G. Zampogna

Timing of transition between capillaroscopic patterns in systemic sclerosis.

OBJECTIVE To investigate the timing of transition through different patterns of nailfold microvascular damage in patients with systemic sclerosis (SSc). METHODS In this medium-term longitudinal study, 38 SSc patients (median disease duration 12 months) with the early scleroderma pattern of microangiopathy seen on baseline nailfold videocapillaroscopy (NVC) were followed up by NVC for a median of 84 months. The evolution of the NVC pattern over time was monitored and recorded. RESULTS At the end of followup, the NVC pattern was still that of early scleroderma in 47% of the patients. The active scleroderma pattern was seen in 34%, the late scleroderma pattern in 13%, and a normal pattern in 5%. The mean± SD time of progression from the early to the active pattern and from the early to the late pattern was of 28 ± 20 months and 36± 29 months, respectively. In the subgroup of patients whose microangiopathy progressed from the early to the late NVC pattern, the time of progression from the early to the active pattern was only 8± 1 months (P = 0.01), demonstrating that there is a subset of patients with rapid progression of microangiopathy. Clinical symptoms progressed in accordance with the nailfold morphologic changes in 60% of the SSc patients. CONCLUSION The results of this longitudinal study demonstrate dynamic transition of microvascular damage through different NVC patterns of microangiopathy in ∼50% of SSc patients. It is recommended that patients exhibiting rapid progression from the early to the active NVC pattern (<1 year) should be monitored closely, since the evidence suggests that they are at risk of rapid progression to the advanced (late) NVC pattern of microangiopathy that is associated with further clinical manifestations of SSc.

Longterm effects of endothelin receptor antagonism on microvascular damage evaluated by nailfold capillaroscopic analysis in systemic sclerosis.

Objective. Systemic sclerosis (SSc) is characterized by microvascular injury, fibrosis, and hypoxia of involved tissues. The vasoactive peptide endothelin-1 (ET-1) seems to be implicated in these events. Using nailfold videocapillaroscopy (NVC), we evaluated longterm effects of ET-1 antagonist treatment on nailfold microvascular damage in patients with SSc, over a 3-year followup period. Methods. Thirty patients with SSc (mean age 64 ± 5 yrs, mean disease duration 8 ± 1 yrs) were recruited during their programmed standard treatment protocols. At baseline (T0), 15 patients with SSc (mean age 63 ± 15 yrs, mean disease duration 7 ± 3 yrs), already receiving cyclic intravenous infusion of iloprost (5 continuous days, average 80 μg/day, every 3 mo), continued the treatment for a further 3 years (ILO group). The remaining 15 patients with SSc (mean age 68 ± 13 yrs, mean disease duration 8 ± 4 yrs), although they continued the same cyclic intravenous iloprost treatment as the previous group, also received bosentan 125 mg twice a day for 3 years (ILO+BOS group). Qualitative analysis (scleroderma patterns) and semiquantitative scoring of the microvascular damage were performed by validated routine NVC methods. Results. During followup, a statistically significant increase of capillary number was observed in the ILO+BOS group (p < 0.02), with a significant and progressive increase of angiogenesis (p < 0.01). In contrast, the ILO group showed a statistically significant decrease of capillary number (p < 0.05). After 3 years the number of capillaries was significantly higher in the ILO+BOS group than in the ILO group (p < 0.05). The score for giant capillaries decreased significantly in both groups of patients with SSc (p < 0.05). Conclusion. In this open study, longterm treatment with ET-1 receptor antagonist in combination with iloprost was found to interfere with progression of nailfold microvascular damage in patients with SSc, as assessed by NVC over a 3-year followup period.

Correlations between nailfold microangiopathy severity, finger dermal thickness and fingertip blood perfusion in systemic sclerosis patients

Objective The aim of this study was to identify possible correlations between nailfold microangiopathy severity, finger dermal thickness (DT) and fingertip blood perfusion (FBP) in systemic sclerosis (SSc) patients. Methods Fifty-seven SSc patients and 37 healthy subjects were enrolled. All patients were evaluated by nailfold videocapillaroscopy (NVC) to classify and score the severity of microangiopathy. Both modified Rodnan skin score (mRss) and skin high-frequency ultrasound were used to detect finger DT. Laser Doppler flowmetry (LDF) was employed to detect FBP. Results A positive correlation was found between nailfold microvascular damage severity and both ultrasound-DT (p=0.028) and mRss values (p<0.0001). In particular, both ultrasound-DT and mRss were found progressively higher in patients with ‘Early’, ‘Active’ or ‘Late’ NVC pattern of microangiopathy. A negative correlation was observed between nailfold microvascular damage severity and FBP (p<0.0001), showing the lowest FBP of the patients with more advanced NVC patterns. A negative correlation was observed between FBP, and both ultrasound-DT (p=0.007) and mRss values (p=0.0002). SSc patients showed a higher ultrasound-DT at the level of the fingers, as well as a lower FBP than healthy subjects (p<0.0001). Conclusions This study demonstrates a relationship between nailfold microangiopathy severity, DT and FBP in SSc patients.

Longterm treatment with endothelin receptor antagonist bosentan and iloprost improves fingertip blood perfusion in systemic sclerosis.

Objective. To evaluate the longterm effects of endothelin-1 (ET-1) antagonism on peripheral blood perfusion (PBP) in patients with systemic sclerosis (SSc). Methods. Twenty-six patients with SSc already receiving cyclic intravenous iloprost (ILO) for severe Raynaud phenomenon were enrolled. Thirteen patients continued the treatment for a further 3 years (ILO group) and 13 patients, because of the appearance of digital ulcers, received in addition bosentan (BOS; 125 mg twice/day) for 3 years (ILO + BOS group). Both PBP at fingertips and nailfold microangiopathy were evaluated yearly by laser Doppler flowmetry and nailfold videocapillaroscopy, respectively. Results. A progressive significant increase of PBP was observed in the ILO + BOS group during the 3 followup years (p = 0.0007, p = 0.0002, p = 0.01, respectively). In contrast, an insignificant progressive decrease of PBP was observed in the ILO group. Difference of perfusion between the PBP evaluations at basal temperature and at 36°C (to test capillary dilation capacity), was found progressively decreased during the 3-year followup only in the ILO group (p = 0.05, p = 0.26, p = 0.09, respectively). A progressive increase of nailfold capillary number was observed only in the ILO + BOS group after 2 and 3 years of followup (p = 0.05). Conclusion. Longterm treatment of SSc patients with ET-1 antagonism, in combination with ILO, seems to increase fingertip blood perfusion, as well as both capillary dilation capacity and number.

Dynamic Contrast-enhanced Magnetic Resonance Imaging of Articular and Extraarticular Synovial Structures of the Hands in Patients with Psoriatic Arthritis

Objective. Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriatic arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA). Methods. Seven patients with PsA and 10 with RA were studied. After DCE-MRI was performed on 3 axial slices of the wrist, the enhancement ratio was calculated on 6 different regions of interest (ROI) of the synovial membrane outlined by the operator: the wrist compartment, 3 extensor tendon compartments, and 2 flexor compartments. DCE-MRI results were quantitatively analyzed using the Dynamika software, a computer-aided semiautomated method. Results. In PsA, the area of the ROI outlined around the first and second extensor compartments was larger than in RA; the opposite was true for the extensor carpi ulnaris region. The volume of inflammation was significantly higher in RA than in PsA for all the extensor compartments except the second, and in the joint synovial membrane. The DCE-MRI indicators of the degree of inflammation were higher for PsA in the joint synovial membrane (p = 0.002 and p < 0.001, respectively). There was a significant correlation between volume of inflammation but not its degree and 28-joint Disease Activity Score at the level of the wrist joint (r = 0.6; p = 0.01). Conclusion. DCE-MRI can reveal useful and potentially clinically important information on the characteristics of different types of arthritis.

MRI synovitis and bone lesions are common in acute gouty arthritis of the wrist even during the first attack

Gouty arthritis (GA), a recurrent arthritis induced by precipitation of monosodium urate (MSU) crystals, has a 1.4% prevalence.1 2 The hands are affected in 24.7% of patients3 often with long-standing and diuretic-induced disease. Imaging can help in the differential diagnosis of GA and in understanding its pathogenic mechanisms. MRI has been mainly used to evaluate tophi4; information on synovitis, bone marrow oedema (BME) and erosions is scanty. Eight patients affected by acute GA involving the wrist were considered. Gout was diagnosed using the American College of Rheumatology (ACR) criteria5 and confirmed by the identification of MSU crystals in tophi or synovial fluid. Immunoglobulin M rheumatoid factor (RF), anticyclic citrullinated protein (anti-CCP) antibodies, psoriasis or family history of psoriasis were absent. Gout patients were compared with eight patients with active (mean Disease Activity Score 28-CRP 5.78±0.95), RF and anti CCP antibodies positive, RA diagnosed according to the ACR criteria.6 All patients signed an informed consent. The study was approved by the local ethical committee. MRI was performed during the …

Progression of nailfold microvascular damage and antinuclear antibody pattern in systemic sclerosis.

Objective. This study evaluates possible correlations between the pattern of antinuclear antibodies (ANA) on indirect immunofluorescence (IIF) testing and nailfold microangiopathy stage (early, active, and late stage) in systemic sclerosis (SSc). Patients with SSc were followed prospectively to monitor progression of microvascular damage. Methods. The ANA pattern on IIF was searched in 42 patients with SSc showing an early pattern of nailfold microangiopathy at baseline, and was followed using nailfold videocapillaroscopy (NVC) for a median time of 91 months. Results. Among patients whose microangiopathy showed a rapid progression from early to late pattern on NVC, the IIF pattern was fine-speckled + nucleolar (Scl-70+) in 44%, centromeric in 33%, nucleolar in 11%, and homogeneous in 11% of patients with SSc. Antitopoisomerase I antibodies were significantly more frequent (57%) in patients with late pattern of microangiopathy on NVC. The median time of progression from early to active disease was significantly lower in patients with both fine-speckled + nucleolar and nucleolar ANA positivity. The severity of microangiopathy was higher in patients with the nucleolar pattern on IIF. Patients already showing a slight reduction of capillary number at baseline were likely to have either the nucleolar or the fine-speckled + nucleolar pattern on IIF. Of note, 37% of patients still showing the early microangiopathy pattern on NVC at the end of the followup were ANA-negative. Conclusion. ANA-negative patients with SSc display a slower progression of nailfold microangiopathy characterized by the early pattern on NVC. Progression to the late NVC pattern (more advanced stage of microvascular damage) seems to be associated with a different autoantibody pattern on IIF (fine-speckled + nucleolar pattern being the most prevalent).

Magnetic Resonance Imaging of the Hand in Psoriatic Arthritis

Although magnetic resonance imaging (MRI) studies of psoriatic arthritis (PsA) are fewer than those of rheumatoid arthritis (RA), interest in this field is growing. The type and site of the lesions, rather than the mere severity of synovitis, can help differentiate PsA from other arthritides. Extracapsular enhancement and enthesitis are features emphasized as typical of PsA, but their relevance for the diagnosis is more quantitative than qualitative. Erosions in PsA are probably less frequent and progressive than in RA. Bone edema is unlikely to predict the appearance of erosions in patients with PsA. The Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system has been adapted to peripheral PsA, but standardization is still in progress. Dactylitis is a relatively specific feature of PsA. Its pathogenic mechanisms have been investigated with MRI. MRI evaluation of PsA may facilitate diagnosis, evaluation of treatment effects, and understanding of associated mechanisms.

Polymyalgia rheumatica is associated with extensor tendon tenosynovitis but not with synovitis of the hands: a magnetic resonance imaging study

OBJECTIVES To study with MRI the hands of consecutive PMR patients, who were not selected on the basis of peripheral arthritis, with a correlation to clinical and laboratory findings. METHODS Twenty-six hands of 15 PMR patients and 26 hands of 13 healthy controls were studied by extremity-dedicated MRI for the presence of synovitis, tenosynovitis, soft-tissue oedema, bone marrow oedema and erosions. RESULTS Sixteen (61.6%) of the 26 PMR hands and 4 (15.4%) of the 26 control hands showed tenosynovitis (P = 0.001). Extensor tendon tenosynovitis was seen in 9 (34.6%) of the 26 PMR hands, but in only 1 (3.8%) control hand (P = 0.002) and flexor tenosynovitis was seen in 12 (46.1%) of the 26 PMR hands and in 4 (15.4%) of the 26 control hands (P = 0.03). All other features were similar in the two groups. CONCLUSIONS Our data support the view that tenosynovitis, especially of the extensor tendons, is a frequent event in PMR, unrelated to clinical involvement of the hand. This finding is in agreement with the concept of PMR as a disease of extra-articular structures.

Prospective capillaroscopy-based study on transition from primary to secondary Raynaud’s phenomenon: preliminary results

The objective of this prospective study was to investigate the transition from primary (PRP) to secondary (SRP) Raynauds phenomenon (RP), in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC). Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late). NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years). Sixty-eight patients (16%) achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases), Early scleroderma-pattern 57%, Active scleroderma-pattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns) and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01). This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.