Successful treatment of refractory lupus erythematosus profundus with the interleukin-6 antagonist tocilizumab: a case report.

Lupus erythematosus profundus (LEP) is an unusual form of cutaneous lupus erythematosus (CLE) characterized by multiple subcutaneous induration and associated with considerable physical and psychological morbidity. The heterogeneity of CLE makes it difficult to understand its underlying pathogenesis and represents a therapeutic challenge. Recently, new insight into the pathogenesis of CLE has implicated various cytokines, opening doors to targeted biologic agents. We report a case of a 23-year-old female who presented with refractory LEP ulcers as an initial presentation of systemic lupus erythematosus. The lesions were resistant to multiple conventional therapies and remarkably responded to tocilizumab.

Serum cystatin C and ßeta-2 microglobulin as potential biomarkers in children with lupus nephritis.

Objectives: In this study, we aimed to assess serum levels of Cystatin C (Cys C) and beta-2 microglobulin (ß2M) in juvenile systemic lupus erythematosus (JSLE) patients and to investigate their role as potential biomarkers of lupus nephritis (LN) and overall disease activity. Patients and methods: Between December 2018 and November 2019, a total of 40 patients with JSLE (11 males, 29 females; mean age: 12.6±2.5 years; range, 7.5 to 16 years) and 40 age- and sex-matched controls (10 males, 30 females; mean age: 12.3±2.4 years; range, 7 to 16 years) were included in this study. Serum (s) Cys C and ß2M levels were compared between the groups. The SLE Disease Activity Index (SLEDAI-2K), the renal SLEDAI (rSLEDAI), and the Renal Damage Index were used. Results: JSLE patients had significantly elevated mean sCyc C and sß2M levels (1.4±0.8 mg/mL and 2.8±0.9 mg/mL, respectively) compared to the controls (0.6±0.1 mg/mL and 2.0±0.2 mg/mL, respectively; p<0.00). The mean sCys C and sß2M levels were significantly higher in the LN group, compared to non-LN patients (1.8±0.7 mg/mL and 3.1±1.0 mg/mL, respectively vs. 0.8±0.3 mg/mL and 2.4±0.6 mg/mL, respectively; p=0.002 and p=0.02, respectively). The sCys C levels had significant positive correlations with erythrocyte sedimentation rate (r=0.3, p=0.05), serum creatinine (r=0.41, p= 0.007), 24-h urinary protein (r=0.58, p<0.001), anti-double stranded deoxyribonucleic acid antibodies titers (r=0.55, p=0.002), extra-renal SLEDAI scores (r=0.36, p=0.04), rSLEDAI (r=0.46, p=0.002), and renal class (r=0.7, p=0.0001). Serum ß2M levels were significantly negatively correlated with complement 4 levels (r=-0.31, p=0.04) and significantly positively correlated with extra-renal SLEDAI scores (r=0.3, p=0.05). Conclusion: These findings confirm that sCys C and sß2M levels are increased in JSLE patients in association with the overall active disease. However, sCys C level may act as a promising non-invasive biomarker for predicting kidney disease activity and biopsy classes in children with JSLE.

Active tuberculosis infection in moroccan patients with rheumatic diseases under biologic therapy: A multicenter national study.

Background: The aim of this study was to evaluate the prevalence of active tuberculosis (TB) infection in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. Methods: This 14-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated comorbidities, and TB-related data. Results: In total, 1407 eligible patients were studied, detailed records were obtained for only 130 patients; 33 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9 ± 12 years and 75.8% were males. Ankylosing spondylitis accounted for 84.8% of active TB cases, and the majority of the cases (31/33) occurred among antitumor necrosis factor-alpha (TNF-α) users. A total of 8 out of 33 patients were positive at initial latent TB infection (LTBI) screening by tuberculin skin test and/or interferon-gamma release assay. Consumption of unpasteurized dairy products (odds ratio [OR], 34.841; 95% confidence interval [CI], 3.1-389.7; P = 0.04), diabetes (OR, 38.468; 95% CI, 1.6-878.3; P = 0,022), smoking (OR, 3.941; 95% CI, 1-159.9; P = 0.047), and long biologic therapy duration (OR, 1.991; 95% CI, 1.4-16.3; P = 0.001) were identified as risk factors for developing active TB. Conclusion: Moroccan patients with rheumatic diseases under anti-TNF-α agents are at an increased TB risk, especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas.

Hypovitaminosis D in Patients with Ankylosing Spondylitis: Frequency and Consequences.

OBJECTIVES: This study aimed to assess the frequency of hypovitaminosis D in patients with Ankylosing Spondylitis (AS) compared to healthy controls and evaluate its association with disease activity, structural damage and Bone Mineral Density (BMD). METHODS: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS- CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility, respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. RESULTS: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001). Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), and mSASSS (p=0.003). ASDAS - CRP was the only significant predictor of hypovitaminosis D in AS patients. CONCLUSION: Hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with a larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control the active disease.

Health-Related Quality of Life in Patients with Ankylosing Spondylitis: Relationship with Disease-Related Variables.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease leading to functional limitations and subsequently impaired quality of life (QoL). Despite the fact that QoL was recognized as a significant perception, it was excluded from the core domains (defined by the Assessment of Spondyloarthritis International Society), because of ambiguity of measurement choice. AIM: To assess QoL in patients with AS using a generic; Short Form-36 (SF-36) and a diseasespecific; Ankylosing Spondylitis quality of life (ASQoL) instruments and to explore its relationship to the clinical characteristics, disease activity, functional status, and radiographic severity. METHODS: A total of 47 AS patients who fulfilled modified New York criteria were included. Disease activity, functional status, spinal mobility, and radiographic severity were assessed by Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI) and Bath AS Radiology Index (BASRI) respectively. SF-36 and ASQoL instruments evaluated Qol. RESULTS: Physical health was more affected especially in patients with peripheral arthritis by SF-36 (p=0.008) and ASQoL (p=0.022) scores. Both SF-36 total and ASQoL scores correlated significantly with BASDAI (r = -0.329, p = 0.024 and r = 0.420, p = 0.003), BASFI (r = -0.399, p = 0.005 and r = 0.513, p=0.001) and BASMI (r = -0.382, p = 0.008 and r = 0.482, p= 0.001) respectively. CONCLUSION: QoL was impaired in AS patients with highest impact on physical health especially in association with peripheral arthritis. SF-36 and ASQol have a comparable achievement in the evaluation of QoL in AS patients and both physical function and spinal mobility were identified as predictors of poor QoL.

Human Parvovirus B19 Infection in Rheumatoid Arthritis Patients: Screening and Clinical Significance.

Rheumatoid arthritis (RA) is a common chronic inflammatory disease, affecting about 1% of the general population. Conflicting data are available regarding the etiologic association of human parvovirus B19 (B19) infection with RA. This study aimed to determine the prevalence of B19 infection in patients with RA compared to healthy controls and to assess its possible association with disease activity or severity. The study included 40 RA patients and 40 age and sex matched apparently healthy controls. Detection of B19 DNA by nested PCR and the detection of anti-B19 IgM and IgG by ELISA) were performed for patients and controls. It was found that B19 infection is more prevalent in patients with RA than healthy controls as the frequency of detection of B19 DNA and anti-B19 IgG was significantly higher in RA patients than healthy controls (P=0.003 and P=0.04, respectively) but not IgM. It was concluded that B19 infection may have a role in the etiopathogenesis of RA but not involved in disease activity or severity.

Ultrasonographic Enthesopathy and Disease Activity in Psoriatic Arthritis.

BACKGROUND: To our knowledge, the correlation between ultrasonographic enthesopathy and severity in psoriatic arthritis (PsA) has been done before. However, the correlation between ultrasonography of enthesopathy and the Psoriatic Arthritis Disease Activity Score (PASDAS) have not been done. AIM: To compare the results of ultrasonographic enthesopathy of foot and PASDAS in PsA. MATERIALS AND METHODS: A total of 65 PsA patients were involved and divided into two groups. The first group of 35 active PsA and the second group of 30 ages and sex matched inactive PsA as a control group were recruited in this study. Both groups were evaluated by examination, radiological findings and ultrasonography. RESULTS: Of 70 entheses in 35 active PsA patients, the most entheseal abnormalities were tender plantar fascia (18.5%), tender Achilles tendon (37.8%). PASDAS was a direct highly significant correlated with plantar fascia and Achilles tendon thickness in in active PsA (r = 0.823 and r = 0.796, p < 0.001 respectively). CONCLUSION: Musculoskeletal US is an accurate and low-cost method for assessment of enthesopathy with significant correlation to disease activities in psoriatic arthritis.

Role of T helper 17 cells in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that occurs in genetically prone individuals. Autoimmunity could not be simply explained by Th1/Th2 cell paradigm. T helper 17(Th17) cells producing the cytokine interleukin-17 (IL-17) may explain the promotion and progression of autoimmune phenomena. This study aimed to investigate the role of Th17cells, IL-17 and interleukin-23 (IL-23) in the pathogenesis of SLE and their correlation with disease activity. The frequencies of circulating Th17 cells in 15 patients with active SLE, 15 patients with inactive disease and 15 healthy control subjects were measured using Flowcytometry after stimulation with phorbol myristate acetate (PMA) and ionomycin for 4 hours. Serum levels of IL-17 and IL-23 were measured using the enzyme linked immunosorbent assay (ELISA). Significantly higher mean frequencies of circulating Th17 cells were found in active SLE patients (1.54 +/- 0.38%, P < 0.001) and inactive SLE patients (1.23 +/- 0.25%, P = 0.009) compared to the control group (0.88 +/- 0.41%). The frequencies of circulating Th17 cells positively correlated with the SLEDAI score (r = 0.812, P < 0.001). The serum levels of IL-17 and IL-23 were significantly higher in active SLE (P < 0.001) and inactive SLE patients (P < 0.001) than the control group while, serum levels of both cytokines correlated positively with SLEDAI score (r = 0.661, P < 0.01 and r = 0.701, P < 0.01 respectively). There was significant positive correlation between the frequency of circulating Th17 cells and plasma levels of IL-17 and IL-23 (r = 0.789, P < 0.001) and (r = 0.792, P < 0.001) respectively. Results of this study provides evidence of a role of Th17 cells in the pathogenesis of SLE, and offer scientific rationale for the utility of Th17 cells, IL-17 and IL-23 as biological markers for SLE disease activity. This would raise the possibility of anti-IL-17 and anti-IL-23 as innovative therapeutic options in controlling disease activity of SLE.