IgG4- related disease: an orphan disease with many faces

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21(st) century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD

HFE hemochromatosis screening in patients with severe hip osteoarthritis: A prospective cross-sectional study.

OBJECTIVE:Despite the high frequency of HFE gene mutations in Western Europe, widespread screening for HFE hemochromatosis is not recommended due to its variable phenotype. Joint pain and a premature osteoarthritis-like disease including the hip joints are the most frequent manifestation in patients with HFE hemochromatosis and iron overload. Therefore, screening of patients with severe osteoarthritis of the hip could identify patients with HFE hemochromatosis. METHODS:In this prospective cross-sectional study, 940 patients aged <70 years with end-stage osteoarthritis of the hip undergoing elective joint replacement surgery were screened for HFE hemochromatosis and compared to age- and sex-matched controls. RESULTS:No greater prevalence of C282Y homozygosity mutation or elevated serum ferritin or transferrin saturation levels was found in the study cohort with severe osteoarthritis of the hip than in controls from the general population. CONCLUSION:Our screening approach could not identify an increased prevalence of HFE gene mutations and iron overload in younger patients with severe osteoarthritis of the hip

Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) with highly active disease. The role of these biomarkers in relapsing disease is unclear.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients). Epidemiological, clinical and laboratory data were available for all visits.At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use

Serum biomarkers of patients with EGPA based on use of immunosuppressive agents at time of study visit.

<p>Data are shown as median (range in parenthesis); EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss); immunosuppr., immunosuppressive agents (9 patients were on methotrexate, 7 on azathioprine and 1 on mycophenolate mofetil); LR, Logistic regression analysis as described in Materials and Methods; MWU, Mann Whitney U test; n, number of visits</p><p>Serum biomarkers of patients with EGPA based on use of immunosuppressive agents at time of study visit.</p

Clinical manifestations of study patients with EGPA.

<p>EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss); BVAS: Birmingham Vasculitis Activity Score; BVAS/WG: BVAS for Wegener’s Granulomatosis; n (%), number and percentage of patients (out of those with known outcome) with manifestation since previous visit</p><p>*p<0.05</p><p>**p<0.01</p><p>***p<0.001 according to Fisher’s exact test (not corrected for multiple testing).</p><p>† p<0.05</p><p>‡ p<0.001 according to Mann Whitney U test (not corrected for multiple testing)</p><p>Clinical manifestations of study patients with EGPA.</p

Serum biomarkers of patients with EGPA in remission and at relapse.

<p>Data are shown as median (range in parenthesis); EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss); LR, Logistic regression analysis as described in Materials and Methods; MWU, Mann Whitney U test; n, number of visits</p><p>Serum biomarkers of patients with EGPA in remission and at relapse.</p

Serum biomarkers of patients with EGPA based on prednisone usage at time of study visit.

<p>Data are shown as median (range in parenthesis); EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss); LR, Logistic regression analysis as described in Materials and Methods; MWU, Mann Whitney U test; n, number of visits; pred., prednisone</p><p>Serum biomarkers of patients with EGPA based on prednisone usage at time of study visit.</p