Abstract
INTRODUCTION: Amyopathic dermatomyositis (ADM) is a subtype of dermatomyositis (DM) which encompasses the hallmark cutaneous features of DM, such as Gottron papules and heliotrope rash, in the absence of clinical or laboratory findings of muscle involvement. ADM can cause pulmonary complications including interstitial lung disease (ILD), spontaneous pneumothorax or pneumomediastinum. ADM-ILD has poor prognosis, especially the rapidly progressive (RP-ILD) type, posing significant therapeutic challenges as it is resistant to aggressive immunosuppressive treatment. We present a case of RP-ILD in a patient with anti-Ro52 positive ADM and the difficulties encountered in management of the patient. CASE DESCRIPTION: A 55-year-old female presented to the ambulatory clinic with one-week history of pleuritic chest pain, exertional dyspnoea and rash affecting her hands, back and face for months. Examination revealed an annular rash with central scabbing over her metacarpophalangeal and interphalangeal joints (Gottron’s papules) and a violaceous malar rash. A CT thorax was performed which showed mild inflammatory changes bilaterally. Her autoimmune screen was strongly positive for anti-Ro52 antibodies. A connective tissue disease was suspected; she was given an intramuscular depo-medrone injection and rheumatology follow-up booked. Unfortunately, within two weeks she was admitted to the hospital with worsening dyspnoea, hypoxia and rash. A repeat CT thorax showed multi-lobar, multi-segmental consolidation, suggestive of cryptogenic organising pneumonia. A full myositis screen was positive for anti-Ro52 with titres >190 U; importantly, anti-MDA5 antibodies were negative on two occasions. While her skin rash was suggestive of dermatomyositis, in the absence of muscle weakness and normal creatine kinase, she was diagnosed with anti-Ro52 positive amyopathic dermatomyositis. Despite high dose oral prednisolone, she deteriorated from a respiratory standpoint. Worsening lung imaging prompted the diagnosis of rapidly progressive ILD. Cyclophosphamide and methylprednisolone were commenced; she subsequently required intensive care admission for high flow nasal oxygen and CPAP. She received a single cycle of plasma exchange, followed by a 5-day course of intravenous immunoglobulins (IVIG). Tacrolimus was added to achieve further immunosuppression. Her case was complicated by the development of pneumomediastinum and bilateral pneumothoraces requiring chest drains. She was then intubated due to refractory hypoxia. With rising inflammatory markers, broad spectrum antibiotics and anti-fungals were started due to growth of candida in blood cultures. Baricitinib was added on once inflammatory markers improved, in hopes of curtailing progression of ILD. Unfortunately, due to multi-organ failure and poor clinical response, life support was withdrawn and the patient died soon after extubation. DISCUSSION: Several autoantibodies have been associated with systemic autoimmune rheumatic diseases-related ILD (SARD-ILD). Among myositis-specific antibodies, anti-MDA5 is particularly linked with RP-ILD. Our patient experienced a rapid decline in her respiratory function over two months since initial presentation to the hospital. Initially, the severity of her symptoms prompted suspicion of anti-MDA5 RP-ILD. However her myositis screen was strongly positive for anti-Ro52, with negative anti-MDA5 on two occasions. Significant therapeutic challenges were encountered while treating our patient with anti-Ro52 ILD. Early ILD specialist respiratory input was sought, and the patient was commenced on high dose prednisolone; this was quickly escalated to IV cyclophosphamide and methylprednisolone as she deteriorated. Due to inefficient treatment response, IVIG was added due to evidence of mortality benefit as an adjunct therapy. As subsequent CT imaging continued to show worsening ILD, the patient was also given tacrolimus after completing a course of IVIG. A combination of intravenous glucocorticoids, with addition of one or two immunosuppressive agents (calcineurin inhibitors/ rituximab/cyclophosphamide) is recommended for induction therapy in RP-ILD in both British Society for Rheumatology and American College of Rheumatology (ACR) guidelines. ACR also recommends the use of IVIG, mycophenolate or JAK inhibitors as part of a triple therapy induction in SARD RP-ILD. Despite our patient deteriorating on three agents (steroids, tacrolimus, cyclophosphamide), further immunosuppression was withheld due to candidaemia on blood cultures. When she showed an improvement in infection markers, a dose of baricitinib was given. Unfortunately, further treatment was severely limited by development of multi-organ failure. There is an abundance of literature describing poor prognosis in anti-MDA5 related RP-ILD. Amongst these documented cases, co-positivity with anti-Ro52 inferred an increased mortality risk. Our case advocates the need to study anti-Ro52 as an independent risk factor in development of severe RP-ILD. KEY LEARNING POINTS: • Early recognition of classic cutaneous features of dermatomyositis, such as Gottron papules and heliotrope rash, are imperative in investigation and establishing timely diagnosis of amyopathic dermatomyositis. • Evidence suggests that a combined approach with high dose steroids, tacrolimus and cyclophosphamide at onset of RP-ILD has a significant 6-month survival benefit compared to escalation of immunosuppression in a step-up manner (89% vs 33%; p < 0.0001). This poses a question as to whether our patient might have had a better outcome if a more aggressive approach was adopted at the beginning of her symptoms once the diagnosis of AMD RP-ILD was established. However, a combined strategy can predispose to the development of opportunistic infections and reactivation of certain viruses. Ultimately, infection was the one of the biggest limiting factors in escalating immunosuppression for our patient. • While a lot of evidence exists for anti-MDA5 RP-ILD, its association with severity of RP-ILD and various treatment options that can be employed, further research needs to be undertaken to investigate association of anti-Ro52 with worse ILD outcomes and potentially recognise it as an independent predictive risk factor for RP-ILD. • In patients with rapidly worsening ILD, a myositis screen should be considered especially if the patient has concurrent cutaneous and/or muscular involvement, as this could be secondary to underlying idiopathic inflammatory myopathy. • Pneumomediastinum and spontaneous pneumothoraces are serious complications of ADM-ILD; it is hypothesised that these occur due to subpleural infarctions and bleb rupture secondary to ongoing vasculitis and are associated with poorer outcomes. • A multi-disciplinary approach is required in management of these patients, with early specialist input from respiratory, immunology and infectious diseases departments.