Rheumatological features of Whipple disease

Whipple disease (WD) is a rare infectious systemic disease. Rheumatologists are at the frontline of WD diagnosis due to the early rheumatological manifestations. An early diagnosis is crucial, as usual anti-rheumatic drugs, especially TNF inhibitors, may worsen the disease course. We conducted a retrospective multicentre national study from January 2010 to April 2020 to better characterize the rheumatological features of WD. Classic WD (CWD) was defined by positive periodic acid-Schiff (PAS) staining of a small-bowel biopsy sample, and non-CWD (NCWD) was defined by negative PAS staining of a small-bowel biopsy sample but at least one positive Tropheryma whipplei (TW) polymerase chain reaction (PCR) for a digestive or extradigestive specimen. Sixty-eight patients were enrolled, including 11 CWD patients. Twenty patients (30%) received TNF inhibitors during the WD course, with inefficacy or symptom worsening. More digestive symptoms and systemic biological features were observed in CWD patients than in NCWD patients, but both patient groups had similar outcomes, especially concerning the response to antibiotics and relapse rate. Stool and saliva TW PCR sensitivity were both 100% for CWD and 75% for NCWD and 89% and 60% for small-bowel biopsy sample PCR, respectively. WD encountered in rheumatology units has many presentations, which might result from different pathophysiologies that are dependent on host immunity. Given the heterogeneous presentations and the presence of chronic carriage, multiple TW PCR tests on samples from specific rheumatological sites when possible should be performed, but samples from nonspecific digestive and extradigestive sites also have great value.

Progression of pediatric celiac disease from potential celiac disease to celiac disease: a retrospective cohort study

Background A subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease. Methods We performed a retrospective analysis of children (0–18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children’s Hospital between 2013 and 2018. Results Three hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6–5) X upper limit of normal (ULN) vs. 6.41 (3.4–10.5) X ULN) at time of first biopsy. Their median anti-TTG IgA concentrations rose from 2.4 (1.6–5) X ULN to 3.6 (3.1–9.2) X ULN between biopsies. Conclusions Four percent of biopsy confirmed celiac patients initially had a negative biopsy, but later developed histopathologic celiac disease. This is likely an underestimate as no surveillance algorithm was in place. We recommend repeat assessment in children whose serology suggests celiac disease despite normal small bowel biopsy.

Celiac Disease and Sensitization to Wheat, Rye, and Barley: Should We Be Concerned?

<b><i>Background:</i></b> Concomitance of celiac disease (CD) and IgE-mediated wheat allergy is described in some case reports. The objective was to evaluate the frequency of sensitization to wheat, rye, barley, and malt in children and adolescents with CD. <b><i>Methods:</i></b> Measurement of serum levels of specific IgE to wheat, rye, barley, and malt (ImmunoCAP; sensitization IgE ≥0.35 kUA/L) in CD patients followed in specialized clinics to verify allergy history, general characteristics, small bowel biopsy characteristics, compliance with gluten-free diet (GFD), and occurrence of symptoms in case of noncompliance. <b><i>Results:</i></b> We evaluated 74 patients; the median of age and age at diagnosis of CD were 8.6 years (5.0–12.8) and 3.6 years (1.6–7.0), respectively. Median time of GFD was 3.5 years (1.4–5.8). History of asthma occurred in 17.3% of subjects, allergic rhinitis in 13.5%, and AD in 5.4%. Frequency of sensitization was 4% for wheat, 10.8% for rye, 5.4% for barley, and 2.7% for malt. There was no association between wheat sensitization and age at diagnosis, time of GFD, small bowel biopsy characteristics, allergy history, and gluten consumption. There was no relationship between sensitization to wheat and occurrence of immediate symptoms when not complying with GFD. <b><i>Conclusion:</i></b> In conclusion, the frequency of sensitization to wheat, rye, barley, and malt in CD patients was 4, 10.8, 5.4, and 2.7%, respectively. Therefore, to ensure that cutaneous and respiratory contact with wheat is safe, we advise patients with CD to investigate their sensitivity to wheat, rye, and barley because not all patients with CD are allergic to these cereals.

Diagnostic Approach for Classic Compared With Localized Whipple Disease

Background Whipple disease (WD), a rare systemic infection caused by Tropheryma whipplei, can be a diagnostic challenge due to its variable presentation. The role of T. whipplei polymerase chain reaction (PCR) is unclear as small bowel biopsy with Periodic acid-Schiff (PAS) staining remains the diagnostic gold standard. Individualized diagnostic approaches based on variable clinical manifestations are underutilized. We investigated the methodologies employed at our institution to diagnose WD. Methods We retrospectively collected all cases of WD diagnosed from 1994 to 2016. Microbiology laboratory and anatomic pathology databases were queried. Case characteristics and disease clinical phenotypes (classical, localized WD arthritis, and localized central nervous system [CNS] disease) were described. The diagnostic approach and testing yield were analyzed and reported. Results Thirty-three cases of WD were diagnosed (18 classic WD [CWD], 9 localized WD arthritis [LWD], 6 CNS WD). Misdiagnosis and delay in diagnosis were frequent. Diagnostic approach and test yield differed by classical vs localized WD involvement. Small bowel tissue biopsy PAS stain/PCR was overwhelmingly positive (86%/92%) in CWD, yet seldom positive (12%/42%) in LWD (P &lt; .001). Affected joint synovial fluid PCR was frequently positive in both CWD (100%, 3/3) and LWD (85%, 6/7). Conclusions These results support the role of small bowel biopsy PAS stain/PCR in the diagnosis of CW, though this approach may be of limited utility in LWD or CNS WD without gastrointestinal symptoms. Affected joint synovial fluid or cerebrospinal fluid PCR was frequently positive in both CWD and LWD, supporting its diagnostic usefulness.