Microscopic polyangiitis (microscopic polyarteritis)

Microscopic polyangiitis ("microscopic polyarteritis") is a form of necrotizing small vessel vasculitis that most often affects venules, capillaries, arterioles, and small arteries, although it occasionally involves medium-sized arteries. Microscopic polyangiitis is a more appropriate name than microscopic polyarteritis because some patients have no evidence for arterial involvement. The absence or paucity of immunoglobulin localization in vessel walls distinguishes microscopic polyangiitis from immune complex mediated small vessel vasculitis, such as Henoch-Schonlein purpura and cryoglobulinemic vasculitis. Clinical, epidemiological, and pathologic differences warrant the separation of microscopic polyangiitis from polyarteritis nodosa on the basis of involvement of capillaries and venules by the former but not the latter. Pauci-immune necrotizing and crescentic glomerulonephritis, and hemorrhagic pulmonary capillaritis are common in patients with microscopic polyangiitis. Microscopic polyangiitis is the most common cause for pulmonary-renal vasculitic syndrome. The vasculitis in patients with microscopic polyangiitis is pathologically indistinguishable from the vasculitis of Wegener's granulomatosis and Churg-Strauss syndrome. Granulomatous inflammation distinguishes Wegener's granulomatosis from microscopic polyangiitis. Asthma and eosinophilia distinguish Churg-Strauss syndrome from microscopic polyangiitis. Microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome are all associated with circulating antineutrophil cytoplasmic autoantibodies.     

Diagnostic features and differential diagnosis of Churg-Strauss syndrome in the lung. A review

Churg-Strauss syndrome is a rare systemic vasculitis occurring in patients with asthma and blood eosinophilia. Lungs, skin, and nervous system are the most common sites of involvement, although many other organs are affected frequently. The diagnosis often is established from clinical findings or biopsy of extrapulmonary sites, and lung biopsy is performed infrequently. The classic pathologic findings in the lung include a combination of eosinophilic pneumonia, granulomatous inflammation, and vasculitis. All 3 features may not be present in every case, however, and diagnosis often requires careful correlation of the clinical and pathologic findings. The differential diagnosis in the lung includes diseases that are associated with eosinophil infiltrates or a combination of eosinophil infiltrates and granulomatous inflammation. Distinguishing these various diseases from Churg-Strauss syndrome is especially important, since many are more common than Churg-Strauss syndrome, and treatment is usually different.     

Churg-Strauss syndrome and sudden cardiac death.

Churg-Strauss syndrome is a rare disorder characterized by necrotizing vasculitis, granulomas with eosinophilic necrosis, and tissue infiltration by eosinophils. Sudden cardiac death is rarely described in Churg-Strauss syndrome. In this article, we describe a case of Churg-Strauss syndrome with multiorgan involvement manifested as sudden cardiac death. To the best of our knowledge, this form of presentation has not been reported. A 49-year-old woman was found dead in her room. No premonitory complaints had been noted during the days preceding her death. Past medical history did not reveal any relevant illness. At autopsy, multiorganic Churg-Strauss syndrome with prominent cardiac involvement was found. Therefore, this syndrome in the active vasculitic phase may be asymptomatic and may involve predominantly the heart. This variant of the syndrome may be fulminant and present as sudden cardiac death. This form can only be elucidated by autopsy study.     

A variant form of Churg-Strauss syndrome: initial temporal non-giant cell arteritis followed by asthma--is this a distinct clinicopathologic entity?

The clinical manifestations of the classical vasculitis syndromes are extraordinarily heterogenous with considerable overlap among them. Recently, several cases of unusual presentation of the vasculitis syndromes have been reported. We describe a patient who initially manifested with temporal arteritis and Raynaud's phenomenon and subsequently developed bronchial asthma, ie, a case of an atypical form of Churg-Strauss syndrome (allergic angiitis and granulomatosis) and discuss whether this case is a distinct clinicopathological entity.     

IgE-Containing Circulating Immune Complexes in Churg-Strauss Vasculitis

In five patients with vasculitis, hypereosinophilia, and elevated serum IgE levels a diagnosis of Churg-Strauss syndrome was established. To identify a possible role of IgE in pathogenic mechanisms leading to the vasculitis, we performed a sequential precipitation of the patients' sera with different concentrations of polyethylene glycol (PEG) 6000. Using a radio immunosorbent test, we tested the precipitates obtained for IgE. Considerable amounts of IgE were traced in the serum precipitates of all patients, especially after the second precipitation step (4.0% PEG). In contrast, no IgE-containing precipitates were detectable in sera from patients with different allergic diseases and high IgE serum levels. Together with an increase in C3d serum levels and the failure to demonstrate C1q-binding material in patients' sera, these data suggest the involvement of IgE-containing immune complexes in the pathogenesis of Churg-Strauss vasculitis, activating the complement via the alternate pathway.     

A case report of Churg-Strauss syndrome combined with various vessel diseases]

A 73-year-old woman with a three-year history of allergic rhinitis and bronchial asthma was found to have Churg-Strauss syndrome combined with fever, eosinophilia, mononeuritis multiplex, and acute coronary syndrome. After the treatment with a methylprednisolone pulse therapy and a high dose of corticosteroids were initiated, eosinophilia normalized together with decline of fever, but acute superior mesenteric artery occlusion occurred, which improved with conservative therapy. Severe stenosis of bilateral carotid arteries was found, so immunosuppressive drugs were added. In general, Churg-Strauss syndrome is a disease with vasculitis affecting small arteries, arterioles, venules, or capillaries, and cases with arteritis in large and medium-sized arteries, such as this case are rare. This suggested that in cases of Churg-Strauss syndrome of the elderly patients, physicians must be careful about involvement of larger vessels.     

Seven cases of complete and incomplete forms of Churg-Strauss syndrome not related to leukotriene receptor antagonists.

BACKGROUND: Various forms of Churg-Strauss syndrome have been reported in association with the use of leukotriene receptor antagonists in asthmatic patients. OBJECTIVE: Our purpose was to increase awareness that different forms of the Churg-Strauss syndrome occur in patients not receiving leukotriene modifiers. METHODS: We searched for all the cases of Churg-Strauss syndrome that were seen in the University of Rochester Medical Center, New York, in the past 4 years. RESULTS: We identified 7 patients, 6 of whom fulfilled the American College of Rheumatology criteria for the classification of Churg-Strauss syndrome. None of them used leukotriene receptor antagonists. All had asthma and sinus disease. The duration and severity of their asthma varied considerably. In the majority of the patients the features of Churg-Strauss syndrome became obvious as the systemic corticosteroid dose was being tapered or discontinued, although 3 patients had not been receiving maintenance oral corticosteroids at disease onset. Three patients had positive antineutrophil cytoplasmic antibodies test result (perinuclear pattern). There was histologic documentation of vasculitis in 4 patients. Five of 7 patients responded to high-dose corticosteroid treatment. CONCLUSION: Our 7 cases are similar to the various forms of Churg-Strauss syndrome that have been reported in association with the leukotriene receptor antagonists. Complete or incomplete forms of this syndrome can become apparent in asthmatic patients as systemic corticosteroids are being tapered but can also occur in patients with mild asthma of short duration who use only inhaled corticosteroids.     

Churg-Strauss syndrome: survival for 26 years.

BACKGROUND: Churg-Strauss syndrome (CSS), a necrotizing vasculitis characterized by asthma and eosinophilia, was described initially in 1951. Before the use of oral corticosteroids, the average patient survived for only a few months. Today with the use of oral corticosteroids and immunosuppressants, survival has increased significantly. METHODS: We report the case of a patient with CSS treated with prednisone and azathioprine. A review of the English literature was performed with MEDLINE from 1966 to the present using these keywords: Churg-Strauss syndrome, survival, prognosis, morbidity, mortality, and treatment. RESULTS: This patient survived 26 years after the diagnosis of CSS and died without autopsy findings of active vasculitis. This is the longest reported survival with CSS in the English literature to our knowledge. The patient's disease course was marked by two acute (vasculitic) episodes, with intermittent subacute disease, and finally a state of disease remission. CONCLUSIONS: Survival in patients with CSS can be prolonged with early initiation of corticosteroids and immunosuppressants, close outpatient followup, and prompt, aggressive treatment of relapses. This case exemplifies the disease progression and remission as reported by other authors. We propose that CSS can be classified into acute (vasculitic), subacute, and remittable stages.     

Renal Involvement in Wegener’s Granulomatosis

The term pauci-immune glomerulonephritis with vasculitis encompasses a group of auto-immune disorders, which includes Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and renal-limited vasculitis. Over the past few years, progress has been made in understanding the epidemiology and environmental and genetic risk factors of the role of antineutrophil cytoplasmic antibodies (ANCA) in kidney pathogenesis and the utilization of ANCA in diagnosis. However, certain aspects are still subject to debate including the classification and the place of ANCA in treatment.     

Immunkomplexe bei Allergien: Nachweis von IgE-haltigen Immunkomplexen bei der Vaskulitis Churg-Strauss

Summary In five patients with vasculitis, hypereosinophilia and elevated serum-IgE levels, the diagnosis of Churg-Strauss syndrome was established. To identify a possible role of IgE in pathogenic mechanisms leading to vasculitis, a sequential precipitation of patients' sera was performed using various concentrations of polyethylene glycol 6000 (PEG). Using a radioimmunosorbent test, the precipitates obtained were tested for their IgE contents. Considerable amounts of IgE were found in the serum precipitates of all patients. In parallel studies, no IgE-containing precipitates were detected in sera from patients with different allergic diseases and high IgE serum levels. The demonstration of IgE-containing PEG precipitable material in all patients suffering from Churg-Strauss syndrome, together with the finding of an elevated C3d and C4 level and a decreased C3 level in one patient and an increased C3d level in a second patient, suggests that IgE-containing immune complexes play a pathogenic role in the Churg-Strauss syndrome.

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Abkürzungen ARA American Rheumatism Association - CIC, IC Zirkulierende Immunkomplexe - C1q BA C1q Bindungstest - PEG Polyethylenglycol     

Churg-Strauss综合征的肺部病理形态学观察

目的 探讨Churg-Strauss综合征的临床及肺部病理特点.方法 收集3例Churg-Strauss综合征患者的临床资料并进行分析,对3例肺组织(包括1例尸检和2例开胸肺活检标本)行4%甲醛固定,常规石蜡切片,HE染色,观察病理改变.结果 2例男性,1例女性;年龄分别为68、58、12岁;3例均有反复哮喘,2例有外周血嗜酸性粒细胞计数升高,胸部CT示肺部有多发实变影,临床上有诊断Churg-Strauss综合征的线索.1例因累及心脏导致嗜酸性粒细胞浸润性心肌炎及血管炎,并发心肌梗死而死亡.显微镜下,3例均可见血管炎、血管周的过敏性肉芽肿、嗜酸性粒细胞肺炎和哮喘性支气管炎表现.结论 应对Churg-Strauss综合征有充分的认识,对有相关症状的患者,应复查CT;一些病例临床体征虽不典型,但肺部有典型的病理改变,必要时需进行肺部活检.     

Vasculitis from the dermatological point of view]

In vasculitis, dermatologists generally examine two kinds of patient who present with small-vessel vasculitis as defined by the Chapel Hill Consensus Conference nomenclature, and idiopathic cutaneous polyarteritis nodosa (CPN). CPN is a vasculitis of small and medium-sized arteries within the skin that does not involve internal organs. When these patients visit my clinic, I characterize the cutaneous manifestations at initial presentation and assess the histopathological findings. In systemic antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, the characteristic cutaneous clinical pattern of microscopic polyangiitis is livedo reticularis, whereas Churg-Strauss syndrome presents as purpura and petechiae with paresthesias on the lower extremities. When a patient presents with nodules on the elbows with histological palisading granuloma, diagnosis of three ANCA-associated vasculitis including Wegener's granulomatosis should be considered. In immune-complex-mediated vasculitis, Henoch-Sch?nlein purpura (HSP) is characterized by palpable non-thrombocytopenic purpura on initial clinical presentation. These clinical cutaneous investigations in vasculitis patients may allow us to refine our earlier diagnostic strategies. On the other hand, histological examination in a cryoglobulinaemic vasculitis patient revealed microvascular thrombus and leucocytoclastic vasculitis in the dermis. From these findings, I speculated that the presence of thrombosis may be somehow related to the pathogenesis of the vasculitis process and investigated the association between vasculitis, especially immune-complex-mediated vasculitis, and antiphospholipid antibodies (Abs). Serum levels of IgA anticardiolipin antibody (aCL) are elevated in the initial active stage of adult HSP, suggesting that the IgA aCL may play some role in the onset of adult HSP. We also suggest that CPN could be dependently associated with the presence of anti-phosphatidylserine-prothrombin complex Abs.     

Disorders characterized by predominant or exclusive dermal inflammation

Some cutaneous inflammatory disorders are typified by a predominant or exclusive localization in the dermis. They can be further subdivided by the principal cell types into lymphocytic, neutrophilic, and eosinophilic infiltrates, and mixtures of them are also seen in a proportion of cases. This review considers such conditions. Included among the lymphoid lesions are viral exanthems, pigmented purpuras, gyrate erythemas, polymorphous light eruption, lupus tumidus, and cutaneous lymphoid hyperplasia. Neutrophilic infiltrates are represented by infections, Sweet syndrome, pyoderma gangrenosum, and hidradenitis suppurativa, as well as a group of so-called “autoinflammatory” dermatitides comprising polymorphonuclear leukocytes. Eosinophil-dominated lesions include arthropod bite reactions, cutaneous parasitic infestations, the urticarial phase of bullous pemphigoid, Wells syndrome (eosinophilic cellulitis), hypereosinophilic syndrome, and Churg-Strauss disease. In other conditions, eosinophils are admixed with neutrophils in the corium, with or without small-vessel vasculitis. Exemplary disorders with those patterns include drug eruptions, chronic idiopathic urticaria, urticarial vasculitis, granuloma faciale, and Schnitzler syndrome (chronic urticarial with a monoclonal gammopathy).     

Rituximab in induction therapy for anti-neutrophil cytoplasmic antibody (ANCA) vasculitis

Anti-neutrophil cytoplasmic antibodies (ANCA) have been associated with a spectrum of vasculitis that includes granulomatous polyangiitis (formerly known as Wegener's granulomatosis), microscopic polyangiitis, the Churg-Strauss syndrome, primary pauciimmune necrotizing and crescentic glomerulonephritis and related forms of vasculitis. In vitro, in vivo and clinical evidence support the conclusion that ANCA participate in the pathophysiology of this disease spectrum. Rituximab is a potent tool that can interrupt B cell-mediated immunity without major compromise of T cell-mediated immunity. Thus, it has great appeal as a tool to interrupt antibody-mediated autoimmune disease. The results of two prospective randomized trials confirm that rituximab can be effective as part of induction therapy for active ANCA-associated vasculitis. The safety profile for rituximab appears favourable relative to cyclophosphamide and steroids. However, there remain many patients who require individualized adjustments of ancillary therapy, as breakthrough disease, relapses and infectious complications do occur. Based on our current knowledge, rituximab should now be incorporated as part of induction therapy in many patients with ANCA-associated vasculitis. However, more work is needed to determine how rituximab may best be integrated into the overall immunosuppression of these patients.     

Antineutrophil cytoplasmic antibody—A useful serological marker for vasculitis

Systemic necrotizing vasculitides, including polyarteritis nodosa, Churg-Strauss syndrome, overlap systemic vasculitis, Wegener's granulomatosis, and idiopathic crescentic glomerulonephritis, are frequent clinical diagnostic problems. These diseases have diverse presentations and are often rapidly progressive, causing irreversible injury to the vessels of the kidneys and lungs before effective immunosuppressive therapy is instituted. Even in their less fulminant forms, they are a cause of significant morbidity and mortality. Antineutrophil cytoplasmic antibody, a recently identified autoantibody, has a high sensitivity and specificity for this spectrum of diseases. The clinical and pathological similarities, the high frequency of antineutrophil cytoplasmic antibody expression, and the similar good response to immunosuppressive therapy suggest that these diseases may be linked by a common pathophysiological mechanism. Evidence is growing that antineutrophil cytoplasmic antibody plays a central role in this mechanism. A revision in the classification scheme of vasculitides to recognize that the polyarteritis group (polyarteritis nodosa, Churg-Strauss syndrome, and overlap systemic vasculitis), Wegener's granulomatosis, and idiopathic crescentic glomerulonephritis are closely related diseases may be warranted. The clinical and pathological features of systemic necrotizing vasculitides and the current knowledge concerning antineutrophil cytoplasmic antibodies are reviewed.     

Recent advances in the diagnosis of Churg-Strauss syndrome.

Most pathologists assume that a diagnosis of Churg-Strauss syndrome (CSS) requires the finding of necrotizing vasculitis accompanied by granulomas with eosinophilic necrosis in the setting of asthma and eosinophilia. However, recent data indicate that this definition is too narrow and that adherence to it leads to cases of CSS being missed. CSS has an early, prevasculitic phase that is characterized by tissue infiltration by eosinophils without overt vasculitis. Tissue infiltration may take the form of a simple eosinophilia in any organ, and a fine-needle aspirate showing only eosinophils may suffice for the diagnosis in this situation. The prevasculitic phase appears to respond particularly well to steroids. Even in the vasculitic phase of CSS, many cases do not show a necrotizing vasculitis but often only an apparently nondestructive infiltration of vessel walls by eosinophils. In modern biopsy materials, granulomas frequently cannot be found. In the postvasculitic phase of CSS, healed vascular lesions resemble organized thrombi but typically show very extensive destruction of elastica and, often, an absence of eosinophils. The widespread use of steroids as therapy for asthma has led to the peculiar and confusing situation in which the steroid therapy accidentally suppresses CSS and changes in steroid treatment uncover the disease; this type of "formes frustes" CSS is now well recognized with leukotriene receptor antagonist treatment and will be seen with increasing frequency as other steroid-sparing therapies for asthma are introduced.     

Ileal ulcers and cytomegalovirus infection in a case of Churg-Strauss syndrome

Churg-Strauss syndrome, or allergic granulomatous angiitis, is an uncommon vasculitic syndrome. We describe a 53-year-old man with Churg-Strauss syndrome and subsequent opportunistic cytomegalovirus enterocolitis. During intensive care, including steroid-pulse therapy, the patient developed rapidly progressive anemia caused by active bleeding from his small intestine, resulting in resection of 20 cm of ileum. Diagnosis of Churg-Strauss syndrome was confirmed both by characteristic clinical features and by histology. Histologic examination also revealed multiple shallow ulcers accompanied by cytomegalovirus infection. Characteristic angiitis was found in the ileum with normal-like mucosa, and it was not necessarily associated with ileal ulcers. This finding suggests that cytomegalovirus infection may be one of the causes or exacerbating factors for ileal ulcers in Churg-Strauss syndrome, although ulcers of the intestine have usually been considered to be caused by ischemia resulting from angiitis.     

Potential target of infliximab in autoimmune and inflammatory diseases

Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine produced by many cell types (blood monocytes, macrophages, mast cells and endothelial cells), that play a key role in the pathogenesis of multiple autoimmune and nonautoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well tolerated in patients with Crohn's disease, rheumatoid arthritis and spondiloarthritides and has become a widely used treatment for these diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists: Beh?et's disease, Churg-Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener's granulomatosis and sarcoidosis have been shown to improve with infliximab. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sj?gren's syndrome as evidenced by the lack of efficacy of TNF antagonists. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. A number of other more rare disorders also may be responsive to TNF blockade. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions.     

Churg-Strauss syndrome with necrosis of toe tips

Churg-Strauss syndrome (CSS) is a granulomatous necrotizing vasculitis of unknown etiology associated with bronchial asthma. Despite affecting small to medium-sized vessels, necrosis of the digits due to vasculitis is extremely rare. We report a case of CSS with necrosis of the toe tips. A 37-year-old woman with asthma, who had been diagnosed with CSS 2 years ago, was admitted to our hospital with an exacerbation of CSS. The patient had a high grade fever and complained of abdominal pain and numbness of the lower extremities. Blood examination revealed marked eosinophilia. The fever pattern, abdominal pain and blood eosinophilia showed improvement by combination treatment with prednisolone and cyclophosphamide. However, the color of her right toe tips changed, and necrosis finally resulted despite antithrombotic therapy. Arteriography showed narrowing of the dorsalis pedis artery and of the more peripheral arteries of her right leg. Stump plasty with negative pressure dressing therapy for the toe tips, but not amputation, was done to preserve the leg function. While numbness of the extremities remained, no recurrence of necrosis was seen. Clinicians need to be aware that rare complications of CSS, including necrosis of the digits, can occur.