1. MDA-5 Dermatomyositis: An Atypical Variant
Leanna Wise, M.D., Elizabeth Ortiz M.D.
Keck School of Medicine, University of Southern California-Los Angeles County Medical Center
CT chest on first presentation, 8/30/17
CT chest 9/30/17
Background
Radiologic and Pathologic Findings
Anti-melanoma differentiation antibody 5 dermatomyositis (MDA-5 DM) is a rare but clinically significant form of inflammatory myopathy. Studies thus far have associated MDA-5 DM with clinically amyopathic DM (CADM; primarily in Japanese populations), tender digital ulcerations and papules, and most notably, rapidly progressive interstitial lung disease (RP-ILD). Recently this phenotype has been better characterized, bringing to light the importance of correct and early diagnosis, as aggressive and early treatment is likely needed to impact both morbidity and mortality.
CT chest 11/2017 (compared to 10/2017):
Multiple bilateral pneumatoceles
Increased consolidative opacities
Increased right upper lobe consolidation with air bronchograms
Persistent diffuse ground glass opacifications
Complete collapse of the right lower lobe and near complete collapse of the left lower lobe, worsened from prior
Skin biopsy:
Perivascular lymphocytic dermatitis with subtle focal interface change that may be seen in drug reaction or dermatomyositis
Case Report
Discussion
62yo Caucasian female with no past medical history presented to our institution for higher level of care. History notable for approximately 3 months of:
She initially received 1mg/kg of oral prednisone with slight improvement, but her dyspnea worsened. She then received sequentially pulse steroids, IVIG, cyclophosphamide (CYC; 4 weekly doses of 750mg), plasma-pheresis, and tacrolimus. Unfortunately, her respiratory status continued to decom-pensate and she eventually succumbed to her disease.
Faint rash on chest and face
Dyspnea
Neuropathy
Arthralgias
Dysphagia
Raynaud’s
Lack of weakness
MDA-5 dermatomyositis has previously been shown to be correlated with RP-ILD and CADM in Asian populations, and has also been correlated with cutaneous findings such as palmar papules, digital ulcers, and gingival pain and ulcers. Multiple US cohorts also show an significant association between MDA-5 positivity and both ILD and RP-ILD, although there appears to be less of a correlation with CADM in the US population. Regardless, MDA-5 positivity is a poor prognostic factor, as a meta analysis has shown the odds ratio of developing RP-ILD in these patients to be greater than 20x high than in MDA-5 negative DM patients. As MDA-5 positivity is a fairly rare entity, with an incidence ranging from 13 – 35% of all dermatomyositis patients, most treatment options are based on retrospective reviews. Prior attempts at treating MDA-5 patients with RP-ILD have included pulse steroids, CYC, calcineurin inhibitors, rituximab and tofacitinib, while patients with “only” ILD have been treated with mycophenolate mofetil as well. Interestingly, serum ferritin has been shown to correlate with disease activity and response to treatment. From review of the literature, it appears that in order for these immunomodulators to prevent a worsening of disease or even reverse the underlying pathology, a rapid diagnosis is needed in order to start therapy as soon as possible.
CT chest on arrival to our institution, 10/30/17
CT chest 11/16/17, after intensive therapy
Conclusion
Laboratory Findings
Recognition of the salient features of MDA-5 positive patients, such as subtle skin findings and prominent pulmonary involvement, with or without significant myopathy component, will lead to more timely aggressive management as these patients have a poor prognosis from a pulmonary perspective. Complicating the situation is a paucity of data on treatment and the scarcity of these patients; currently treating with high-dose steroids, CYC, and a calcineurin inhibitor may have the best effect on patient outcomes.
Leukopenia, anemia, high ESR and CRP; ALT 84; AST 36
MDA-5 myomarker positive; all other myomarkers and antibodies negative
CK and aldose normal; ferritin 1,709; LDH 751
Infectious workup: bronchoalveolar lavage and blood cultures negative including TB negative and crypto/cocci negative
Anti-melanoma differentiation–associated gene 5 (MDA5) dermatomyositis: A concise review with an emphasis on distinctive clinical features. Kurtzman, Drew J.B. et al. Journal of the American Academy of Dermatology , Volume 78 , Issue 4 ,