Background and aims. To investigate baseline predictors of response to mucocutaneous and musculoskeletal manifestations in belimumab-treated patients affected with SLE.
Methods. We analyzed baseline features from a multicentric cohort of SLE patients with active disease (SLEDAI-2K>0), treated with belimumab (BeRLISS). Mucocutaneous response was defined as Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)=0 and musculoskeletal response as Disease Activity Score (DAS28) <2.6 or <3.2. Response was evaluated at 6, 12, 24 months and predictors were assessed with logistic regression analysis.
Results. Among patients with available CLASI records at baseline (n=318), 195 (61.3%) achieved CLASI=0 throughout a mean follow-up of 26.9 ±14.8 months. Baseline negative predictors of CLASI=0 were mucocutaneous damage (CLASId, OR: 0.63 95%CI 044-090, p 0.011), disease duration before belimumab treatment (OR 0.89, 95%CI 0.83-0.97, p 0.005) and anti-SSB antibodies (OR 0.15, 95% CI 0.04-0.61, p 0.008). Consistently, anti-SSB antibodies negatively predicted mucocutaneous response at all timepoints (p<0.01 for all) while CLASId >1 was an independent negative predictor at 6 and 12 months (p<0.001 for both). Among 328 patients with DAS28 records at baseline, increased baseline SLE-Damage Index was negatively associated with DAS28<2.6 or <3.2 at 12 months (p<0.01 for both). Among patients with both mucocutaneous and musculoskeletal involvement at baseline (n=231), positive anti-SSB and disease duration negatively predicted response in both domains (OR 0.93 95%CI: 0.26 0.08-0.95, p=0.025; and 0.88-0.99, p 0.024, respectively).
Positive anti-SSB, a longer disease duration and mucocutaneous damage may negatively impact musculoskeletal and mucocutaneous response to belimumab in SLE patients.
To observe if nailfold capillary patterns in childhood-onset SLE (cSLE) change over time and if a scleroderma pattern is associated with higher disease activity, -damage or scleroderma-like features.
Prospective data from cSLE-patients (onset < 18 years) were analyzed. Disease activity was defined by SLEDAI score and disease damage by SDI index. A scleroderma pattern was defined according to the ‘Fast track algorithm’ from the EULAR Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as ‘microangiopathy’.
We studied 53 cSLE patients with median disease onset of 14 years (IQR 12.5-15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8-16). N=9 (17%) showed a scleroderma pattern (ever) and n=37 (70%) showed microangiopathy. N=30 patients had follow-up capillaroscopy of which 24/30 (80%) showed no changes in capillary pattern over time. Median SLEDAI score at diagnosis did not differ between capillary pattern groups. A scleroderma pattern in cSLE was significantly associated with the presence of anti-RNP antibodies and with occurrence of disease damage. Patients with a scleroderma pattern did not develop clinical features for systemic sclerosis during follow-up (range 1-10 years after diagnosis), but showed significantly increased risk for SLE-related disease damage (Hazard ratio 9.4, p=0.003).
This prospective study shows that the majority of abnormal capillary patterns in cSLE do not change over time, irrespective of treatment and SLE disease activity. Capillary scleroderma pattern in cSLE might reflect a more severe disease course and seems a prognostic red flag for disease damage.
Cutaneous lupus erythematosus (CLE) is an autoimmune disease characterized by inflammation of the skin. Healthy skin is maintained by proliferation and differentiation of basal progenitor cells, and supra-basal transient amplifying (TA) cells. Senescence is a state of cell cycle arrest, inducible by various triggers including inflammation, and characterized by p16 and p21 expression. This study evaluates senescence marker expression by cells in the epidermal basal and supra-basal layers in CLE patients, compared with other inflammatory dermatoses and unaffected skins.
Senescence markers p16 and p21 expression in the epidermal basal and supra-basal layers in lesions from age-matched CLE patients (n=20), 7 other conditions with dermoepidermal junction (DEJ) infiltration (n=22), 9 dermatoses without EDJ infiltration (n=27), and unaffected skins (n=3) was examined by immunohistochemistry.
Significantly more p16+ and p21+ cells in basal and supra-basal layers were detected by immunohistochemistry in age-matched CLE skin lesions and other dermatoses with DEJ infiltration, compared to those without and to unaffected skin biopsies (p<0.05). p16+ cell number correlated with p21+ cells in the basal (R=0.45, p<0.0001) and supra-basal (R=0.47, p<0.0001) layers. p16+ cells were more frequently found in the basal layer, and p21+ cells conversely in the supra-basal layer (p<0.0001). p16+ and p21+ cells in CLE lesions did not differ from other dermatoses with DEJ infiltration (p>0.05).
DEJ infiltration may play a role in development of skin progenitor/TA cell senescence. Progenitor and TA cells in skin lesions of patients with CLE may be regeneratively dysfunctional, as a consequence of senescence.