Progressive, refractory macrophage activation syndrome as the initial presentation of anti-MDA5 antibody positive juvenile dermatomyositis: a case report and literature review

Abstract

Background Macrophage activation syndrome (MAS) is a severe and under-recognized complication of rheumatologic diseases. We describe a patient who presented with rapidly progressive, refractory MAS found to have anti-MDA5 antibody Juvenile Dermatomyositis (JDM) as her underlying rheumatologic diagnosis. Case presentation We describe a 14-year-old female who at the time of admission had a history of daily fevers for 6 weeks and an unintentional sixteen-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, rash, nausea, and loss of appetite. An extensive initial workup revealed findings consistent with an autoimmune process. While awaiting results of her workup she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation, significant interstitial lung disease, and likely underlying rheumatologic condition she was started on high dose pulse steroids and mycophenolate. An MRI was performed due to her transaminitis and shoulder pain revealing significant myositis. Intravenous immunoglobulin was then initiated. The myositis antibody panel sent early in her workup was significant for anti-MDA5 and anti-SSA-52 antibodies. Despite high dose pulse steroids, mycophenolate, and IVIG, her disease progressed requiring escalating therapies. Ultimately, she responded with resolution of her MAS as well as significant and steady improvement in her feeding intolerance, interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings. Conclusions JDM in the pediatric patient is rare, as is MAS. In patients with complex rheumatologic conditions and lack of response to treatment, it is important to continually assess the patient’s clinical status with MAS in mind, as this may change the treatment approach. Without proper recognition of this complication, patients can have a significant delay in diagnosis leading to life-threatening consequences.

The clinical features and prognoses of anti-MDA5 and anti-aminoacyl-tRNA synthetase antibody double-positive dermatomyositis patients

“…Notably, one patient in our cohort died of respiratory failure with extremely high levels of ferritin (> 15,000.0 ng/mL). Systemic macrophage activation, which is correlated with hyperferritinemia, is potentially related to the pathogenesis of anti-MDA5 antibody-associated RPILD ( 26 , 27 ). Whether macrophage activation is also involved in the pathophysiology of anti-MDA5+/ARS+ DM and directly modulates ferritin levels remains to be tested.…”

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 ).…”

“…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 ). Conversely, sometimes MDA5 + DM might onset firstly and MAS developed successively ( 48 – 53 ).…”