A 54-year-old male was referred to the Rheumatology Division of Fornaroli Hospital from the Infective Department. In February 2014, he was admitted to hospital because of interstitial lung disease of uncertain origin accompanied by fever with shiver, dry cough, and chest pain. Chest X-ray showed a right subclavicle interstitial consolidation. A lung/abdominal CT (Computerized Tomography) with contrast enhancement showed an interstitial consolidation with centrilobular branching linear structures with bronchial dilatation and multifocal areas of ground-glass attenuation at the right superior and medium lobe of lung in the posterior segment. There were pleura's thickening at the lingula and fibrotic lines with consolidation at the left superior lobe of lung in the anterior segment, also. Moreover, there were some mediastinic bilateral lymphadenopathies (Figure 1). Laboratory tests showed ESR 28 mm/h (cut-off value <=10 mm/h) and C-reactive protein 6.66 mg/dL (range of normality: 0-5). Antinuclear antibodies (ANA), cryoglobulin, extractable nuclear antibodies (ENAs), anti-DNA native antibodies, antiphospholipid antibodies, and antineutrophil cytoplasmic antibody (ANCA) were negative. Complementemia (C3, C4) was at range of normality. Rheumatoid factor (RF) was 24 UI/mL (range of normality <12) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were 17 UA/mL (range of normality <5). Serum angiotensin-converting enzyme (ACE) levels were normal. Quantiferon-TB Gold was negative. Microbial agents were excluded (serology for Legionella, Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydia was negative). A restrictive defect on functional lung exams was excluded and diffusion capacity of the lung for carbon monoxide (DLCO) was normal. Smoking history was absent. A lung bronchoscopy with a bronchoalveolar lavage (BAL) was made. Bacterial BAL fluid cultures were negative. Culture and genome for Koch's bacillus were negative. BAL cytology excluded monoclonality disorders and showed increased numbers of neutrophils and eosinophils. Lung CT showed multifocal areas of ground-glass and we hypothesized a rheumatologic versus infective interstitial lung disease. So, lung biopsy was not performed in this patient because we think that it was excessive forasmuch as BAL was performed (including cultures and cytology) which supported inflammatory diagnosis. A positron emission tomography-computed tomography (18F-FDG PET/CT) showed an elevated glucometabolic activity at bilaterally axillary lymphadenopathies and at level of pulmonary consolidation seen at HR-CT; these abnormalities were hypothesized to inflammatory nature and possible rheumatic disease (such as vasculitis). Heart ultrasound, nailfold videocapillaroscopy, and superior abdomen ultrasound did not show abnormalities. After some weeks, painful swelling of right knee appeared. Doppler ultrasound (US) of low limbs excluded deep venous thrombosis. He received a large spectrum antibiotic therapy (before, at home he had assumed oral levofloxacin therapy and later oral amoxicillin clavulanate; during the recovery he received oral doxicilin and azithromycin at standard dosage) with reduction of fever but persistence of lung abnormities to radiologic exams. So, It was started a steroid therapy ex adiuvantibus with a clinical subjective improvement. In the suspect of rheumatologic disease patient was assigned to our division. During rheumatologic recovery painful swelling of right wrist, knee, and ankle appeared. We made an ultrasound (US) echographic of the lung (Figure 2). Commercially available echographic equipment with a 7.5 MHz linear probe was used (Mylab25, Esaote, Genoa, Italy). US of right lung, at the fifth posterior intercostal space, showed the presence of Ultrasound Lung Comets (ULCs) (as echographic sign of interstitial lung involvement). On the basis of clinical features and laboratory/functional/radiologic tests we made a diagnosis of NSIP in RA seropositive for RF. We started immunosuppressive therapy with intravenous cyclophosphamide 1 gr every 28 days for a cumulative dose of 6 gr (from 3 April to 10 September 2014) associated with steroid tapering therapy. We observed any adverse events during treatment with cyclophosphamide. At the end of intravenous infusion of cyclophosphamide, a lung high-resolution CT was performed. It showed a significant improvement of interstitial lung disease with disappearance of multifocal areas of ground-glass attenuation and consolidations (Figure 3). Also ultrasound evaluation at the end of therapy showed complete resolution of ULCs (Figure 4). So we decided to stop other infusions of cyclophosphamide and to start treatment with methotrexate 10 mg/weekly for arthralgia of right wrist as well as maintenance therapy associated with low dose of steroids (prednisone 5 mg/day tapering).