This issue of Best Practice & Research Clinical Rheumatology is about a variety of systemic diseases or subgroups of systemic diseases that are relatively rare, clinically important, and can create diagnostic and therapeutic challenges. Although these diseases can be the subject of many disciplines, especially when the diagnosis is uncertain or the treatment decision is finalized without evidence-based studies, rheumatology is usually in the foreground of the management team. The rheumatologist, with an internal medicine background, is generally well educated in systemic diseases and, more importantly, experienced in the use of corticosteroids and new agents that block inflammatory/immunologic mechanisms, which may be useful in treating heterogeneous diseases.

In these rare systemic diseases, experts who have treated a large volume of patients collect their own data, given that evidence-based large-scale collaborative studies are rare. While selecting the titles and authors of this issue, we have tried to select the subjects that should be included in the differential diagnosis of rheumatologic conditions, and we also wanted to focus on the use of new therapeutic agents including biologicals. The articles in this issue cover basic problems that will be helpful for the physicians who initially treat patients with adult-onset Still’s disease, catastrophic antiphospholipid syndrome, multicentric reticulohistiocytosis, IgG-4-related disease, Behçet’s disease, familial Mediterranean fever, inflammatory eye disease, Cogan’s syndrome, relapsing polychondritis, amyloidosis, and sarcoidosis; moreover, the issue includes recent developments in the concepts, diagnosis, and treatment of those diseases that are important for a rheumatologist.

We thank all authors of this issue for their tremendous effort and time to reflect their valuable experience, amalgamated with available references.