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Cutaneous vasculitis encompasses cutaneous components of systemic vasculitides, skin-limited variants of systemic vasculitides, such as IgA vasculitis or cutaneous polyarteritis nodosa, and single-organ cutaneous vasculitis, as individualized in 2012 in the Chapel Hill Consensus Conference Nomenclature. In this article, we focus on the management of skin-limited and single-organ vasculitides, often referred to, in clinical practice, as isolated "cutaneous leukocyctoclastic vasculitis", terms which may correspond to histological findings or descriptions, but are imprecise and not specific. Since most cases of isolated cutaneous vasculitis are self-limited and resolve spontaneously over 3 to 4 weeks, most patients require no systemic treatment. For those with severe, intractable, or chronic and recurring vasculitis, systemic therapy can be indicated and should be tailored to the severity of the disease. High-quality literature is lacking to guide management. Oral glucocorticoids may be required for a short period of time for painful, ulcerative, or otherwise severe disease in order to speed resolution. Among drugs which are reasonable longer-term options are colchicine, dapsone, azathioprine or hydroxychloroquine. Additional studies, including an ongoing multicenter randomized trial, are needed to determine the most effective therapies for skin-limited vasculitis., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Cerebral vasculitides can be secondary to a broad variety of conditions such as systemic disease, infections, malignancies and toxic exposures, or can be isolated to the central nervous system. When cerebral vasculitis is suspected, the diagnostic work up must be exhaustive to rule out all these potential causes of secondary vasculitis. Most often, the diagnosis of cerebral vasculitis relies on the combination of clinical, biological and radiological findings. It is definite only when based on a positive leptomeningeal biopsy. This latter should be done when the diagnostic uncertainty remains high, especially in patients with underlying systemic disease and/or infrequent or rapidly-progressive symptoms. One can probably rule out the diagnostic of cerebral vasculitis in patients in whom both MRI and cerebrospinal fluid examination are normal. For secondary cerebral vasculitis, treatment depends on the identified underlying etiology. However, corticosteroids combined with immunosuppressive drugs are usually used. Actually, there is no consensual treatment for primary angiitis of the central nervous system. The prognosis is better when diagnosis is made early and treatment started promptly., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To assess the prevalence of mood and anxiety disorders in systemic sclerosis (SSc) patients and the association of these disorders with clinical features., Methods: Between May 2002 and May 2004, 100 SSc patients fulfilling the American Rheumatism Association and/or Leroy & Medsger criteria were recruited: 51 were from a SSc patient association meeting, and 49 were hospitalized in an internal medicine department and recruited consecutively. Mood and anxiety disorders were assessed by use of a structured clinical interview [the Mini International Neuropsychiatric Interview (MINI)] performed by a psychiatrist and a self-reporting questionnaire [the Hospital Anxiety and Depression Scale (HADS)]. On the same day, psychiatric treatment and clinical features were recorded by a physician., Results: As assessed by the MINI, 19% [95% confidence interval 12-28%] of all SSc patients were currently experiencing a major depressive episode (MDE), 56% [46-65%] had a lifetime history of MDE and 14% [8-22%] had current dysthymia. Current MDE was more prevalent among hospitalized patients than among other patients (28% versus 10%, p=0.02). Specific anxiety disorders were diagnosed in 37 [28-47] patients. Less than 50% of the patients with mood disorders received psychiatric treatment. Patients with or without current depression did not differ in clinical symptoms of SSc, except for digestive symptoms., Conclusion: The current and lifetime prevalence of major depression and anxiety disorders is high in SSc patients, especially during hospitalization. However, only half of such patients receive adequate psychiatric treatment. Therefore, a better assessment of psychiatric disorders in SSc patients is needed., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To compare patients with systemic sclerosis (SSc) recruited from a patient association or a tertiary care setting., Methods: We evaluated 248 SSc patients attending 4 annual meetings of a patient association between 2004 and 2007 (177) or during hospitalization (71). health-related quality of life (HRQoL) was assessed by the SF-36, global disability by the health assessment questionnaire (HAQ), hand disability by the Cochin Hand Function Scale (CHFS), mouth disability by the Mouth Handicap in Systemic Sclerosis (MHISS) scale, global hand and wrist mobility by the Kapandji index., Results: As compared with hospitalized patients, those from the patient association were significantly older (mean age 58.73 ± 12.04 vs 53.818 ± 13.1; p=0.001) and had a longer disease duration (10.98 ± 8.7 vs 7.13 ± 6.723 p=0.0001). Association patients had significantly increased disability of the hand (CHFS 21.8 ± 19.8 vs 9.8 ± 14.1; p=0.0001) and mouth (MHISS 20.65 ± 10.8 vs 13.25 ± 9.3; p=0.0001) and impaired hand and wrist mobility (Kapandji score 38.05 ± 10.26 vs 43.90 ± 8.26, p=0.001). The 2 groups did not differ in global disability or physical and mental scores of the SF36., Conclusion: Patients recruited from a patient association have more severe SSc than do hospitalized patients. This finding must be taken into account in the design of surveys and clinical trials., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background: Periostitis (periosteal new bone formation) is a rare manifestation of systemic necrotizing vasculitis., Patients and Methods: We searched the French Vasculitis Study Group (FVSG) database, established in 1980 and containing the data on 1762 patients with a systemic necrotizing vasculitis, i.e., polyarteritis nodosa (PAN), microscopic polyangiitis, Churg-Strauss syndrome or Wegener's granulomatosis, for those with periostitis. Herein, we describe their characteristics and outcomes., Results: Only 4 patients with periostitis were identified. All had limited and localized PAN-like vasculitis, without poor prognosis factors. Periostitis was painful and localized to the lower limbs in all of them and associated with local myositis in 2. Pain and inflammation resolved under corticosteroids in all, but relapses or corticosteroid-dependence ultimately required the adjunction of an immunosuppressant for 3. With a median follow-up of 10 [range: 4-11] years, only 1 developed peripheral neuropathy and none progressed to a more systemic form of vasculitis, i.e., with severe visceral involvement., Discussion and Conclusions: Physicians should be aware that periostitis, usually localized, is a potential manifestation of systemic necrotizing vasculitis, especially polyarteritis nodosa. The overall long-term outcome of these patients is good, but relapses or corticosteroid-dependence is frequent., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Published studies on birdshot chorioretinopathy (BCR) did not provide definitive information on possibly associated extraocular manifestations., Methods: Single-center cross-sectional analysis of extraocular manifestations in a cohort of patients with BCR., Results: Since 2002, 118 patients (45 men, 73 women) were enrolled. Their mean age was 51.5 years at diagnosis. The most common features of their medical histories were: hypertension (32 patients), drug allergy (19), sinusitis (17), thyroid disease (12), otitis media (11), asthma (11); diabetes (10); cancer (8); psoriasis (5); monoclonal gammopathies (3). At the time of disease onset, arthralgias were noted in 23, ENT manifestations in 26, Raynaud's phenomenon in 6, headaches in 10, psoriasis in 3 others. Between diagnosis and cross-sectional evaluation visits, only the frequency of hypertension has increased significantly (11 additional patients)., Discussion and Conclusions: No predominant extraocular manifestation of BCR was identified in our patients. Their ongoing follow-up may yet discern whether BCR is definitively eye-restricted., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Systemic vasculitides, like Takayasu's arteritis, polyarteritis nodosa, Wegener's granulomatosis, Churg-Strauss syndrome, Henoch-Schönlein purpura, or Behçet's disease can affect women of child-bearing years. The rarity of these vasculitides, their frequent fatal outcomes until recent years, and the use of toxic immunosuppressants to treat patients, contra-indicating pregnancy and/or potentially inducing hypofertility or sterility, explain the few pregnancies reported in the literature so far. Notably, it does not seem that pregnancy has a major impact on vasculitis outcome, in contrast with systemic lupus erythematosus, but a specialized management of these pregnant patients is mandatory. There are some reported cases of vasculitis revealed during pregnancy. Even though some of these pregnant patients had a severe disease and died, most of them had a favourable outcome, and a living inborn, providing prompt care and adequate treatment. When vasculitis is already known and treated, pregnancy should at best be planned, when the disease is in sustained remission and all toxic immunosuppressants have been stopped for months. Vasculitis sequella, like hypertension, renal insufficiency, or asthma, must also be taken into account, monitored and appropriately managed throughout the pregnancy and a few weeks following delivery. In case of vasculitis' flare during pregnancy, potential treatments include corticosteroids, intravenous immunoglobulins, azathioprine, plasma exchanges, and, for limited skin manifestations or Behçet's disease, hydroxychloroquine or colchicine. Importantly, when the disease is severe, a delay in the prescription of a stronger, immunosuppressant, chiefly intravenous cyclophosphamide, can be more detrimental, although being potentially toxic, for both the mother and the foetus than an ineffective and/or inappropriate regimen with less active drugs. Safety data on biologics, like rituximab, for pregnant women are very sparse to date and their use is therefore not recommended, unless confronted with a severe and refractory disease, and after referring to a specialized center for vasculitides.

In general, pregnancies in women with inflammatory myopathy (IM) in sustained remission have a favourable outcome, whereas those pregnant patients with active IM have an increased risk for foetal loss, intra-uterine growth retardation and/or prematurity. The effect of pregnancy on disease activity is variable. All patients with active IM need to be followed by a multidisciplinary team including obstetricians, rheumatologists and/or internists in close relationship with a neonatal intensive care unit. Maternal disease should be treated with corticosteroids, using the same dosage and regimen as for non-pregnant women and according to the disease activity and severity.

Introduction: Cardiac involvement is a rare manifestation of Wegener granulomatosis (WG). Because its prognosis can be poor, it must be diagnosed early to be treated adequately. We report the disease course of a patient who received rituximab to treat cardiac involvement documented by contrast-enhanced cardiac magnetic resonance imaging (ceCMR)., Case: This WG patient developed myocarditis with atrioventricular block. CeCMR proved useful in the diagnosis and follow-up of cardiac involvement. Several unsuccessful regimens preceded the prescription of rituximab. Two months later, regression of the myocarditis shown by ceCMR images was correlated with electrophysiological improvement., Discussion: CeCMR assessment of a heart conduction defect in a patient with WG showed that this tool was useful for the diagnosis and follow-up of cardiac involvement in this vasculitis. Rituximab was an effective treatment in this patient.

Treatment for ANCA-associated vasculitides is now well defined, but must be adjusted for each patient according to the type of vasculitis, its precise form (e.g., limited versus systemic Wegener's granulomatosis) and severity, and patients' characteristics, such as age and renal function. The therapeutic decision must also take into account the risk of adverse events inherent to each treatment. The efficacy of adequate induction treatment has been demonstrated: more than 80% of patients now achieve remission. Relapse rates nonetheless remain high, especially in Wegener's granulomatosis. Patients with microscopic polyangiitis or Churg-Strauss syndrome with no poor prognostic factors can be treated with corticosteroids alone, with immunosuppressants added only in case of treatment failure. Patients with Wegener's granulomatosis or microscopic polyangiitis or Churg-Strauss syndrome and one or more poor prognostic factors must receive a combination of corticosteroids and immunosuppressants, mainly intravenous pulsed cyclophosphamide. Plasma exchange is indicated as an adjuvant therapy for patients with severe renal involvement. Once remission is achieved, maintenance therapy can replace cyclophosphamide by a less toxic immunosuppressive drug, such as azathioprine or methotrexate. For these latter patients, the optimal duration of induction therapy remains to be determined, but should not be shorter than 18 months. Conversely, there is no need to prescribe high-dose corticosteroids for months. Prednisone must be started at 1 mg/kg/d then rapidly tapered so that patients are not receiving more than 15 mg/d after 3-4 months of therapy. Biological therapies also appear to have a place in the therapeutic armamentarium for ANCA-associated systemic vasculitides, at least for patients whose disease is refractory to conventional therapy. However, the precise indications for anti-TNFalpha or anti-CD20 monoclonal antibodies and their optimal regimens (doses and durations) have not yet been defined. Anti-IL5, interferon-alpha and anti-IgE monoclonal antibodies might also be useful for Churg-Strauss syndrome. These biologics must be prescribed extremely cautiously and only in trial settings, especially in view of the adverse effects, few but severe, recently been reported with them.

Wegener's granulomatosis is described by the Chapel Hill nomenclature (1994) as a systemic necrotizing vasculitis affecting small to medium-sized vessels. Cytoplasm-labeling antineutrophil cytoplasmic autoantibodies (cANCA) directed against proteinase 3 (PR3) are detected in the sera of approximately 90% of patients. Reported incidence varies from 2 to 12 cases/million inhabitants/year and prevalence from 24 to 157 cases/million inhabitants, depending on the series. While still rare, incidence seems to have increased slightly over the past few decades. Most new cases involve adults aged 45-60 years. Many of the immune mechanisms involved in its pathogenesis have been identified. These involve cANCA as well as neutrophils, various lymphocyte subtypes, activation molecules, and cytokines. Genetic and environmental factors have been observed in some cases. However, the precise causes of the disease and of the initial immune process leading to cANCA production remain unknown. The most characteristic clinical manifestations are involvement of the upper and lower respiratory tracts and glomerulonephritis. Diffuse/systemic forms may be clinically distinguished from localized/limited forms: the former are mainly associated with vasculitis, and the latter with granulomatous inflammation. Diagnosis relies largely on the combination of characteristic clinical symptoms and cANCA anti-PR3, but histological confirmation should always be obtained when biopsy of affected organs is feasible and safe. Kidney biopsy is particularly useful in cases with renal manifestations, because it also provides some prognostic information. Current recommendations for treatment of systemic forms call first for an induction phase that combines corticosteroids and intravenous cyclophosphamide; the first three pulses are given every 2 weeks and then every 3 weeks until remission is achieved, followed by a maintenance phase with a less toxic immunosuppressant. The optimal duration of this regimen has not yet been determined, but it must certainly not be less than 18 months. Continuation of cotrimoxazole for two additional years is advised once immunosuppressants have been withdrawn. Remission is obtained in more than 85% of the cases to date, but the high relapse rate remains a matter of concern: approximately half of all patients will relapse within the five years following diagnosis. Promising new therapeutic agents, including rituximab, anti-TNF-alpha, and abatacept, are currently under evaluation and may substantially modify management of this disease in the years to come. Today, however, they are reserved for refractory cases.

Churg-Strauss syndrome is a systemic necrotizing vasculitis involving small and medium-sized vessels. Classic features include asthma and hypereosinophilia. Antineutrophil cytoplasm antibodies (ANCA) are detected in about 40% of patients. Churg-Strauss syndrome has been reported in patients receiving leukotriene modifiers for asthma, in particular, leukotriene receptor antagonists (LTRA) (montelukast, zafirlukast or pranlukast). Clinical manifestations cases do not differ in these cases from those in Churg-Strauss syndrome without antileukotriene exposure. It is increasingly less likely that LTRA is the direct cause of this syndrome in those patients, although this hypothesis has not been completely ruled out. In many patients, LTRA treatment is prescribed because of worsening asthma, which is an early sign of Churg-Strauss syndrome. LTRA for asthma patients should be prescribed with great care, especially in cases of atypical or rapidly aggravated asthma. The onset of Churg-Strauss syndrome in patients treated with LTRA usually requires that they stop this treatment. Prescription of LTRA In patients with Churg-Strauss syndrome should be discussed with specialists.

Vasculitides are defined by inflammation of blood vessel walls leading to vascular stenosis or occlusion, with various degrees of fibrinoid necrosis of the media and inflammatory infiltration, mainly neutrophilic and sometimes granulomatous. Various classifications of the vasculitides have been proposed. The classifications used most today are the 1990 American College of Rheumatology classification and the Chapel Hill nomenclature, published in 1994 . Only the latter distinguished between polyarteritis nodosa and microscopic polyangiitis and stressed the importance of antineutrophil cytoplasm autoantibodies (ANCA). In practice, primary systemic vasculitides are classified according to their clinical presentations, their precise histological features, and the size of the predominantly affected vessels. Some small-vessel vasculitides are associated with the presence of ANCA: 90% of patients with systemic Wegener's granulomatosis (mainly ANCA with cytoplasm labeling on indirect immunofluorescence and proteinase 3 specificity), 80% of the subjects with microscopic polyangiitis (mostly pANCA with myeloperoxidase specificity), and more than one third of those with Churg-Strauss syndrome (mostly pANCA).

Microscopic polyangiitis was initially considered a "microscopic" form of polyarteritis nodosa and was not definitively distinguished from it until the Chapel Hill nomenclature (1994). Microscopic polyangiitis is a systemic necrotizing vasculitis of small vessels. Its typical clinical manifestations are rapidly progressive glomerulonephritis and alveolar hemorrhage. Other possible symptoms resemble those encountered in polyarteritis nodosa. Microscopic polyangiitis belongs to the group of ANCA-associated vasculitides, and 75-80% of patients have pANCA to myeloperoxidase (MPO). Anti-MPO ANCA pathogenicity has been established in animal models, and a recent report describes transplacental transfer of these antibodies in humans, resulting in pulmonary hemorrhage and renal involvement in the newborn. Patients with no poor prognostic factors, as defined by a five-factor score, can be treated with corticosteroids alone, with immunosuppressants added only in case of treatment failure. Patients with one or more poor prognostic factors must receive a combination of corticosteroids and immunosuppressants, mainly intravenous pulsed cyclophosphamide, with plasma exchange as an adjuvant therapy for those with severe renal involvement. Once remission is achieved, maintenance therapy can replace cyclophosphamide by azathioprine or methotrexate. Biological therapies are under evaluation. The remission rate is above 80% with these regimens, and the relapse rate is around 30% at 5 years, lower than for Wegener's granulomatosis.

Objectives: This prospective study sought to assess the long-term outcome and identify prognostic factors of patients with kidney disease related to Wegener's granulomatosis (WG)., Methods: Of 50 patients with newly diagnosed WG who were enrolled between 1990 and 1993 in a trial comparing IV and oral cyclophosphamide (CYC), 37 had renal disease, either histologically proven or diagnosed based on laboratory findings. Their principal demographic, laboratory and therapeutic data, and progression to end-stage renal disease and/or death (ESRD) provided a basis for survival analysis, using Cox proportional hazards models., Results: Of the 37 patients (M/F ratio, 23/14; mean age, 55.1+/-12.1 years; antineutrophil cytoplasm antibody-positivity, 97%; ear-nose-throat involvement, 75%; pulmonary involvement, 78%; IV/oral CYC, 23/14), 36 had glomerulonephritis and one had a granulomatous renal tumor; 22 (59%) had initial serum creatinine levels >150 micromol/L. During a mean follow-up of 6.4+/-4.7 years, 15 (41%) patients died and two developed ESRD (10-year dialysis-free survival: 51+/-17%). Only one of the nine patients with renal relapses was alive without ESRD at the end of the study. According to uni- and multivariate analyses, dialysis-free survival was significantly shorter for patients with initial serum creatinine >150 micromol/L (10-year dialysis-free survival, 24+/-18% versus 89+/-21%) (hazard ratios=20.2 and 21.7; P<0.005), while the initial route of CYC administration did not influence outcome., Conclusion: These observations confirm the poor survival and functional outcome associated with renal involvement of WG and highlight the strong prognostic impact of renal function at diagnosis and of renal relapses during follow-up. Conversely, the initial route of CYC administration appears to have no effect on survival.