Primary biliary cirrhosis associated pustular vasculitis

The association between primary biliary cirrhosis (PBC) and cutaneous vasculitides is well recognized. Pustular skin lesions though, have been described in association with hepatobiliary diseases other than PBC. Once the more common infective pustular rashes have been excluded, the differential diagnoses for a pustular skin rash are acute generalized exanthematous pustulosis (AGEP), Sweet's Syndrome (SS), pyoderma gangrenosum (PG) and pustular vasculitis(PV). We present a case of pustular vasculitis associated with PBC.     

Cutaneous vasculitis

Cutaneous vasculitis comprises a wide spectrum of clinical syndromes and histopathologic findings which share the common theme of vascular inflammation and changes in the adjacent tissue. This article discusses several types of cutaneous vasculitides including leukocytoclastic vasculitis, Henoch-Sch?nlein purpura, urticarial vasculitis, livedoid vasculitis, and granulomatous vasculitides. The clinical patterns of these types of vasculitic syndromes as well as associated diseases and histopathology are discussed.     

Classification and diagnostic criteria in systemic vasculitis

Approximately 20 different primary forms of vasculitis are recognized, not all of which have been included in classification schemes or consensus statements regarding nomenclature. A variety of classification schemes have been proposed over the past 50 years, many predicated upon the size of the primary type of vessel involved in a given disease, as well as other considerations that include demographic features, organ tropism, the presence or absence of granulomatous inflammation, the role of immune complexes in pathophysiology and the association of autoantibodies with some forms of vasculitis. All classification schemes to date have had shortcomings owing to the substantial gaps in knowledge about vasculitis, but the American College of Rheumatology criteria for the classification of some forms of vasculitis are useful for the purpose of including patients in research studies. The Chapel Hill Consensus Conference has clarified some existing controversies in nomenclature of the systemic vasculitides. Robust diagnostic criteria for the various forms of vasculitis have, however, remained elusive.     

Pediatric forms of vasculitis

Primary vasculitides that affect children are a challenging and complex group of disorders that may involve any system of the body and lead to significant morbidity and mortality. In recent years, there have been significant advances in the field of childhood vasculitides, including the development of classification criteria and outcome assessment. Although some forms of vasculitis occur in both children and adults, considerable differences exist between childhood and adult vasculitides; we review childhood vasculitides, thus highlighting their differences with the adult forms of the disease. We will also discuss monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2) and haploinsufficiency of A20 (HA20).     

Introduction,epidemiology and classification of vasculitis

Classification of the vasculitides has been traditionally based on vessel size. The American College of Rheumatology (ACR) criteria were developed in the 1980s and published in 1990 before the development of ANCA testing and modern imaging techniques such as MRI and PET scanning, and therefore, these criteria are not fit for use in 2010s. The Chapel Hill Consensus Conference provided a framework for defining various types of vasculitis. In the next two years, new classification criteria will be published from the DCVAS study, which will provide a modern system for the classification of vasculitis for clinical studies.The epidemiology of vasculitides is increasingly well studied; however, there remain gaps in our knowledge of the occurrence of vasculitis in many populations, especially from the third world or those with health care systems that do not permit ready collection of accurate epidemiological data. Giant cell arteritis presents in the elderly and those of Northern European ancestry; ANCA-associated vasculitis appears to have a consistent overall occurrence, but there are differences in the occurrence of MPO and PR3 vasculitis between populations. Kawasaki disease occurs most commonly in Asian populations, especially Japanese, and in those aged less than 5 years. It is currently the most common cause of acquired cardiac disease in those populations.     

Hautmanifestationen der verschiedenen Vaskulitiden

The skin not only represents the organ which often reveals the first signs of systemic vasculitis, but also the organ which is most frequently involved in vasculitis. These diseases encompass systemic vasculitides and those which appear to involve the skin only. Among those vasculitides restricted to the skin, some are yet typically associated with other systemic diseases, such as nodular vasculitis, which often occurs during infections by M. tuberculosis, or erythema elevatum diutinum in patients with gammopathy. The type and localization of skin lesions give valuable indications as to the type of vasculitis. Subcutaneous nodules which ulcerate and are surrounded by livedo racemosa are suggestive of polyarteritis nodosa, a palpable purpura with predilection for the lower legs is almost pathognomonic for immune complex vasculitis (e.g. IgA vasculitis or cutaneous leukocytoclastic vasculitis), hemorrhagic papules and necrotic plaques which occur in acral areas after cooling indicate cryoglobulinemic vasculitis, hemorrhagic papules and macules which develop in patients who start to feel worse and develop fever should arouse suspicion of septic vasulitis, while the simultaneous presence of ulcerating nodules and hemorrhagic papules without predilection for the lower legs will suggest ANCA-associated vasculitis. The different morphology of the cutaneous signs of the various vasculitides depends to a large extent on the size of the vessels primarily involved. In this review the cutaneous signs of vasculitides will be presented with reference to the revised nomenclature of the Chapel Hill Consensus Conference from 2012.     

Ocular vasculitis: a multidisciplinary approach

PURPOSE OF REVIEW: The ophthalmologist has direct visual access to inflamed vessels when examining the retina, and "vasculitis" in ophthalmology has so far mainly referred to retinal vasculitis. In the past few years the means to explore vasculitis in the ocular sphere have improved. Indocyanine green angiography now enables the analysis of choroidal inflammatory vasculopathy as well as vasculitis of the sclera (scleritis) and episclera (episcleritis) in addition to retinal vasculitis. Because vasculitis detected by the ophthalmologist can be the presenting sign of a systemic disease and has to be approached in a multidisciplinary fashion, the emerging term "ocular vasculitis," instead of retinal vasculitis, should be used in the future. The term covers vasculitis affecting all structures of the eye and the periocular tissues as detailed in this article. The ocular findings have to be integrated within the established and accepted classification of systemic vasculitis, which is divided into primary vasculitides, where the vessel itself is the target of the inflammatory reaction, and secondary vasculitides, caused by other inflammatory processes. This review will deal with recently published articles on ocular vasculitis, including its clinical aspects, its link with systemic diseases, and its investigation and management. The discussion will be conducted within the framework of the new classification put forward here. RECENT FINDINGS: Novel imaging techniques such as indocyanine green angiography have made it possible to explore inflammation of choroidal vessels and of scleral vasculitis in addition to retinal vasculitis, contributing to the global concept of ocular vasculitis. It has been shown, in particular, that the choriocapillaris, a vascular structure adjacent to the retina, can be the site of a primary inflammatory vasculopathy unrecognized so far. Most of the recent articles cited, however, deal not so much with new findings but with the integration of ocular pathologic changes into the systemic diseases they are part of. New knowledge about disease mechanisms and novel therapeutic modalities with biologic agents cited in this review are coming from other fields but have contributed to progress in the management of ocular vasculitis. SUMMARY: New investigational techniques of vasculitis in ocular structures other than the retina have contributed to the development of the global concept of ocular vasculitis. This review shows the importance of promoting a comprehensive and global classification of ocular vasculitis compatible with the concepts accepted for systemic vasculitis to contribute to its multidisciplinary approach.     

Pulmonary vasculitis

The granulomatous vasculitides frequently involve the lung. These syndromes include Wegener's granulomatosis, allergic angiitis and granulomatosis, and the polyangiitis overlap syndrome. Although not a true systemic vasculitis, necrotizing sarcoid granulomatosis also represents a type of pulmonary vasculitis. It is clear that many infectious agents can cause a picture in the lung that can be confused with granulomatous vasculitis and that an infectious process must be ruled out before a diagnosis of pulmonary vasculitis can be established. Pulmonary vasculitis can be associated with the hypersensitivity vasculitides, and pulmonary hemorrhage can be secondary to pulmonary capillaritis. Therapy of the hypersensitivity vasculitides consists of removing the offending antigen and instituting a limited course of corticosteroids. If the vasculitis is secondary to an underlying disease, such as lymphoma, therapy should be directed at the primary disease. Combination therapy with cyclophosphamide and corticosteroids is effective in the systemic vasculitides and the 5-yr survival rate is approximately 90%.     

Cutaneous necrotizing granulomatous vasculitis with evolution to T cell lymphoma

The evolution of unusual cutaneous vasculitis to a systemic T cell lymphoma was observed over a 12-year period. Precise classification of the skin biopsy specimens during the course of this patient's illness was difficult. Different observers suggested malignant hemangioendothelioma, malignant lymphoma, regressing atypical histiocytosis, and granulomatous vasculitis. In retrospect, the biopsy specimens likely represented the spectrum of cutaneous lymphomatoid granulomatosis. This condition is yet another example of a reactive lymphoid proliferation proceeding to a malignant lymphoma.     

Update in the diagnosis and management of pulmonary vasculitis

The term vasculitis encompasses a number of distinct clinicopathologic disease entities, each of which is characterized pathologically by cellular inflammation and destruction of the blood vessel wall, and clinically by the types and locations of the affected vessels. While multiple classification schemes have been proposed to categorize and simplify the approach to these diseases, ultimately their diagnosis rests on the identification of particular patterns of clinical, radiologic, laboratory, and pathologic features. While lung involvement is most commonly seen with the primary idiopathic, small-vessel or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides of Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, one should remember that medium-vessel vasculitis (ie, classic polyarteritis nodosa), large-vessel vasculitis (ie, Takayasu arteritis), primary immune complex-mediated vasculitis (ie, Goodpasture syndrome), and secondary vasculitis (ie, systemic lupus erythematosus) can all affect the lung. However, for the purpose of this review, we will focus on the ANCA-associated vasculitides.     

Clinical approach to cutaneous vasculitis

PURPOSE OF REVIEW: This review provides the readers with an update on the clinical approach of a patient seeking treatment with cutaneous vasculitis. It outlines the work-up for assessing patients with cutaneous vasculitis and discusses the essential features of the main conditions included within this category. RECENT FINDINGS: Recent works on genetic and infectious factors implicated in the pathogenesis of Henoch-Schonlein purpura are discussed. Special attention is given to the prognosis and response to treatment. Also, recent reports on cutaneous vasculitis secondary to connective tissue diseases are reviewed. SUMMARY: With this review, the reader will be able to establish the steps to be followed in the clinical approach to a patient seeking treatment with cutaneous vasculitis.     

Pulmonary vasculitis

Pulmonary vasculitis describes a number of distinct disorders that are pathologically characterized by the destruction of blood vessels. The clinical manifestations of each disorder are defined by the size, type, and location of the affected vasculature. The clinical approach to these disorders rests upon an astute clinician considering the diagnosis and identifying the specific patterns of clinical, radiologic, laboratory, and pathologic abnormalities. Lung involvement is most commonly seen with the primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody-associated vasculitides; Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. However, primary, idiopathic medium and large-vessel vasculitis, primary immune complex-mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement. In this article, we focus on the more common, antineutrophil cytoplasmic antibody-associated disorder, vasculitides.     

Roadmap to vasculitis

Vasculitis is characterized by vessel wall injury caused by an immunologically initiated inflammatory reaction. Vesselwall injuryleads to vascular stenosis, aneurysm, bleeding, thrombosis, embolism, vasospasms and ischemia. The vasculitis is clinically important when the patient has general inflammatory and multifocal symptoms, which progress in episodes and can be explained by these vascular lesions. The clinical manifestations of these depend on the size, localization and number of blood vessels involved. This forms the basis of the current vasculitis classification. It is important to recognize the secondary vasculitides, as their treatment is mainly based on elimination of the triggering factor. In primary vasculitides, immunosuppression alone is the basis of treatment in almost all cases, whereas the management of pseudovasculitis is dependent on its aetiology. In primary care, basic evaluation should be done: patient history, physical examination, basic laboratory tests and other non-invasive tests to verify suspected surrogate findings. After this, patients should be urgently referred to a specialized centre, where the required histological and radiological tests are performed for diagnosis and immunosuppressive and other necessary treatment is initiated.     

Primary cutaneous small vessel vasculitis

Disorders associated with cutaneous vasculitis include numerous well-described etiologies. Primary cutaneous vasculitis limits discussion to primary leukocytoclastic vasculitis, essential mixed cryoglobulinemia, urticarial vasculitis, Henoch-Sch?nlein purpura, and erythema elevatum diutinum. Although the therapeutics for these disorders are based on limited data, we attempt to construct a consensus opinion on the management of primary cutaneous vasculitis. Therapy of primary cutaneous vasculitis is indicated for symptomatic or systemic involvement, because cutaneous small vessel vasculitis is frequently a self-limited, single episodic disease. Conservative, symptomatic treatment includes leg elevation, warming, antihistamines, and nonsteroidal anti-inflammatory drugs. For mild recurrent disease, colchicine, dapsone, and prednisone are first-choice agents. Systemic or severe cutaneous disease requires more potent immunosuppression (eg, prednisone, azathioprine, or mycophenolate mofetil). Plasmapheresis/plasma exchange and intravenous immunoglobulin are viable considerations for refractory disease, but are cumbersome and expensive modalities. There is insufficient evidence to advocate the use of new biological or monoclonal antibody therapies in primary cutaneous vasculitis.     

Historical perspective of vasculitis: Polyarteritis nodosa and microscopic polyangiitis

The original and early case reports of vasculitis provide a historical context and foundation for understanding current concepts of these diseases. These early case reports are valuable as reference points for the current efforts in diagnosing, treating, and classifying vasculitis. In addition, they emphasize the importance of careful clinical observation in these efforts and the essential nature of medical science. Polyarteritis nodosa was the first noninfectious vasculitis to be described and studied in detail. Research on this group of vasculitides has been the cornerstone for understanding the pathophysiology of other forms of idiopathic vasculitis. Historically, most forms of vasculitis described subsequently have been characterized and classified on the basis of features similar to or distinct from polyarteritis.     

Pre-pregnancy counselling of patients with vasculitis

The knowledge about the risk of pregnancy in vasculitides mostly derives from single case reports or at best from retrospective studies with all the caveats that these observations include. Primary systemic vasculitides are uncommon, encompassing a broad spectrum of severity, from mild to life-threatening manifestations and with different natural histories, from self-limiting to relapsing or chronic active disease. The treatments require a cautious use of immunosuppressants tailored to each specific condition. Furthermore, most of the cytotoxic drugs necessary to treat vasculitis act by modifying the cell cycle and cell differentiation, biological effects that are particularly hazardous for the foetus. In order to have an uncomplicated pregnancy, conception should be planned when the disease is inactive. Moreover, organ failure or damage, due to previous disease activity, must also be taken into account since it can lead to adverse obstetrical and fetal outcomes.     

Hypersensitivity vasculitis and Henoch-Sch?nlein purpura: a comparison between the 2 disorders.

Leukocytoclastic vasculitis of small vessels and predominant involvement of the skin are common features of both hypersensitivity vasculitis (HV) and Henoch-Sch?nlein purpura. In a study comparing 93 patients with HV and 85 patients with Henoch-Sch?nlein purpura we found major differences with respect to frequencies and type of organ involvement (gastrointestinal tract, kidneys, skin and joints) which were present in both younger and older patients when analyzed separately. To investigate which clinical criteria best differentiate between these 2 vasculitides, 2 methodologies were employed. A rule requiring 3 or more criteria to be present from a list of 6 yielded 87.1% of correctly classified Henoch-Sch?nlein purpura cases; and 2 or fewer criteria from the same list of 6 correctly classified 74.2% of HV cases. A classification tree was associated with respective values of 83.5 and 84.9%. The results indicate that HV and Henoch-Sch?nlein purpura are similar but separable clinical syndromes.     

Drug-induced vasculitis.

DIV is a relatively common cause of inflammatory vasculitis. Drugs from almost every pharmacologic class have been implicated in causing vasculitis in sporadic cases. The level of certainty and quality of evidence for these associations between specific agents and vasculitis vary greatly. The clinical manifestations of DIV range from single organ involvement (most commonly, skin) to life-threatening multiorgan disease. The recently described subset of cases of DIV associated with positive tests for ANCA are an interesting subset of DIV. The diagnosis of DIV is usually one of exclusion. The treatment of DIV is dependent on the severity of disease activity but should always include withdrawal of the suspected drug. If no agent can be implicated, as many drugs as feasible should be discontinued. The necessity of prescribing glucocorticoids or immunosuppressive agents depends on the disease severity and other case-specific information. Increasing understanding of the pathophysiologic characteristics of all inflammatory vasculitides should lead to better diagnostic and therapeutic approaches to DIV.     

Cutaneous vasculitis associated with fluoroquinolones

Cutaneous vasculitis is a clinical entity with a broad differential diagnosis, including an adverse drug reaction. It is defined as inflammation of skin blood vessel walls. During a 7-year-period, we observed three patients who developed isolated cutaneous vasculitis during antibiotic therapy of bacterial infection. All were treated with a fluoroquinolone (ciprofloxacin or levofloxacin) combined with rifampin (two cases) or flucloxacillin (three cases), respectively. In all three cases the lesions gradually resolved after treatment with the inciting fluoroquinolone had been stopped. In one patient, leukocytoclastic small-vessel vasculitis was histologically confirmed. Fluoroquinolone-associated cutaneous vasculitis consists of an isolated self-limiting disorder that is part of a systemic vasculitis, or even life-threatening disease. Clinicians should be aware of this serious adverse event because any continuation of treatment may be fatal.     

Drug associated cutaneous vasculitis in adults in northwestern Spain.

OBJECTIVE: To examine the incidence and clinical features of adults with biopsy proven cutaneous vasculitis (CV) associated with drugs. METHODS: Retrospective study of an unselected population of adults (age >20 years) with biopsy proven leukocytoclastic CV from 1988 through 1997. Drug associated CV was considered if CV was confirmed by a skin biopsy and there was a history of drug use within one week before the development of CV. Drug associated CV was classified by American College of Rheumatology (ACR) criteria. To differentiate Henoch-Schonlein purpura (HSP) from hypersensitivity vasculitis (HV), the traditional criteria proposed by Michel, et al were used (J. Rheumatol. 1992;19:721-8). RESULTS: Thirty-three of 138 patients (23.9%) presenting with biopsy proven CV were diagnosed with drug associated CV. The annual incidence rate of biopsy proven drug associated CV in adults was 17.49 cases/million (95% CI 11.53-23.46): men 25.10/million (95% CI 14.85-35.36), women 10.31/million (95% CI 3.92-16.70). Antibiotics (n = 13), especially amoxicillin, and analgesics or nonsteroidal anti-inflammatory drugs (n = 11) were the drugs more commonly associated with CV. All adults with drug associated CV met the ACR classification criteria for HV or HSP. Based on Michel's criteria 26 patients (78.8%) were classified as having HV and 7 HSP. No patient met ACR criteria for other systemic vasculitides. Complete recovery with no sequelae was observed in most cases. CONCLUSION: Among patients with CV, drug associated disease is common and usually has a good clinical outcome.