Since 1975, various attempts at reclassification of inflammatory myopathies have incorporated inclusion body myositis & immune-mediated necrotizing myopathy.
Ferritin as a Prognostic Indicator
Other studies have also sought to better characterize differences even within the subset of anti-MDA5 myositis patients. A retrospective study from Japan by Gono et al. evaluated 27 patients with dermatomyositis who were positive for anti-MDA5 antibody. They stratified these patients into those with (n=20) and without (n=7) rapidly progressive interstitial lung disease (ILD) and compared them. A statistically significant difference in ferritin levels between the two groups was noted, with higher ferritin in those with rapidly progressive ILD (mean of 835 ng/mL) compared to those without ILD (186 ng/mL). Because no significant difference in C-reactive protein was seen between these groups, the researchers hypothesized the hyperferritinemia is not simply a reflection of acute phase reactant response, but pathologic.
The researchers also compared those patients with MDA5 antibody and rapidly progressive ILD who lived (n=11) with those who died (n=9). They found those who died had higher ferritin (1,600 ng/mL) levels than those who lived (409 ng/mL), a difference that reached statistical significance (P=0.017).7 This helped establish ferritin as a prognostic indicator in patients with clinically amyopathic DM with MDA5 positivity.
Studies have demonstrated that serum IL-18 levels are higher in patients with dermatomyositis and are associated with developing ILD and more severe disease activity.1 Interestingly, high levels of ferritin and IL-18 are implicated in macrophage activation syndrome (MAS), and MDA5 encodes an RNA-specific helicase that functions to recognize single-stranded RNA (ssRNA) viruses, leading some to hypothesize anti-MDA5 myositis as a form of MAS targeting skin and lungs related to an infectious trigger.11
Ovoid Palatal Patch
In 2016, Dr. Fiorentino also described a novel palatal lesion in dermatomyositis that he termed the ovoid palatal patch. He says his team would look for perioral manifestations described in the literature, including gum telangiectasias and gum erythema, but rarely saw them in the clinic.
“In a few patients, I noticed a distinctive look of semicircular, symmetric erythema always positioned in the same place in the palate,” he says.
To determine the significance of this cutaneous lesion, Dr. Fiorentino and his team evaluated 45 patients who met criteria for dermatomyositis seen in the outpatient clinic over a five-month period from 2014 to 2015. The study found 40% of the patients had an ovoid palatal patch. He and his team wanted to see whether the presence of the patch was associated with any specific clinical or laboratory findings. Comparing the clinical findings of patients with this palatal lesion to those without, they found the patch had a statistically significant association with the presence of transcription intermediary factor 1-γ (TIF1-γ) antibodies, as well as clinically amyopathic disease and cancer-associated dermatomyositis.8
This study helped further improve the characterization of the TIF1-γ antibody phenotype, including an association with malignancy and the ovoid palatal patch. Dr. Christopher-Stine calls the TIF1-γ association being described practice changing: “I look more closely at the palates of patients than I ever did before.”
