Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis.

OBJECTIVE: Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent. METHODS: Patients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks. Baseline and follow-up 18F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta. RESULTS: 115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups-ΔTNFi: -0.24 (SD=0.51), Δtriple therapy: -0.19 (SD=0.51)-without difference between groups (difference in Δs: -0.02, 95% CI -0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (ß=0.04, 95% CI -0.03 to 0.10). CONCLUSION: We found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy. TRIAL REGISTRATION NUMBER: NCT02374021.

Aspergillus spp. renal arteritis after kidney transplantation: A reappraisal.

BACKGROUND: Aspergillus spp. is an uncommon and life-threatening cause of transplantrenal artery pseudoaneurysm after kidney transplantation. CASE: We report the case of a 62-year-old woman who underwent kidney transplantation 10 months before and presented a 7-cm asymptomatic transplant renal artery pseudoaneurysm. Transplanted kidney and pseudoaneurysm were surgically removed in emergency. Renal graft, urine, and pseudoaneurysm cultures grew Aspergillus flavus. She recovered after 12 months of antifungal therapy. LITERATURE REVIEW: To date 14 cases of Aspergillus spp. renal arteritis after kidney transplantation have been published, including 50% Aspergillus flavus arteritis. Vast majority were diagnosed within 90 days after transplantation (73%). Despite allograft nephrectomy and antifungal therapy, mortality rate was high (33%).

Recombinant Human Soluble Thrombomodulin Suppresses Arteritis in a Mouse Model of Kawasaki Disease.

INTRODUCTION AND OBJECTIVE: Kawasaki disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and primarily affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, which increases their risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulant, anti-inflammatory, and cytoprotective properties on the development of coronary arteritis in a mouse model of vasculitis. METHODS: An animal model of KD-like vasculitis was created by injecting mice with Candida albicans water-soluble fraction (CAWS). This model was used to investigate the mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-α), and tissue factor (TF), in addition to histopathology of heart tissues. RESULTS: rTM treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 days after CAWS treatment. In addition, mRNA expression analysis revealed that rTM administration increased cardiac IL-10 expression until day 27, whereas expression of TNF-α was unaffected. Moreover, in the spleen, rTM treatment restores IL-10 and TF expression to normal levels. CONCLUSION: These findings suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. Therefore, rTM may be an effective treatment for KD.

Self-Assembled CuCo2S4 Nanoparticles for Efficient Chemo-Photothermal Therapy of Arterial Inflammation.

Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo2S4 nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo2S4 NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo2S4 NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo2S4 NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.

Combination of Prednisolone and Azathioprine for Steroid-Responsive Meningitis-Arteritis Treatment in Dogs.

Treatment with high corticosteroid dosages for steroid-responsive meningitis-arteritis (SRMA) is correlated with severe adverse effects and worse quality of life. In order to improve immunosuppression and decrease dosage and duration of glucocorticoid treatment, a second immunosuppressive drug is commonly used in most of the immune-mediated diseases. The objective of this retrospective study was to evaluate the efficacy, tolerability, and occurrence of relapse for the combination of prednisolone and azathioprine. All dogs received azathioprine 2 mg/kg q 24 hr for 1 mo and then 2 mg/kg every other day for 2 mo; prednisolone was started at an immunosuppressive dosage and tapered off gradually during a mean of 3 mo. Twenty-six dogs met inclusion criteria. Twenty-one dogs (81%) were in clinical remission with no relapse observed within the 2 yr follow-up period. Treatment was well tolerated in all dogs and side effects were most of the time mild and self-limiting. The relapse rate (19%) was lower than most published rates. A prednisolone and azathioprine combination appeared to be effective for primary treatment of dogs with SRMA and allows a quicker tapering in prednisolone dosage, a decrease in long-term side effects of steroids, a shorter duration of treatment, and a low relapse rate.

Cutaneous arteriolitis: A novel cutaneous small vessel vasculitis disorder clinicopathologically different from cutaneous polyarteritis nodosa and cutaneous venulitis.

Cutaneous vasculitis can be classified into two types based on the affected vessel size: small vessel vasculitis predominantly affecting dermal venules, and muscular vessel vasculitis as found in cutaneous arteritis predominantly affecting arteries located at the dermal-subcutaneous junction. We describe two cases with a novel small vessel vasculitis disorder, which exclusively affected arterioles in the mid-dermis, and show clinical and pathological difference distinct from cutaneous polyarteritis nodosa and cutaneous venulitis. Both patients were male, and presented with painful infiltrative plaques, involving the palms, soles, and thighs without extracutaneous involvement except for fever and arthralgia. Histopathological examination revealed vasculitis in the mid-dermis characterized by a predominant infiltration of neutrophils with vessel wall fibrinoid necrosis and leukocytoclasia identical to the features of leukocytoclastic vasculitis, except that the affected vessels were arterioles rather than venules. Serological examinations showed normal levels of serum complements, immune complexes, and antineutrophil cytoplasmic antibodies, and vasculitis disorders associated with systemic diseases were excluded in both patients. The patients showed a good response to short-term treatment with prednisolone up to 30 mg. This novel cutaneous arteriolitis clinicopathologically different from both cutaneous venulitis and cutaneous arteritis appears to be a skin-limited disorder.

Salmonella enterica subspecies houtenae as an opportunistic pathogen in a case of meningoencephalomyelitis and bacteriuria in a dog.

BACKGROUND: We report the first case of canine Salmonella meningoencephalomyelitis and second case of canine Salmonella bacteriuria, as well as the first reported case of Salmonella enterica subspecies houtenae in a dog. CASE PRESENTATION: Immunosuppressive treatment in a dog for a relapse of steroid-responsive meningitis and arteritis (SRMA) allowed for the opportunistic establishment of a bacteremia with Salmonella enterica subsp. houtenae, ultimately causing meningoencephalomyelitis and subclinical bacteriuria. The bacterial infections were treated with a four-month course of amoxicillin; clinical treatment success was determined by serial negative urine cultures and lack of clinical signs correlated to the meningoencephalomyelitis. CONCLUSIONS: Both the bacteriuria and meningoencephalomyelitis represented opportunistic infections in a dog immunosuppressed for SRMA. The clinical course of this infectious meningoencephalitis emphasizes the importance of differentiating relapse of initial disease from opportunistic infection occurring in a compromised central nervous system. The novel Salmonella species identified in this case acts as a reminder that infectious disease diagnostics should not be curbed by anecdotal prediction of routine pathogenic suspects.

Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment.

AIMS: Subjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a). METHODS AND RESULTS: In this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)]: age 60.0 [54.0-67.0] years, Lp(a) 200.0 [155.5-301.5] nmol/L [80.0 (62.5-121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8-55.5] and Lp(a) by 13.9% (95% CI 19.3-8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0-268.0) nmol/L [75.2 (56.0-107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (-8.3%) vs. placebo (-5.3%) [treatment difference -3.0% (95% CI -7.4% to 1.4%); P = 0.18]. CONCLUSION: Evolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.

Association of IgG4-Related Arteritis With Recurrent Stroke.

Immunoglobulin G4-related disease (IgG4)-related disease is a newly recognized form of immune-mediated disease, which is characterized by IgG4+ lymphoplasmacytic infiltration and fibrosis in the systemic organs. Although aortitis/periaortitis is a phenotype of IgG4-related disease, the relationship between cerebrovascular disease and IgG4-related disease remains unclear. Herein, we report the case of a 49-year-old man with recurrent stroke induced by IgG4-related arteritis. Case reports or studies examining the association between IgG4-related arteritis and stroke are limited. Although a definitive link between IgG4-related arteritis and stroke has not been established, IgG4-related arteritis should be considered as an etiology in patients with recurrent idiopathic stroke.

Common carotid arteritis and polymyalgia with Mycoplasma pneumoniae infection.

A few pediatric cases with brain vasculitis most frequently affecting the middle cerebral artery have been reported in association with Mycoplasma pneumoniae infection, but involvement of the common carotid artery (CCA) before the bifurcation has not been reported to date. We report herein a case of 10-year-old boy with common carotid arteritis and polymyalgia associated with Mycoplasma pneumoniae infection. His fever and cough began 2 weeks before, and his right upper and lower extremity pains began 2 days before admission. He had initially been treated with clarithromycin followed by tosufloxacin, but his symptoms persisted. His M. pneumonia-specific antibody titer was high on admission (1:10240 by particle agglutination method) and the gene of M. pneumoniae was detected in a throat swab specimen by the loop-mediated isothermal amplification method with initial high levels of serum interleukin-8, tumor necrosis factor-α, and interleukin-18 along with elevated blood levels of complements. On the 5th day of hospitalization, vascular echograms of the extremities and neck showed increasing intima-media thickness of bilateral CCAs without stenosis and/or thrombosis and T2-weighted with lipid suppression magnetic resonance imaging of the neck showed high signal intensity of bilateral CCA walls. Coagulation studies were unremarkable and no autoantibodies were detected as far as tested. He was successfully treated by intravenous administration of prednisolone and was stable without any neurological sequelae 17 months after the onset without medication. His particle agglutination titer decreased to 1:5120, and serum interleukin-8, tumor necrosis factor-α, interleukin-18, and complement levels returned to normal.

Three cases of lymphocytic thrombophilic arteritis presenting with an annular eruption.

We describe three patients who presented with a striking erythematous non-blanching annular eruption and features of lymphocytic thrombophilic arteritis (LTA), with a prominent lymphocytic vasculitis involving deep dermal vessels. Lymphocytic inflammation was also evident in the superficial vessels and one patient had small superficial ulcers over the ankle area resembling livedoid vasculopathy (LV). Multiple biopsies demonstrated a persistent absence of neutrophils in the infiltrate consistent with a lymphocytic process. In addition to highlighting the annular morphology as a novel presentation of LTA, these cases suggest a possible relationship between LV and LTA and support the notion that they are distinct from neutrophilic vasculitides such as cutaneous polyarteritis nodosa.

Lymphocytic thrombophilic arteritis complicated by systemic involvement.

Lymphocytic thrombophilic arteritis (LTA) is a recently described entity defined by primary lymphocytic vasculitis; it typically has a chronic indolent course. We describe a patient who presented with clinical and histological findings consistent with LTA and later developed bilateral focal testicular infarcts as well as an acute median nerve neuropathy.

Tacrolimus therapy for dermal arteritis of the nasal philtrum refractory to surgery and anti-inflammatory therapy (doxycycline/niacinamide and topical fluocinolone) in a dog.

BACKGROUND: Dermal arteritis of the nasal philtrum is a rarely reported condition commonly affecting large breed dogs. OBJECTIVE: To describe the effective treatment of nasal philtrum arteritis with topical tacrolimus in one dog. ANIMAL: A 9-year-old, intact male German shorthair pointer dog was presented with well-demarcated deep erythematous ulcers targeting exclusively the skin of the nasal philtrum, accompanied by frequent series of haemorrhage. METHODS: Complete blood count, serum chemistry profile, urinalysis, histopathological examination and immunohistochemistry of skin biopsies. RESULTS: The presence of a V-shaped ulcer with subendothelial spindle cell proliferation resulting in stenosis of dermal arteries and arterioles on histological evaluation, together with a well-demarcated deep nasal philtrum ulcer was consistent with arteritis of the nasal philtrum. Treatment was initiated with twice daily oral doxycycline and niacinamide in conjunction with topical fluocinolone cream. Over the course of two years, the lesions progressed with frequent bleeding episodes. A novel surgical approach provided deep resection of all grossly affected tissue; four months later a recurrence of fissures and occasional mild bleeding from the original site was noted and there was no improvement after another two months of oral doxycycline/niacinamide and topical fluocinolone treatment. Topical application of 0.1% tacrolimus twice daily resulted in complete healing of the ulceration and normalization of the epidermis. Over the subsequent 15 months, the dog's lesions remained in remission with topical tacrolimus application twice daily. CONCLUSIONS AND CLINICAL IMPORTANCE: Topical tacrolimus ointment appeared effective at inducing and maintaining lesion remission in this dog with nasal philtrum arteritis.

The suppressive effect of the three-herb extract mixture on vascular and liver inflammation in atherogenic diet with high fructose-fed mice.

CONTEXT: Cynanchum wilfordii (Maximowicz) Hemsley (Apocynaceae), Arctium lappa L. var. rubescens Frivald (Asteraceae) and Dioscorea opposite Thunb (Dioscoreaceae) root extracts have been widely used as an alternative for intervening obesity. OBJECTIVES: The synergistic effect of three-herb mixture of C. wilfordii, A. lappa and D. opposita was determined on aortic and liver inflammatory responses. MATERIALS AND METHODS: CWE, ALE and DOE were prepared from the root of C. wilfordii, A. lappa and D. opposite by 70% ethanol extraction, respectively. CADE was prepared using a powder mixture of 2 CWE:1 ALE:1 DOE. C57BL/6 mice were fed an atherogenic diet combined with 10% fructose (ATHFR) in the presence of 200 mg/kg/day CWE, ALE, DOE or CADE for 8 weeks (each group, n = 6). Biochemical profiles, protein expression of vascular cell adhesion molecule-1 (VCAM-1) on the aorta and liver were determined. RESULTS: CADE could significantly suppress the protein expression of VCAM-1 in both the aorta and liver (80% reduction) compared to ATHFR-fed mice. Impairment of liver function was significantly ameliorated by CADE supplement, as determined by GOT (60% reduction) and GPT (51% reduction) levels. CONCLUSIONS: CADE should be considered when developing medications to suppress the vascular and liver inflammatory responses for individuals who are either non-responsive or resistant to lipid-lowering drugs.

Isolated Arteritis of Both Lower Limbs.

Isolated arteritis of the lower limb vessels is an extremely rare condition. The use of modern vascular imaging techniques substantially facilitates and accelerates the diagnostics. In the isolated lower limb arteritis, it is always necessary to exclude Takayasu's and giant-cell arteritis. We present the case of a female patient with an isolated lower extremity arteritis without any other symptoms of systemic vascular damage or systemic autoimmune disease. Immunosuppressive therapy is obligatory in this case. Interdisciplinary co-operation is required for rapid diagnosis and successful therapy. Our patient has consented to the publication of this report.

Th17-skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis.

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is an immune-mediated disorder characterized by neutrophilic pleocytosis and an arteritis particularly in the cervical leptomeninges. Previous studies of the disease have shown increased levels of IL-6 and TGF-ß1 in cerebrospinal fluid (CSF). In the presence of these cytokines, naive CD4+ cells differentiate into Th17 lymphocytes which synthesize interleukin 17 (IL-17). It has been shown that IL-17 plays an active role in autoimmune diseases, it induces and mediates inflammatory responses and has an important role in recruitment of neutrophils. The hypothesis of a Th17-skewed immune response in SRMA should be supported by evaluating IL-17 and CD40L, inducing the vasculitis. METHODS: An enzyme-linked immunosorbent assay (ELISA) was performed to measure IL-17 and CD40L in serum and CSF from a total of 79 dogs. Measurements of patients suffering from SRMA in the acute state (SRMA A) were compared with levels of patients under treatment with steroids (SRMA T), recurrence of the disease (SRMA R), other neurological disorders, and healthy dogs, using the two-part test. Additionally, secretion of IL-17 and interferon gamma (IFN-γ) from the peripheral blood mononuclear cells (PBMCs) was confirmed by an enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant higher levels of IL-17 were found in CSF of dogs with SRMA A compared with SRMA T, other neurological disorders and healthy dogs (p < 0.0001). In addition, levels of CD40L in CSF in dogs with SRMA A and SRMA R were significantly higher than in those with SRMA T (p = 0.0004) and healthy controls (p = 0.014). Furthermore, CSF concentrations of IL-17 and CD40L showed a strong positive correlation among each other (rSpear = 0.6601; p < 0.0001) and with the degree of pleocytosis (rSpear = 0.8842; p < 0.0001 and rSpear = 0.6649; p < 0.0001, respectively). IL-17 synthesis from PBMCs in SRMA patients was confirmed; however, IL-17 is mainly intrathecally produced. CONCLUSIONS: These results imply that Th17 cells are inducing the autoimmune response in SRMA and are involved in the severe neutrophilic pleocytosis and disruption of the blood-brain barrier (BBB). CD-40L intrathecal synthesis might be involved in the striking vasculitis. The investigation of the role of IL-17 in SRMA might elucidate important pathomechanism and open new therapeutic strategies.

Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease.

Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)-/- and myeloid differentiation primary response gene 88 (MyD88)-/- mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9-/- mice but not in MyD88-/- mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD.

Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

Purpose: Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline's post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)-neuroprotective ability. Methods: We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in flat mounted retinas. Results: Post-rNAION, oligodendrocytes exhibit a delayed pattern of apoptosis extending over a month, with extrinsic monocyte infiltration occurring only in the primary rNAION lesion and progressive distal microglial activation. Post-induction minocycline failed to improve retinal ganglion cell survival compared with the vehicle treated (893.14 vs. 920.72; p>0.9). Cytokine analysis of the rNAION lesion 3 days post-induction revealed that minocycline exert general inflammatory suppression without selective upregulation of cytokines associated with the proposed alternative or neuroprotective M2 inflammatory pathway. Conclusions: The pattern of cytokine release, extended temporal window of oligodendrocyte death, and progressive microglial activation suggests that selective neuroimmunomodulation, rather than general inflammatory suppression, may be required for effective repair strategies in ischemic optic neuropathies.

Conservative treatment of patients with thromboangiitis obliterans or cannabis-associated arteritis presenting with critical lower limb ischaemia.

BACKGROUND: Proper management of patients with thromboangiitis obliterans (TAO) or cannabis-associated arteritis (CAA), presenting with critical lower limb ischaemia (CLI) remains controversial, and data are limited. PATIENTS AND METHODS: Patients with TAO or CAA presenting with CLI between 2011 and 2016 were retrospectively evaluated. Patients requiring primary intervention were excluded. Conservative treatment included: (a) weight-adjusted bemiparin plus six hours/day intravenous iloprost for 28 days, (b) aspirin (100 mg/day) plus cilostazol (100 mg twice/day) after discharge, and (c) strict recommendations/monitoring for smoking cessation. Main outcomes included symptom recession, ankle-brachial index (ABI) improvement, and healing of lesions at the time of discharge as well as amputation, revascularization, and abstinence rate during follow-up. RESULTS: Overall, 23 patients (TAO: 15; CAA: 8) were included within six years, none of the patients reported any other factor than smoking. All patients presented with rest pain and 12 patients with ulcer or necrotic lesions. Mean ABI measurement at presentation was 0.46 ± 0.2, after 28 days of treatment, all patients showed improvement regarding clinical picture and ABI measurement (0.54 ± 0.1; p < 0.05). During follow-up, only three patients underwent bypass surgery and two patients underwent major amputation, although the smoking abstinence rate was very low (13 %). CONCLUSIONS: Intravenous iloprost plus bemiparin for 28 days together with per os aspirin plus cilostazol seem to produce promising results in patients with TAO/CAA, treated for CLI, even with a low smoking abstinence rate. However, larger series are needed to further evaluate inter-group differences and potential prognostic factors.

Influence of triple disease modifying anti-rheumatic drug therapy on carotid artery inflammation in drug-naive patients with recent onset of rheumatoid arthritis.

OBJECTIVE: Increased atherosclerosis in RA is not fully explained by the ordinary risk factors, but it may be related to vascular inflammation. The aim of this study was to investigate the degree of carotid artery inflammation in drug-naive patients with early RA before and after DMARD triple therapy. METHODS: Fifteen non-diabetic patients with recently diagnosed RA [age 51 (16) years, 6 males] were examined before and at 2 and 4 weeks after the initiation of combination therapy with MTX, SSZ, HCQ and ⩽10 mg/day oral prednisolone. Eight healthy males aged 49 (6) years were examined once as controls. Inflammation in the carotid artery was quantified, using [(18)F]fluorodeoxyglucose ((18)F-FDG)-PET/CT, as the maximum standardized uptake value (SUVmax) and the maximum target-to-background ratio (TBRmax). RESULTS: Before the treatment, patients with RA had significantly higher carotid artery (18)F-FDG uptake, as compared with healthy controls [TBRmax 1.78 (0.07) vs 1.51 (0.08), P = 0.03]. The 4-week DMARD therapy reduced the TBRmax to the level of healthy controls [1.53 (0.05), P = 0.84]. Compared with the baseline, the TBRmax decreased by 12.4 (16.8)% (P = 0.01) during 4-week DMARD therapy. At baseline, the SUVmax correlated with ESR (r = 0.52, P = 0.02) and CRP (r = 0.65, P = 0.01). Change in SUVmax correlated with changes in ESR and CRP after 4 weeks of treatment, as did the changes in TBRmax and SUVmax with DAS at 12 weeks of treatment. CONCLUSION: (18)F-FDG-PET/CT revealed that drug-naive patients with early RA show carotid artery inflammation that can be efficiently reduced by 1-month DMARD triple therapy.