et al, 2013;Lin et al, 2013).…”

“…Second, the concept of MCTD has clinical relevance since malfunction of vital organs has been reported to be prevalent in this syndrome when compared to SLE, for example (Everett and Harrell, 1956;Natali et al, 1972;Shirai et al, 2012;Watanabe et al, 2012;Gunnarsson et al, 2013). Third, new classification rules with significant power to distinguish between SLE and MCTD patients need to be developed given that available classification criteria sets were designed to identify either SLE or MCTD subjects but not to segregate between these two autoimmune disorders (Sharp, 1987;Kasukawa et al, 1988;Kahn et al, 1991;Amigues et al, 1996;Hochberg et al, 1997;Petri et al, 2012).…”

“…For example, SLE patients show elevated immunoglobulin G (IgG) autoimmune responses to Sm proteins while those with the autoimmune response directed to snRNP subunits are frequently MCTD individuals (Luyckx et al, 2005). Clinically, kidney damage is more frequent in SLE while lung malfunction is often observed in MCTD patients (De Clerck et al, 1989;Sawai et al 1994;Yoshida et al, 1994;Watanabe et al, 2012). Previous studies have described elevated IgG autoimmune response to U1Ap fragments in both SLE and MCTD patients (Sato et al, 2010).…”

“…Furthermore, the initial description of MCTD as a benign autoimmune disease (Sharp et al, 1972) most likely has jeopardized its relevance as independent identity. Nevertheless, involvement of vital organs such as lung and heart in MCTD patients has long been reported by several independent investigations (Badui et al, 1984;Smolen and Steiner, 1998;Venables, 2006;Watanabe et al, 2012;Gunnarsson et al, 2013), however; these findings have not caught sufficient attention from the research community. Consequently, new efforts to improve current classification methods for MCTD that could facilitate its early diagnosis and potential treatment have been limited.…”

“…Moreover, even though some SLE patients develop anti-U1 snRNP response; they are able to retain IgM reactivity against these antigens while those with MCTD class switch to IgG response instead (Vlachoyiannopoulos et al, 1996;Somarelli et al, 2011;. Likewise, severe renal and central nervous system (CNS) manifestations are observed in SLE patients (Zidan et al, 2013) while lung and heart malfunctions are frequent in MCTD subjects (Watanabe et al, 2012;Gunnarsson et al, 2013).…”