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A special six-part section on vasculitis, available for free in full text online for six months, focuses on pathogenesis, treatment strategies, and the need to reconsider mechanisms in defining the subtypes.
Hoffman GS and Calabrese LH. Vasculitis: Determinants of Disease Patterns.Nature Reviews Rheumatology (2014) !0:454-462. doi:10.1038/nrrheum.2014.89
Jennette JC and Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nature Reviews Rheumatology (2014) 10:463-473. doi:10.1038/nrrheum.2014.103
Khoury P, Grayson PC and Klion AD. Eosinophils in vasculitis: characteristics and roles in pathogenesis. Nature Reviews Rheumatology (2014) 10:474-483. doi: 10.1038/nrrheum.2014.98
Kallenberg CG. Key advances in the clinical approach to ANCA-associated vasculitis. Nature Reviews Rheumatology (2014) 10:484-493. doi: 10.1038/nrrheum.2014.104
Csernok E and Moosig F. Current and emerging techniques for ANCA detection in vasculitis. Nature Reviews Rheumatology (2014) 10:494-501. doi: 10.1038/nrrheum.2014.78
Tarzi RM, Mason JC and Pusey CD. Issues in trial design for ANCA-associated and large-vessel vasculitis. Nature Reviews Rheumatology (2014) 10:502-510. doi:10.1038/nrrheum.2014.67
Fire up the laptop, check the ink level on the printer, and prepare to get comfortable sometime. The August edition of Nature Reviews Rheumatology contains a special six-part section on vasculitis, available in full text online for free for the next six months, thanks to funding from Genentech.
Articles are illustrated with vivid color diagrams depicting molecular interactions and cellular pathways.
The details in brief:
• First, the names are all wrong, Hoffman and Calabrese point out. Even after defrocking Wegener and downplaying Churg and Strauss, rheumatologists who continue to define vasculitis by vessel size (large, medium, small) ignore the fact that vessels serve distinctly different organs in unique environments, and arise from different embryonic origins. Their highly illustrated review describes the different varieties of infectious vasculitis, as well as what little is known about the drivers of autoimmunity in the idiopathic vasculidites.
• Of course there are distinct subtypes, as Jennette and Falk point out, defined by the presence or absence of asthma, granulomatosis, or eosinophilia, as well as (when possible) by the autoantigen targets MPO and PR3. They describe the varieties of immunological mayhem in vivid detail: the occult onset of epitope spreading, the fragmenting leukocytes, the "amorphous necrotic debris" and the cellular campaign to wall it off, the terminal mass of scar tissue that may or may not be repaired eventually. Fascinating reading, indeed.
• Confusion follows in the Khoury, Grayson, and Klion account about the eosinophils that add an E to GPA (granulomatosis with polyangiitis), because these tissue-toxic cells may feature in other vasculitides as well. There's no good animal model for EGPA. What liittle is known about it, absent any randomized controlled trials (EGPA is too rare), comes from clinical observation. The review describes the nature of these immune cells and their actions, as well as our meager current knowledge about how to respond therapeutically.
• In contrast, Kallenberg portrays a steady advance toward order in the decades of effort to classify the vasculidites. With a caveat: The few diagnostic criteria (as opposed to classifications) that exist are not universally agreed. The article includes a consortium's therapeutic algorithm for patients with ANCA-associated vasculitis (AAV), and descriptions of variations in response rates for patients with different antigen profiles. After recounting this progress, Kallenberg concludes with a list of difficult uanswered questions.
• Here's another catch: The patient may be ANCA-positive, but may not have AAV. So what is the meaning of a positive test for diagnosis and monitoring, and which of the many tests available to detect these antibodies is best? Csernok and Moosig warn against overestimating the value of a positive test, offering an informative description of the options and a logical procedure for applying tests and following up on them.
• Despite their rarity, the vasculitis syndromes now benefit from several large multicenter trials thanks to global collaboration. Tarzi et al describe the benefits: the knowledge (from RAVE and RITUXVAS) that rituximab offers a good alternative to cyclophosphamide, as well as information about long-term outcomes gained by pooling of results from a number of trials. The authors provide an encouraging list of large collaborative trials now underway. But their concluding review of questions that should be addressed in future trials indicates what a great deal we have yet to learn about these diverse syndromes that share a one-word name.