Original contributionIncreased immunoglobulin G4–positive plasma cells in collagenous sprue☆
Introduction
Collagenous sprue is a small intestinal enteropathy of unknown etiology. Its precise origin as a pathologic entity is similarly unclear, with reports of clinically and pathologically compatible cases as early as 1947 [1]. However, it was not until the introduction of the diagnostic term collagenous sprue by Weinstein et al [2] in 1970 did this rare disease become increasingly clinically recognized and reported in the literature.
Although no definitive diagnostic criteria for collagenous sprue have been established, it is histologically characterized by a thickened subepithelial collagen band and villous atrophy [3]. Some authors have attempted to delineate reproducible diagnostic features of collagenous sprue such as a thickened subepithelial collagen table often containing entrapped cellular components of the lamina propria with variable villous atrophy and increased intraepithelial lymphocytes [4]. Clinical manifestations include chronic diarrhea and some degree of malabsorption, often leading to significant morbidity and mortality in patients with disease [5].
Where collagenous sprue lies in the spectrum of sprue disease continues to be debated [6]. Collagenous sprue has previously been regarded as an end point in the evolution of refractory celiac disease, explaining its strong correlation with poor prognosis [7], [8]. However, studies have shown that through diet modification and immunomodulation, some cases of collagenous sprue are responsive to therapy and may result in favorable outcomes [9], [10], [11]. The diversity in clinicopathologic features and outcomes has led to the opinion that collagenous sprue represents a distinct but heterogeneous disease with an assortment of etiologies [6].
Immunoglobulin G4 (IgG4)–related autoimmune disease is a recently established continuum of systemic and multiorgan conditions associated with fibrosis and a robust lympoplasmocytic infiltrate populated by a relatively increased quantity of IgG4-positive plasma cells [12]. Its role as an autoimmune sclerosing disease was first discovered in autoimmune pancreatitis (AIP) and linked to increased IgG4-positive plasma cells [12], [13]. Manifestations of IgG4-related autoimmune disease may range from single-organ involvement to widespread disease with or without concomitant AIP [14]. We postulate that collagenous sprue may be a consequence of autoimmune disease. Whether autoimmune mechanisms linked to IgG4-positive plasma cells play a role in the pathogenesis of collagenous sprue has not been previously investigated. Our study is the first to examine the presence and quantification of IgG4-positive plasma cells in biopsy specimens of collagenous sprue, celiac disease, peptic duodenitis, and normal duodenum.
Section snippets
Materials and methods
The archives of Mayo Clinic's Department of Laboratory Medicine and Pathology were searched for cases with a histologic diagnosis of collagenous sprue between 2001 and 2010. Forty cases of collagenous sprue from 35 patients were identified. Thirty of these cases have been previously reported in a series published from Mayo Clinic [10]. In addition, 25 cases of celiac disease, 15 cases of peptic duodenitis, and 25 cases of normal duodenal biopsies were similarly retrieved to serve as control
Results
The vital information of patients is shown in Table 1. Patients with collagenous sprue comprised 24 women (68.6%) and 11 men (31.4%) aged 2 to 85 years (mean, 68.5 years). The collagenous sprue group was significantly older than each of the control groups (P < .0001). The celiac disease cohort had 11 (44.0%) women and ranged in age from 6 to 65 years (mean, 45.0 years); the peptic duodenitis group had 7 (46.7%) women and ranged in age from 22 to 82 years (mean, 45.5 years); and patients in the
Discussion
Definitional histologic criteria for collagenous sprue have yet to be established. There is controversy regarding the significance of a thickened subepithelial collagen band in the small intestine. Some authors dispute its specificity for collagenous sprue and even whether collagenous sprue is a distinct enteropathy rather than a histologic change within the small bowel malabsorption spectrum [3]. Collagenous sprue has been reported in association with other collagenous gastrointestinal
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The authors declare no conflict of interest.