La paziente era una bambina giapponese di 5 anni, senza storia familiare rilevante nota, che presentava un progressivo disturbo della deambulazione, un rallentamento dello sviluppo motorio, il fenomeno di Raynaud e un aspetto lucido della pelle del viso e degli arti inferiori all'età di 2 anni. La pelle presentava anomalie che diventavano più evidenti e fu eseguita una biopsia della pelle dal dorso del piede sinistro in un istituto precedente quando aveva 5 anni. La biopsia rivelò un ispessimento fibroso del derma, un intrappolamento relativo di una ghiandola sudoripara eccrina e un ispessimento collageno della pelle del viso e degli arti inferiori oltre il gomito e il ginocchio (18/51 del punteggio mRSS totale della pelle modificato) []. Grave emorragia capillare visibile sulla piega ungueale e gravi anomalie capillariologiche, tra cui sanguinamento, loop gigante e scomparsa delle ghiandole sudoripare, dita gonfie con fenomeno di Raynaud e ispessimento della pelle degli arti inferiori oltre il gomito e il ginocchio (18/51 del punteggio mRSS totale della pelle modificato) [] Grossly visible capillary hemorrhage on nail fold and severe capillaroscopy findings including bleeding, giant loop and disappearance of capillary consistent with the late phase in SSc. Contractures in the ankle and proximal interphalangeal joints resulted in gait disturbance and finger motion difficulty, respectively. Non-abnormal neurological findings or evidence suggesting myositis from information such as clinical muscle weakness, muscle-derived enzyme, and muscle Magnetic Resonance Imaging at baseline intensive examination were not detected. Chest high-resolution computed tomography (HRCT) demonstrated patchy areas of ill-defined air-space opacity and consolidation predominantly involving the posterior basilar aspects of the lower lobes presenting with interstitial lung disease, although she had no symptoms suggesting respiratory abnormality, and no obvious finding could be detected by plain chest radiography. Serum KL-6 level was 197 U/mL and was within the normal range. Non-abnormal findings were detected by electrocardiography or echocardiography. She manifested neither heartburn nor dysphagia, and findings of gastroesophageal reflux disease were not identified by esophagogastroduodenoscopy. Esophageal dilatation and/or dysmotility was not indicated by the upper gastrointestinal series. Blood examination showed positive ANA (nucleolar and homogeneous nuclear staining at a serum dilution of 1:160 by indirect immunofluorescence). The commercially available SSc-related autoantibodies, including anti-topoisomerase I (Scl-70), anticentromere, and anti-U1RNP, were not detected. We then conducted an RNA immunoprecipitation assay and immunoprecipitation-immunoblot assay as previously described [, ]. Il paziente’s serum immunoprecipitated ribosomal RNAs and a 7 − 2 RNA that was consistent with the RNA component precipitated by a reference anti-Th/To-positive serum. In addition, the immunoprecipitation-immunoblot assay probed with anti-hPOP1 and anti-PM-Scl-100 antibodies revealed that the patient’s serum contained both anti-Th/To and anti-PM-Scl antibodies. The patient was diagnosed with diffuse cutaneous SSc, based on the Pediatric Rheumatology European Society/American College of Rheumatology/European League Against Rheumatism Provisional Classification Criteria for Juvenile Systemic Sclerosis []. She was treated with 2 courses of methylprednisolone pulse therapy (30 mg/kg/day for 3 days each course) followed by 10 mg/day of oral prednisolone (PSL). Subsequently, 6 courses of monthly intravenous cyclophosphamide (IVCY, 500 mg/m2 each course) therapy were administered. In the second course of IVCY, her skin thickening improved and the mRSS was 4/51. Just before the third course of IVCY, the interstitial lesions at the basal lung field were not identifiable on follow-up HRCT, and joint contracture also improved. After completing 6 courses of IVCY without major adverse events, she was maintained with 25 mg/day of azathioprine and PSL. Her PSL dose was reduced from 10 mg/day to 3 mg/day during 7 months of the time course.