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Cutaneous vasculitis and their differential diagnoses
Abstract
Vasculitis is defined as an inflammatory cell infiltration and destruction of blood vessels identified upon histologic examination. Cutaneous manifestations are frequent during the course of many systemic vasculitis. Lesions are often not specific, the most frequent being palpable purpura. They may be the first and only manifestation of the disease or be a part of a systemic condition. Histology is mandatory to confirm the diagnosis of vasculitis to avoid a delayed and inappropriate diagnosis that could lead to improper management. Cutaneous histology gave some data that may help to classify the vasculitis without determining precisely its type. A histological examination of all other skin lesions is necessary. The result of the biopsy has to be correlated to DIF data, medical history, physical examination, laboratory and radiological findings leading to the correct diagnosis and effective treatment.In this review, we discuss the diagnosis of cutaneous vasculitis (CV) and the pitfalls related to the cutaneous pathology. We also describe the essential features of the major categories of skin vasculitis.
... Even though a certain number of syndromes have been described, a patient may present with symptoms that overlap with another clinical diagnosis making a diagnosis "at first sight" impossible. Most of all, vasculitis has a histopathologic definition; therefore, its confirmation comes only from the microscopic examination of the lesion [1][2][3][4][5]. ...
... In the absence of fibrinoid necrosis, the diagnosis of CV becomes more difficult. Lamination of the adventitia, media, and/or intima; perivascular nuclear dust (leukocytoclasia) without fibrinoid necrosis; loss of the elastic lamina with acellular scar tissue; or subendothelial intramuscular and/ or adventitial inflammatory cells in large vessels are all other indications for vessel wall damages [1][2][3][4][5]. ...
... After 72 h, only C3 is detected. Therefore, a negative DIF does not rule out the diagnosis of CV [1][2][3][4][5]. ...
Vasculitis is defined as an inflammatory cell infiltration and destruction of blood vessels identified upon histologic examination. Cutaneous manifestations may be the first and only manifestation of the disease or be a part of a systemic condition.
Cutaneous vasculitis (CV) affects small vessel (<50 μm) and medium (<50–150 μm) vessels located in the dermis and the hypodermis.
Cutaneous lesions are frequent during the course of many systemic vasculitis. Lesions are often not specific, the most frequent being palpable purpura. Histology is mandatory to confirm the diagnosis of vasculitis to avoid delayed and inappropriate diagnosis that could lead to improper management. Cutaneous histology gave some data that may help to classify the vasculitis without determining precisely its type. A histological examination of all other skin lesions is necessary. The result of the biopsy has to be correlated to direct immunofluorescence data, medical history, physical examination, and laboratory and radiological findings leading to the correct diagnosis and effective treatment.
... A diagnosis of cutaneous vasculitis affecting small-and medium-sized vessels in the skin and subcutaneous tissue was made primarily through biopsy and an examination of hematoxylinand eosin-stained sections, as described in the literature [17]. An immediate diagnosis of vasculitis was made if inflammatory infiltrates were identified within and around the vessel walls, accompanied by fibrin deposition [18,19]. In addition, a diagnosis of LCV was confirmed with a punch biopsy showing (1) a superficial perivascular inflammatory infiltrate; (2) the predominance of neutrophils in the capillary walls and postcapillary venules; (3) leukocytoclasis (the fragmentation of neutrophils into scattered nuclear fragments secondary to karyorrhexis); and (4) the perivascular and interstitial extravasation of erythrocytes [18,19]. ...
... An immediate diagnosis of vasculitis was made if inflammatory infiltrates were identified within and around the vessel walls, accompanied by fibrin deposition [18,19]. In addition, a diagnosis of LCV was confirmed with a punch biopsy showing (1) a superficial perivascular inflammatory infiltrate; (2) the predominance of neutrophils in the capillary walls and postcapillary venules; (3) leukocytoclasis (the fragmentation of neutrophils into scattered nuclear fragments secondary to karyorrhexis); and (4) the perivascular and interstitial extravasation of erythrocytes [18,19]. ...
... In all five patients, the results of detailed laboratory investigations for inflammatory markers, autoimmune markers, immunoglobulin (IgG, IgA, and IgG4) and complement (C3 and C4) serum levels, viral serology, infectious work-up, urinalysis, creatinine, and liver function were unremarkable. Although a patient's clinical history and a physical examination and laboratory work-up are important for a differential diagnosis of LCV, a histology is essential to confirm a diagnosis of vasculitis and to avoid a delayed or erroneous diagnosis that could lead to improper management [19,28]. The differential diagnosis includes systemic primary small-vessel vasculitis (such as ANCA-associated vasculitis, cryoglobulinemic vasculitis, and IgA vasculitis), thrombocytopenic purpura, infections, and rheumatic and autoimmune diseases, such as rheumatoid arthritis, Sjogren's syndrome, Behçet's disease, systemic lupus erythematosus, and relapsing polychondritis [7]. ...
Background:
Vasculitis is an uncommon complication of biologics used to treat inflammatory bowel disease (IBD). This study describes a case series of vasculitis induced by anti-tumor necrosis factor (TNF) therapy in IBD patients.
Methods:
Retrospective assessments were performed using the medical records of adult IBD patients who underwent outpatient clinical follow-ups between January 2010 and December 2019 in order to identify patients with vasculitis caused by anti-TNF therapy.
Results:
There were 2442 patients altogether. Of these, 862 (35%) took anti-TNF medication. Five patients (0.6% of the overall patients; n = 3 (60%) Crohn's disease; n = 2 (40%), ulcerative colitis) were identified as having leukocytoclastic vasculitis (LCV) due to anti-TNF therapy; these patients were white, female, and non-smokers. The mean age of LCV diagnosis was 32.2 years, and the mean IBD duration was 7.2 years. The mean time between the start of biologic therapy and LCV onset was 30.8 months. Most of the patients were using adalimumab (80%; n = 4). All the patients were in remission at the time of the LCV diagnosis, and the vasculitis affected the skin in all cases. Anti-TNF therapy was discontinued in the five abovementioned patients, and the response of LCV to the oral steroids was significantly positive. Remarkably, all five patients experienced complete remission from LCV within 4-12 weeks after starting prednisone therapy, and none of them had LCV recurrence in the follow-up period (a mean duration of 28 months).
Conclusions:
LCV is an unusual complication of anti-TNF therapy in the IBD setting. In this context, clinicians should have a high degree of suspicion of LCV in patients who develop an unexplained cutaneous rash.
... Direct immunofluorescence may be an additional feature supporting the diagnosis of IgA vasculitis in case of predominant IgA deposits into the capillary wall, though it is not specific [11]. Also, IgM deposits are not specific and are conventionally mentioned in the presence of rheumatoid factor or cryoglobulinemia [12]. Conversely, immunoglobulin deposits into the vascular wall without any evidence of vasculitis have no pathological significance. ...
... However, direct immunofluorescence reveals predominant IgA deposits in the capillary wall. Thus, predominance of perivascular IgA deposits on skin biopsy is an additional positive argument for the diagnosis of IgA vasculitis, without being specific [11], since other vasculitis as cryoglobulinemic vasculitis may have IgA deposits [12]. ...
Cutaneous vasculitis is an inflammatory disease affecting the dermal blood vessel walls. The skin is a privileged organ in the setting of vasculitis since it is easily accessible for physical examination and safe biopsy, allowing an accurate characterization of inflammatory lesions. The skin is often involved. Also, cutaneous vasculitis can reflect a cutaneous component of a systemic vasculitis, a skin-limited or skin-dominant expression or variant of a systemic vasculitis, or be a single-organ vasculitis per se. Vasculitis lesions are multiple and polymorphic. They may induce a wide spectrum of clinical manifestations depending on the location and the size of the vessels involved. The depth of affected vessels is correlated with the type of cutaneous lesions. Involvement of small superficial vessels results mostly in urticarial, but relatively persistent plaques, papules, and palpable purpura. Involvement of vessels in the dermohypodermic junction or hypodermis results in ulcers, nodules, or livedo. The type of inflammatory infiltrate is also a key finding for the diagnosis of cutaneous vasculitis. Leukocytoclastic vasculitis is not a disease per se but the result of a pathophysiological process common to different causes. A better knowledge of the vascular anatomy of the skin, elementary lesions, and histological characteristics of dermatologic manifestations would allow a more relevant and more efficient diagnostic approach. We also propose a list of additional exams to be performed in front of skin lesions suggestive of vasculitis. The aim of our article is to provide an overview of elementary skin lesions and clinicopathologic correlations in cutaneous and systemic vasculitis.
... The older the biopsied lesion, the fewer immunoglobulins are found. After 72 h, only C3 is detected [76,77]. ...
... In those patients in whom a well-defined entity is suspected, specific studies aimed to determine the presence of an underlying condition that may explain the presence of CV should be considered (e.g., blood cultures and lumbar puncture in cases of CV associated with infections or colonoscopy and renal biopsy when the presence of an underlying malignancy is suspected) [30,77]. Figure 1 shows a work-up in a patient with CV in whom a skin biopsy discloses the presence of a leukocytoclastic vasculitis. ...
Cutaneous vasculitis (CV) comprises a wide spectrum of diseases and displays a variety of clinical lesions, the most common being a palpable purpura. CV may be a process confined exclusively to the skin or be a manifestation of a more widespread entity associated to a variable grade of visceral involvement. In this regard, CV may occur as part of the clinical spectrum of primary systemic vasculitis, autoimmune diseases or less commonly as presenting manifestation of cancer or severe infections. An adequate clinical approach is required to establish optimal management of this condition.
... Urticarial vasculitis (14.9%), polyarteritis nodosa (5.4%) and Henoch-Schönlein purpura (HSP) (4.1%) were other types of cutaneous vasculitis in our study. The low incidence of HSP in our study was roughly in line with other studies reported a prevalence of 10% for HSP which mainly involves children between 5 and 15 years [16,17,18]. This might be explained by the fact that most of our patients were adults in whom HSP has a lower prevalence. ...
Background & objective
Cutaneous vasculitis has different clinical manifestations. It may be idiopathic or associated with infections, medications, etc.Skin is involved in both small vessel vasculitis (SVV) and medium vascular vasculitis.We aimed to evaluate clinical signs, laboratory and pathological changes of cutaneous vasculitis among Iranian people.
Material & methods
This study was a descriptive study performed on 74 patients with cutaneous vasculitis from March 2011 to February 2019. Information includes histopathological data, as well as clinical variables including the age of onset, sex, area of involvement, type of lesion, symptoms, and diagnosis. Pathological and laboratory changes were collected and recorded as well.
Results
Of the 74 patients studied, hypersensitivity vasculitis 52(70%) was the most common form.Most of the patients had lower extremities involvement. The most common clinical features and symptoms were petechiae or purpura and itching. Fever, limb edema, and arthralgia were the most common symptoms, occurring in 26%, 20%, and 18% of patients, respectively. Among patients, 18 (24%) had taken medication before the lesions, 10 (13%) had vasculitis due to infection, and 44 (59%) were diagnosed as idiopathic form. The most common treatment was prednisolone in 69 patients (93%) with a mean dose of 15.6 ± 35 mg.
Conclusion
The study would be useful in understanding the various specific and non specific features of cutaneous vasculitis, helping the clinician to manage the condition.
... IgA vasculitis is the most common vasculitis of childhood. It constitutes approximately 10% of cutaneous vasculitides (16,17). Similarly, the diagnosis of IgM/G vasculitis is achieved in patients who show IgM/G deposition instead of IgA deposition in DIF with a similar clinical presentation with palpable purpura, urticaria and sometimes necrotic/ulcerous lesions symmetrically located on the lower extremities (18). ...
Vasculitides, characterized by inflammation and damage of blood vessels, encompass a broad spectrum of diseases. They can occur with different pathophysiological mechanisms and have a rich clinical heterogeneity depending on the vessel diameters they affect. Vasculitides may also present with a broad spectrum of severity, ranging from a mild self-limiting to a potentially life-threatening disease. The high prevalence of skin involvement in vasculitis, visible character and, finally, the easy accessibility of the skin for both physical examination and biopsy offers important advantages for prompt disease recognition and diagnosis. Thus, dermatologists are privileged to diagnose the disease earlier and more effectively than any other discipline. As a consequence, a detailed clinical and histopathological evaluation of the skin is one of the most critical steps in diagnosing vasculitis. Besides obtaining a good medical history, laboratory and radiological evaluation methods are used in the diagnosis. In this review, a practical and algorithmic approach is aimed to assist in the diagnosis of vasculitis. However, this approach should not be seen as strict rules. This stepwise algorithmic diagnostic approach for vasculitis was developed by combining the current literature knowledge and the author's experience in this field to provide a rational framework for selecting the most appropriate among various diagnostic approaches.
... The classic clinical features of IgA vasculitis (HSP) comprise non-thrombocytopenic purpuric skin rash, abdominal pain, arthralgia or arthritis, and renal involvement, usually with a self-limiting disease course [1]. Skin involvement is the mandatory criterion in patients with IgA vasculitis (HSP) [7]; nevertheless, this is a nonpathognomonic sign of the disease [8]. About 10 % of patients with systemic lupus erythematosus (SLE) can present with cutaneous vasculitis [9]. ...
Background:
We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature.
Aim:
To know the age and gender distribution of children with IgA vasculitis (HSP), compare it to our IgA vasculitis (HSP) + jSLE cases, and identify prognostic factors to develop jSLE within our case series, IgA vasculitis (HSP) vs. IgA vasculitis (HSP) + jSLE.
Methods:
A systematic review was carried out to know the age and gender distribution of children with IgA vasculitis (HSP). The information obtained plus data from 110 children with IgA vasculitis (HSP) from the Instituto Nacional de Pediatría were used to compare groups and identify prognostic factors. We performed a case-control study in patients < 18 years, consisting of 15 cases retrospectively identified with IgA vasculitis (HSP) + jSLE, and 110 IgA vasculitis (HSP) control subjects.
Results:
The information of 12,819 IgA vasculitis (HSP) subjects from the systematic review and 110 IgA vasculitis (HSP) controls was obtained and compared to our 15 IgA vasculitis (HSP) + jSLE cases. The mean age of IgA vasculitis (HSP) was 7.1-years vs. 10.4-years of IgA vasculitis (HSP) + jSLE at the HSP diagnosis. Female to male ratio of IgA vasculitis (HSP) was 1:1.33 vs. 1:0.25 of IgA vasculitis (HSP) + jSLE. Patients with IgA vasculitis (HSP) + jSLE had lower levels of Hemoglobin (Hb) compared to patients with IgA vasculitis (HSP) 109 g/L vs. 141 g/L. For the development of jSLE, we found older age and lower levels of Hb as prognostic factors with OR [95% CI]: 1.37 [1.06, 1.89] and 5.39 [2.69, 15.25], respectively.
Conclusion:
IgA vasculitis (HSP) + jSLE patients are older and have lower levels of Hb than patients with IgA vasculitis (HSP). It is necessary to confirm these findings through a prospective study.
... Kutanöz vaskülitler %30-40 idiopatik, %20 çoğunlukla üst solunum sistemi olmak üzere enfeksiyonlara ikincil, %20 ilaçlara bağlı , %10-15 bağ dokusu hastalıklarına, %10 Henoch-Schönlein purpurası ve %5 oranında çeşitli malignitelere bağlı olarak gelişebilir (9,10). Kutanöz vaskülitlerde olguların Sonuç olarak; Hemodiyaliz hastaları enfeksiyonlara meyillidirler ve özellikle kateter kullanımı bu enfeksiyonların sıklığını artırmaktadır. ...
Patients treated with hemodialysis are predisposed to infections. Catheter-related infections are the most common infections in patients who have a central venous hemodialysis catheter. These infections may lead to bacteremia or metastatic infection. Cutaneous vasculitis is a form of vasculitis characterized by purpuric eruption localized to the lower extremity. This entity may be related to drugs, infections or have an unknown etiology. Here we present two chronic hemodialysis patients who had fever and increased infection parameters such as leukocytosis and C-reactive protein (CRP). During follow-up, they developed purpuric eruptions on the legs. Infection-related cutaneous vasculitis was diagnosed in these patients and they were successfully treated with antimicrobial therapy.
... Anamnesis aimed to exclude trigger factors, immunological investigation for vasculitis and connective tissue diseases (CTDs), assessment of the coagulatory function, lesional biopsy, and histological examination are mandatory. mediated angiocentric inflammation, characterized by neutrophils (prevalent) and lympho-monocyte infiltration, fibrinoid necrosis of the vessel walls, and extravasation of red cells 4 (Figure 3). It may result in destruction, thrombosis, or fibrosis of the vessel, narrowing of the lumen and reduction of tissue blood supply, and focal ischemia (Table 1). ...
Vasculitic ulcers are an emerging problem in wound care that needs to be well defined and adequately approached by caregivers. Cutaneous vasculitis includes several inflammatory disorders that compromise microvessels and specifically the cutaneous vascular system: arterioles, capillaries, postcapillary venules. The pathogenetic role of circulating immunocomplexes and autoantibodies (antineutrophil antibodies) in these diseases has been widely demonstrated in animal models and in humans. Vasculitis can be limited to the skin or represent the cutaneous signs in case of systemic vasculitis with visceral involvement. The injury of cutaneous microvessels may result in impairment of blood flow and consequent focal ischemia and formation of skin ulcers. The ulcers are often multiple and localized on the lower leg and foot where the microcirculatory anatomy and rheologic dynamics are predisposing factors. Approximately 3% to 5% of skin ulcers may be caused by a vasculitic disorder.
... Asimismo, en el diagnóstico diferencial de las vasculitis debe considerarse la existencia de púrpura con un origen primariamente trombótico. Es el caso del síndrome antifosfolipídico, la coagulación intravascular diseminada o el déficit de proteínasCyS .S i n embargo, en pacientes sometidos a intervenciones endovasculares, politraumatizados o portadores de cardiopatías embolígenas debe sospecharse la existencia de un proceso embolígeno subyacente 81,82 . Otros cuadros que por diversos mecanismos conducen a la obliteración de las luces vasculares simulando vasculitis son la calcifilaxia, la enfermedad por émbolos de colesterol, la hiperoxaluria o la hiperhomocisteinemia, entre otros. ...
Vasculitis is a term that refers to damage and inflammation of the walls of blood vessels of any size. The classification of types of cutaneous vasculitis continues to be a challenge, probably because of our lack of understanding of the etiology and pathogenesis of this condition. Changes in the vessel wall will be visible on microscopy and will enable the different clinical forms to be distinguished according to the caliber of affected vessels, the type of cell that predominates in the inflammatory infiltrate, or the presence of such key findings as extravascular granulomas. Skin manifestations (macules, papules, nodules, livedo reticularis, etc) correlate with the size of the vessel affected. The prognosis in cases of vasculitis with skin involvement will be determined by the presence or absence of extracutaneous disease. Systemic vasculitis shows a predilection for certain organs, such as the kidney or lung. The introduction of immunosuppressant drug treatments has led to evident improvement in survival rates for patients with vasculitis. This review covers practical aspects of the pathophysiology, histopathology, treatment, and differential diagnosis of the main clinical presentations of vasculitis with cutaneous involvement.
Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.
This review discusses the clinical manifestations of cutaneous small vessel vasculitis. The etiologies and work up will be explored as well as the treatment considerations. This entity is multifactorial and usually involves multiple specialties. The presentation can range from self-limited to life threatening, multi-organ failure. It is essential to be able to diagnose vasculitis and proceed with the appropriate laboratory studies and work-up. Finally, investigation of associated etiologies such as infection and drugs will guide additional diagnostic studies.
Cutaneous vasculitis (CV) includes a wide spectrum of entities characterized by predominant skin manifestations and a variable grade of systemic involvement. CV exhibits a variety of cutaneous lesions depending on the size of the involved vessels, with the most common being palpable purpura. CV can be found as part of the clinical spectrum of primary systemic vasculitis, autoimmune diseases, or less commonly as presenting manifestation of mimicking conditions such as infections and neoplastic diseases. In this regard, an adequate clinical approach is required to establish optimal management of this condition. CV limited to the skin usually respond to bed-rest and low-dose glucocorticosteroid therapy. However, when systemic involvement exists, immunosuppressive drugs such as azathioprine, intravenous cyclophosphamide, or rituximab may be considered.
Vasculitis is an inflammation and destruction of the blood vessel wall. It can occur in any organ system of the body, and can present in a systemic form with multi-organ involvement, or in a limited form with only one organ system involved. The skin is one of the most frequently involved organs in vasculitis with the most frequent clinical presentation being purpura. Although symptomatic cardiac involvement is relatively rare, it is clinically important because of its prognostic value. Cardiac involvement is most common in Takayasu arteritis, polyarteritis nodosa, and eosinophilic granulomatosis with polyangiitis. Pericarditis, myocarditis, coronary arteritis, valvulopathy, and intracavitary cardiac thrombosis are the major cardiac manifestations in primary vasculitis. The diagnosis of cardiac involvement often requires high suspicion. Endomyocardial biopsy is not always possible. Echocardiography is the primary imaging modality and an important tool for the diagnosis and follow-up of cardiac involvement. Cardiac magnetic resonance imaging might be the most sensitive imaging modality for the evaluation of cardiac involvement. Treatment of cardiac involvement depends on cardiac manifestations. Treatment of myocarditis and coronary arteritis is much more aggressive than pericarditis.
Vasculitis is an inflammatory disease which leads to destruction of blood vessels. Cutaneous manifestations of vasculitis may be the first presentation to the medical practitioner and may be the only manifestation of a systemic disease. The diagnosis is usually made by the combination of clinical history, examination findings, and laboratory findings especially histopathological evaluation of skin biopsy with direct immunofluorescence studies. In this chapter, we discuss common cutaneous vasculitis cases with illustrations.
Leukocytoclastic vasculitis is an autoimmune disorder that affects small vessels, and causes inflammation, destruction and necrosis of the same. It is often underdiagnosed. The etiology is multifactorial, the pathophysiology is complex and immunomodulators are the most important medications in their treatment. This article aims to review the current state of knowledge in leukocytoclastic vasculitis with emphasis on diagnosis and treatment. Articles published in the period from 1990 to 2017 were reviewed. The browsers were Google Crome and Firefox and the search engine was Scholar google. The database consulted was: MEDLINE, RIMA Astra-Zeneca and the clinical practice guidelines of the Mexican health system (CENETEC); 108 relevant publications to the subject were reviewed, prioritizing those belonging to journals indexed in MEDLINE and Science Citation Index-JCR. Studies are required to integrate clinical and treatment subgroups and investigate the mechanisms of tissue damage in each subgroup. Immunomodulation plays a central role in the treatment.
Cutaneous vasculitis encompasses cutaneous components of systemic vasculitides, skin-limited variants of systemic vasculitides, such as IgA vasculitis or cutaneous polyarteritis nodosa, and single-organ cutaneous vasculitis, as individualized in 2012 in the Chapel Hill Consensus Conference Nomenclature. In this article, we focus on the management of skin-limited and single-organ vasculitides, often referred to, in clinical practice, as isolated “cutaneous leukocyctoclastic vasculitis”, terms which may correspond to histological findings or descriptions, but are imprecise and not specific. Since most cases of isolated cutaneous vasculitis are self-limited and resolve spontaneously over 3 to 4 weeks, most patients require no systemic treatment. For those with severe, intractable, or chronic and recurring vasculitis, systemic therapy can be indicated and should be tailored to the severity of the disease. High-quality literature is lacking to guide management. Oral glucocorticoids may be required for a short period of time for painful, ulcerative, or otherwise severe disease in order to speed resolution. Among drugs which are reasonable longer-term options are colchicine, dapsone, azathioprine or hydroxychloroquine. Additional studies, including an ongoing multicenter randomized trial, are needed to determine the most effective therapies for skin-limited vasculitis.
Background
Skin involvement in granulomatosis with polyangiitis (GPA) is common and can appear as an initial presentation of the disease or more commonly through its course.
Case presentation: We report a case of a 24-year-old male patient, previously diagnosed as having GPA, admitted with fever, hemoptysis, generalized hemorrhagic blisters associated with arthralgia, fatigue, myalgia, nasal crusting, and vertigo. Three weeks prior to admission, he developed erythematous papules on both elbows, and purpuric papules on both lower limbs. Histopathological examination revealed: interstitial granulomatous dermatitis (elbows) and foci of dermal hemorrhage, foci of interstitial histiocytes and zones of altered necrobiotic collagen (lower limbs) consistent with cutaneous lesions of GPA. Two weeks later, his rash progressed to widespread purpura associated with hemorrhagic blisters. Another biopsy revealed leukocytoclastic vasculitis with fibrinoid necrosis of the vessel walls associated with perivascular infiltrate of neutrophils, nuclear dust and extravasated erythrocytes without an associated granulomatous inflammation or necrobiosis. The constellation of the results of the three biopsies together with clinical correlation pointed to a flare of GPA.
Conclusion
Skin involvement in GPA is quite common, and it can manifest in different forms in the same patient. Our patient developed three different skin pathologies within a short period of time.
Cutaneous small vessel vasculitis (CSVV) are a spectrum of conditions characterized by an angiocentric inflammation mainly limited to the post-capillary venules of the skin. Neutrophils are the predominant cellular effectors of the inflammatory infiltration and destruction of the blood vessels. The most common clinical presentation is palpable purpura of the lower half of the legs but type, site and calibre of the involved vessel district influence the localization and severity of the clinical features that may include urticarial, bullous, nodular and necrotic-ulcerative lesions. CSVV are idiopathic in 50% of cases and associated with drug intake, infections, connective tissue diseases or malignancies. The histological confirm of the diagnosis is mandatory and a laboratory investigation protocol is useful to discriminate skin-limited forms from extracutaneous visceral involvement. Treatment is strictly dependent on the clinical aspects and potential chronicity. First line drugs are colchicine and dapsone in combination with general measures such as leg elevation, warming and rest, but in case of recurrences, systemic involvement or coexistence of associated diseases, immunosuppressive agents may be necessary.
To learn about the two forms of Cogan syndrome, typical and atypical, and understand the need for early diagnosis to prevent complications such as deafness
Objective:
For many physicians, palpable purpura is synonymous with vasculitis. However, a skin biopsy is almost always performed in common clinical practice in order to confirm the diagnosis. The aim of our study was to assess whether palpable purpura is always indicative of an inflammatory infiltrate in a vessel wall.
Patients and methods:
Eighty-seven patients were included in this prospective monocentric study, 45 of whom were presenting a palpable purpura. Patients were classified in two categories: "leukocytoclastic vasculitis" or "other diagnosis". The clinical and histopathological features of patients with a palpable purpura were studied.
Results:
The mean age of patients presenting a palpable purpura was 69 years. There were 26 men and 19 women. Of the 43 patients biopsied, 37 were included in the vasculitis group. The sensitivity, specificity, positive predictive value and negative predictive value for a diagnosis of vasculitis in patients with palpable purpura were respectively 82, 65, 86 and 58 %. The Odds ratio was 8.48 (95 % CI, 2.52-31.80; P<0.05).
Conclusion:
Most of the palpable purpuras examined were indeed related to leukocytoclastic vasculitis. In the remaining cases, biopsy did not contribute to the diagnosis since it only showed purpura without vessel wall inflammation. In our opinion, a skin biopsy is thus not essential where the clinical presentation is typical.
Microscopic polyangiitis is a pauci-immune necrotizing small- and medium-vessel vasculitis mainly involving the lung and kidneys but also the peripheral nerves and skin. A variety of skin lesions are observed in about half of patients. The most common cutaneous manifestations are palpable purpura, livedo racemosa, and skin nodules. Histology of skin lesions typically shows leukocytoclasia with fibrinoid degeneration, neutrophil infiltration, and sometimes erythrocyte extravasation around the affected capillaries and small vessels in the dermis. Direct immunofluorescence shows absence of immunoglobulin deposits. A detailed clinical history and physical examination complemented by histological studies can aid in discriminating microscopic polyangiitis from other vasculitides affecting the skin.
Sjögren’s syndrome (pSS) is a common systemic autoimmune disease which primarily affects the salivary and lachrymal glands and usually leads to a persistent dryness of the mouth and eyes due to the lymphocytic infiltration and functional impairment of the exocrine glands. The disease is commonly included in the spectrum of connective tissue diseases (CTDs), and together with the other members of this disease family, it shares the possibility of a multisystemic involvement, a variable clinical picture, and a very large range of clinical and serological manifestations. Cutaneous manifestations are considered one of the most common extra-glandular features of pSS and can be distinguished as nonvascular lesions
(i.e., xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular lesions
(i.e., Raynaud’s phenomenon and vasculitis). In this chapter, the definition, differential diagnosis, and histological features of skin manifestations in pSS will be provided.
Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis characterized by multiple organ involvement due to the vascular deposition of immune complexes, mainly the cryoglobulins. B-lymphocyte expansion represents the underlying pathological alteration frequently triggered by hepatitis C virus (HCV) infection. Purpura and skin ulcerations, especially of the lower extremities, are the most frequent cutaneous manifestations representing one of the hallmarks of the disease. Ulcers appear torpid and deep and are associated with high levels of pain, inflammation, and tissue necrosis. In this chapter the definition, differential diagnosis, and histological features of skin manifestations in MC will be provided.
Granulomatosis with polyangiitis (Wegener’s granulomatosis; GPA) is a small-sized vessel ANCA-associated vasculitis. Dermatologic lesions may be the initial manifestations (8–13 %) or occur later during the course of the disease (12–67 % of the patients). Most frequent skin manifestations include purpura, mainly on the lower limbs, sometimes necrotic, papulonecrotic lesions, subcutaneous nodules, livedo reticularis, mucosal and skin ulcerations or ulcers, and gangrene. Hypertrophic gingivitis is another rare but suggestive manifestation. On histology, purpura is usually secondary to leukocytoclastic vasculitis, whereas papulonecrotic lesions and ulcerations correspond to leukocytoclastic or granulomatous vasculitis involving small vessels or extravascular granuloma(s). Small nodules mainly reflect necrotizing vasculitis involving medium-sized arterioles of the deep dermis or hypodermis that may be suggestive of polyarteritis nodosa for the pathologist.
Vasculitis is defined as an inflammatory cell infiltration and the destruction of blood vessels identified upon histological examination. Cutaneous manifestations may be the first and only manifestation of the disease or be a part of a systemic condition.
Cutaneous vasculitis (CV) affects small (<50 μm) and medium (<50–150 μm) vessels located in the dermis and the hypodermis.
Cutaneous lesions are frequent during the course of many systemic vasculitis. Lesions are often not specific, the most frequent being palpable purpura. Histology is mandatory to confirm the diagnosis of vasculitis to avoid delayed and inappropriate diagnosis that could lead to improper management. Cutaneous histology gives some data that may help to classify the vasculitis without determining precisely its type. A histological examination of all other skin lesions is necessary. The result of the biopsy has to be correlated to direct immunofluorescence data, medical history, physical examination, laboratory, and radiological findings leading to the correct diagnosis and effective treatment.
Rheumatoid arthritis (RA) and systemic connective tissue diseases including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, Sjögren’s syndrome, Behcet’s syndrome, and scleroderma are considered to be rheumatic conditions with secondary skin involvement. Rheumatoid vasculitis (RV) is the most serious systemic disease manifestation of RA and manifests almost exclusively in patients with RA. The frequency of leg ulceration in patients with RA may be up to 10 %. Ulcers in RA are usually multifactorial in etiology. Cutaneous vasculitis, skin fragility due to poor nutrition and corticosteroids, peripheral arterial disease, venous insufficiency, minor trauma, foot deformity, peripheral neuropathy, and peripheral edema are all factors to develop complex ulceration.
Systemic vasculitis requires aggressive therapy, such as the combination of high doses of glucocorticoids and a cytotoxic agent. Topical wound treatments of ulcers in association with RA can be developed by use of the principle of “wound bed preparation.” When infectious signs are noted, cleansing, wet-to-dry dressing or irrigation, and surgical debridement if necessary should be performed. Combination treatment with fibroblast growth factor, artificial dermis, and negative pressure wound therapy promotes preparing a favorable wound bed. When a wound is covered with suitable granulation, split-thickness autologous skin grafts should be performed as soon as possible.
Objective:
The increased cardiovascular risk associated with AS is attributable to multiple factors: disease activity, systemic inflammation, traditional risk factors and NSAIDs. This study aimed to investigate the effects of 24 and 52 weeks of TNF-α inhibitor treatment on arterial stiffness and cardiovascular risk factors.
Methods:
Arterial stiffness was measured using the augmentation index (AIx) and pulse wave velocity (PWV), while other cardiovascular risk factors [lipid profile, blood pressure (BP) and BMI] were collected for active AS patients.
Results:
In total, 49 patients, comprising 30 men, were included in the study, with a mean age of 46.9 (12.1) years. Of these, 20 (40.8%) patients were current smokers, while 10 were treated for hypertension. Patients had long-standing [11.9 (9.2) years] and active AS, with a high initial BASDAI [55.0 (18.2)]. Regarding treatment, 26 patients received etanercept, 17 adalimumab and 6 infliximab. No changes were observed in PWV and AIx after 6 or 12 months following TNF-α blockade [PWV 6.97 (2.03) m/s, 6.92 (1.81) m/s and 7.10 (1.95) m/s at baseline, 6 months and 1 year, respectively, P = 0.64; AIx 19.5 (13.1%), 20.2 (12.8%), 18.3 (13.5%), respectively, P = 0.87]. Lipid profiles and other cardiovascular risk factors were unchanged. However, BASDAI, BASFI and biological inflammation were significantly improved.
Conclusion:
Arterial stiffness was not improved after 6 and 12 months of anti-TNF-α therapy. However, treatment decreased biological inflammation and disease activity without causing any changes in lipid profiles and other traditional cardiovascular risk factors.
Permanent decorative tattooing involves the introduction of exogenous pigments and/or dyes into the dermis to produce the permanent design. Despite improved hygiene in the tattoo parlors of Western countries, this procedure still carries risk. Various complications may occur right after tattooing, from benign complications such as transient limb edema, palpable lymph nodes, and contact eczema, to more severe ones such as the inoculation of virulent microorganisms into the dermis, potentially life-threatening cellulitis, and necrotizing fasciitis or cutaneous vasculitis. This review focuses specifically on the complications that occur within the first month of tattooing that emergency physicians may have to manage.
To test the efficacy of treatment with rituximab in refractory rheumatoid vasculitis in patients with rheumatoid arthritis (RA).
Retrospective study of four female patients with histologically proven RA associated vasculitic cutaneous ulcers. All patients developed the lesions on long term treatment with methotrexate or leflunomide, and three of them with tumour necrosis factor alpha (TNF) blockers. All patients were refractory to prednisolone in the dosage between 0.5 and 1 mg/kg body weight for at least 4 weeks prior to rituximab. Rituximab were administered in two intravenous applications in the interval of 14 days accompanied by continued treatment with methotrexate or leflunomide and prednisolone.
Three out of four patients achieved a rapid clinical remission of the lesions within 4 to 6 weeks after rituximab therapy continuing at least for four months with a successful corticoid reduction till prednisolone 10 mg a day. One patient showed no remission of the skin lesions accompanied by increasing levels for ESR and CRP.
Rituximab treatment seems to be very effective in several cases of vasculitis-associated cutaneous ulcers in RA patients. However, the effectiveness of rituximab in cases with this indication remains to be shown in larger number of patients.
Henoch-Schönlein purpura (HSP) is an immune complex-mediated systemic vasculitis. Its genetic etiology remains unknown. CD18, the subunit of integrin beta2 in leukocytes, has essential roles in the expression and function of ITGB2, mediating immune responses. CD18 has been proved to be associated with some systemic vasculitides, such as microscopic polyangiitis and Churg-Strauss syndrome. We aimed to assess the influence of CD18 AvaII polymorphism (rs235326, C->T) in the incidence of HSP and determine its possible implication in severe systemic complications by studying 73 patients with HSP and 156 controls in China. Our results showed that AvaII polymorphism was not associated with HSP susceptibility (odd ratio (OR)=0.48, 95% confidence interval (CI)=0.53-1.39, p=0.63) or with HSP nephritic syndrome (OR=0.88, 95%CI=0.35-2.06, p=0.90). Moreover, we did not observe any significant association between serum parameters, such as CRP, IgA, IgE, C3 and C4, and HSP severity. In conclusion, our results suggested that CD18 AvaII is not associated with HSP susceptibility and its clinical outcomes.
Churg-Strauss syndrome (CSS) is a small-vessel vasculitis characterized by severe asthma, lung/tissues infiltrates, extravascular necrotizing granulomas, and eosinophilia. Cutaneous involvement is common but may not be highly suggestive. Two typical cases of CSS with cutaneous involvement are herein reported, both females, 37 and 54 years old, presenting with lower limbs palpable purpura and urticarial lesions of the neck, respectively. A comprehensive review of the literature showed that cutaneous manifestations occurred in 40-81% of CSS patients and were the presenting sign in 14% of the patients. Moreover, a total of 68 cases of CSS with a detailed description of the cutaneous lesions have been published. In the majority of these patients, skin lesions allowed for the histopathological diagnosis of CSS. The most common clinical features were papulo-nodules with the histological picture of extravascular Churg-Strauss granuloma followed by purpuric and/or necrotic lesions in the lower limbs corresponding to small-vessel vasculitis with eosinophils. Less common lesions included urticarial lesions and livedo reticularis. Therefore, a high index of suspicion on skin lesions and the proper lesion selection for histological examination may be very important for early diagnosis of CSS. Clinical-pathological correlation is essential, as both clinical and histological features are not pathognomonic.
Cutaneous polyarteritis nodosa (CPAN) is a self-limited cutaneous vasculitis characterized by painful nodules, affecting mostly the lower limbs, and livedo reticularis. Despite its benign course, CPAN may display a chronic relapsing evolution with repeated exacerbations. Ulcerative CPAN has a more prolonged evolution and is associated with peripheral neuropathy. We report on a patient with a 20-year history of ulcerative and painful CPAN, refractory to multiple immunosuppressive treatments, treated successfully by mycophenolate mofetil and pentoxifylline.
Comparison of vasculitis occurring in rheumatoid arthritis (RA) patients undergoing anti-tumor necrosis factor (TNF) treatment and those not.
Systematic, retrospective, observational study of all RA patients in one center (1997-2004). Vasculitis cumulative incidence in RA patients was calculated in patients receiving anti-TNF or those not. Clinical characteristics of RA and vasculitis were collected. Begaud's imputability tables were used to evaluate the role of anti-TNF in inducing vasculitis.
Out of 2707 RA patients, 440 received an anti-TNF. A vasculitis occurred in 6 patients treated with anti-TNF (cumulative incidence: 1.3%), and in 12 patients treated without anti-TNF (cumulative incidence: 0.5%). Characteristics of patients not treated with anti-TNF or treated were respectively (mean): age (years) at vasculitis occurrence: 66.5 vs. 55.3, disease duration (years): 12.2 vs. 13.8, extra-articular features before vasculitis: 16% vs. 60%, number of previous DMARDs: 3.2 vs. 4.5, corticosteroid cumulated dosage (grams): 40.8 vs. 64.3. Vasculitis was cutaneous (58% vs. 67%), neurologic (58% vs. 67%), visceral (8% vs. 17%), and required a treatment in 66% vs. 83%. Using Begaud's tables, anti-TNF could be responsible for inducing vasculitis in 2 out of 6 patients.
In RA, vasculitis is more frequent during anti-TNF treatment than without anti-TNF. Anti-TNF could be responsible for inducing vasculitis in 2 patients. Patients treated with anti-TNF had more severe RA. It remains to be determined whether vasculitis is a consequence of anti-TNF inefficacy or whether it is treatment-related. In vasculitis occurring with anti-TNF, classical treatment seems more suitable than a switch to another anti-TNF.
Vasculitis is defined as inflammation directed at vessels, which compromises or destroys the vessel wall leading to haemorrhagic and/or ischaemic events. Although the most common clinical finding of vasculitis is palpable purpura, patients may also present with other lesions including urticaria, infiltrative erythema, petechiae, purpura, purpuric papules, haemorrhagic vesicles and bullae, nodules, livedo reticularis, deep ulcers and digital gangrene. Classification systems have been important in the study of vasculitic diseases, and the most widely accepted one is based on the size of the vessel involved. This article will focus on the most common forms of cutaneous vasculitis.
Crohn's disease (CD) and ulcerative colitis (UC) share common clinical features with Behçet's syndrome (BS). We surveyed UC and CD patients for pathergy phenomenon and features of BS with the aim of determining how much overlap is present between these 2 entities in a setting where BS is relatively common, the frequency of pathergy positivity in inflammatory bowel disease (IBD) patients and evaluating how International Study Group (ISG) criteria perform in differentiating IBD from BS.
This study was conducted among patients with CD and UC attending the gastroenterology outpatient clinic of a university hospital which is also a referral center for BS. Consecutive CD and UC patients were screened for BS using ISG criteria. Pathergy test was performed and evaluated by 2 independent observers in a masked manner.
Ninety-three patients with CD and 130 with UC were surveyed. None of the CD patients fulfilled ISG criteria for BS while 2 of 130 UC patients did. Twenty CD patients had oral ulcers while 4 reported having genital ulcers but no scars could be observed. Twenty-two CD patients had papulopustular lesions, 2 had nodular lesions, 3 had arthritis and none had uveitis. Thirty-two UC patients had oral ulcers, none had genital ulcers, 23 had papulopustular lesions, 3 had nodular lesions, 2 had arthritis and 2 had uveitis. Pathergy test was positive according to at least one of the observers in 10/93 CD and 8/130 UC patients and according to both observers in 4/130 UC patients.
Despite similarities between the clinical features of CD and UC with BS, coexistence is uncommon. ISG criteria perform well in differentiating these diseases. About 8% of IBD patients show the pathergy phenomenon.
Serum levels of the B-cell activating factor in the tumor necrosis factor family (BAFF), a potent contributor to B-cell survival, are elevated in patients with systemic autoimmune diseases. The objective of this study was to determine serum BAFF levels and to link the results to the clinical features in patients with skin manifestations.
Serum BAFF levels were examined by an enzyme-linked immunosorbent assay (ELISA) in 42 patients with BD (16 with active disease), 20 healthy controls, and in 20 patients with systemic lupus erythematosus (SLE) and 15 patients with multiple sclerosis (MS), who served as the disease control groups. Expression of BAFF messenger RNA (mRNA) in the skin was quantified by a real-time reverse transcription-polymerase chain reaction; the expression of BAFF receptor (BAFF-R) on CD19+ B cells was assessed by flow cytometry; and ELISA was used to evaluate the production of IgG, interleukin-6 (IL-6) and IL-10 by isolated B cells.
Serum BAFF levels were elevated in patients with active BD compared to the healthy controls, and correlated positively with the extent of skin lesions. Disease remission was accompanied by decreased BAFF levels. SLE patients had the highest serum BAFF levels. Skin biopsies showed BAFF mRNA expression to be up-regulated in active BD patients. BAFF-R expression on B cells was increased in BD patients with vasculitis. Furthermore, in BD patients the ability to produce IgG and IL-6 (but not IL-10) was enhanced in BAFF-stimulated B lymphocytes.
These results suggest that BAFF and its signalling in B cells contribute to B cell abnormalities and the development of skin disease in patients with BD.
To analyze the different clinical and histologic types of cutaneous vasculitis in patients with primary Sjögren syndrome (SS), we investigated the clinical and immunologic characteristics of 558 consecutive patients with primary SS from our units and selected those with clinical evidence of cutaneous lesions, excluding drug reactions and xeroderma. All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. A total of 89 (16%) patients presented with cutaneous involvement (88 female patients and 1 male; mean age, 51.8 yr). The main cutaneous involvement was cutaneous vasculitis, present in 52 (58%) patients. There were 51 (98%) female patients and 1 (2%) male, with a mean age at diagnosis of cutaneous vasculitis of 51 years (range, 20-80 yr). Fourteen presented with cryoglobulinemic vasculitis, 11 with urticarial vasculitis, and the remaining 26, with cutaneous purpura not associated with cryoglobulins. A skin biopsy specimen was obtained in 38 patients (73%). Involvement of small-sized vessels was observed in 36 (95%) patients (leukocytoclastic vasculitis), while the remaining 2 (5%) presented with medium-sized vessel vasculitis (necrotizing vasculitis). Patients with cutaneous vasculitis had a higher prevalence of articular involvement (50% vs 29%, p = 0.044), peripheral neuropathy (31% vs 4%, p < 0.001), Raynaud phenomenon (40% vs 15%, p = 0.008), renal involvement (10% vs 0%, p = 0.028), antinuclear antibodies (88% vs 60%, p = 0.002), rheumatoid factor (78% vs 48%, p = 0.004), anti-Ro/SS-A antibodies (70% vs 43%, p = 0.011), and hospitalization (25% vs 4%, p = 0.005) compared with SS patients without vasculitis. Six (12%) patients died, all of whom had multisystemic cryoglobulinemia.In conclusion, cutaneous involvement was detected in 16% of patients with primary SS, with cutaneous vasculitis being the most frequent process. The main characteristics of SS-associated cutaneous vasculitis were the overwhelming predominance of small versus medium vessel vasculitis and leukocytoclastic versus mononuclear vasculitis, with a higher prevalence of extraglandular and immunologic SS features. Small vessel vasculitis manifested as palpable purpura, urticarial lesions, or erythematosus maculopapules, with systemic involvement in 44% of patients in association with cryoglobulins in 30%. Life-threatening vasculitis was closely related to cryoglobulinemia.
Cutaneous vasculitis (CV), a condition characterized by palpable purpura and nonspecific histopathologic findings, presents a diagnostic and therapeutic challenge because it may be a primary disorder or it may be a cutaneous manifestation of another entity, such as systemic necrotizing vasculitis, connective tissue disease, systemic bacterial infection, or malignancy. We studied 303 unselected patients (172 adults and 131 children) with CV to assess the disease associations and etiologic factors, to identify the frequency of primary and secondary CV in different age-groups, and to characterize features that help to distinguish between primary and secondary CV. Of the 131 children, 130 had primary CV: Henoch-Schönlein purpura (HSP) in 116 and hypersensitivity vasculitis (HV) in 14. In contrast, of the 172 adults, only 120 had primary CV: HSP in 39, HV in 70, and essential mixed cryoglobulinemia in 11. CV was a manifestation of systemic necrotizing vasculitis in 23 adults (polyarteritis nodosa in 17, Wegener granulomatosis in 4, and Churg-Strauss syndrome in 2). CV was secondary to other processes in 29 adults: in 20 patients CV was associated with connective tissue disease or another autoimmune or rheumatic disease, in 5 patients CV was a manifestation of severe bacterial infection, especially bacterial endocarditis (4 cases), and in the other 4 patients CV was the presenting symptom of an underlying malignancy. The patients for whom CV was a manifestation of systemic necrotizing vasculitis or secondary to a connective tissue disease, severe bacterial infection, or malignancy had clinical and laboratory data suggestive of the associated disorder. The clinical picture and outcome of primary CV in both children and adults were benign. By contrast, the prognosis of patients with CV in the context of systemic necrotizing vasculitis or secondary to other entities depended on the primary process. Given the different disease association in children and adults, we propose a simple diagnostic workup in children with CV. By contrast the diagnostic approach in adults with CV should be more cautious and the workup more extensive. The early differentiation between primary CV, secondary CV, and CV presenting as a symptom of systemic necrotizing vasculitis, especially in adults, is of paramount importance for an adequate diagnosis and appropriate treatment.
PurposeCryoglobulinemia are immune complexes that may induce systemic cryoglobulinemic vasculitis. Cryoglobulin may be an isolated biological abnormality or may induce clinical manifestations of a systemic vasculitis, involving the skin, the joints, the peripheral nerve system and the kidneys.
Purpose. – Horton disease or ‘giant cell arteritis’ is a known entity in its typical form; the difficulty in diagnosis is due to the atypical signs and symptoms.Methods. – We review 260 medical files presenting Horton disease between 1979 and 1999 in five different departments: three internal medicine departments, one rheumatology department and one geriatric department.Results.– The study shows a female domination with a mean age of 75 years. Temporal artery biopsy was done on all patients. Ten patients presented a vascular manifestation. The neurological manifestation was the first symptom in four patients. Five patients had cutaneous symptomatology, with positive temporal artery in three cases. Renal manifestation was present in two patients. Two symptoms are important to discuss because of their frequency: the cough and the peripheral arthritis. We found nine observations with arthritis affecting large joints and responding to nonsteroidal anti-inflammatories with positive temporal artery biopsy in seven patients, and 21 observations manifesting by cough without radiological signs; in 57% of cases the temporal artery biopsy was positive, and the cough regressed with corticoids.Conclusion. – These atypical symptoms have to be known to make a diagnosis and to begin a corticotherapy as soon as possible.
Wegener''s granulomatosis and Churg--Strauss syndrome are the two primary systemic necrotizing vasculitides that are most typically characterized by granulomatous inflammation of small vessel walls. The skin may be involved in both, with biopsies often showing nonspecific leukocytoclastic vasculitis but also, in some cases, granulomatous vasculitis and/or extravascular granulomas. Such lesions can also be seen, but rarely, in Takayasu''s arteritis and giant-cell arteritis, which are large-vessel vasculitides. At onset, these systemic vasculitides usually have other severe systemic and/or organ-specific symptoms that contribute to achieving the diagnosis. However, other diseases or conditions can also be associated with cutaneous granulomatous vasculitis and/or extravascular granulomas and have to be considered in the differential diagnosis, for instance, lymphomatoid granulomatosis, lymphoproliferative hemopathies, inflammatory and autoimmune diseases, such as rheumatoid arthritis or systemic lupus erythematosus, inflammatory bowel disease and, rarely, infections with herpes simplex, varicella-zoster or hepatitis C virus.
The cutaneous manifestations of microscopic polyangiitis (MPA) and polyarteritis nodosa (PAN) have not been compared since their distinction. Objectives To compare the clinical and pathological cutaneous manifestations in a series of patients with systemic MPA and PAN.
Patients with MPA (n = 162) and PAN (n = 248) from the database of the French Vasculitis Study Group were diagnosed according to the American College of Rheumatology and/or the Chapel Hill Consensus criteria. Purpura, livedo, nodules, urticaria, skin necrosis, oral and genital ulcers were recorded when present. Fifty-five skin biopsies were analysed. Clinical and histological skin data were compared in the following groups: MPA, PAN and two PAN subsets: PAN with and PAN without hepatitis B infection. The prevalence of systemic and biological manifestations were analysed in relation to the presence or absence of skin lesions. The chi(2) test was used for statistical studies.
Cutaneous manifestations were present in 44% of MPA and PAN. Purpura was the most frequent manifestation (26% cases of MPA vs. 19% cases of PAN, P = 0.026). Urticaria was more frequent during PAN (6% vs. 1.2%, P = 0.015). Skin lesions were more frequent during PAN in the absence of HBV infection (54% vs. 30%, P < 0.05). No significant difference was detected from the histological data. Patients with skin lesions (either MPA or PAN) presented arthralgias and ocular manifestations more frequently. Mononeuritis multiplex was associated with skin lesions in the MPA group (P < 0.05).
The clinical or histological analysis of cutaneous lesions is not helpful for distinguishing PAN from MPA.
A 6-year-old Caucasian girl presented with a 4-month history of a mildly pruritic, brown and pink, focally petechial macules on the posterior aspect of her left leg, clinically consistent with a pigmented purpuric dermatosis. Biopsy, however, revealed lymphocytic inflammation with occlusion of the lumen of a small artery at the dermal-subcutaneous junction, characteristic of macular arteritis. This is a recently described entity that is not known to be associated with systemic disease, and remains stable over years without treatment. So far, it has not been reported in a Caucasian patient. We review the clinical and histologic features, as well as the laboratory evaluation of this case, and the previously reported cases.
To prospectively study the clinical features, pathophysiology, treatment and prognosis of Wegener granulomatosis.
Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years).
Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system.
The Warren Magnuson Clinical Center of the National Institutes of Health.
Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low-dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for greater than 5 years, 44% had remissions of greater than 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%).
The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens.
In the 72 cases of cryoglobulinemia reviewed, erythematous to purpuric macules or papules were present in 92%. Infarction, hemorrhagic crusts, and ulcers were present in 10% to 25% of the patients and were relatively more common in type I cryoglobulinemia than in the other types. Postinflammatory hyperpigmentation was noted in 40%. Lesions on the leg were common in all types of cryoglobulinemia; however, lesions on the head and mucosal surfaces suggested type I cryoglobulinemia. Histopathologic features were classified as vasculitis in 50%, inflammatory or noninflammatory purpura in 15%, noninflammatory hyaline thrombosis in 10%, and postinflammatory sequelae in 10%. Noninflammatory hyaline thrombosis was relatively more frequent in type I. Thus erythematous to purpuric lesions on the legs and leukocytoclastic vasculitis are the common cutaneous findings in cryoglobulinemia. Type I cryoglobulinemia is suggested by noninflammatory hyaline thrombosis, cutaneous infarction, hemorrhagic crusts, skin ulcerations, and lesions of the head and neck and of oral or nasal mucosa.
The aim of this retrospective study is to delineate in Europe the frequency and type of cutaneous manifestations associated with Takayasu arteritis (TA). Eighty patients with TA were analyzed. Symptoms suggestive of Raynaud's syndrome were noted in 11 patients (14%) and could be directly related to large vessel involvement. Other skin lesions were observed in 10 patients (12.5%). Five had acute tender erythematous nodules on the legs with a clinical diagnosis of erythema nodosum; 2 had subacute ulcerated nodules of the legs; 1 had pyoderma-gangrenosum-like ulcerations of the four limbs which resulted from the breakdown of subcutaneous nodules; 1 had lupus-like malar flush, and the last one had urticarial lesions with livedo reticularis. Skin samples were obtained from 4 patients. Three of them agreed that reiterated biopsies be done on recurrent lesions. A granulomatous vasculitis was observed in 2 cases involving hypodermal arterioles in one case and veins in the other. The other pathological findings were septal and lobular panniculitis which can be associated with granulomatous vasculitis. Different histological findings on reiterated biopsies were frequently found. The absence of any other etiology and chronological arguments suggested a relationship between these skin lesions and TA. Tuberculosis was probable in 1 case but apparently was not related to the skin lesions.
Wegener's granulomatosis, lymphomatoid granulomatosis, and Churg-Strauss granulomatosis may all have cutaneous involvement. The morphology of cutaneous lesions in these disorders varies from macular erythema to frank gangrenous ulceration. Most often lesions are located on the extremities; however, truncal or facial involvement has been reported, the latter especially in Wegener's granulomatosis. A common histologic finding in these cutaneous lesions is necrotizing vasculitis. However, it is also possible to see Churg-Strauss extravascular granulomas and even periarteritis. Cutaneous involvement with these three forms of systemic granulomatosis generally parallels the systemic course. The treatment for the cutaneous lesions is dictated by the treatment for the systemic vasculitis. It is important to recognize that the cutaneous extravascular granuloma and cutaneous granulomatous vasculitis can be associated with other disorders in addition to systemic granulomatosis. These disorders include most importantly lymphoproliferative diseases, inflammatory disorders such as arthritis, autoimmune diseases, and other inflammatory disorders such as sarcoidosis. Cutaneous involvement with giant cell or temporal arteritis is not common, but ulcerative temporal-parietal scalp lesions are distinctive. Although not common in the United States, Takayasu's arteritis may have several cutaneous manifestations, including erythema nodosum-like lesions. Granulomatous vasculitides have a myriad of cutaneous manifestations. Knowledge of these manifestations may allow for prompt diagnosis in many cases and increased surveillance in other cases for associated systemic illnesses.
Criteria for the classification of hypersensitivity vasculitis were developed by comparing 93 patients who had this disease with 714 control patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than 16 at disease onset, history of taking a medication at onset that may have been a precipitating factor, the presence of palpable purpura, the presence of maculopapular rash, and a biopsy demonstrating granulocytes around an arteriole or venule. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 71.0% and a specificity of 83.9%. A classification tree was also constructed. The criteria appearing in the tree structure were the same as for the traditional format, except there were 2 pathology criteria: one required the presence of granulocytes in the wall of an arteriole or venule, and the other required the presence of eosinophils in the inflammatory exudate. The classification tree was associated with a sensitivity of 78.5% and a specificity of 78.7%.
Takayasu's arteritis is a chronic, granulomatous, large-vessel arteriopathy of unknown cause. We retrospectively reviewed the medical records of 38 patients with Takayasu's arteritis and identified 21 with cutaneous findings. Seven patients had lesions that were related to their systemic vasculitis. We found a Churg-Strauss granuloma, a pyodermatous leg ulcer, and inflammatory leg nodules in these patients. Biopsy specimens from three patients with presumed "erythema nodosum" did not support the clinical diagnosis but did show arteritis. In patients with Takayasu's arteritis, small-vessel inflammation, and other inflammatory lesions may be present, in addition to large-vessel disease. Histopathologic study is necessary to categorize the nature of inflammatory leg nodules of these patients.
The origin of leukocytoclastic vasculitis (LV) being often difficult to determine, we have undertaken since 1980 a prospective study of factors associated with LV. We selected 53 patients whose LV was clinically predominant, and excluded patients in whom LV was an expected phenomenon in a known autoimmune or infectious disease. Twenty-eight of the 53 patients presented with a typical Gougerot-Ruiter disease, 15 with a bullous or necrotic form of the disease and 10 with urticarial lesions. Detail of the prospective laboratory tests performed is given in table I. Correlations between laboratory values and LV-associated factors were significant with the decrease of complement but not with the presence of circulating immune complexes, rheumatoid factor, cryoglobulin or direct immunofluorescence test positivity. Most of the associated factors in our series were infectious agents (streptococci, hepatitis virus), immunological agents (rheumatoid factor, cryoglobulin) or drugs known to be potential LV-inductors; other factors were less common or quite recently described (enterovirus, Yersiniae, cirrhosis, primary liver cancer, Chlamydiae, refractory anemia with an excess of myeloblasts. We do not feel that a large series of laboratory tests should be performed in every case of LV. The clinical context and simple laboratory tests, such as blood cell count, complement assay, plasma electrophoresis and a search for rheumatoid factor should be enough to guide the clinician and help him decide whether further investigations are needed. However, it should be noted that in some cases without clinical pointers only full virological evaluation enabled us to determine that enteroviruses may be involved in the pathogenesis of LV.
Eighty-six patients with cryoglobulinemia repeatedly underwent complete immunochemical and clinical evaluation during the course of their disease. Immunochemical analysis of the purified cryoglobulins allowed us to classify them into three groups. Type I cryoglobulins are made of isolated monoclonal immunoglobulin: IgM (11 cases), IgG (7 cases), IgA (2 cases) or Bence Jones protein (1 case). Type II cryoglobulins are mixed cryoglobulins with a monoclonal component possessing antibody activity towards polyclonal IgG. These cryoglobulins were mainly IgM-IgG (19 cases), sometimes IgG-IgG (2 cases) or IgA-IgG (1 case). Type III cryoglobulins (43 cases) are mixed polyclonal cryoglobulins, i.e., composed of one or more classes of polyclonal immunoglobulins and sometimes nonimmunoglobulin molecules such as beta1C or lipoprotein. Most of these type III cryoglobulins are also immunoglobulin-anti-immunoglobulin immune complexes. This classification enabled us to establish correlations between the biologic findings and the clinical features as well as the underlying diseases.Cutaneous and vasomotor symptoms were most severe in patients with type I and II cryoglobulins. The usual clinical picture in patients with type II or III cryoglobulins consisted of chronic vascular purpura and mild Raynaud's phenomenon. Renal and neurologic involvement were more frequent in patients with type II and III cryoglobulins, and were of major prognostic significance. In our series, immunoproliferative and autoimmune disorders were the most frequent diseases associated with cryoglobulinemia. The former were associated with type I or II cryoglobulins and the latter mainly with type III cryoglobulins. Of note is that idiopathic cryoglobulinemia accounted for nearly 30 per cent of the cases despite repeated careful clinical evaluation and a mean follow up of 9 years.In 10 per cent of the cases, acute and severe symptoms necessitated emergency treatment with plasmapheresis and chemotherapy which allowed a satisfactory initial remission in all but one patient. Conversely, no treatment was definitively effective in patients with chronic symptoms such as vascular purpura.
Eighty-five patients with Wegener's granulomatosis were studied for 21 years at the National Institutes of Health. Patients were treated with a protocol consisting of cyclophosphamide, 2 mg/kg body weight d, together with prednisone, 1 mg/kg body weight d, followed by conversion of the prednisone to an alternate-day regimen. Complete remissions were achieved in 79 of 85 patients (93%). The mean duration of remission for living patients was 48.2 (+/- 3.6) months. Twenty-three patients are off all therapy for a mean duration of 35.3 (+/- 6.3) months without therapy. This study provides a prospective experience with Wegener's granulomatosis and shows that long-term remissions can be induced and maintained in an extremely high number of patients by the combination of daily cyclophosphamide and alternate-day prednisone therapy.
An association between essential mixed cryoglobulinemia and hepatitis C virus (HCV) infection has been reported. Dermatologic manifestations are a classic presenting complaint in essential mixed cryoglobulinemia. The aim of this study was to compare the frequency and the nature of dermatologic manifestations in essential mixed cryoglobulinemia according to the presence of anti-HCV antibodies. Sixty-two consecutive patients with essential mixed cryoglobulinemia were tested for anti-HCV antibodies. Dermatologic manifestations were systematically assessed.
Anti-HCV antibodies were detected in 35 patients. Palpable purpura corresponding histologically to leukocytoclastic vasculitis was the more frequently observed dermatologic manifestation and occurred mainly in HCV-antibody-positive patients. The patients with purpura had significantly higher serum cryoglobulin levels than patients without purpura.
The frequency of palpable purpura is higher in HCV-antibody-positive patients and is related to the serum cryoglobulin levels.
While no cutaneous lesion is specific for Wegener's granulomatosis (WG), several histopathologic entities, including leukocytoclastic vasculitis and necrotizing granulomatous inflammation, are characteristic. This report details the histopathologic features of 75 cutaneous biopsies from 46 patients with WG. Biopsies were subdivided into histologic groups that included leukocytoclastic vasculitis (31%), granulomatous inflammation (GI) (19%), nonspecific ulceration (4%), superficial dermal and epidermal necrosis without inflammation (2.7%), erythema nodosum (2.7%), granuloma annulare (1%), chronic inflammation (31%), and acute inflammatory lesions without vasculitis (9%). No convincing example of granulomatous vasculitis was observed. The histopathologic subgroups were correlated with clinical features, and the results were compared with those from a control group of 82 WG patients with no skin involvement. We found that the histopathologic subgroups of leukocytoclastic vasculitis and granulomatous inflammation correlated with different clinical courses. Patients with leukocytoclastic vasculitis developed WG at an earlier age (median age, 30 years) than did the control group (median age, 45 years). Leukocytoclastic vasculitis developed shortly after onset of WG (median, 15 months vs. 35 months for patients with nonspecific chronic inflammation). All lesions occurred during active disease. Active disease with leukocytoclastic vasculitis was associated with a mean erythrocyte sedimentation rate twice that of active disease in the same patient when leukocytoclastic vasculitis was absent. The patients with leukocytoclastic vasculitis had more rapidly progressive and widespread WG than patients with granulomatous skin lesions or patients without skin lesions. A marked excess of joint and musculoskeletal symptoms and renal disease was seen in patients with leukocytoclastic vasculitis. Patients with granulomatous inflammation also developed WG at an early age (median age, 30 years) when compared with the control group. Cutaneous granulomatous lesions also developed shortly after presentation (median, 12 months). Only 64% of granulomatous biopsies were from patients with active disease. These patients frequently had neither renal nor pulmonary manifestations of WG, and their disease progressed at a slower rate than that of the patients with leukocytoclastic vasculitis. These findings suggest that the cutaneous lesions characteristic of WG may correlate with the activity, distribution, and course of the disease.
Mucosal and cutaneous manifestations of Wegener's granulomatosis (WG) are usually described separately. Both frequently occur at any time of the illness. The aim of this work was to analyze, retrospectively, dermatologic symptoms of 75 WG cases encountered from 1973 through 1992. All patients fulfilled the American College of Rheumatology criteria for WG. We compared clinical and histologic findings and looked for a relationship between these manifestations, disease activity, and other symptoms of WG.
Thirty-five patients had skin or mucosa involvement. Clinical features were palpable purpura (26 cases), oral ulcers (15), skin nodules (six), skin ulcers (five), necrotic papules (five), gingival hyperplasia (three), pustules (two), palpebral xanthoma (two), genital ulcer (one), digital necrosis (one), and livedo reticularis (one). Pathologic findings depended on clinical aspects. Thirty-five involved skin or mucosa biopsy specimens were obtained from 24 patients. Nongranulomatous vasculitis was associated with purpuric lesions. Granulomatous inflammation was associated with nonpurpuric lesions. Dermatologic manifestations were associated with a higher frequency of articular and renal involvement (68% vs 25%; 80% vs 47%, respectively). Except for xanthoma, onset of skin or mucosa lesions indicated active systemic disease. These manifestations responded well to steroids and cyclophosphamide.
Various dermatologic manifestations are frequently observed in WG. They have distinctive pathologic features and usually indicate the presence of active systemic disease, especially with kidney and joint involvement.
A 69-year-old man had erythema elevatum diutinum for several years before he developed IgA paraproteinemia and a limited form of Wegener's granulomatosis. This is the first report of an association between erythema elevatum diutinum and Wegener's granulomatosis. IgA paraproteinemia has been reported in association with erythema elevatum diutinum but not with Wegener's granulomatosis.
Many people develop skin symptoms after long-distance walks, but little is known about the aetiology of these. In this study we took 11 biopsies from 10 long-distance walkers who walked 80 km. All biopsies originated from purpuric lesions on the lower legs, which had appeared during walking. In all 11 specimens, signs of a leucocytoclastic vasculitis were present with leucocytoclasis, exocytosis of erythrocytes and a granulocyte/mononuclear perivascular infiltrate. Immunofluorescence investigations showed deposition of C3c in many specimens and immunoglobulin M in some. The occurrence of a leucocytoclastic vasculitis after prolonged exercise may be explained by the existence of an exercise altered cutaneous microcirculation, complement activation and an altered immune function.
Vasculitis resulting from drug use includes a wide variety of clinical and pathologic conditions that are, in general, empirically defined and poorly understood. Further complicating our grasp of these disorders are ambiguous terms such as hypersensitivity vasculitis, allergic vasculitis, leukocytoclastic vasculitis, serum sickness, and others, which are often used interchangeably without clear definition. The clinical picture varies widely from self-limiting to progressive and even fatal illness. These syndromes have now been reported in association with newer classes of therapeutic agents including biologic response modifiers. Vasculitis affecting the central nervous system may be related to a variety of drugs and remains one of the more important syndrome sets within the spectrum of drug-induced vasculitis. These disorders are clinically important, because removal of the offending drug often is associated with regression of the vasculitic condition.
To evaluate the incidence of extracutaneous manifestations and to identify predictive factors for renal involvement in adult patients with Schönlein-Henoch purpura.
Retrospective study with a comparative analysis of patients with and without renal involvement.
Patients who were attending the dermatologic department of an academic medical center.
In patients with purpura of the lower limbs and cutaneous vascular IgA deposits for which cases were recorded from 1985 to 1993, the following selection criteria were used: age older than 15 years and absence of thrombocytopenia, of IgA deposits in the basement membrane zone, and of a known hematologic or connective tissue disorder.
Clinical and biological data, results of histological studies, and findings from direct immunofluorescence studies of skin biopsy specimens were compared in patients with and without renal involvement.
Fifty-seven patients were included: 23% had an IgA glomerulonephritis confirmed by results of a renal biopsy, and a further 26% showed abnormalities on urine microscopy. Joint and gastrointestinal involvement was noted in, respectively, 33% and 19% of the patients. A comparative analysis of patients with and without renal involvement failed to reveal significant differences with regard to age, sex, the presence of bullous or necrotic cutaneous lesions, gastrointestinal or joint involvement, histological features, and findings from direct immunofluorescence studies. An IgA glomerulonephritis was significantly associated with purpura above the waist (P = .03), a recent infectious history (P = .02), pyrexia (P = .01), and biological markers of inflammation (P = .006).
Despite a lower incidence of systemic involvement compared with that in other published series, the incidence of renal involvement remained high (ie, between 23% and 49%). A recent infectious history, pyrexia, the spread of purpura to the trunk, and biological markers of inflammation were predictive factors for renal involvement.
A patient with giant cell arteritis (GCA) who developed scalp necrosis (SN) is described and 23 other cases in the English language literature are reviewed. SN is rare and occurs in older patients of mean age 77 yr. Thirteen patients presented to dermatologists. Nineteen (79%) had other serious complications of GCA: visual loss in 16, gangrene of the tongue in four and nasal septum necrosis in one. The mean interval between the onset of symptoms of GCA and SN was 3.0 months in the 19 cases which antedated corticosteroid therapy. SN resulted from active arteritis and no case was definitely linked to temporal artery biopsy. Scalp healing was complete or progressing satisfactorily in 18 cases (75%). SN is a potentially reversible complication of GCA and adequate corticosteroid therapy is mandatory. In the current case. SN related to inadequate dosage of prednisolone.
Allergic granulomatosis of Churg-Strauss (Churg-Strauss syndrome) is a distinct clinical disease of multisystem vasculitis.
We characterize the clinical and histologic features of cutaneous findings in Churg-Strauss syndrome.
All patients with Churg-Strauss syndrome seen between 1976 and 1995 were retrospectively reviewed.
Ninety patients with the diagnosis of Churg-Strauss syndrome were identified; 36 (40%) had cutaneous findings. Five patients (6%) had skin lesions as the initial manifestation. The most frequent cutaneous findings were purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows. In 37 biopsy specimens from 29 patients, the most common findings were extravascular necrotizing granuloma (15 specimens) and leukocytoclastic vasculitis (16 specimens).
Cutaneous lesions in Churg-Strauss syndrome are common. Their characteristic clinical and histologic pattern may help establish the diagnosis.
To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group.
A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings.
Forty-seven men and 38 women, with a mean +/- SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%.
This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent.
Oral and genital aphthae are the main clinical dermatologic manifestations of Behçet's disease. They look like those that occur in other aphthosis. Cutaneous lesions include pseudofolliculitis, folliculitis, erythema nodosum-like lesions, Sweet's-like lesions and pyoderma gangrenosum-like lesions. Histologically, these lesions are frequently perivascular with proeminent infiltrates of neutrophils and/or lymphocytes. Hypersensibility to needle pricks is explored by the pathergy test which sensibility is highly variable depending on the countries. When there is no systemic lesions requiring oral corticosteroids or immunosuppressive therapy, colchicine, aspirine, or dapsone may be prescribed. Thalidomide is sometimes required if aphthosis is refractory to other treatments despite its neurotixic and teratogenic effects.
Takayasu arteritis (TA) is an inflammatory arteriopathy involving predominantly the aorta and its main branches. The disease evolves in two phases: a first, nonspecific inflammatory stage and a late 'pulseless' stage, in which complications related to arterial stenosis and aneurysm formation predominate. In both phases, skin manifestations, such as inflammatory nodules, erythema-nodosum- and pyoderma-gangrenosum-like ulcers, have been described. We report 2 patients with TA, who had cutaneous necrotizing vasculitis as presenting manifestation of the disease. A review of the literature revealed 8 similar cases. TA does not only involve large arteries, but also small blood vessels. The observation that in TA the inflammatory process of the large arteries affects regions of the walls supplied by the vasa vasorum, the anatomy of which bears resemblance to the cutaneous vessel system, suggests that primary involvement of small vessels contributes to the development of the clinicopathological features of TA. Knowledge of the skin manifestations associated with TA remains important for its diagnosis and prompt instauration of life-saving treatment.
To evaluate the literature for published cases of drug-induced vasculitis with cutaneous and/or systemic manifestations.
The MEDLINE database was searched from 1965 to December 1999 for articles focusing on drugs and vasculitis, using various search terminologies (e.g., Churg-Strauss syndrome, Goodpasture's syndrome, Henoch-Schönlein purpura, various drugs suspected to induce vasculitis). Cases were included when they met the established criteria as described in the methodology.
Drugs found to be most frequently associated with vasculitis were propylthiouracil, hydralazine, colony-stimulating factors, allopurinol, cefaclor, minocycline, D-penicillamine, phenytoin, isotretinoin, and methotrexate. The interval between the first exposure and appearance of symptoms was reported to be extremely variable (hours to years). Vasculitis has occurred after drug dosage increases and after rechallenge with the suspected drug. In the majority of cases, vasculitis has resolved after discontinuing the drug. Patients with more severe, often life-threatening, manifestations have required treatment with corticosteroids, plasmapheresis, hemodialysis, or cyclophosphamide. Death was the result in 10% of all published cases, with a predominance in patients in whom multiple organ systems were involved.
Clinicians need to be suspect of drug-induced vasculitis to enable prompt diagnosis and treatment. This should improve patient outcomes based on the data referenced for this article.
Sweet syndrome is characterized by painful, erythematous plaques of rapid onset accompanied by fever. Absence of vasculitis is a histologic criterion for diagnosis. However, recent reports suggest that vasculitis should not exclude the diagnosis. We hypothesized that vasculitis can occur in Sweet syndrome and that it represents an epiphenomenon rather than a primary immune-mediated process.
Skin biopsy specimens from patients with Sweet syndrome were reviewed to determine the prevalence of vasculitis. The clinicopathologic features of cases with vasculitis were evaluated for statistically significant associations. Specimens with vasculitis underwent immunofluorescence staining.
University department of dermatology, university hospital, and private practice.
Medical records and biopsy specimens of 21 patients meeting diagnostic criteria for Sweet syndrome were reviewed.
None.
The prevalence of vasculitis was 29% (6 of 21 patients). There was a significant association of vasculitis with lesions of longer duration (P =.02). Vascular immunoglobulin and complement could not be demonstrated in cases of Sweet syndrome with vasculitis.
Vasculitis is not a primary, immune-mediated process in Sweet syndrome but occurs secondary to noxious products released from neutrophils. Blood vessels in lesions of longer duration are more likely to develop vasculitis than those of shorter duration because of prolonged exposure to noxious metabolites. Vasculitis does not exclude a diagnosis of Sweet syndrome.
Cutaneous manifestations are the most frequent, and often the initial feature of extra-articular involvement in patients with rheumatoid vasculitis.
The purpose of the study was to evaluate the clinical and histological spectrum of cutaneous vasculitis and the associated systemic involvement in patients with rheumatoid vasculitis.
Among 525 patients with rheumatoid arthritis, 20 tissue specimens with histologically proven cutaneous necrotizing vasculitis from 11 patients were investigated by studying the types and levels of affected vessels and related clinical features.
Small-vessel vasculitis identified as dermal necrotizing venulitis was found in 10 patients, clinically characterized by palpable purpura, maculopapular erythema, erythema elevatum diutinum and haemorrhagic blisters. Arteritis histologically resembling cutaneous polyarteritis nodosa, clinically characterized by subcutaneous nodules, livedo reticularis, atrophie blanche and deep ulcers was identified in four patients all with systemic complications. Coexistence of venulitis and arteritis was identified in three patients. Different cutaneous vasculitic manifestations often coexisted and recurred in the same patient. Three patients with systemic complications of mononeuritis multiplex (two of three), interstitial pulmonary fibrosis (two of three) and abdominal microaneurysms (one of three) died within 1 year of onset of the cutaneous vasculitis. Immunofluorescence demonstrated vessel wall deposition of IgM and/or complement in six of the seven patients examined.
Features of cutaneous rheumatoid vasculitis overlapping both the characteristics of cutaneous necrotizing venulitis and cutaneous polyarteritis nodosa together with coexistence of these different type of vasculitis in the same or different lesional skin account for the associated diverse cutaneous vasculitic manifestations. Although dermal venulitis (leucocytoclastic vasculitis) was the most common presentation, the presence of leucocytoclastic vasculitis in rheumatoid patients did not necessarily indicate a favourable prognosis. Associations with mononeuritis multiplex and bowel involvement had a fatal prognosis, while patients with superficial dermal venulitis without other extra-articular involvement may follow a favourable prognosis.
We report the case of a 75-year-old-woman who presented with bilateral scalp ulcerations and blindness, accompanied by severe headache and scalp tenderness, due to bilateral temporal arteritis without systemic involvement. A biopsy taken from the border of an ulceration showed evidence of giant cell arteritis. She was treated with oral prednisone, 60 mg per day. The ulcerations healed in a few weeks but the vision loss was irreversible.
This case highlights for temporal arteritis the importance of accurate and timely diagnosis as well as the need for prompt therapy with systemic steroids in order to avoid major complications, namely loss of vision. It also demonstrates that scalp necrosis and ulcerations are skin signs associated with a poor prognosis.
Unlabelled:
Vasculitis can range in severity from a self-limited single-organ disorder to a life-threatening disease with the prospect of multiple-organ failure. This condition presents many challenges to the physician, including classification and diagnosis, appropriate laboratory workup, treatment, and the need for careful follow-up. The physician must not only be able to recognize vasculitis but also be able to provide a specific diagnosis (if possible) as well as recognize and treat any underlying etiologic condition. Most diagnostic criteria are based on the size of vessel involvement, which often correlates with specific dermatologic findings. This may allow the dermatologist to provide an initial diagnosis and direct the medical evaluation. This article reviews the classification and diagnosis of cutaneous vasculitic syndromes and current treatment options; it also presents a comprehensive approach to diagnosing and treating the patient with suspected cutaneous vasculitis. (J Am Acad Dermatol 2003;48:311-40.)
Learning objective:
At the completion of this learning activity, participants should be familiar with the classification and clinical features of the various forms of cutaneous vasculitis. They should also have a rational approach to diagnosing and treating a patient with vasculitis.
We present a patient with bilateral scalp necrosis caused by giant cell arteritis (temporal arteritis). A 67-year-old woman, who had been treated with 5 mg of oral prednisolone every other day for polymyalgia rheumatica, developed painful egg-sized regions of necrosis on both of her temples. Doppler pulsemetory revealed bilateral obstruction of the temporal arteries. Biopsy revealed ischemic necrosis of the skin and necrotic angiitis of the temporal arteries with giant cell infiltration. Bilateral stenosis of the internal carotid arteries and moderate retinal bleeding were revealed by angiography. Daily administration of prednisolone (20 mg/day) with intravenous and topical limaprost alphadex markedly improved her condition. The ulcers reepithelized without surgical treatment. There are few reports of bilateral scalp necrosis. Rapid and complete obstruction of the temporal artery may result in this condition. Simultaneous development of two ulcerative lesions in the ventro-parietal cranial regions is thought to correspond to systemic arterial involvement, including involvement of the internal carotid arteries.
The term 'atrophie blanche' is used both as a descriptive term denoting ivory-white stellate scars on the lower limbs as well as a diagnostic label synonymous with livedoid vasculitis, an ill-defined entity. Medium-sized vasculitides, such as polyarteritis nodosa (PAN), occasionally present with ulceration resulting in ivory-white stellate scarring on the lower limbs and may potentially be misdiagnosed as livedoid vasculitis.
To assess the occurrence, clinical and immunopathological features of medium-sized vasculitis in patients presenting with atrophie blanche without clinical and/or compression duplex ultrasonographic evidence of venous insufficiency.
We retrospectively evaluated patients presenting with atrophie blanche at the Department of Dermatology of Johns Hopkins Medical Institutions, from April 1996 until April 2002, following the diagnostic guidelines for leg ulcers of the Division of Immunodermatology. Deep and multiple skin biopsies were performed for histology. Investigations for underlying vasculitis, thrombophilia, nerve conduction studies and compression duplex ultrasonography of the lower extremities were performed in all patients.
Of 29 consecutive patients presenting with atrophie blanche, six had underlying medium-sized vasculitis consistent with PAN, three of whom had previously been diagnosed to have segmental hyalinizing vasculitis/vasculopathy (livedoid vasculitis/vasculopathy) on superficial biopsies. All six patients with cutaneous PAN were women with a median age of 36.5 years (range 34-46) and with a median duration of the disease prior to diagnosis of 18 years (range 3-30). Of the six cutaneous PAN patients, four had neurological involvement evidenced by clinical symptoms and nerve conduction studies. No evidence of any other extracutaneous involvement was found. Erythrocyte sedimentation rate and tests for vasculitis and thrombophilic were normal in all six patients. None had evidence of venous insufficiency. Immunosuppressive therapy was effective in controlling PAN-associated cutaneous and neurological disease. Of the remaining 23 patients, two had antiphospholipid syndrome and one had homocystineaemia; all three also had evidence of venous insufficiency. One patient had multiple myeloma-associated type I cryoglobulinaemia and 19 patients had venous insufficiency alone. None of the non-PAN patients had abnormalities in the nerve conduction studies.
In patients presenting with atrophie blanche without evidence of venous insufficiency and thrombophilia, PAN should be excluded, particularly in the presence of mononeuritis multiplex. Repeated and deep biopsies are often necessary to reveal the accurate underlying pathology of necrotizing medium-sized vasculitis in the reticular dermis and the subcutis, especially in the setting of atrophie blanche lesions. Immunosuppressive therapy was effective in controlling the PAN-associated clinical manifestations.
Giant cell arteritis is a systemic disease of the elderly which affects large and medium-sized arteries and which may occur in association with polymyalgia rheumatica. Scalp necrosis is a rare cutaneous complication of giant cell arteritis, and this dermatological presentation is not commonly reported.1-4 Giant cell arteritis should be considered in all elderly patients with scalp ulceration. We describe two patients who presented in this manner.
Takayasu's arteritis (TA) is a chronic inflammatory and fibrosing arteriopathy that can also involve cutaneous vessels. The disease typically presents with a prepulseless phase that overlaps or is followed by the characteristic pulseless stage. In both phases of TA, cutaneous manifestations may be present. Lesions considered to be 'specifically' associated with TA have been described most frequently simulating erythema nodosum, erythema induratum and pyoderma gangrenosum. We report 2 Caucasian patients with TA and nodular cutaneous lesions. Nine skin biopsies from these patients were studied. A necrotizing vasculitis was present in 5 biopsies. We review those patients with TA and well-documented cutaneous manifestations in the English literature, with special interest in nodular lesions, the most frequent cutaneous manifestation of TA in Caucasian patients. Biopsies from lesions with similar morphology frequently show different histological findings.
Exercise-induced purpura (EIP) occurs on the lower legs after unusual or major muscular activity, as in marathon runners or as after long walks, especially in the mountains in hot weather. In leisure walkers, patients are otherwise healthy females. There is no relation with chronic venous disorder. Erythematous, urticarial or purpuric plaques arise on the lower leg, usually sparing the skin compressed by socks. Symptoms include itch, pain and a burning sensation. Histopathology demonstrates leukocytoclastic vasculitis. The lesions fade after some days, with frequent relapses at further muscular exercises and may be prevented in some cases by compression, intake of venoactive drugs and local application of steroids. EIP is not uncommon, even if very few descriptions have yet been published. It appears to be consecutive to venous stasis induced by an acute failure of the muscle pump of the calf and thermoregulation decompensation, after a prolonged and unusual exercise, such as running or walking in hot weather.
A number of patients presented with an erythematous, purpuric rash occurring on the legs in association with playing golf and also after prolonged walks or hikes. Many patients believed that it was an allergic reaction to grasses or insecticides and had sometimes undergone extensive allergy testing. We collected reports of 17 such cases from dermatologists in the state of Victoria, Australia. Patients were interviewed by phone and asked to submit photographs of the rash if possible. Of these, the eruption developed in 15 after playing 18 holes of golf and in three following prolonged hikes. The rash would usually develop over the summer months under hot conditions. Most patients were over 50 years of age when the tendency to develop the eruption began. Biopsies of the rash in the active phase showed leukocytoclastic vasculitis. Patch testing and investigations for potential underlying causes for vasculitis were negative or unremarkable. It would seem that this is a common but poorly documented condition. The clinical presentation and histology would support the conclusion that it represents a leukocytoclastic vasculitis induced by prolonged exercise under hot conditions. The findings would suggest that it occurs in healthy people and extensive investigation with blood tests or allergy testing is inappropriate. We believe the condition should be termed 'golfer's vasculitis', as golf appears to be the most common precipitating event and such a term would enable the condition to become more widely recognized.
To determine the type and frequency of clinical features of Behçet's disease in a population of Italian patients.
We retrospectively studied 137 Italian patients (76 males and 61 females, age at onset 29.6 +/- 12.2 [mean +/- SD] years) seen consecutively in nine different referral centers. The duration of follow-up at study entry was 10.9 +/- 8.2 years. Virtually all patients fulfilled the classification criteria developed by the International Study Group for Behçet's disease. The clinical manifestations of the patients were recorded by the attending physicians using specifically designed forms.
The most frequent manifestations at disease onset were oral (78.3%) and genital aphthae (29.2%) followed by inflammatory ocular involvement (20%) and arthritis (14.2%). The commonest (>50% of cases) manifestations observed throughout the disease course were oral aphthae (99.3%), genital aphthae (62.8%), various cutaneous lesions including erythema nodosum (81.8%), and inflammatory ocular disease (60.6%). Panuveitis and posterior uveitis/retinitis occurred more frequently in males compared with females (28.9% versus 11.5% and 57.9% versus 36.1%, respectively; p < 0.05). 61.6% of our patients were HLA-B51 positive.
Behçet's disease in Italian patients is characterized by a variety of clinical manifestations in agreement with the medical literature. Panuveitis and posterior uveitis/retinitis occur more frequently in male patients.
Usually misdiagnosed and ignored in the literature, exercise-induced vasculitis (EIV) is not uncommon, occurring mostly in long-distance runners and in females after long walks, especially in hot weather.
I report 23 otherwise healthy patients (22 females, 1 male) who developed EIV after walking or hiking in hot weather. Erythematous, urticarial or purpuric plaques arose on the lower legs, not involving skin compressed by socks. Symptoms included itch, pain, and burning sensation. Lesions resolved after some days. Relapses were frequent at further muscular exercise, and could be prevented in some cases by compression hosiery, manual lymphatic drainage, intake of oedema protective agents, or steroids (local or systemic).
Histopathology demonstrated leucocytoclastic vasculitis in five biopsies, and urticarial vasculitis in one. Extensive blood investigations have been performed in six patients and were negative. No clear relation with chronic venous disease (duplex or Doppler) had been established in 12 patients.
I suggest denominating this condition exercise-induced vasculitis. This clinical entity is well defined, but poorly recognized. The presentation of 23 original cases demonstrates its reality.
To determine the frequency of occurrence of malignancy concurrently with temporal arteritis (TA), as well as features and outcome of the vasculitis in such cases.
In a series of 271 consecutive patients with TA (219 biopsy-proven), we retrospectively analyzed the frequency and type of malignancy concurrent with vasculitis (less than 1 year before or after), as well as the main features and outcome of TA in this setting. We also surveyed all cases published in the French-British literature.
We observed 20 patients with TA and concurrent malignancy and reviewed 27 similar published reports. GCA was documented pathologically in 86% of the cases. The time between diagnosis of TA and that of malignancy averaged 3.5 months (synchronous diagnoses in 27 patients). Various locations of cancers were found, particularly the gastrointestinal tract (9 cases); blood malignancies accounted for 45% of cases (lymphoid disorder in 9, myelodysplastic syndrome in 11, chronic myelogenous leukemia in 1). In our patients, logistic regression analysis failed to demonstrate differences between those with and without malignancy, except for a higher frequency of rheumatic involvement in the former group (60% vs 30%; p = 0.01). The initial response to steroid treatment was good in 92% of 40 assessable patients, and the vasculitis course mirrored that of malignancy in only 2 patients. Regarding the outcome of TA, no differences were observed in our patients with and without malignancy.
Concurrent malignancy in TA is not a rare finding, being observed in up to 7.4% of the cases. Solid malignancies and hematological disorders, especially myelodysplastic syndromes, may represent precipitating factors for development of TA, which infrequently run a paraneoplastic course. Patients with and without malignancy seem almost indistinguishable regarding features and outcome of TA. Physicians who care for patients with TA should be mindful of this potential association, even in typical cases.
A broad and diverse spectrum of vasculitic syndromes exists. These syndromes affect the skin with varying levels of associated systemic manifestations, running the gamut from a self-limited, localized, cutaneous phenomenon to rapidly progressive, multiorgan disease. The majority of cases of cutaneous vasculitis will show a neutrophilic small vessel vasculitis that can be either a primary (idiopathic) disorder (eg, cutaneous leukocytoclastic angiitis) or a secondary disorder that is associated with drugs, infection (eg, streptococcal infection, viral hepatitis), or underlying disease (eg, connective tissue disease, malignancy). Biopsy is the gold standard for the diagnosis of cutaneous vasculitis and also necessary for the detection of cutaneous vascular immune complexes by direct immunofluorescence. Based on the type of vessel disrupted by inflammation (small and/or muscular), the distribution of vasculitis in the dermis and subcutis, and predominate inflammatory cell-type mediating vessel wall damage, a list of relevant differential diagnoses can be generated. This histologic information coupled with extravascular findings such as tissue eosinophilia, tissue neutrophilia, and/or granulomas, plus pathophysiologic markers such as direct immunofluorescent examination for immune complexes and serologic evaluation for antineutrophil cytoplasmic antibodies allows for more accurate diagnosis of specific vasculitic entities. Herein, we review both primary and secondary vasculitic syndromes that affect the skin and show a small vessel neutrophilic mediated vasculitis.