Abstract
Case history
A previously fit 46-year-old male presented with 2 weeks of exertional breathlessness, dry cough and flu-like symptoms following a recent trip abroad. He was initially treated for pneumonia with antibiotics and steroids. Preliminary bloods and X-ray were normal.
Following worsening breathlessness, pleuritic pains, palpitations and low-grade fever he was referred into hospital. Repeat investigations again were normal apart from an erythrocyte sedimentation rate (ESR) of 24. A high-resolution computed tomography (HRCT) scan showed no embolism. He was treated with intravenous Tazocin® and discharged with outpatient follow-up.
Three weeks later he presented again with a now persistent breathlessness, dry cough, weight loss, oral ulcers and arthralgia. An erythematous skin rash was noted on examination. There was no muscle weakness. On admission, a battery of tests including, lung function tests, sputum cultures, echocardiogram, immunoglobulins, autoimmune profile and creatinine kinase, all returned normal. However, the ESR had increased to 51.
Repeat HRCT showed subtle ground glass opacities but no fibrosis. Following rheumatology review he was started on a maintenance dose of prednisolone and discharged with urgent outpatient follow-up.
He was then referred privately to see an immunologist, by which time he had developed dryness to his eyes and burning sensations in the fingertips. An ‘unusual multi-systemic autoimmune condition associated with a dermatomyositis’ was suspected. Rare t-RNA antibodies and extended myositis screen was requested.
While awaiting results, acute deterioration resulted in readmission to hospital with tachycardia and saturations of 84%. The latest HRCT showed a progression with now ‘features highly suspicious of an organizing pneumonia’. There was no evidence of lung fibrosis. Magnetic resonance imagining and muscle biopsies showed no myositis. Skin biopsy revealed findings consistent with an immune mediated reaction.
Subsequently his melanoma differentiation-associated gene 5 (MDA5) antibody came back strongly positive and a provisional diagnosis of MDA5 antibody positive dermatomyositis with interstitial lung disease was made.
Following further deterioration, despite commencement of high dose intravenous steroids, he was urgently transferred to a specialist tertiary unit where he was enrolled onto a clinical trial. It was decided that he should remain for full treatment escalation owing to his young age and premorbid fitness.
Discussion
Dermatomyositis (DM) as in autoimmune, multi-systemic, inflammatory condition that classically present with skin changes and muscle weakness. Diagnosis centres around symptom recognition, presence of inflammatory markers, electromyography and muscle biopsy. However, the prognosis of different subtypes of DM depends greatly on the presence of specific autoantibodies.
In 2005, a Japanese study described for the first time an antibody to the Melanoma differentiation-associated gene 5 (MDA5) in Asian patients who tended to develop a concurrent, rapidly progressive, interstitial lung disease. Patients with anti-MDA5 antibodies showed skin manifestations of DM but without muscle involvement.
Numerous studies have since confirmed MDA5 positive DM with interstitial lung disease as a rare subtype that is associated with a very poor prognosis and high mortality. Presentation is with symptoms of DM and progressive breathlessness. Examination reveals the typical Gottron’s papules associated with DM. Bloods show normal inflammatory markers but often a raised ESR. Muscle biopsy is usually negative. HRCT often exhibits a cryptogenic organizing pneumonia. Ultimately an extended myositis screen reveals positive anti-MDA5 antibodies.
Treatment is an evolving area, with various clinical trials and studies in progress. The mainstay of management is early and aggressive treatment with combined intravenous immunosuppressive therapies, such as cyclophosphamide and rituximab. However, anti-MDA5 is often resistant to treatment and this coupled with the often-delayed diagnosis and rapid deterioration of lung function results in its poor prognosis. Therefore, it is crucial to consider this differential and thereby arrange a myositis-specific autoantibody screen in any patient presenting with breathlessness and symptoms of DM. Owing to its complexity and severity, a multidisciplinary approach is vital, with early collaboration between rheumatology, respiratory, dermatology as well as intensive care specialists.
On reflection, this patient presented with the classical symptoms anti-MDA5 positive DM. A literature review shows an average time frame of 2–3 years before a definitive diagnosis is confirmed. Comparatively, this patent’s diagnosis (although may have appeared delayed) was relatively quick and reached within a few months of presentation.
He remained on the Recital trial for 18 months, which compared the efficacy of cyclophosphamide versus rituximab in the treatment of connective tissue disease associated interstitial lung disease. Despite developing complications, including sepsis, embolisms and haematomas, he is now 3 years post-diagnosis and has achieved 78% of lung capacity back. He is currently on prophylactic antibiotics, a maintenance dose of prednisolone and has regular annual reviews. Most importantly he remains asymptomatic and has returned to work.
ORCID iD
Dr Mahmudul T Haque https://orcid.org/0000-0003-3170-0168