Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis complicated with macrophage activation syndrome

Abstract

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) has low survival rate, whereas macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases. Their coexistence is very rare. This study aimed to describe the prevalence, clinical characteristics, and outcomes of anti-MDA5 antibodies-positive DM patients complicated with MAS. Methods: In this retrospective study, we enrolled DM patients with anti-MDA5 antibodies, who were hospitalized between 2016 and 2020 and included patients diagnosed with MAS. Results: We identified four (2%) DM patients with anti-MDA5 antibodies. They were females with interstitial lung disease (ILD). The level of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and ferritin were significantly higher in the MAS group than those without MAS ( p < 0.05). Patients with MAS were significantly more likely to develop a dysphagia ( p = 0.012). Literature review revealed eight similar cases. Together with the present study, we identified 12 patients complicated with ILD. The median age of disease onset was 52 years with a male to female ratio of 1:6. The median duration between DM onset and MAS diagnosis was 3 months. The mortality of MAS in anti-MDA5 antibody-positive DM was 50%. Patients who died were older than those who survived (56.7 years versus 35.5 years; p = 0.015). Conclusions: MAS was rare in anti-MDA5 antibody-positive DM. The higher the level of AST, LDH, and ferritin, the greater the risk of MAS. They were associated with high mortality rates, particularly in older patients.

Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study

“…It is of note that two dermatomyositis patients in the TCZ group also had a poor treatment outcome. Previous studies suggested that dermatomyositis-related MAS is associated with high mortality rate but no standard treatment strategy has been established yet [ 26 , 27 ]. Although a few studies reported cases of anti-MDA-5 amyopathic dermatomyositis complicated by MAS that were successfully treated with TCZ, these patents were concomitantly treated with glucocorticoid and other immunosuppressants, such as cyclosporine and rituximab [ 28 ].…”

“…Lang et al reported that patients treated with TCZ showed higher rates of infectious complication [ 31 ]. Furthermore, a recent study on patients with COVID-19 related cytokine release syndrome demonstrated that late-onset infections (> 48 h following admission) were more common among those who received TCZ [ 26 ]. Although the cause of this phenomenon is undeciphered, discrepancies in the levels of acute phase reactants such as C-Reactive Protein following the administration of TCZ, which might mask the typical signs of infection and therefore delay diagnosis have been previously reported [ 32 , 33 ].…”

Rare complications of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis: Time to nip them in the bud

“…Conversely, sometimes MDA5 + DM might onset firstly and MAS developed successively ( 48 – 53 ). Among these cases of MDA5 + DM patients, most cases reported obviously high level of serum ferritin, among which some even reached more than 10,000 ng/ml ( 46 – 54 ). Elevation of transaminase and/or persistent fever also could be common features among some cases ( 46 – 48 , 51 – 54 ).…”

“…Among these cases of MDA5 + DM patients, most cases reported obviously high level of serum ferritin, among which some even reached more than 10,000 ng/ml ( 46 – 54 ). Elevation of transaminase and/or persistent fever also could be common features among some cases ( 46 – 48 , 51 – 54 ). MDA5 + DM patients with HLH/MAS might be combined with pre-existing infections ( 48 ), but most cases of MDA5 + DM-related MAS were reported no evidence of pre-existing infections on admission.…”

“…MAS not only can be the first manifestation of MDA5 + DM, but also appears along with the progression of MDA5 + DM. Some published case reports revealed the relationship between MAS and MDA5 + DM ( 46 – 54 ). Thereinto, MAS sometimes acted as the initial presentation before the confirmation of MDA5 + DM in juvenile and adult populations ( 46 , 47 , 49 ).…”