Part 5: Allogeneic HSCT in refractory SJIA with lung disease; recent cases from centers in North America & Europe.

It has been increasingly recognized that there is a subset of patients with refractory systemic JIA, who have failed all available medications and may benefit from HSCT. The increasing experience with HSCT in SJIA, suggests that despite the complicated post-HSCT course, short-term, the transplanted patients either achieved SJIA remission or reduced burden of disease. Longer follow-up, however, is needed to better define the long-term outcomes. The discussion at the NextGen 2022 conference was focused on the optimal timing for the procedure, the need for a good control of inflammatory SJIA activity prior to HSCT, and the role of the reduced intensity conditioning regimens as there was a remote concern that such regimens might increase the risk of SJIA relapse after the transplantation. There was unanimous agreement about the importance of long-term registries to address these questions.

The 4th NextGen therapies for SJIA and MAS: part 2 phenotypes of refractory SJIA and the landscape for clinical trials in refractory SJIA.

Although the introduction of the IL-1 and IL-6 inhibiting biologics in 2012 has revolutionized the treatment and markedly improved outcomes for many patients with SJIA, about 20% of these patients continue to have active disease, have markedly decreased quality of life and high disease activity as well as treatment-related morbidity and mortality. There is a clear need to define these disease states, and then use these definitions as the basis for further studies into the prevalence, clinical features, and pathophysiologic mechanisms. While such patients are most likely to benefit from novel therapies, they are very difficult to enroll in the ongoing clinical trials given the unique features of their disease and large numbers of background medications. The discussions at the NextGen 2022 conference focused on strategies to overcome these obstacles and accelerate studies in refractory SJIA.

Lung Involvement in Systemic Juvenile Idiopathic Arthritis: A Narrative Review.

Systemic juvenile idiopathic arthritis associated with lung disorders (sJIA-LD) is a subtype of sJIA characterized by the presence of chronic life-threatening pulmonary disorders, such as pulmonary hypertension, interstitial lung disease, pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia, which were exceptionally rare before 2013. Clinically, these children show a striking dissociation between the relatively mild clinical manifestations (tachypnoea, clubbing and chronic cough) and the severity of the pulmonary inflammatory process. Our review describes sJIA-LD as having a reported prevalence of approximately 6.8%, with a mortality rate of between 37% and 68%. It is often associated with an early onset (<2 years of age), macrophage activation syndrome and high interleukin (IL)-18 circulating levels. Other risk factors may be trisomy 21 and a predisposition to adverse reactions to biological drugs. The most popular hypothesis is that the increase in the number of sJIA-LD cases can be attributed to the increased use of IL-1 and IL-6 blockers. Two possible explanations have been proposed, named the "DRESS hypothesis" and the "cytokine plasticity hypothesis". Lung ultrasounds and the intercellular-adhesion-molecule-5 assay seem to be promising tools for the early diagnosis of sJIA-LD, although high resolution computed tomography remains the gold standard. In this review, we also summarize the treatment options for sJIA-LD, focusing on JAK inhibitors.