Roadmap to vasculitis: a rheumatological treasure hunt: Part II. Classification,features of individual vasculitides and differential diagnosis against pseudovasculitis

Since the triggering factors causing primary vasculitides are by definition not (yet) known, we have to classify them to clinical syndromes based on the size, site, type and effect of the blood vessel involvement. ACR classification criteria and Chapel Hill nomenclature are useful tools to familiarize with the primary vasculitides, although a lot of criticism has been voiced in the literature indicating that they only represent the best available consensus. The present text takes advantage of the recent developments such as introduction of the anti-neutrophilic cytoplasmic auto (ANCA) antibodies, and divides the vasculitides to those affecting typically the large, medium and small arteries or only small blood vessels. In addition, some vasculitides, which are still difficult to place to the vasculitis map, like Bürger's disease, Goodpasture's syndrome, primary angiitin of the central nervous system (PACNS) and panniculitis, are dealt with. As it is a long and winding road, attention has to be paid to the clinical details to follow the road sign to “pseudovasculitis”, when that is the right way to go. They represent a bunch of non-vasculitic conditions, which lead to structural or vasospastic impairment of the blood flow, bleeding or thromboembolism and hyperviscosity. These imitators have to some extent, similar clinical symptoms and signs as well as laboratory and radiological findings to those found in true systemic vasculitides. This also emphasizes the importance of internal medicine as the intellectual (albeit not necessarily organizational) home of rheumatology and rheumatologists as we deal with conditions like atherosclerosis, antiphospholipid antibody syndrome, infectious endocarditic, myxoma of the heart and cholesterol embolism.     

"Essential" cutaneous vasculitis: what every rheumatologist should know about vasculitis of the skin

Although the classification of small-and medium-vessel vasculitides involving the skin remains complex and imperfect, a substantial body of knowledge related to cutaneous vasculitis exists. Some components of this knowledge, though beyond the usual purview of rheumatologists, are essential to understanding the vasculitides. The correct interpretation of cutaneous findings combined with a properly performed skin biopsy yields important insights not only into underlying diagnoses, but also into the pathophysiological mechanisms of individual cases. In this review, we discuss a classification scheme for the cutaneous vasculitides, outline the work-up for evaluating patients with these disorders, and describe the essential features of the major categories of skin vasculitis.     

Abdominal and digestive manifestations in systemic vasculitides

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.     

Therapeutische Strategien im Frühstadium der systemischen Sklerose

Increasing knowledge about the rare disease systemic sclerosis and improved diagnostic methods in the course of recent decades has led to the possibility of diagnosing systemic sclerosis at earlier disease stages. However, earlier diagnosis has an impact on routine clinical care of affected patients, and rheumatologists need to know about early symptoms, their diagnosis, and clinical management. In this review, the therapeutic management of early disease stages is described. In particular, we focus on diagnostic tools which should be included in a “basic assessment” of systemic sclerosis and discuss the diagnosis and treatment options of early symptoms such as Raynaud phenomenon, puffy fingers and hand edema, digital ulcers, calcinosis cutis, and cardiopulmonary, renal, and gastrointestinal involvement. Finally, the options of early immunosuppressive treatment and autologous stem cell transplantation for patients with rapid progressive and severe disease are reviewed.     

Früher Lupus erythematosus

Early diagnosis of systemic lupus erythematosus (SLE) is a challenge even for experienced rheumatologists due to the heterogeneous appearance of the disease. The initial phase of SLE often comprises unspecific general symptoms and only few characteristic clinical and laboratory abnormalities in the early course. Seriously affected patients meet the classification criteria in early stages but many other affected patients do not. A concentration only on young women as possible new cases means that more than 50?% of all persons affected will not be identified. Therapy is mainly guided by the type and severity of symptoms. Organ manifestations need to be examined at each presentation because there is a high possibility for modification in the course of the disease especially in the early stages. Early intervention should prevent increasing damage. Key elements of medical treatment are antimalarial agents. Furthermore, control of co-morbidities and optimization of lifestyle are crucial.     

Vasculitis and the gastrointestinal tract

Vasculitis, defined as a non-infectious inflammatory disorder of blood vessels, can affect vessels of any type in any organ. The gastrointestinal (GI) tract may thus also be involved. In systemic disorders as mixed connective tissue disease (MCTD) and systemic lupus erythematodes (SLE), patients may present with symptoms of gastrointestinal disfunction such as motility disorders, caused by alterations in the connective tissue. True vasculitis however also occurs in the GI tract. Severe, occlusive damage often leads to ischemia that may result in ulceration and perforation. Non-occlusive vascular disease may lead to vascular leakage resulting in oedema and haemorrhage. Those patients often present with diarrhoea or symptoms of bleeding. GI involvement is frequent in Henoch-Sch?nlein purpura and also often noted in polyarteritis nodosa (PAN), microscopic polyangiitis, Wegener's syndrome and Churg-Strauss syndrome. Furthermore, GI vasculitis has also been described in giant cell arteritis, Takayasu's disease, Buerger's disease and leucocytoclastic vasculitides as essential mixed cryoglubulinemia, lupus vasculitis, rheumatoid disease, MCTD, drug-induced vasculitis and Beh?et's disease. The diagnosis and classification of vasculitis relies upon a combination of clinical, serological, haematological, radiological and histological findings. Establishing a precise diagnosis can be difficult but is important because treatment and prognosis can be highly variable.     

Rheumatological medicine literacy among Middle Eastern populations

Background: It has been observed for years that many Middle Eastern patients with autoimmune rheumatic disorders, are more likely to be delayed in seeing a rheumatologist for their symptoms and that the rheumatology services are in general under‐utilized by the population. Aim: To explore if patients with autoimmune rheumatic disorders were truly delayed in seeing rheumatologists and to explore the possible reasons for that delay should any delay be documented. Subjects and methods: Patients suffering from chronic autoimmune rheumatic disorders were interviewed and were asked to answer a questionnaire that assesses their initial set of actions when they had their first symptoms of disease, how much time they took to see a rheumatologist and their background knowledge about rheumatology as a specialty before and after they saw a rheumatologist. Results: Seventy‐eight patients, 57 (73%) females and 21 (27%) males were included in this study. Their ages ranged from 11 to 72 years with a mean of 38.9 ± 13 years. Patients’ explanations for their initial symptoms were ‘evil eye doing’, disease, exertion, cold weather and trauma in 44%, 37%, 20%, 16% and 8% respectively. Ninety‐six percent of patients had to make a total of 166 consultations first at other specialties before they were finally advised or directed to see a rheumatologist. Non‐rheumatologist referrals to rheumatologists happened in only 33% of the time. The duration from the onset of the disease until patients finally came to see a rheumatologist ranged from 0.5 weeks to 432 weeks with a mean of 51 ± 88 weeks. Conclusions: General health literacy and knowledge of the rheumatology scope of service is extremely limited among Middle Eastern patients. Most patients with autoimmune rheumatic diseases make their initial consultations at clinics other than rheumatology clinics and non‐rheumatologists have been shown to consistently not refer patients with rheumatic diseases to rheumatologists. Wrong diagnosis is attributed to rheumatology symptoms by non‐rheumatologists 82% of the time. Level of education of patients, has no impact on their choice of the right specialty to be consulted for their disease symptoms.     

National survey of knowledge,attitude and practice of fibromyalgia among rheumatologists in China

Aim

Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain and fatigue. It is a less frequently diagnosed disease in China, thus Chinese rheumatologists may have lower awareness of FM compared with colleagues in Western countries. The aim of this study is to investigate the perceptions of FM in Chinese rheumatologists and analyze their therapeutic approach in clinical practice.

Method

An anonymous questionnaire survey was conducted among a nationwide sample of Chinese rheumatologists at the 15th National Rheumatology Conference in 2010. The 20‐question survey included questions regarding background, work experience, perceptions of diagnosis and behaviors of treatment related to FM. Continuing medical education (CME) information was also collected in the survey.

Results

Seven hundred and seven rheumatologists responded to the questionnaire, a response rate of 60%. Less than one‐fifth of the respondents were experienced in dealing with FM. Although most of the respondents regarded FM as a distinct pathological entity, nearly 30% of Chinese rheumatologists believed that FM was only a psychological disorder. The respondents recognized some of the FM‐related symptoms, but had limited knowledge on the diagnostic criteria. Eighty percent of the respondents declared they had difficulties in treating FM patients. However, nearly all (90.8%) respondents believed that the prognosis of FM patients was usually benign. Our data also showed that most Chinese rheumatologists were eager for CME on FM.

Conclusion

The awareness and perception of FM are still low among Chinese rheumatologists. CME on FM is needed for improving the quality of health care in China.     

Circulating endothelial cells and vasculitis

Systemic vasculitides are a heterogeneous group of disorders with inflammation of blood vessels as their common pathogenetic hallmark. They often pose difficulties with regard to diagnosis and monitoring of disease activity, both at the initial presentation and during follow-up. Novel markers of disease activity are therefore eagerly awaited. Circulating endothelial cells have recently emerged as one such marker and we have demonstrated their clinical use in ANCA-associated small-vessel vasculitis. Not only entire cells but also endothelial microparticles can be detected in vasculitis although their use is not established to date. Repair of endothelial damage is believed to occur via endothelial progenitor cells and their precise role in vasculitis is also unclear at present. Circulating endothelial cells may complement, rather than replace, conventional markers of disease activity. The ultimate aim of our studies may thus be a panel of various laboratory markers for systemic vasculitis.     

Lower extremity entrapment neuropathies

Entrapment neuropathies are frequently encountered by rheumatologists, not only because they are common but also because of their association with certain rheumatological and systemic disorders. Recognizing entrapment neuropathy early can help avoid progressive neurological deficits, as well as facilitate appropriate treatment measures, which can effectively minimize a patient's symptoms. Entrapment neuropathies may be distinguished from other musculoskeletal causes of lower extremity pain by identifying characteristic patterns of weakness and/or sensory loss, so a focused bedside neurological examination is key for diagnosis. In this chapter, we review the most common entrapment neuropathies that occur in the lower extremities, review the relevant neuroanatomy, outline a diagnostic approach to distinguish them from other mimics, and highlight appropriate management options.     

Biologic immunomodulatory therapies in the vasculitic diseases

The expanding range of biologic agents capable of modulating the immune response has opened up a new realm for therapeutic exploration in the vasculitic diseases. Partnered with increasing knowledge regarding the mechanisms of vascular inflammation, these agents have raised the question as to whether it may be possible to treat systemic vasculitis syndromes by selectively targeting pathways involved in disease pathogenesis. The action of these agents to directly modulate specific immunologic components offers the potential not only to impact disease activity but also to reduce the risk of morbidity that can result from currently available treatment options. The study of biologic therapies in the vasculitides must, however, be approached with caution because unanticipated effects on disease activity and disease-specific toxicities can occur. The only biologic agent that has currently been shown to have therapeutic efficacy in a systemic vasculitis syndrome is interferon-alpha in the treatment of hepatitis C-associated cryoglobulinemic vasculitis. The use of biologic agents to treat other vasculitides remains investigational. Methodical evaluation of biologic agents prior to their use in general clinical practice is essential to understand their safety and efficacy. Rigorous, standardized investigations may also provide important insights into pathogenesis of the vasculitic diseases.     

Therapy Insight: gastrointestinal complications of diabetes--pathophysiology and management

Patients with diabetes often have gastrointestinal symptoms, but the extent and severity of this problem and the specificity of the symptoms are not nearly as well defined as frequently assumed. Any part of the gastrointestinal tract can be affected, and the presenting symptoms depend on the composite of dysfunctional elements. Gastroesophageal reflux, Candida esophagitis, gastroparesis, diarrhea and constipation are among the many common gastrointestinal complications of diabetes. No specific risk factor for the development of these complications has been identified and their etiology is most likely to be multifactorial, involving both reversible and irreversible processes. Treatment should be directed at tighter glycemic and symptom control, which can bring about clinical improvement for many patients. For other patients, however, effective clinical management is problematic because no therapies are available to prevent or correct the underlying disease mechanisms. Studies now suggest that reduced levels of key trophic factors cause transdifferentiation of pacemaker interstitial cells of Cajal into a smooth-muscle-like phenotype. If this really is the case, therapies directed at restoring the normal milieu of trophic signals could correct the dysfunction of the interstitial cells of Cajal and resolve many gastrointestinal complications. Advances in stem cell technology also hold promise to provide a cure for diabetes and to correct abnormalities in gastrointestinal pathology.     

Bestandsaufnahme und Perspektiven der ambulanten rheumatologischen Versorgung in Deutschland

AIM: To gather information about current structures in rheumatologic ambulatory health care in Germany. Based on the results recommendations on future structures will be evaluated. METHODS: Data collection and statistical analysis via a structured 10-page questionnaire answered by members of the German Association of Rheumatologists. Questions in this second part of the study related to two topics: economic factors and a subjective assessment of the health care structures by the participants. RESULTS: Data from 197 ambulatory rheumatologists who participated in health care could be included in the analyses. Extensive and detailed data on economic issues surrounding ambulatory patient treatment and practice management from the perspective of ambulatory rheumatologists are presented (e.g., revenue, income, income differences between regions or practice size). In addition, perceptions of participating rheumatologists on future perspectives of patient treatment, health policy, and their own economical survival are reported. CONCLUSIONS: As in other specialties there is a significant difference not only between the eastern and western regions in Germany but also between the north and the south looking at e.g., revenue, income, with rheumatologists in the east treating significantly more patients. Reasons for those differences are not only related to regional remuneration schemes or the number of patients with a private but statutory health insurance, but are also driven by the number of different services provided (e.g., own laboratory). Physicians perceptions towards their own future in rheumatology are generally positive. Scepticism was reported for the individual economic survival in ambulatory treatment and future changes in health policy.     

Technology Insight: the role of color and power Doppler ultrasonography in rheumatology

An increasing number of rheumatologists have access to ultrasound equipment that provide both color and power Doppler modes, which can be used to investigate musculoskeletal and vascular pathologies. Musculoskeletal Doppler ultrasonography can be used to estimate levels of inflammation, to document the anti-inflammatory effect of agents such as corticosteroids and tumor necrosis factor inhibitors, to differentiate between inflammatory and degenerative disease, and to distinguish between normal and inflamed joints in cases of minor synovial swelling. Vascular Doppler ultrasonography can be used to determine organ involvement in small-vessel vasculitides, to delineate aneurysms in vasculitides of medium-sized arteries, and to assess the characteristic findings in large-vessel vasculitis. Numerous studies, including a meta-analysis, have been published on the use of temporal-artery ultrasonography for the diagnosis of giant cell arteritis. Duplex ultrasonography is a sensitive approach for detecting characteristic edematous wall swellings in active temporal arteritis and for assessing vasculitis of the axillary arteries (large-vessel giant cell arteritis) in patients with suspected temporal arteritis, polymyalgia rheumatica, or fever of unknown origin. Duplex ultrasonography can also be used to assess vasculitis of subclavian and carotid arteries in younger patients with Takayasu's arteritis and acute finger artery occlusions in patients with small-vessel vasculitides.     

New insights into culture driven disorders

Rheumatologists frequently encounter patients whose illnesses lack face-value; that is, they lack the typical objective features of pathology that rheumatologists traditionally rely on for diagnosis and developing effective treatment approaches: namely fibromyalgia, chronic fatigue syndrome, Gulf War syndrome, chronic whiplash, chronic low back pain, etc. In this article, we examine this group of illnesses as culture-driven disorders to emphasize the central importance of various societal constraints in the ultimate presentation of patients with these illnesses. We will examine them by first understanding the purpose they serve, the underlying factors that compel societal institutions to sanctify these disorders as diseases, and how research is beginning to examine the behaviour that captures and packages these symptoms to produce their clinical presentation. With this research understanding, rheumatologists may be able to offer patients more useful action plans, but likely changes in societal approaches to the expressions of distress and changes in disability and compensation systems will also be required.     

重视心理社会因素在功能性胃肠病中的作用

功能性胃肠病（FGIDs）是生理、精神心理和社会因素相互作用而产生的消化系统疾病，在临床上十分常见。心理社会因素在FGIDs的发病中起重要作用，不仅影响患者的胃肠生理、症状表现和疾病行为，也影响患者的生活质量、就诊要求和医疗费用。心理治疗能改善FGIDs患者的症状和病理生理异常。心理社会因素与FGIDs的关系密切，加强对精神心理社会因素在FGIDs中作用的认识十分重要。     

Granulomatous inflammation: The overlap of immune deficiency and inflammation

Pediatric granulomatous diseases constitute a heterogenous group of conditions in terms of clinical phenotypes, pathogenic mechanisms, and outcomes. The common link is the presence of multinucleated giant cells in the inflammatory infiltrate. The clinical scenario in which a tissue biopsy shows granulomatous inflammation is not an uncommon one for practicing adult and pediatric rheumatologists. Our role as rheumatologists is to develop a diagnostic plan based on a rational differential diagnostic exercise tailored to the individual patient and based mainly on a detailed clinical assessment.This chapter presents a comprehensive differential diagnosis associated with a classification developed by the authors. We describe with some detail extrapulmonary sarcoidosis, Blau syndrome, and immunodeficiency associated granulomatous inflammation, which in our view are the paradigmatic primary forms of granulomatous diseases in childhood. The other entities are presented only as differential diagnoses listing their most relevant clinical features.This chapter shows that almost all granulomatous diseases seen in adults can be found in children and that there are some entities that are essentially pediatric at onset, namely Blau syndrome and most forms of immunodeficiency associated granulomatous diseases.     

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis

OBJECTIVES: To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. METHODS: An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence-based and expert opinion-based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. RESULTS: Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis-specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. CONCLUSIONS: On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well-designed research in non-AAV systemic vasculitides.