key: cord-1043424-i6s6ehew
authors: Blake, Tim; Noureldin, Basil
title: Anti-PL-7 antisynthetase syndrome presenting as COVID-19
date: 2021-03-01
journal: Rheumatology (Oxford)
DOI: 10.1093/rheumatology/keab129
sha: bee2de929702885cd559c5b8f1d6134fa1aa3a26
doc_id: 1043424
cord_uid: i6s6ehew

nan

11.00), neutrophils 18.11 Â 10 9 (2.00-7.00), lymphocytes 1.41 Â 10 9 (1.00-3.00), monocytes 0.77 Â 10 9 (0.20-1.00), platelets 391 Â 10 9 (140-400), CRP 143 mg/l (<11), ESR 44 mm/h, ferritin 592 lg/l (15-350), troponin T 115 ng/l, procalcitonin 0.14 ug/l (< 0.06) and brain natriuretic peptide (NT-pro BNP) 109 pmol/l (<42). Immunology was negative for ANA, ANCA, anti-dsDNA antibodies, PR3, MPO, cardiolipin IgG, IgM and beta-2glycoprotein-1 antibodies, and original C3 was 1.24 g/l (0.75-1.75) and C4 0.20 g/l (0.14-0.54). Creatine kinase (CK), checked 1 week into the hospital episode (5 days after starting steroids), was 491 U/l (30-175). SARS-Cov-2 RNA Â 4 was not detected by RT-PCR, three sets of blood cultures showed no growth, HIV, HBV and HBC serology were negative, and Legionella urinary antigen was not detected. Urinalysis by dipstick and microscopy was unremarkable. Chest radiogram showed bilateral, mainly left lower lobe, areas of opacification, as well as minor right and mild left pleural effusions, the findings of which were thought to represent infection. The patient was treated with ward-based oxygen, i.v. antibiotics and diuretics, later followed by prednisolone 30mg daily; however, he failed to improve and developed worsening digital vasculitis with necrotic fingertips and respiratory compromise ( Fig. 1A and B ). High-resolution CT depicted bilateral subpleural consolidation and developing fibrosis within the areas of consolidation, which raised the possibility of organizing pneumonia (Fig. 1C ). On day 8, the patient underwent a trans-oesophageal echocardiogram, which confirmed normal biventricular size and systolic function, no significant valve dysfunction and no echocardiographic features of endocarditis. Twelve days into admission, myositis-specific antibody screening confirmed the presence of anti-PL-7 antibodies. Consequently, the patient received urgent treatment with i.v. methylprednisolone and CYC 10 mg/kg (2-weekly for first three, then 3-weekly for six), in conjunction with mesna, co-trimoxazole and nystatin. He was also given aspirin 75 mg daily, HCQ 200 mg daily, prednisolone reducing regime and sildenafil 25 mg three times daily. After 3 months, the patient had made a rapid recovery, with no further symptoms, and repeat high-resolution CT showed near-complete resolution of earlier changes.

Myalgia, fatigue and weakness are frequently encountered with viral pathogens, not least with the coronavirus family. The Lancet published a report of 41 patients hospitalized with pneumonia: 33% of them showed CK elevation and that number increased up to 46% in intensive care unit patients [1] . Antisynthetase syndrome (ASS) is a rare autoimmune disease characterized by interstitial lung disease (ILD) and/or inflammatory myositis, with positive antisynthetase antibodies (anti-Jo-1, anti-PL-7, anti-PL-12, anti-ZO, anti-OJ, anti-KE or anti-KS). 

Other symptoms described include arthritis, fever, RP and mechanic's hands [2] . A large retrospective study revealed a high prevalence of ILD (100%) and relatively low prevalence of other symptoms, including myositis (50%), findings of which corroborated previous anti-PL-7 series [3].

In conclusion, it is imperative when considering flulike or multisystem presentations in the current climate, to be aware of one's cognitive biases and maintain a sense of skepticism, so that important diagnoses do not go amiss. Emerging reports highlight missed or delayed treatment for infections such as Pneumocystis jiroveci pneumonia that imitate COVID-19; however, there is little reference in the literature to autoimmune mimics of . ASS is a rare clinical entity that is, even at the best of times, difficult to recognize; diagnosis requires a thorough multidisciplinary approach, synthesizing rheumatology and pulmonary assessments, along with serology, radiology, and occasionally muscle and/ or lung biopsy results. It shows high heterogeneity between patients with respect to clinical phenotype and disease severity. Moreover, there is often a variable temporal relationship between the onset of ILD and that of myositis or other ASS-specific features. Early diagnosis followed by immunosuppressive therapy can significantly increase both the quality of life and life expectancy of patients, largely by reversibility of ILD [2] . Patients with anti-PL-7 or anti-PL-12 often have severe ILD, frequently without myositis. A meta-analysis of 27 studies on ASS, found that arthralgia and ILD predominate in ASS, as compared with the other idiopathic inflammatory myopathies, and patients with Jo-1 have more myositis and a better prognosis compared with patients with PL-7 or PL-12 [7] .

Our case highlights the importance of a thorough multisystem assessment of patients presenting with COVID-19-like features and raised creatine kinase, and greater awareness of the clinical features of ASS in acute settings, in order that earlier recognition and appropriate treatment may improve outcomes. One should consider, according to local availability, formal nailfold videocapillaroscopy and a Myositis Panel for the detection of myositis antibodies in the diagnostic work-up.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

The diagnosis and treatment of antisynthetase syndrome

1 (A) Nailfold infarcts and splinter haemorrhages

B) progressive necrotic and vasculitic digital changes

HRCT appearances of bibasal and subpleural consolidation and fibrosis Letter to the Editor diagnostic dilemma in HIV

Pneumocystis jiroveci pneumonia and SARS-Cov-2 coinfection in newly diagnosed HIV-1 infection

The clinical phenotype associated with myositis-specific and associated autoantibodies: a meta-analysis revisiting the so-called antisynthetase syndrome

T.B. collected the data and wrote the initial draft. All authors provided clinical and radiological data for the patient, reviewed the article, participated in editing and approved the final version of the manuscript.

Funding: No specific funding was received from any funding bodies in the public, commercial or not-forprofit sectors to carry out the work described in this manuscript.Disclosure statement: The authors have declared no conflicts of interest.