1. A relapsing case of Mi-2 antibody associated dermatomyositis with severe proximal weakness and bulbar involvement

INTRODUCTION: We present a relapsing case of dermatomyositis in a 73-year-old female with a severe disease phenotype involving cutaneous manifestations, severe symmetrical muscle weakness and bulbar involvement. Her case highlights factors associated with poorer prognosis. It further points to the first year post remission as being the highest risk for relapse, during the tapering of immunosuppression. She responded well to treatment with rituximab. Her case also highlights a potential viral trigger in the form of human parechovirus (HPeV), which has been highlighted previously in Japanese literature and is worthy of further consideration. CASE DESCRIPTION: A 73-year-old female with no significant past medical history was transferred from the Cayman Islands with a three-week history of profound muscle weakness, rash and dysphagia. There was a preceding pyrexial illness. Examination demonstrated symmetrical proximal muscle weakness with bulbar involvement, a classical heliotrope rash and gottron’s papules. Bloods revealed a creatinine kinase over 20,000 IU/L, elevated inflammatory indices and Mi-2 antibody positivity. An infective screen was normal. A CT chest abdomen and pelvis reported patchy consolidative changes but no malignancy. A MRI demonstrated myositis with muscle oedema affecting all muscle compartments in the pelvis and thighs. A muscle biopsy performed was consistent with an idiopathic inflammatory myositis (IIM). She received three pulses of methylprednisolone 500mg whilst in Grand Cayman and commenced prednisolone 60mg and antibiotics for chest sepsis on admission. She required PEG feeding, physiotherapy and speech and language therapy but made slow progress. Treatment with rituximab was initiated. Ten days later she developed heart failure and chest sepsis requiring intubation and ventilation. Her ICU stay was complicated by gastrointestinal bleeding, pulmonary embolism and the isolation of human parechovirus (HPeV). She gradually improved and was discharged to a medical ward, prior to transfer to the rehabilitation unit. She was commenced on methotrexate in order to facilitate steroid tapering. She was discharged home after 10 months, independently mobile with a rollator. Fifteen months after her initial diagnosis she relapsed in an identical fashion with dysphagia, muscle weakness, heliotrope rash and elevated creatinine kinase at 3500 IU/L post infection. She received two further rituximab infusions and intravenous methylprednisolone. Her oral prednisolone was increased to 60mg before tapering and methotrexate was substituted initially for azathioprine and latterly mycophenolate mofetil. PEG feeding was reintroduced. Her admission was complicated by an aspiration pneumonia but she was subsequently fit for further rehabilitation. DISCUSSION: She satisfied the Bohan and Peter classification criteria for dermatomyositis with symmetrical proximal muscle weakness, elevated creatinine kinase, consistent muscle biopsy findings and classical skin manifestations. Investigation results were consistent. She had a severe disease phenotype with striking bulbar involvement and moderate to severe weakness of upper and lower limbs. She was relatively unresponsive to high dose corticosteroids and physiotherapy. Given the severity of her initial chest sepsis, induction treatment with methotrexate, mycophenolate or azathioprine was felt suboptimal. Intravenous cyclophosphamide was considered but discounted due to the patient’s age and the increased infection risk given her potential for aspiration. We proceeded with rituximab, whilst acknowledging that infection would still be a major concern moving forward. Rituximab was considered efficacious in the treatment of dermatomyositis based on data from the RIM trial, albeit statistical significant results were not generated. HPeV was considered a possible disease trigger. It is transmitted via respiratory droplets or the faecal-oral route and this could have explained the preceding pyrexial illness. HPeV has been demonstrated as an aetiological agent for epidemic myalgia and cases of myositis in Japan, where seroprevalence is higher. Management of HPeV is supportive and as such our management remained unchanged. She suffered a relapse within a year of remission, which is a high-risk period as per the literature. Her immunosuppressive treatment entailed prednisolone 5mg daily and methotrexate 15mg weekly at that stage. The tapering of immunosuppressive therapy is a difficult time to navigate. She had poor prognostic factors given her age and dysphagia at onset. Conversely, Mi-2 antibody positivity tends to be good prognostically and not usually associated with underlying malignancy. Mi-2 antibody positivity is a predictive biomarker of treatment response to rituximab. Given these prognostic factors, severe phenotype and her Mi-2 status, ongoing treatment with rituximab for maintenance should be considered. KEY LEARNING POINTS: This patient had more severe bulbar involvement than most patients we have treated previously. This led to repeated episodes of aspiration pneumonia and suboptimal nutrition, which undoubtedly contributed to her stormy initial course with severe sepsis. Dietetic involvement is of paramount importance in patients with oropharyngeal involvement. Attempts to balance the ongoing risk of infection by tapering immunosuppression against the risk of relapse can be difficult. Extreme vigilance should be employed, especially within the first year post-remission when relapse rates are highest. Our initial experience of severe life-threatening chest sepsis in her case may have resulted in a lower level of immunosuppression moving forward. In spite of frequent follow-up and acting quickly on the initial signs of relapse (reinstituting high dose steroids and rituximab) her condition progressed rapidly. Given the factors already discussed, we plan to use rituximab every 6 months as a maintenance therapy. There is evidence for its use in treatment refractory cases such as this. This 6-monthly regimen has been extrapolated from its use in other autoimmune disease but there is a lack of evidence informing the clinician when to retreat patients with IIM. We plan to use low dose mycophenolate mofetil in between treatments with rituximab. The relevance of a positive HPeV test was considered and discussed with microbiology during her stay in ICU. It was felt that the positive anti Mi-2 antibody test and typical clinical phenotype pointed towards classical dermatomyositis rather than a viral myositis. It may still have been a trigger for the autoimmune disease in this case. CONFLICT OF INTEREST: The authors declare no conflicts of interest.