Intravenous benzylpenicillin is the gold-standard treatment for neurosyphilis, but it requires prolonged hospitalisation. Ceftriaxone is a possible alternative treatment, the effectiveness of which ...remains unclear. We aimed to assess the effectiveness of ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis.
We did a retrospective multicentre study including patients with neurosyphilis who were treated at one of eight tertiary care centres in France, from Jan 1, 1997, to Dec 31, 2017. We defined neurosyphilis as positive treponemal and non-treponemal tests and at least one of otic syphilis, ocular syphilis, either neurological symptom with a positive result on cerebrospinal fluid (CSF)-VDRL or CSF-PCR tests, or more than five leukocytes in a CSF cell count. Patients with neurosyphilis were identified from the medical information department database of each centre and assigned to one of two groups on the basis of the initial treatment received (ie, benzylpenicillin group or ceftriaxone group). The primary outcome was the overall clinical response (ie, proportion of patients with a complete or partial response) 1 month after treatment initiation. The secondary endpoints were proportions of patients with a complete response at 1 month and serological response at 6 months, and length of hospital stay.
Of 365 patients with a coded diagnosis of neurosyphilis in one of the eight care centres during 1997–2017, 208 were included in this study (42 in the ceftriaxone group and 166 in the benzylpenicillin group). The mean age of patients was 44·4 years (SD 13·4), and 193 (93%) were men. We observed 41 instances of overall clinical response (98%) in the ceftriaxone group versus 125 (76%) in the benzylpenicillin group (crude odds ratio OR 13·02 95% CI 1·73–97·66, p=0·017). After propensity score weighting, overall clinical response rates remained different between the groups (OR 1·22 95% CI 1·12–1·33, p<0·0001). 22 (52%) patients in the ceftriaxone group and 55 (33%) in the benzylpenicillin group had a complete response (crude OR 2·26 95% CI 1·12–4·41, p=0·031), with no significant difference after propensity score weighting (OR 1·08 95% CI 0·94–1·24, p=0·269). Serological response at 6 months did not differ between the groups (21 88% of 24 in the ceftriaxone group vs 76 82% of 93 in the benzylpenicillin group; crude OR 1·56 95% CI 0·42–5·86, p=0·50), whereas hospital stay was shorter for patients in the ceftriaxone group than for those in the benzylpenicillin group (mean 13·8 days 95% CI 12·8–14·8 vs 8·9 days 5·7–12·0, p<0·0001). No major adverse effects were reported in either group.
Our results suggest that ceftriaxone is similarly effective to benzylpenicillin for the treatment of neurosyphilis, potentially decreasing the length of hospital stay. Randomised, controlled trials should be done to confirm these results.
None.
Cerebral vasculitis caused by neurosyphilis is a re-emerging problem with diagnostic and treatment issues, especially for human immunodeficiency virus patients.
We present a case of relapsing ...syphilis-associated cerebral vasculitis, despite the recommended first-line antibiotic treatment, that was successfully treated with a second intravenous penicillin G course and corticosteroids.
A 50-year old man went to the emergency department for bilateral episodes of red and painful eyes with progressive but severe visual acuity loss. He was diagnosed with bilateral panuveitis and neurosyphilis favored by an unknown human immunodeficiency virus infection with a CD4 count of 236 mm3. Despite appropriate and well-conducted treatment including intravenous penicillin G, short-term corticosteroid, and highly active antiretroviral therapy, a symptomatic relapse of the syphilis-associated cerebral vasculitis occurred. After a second course of penicillin and corticosteroids, he made a complete recovery.
Neurosyphilis and human immunodeficiency virus co-infection is a reappearing challenging situation that should be considered with care by physicians because recommended antibiotic treatment sometimes fails. Corticosteroid therapy should be discussed in case of cerebral vasculitis.
Little is known about systemic sclerosis (SSc)-associated myopathy (SScAM) treatment. Herein we evaluated the use of intravenous immunoglobulin (IVIg) in SScAM.
We conducted a retrospective study of ...patients with SScAM in the Internal medicine department of Cochin University Hospital between 1993 and 2017.
Fifty-two patients were included comprising 18 (34.6%) with limited SSc and 34 (65.4%) with diffuse SSc. SScAM occurred at a median interquartile range (IQR) time of 1 month 0–15 after SSc diagnosis. Thirty-four patients (65.4%) had muscle weakness, 28 (53.8%) had myalgia and 24 (46.2%) had dysphagia. Fifty patients (96.2%) had increased creatine kinase, 22/26 (84.6%) had myopathic electromyography, 10/12 (83.3%) had a high intensity signal of girdle muscles on MRI and 49/50 (98%) had abnormal muscle biopsy. Eighteen (34.6%) patients received IVIg. Severe adverse events occurred in 3/18 (16.7%) patients. When compared to patients who did not receive IVIg, patients who received IVIg had a significantly higher maximal corticosteroid (CS) dose ever, a greater decrease of CS at 3 months, and a lower CS dose at one year and at the end of follow up.
This study suggests the benefit of IVIg as adjunctive therapy, with an acceptable tolerance profile, and supports its use as a CS-sparing agent, in SScAM.
•This study reports 52 cases of systemic sclerosis-associated myopathy (SScAM).•IVIg can be used as an adjunctive therapy in SScAM.•Is has an acceptable tolerance profile and is used as a CS-sparing agent, in SScAM.
Subglottic stenosis (SGS) and tracheal stenosis (TS) are characterized by a narrowing of the airways. The goal of this study was to describe the characteristics and prognosis of nontraumatic and ...nontumoral SGS or TS.
What are the inflammatory etiologies of SGS and TS, and what are their characteristics and prognosis?
This multicenter, observational retrospective study was performed in patients with SGS or TS that was neither traumatic nor tumoral.
Eighty-one patients were included, 33 (41%) with granulomatosis with polyangiitis (GPA) and 21 (26%) with relapsing polychondritis (RP). GPA-related stenoses exhibited circumferential subglottic narrowing in 85% of cases, without calcifications. In contrast, RP-related stenoses displayed anterior involvement in 76%, in a longer distance from vocal cords (4 cm), with calcifications in 62%, and extension to bronchi in 86%. Other diagnoses included bullous dermatoses (n = 3), amyloidosis (n = 3), sarcoidosis (n = 2), and Crohn’s disease (n = 2); the remaining stenoses (n = 15) were idiopathic. SGS/TS was the initial manifestation of the disease in 66% of cases, with a median interval from stenosis to disease diagnosis of 12 months (interquartile range, 0-48 months). Despite the use of glucocorticoids in 80%, combined with methotrexate in 49%, endoscopic procedures were required in 68% of patients. Relapses of stenoses occurred in 76% without any difference between causes (82% in GPA, 67% in RP, and 75% in idiopathic SGS/TS). Three patients died due to the stenosis, two of RP and one of GPA.
These data show that GPA and RP are the two main inflammatory diseases presenting with SGS/TS. GPA-related stenoses are mostly subglottic and circumferential, whereas RP-related stenoses are mostly tracheal, anterior, and calcified with a frequent extension to bronchi. Relapses of stenoses are common, and relapse rates do not differ between causes. Diagnosis and management of SGS/TS require a multidisciplinary approach.
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Objective
To study the role of B lymphocytes in systemic sclerosis (SSc).
Methods
Peripheral B cell subpopulations and the production of interleukin‐6 (IL‐6) and transforming growth factor β (TGFβ) ...were analyzed using flow cytometry and multiplex assay. The fibroblast proliferation rate upon incubation with supernatants from B cells isolated from SSc patients or healthy controls was assessed using XTT, bromodeoxyuridine, and Ki‐67. Collagen production was assessed using a collagen assay.
Results
Ninety untreated patients (12 males) fulfilling the American College of Rheumatology/European League Against Rheumatism criteria for SSc (23 with diffuse cutaneous SSc dcSSc and 67 with limited cutaneous SSc lcSSc) and 30 healthy controls were recruited. Increased proportions of B cells expressing CD69 and CD95 were identified among the patients with SSc. B lymphocytes from dcSSc patients versus lcSSc patients and healthy controls expressed increased proportion of cells positive for CD5 (mean ± SD 24.12 ± 7.93% versus 14.09 ± 6.58% P = 0.03 and 14.21 ± 5.34% P = 0.01), CD86 (39.89 ± 22.11% versus 17.72 ± 13.98% P = 0.0007 and 11.68 ± 11.09% P < 0.001), IL‐6 receptor (IL‐6R; 33.64 ± 23.12% versus 17.91 ± 13.62% P < 0.0001 and 12.08 ± 8.68% P = 0.0009), or IL‐21R (32.55 ± 20.19% versus 5.76 ± 4.40% P < 0.0001 and 5.93 ± 3.29% P < 0.0001). In addition, the levels of IL‐6 (mean ± SD 314.3 ± 317.8 pg/ml versus 6.10 ± 2.58 pg/ml; P = 0.0007) and TGFβ (mean ± SD 1,020 ± 569 pg/ml versus 163.8 ± 98.69 pg/ml; P = 0.001) secreted by B lymphocytes from patients with SSc were increased compared to healthy controls. Fibroblast proliferation and collagen production were also significantly increased in the presence of B cell supernatant from SSc patients as compared to healthy controls.
Conclusion
The numbers of activated B cells were increased in SSc patients, and the up‐regulation of CD5, CD86, IL‐6R, and IL‐21R discriminated between patients with dcSSc and those with lcSSc. Peripheral B lymphocytes from SSc patients secreted both IL‐6 and TGFβ, and they activated fibroblasts in vitro.
Abstract Giant cell arteritis (GCA) is characterized by intimal hyperplasia and luminal obstruction leading to ischemic manifestations involving extra-cranial branches of carotid arteries and aorta. ...Histopathological lesions involve all layers of the arterial wall and are associated with multinucleated giant cells, fragmented internal elastic lamina and polymorphic cellular infiltrates, including T lymphocytes and macrophages. The pathophysiology of GCA is still poorly understood. After dendritic cell activation, CD4+ T lymphocytes, T helper 1 (Th1) cells, produce interferon γ and modulate macrophage activation and functions, and Th17 cells produce interleukin 17 (IL-17), which can induce cytokine production by macrophages and fibroblasts. Macrophages in the adventitia produce pro-inflammatory cytokines such as IL-1, IL-6 and tumor necrosis factor α. These cytokines promote arterial wall and systemic inflammation. Questions remain regarding the nature of the antigen(s) triggering dendritic cell activation and the mechanisms underlying vascular remodeling. Here we review recent advances in the pathogenesis of GCA, with emphasis on the interactions between cells of the immune system and components of the vessel wall, including vascular smooth muscle cells and endothelial cells, leading to vascular remodeling. Finally, we propose new areas of investigation that could help understand the triggering factors and key pathogenic events in GCA.
Abstract
Objectives
Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing eosinophil-rich vasculitis. Specific cardiomyopathy (CM) was described in early studies as the most important ...predictor of mortality. We aimed to revisit EGPA-related CM and investigate its outcome in recent decades.
Methods
We reviewed all EGPA patients managed from 2000 to 2019 in our vasculitis clinic. Baseline characteristics and outcomes were analysed. EGPA-related CM was defined as clinical or extra-clinical manifestations of patent myocardial involvement, after exclusion of other causes.
Results
We included 176 patients. The median age was 47 years interquartile range (IQR) 36–58 years. Specific CM was observed in 70 patients (40%). Cardiac symptoms were observed in 81% of CM+ patients, including mainly typical or atypical chest pain and peripheral oedema. Abnormal ECG, transthoracic echocardiography and cardiac MRI (CMRI) were found in 72%, 72% and 99% of CM+ patients, respectively, contrasting with abnormalities in 32%, 38% and 60% of CM-negative patients, respectively. Late gadolinium enhancement (LGE) was the most frequent abnormality on CMRI (70%). CM+ patients were less frequently ANCA-positive, had less frequent peripheral neuropathy and had higher eosinophil count. Major adverse cardiovascular events (MACEs) occurred in 13% of patients, both in CM+ and CM– patients. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs. Four patients died, but none from cardiac causes.
Conclusion
Specific cardiomyopathy is frequent in EGPA, especially in ANCA-negative patients with high eosinophil counts. Long-term outcome was better than previously reported. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs.
Abstract
Objectives
To assess efficacy and safety of rituximab (RTX) induction and maintenance therapy for granulomatosis with polyangiitis (GPA) in a single-centre cohort study.
Methods
All patients ...with active GPA, not enrolled in trials, who received ⩾1 RTX infusion(s) for induction were included. At remission, protocolized maintenance RTX infusions were given every 6 months for 18 months. Kaplan–Meier curves were used to estimate survival rates. Univariable analyses identified factors associated with remission failure and relapse, and Cox models retained independent predictors of relapse.
Results
One hundred and fourteen adults with relapsing (65%), refractory/grumbling (22%) or new-onset (13%) GPA received RTX for induction; 100 were given ⩾1 RTX maintenance infusion(s) and 90 received 500 mg every 6 months. Median daily prednisone induction dose was 30 mg; 76% of patients were still receiving a median daily prednisone dose of 5 mg at 2 years. Median follow-up was 3.6 years. Respective 2-year relapse-free survival and RTX retention rates were 85 and 78%. Serious infection and serious adverse event rates were 4.9 and 8.1 per 100 patient-years, respectively. Refractory/grumbling vs new-onset and/or relapsing GPA (P < 0.01 for each individually; P < 0.001 vs the latter two taken together), pachymeningitis (P < 0.05), pure granulomatous disease (P < 0.05) or estimated glomerular filtration rate ⩾60 ml/min (P < 0.01) were associated with remission failure. Multivariate analyses retained refractory/grumbling GPA (P = 0.05), subglottic stenosis (P < 0.005), ENT involvement (P = 0.01) and skin involvement (P < 0.0005) as independent predictors of relapse.
Conclusion
RTX induction and low-dose preemptive maintenance can effectively and safely induce sustained remission in GPA in a real-life setting.
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