History of present illness
A 61-year-old Caucasian man presented to the outpatient pulmonology clinic due to dyspnea that had progressively worsened over the past 2 years.
He previously consulted his general practitioner, who suggested performing a chest radiograph and then a high-resolution computed tomography (HRCT) scan of the chest. This revealed an interstitial lung disease (ILD) characterized by diffuse honeycombing with subpleural and basal predominance, associated with traction bronchiectasis and areas of ground-glass opacities superimposed on reticulations ( Fig. 13.1 ). The radiological findings were classified as a usual interstitial pneumonia (UIP) pattern.
For this reason, he was invited to undergo a consultation with a pulmonologist, who hypothesized a diagnosis of idiopathic pulmonary fibrosis (IPF) and sent the patient to the regional referral center for rare lung diseases in order to set the appropriate treatment.
Past medical history
The patient was a tradesman, with no reported significant exposure to noxious agents. He was a mild former smoker (calculated 12 pack-years) who quit about 10 years before the visit. He took daily medication for slight systemic hypertension (ramipril 2.5 mg once a day). Recently, another pulmonologist introduced oral prednisone 37.5 mg/day and oxygen supplement at 2 L/min due to the evidence of respiratory failure already at rest.
Physical examination and early clinical findings
At the first assessment in the regional referral center for rare lung diseases, the patient showed severe dyspnea for minimal exertion. He was apyretic and had slightly increased blood pressure (140/85 mmHg). The heart rate was 111 beats/min, whereas the respiratory rate was 21 breaths/minute. Chronic type 1 respiratory failure was confirmed: oxygen saturation (SpO 2 ) at rest was 87% in room air, with pO 2 54.4 mmHg and pCO 2 36.8 mmHg at the arterial blood gas analysis. He reached SpO 2 of 92% with 2 L/min oxygen supplement. On chest examination, there were bilateral Velcro-like crackles in the mid-low lung fields. The patient complained of gastroesophageal reflux but no other symptoms compatible with connective tissue diseases (CTDs).
The patient was evaluated by a rheumatologist who used to work alongside the pulmonologists as part of the unit’s multidisciplinary team. During the physical examination, the rheumatologist found a microstomia (i.e., limited mouth opening due to tightening and hardening of the skin around the mouth) and thickening of the skin on the hands proximal to the metacarpophalangeal joints, as well as proximal to the elbows and knees, without any sign of acral ulcers or pitting scars ( Fig. 13.2 ). The rheumatologist suspected an SSc in a diffuse subset; he subjected the patient to a nailfold videocapillaroscopy (NVC) directly at the first assessment. NVC was positive for a “late” scleroderma pattern, characterized by a low number of giant capillaries and extensive avascular areas ( Fig. 13.3 ). Considering that the patient did not refer symptoms compatible with Raynaud phenomenon (RP), he underwent a provoking test, clearly showing a complete RP. Therefore, the patient was invited to gradually reduce corticosteroids and to have blood tests including autoimmunity. A week later, the diagnosis of SSc was further confirmed by the presence of antinuclear antibodies (ANA) 1:640 with nucleolar staining and anti-Scl70 positivity at a high titer.
Clinical course
At the confirmation of the diagnosis, the patient underwent PFTs, which showed a restrictive pattern with forced vital capacity (FVC) of 55% predicted and total lung capacity (TLC) of 59% predicted. Diffusion lung capacity for carbon monoxide (DLCO) was also reduced to 42% of predicted. For the treatment of SSc with lung involvement, the patient was put on oral prednisone 7.5 mg daily and mycophenolate mofetil (MMF) 2 g daily. Acetylsalicylic acid 100 mg/day, nifedipine 60 mg/day, and esomeprazole 20 mg/day were also introduced. The patient showed persistent 3-year disease stabilization in terms of symptoms, lung function, and imaging. He tolerated the treatment well, without significant side effects, and the sole new clinical change was the onset of anxiety requiring therapy.
After this period of time, the patient complained of worsening dyspnea without a fever and needed a higher oxygen supplement at rest. Significant functional deterioration was found on PFTs with FVC 44% predicted (11% decline) and DLCO 28% predicted. The patient performed a new chest HRCT scan that showed a reduction of ground-glass opacity with no other signs of acute infection and a more evident UIP pattern ( Fig. 13.4 ). Although the quantitative involvement of the lung was substantially similar to what was observed in the first HRCT, its quality showed a clear fibrotic evolution.
Recommended therapy and further indications
The new clinical picture was interpreted as a progression of the disease. Therefore, the patient was treated with a high dosage of methylprednisolone (100 mg/day for 3 days), and he started antifibrotic therapy with oral nintedanib 150 mg twice daily, in add-on with MMF that was increased to 3 g/day. The patient acquired new stabilization in 2 months.
Follow-up and outcomes
After 6 years of follow-up, the patient was in poor, but stable, condition. Interestingly, throughout this period, the patient’s RP was responsive to nifedipine without requiring second-line treatment. Despite the diffuse subset of SSc, the patient did not develop any other visceral involvement. Sporadically, he had some traction ulcers on the anterior surface of proximal interphalangeal joints but with relatively rapid healing and very small pitting scars. He had no acral ulcers, calcifications, or pulmonary artery hypertension.
SSc is an autoimmune disorder characterized by parallel fibrotic and vascular damage in the skin and internal organs. It is about 4 times more common in women than in men.
Antinuclear antibodies (ANA) may be present in > 90% of cases of SSc, and at least one of the more specific autoantibodies (anti-centromere, anti-SCL70, and anti-RNA polymerase III) is present in up to 70% of the cases. Based on the skin involvement, SSc can be classified as diffuse, limited, or sine scleroderma.
The diffuse subset is characterized by a rapid onset and severe fibrotic damage in multiple organs (most frequently, skin, gastrointestinal tract, lungs, kidneys, skeletal muscle, and pericardium).
The limited subset was formerly known as the CREST syndrome (due to its main features: calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia). This shows a slower progression but with prevalent vascular damage, acral ulcers, and pulmonary artery hypertension.
In sine scleroderma SSc, the patient has SSc-related antibodies and visceral manifestations without skin tightening.
Table 13.1 shows the most used criteria for the diagnosis of SSc.
