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The nomenclature system agreed upon by the Chapel Hill Consensus Conference (CHCC) with respect to the terminology and precise definition of the various types of vasculitis has gained widespread interdisciplinary and international acceptance. As the revised version from 2012 (CHCC 2012) does not address the special features of vasculitis of the skin, it has recently been supplemented with an addendum containing the nomenclature of cutaneous vasculitides (D-CHCC). The present article provides the German translation of the terms and defintions of the D-CHCC as well as additional explanatory comments. The goal is to enable German-speaking health care providers to more readily apply these defined terms - which are based on interdisciplinary consensus - in everyday clinical practice and to facilitate assessment of their practicability and relevance in patient care. If the majority of cutaneous vasculitides diagnosed can be matched with any of the defined entities presented herein, it might subsequently be possible to develop a classification system and diagnostic algorithms., (© 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Objective: To prepare a dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (CHCC2012) to address vasculitides affecting the skin (D-CHCC). The goal was to standardize the names and definitions for cutaneous vasculitis., Methods: A nominal group technique with a facilitator was used to reach consensus on the D-CHCC nomenclature, using multiple face-to-face meetings, e-mail discussions, and teleconferences., Results: Standardized names, definitions, and descriptions were adopted for cutaneous components of systemic vasculitides (e.g., cutaneous IgA vasculitis as a component of systemic IgA vasculitis), skin-limited variants of systemic vasculitides (e.g., skin-limited IgA vasculitis, drug-induced skin-limited antineutrophil cytoplasmic antibody-associated vasculitis), and cutaneous single-organ vasculitides that have no systemic counterparts (e.g., nodular vasculitis). Cutaneous vasculitides that were not included in the CHCC2012 nomenclature were introduced., Conclusion: Standardized names and definitions are a prerequisite for developing validated classification and diagnostic criteria for cutaneous vasculitis. Accurate identification of specifically defined variants of systemic and skin-limited vasculitides requires knowledgeable integration of data from clinical, laboratory, and pathologic studies. This proposed nomenclature of vasculitides affecting the skin, the D-CHCC, provides a standard framework both for clinicians and for investigators., (© 2017, American College of Rheumatology.)

Purpose: We aimed to assess the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis., Methods: An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of (18)F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the (18)F-FDG PET results were compared using logistic regression models., Results: The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. (18)F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1-87.7%], a specificity of 83.9% (95% CI 66.3-94.5%), a positive predictive value of 81.5% (95% CI 61.9-93.7%) and a negative predictive value of 76.5% (95% CI 58.8-89.3%). The diagnostic accuracy of (18)F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p = 0.006). Taken in context with other available diagnostic modalities, the addition of (18)F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p = 0.04). The addition of (18)F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication., Conclusion: (18)F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patients.

Vasculitides are a heterogeneous group of inflammatory disorders of the blood vessels. The etiology and pathogenesis of vasculitides is incompletely understood, and the nomenclature and classification of vasculitides remains a challenge. A number of vasculitides were not included in the Chapel Hill Consensus (CHC) Conference definitions, thus, have remained 'unclassified', but may be included in a revised version of the nomenclature, e.g. Goodpasture's syndrome. In other cases the term 'unclassified' implies 'unclassifiable', i.e. a vasculitis cannot be assigned to any of the known entities. Vasculitis-induced acral necrosis including giant cell arteritis of small arteries as well as isolated forms of intestinal vasculitis including granulomatous giant cell polyphlebitis may belong to this category of rare 'unclassified' vasculitides. In some entities the relationship between vasculitis and other manifestations remains unclear, e.g. in Behçet's disease and IgG4-related systemic disease. In this review the clinical and pathological aspects of 'unclassified' vasculitides are briefly discussed.

gammadelta T-cells are a numerically small subset of T-cells with distinct features. They recognise antigens that are not seen by other immune cells. At the functional level, gammadelta T-cells share some features with alphabeta T-cells but also exert functions that are otherwise performed by specialised subsets of alphabeta T-cells (e.g. IL-17 production, regulatory activity). We discuss the potential role of gammadelta T-cells in various clinical forms of vasculitis.

Conventional immunosuppressive treatment of systemic vasculitides has improved their often fatal outcome, but is burdened by cytotoxic side effects and frequent relapses. Recent advances in the therapy of systemic vasculitides with biologicals have helped to establish new options for patients resistant to conventional treatment. Moreover, early intervention aiming to interfere with specific targets important in the break of tolerance and/or persistence of the autoimmune response might further improve the prognosis of autoimmune vasculitides such as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). In vitro and in vivo studies suggest that the interaction of ANCA and cytokine (TNF-alpha, IL-1)-primed neutrophils results in premature neutrophil activation and degranulation, subsequent endothelial cell damage, and further leukocyte recruitment. For one of the AAV, Wegener's granulomatosis, recent ex vivo data have provided evidence that WG-granulomata might provide the necessary "proinflammatory environment" for the break of tolerance and display features of lymphoid-like tissue neoformation, in which autoimmunity to "Wegener's autoantigen" proteinase 3 PR3 could be sustained. Blocking TNF-alpha and eliminating autoreactive B cells seem promising treatment targets to interfere with these fundamental disease processes. While the recombinant TNF-alpha receptor/IgG1 fusion protein etanercept, in addition to standard therapy with subsequent tapering of standard medications, was found to be not effective for maintenance of remission, open clinical studies suggest a beneficial effect of the anti-TNF-alpha antibody infliximab in addition to standard therapy for the induction of remission in patients with refractory AAV. Peripheral B cell depletion with the anti-CD20 antibody rituximab also induced remissions in AAV in uncontrolled trials.

Biological therapies enable us to apply highly selective targeting components to modulate the immune response. Until now, a few controlled studies investigated the efficacy of TNF-alpha blocking agents in systemic vasculitis have been carried out, but, in general, they were falling short of expectations. However, there is conducive evidence that TNF-alpha blockers are advantageous in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, at least in selected disease stages. Likewise, although the efficacy of the monoclonal CD20 antibody rituximab in ANCA-associated vasculitis is obvious, the effect on predominantly granulomatous disease activity in Wegener's granulomatosis is less clear. In addition, interferon-alpha is used for induction treatment particularly in Churg-Strauss syndrome. Even though the effectiveness and safety of short-term administration was confirmed by case series, severe side effects after long-term treatment relativized the initial results. This review presents the recent data on the use of biologicals in vasculitis and appraises the knowledge in the clinical context.

Antineutrophil cytoplasmic autoantibody-(ANCA-)associated vasculitides, immune complex-mediated vasculitides and granulomatous arteritides of unknown etiology belong to the group of primary systemic vasculitides. Numerous in vitro and in vivo studies have underscored the role of ANCA in the pathogenesis of ANCA-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) in the meantime. Whereas the pathogenicity of myeloperoxidase (MPO) ANCA has been supported by data from various animal models in the past, the in vivo pathogenicity of proteinase 3 (PR3) ANCA has been demonstrated in an animal model only recently. Other studies showed an altered T-cell response in Wegener's granulomatosis. Hepatitis C virus-(HCV-)associated cryoglobulinemic vasculitis is mediated by immune complexes. Recent data suggest that the HCV core particles concentrated in the cryoprecipitate apparently play a role in the interaction of cryoglobulin and endothelial cells and neutrophil granulocytes. Data from the European Vasculitis Study Group (EUVAS) demonstrate the efficacy of azathioprine in maintaining remission in ANCA-associated vasculitides on the basis of large patient numbers. Biologicals play an increasing role in the treatment of refractory vasculitis.

The introduction of TNF-alpha inhibitors in the treatment of rheumatoid arthritis and several other diseases meant a major progress in the management and to the understanding of these chronic inflammatory diseases. In this article, the evidence of the role of TNF-alpha and for TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases is reviewed. TNF-alpha is expressed in inflammatory lesions. TNF-alpha acts as a proinflammatory cytokine in most disease processes analyzed so far, but it might have anti-inflammatory properties under certain conditions as well, e.g. with respect to B-cell regulation in systemic lupus erythematosus. It is not clear to what extent such aspects will be important in the treatment of connective tissue diseases and systemic vasculitides with TNF-alpha inhibitors. So far, most case reports and case series have suggested favourable results with TNF-alpha inhibitor therapy in systemic lupus erythematosus, dermato- and polymyositis, giant cell arteritis, Churg-Strauss syndrome, Wegener's granulomatosis and microscopic polyangiitis. Results of randomized, placebo-controlled trials are awaited for several connective tissue diseases and systemic vasculitides. One randomized, placebo-controlled trial has found no efficacy of infliximab treatment in primary Sjögren's syndrome recently.

Wegener's granulomatosis (WG), microscopic polyangiitis, and Churg-Strauss syndrome belong to the group of ANCA-associated vasculitides. Numerous in vitro studies underscored the role of antineutrophil cytoplasmic antibodies (ANCA) in the pathogenesis of vasculitis. More recently, a mouse model provided in vivo evidence of the pathogenic role of ANCA by inducing a vasculitis after the transfer of splenocytes or MPO-ANCA. The target antigens of ANCA, myeloperoxidase (MPO) and proteinase 3 (PR3), are translocated onto the cell surface after priming of neutrophil granulocytes with cytokines. ANCA bind to target antigens and activate neutrophil granulocytes resulting in premature degranulation and endothelial cell damage (ANCA-cytokine sequence theory). Both the F(ab')2 end and the FcgammaR(eceptor) end of the ANCA are involved in activating neutrophil granulocytes. This mode of activation might account for differences to normal neutrophil activation via the FcgammaR. In addition, an expansion of T-cells lacking the co-stimulatory molecule CD28 is seen in WG suggesting an altered cellular immune response. Data from European multicenter studies demonstrated, among other things, that azathioprine can be used for the maintenance of remission after successful induction of remission with cyclophosphamide in ANCA-associated vasculitides.

Objective: To examine concentrations of circulating antibodies targeting C3a and C5a complement receptors in antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) and analyze their association with disease activity. Methods: Concentrations of antibodies against C3a and C5a complement receptors (anti‐C3aR and anti‐C5aR) and plasma complement fragments C3a and C5a were determined in patients with AAV (n = 110; granulomatosis with polyangiitis [GPA; n = 82] or microscopic polyangiitis [MPA; n = 28]), systemic lupus erythematosus (SLE) patients as disease controls (n = 36), and healthy donors (n = 220). C3aR and C5aR expression by circulating neutrophils, monocytes, and T cells was analyzed using flow cytometry. Clinical data were assessed at time of serum sampling and during follow‐up for 60 months. Results: In AAV, anti‐C3aR and anti‐C5aR antibodies were decreased (P = 0.0026 and P ≤ 0.0001, respectively). In remission, anti‐C3aR antibody concentrations rose to values comparable to healthy donors, whereas anti‐C5aR antibody concentrations did not. In GPA, anti‐C5a and anti‐C5aR antibody concentrations inversely correlated with each other (r = −0.6831, P = 0.0127). In newly diagnosed GPA, decreased concentrations of anti‐C5aR antibodies but not anti‐C3aR antibodies were associated with disease activity (P = 0.0009). Moreover, low anti‐C5aR antibodies were associated with relapse in GPA (hazard ratio 3.54, P = 0.0009) and MPA (hazard ratio 4.41, P = 0.0041). The frequency of C5aR‐expressing cells within T cell populations was increased in GPA (P = 0.0021 for CD4+ T cells; P = 0.0118 for CD8+ T cells), but not in MPA. Conclusion: Low concentrations of anti‐C5aR antibodies reflect disease activity and are associated with an increased risk for relapse in AAV. [ABSTRACT FROM AUTHOR]

Summary: The term "vasculitis" refers to a group of rare immune‐mediated diseases characterized by the dysregulated immune system attacking blood vessels located in any organ of the body, including the skin, lungs, and kidneys. Vasculitides are classified according to the size of the vessel that is affected. Although this observation is not specific to small‐, medium‐, or large‐vessel vasculitides, patients show a high circulating neutrophil‐to‐lymphocyte ratio, suggesting the direct or indirect involvement of neutrophils in these diseases. As first responders to infection or inflammation, neutrophils release cytotoxic mediators, including reactive oxygen species, proteases, and neutrophil extracellular traps. If not controlled, this dangerous arsenal can injure the vascular system, which acts as the main transport route for neutrophils, thereby amplifying the initial inflammatory stimulus and the recruitment of immune cells. This review highlights the ability of neutrophils to "set the tone" for immune cells and other cells in the vessel wall. Considering both their long‐established and newly described roles, we extend their functions far beyond their direct host‐damaging potential. We also review the roles of neutrophils in various types of primary vasculitis, including immune complex vasculitis, anti‐neutrophil cytoplasmic antibody‐associated vasculitis, polyarteritis nodosa, Kawasaki disease, giant cell arteritis, Takayasu arteritis, and Behçet's disease. [ABSTRACT FROM AUTHOR]

Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with polyangiitis (GPA), a neutrophil-driven autoimmune disorder, is characterized by necrotizing inflammation predominantly of the respiratory tract and an anti-neutrophil cytoplasmic autoantibody (ANCA)-associated systemic necrotizing vasculitis. Defective regulation of neutrophil homeostasis and cell death mechanisms have been demonstrated in GPA. Disturbed efferocytosis (i.e., phagocytosis of apoptotic neutrophils by macrophages) as well as cell death-related release of damage-associated molecular patterns (DAMP) such as high mobility group box 1 (HMGB1) contribute to chronic non-resolving inflammation in GPA. DAMP have been shown to induce innate as well as adaptive cellular responses thereby creating a prerequisite for the development of pathogenic autoimmunity. In this review, we discuss factors contributing to as well as the impact of regulated cell death (RCD) accompanied by DAMP-release as early drivers of the granulomatous tissue inflammation and autoimmune responses in GPA. [ABSTRACT FROM AUTHOR]

The authors comment on an editorial on the subclassification of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) which suggested dissecting AAV into non-severe AAV, severe PR3-AAV and severe myeloperoxidase (MPO-AAV). Topics include the basis of the subgrouping, difference in the subgroups of ANCA-positive and -negative eosinophilic granulomatosis with polangiitis (EGPA), and possible impact of age-related immunological factors on phenotypic differences among the AAV.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the impact of F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis. Methods: An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the F-FDG PET results were compared using logistic regression models. Results: The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1-87.7%], a specificity of 83.9% (95% CI 66.3-94.5%), a positive predictive value of 81.5% (95% CI 61.9-93.7%) and a negative predictive value of 76.5% (95% CI 58.8-89.3%). The diagnostic accuracy of F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p = 0.006). Taken in context with other available diagnostic modalities, the addition of F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% ( p = 0.04). The addition of F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication. Conclusion: F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patients. [ABSTRACT FROM AUTHOR]

Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg–Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/ RING1/ RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing ‘NK-like’ T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity. [ABSTRACT FROM AUTHOR]

Background: Secondary vasculitis represents a rare extraintestinal manifestation of Crohn''s disease (CD). Appropriate and prompt diagnosis is often delayed by uncertainties about the relationship of the vasculitic manifestations and CD. Objective: To describe our experience with vasculitis in CD and review the literature with respect to different manifestations and pathophysiological aspects of extraintestinal vasculitic manifestations of CD. Methods: We report 2 new cases of CD with secondary small-vessel vasculitis. We also extensively review the literature (1960-2007) using a broad range of key words related to secondary vasculitis in CD. Relevant publications were evaluated for the number of reported patients and manifestations of vasculitis. Results: Vasculitis is a rare extraintestinal manifestation of CD. Different types of vasculitis affect large-, medium-, and small-sized vessels associated with CD. Common immunologic features include intestinal inflammation as well as an infiltration of γδ-T-cells and/or Th1-type cells into vessel walls. The 2 new cases of secondary vasculitis in CD reported here reflect 2 major types of CD-related inflammatory vascular disorders. The first involves the central nervous system, while the second represents circumscribed Musculus gastrocnemius involvement (so-called “gastrocnemius myalgia syndrome”). Successful treatment of refractory secondary vasculitis in CD with an anti-tumor necrosis factor-α antibody is shown for the first time. Conclusion: Vasculitis secondary to CD is an uncommon finding. Therefore, it has to be carefully differentiated from other forms of primary or secondary vasculitis with intestinal involvement. Treatment with an anti- tumor necrosis factor-α antibody may prove a treatment option in vasculitis as an extraintestinal manifestation of CD. [Copyright &y& Elsevier]

Wegener’s granulomatosis (WG) is an autoimmune disease characterized by granulomatous lesions and a necrotizing vasculitis. Th1-type-cells lacking CD28 are expanded independent of age and immunosuppressive therapy in WG. To address their migratory properties of CD4+CD28− T-cells we studied the expression of the inducible inflammatory Th1-type chemokine receptor CCR5 in localized WG and generalized WG. Expansion of CD4+CD28− T-cells was more prominent in generalized WG compared to localized WG. In localized WG a larger fraction of CD4+CD28− T-cells displayed CCR5 expression compared to generalized WG. CCR5 expression was also higher in granulomatous lesions in localized WG. Higher levels of CCR5 expression on CD4+CD28− T-cells in localized WG may favor stronger CCR5-mediated recruitment of this T-cell subset into granulomatous lesions in localized WG. Expansion of Th-1-type CD4+CD28−CCR5+ effector memory T-cells might contribute to disease progression and autoreactivity, either directly, by maintaining the inflammatory response, or as a result of bystander activation. [Copyright &y& Elsevier]

ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites. [ABSTRACT FROM AUTHOR]

We report on a 78-year-old patient with severe disease manifestations including polyneuropathy and clinically suspected secondary temporal arteritis due to hepatitis C virus-associated cryoglobulinemic vasculitis (CV). Despite intermittent intravenous pulse cyclophosphamide therapy and oral corticosteroid therapy her condition further deteriorated. Only oral cyclophosphamide therapy with high-dose corticosteroid and plasmapheresis was efficient in inducing a remission of her CV. This case report demonstrates that pulse cyclophosphamide therapy may not be sufficient to control severe manifestations of cryoglobulinemic vasculitis. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility. [ABSTRACT FROM AUTHOR]