14. Digital ischemia and interstitial lung disease in antisynthetase syndrome with PL-12 antibody

Abstract

Introduction:Antisynthetasesyndrome(ASS)isarareidiopathicinflammatory myopathy with nearly 89% showing interstitial lung disease (ILD). The hallmark of ASS is the presence of serum autoantibodies directed against aminoacyl-tRNA synthetases that include Jo-1 (most commonly detected), PL-7, PL-12, OJ, EJ, KS,Wa, YRS and Zo. However, in a small subpopulationwithout evidence ofmyositis, the diagnosismay be critically delayed,hinderingmanagementofthisrapidlyprogressivedisease. Wereport an interesting case of anti-PL-12/anti-SSA52kDASSpresenting as acute digital ischemia, an association rarely described previously. In cases with ILD, the severity of lung condition generally determines the prognosis. Case description:A77-year-old Caucasian female presented with sudden onset of painful, blue discolouration in her bilateral fingertips twoweeks after mild lower respiratory tract infection and occasional pyrexia. She was a non-smoker, otherwise independent lady who had background history of ischemic heart disease, diverticulosis and hypertension. Her physical examination revealed dusky blue digits and dry ulceration. She had extensive investigations that showed raised CRP (61mg/L),eGFR39ml/min/1.73m2 ,weakpositive rheumatoid factorand cold agglutinins, equivocal Lupus anticoagulant, negative ANCA, clear urinalysis, bilateral chronic inflammatory change on chest xray and thrombiofdigital arteriesonDopplerultrasoundofhands. She was initially treated for infection due to ongoing temperatures and had multiple scans with no definite source. An inflammatory aetiology was then thought likely due to lack of response to antibiotics and steroid therapy was commenced with settling of fevers and inflammatory markers. Autoimmune screens initially were negative but became more prominent over timewith a positive Ro antibody and ultimately a positive AntiPL12antibody,keepingwithanti-synthetasesyndrome. Shesubsequentlydevelopedflorid interstitial lung disease, further ischemia and ultimately necrosis of her fingertips. Due to the onset of lung disease she was treated with IV steroids, Cyclophosphamide and Prostaglandins with some initial benefit. She received 3 cycles of cyclophosphamide and managed to come off supplemental oxygen. However, she had issues with recurrent chest infections due to immunosuppressive therapy which resulted in delays in her cyclophosphamide pulses and need for antibiotics. She later developed clostridium-difficile gastroenteritis and subsequent ileus of her bowel which was managed conservatively and found it difficult to overcome. As time went on, the progress that she had made with her hands started to deteriorate again. There were also further issues with intestinal obstruction, and sadly ultimatelypassedawaywithaspirationpneumonia. Discussion:ASSisrecognizedasarareautoimmuneinflammatorymyopathy of unknown etiology, 2-3 times more prevalent in women than in men. The clinical manifestations include myositis, polyarthritis, ILD, mechanic's hands, and Raynaud phenomenon. The hallmark of ASS is the presence of serum autoantibodies directed against aminoacyl-tRNA synthetases that include Jo-1, PL-7,PL-12, OJ, EJ, KS,Wa,YRSand Zo. Anti-jo1 is themostcommonly detectedantibody. These autoantibodies may arise after viral infections, or patients may have a genetic predisposition. Our casewas interesting as the autoimmune profilewaspositive for Anti-Ro/SSA and anti-PL-12. Anti-Ro/SSA and anti-La/SSB are traditionally associated with Sjö gren's disease and Sjö gren's-related ILD, however, anti-Ro/SSA has been independently associated with ASS and more severe and fibrotic ILD. It has been described that patients with anti-PL-12-ASS are most often clinically diagnosed with amyopathic dermatomyositis or ILD alone and there is higher prevalence and increased severity of ILD than PM/DM. Moreover, the prevalence of muscle symptoms (weakness and myalgia) is significantly lower in patients with anti-PL7/PL12 as compared to those with anti-Jo1 and less associated with malignancy as compared to DM. Interestingly, anti-PL-12 is also associatedwithhigherratesofRaynaudphenomenon. Our case also reports that not all patients with antisynthetase antibodies or even those classified asASShave all manifestations of this syndrome. Diagnostic criteria refers topresenceof antisynthetaseantibodyplustwo major criteria or onemajor criterion andtwominor criteria (Solomonet all. 2011) or one or more of clinical features (Connors et all.2010). When the lungs are affected, the severity and extent of lung damage generally determines theprognosisbecauserespiratory failure isthe leadingcause of death. Clinical presentation guides towards therapeutic management that mostly includes corticosteroids, immunosuppressive medications, and/orphysicaltherapy Key learning points: Digital ischemia could be a rare presentation of ASS. Clinical features of antisynthetase syndrome (ASS) include interstitial lung disease, 'mechanic' hands, myositis, polyarthritis and Raynaud's phenomenon. Extensive myositis specific antibody testing is strongly recommended even if screening autoimmune serologies are unrevealing. Anti-PL-12 ASS has significantly lower prevalence of muscle symptoms (weakness and myalgia) and more association with Raynaud'sphenomenonascomparedtothosewithanti-Jo1. It isimperative to recognize lesser-known manifestations of ASS in the absence of clinical myositis as delay in diagnosis and treatment worsens the prognosis. Conflicts of interest: The authors have declared no conflicts of interest.