In April 2013, a 61-year-old man suffering from early RA [2-10 small joints, increased erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP), positivity of anticyclic citrullinated peptide antibodies (ACPA)/rheumatoid factor (RF), symptoms lasting 1 year] came to our attention for the worsening of morning stiffness, pain and symmetrical swelling of proximal interphalangeal (PIP), metacarpophalangeal (MCP) joints and wrists.
The patient presented several comorbidities: high blood pressure, type 2 diabetes mellitus, dyslipidemia, class I obesity [body mass index (BMI) = 33.2], prostatic enlargement and depressive mood. In addition, he was a smoker [60 pack-years (PY)].
He was receiving treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids (CCS) in the medium/high doses (up to 15 mg/day prednisone). During the first visit at our division, the patient exhibited laboratory investigation that showed ESR 37 mm/h, CRP 10 mg/l, RF 122 IU/ml, ACPAs 233 IU/ml; quantiferon-TB gold test, antinuclear antibody (ANA) and extractable nuclear antigen (ENA) screening as well as complete hepatitis B and C markers were negative; blood count [white blood cells (WBC) 6.5 x 103/microl, granulocytes 55%, lymphocytes 35%], transaminases, creatinine and serum protein electrophoresis were normal. He did not present other clinical signs and symptoms suggestive of connective tissue disorders such as: Raynaud's phenomenon, skin thickening, dysphagia and acid reflux, rashes, sicca syndrome, myalgia and proximal muscle weakness, nor constitutional symptoms of fever and sweats. X-ray of November 2012 documented a mild increase of the plot in the absence of clinical signs; hands and wrists X-ray reported diffuse arthropathic manifestations with initial erosions of ulnar styloid. Ultrasound of hands and wrists bilaterally demonstrated moderate proliferative, erosive and active synovitis [power Doppler (PD) III] of radiocarpal joints, moderate active (PD II) proliferative tenosynovitis of the flexor tendons of the fingers, mild proliferative synovitis of the II MCP joint (Figure 1(a,b)). On examination, he presented four tender and four swollen joints (radiocarpal and II MCP joints bilaterally). Clinimetric data showed moderate activity with disease activity score in 28 Joints (DAS28) of 4.8 and moderate disability with Health Assessment Questionnaire (HAQ) of 1.5. We also performed the Short Form Questionnaire for general well being (SF-36) to gain a deep insight of his mental and physical quality of life. He presented a severe reduction (>2 standard deviations from the mean) in all the SF-36 subscales with a Physical Component Summary (PCS) of 22 and a Mental Component Summary (MCS) of 26.
MTX 15 mg/week was, therefore, introduced and progressive CCS decrease (up to 5 mg/day) started. After 2 months of therapy with MTX, the patient showed significant improvement of RA signs and symptoms. However, he began to complain of persistent dry cough and dyspnea without fever. The objective examination of the chest documented bilateral basal crackles. In suspicion of ILD, the patient was submitted to lung function tests that documented mild restrictive defect with mild reduction of CO single-breath diffusing capacity (DLCO SB 60%) and CO divided by the alveolar volume (DLCO/VA 87%; forced vital capacity 67%). High-resolution computed tomography (HRCT) showed one micronodule (5 mm) with smooth margins in subpleural parenchymal right upper lobe and notes of bilateral interstitial fibrotic striae type 'ground glass' more evident on the left (Figure 2(a)). MTX was interrupted and therapy with Sulphasalazine 2 g/day was introduced. The consultant pneumologist proposed to also perform a bronchoalveolar lavage (BAL) which excluded concomitant infections and showed an increased cellularity with raised granulocytes (10%) and lymphocytes (20%), eosinophils and macrophages were within the normal range; the CD4/CD8 ratio was 1.3. The CCS dose was not increased; however, after 3 months the patient presented marked arthritic worsening with six tender and six swollen joints and a DAS28 of 5.8 (severe activity), accompanied by a deterioration of its depressive mood. Consequently, treatment with tocilizumab at recommended standard dose (8 mg/kg, total 760 mg ev/monthly) was introduced. After 3 months of treatment with tocilizumab, the clinical condition of the patient visibly improved. The clinimetric data showed low disease activity (DAS28 = 3) and a reduced disability (HAQ = 1) confirmed by the marked amelioration in all the SF-36 subscales (PCS from 22 to 33 and MCS from 26 to 43). The patient presented only one tender and swollen joint (left radiocarpic joint). Ultrasonography of hands and wrists documented a mild synovitis (PD grade I) of radiocarpic joints bilaterally (Figure 1(c)). He no longer complained of cough and dyspnea and bilateral basal crackles were no more present. After 6 months of therapy with tocilizumab, the clinical conditions of the patient were still stable (DAS28 = 3); the tests of lung function showed persistence of mild restrictive defect with normal CO diffusion (DLCO/VA 102%).
At 1-year follow up the patient showed a clinical remission (DAS28 = 2), further improvement in disability (HAQ = 0.5) and SF-36 (PCS 35; MCS 45). The objective examination of the chest was normal and the tests of lung function were stable. HRCT was repeated and it documented the reduction in size and density of ground glass area (Figure 2).
Informed consent was obtained from the patient for his information and images to be included in this article, as well as for diagnostic and therapeutic interventions. Our institution does not require ethics approval for reporting individual cases.