Liver Failure as a Presenting Finding of MDA-5 Positive Dermatomyositis

Summary: Authors: Danielle Henry MBBS(1), Jose Cano MD(2) , Pala Ozlem MD, MPH (2) (1)Internal Medicine Department, University of Miami at Holy Cross Health, Fort Lauderdale, FL, United States, (2) Rheumatology Department, University of Miami, FL, United States. Introduction: Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) characterized by milder muscle involvement, but rapidly progressive ILD. Liver dysfunction has been noted but there are few descriptions of overt liver failure as a presenting feature. Case Presentation: 64-year-old female with history of biopsy proven Interface dermatitis presented with 5-month history of worsening fatigue, dysphagia requiring pureed foods, progressive weakness to becoming wheelchair-bound, and worsening jaundice. A month from current hospitalization she had an episode of GI bleed which required hospitalization at another facility. EGD showed multiple gastric fundic polyps up to two centimeters without varices. MRI of the abdomen showed hepatomegaly & evidence of fatty infiltration. Liver biopsy showed severe steatosis involving 90% of the parenchyma with ballooning and cholestasis, inflammatory infiltrates were minimal & trichrome stain showed no fibrosis. Workup for negative for the following: HIV, leptospirosis, alpha 1 antitrypsin deficiency and HFE gene negative. She was discharged but her clinical status continued to decline. She was admitted to our institution for acute encephalopathy & acute liver failure of unknown origin. Her examination was significant for icterus and swelling, Gottron's papules seen in 4th MCP in the right hand with bogginess in MCP and PIP with slight tenderness, left hand had similar but milder findings. There was hyperpigmentation of the lateral thighs bilaterally. Muscle strength 4/5 in shoulders and 3/5 in hips. Admitted to the ICU for septic shock due to UTI secondary to E faecium requiring antibiotics, pressors and stress dose of steroids. Results as seen in Table 1. Coombs direct positive for IgG, normal complement. Positive ANA 1:640 homogeneous and 1:160 Speckled. SSA slightly positive 3.3. SS-B, dsDNA, Sm RNP, ANCA, APS panel, SPEP and ASMA, AMA and LK1 negative. She was stabilized and transferred to the floor. MRI of femur showed nonspecific diffuse edema and partial fatty atrophy of the left thigh muscles. CT chest without ILD. Anti MDA-5 positive at 152 and SRP mildly elevated at 11. The constellation of skin findings (Holster sign, Gottron's sign, Heliotrope Rash), muscle findings (proximal weakness, dysphagia, high aldolase and MRI findings) in combination with positive serology for Anti MDA-5 was considered for establishing diagnosis of dermatomyositis. IVIG infusion was initiated at 1g/kg for 2 days. Once she was more stable from an infectious perspective, she was started on IV solumedrol. She eventually required PEG tube insertion due to persistent dysphagia then transitioned to prednisone 60 mg PO daily which she was discharged on. Discussion: MDA-5 antibody is a marker usually associated with rapidly progressive ILD and amyopathic disease. The classic skin findings in dermatomyositis can be seen in about 60-70% of patients with MDA5 DM. Muscle injury usually causes liver enzyme elevation and thus the AST and ALT levels usually correlate with the creatinine kinase. Frequency of liver dysfunction ranges from 30 – 72%. Our patient did not have pulmonary symptoms or involvement based on CT chest. Her hallmark features were liver failure, skin, and muscle involvement. Although liver dysfunction could be multifactorial in DM, it seems that her liver involvement was related to some degree of direct (inflammatory infiltration of tissue) or perhaps an indirect (decreased caloric intake plus increase metabolic rate or cytotoxic effect of muscle enzymes on the liver) result of immune dysregulation given dramatic response to IVIG and steroids. Liver dysfunction characterized by disproportionate elevation of AST in comparison to CK has been suggested to be an extra-muscular feature of MDA-5 antibody positive DM. This patient also had severe steatosis and hepatocyte ballooning which is also commonly seen this patient population. Conclusion: Liver dysfunction in MDA-5 positive dermatomyositis may be severe enough to cause overt liver failure and can be considered as a diagnosis of exclusion in patients with liver failure in the correct clinical setting. References: 1) Nagashima, T., Kamata, Y., Iwamoto, M., Okazaki, H., Fukushima, N., & Minota, S. (2019). Liver dysfunction in anti-melanoma differentiation-associated gene 5 antibody-positive patients with dermatomyositis. Rheumatology International, 39(5), 901–909. https://doi.org/10.1007/s00296-019-04255-2 2) Nombel, A., Fabien, N., & Coutant, F. (2021). Dermatomyositis with anti-MDA5 antibodies: Bioclinical features, pathogenesis and emerging therapies. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.773352 3) Bobirca, A., Alexandru, C., Musetescu, A. E., Bobirca, F., Florescu, A. T., Constantin, M., Tebeica, T., Florescu, A., Isac, S., Bojinca, M., & Ancuta, I. (2022). Anti-MDA5 amyopathic dermatomyositis—a diagnostic and therapeutic challenge. Life, 12(8), 1108. https://doi.org/10.3390/life12081108