Complications of adult-onset Still’s disease and their management

Abstract

Adult-onset Still's disease (AOSD) is a rare systemic auto-inflammatory disorder in which management and treatment have considerably progressed over the past decade. Despite wide use of interleukin (IL)-1 or IL-6 inhibitors, serious complications remain possible. Areas covered: A comprehensive literature search in MEDLINE via Pubmed was performed to review AOSD's severe and sometimes life-threatening complications: reactive hemophagocytic lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiac or pulmonary complications and amyloid A amyloidosis. Expert commentary: Early recognition and prompt management is essential to significantly decrease morbi-mortality. The key question is to determine whether the complication is related to the disease itself or related to or favored by (e.g. infection) the ongoing treatment. For all severe AOSD-related complications, high-dose corticosteroids and supportive measures remain the first-line treatment. In case of inadequate response, combination with IL-1 or IL-6 blockers is justified. Cyclosporine A and etoposide remain of interest, especially in case of reactive hemophagocytic lymphohysitocytosis. Plasma exchange may be useful in case of thrombotic microangiopathy. In the near future, new biologic or non-biologic drugs targeting IL-18 or other cytokines or kinases could be of help.

Adult-Onset Still’s Disease

“…In systemic-onset JIA, it is also called macrophage activation syndrome. This serious complication should be suspected in a patient with persisting fever (in contrast to evening spiking fever) and decrease in initially elevated leukocyte and neutrophil counts [3,32,59]. Several other manifestations can be associated.…”

“…Several severe manifestations have been described in AoSD, which explains the potentially pejorative prognosis of the disease [3,59]. The disease can be lifethreatening because of the predominant involvement of one organ or of systemic complications with multiple organ failure from the outset, while the diagnosis isn't clearly confirmed.…”

“…The first disorder, disseminated intravascular coagulation (DIC), is not rare and may occur at a frequency of 1-5% [8,53,[59][60][61][62][63][64][65][66][67]. This diagnosis should be suspected with the combination of thrombotic events and cutaneous or mucosal bleeding and sometimes specific organ involvements, such as fulminant hepatitis, cardiac or respiratory failure, or stroke.…”

“…Organ imaging may reveal multiple infarctions. In addition, ADAMTS13 enzymatic activity needs to be tested because acquired deficiency has been found to predispose to TMA [59,[96][97][98]. TMA has been mainly described during AoSD flare, related to intense inflammation or to concomitant infection with Shiga toxin-producing microorganisms [74].…”

“…PAH may occur at AoSD onset or later and seems to predominate in women. The diagnosis must be suspected with unexplained and often rapidly progressing dyspnea [59,79,81,100,101]. Electrocardiography is rarely contributive, eventually disclosing signs of right atrium hypertrophy.…”