Clinical study on single-organ cutaneous small vessels vasculitis (SoCSVV).

Leukocytoclastic vasculitis (LCV) is a heterogenous group of disorders that may manifest as a mild disease isolated to the skin or be a part of life-threatening systemic vasculitis. According to the 2012 Chapel Hill Consensus Conference nomenclature, patients presenting symptoms of LCV confined only to the skin should be defined as suffering from a single-organ cutaneous small vessel vasculitis (SoCSVV). SoCSVV is a benign disease with a good clinical outcome but with a significant risk of relapse and skin ulcer formation.The aim of the current study was to characterize SoCSVV and to identify factors that may be associated with the risk of recurrence and skin ulcers.Medical records of patients with LCV hospitalized at the Department of Dermatology at University Hospital in Cracow in the years 2010 to 2015 were analyzed.A total of 24 patients fulfilled criteria of SoCSVV. Drugs and preceding infections were identified as precipitating factors in 40% and 20% of cases, respectively. Skin lesions other than palpable purpura (i.e., macules, urticarial vasculitis, or ulcers) were identified in almost half of the patients. Interestingly, the presence of macules independently increased the risk of skin ulcer formation (odds ratio = 16; 95% confidence interval: 1.5-176.6; P = 0.0075) in the multivariate logistic regression analysis. One-quarter of patients with SoCSVV experienced relapse during the 6-month follow-up. The greater number of affected skin areas was an independent risk factor of recurrence (odds ratio = 5; 95% confidence interval: 2-45; P = 0.02).SoCSVV was usually associated with drugs and preceding infections. The disease relapses in approximately one-quarter of the patients. The more severe the skin involvement in the course of SoCSVV, the higher is the risk of recurrence.

Single-organ cutaneous small-vessel vasculitis according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides: a study of 60 patients from a series of 766 cutaneous vasculitis cases.

OBJECTIVE: Cutaneous vasculitis (CV) encompasses a wide group of entities characterized by inflammation of skin blood vessels. The term single-organ vasculitis was recently coined by the 2012 Chapel Hill Consensus Conference (CHCC) to define vasculitis affecting a single organ. To our knowledge there are no published reports on single-organ cutaneous small vessel vasculitis (SoCSVV). Our aim was to characterize this entity from a wide series of patients with CV. METHODS: We analysed cases of SoCSVV from a series of 766 patients with CV from a single university referral centre. According to 2012 CHCC, the following conditions were required to define SoCSVV: (i) skin biopsy showing characteristic leucocytoclastic vasculitis and (ii) vasculitis limited to skin. RESULTS: We included 60 patients (26 women and 34 men) with a mean age of 56 years. The main precipitating factors for SoCSVV were drugs [26 patients (52%)] and previous infection [17 patients (34%)]. The main clinical manifestations were palpable purpura (81.7%) and fever (18.3%). The most frequent laboratory findings were leucocytosis and elevated ESR. Nearly one-quarter of patients with SoCSVV required pharmacological therapy. Corticosteroids (15%) and NSAIDs (13.3%) were the main agents prescribed. After a median follow-up of 4 months, complete recovery was observed in all the patients, although relapses occurred in 8% of patients. CONCLUSION: SoCSVV defined according to the 2012 CHCC may be considered a benign disease usually associated with drugs and/or a previous infection.

Vasculitis in childhood ­ a dermatological approach.

Vasculitis, an inflammatory condition affecting the blood vessels, may be restricted to a single organ or involve several organ systems. The size of the involved vessels is an important criterion for categorization of vasculitides, which is a prerequisite for rapid diagnosis and initiation of treatment. In pediatric patients, this particularly applies to Kawasaki disease. However, making the diagnosis can be challenging for dermatologists as skin involvement may be variable and non-specific. In contrast, Henoch-Schönlein purpura (IgA vasculitis) presents with the classic picture of palpable purpura. It predominantly affects postcapillary venules frequently following upper respiratory tract infections. Severe organ involvement is relatively rare in children and the prognosis is good. As renal involvement may occur during the course of disease, continuous monitoring is required. Acute hemorrhagic edema of infancy is considered as a distinct type of immune complex vasculitis and is characterized by a triad of fever, edema and rosette-shaped purpura. The clinical course of this rare disease is usually benign and self-limited. Due to the variability of clinical symptoms and manifestations, management of childhood vasculitides represents a special challenge requiring interdisciplinary collaboration. Dermatologists should be aware of their important role especially for making an early diagnosis.

Shape and configuration of skin lesions: targetoid lesions.

What is probably the first description of targetoid or iris lesions, as they appear in erythema multiforme (EM), can be found in Thomas Bateman's 1836 textbook "Practical Synopsis of Cutaneous Diseases According to the Arrangement of Dr. Willan." EM was initially described by Bateman and later by von Hebra as an acute self-limiting skin disease, symmetrically distributed on the extremities with typical concentric "targetoid" or "iris" lesions, and often recurrent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were added to this syndrome later. A newer classification has created two disease spectra: EM consisting of EM minor and EM major (or bullous EM), and SJS and TEN. EM minor and EM major are often recurrent, postinfectious (especially after herpes and mycoplasma) disorders with low morbidity and almost no mortality. SJS and TEN are usually severe drug-induced reactions with high morbidity and poor prognosis. The target lesions found in each form of the disease are described and defined. Although the term "target lesion" originated from the description of EM and despite its being the dominant lesion in this disease, it is not pathognomonic for EM, and these lesions can sometimes appear in other diseases. Short descriptions of these other diseases are presented.

Acute hemorrhagic edema of infancy with abdominal pain and elevated transaminases.

Acute hemorrhagic edema of infancy is a rare type of leukocytoclastic vasculitis characterized by a triad of fever, edema, and rosette-shaped purpura, mainly over the face, auricles, and extremities in a nontoxic infant. Visceral involvement is infrequent in acute hemorrhagic edema of infancy. We report a case of acute hemorrhagic edema of infancy with abnormal liver function tests and abdominal pain.

Retrospective analysis of adult patients with cutaneous leukocytoclastic vasculitis.

A retrospective analysis was conducted on 93 adult patients with cutaneous leukocytoclastic vasculitis from St. Vincent's Hospital Melbourne to determine the classification, aetiology, severity and prognosis of this population of patients. We developed a new classification system for the purposes of our study based on modifications to the Chapel Hill Consensus Conference definitions for vasculitic syndromes. The results of our study indicate that an obvious cause was not found in 44.1% of patients. Of the patients with secondary vasculitis, the commonest causes were drugs and infections, accounting for a total of 40.9% of patients. Extracutaneous involvement was found in 39.8% of patients. Patients with symptoms resolving in less than 3 months accounted for 59.1% of the population, whereas 24.8% of patients had either symptoms lasting three or more months or evidence of recurrent symptomatology. There were 6 deaths (6.91%) and the rest were lost to follow up. The majority of patients in this retrospective series were classified as having hypersensitivity vasculitis, which is a relatively benign disorder limited mostly to skin with a low incidence of extracutaneous involvement (15.8%). Nevertheless, evidence of systemic involvement or sepsis need to be excluded as this may have important implications for patient treatment and outcome.

[Leukocytoclastic vasculitis]. / Leukozytoklastische Vaskulitis.

Leukocytoclastic vasculitis (LcV) is the most common form of cutaneous vasculitis. Often LcV results from deposition of immune complexes in the vascular wall. When IgA is the dominant immunoglobulin in these complexes, systemic involvement is likely (Henoch-Schönlein purpura), being more severe in adults. LcV in which immune complexes are composed of IgG or IgM are more often limited to the skin and may additionally show minor systemic involvement. In other forms of LcV additional pathophysiological factors play a role. LcV can also be a presenting or accompanying symptom of severe systemic ANCA-associated vasculitis. In some cases, LcV is a sign of bacteriemia. The aim of diagnostic procedures is to determine the specific type of vasculitis and degree of systemic involvement as well as possible causes. If no trigger or cause can be found, uncomplicated cases of LcV should be treated symptomatically. Corticosteroids are indicated at initial signs of necrosis or ulceration. Chronic recurrent LcV may respond to dapsone or colchicine. Severe systemic vasculitis requires immunosuppressive therapy.

Cutaneous vasculitis: a review.

As the skin is commonly involved in systemic vasculitic disorders as well as those hypersensitivity states whose expression is largely skin-confined, cutaneous vasculitic lesions offer a window to diagnosis and a ready source of accessible tissue for biopsy. In this review, we discuss the pathologic manifestations of chronic vasculitic syndromes such as granuloma faciale and erythema elevatum diutinum; IgA-associated vasculitis including Henoch-Schonlein purpura; vasculitis seen in the setting of cryoglobulinemia and hypergammaglobulinemia of Waldenstrom, hereditary deficiencies of complement, and IgA deficiency; those leukocytoclastic vasculitides resulting from hypersensitivity reactions to drug, chemical and foodstuff ingestion; and those vasculitides seen in patients with systemic diseases such as polyarteritis nodosa, rheumatoid arthritis, mixed connective tissue disease, systemic lupus erythematosus, Sjogren's syndrome, relapsing polychondritis, Behcet's disease, Wegener's granulomatosis, and allergic granulomatosis of Churg and Strauss.

The cutaneous neutrophilic vascular injury syndromes: a review.

The skin manifestations of vasculitis reflect injury by all of the classic immune reactions of Gell and Coombs. As the skin affords a window of opportunity for the clinician to obtain tissue for diagnostic purposes in patients with systemic vasculitic syndromes, a thorough understanding of the dermatopathologic manifestations of those systemic diseases is a considerable asset to the practicing pathologist. This review focuses on those systemic diseases that can provoke a small vessel neutrophilic injury pattern in the skin and provides clues by which these diseases can be separated from each other and from their innocuous mimics in which cutaneous vascular injury is the only significant consequence.

A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature.

OBJECTIVE: To test the usefulness of the Chapel Hill nomenclature, supplemented with surrogate parameters, as diagnostic criteria for primary vasculitides. METHODS: To prospectively evaluate vasculitis patients according to a standardised clinical and para-clinical programme. In accordance with the Chapel Hill publication surrogate parameters were used: proteinuria, haematuria and red blood cell casts (glomerulonephritis), angiographic or ultrasonic demonstration of aneurysms or stenoses (arteritis), radiological lung infiltrates or cavitations of more than one month's duration (granuloma in the lungs), bloody nasal discharge or crusts, chronic sinusitis, otitis and/or mastoiditis, bone and/or cartilage destruction, and acute hearing loss (granuloma in upper airways). RESULTS: The following entities were diagnosed: giant cell arteritis (n=14), Takayasu arteritis (n=1), polyarteritis nodosa (n=2), Wegener's granulomatosis (n=27), Churg-Strauss syndrome (n=2), microscopic polyangiitis (n=12), Henoch-Schönlein purpura (n=2), cutaneous leucocytoclastic angiitis (n=37), and secondary vasculitis (n=21). Giant cell arteritis and cutaneous leucocytoclastic angiitis were in all cases diagnosed by biopsy. Using the Chapel Hill nomenclature supplemented with surrogate parameters, only 8 of 27 patients were diagnosed with Wegener's granulomatosis, and 3 of 12 cases with microscopic polyangiitis. The number of patients in the remaining diagnostic entities were considered to few to evaluate. CONCLUSIONS: The Chapel Hill nomenclature, supplemented with surrogate parameters, failed to act as diagnostic criteria in Wegener's granulomatosis and microscopic polyangiitis. The following diagnostic criteria are proposed for Wegener's granulomatosis: (1) Biopsy or surrogate parameter for granulomatous inflammation in the respiratory system and (2) Biopsy verified necrotising vasculitis in small to medium sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA test and (3) Lack of eosinophilia in blood and biopsy samples. The following diagnostic criteria are proposed for microscopic polyangiitis: (1) Biopsy verified necrotising vasculitis in small vessels and/or glomerulonephritis with few or no immune deposits and (2) Involvement of more than one organ system as indicated by biopsy verified vasculitis in small to medium sized vessels or surrogate parameter for glomerulonephritis and (3) Lack of biopsy and surrogate parameter for granulomatous inflammation in the respiratory system. Using these criteria all Wegener's patients and 9 of 12 patients with microscopic polyangiitis could be diagnosed.

[Infection and vascular purpura]. / Infection et purpura vasculaire.

Palpable purpura is the hallmark of cutaneous vasculitis. Small-vessel vasculitis is a common vasculitis manifestation associated with acute or chronic infection. It is also characteristic of a systemic disease whether infectious or not. The pathogenic mechanisms appear to be complex: immune complex formation, vessel damage or altered vessel function mediated directly by infectious agents, humoral or cellular immunologic response. It is also a reaction to mixed cryoglobulinemia. Diagnosis of cutaneous vasculitis is simple (palpable purpuric eruption, nodules, vesiculobullous lesions, ulcerations), but etiological investigation is often difficult because the infectious origin is only rarely demonstrated. This type of purpura occurs in bacterial endocarditis and therefore blood cultures must be performed in any febrile patient particularly in the presence of a cardiac murmur. In fact the viral, parasitic or bacterial infectious origin is demonstrated in less than 30% of the cases of leucocytoclastic vasculitis. While focal sepsis is often found and its eradication should be followed-up, its role has not been proven particularly as antibiotics alone themselves can cause hypersensitivity vasculitis. Finally, mention must be made of virus induced vasculitis (B and C hepatitis, cytomegalovirus, parvovirus), antiviral treatment which permits better control of vasculitis.

Vasculitis cutanea: conceptos actuales / Citaneous vasculitis: at the present

La vasculitis necrotizante cutánea es un cuadro frecuente en la consulta dermatológica. Puede ocurrir como manifestación de una enfermedad o ser una enfermedad dermatológica pura. En su fisiopatología han sido implicados los complejos inmunes circulantes, los anticuerpos anticitoplasma del neutrófilo y la hipersensibilidad tipo IV. La manifestación clínica más frecuente es la purpura palpable, sin embargo gran variedad de nódulos, vesículas, ampollas, pústulas, lesiones urticariformes, livedo reticular y necrosis, además de síntomas sistémicos pueden estar presentes. Su curso temporal es variable, oscilando entre dos semanas a muchos años. Algunos medicamentos e infecciones pueden desencadenar cuadros de vasculitis cutánea, a la vez que puede observarse a esta última en el contexto de enfermedades sistémicas tales como lupus eritematoso sistémico, artritis reumatoidea, granulomatosis de Wegener, síndrome de Churg Strauss, poliangitis microscópica, además de presentarse sin causa obvia. En la siguiente revisión se exponen los lineamientos actuales en cuanto a la clasificación, fisiopatología, clínica, diagnóstico y tratamiento de la vasculitis necrotizante cutánea

Anti-neutrophil cytoplasm antibodies in patients with ACR criteria for polyarteritis nodosa: help for systemic vasculitis classification?

The american college of rheumatology (ACR) proposed in 1990 revised clinical criteria for systemic vasculitis classification to define homogeneous group of patients for clinical trials. However, microscopic polyarteritis (MPA) was not clearly identified from polyarteritis nodosa (PAN). Since anti-neutrophil cytoplasm antibodies (ANCA) are markers of disease activity of small vessel vasculitides including MPA, we tested the clinical significance of ANCA in 24 patients with PAN according to the ACR 1990 criteria. Two of 24 patients had ANCA, as defined by indirect immunofluorescence on normal human neutrophils, antigen-specific ELISA and Western blot analysis. However, they exhibited histologically proven small vessel but not medium vessel vasculitis. Furthermore, they had neither artery microaneurysms nor large organ injury consequent upon large vessel occlusion. Although they satisfied ACR criteria for PAN, they probably were misclassified and should be considered as MPA. We conclude that: (i) ANCA are not found in patients with classical PAN in the absence of MPA features; (ii) caution should be exercised when defining PAN according to the ACR 1990 criteria; (iii) ANCA may help systemic vasculitis classification.

[Hypersensitivity angiitis, Henoch-Schönlein purpura].

Pathogenesis and treatment of hypersensitivity angiitis and Henoch-Schönlein purpura were summarized. Both diseases were included in the category of "leukocytoclastic vasculitis". Hypersensitivity angiitis was frequently associated with drug or infectious exposure and the involvement of venules and capillaries. Many patients with this disease have detectable autoantibodies to neutrophil cytoplasmic antigens (ANCA) typically reactive with myeloperoxidase. Henoch-Schönlein purpura was characterized by vasculitis in multiple organs such as the skin, joints, gastrointestinal tract and kidneys. Henoch-Schönlein purpura nephritis revealed marked deposition of IgA (mainly IgA1) and C3 in the glomerular mesangial areas and capillary walls by immunofluorescence. Combinations of intensive plasma exchange, steroids and cyclophosphamide were effective for patients with both diseases.

Cutaneous vasculitis and other neutrophilic dermatoses.

During 1991 and 1992 there was an abundance of articles dealing with vasculitis and its cutaneous manifestations, as well as with the perhaps related disorders known as neutrophilic dermatoses. This brief review will deal with some of the more controversial areas. The specific issues discussed are those relating to the "new" American College of Rheumatology classification system and its application to patients who have skin lesions of vasculitis, the recently associated diseases, and the newer therapies for vasculitis. In addition, recent publications regarding acute neutrophilic dermatosis (Sweet's syndrome) and pyoderma gangrenosum are briefly discussed.

Hypersensitivity vasculitis and Henoch-Schönlein purpura: a comparison between the 2 disorders.

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

Classification of vasculitis.

Usually classifications of vasculitic syndromes are based on clinical and histopathologic findings because pathogenetic mechanisms are poorly understood. A subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology recently developed classification criteria for seven major vasculitic disorders through the analysis of prospectively collected patient data from 48 centers. Using two classification methods, the subcommittee derived criteria for polyareritis nodosa, Churg-Strauss syndrome, Wegner's granulomatosis, hypersensitivity vasculitis, Henoch-Schönlein purpura, giant cell (temporal) arteritis, and Takayasu's arteritis. Although such criteria may identify typical patients with a distinct form of vasculitis, they are not intended to establish a diagnosis in an individual patient; rather, they should aid comparability of different patient groups in various research endeavors.