The differential diagnosis in patients with generalized lymphadenopathy includes sarcoidosis, multicentric Castleman disease, infection (eg, tuberculosis), and lymphoma or other malignancy. IgG4-related lymphadenopathy is distinguished from these conditions by the modest lymph node enlargement, histologic distinctions on biopsy, lack of constitutional features, and the usually striking clinical response to glucocorticoids [ 9 ]. Patients with bilateral hilar adenopathy may mimic sarcoidosis. (See "Evaluation of peripheral lymphadenopathy in adults" and "Clinical presentation and diagnosis of non-Hodgkin lymphoma" and "Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma" and 'Lung and pleural disease' below and "Multicentric Castleman's disease" .)
IgG4-SC remains a diagnostic challenge; the key issue being differentiation from other forms of sclerosing cholangitis and pancreatobiliary malignancy. Current therapy is guided by international expert consensus but is not supported by randomized controlled trials. Rituximab provides an option for those experiencing adverse effects and/or refractory to conventional therapy, and it gives clues to disease pathogenesis. The longer-term consequences of irreversible fibrosis, cirrhosis, and risk for malignancy are now becoming apparent. Further work to establish risk factors and determinants of fibrotic disease and the mechanisms underlying this are essential.
PSC is strongly associated with inflammatory bowel disease (IBD), in particular ulcerative colitis (UC) and to a lesser extent Crohn's disease. As many as 5% of patients with IBD are co-diagnosed with PSC  and approximately 70% of people with PSC have IBD.  Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood.  Close monitoring of PSC patients is vital.