Search

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.)

Central nervous system (CNS) vasculitides are a heterogeneous group of diseases that can lead to severe disability and death. Given the poor performance of available diagnostic procedures (magnetic resonance imaging, angiography and brain biopsy), the diagnosis of isolated CNS vasculitis is challenging. Differential diagnosis includes secondary CNS vasculitides (infection, cancer, drug exposure or systemic inflammatory disorders) and several non-inflammatory cerebral vasculopathies, such as the reversible cerebral vasoconstriction syndrome. Despite recent advances in neuroradiology and the publication of large retrospective case series, primary angiitis of the CNS remains a heterogeneous and challenging nosological entity. Prospective interdisciplinary studies are necessary to improve our approach to these patients., (Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier 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.)

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.

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.

Systemic vasculitides are characterized by different histological aspects: fibrinoid necrosis of the arterial wall, giant cell arteritis, non-necrotizing arteritides without granuloma or giant cell infiltration. Each histological form is associated with a spectrum of diseases with variable clinical expression: giant cell angeitides, such as Takayasu's arteritis and giant cell arteritis, necrotizing angeitides, such as polyarteritis nodosa, Kawasaki disease, Wegener's granulomatosis, Henoch-Schönlein purpura or Churg-Strauss syndrome. The detection of anti-neutrophilic cytoplasmic antibodies (ANCA) also makes it possible to classify necrotizing vasculitides by isolating a group of diseases different from necrotizing vasculitidies without ANCA (Wegener's granulomatosis, microscopic polyangitis, allergic granulomatous angiitis).

Wegener's granulomatosis and microscopic polyangiitis are among the main systemic necrotizing vasculitides predominantly affecting small vessels. Their prevalences range from 24 to 157 cases per million inhabitants. Mean age at onset is usually 40 to 60 years old. Most common and suggestive features of Wegener's granulomatosis are upper (sinusitis, crusting rhinitis, saddle nose deformity, otitis media) and lower (excavated lung nodules, alveolar hemorrhage) respiratory tract, and kidney involvements. Alveolar hemorrhage and crescentic necrotizing glomerulonephritis are also characteristic manifestations of microscopic polyangiitis. Mononeuritis multiplex and necrotic purpura are frequent symptoms in both diseases. Antineutrophil cytoplasm autoantibodies (ANCA) directed against proteinase 3 can be found in the serum of 90% of the patients with diffuse forms of Wegener's granulomatosis, whereas ANCA with anti-myeloperoxidase specificity, whose pathogenic role is now well documented, can be detected in more than 60% of those with microscopic polyangiitis. Histologically, Wegener's granulomatosis can be differentiated from its counterpart when the inflammatory infiltrates have a granulomatous pattern. Therapy relies on the combination of corticosteroids and pulse intravenous cyclophosphamide, which can be switched, as soon as remission is achieved, to azathioprine or methotrexate, for a total duration of treatment of at least 18 months. Ten-year survival rate now exceeds 80%, but relapses are frequent. The precise place of new biologics, such as rituximab, needs to be further defined.

The treatment of necrotizing vasculitides may be based on several drugs, depending on the disease itself, its severity, its etiology and the expected prognosis. In practice, the least severe forms, associated with a prognostic score of 0, may be treated with corticosteroids only, while the ones associated with severity factors should be treated with an association of corticosteroids and immunosuppressants. The first-line treatment of viral-associated vasculitides should be based on antiviral drugs. The treatment duration of non-infectious vasculitides is typically 18 to 24 months. The improvement in prognosis is due to the treatment as well as to anti-infectious prophylaxis and careful management of potential complications.

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.

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.

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.

Introduction: Endobronchial stenoses are rare in the course of Wegener's granulomatosis, and they occur even more rarely than subglottic stenoses., Exegesis: We report seven cases of endobronchial stenoses in the setting of Wegener granulomatosis. Neither the pulmonary symptoms nor the systemic manifestations of vasculitis were specific. However 6/7 patients presented a wheezing or an hemoptysis. Bronchial endoscopy has permitted the diagnosis in all cases. Local evolution was cicatricial and symptomatic stenosis in 3 cases (42,8%)., Conclusion: Thus these lesions must be research in any case of pulmonary abnormality in the course of Wegener's granulomatosis, because they may lead to a pejorative prognosis. Moreover general and local treatment must be given early (at the inflammatory stage). After this stage, the local treatments are difficult and not efficient.

Introduction: Focal myositis constitutes an original and rare pathological entity, characterized by a localized inflammation within skeletal muscle, presenting as a soft tissue painful tumefaction. Diagnosis requires histological confirmation because of its non-specific clinical feature and the numerous differential diagnoses., Exegesis: We report a 27 year-old man who presented with suggestive symptoms of focal myositis. MR imaging and echography were compatible with this diagnosis but also demonstrated the existence of a vascular component within the tumefaction. The diagnosis of a benign vascular malformation with intramuscular development was made by a surgically guided biopsy., Conclusion: Vascular malformations are histologically heterogeneous with extremely variable clinical expressions. When they develop within skeletal muscle, they may mimic focal myositis. Hence, their diagnosis has to be evoked before performing muscle biopsy, because of the potential hemorrhagic risk.

Digestive involvement is frequent during the course of systemic small and medium-sized vessel vasculitides. Clinical manifestations range from rapidly regressive abdominal pain to surgical manifestations associated with poor prognosis. These are usually associated with extra-abdominal signs, reflecting vasculitis activity. Isolated gastrointestinal involvement is observed in only 16% of these patients. The main clinical manifestations are common to all vasculitides (ischemia, bowel infarction and perforations, gastrointestinal hemorrhage due to mucosal ulcerations or aneurysmal ruptures), but some are more specific to one type (granulomatous ileo-colitis during Wegener's granulomatosis, eosinophilic colitis during Churg-Strauss syndrome). Gastrointestinal arteriography can be helpful for diagnosis, but has no prognostic value, likewise for the presence of ANCA. As there are no identified factors predictive of a surgical abdomen, therapy must be adapted individually, using steroids and immunosuppressive agents, generally cyclophosphamide. Prompt surgical and medical care of these seriously ill patients has lowered mortality from nearly 100% twenty years ago to approximately 23 to 56% currently.

Introduction: Langerhans'cell histiocytosis is a rare and mainly pediatric disease. Patients with hepatic involvement usually have a disseminated form of the disease, with poor prognosis. Sclerosing cholangitis can occur in 10 to 15% of multivisceral Langerhans'cell histiocytosis. We report the case of a 56-years-old patient who developed sclerosing cholangitis 12 years after the diagnosis of Langerhans'cell histiocytosis., Exegesis: A 56-years-old man was admitted because of rapid general health impairment with epigastric pain. He was diagnosed as having Langerhans'cell histiocytosis 12 years ago because of a diabetes insipidus. Lungs were involved and during follow-up vertebral osteocondensation also developed. However, Langerhans'cell histiocytosis was clinically silent at the time of admission, without any treatment. Biologically, cholestasis and inflammation were noted. Digestive radiological investigations (echo-endoscopy, CT-scan, MRI) showed homogenous hepatomegaly and a diffuse infiltration of intra and extrahepatic bile ducts. Liver biopsy yielded the diagnosis of sclerosing cholangitis. Clinical and biological improvement occurred with oral corticosteroids (at 12 months after sclerosing cholangitis diagnosis)., Conclusion: Sclerosing cholangitis is a potential complication of Langerhans'cell histiocytosis, mainly in its multivisceral form. It can occur at a median of 2 years after diagnosis in children, but occasionally much later in adults, whereas Langerhans'cell histiocytosis seems quiescent. Diagnosis is supported by radiological investigations and liver biopsy. As no drug therapy appears clearly effective, liver transplantation must frequently be considered in these patients.

Emphysematous pyelonephritis is a rare, life-threatening complication of upper urinary tract infections, characterized by the presence of gas in renal parenchyma and perirenal space. It occurs in 90% of cases in diabetic patients and E coli is the most common causative germ. The pathogenesis probably involves several factors including enhanced proliferation of microorganisms due to altered immune defences, mixed acid fermentation of glucose leading to gas production, and decreased elimination of the gas because of impaired tissue perfusion. Diagnosis is often delayed because the symptoms may be non-specific, as illustrated by the two cases we report herein. In patients with diabetes and febrile urinary tract infection, obstruction of the urinary tract should first be eliminated by echography. Then, if the infection does not rapidly respond to antimicrobial therapy, a scan should be performed. Aggressive management including correction of hemodynamics, parenteral antimicrobial therapy, and diabetes control with insulin therapy is mandatory, but a surgical procedure (nephrectomy or drainage) is almost always required.