Cutaneous vasculitis (CV) is a condition in which inflammation of the vessel wall leads to hemorrhage and ischemia [1]. It can be a primary or idiopathic condition (e.g. polyarteritis nodosa (PAN), Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), idiopathic cutaneous leukocytoclastic angiitis) or secondary to drugs (e.g. NSAIDs), infections or systemic diseases (e.g. connective tissue disease, rheumatoid arthritis) and malignancy [2].

Another classification of CV is based on the size of the vessel wall affected - small vessel vasculitis (SVV) and medium vessel vasculitis (MVV) [3]. SVV is associated with urticaria, palpable purpura, target lesions as well as vesiculobullous lesions while lesions in MVV include subcutaneous nodules, livedo reticularis, ulcer, infarct, digital pitted scars and gangrene [1] [2] although overlapping clinical features of SVV and MVV have also been reported [4] in the same patient. The cutaneous lesions are usually found on the lower extremity and their appearance on the upper extremity is an indication of severe and/or systemic disease [5]. Constitutional symptoms like fever, malaise, arthralgias are common to CV of the primary as well as secondary types. Although CV can occur in individuals of all ages, it is commonly seen in adults and has a female preponderance. A majority of the children with CV have Henoch-Schönlein purpura (HSP).

Three patterns of CV presentation and progression have been reported [2]:

1. A self-limiting, single episode following an infection or intake of drug which resolves within six months. This is the most common form of the presentation of CV.
2. Waxing and waning symptoms are seen in HSP and connective tissue associated vasculitis
3. Chronic, progressive vasculitis associated with cryoglobulinemia, hypergammaglobulinemia, and malignancy

CV may be associated with extracutaneous (visceral) vascular inflammation in 20% of the patients and this affects mainly the kidneys [1] [5] [6]. Severe forms of life-threatening CV have been reported in < 7% patients [2] [6].

• Inflammation

  Abstract Matrix metalloproteinases (MMPs) play a critical role in various pathological conditions including cutaneous inflammation. Thus far, serial assessment of MMP activity in ongoing inflammation is hampered due to technical limitations. [ncbi.nlm.nih.gov]

• Fever

  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. [ncbi.nlm.nih.gov]

• Anemia

  The most remarkable laboratory data were increased erythrocyte sedimentation rate (40.2%), presence of serum cryoglobulins (26%), leukocytosis (24.7%), positive antinuclear antibodies (21.1%), anemia (18.8%), and positive rheumatoid factor (17.5%). [ncbi.nlm.nih.gov]

  Hematology revealed a mild normocytic normochromic anemia and a mild mature neutrophilia. On serum chemistry there was a slightly decreased ALT, slightly elevated amylase, slightly elevated creatine kinase, and low iron. [ecommons.cornell.edu]

  CV patients with bacterial infections were likely to be older and male and more frequently had fever, constitutional symptoms, focal infectious symptoms and leukocytosis with left shift and anemia, according to the researchers. [healio.com]

  Investigations that lead to the diagnosis of multiple myeloma, include complete blood count to rule out anemia, thrombocytopenia or leucopenia, total protein, albumin and globulin, blood urea, creatinine and uric acid. [ijdvl.com]

• Lymphadenopathy

  Chest computed tomogram revealed bilateral hilar lymphadenopathy and fine reticulonodular shadows on the bilateral upper lungs. [ncbi.nlm.nih.gov]

  Fever and popliteal lymphadenopathy were observed. Hematology revealed a mild normocytic normochromic anemia and a mild mature neutrophilia. [ecommons.cornell.edu]

  No significant lymphadenopathies were found on palpation, cardiopulmonary auscultation was normal. She had diffuse pain on palpation of the abdomen, which was soft, depressible and with no signs of peritoneal irritation. [archbronconeumol.org]

  The most frequent radiological features are pulmonary infiltrates, hemorrhage, and hilar lymphadenopathy. [thermofisher.com]

• Hodgkin Lymphoma

  As a consequence of the treatment of Hodgkin lymphoma, vasculitis also disappeared. [ncbi.nlm.nih.gov]

  Cutaneous vasculitis in non Hodgkin's lymphoma Haematologica January 1995 80: 529-531; doi: Abstract Cutaneous vasculitis has been described in association with various hematological malignancies, but it seems to be very uncommon among non Hodgkin's lymphomas [haematologica.org]

  lymphomas intravascular lymphoma See also cutaneous vasculitis eosinophilic vasculitis [humpath.com]

  However, in two independent, single agent phase 2 studies of bortezomib in patients with non-Hodgkins lymphoma (one multicenter trial coordinated by Memorial Sloan Kettering Cancer, the second at the M.D. [bloodjournal.org]

  At the age of 28 years, she had non-Hodgkin lymphoma (NHL), large B-cell type, which was localized to her neck and had been successfully treated with 4 courses of nitrogen mustard, vincristine, prednisone, and procarbazine followed by radiation therapy [jamanetwork.com]

• Vascular Disease

  Cutaneous Vasculitis OVERVIEW The vascular system refers to the collection of all blood vessels in the body. Vasculitis is a term used for a group of diseases characterized by the inflammation of and damage to the blood vessels walls. [dramitdutta.com]

  Infective causes are considered as those where there is direct invasion by pathogens into the vascular wall, resulting in inflammation. Examples include rickettsial vasculitis, syphilitic aortitis and aspergillus arteritis. [patient.info]

  The collagen vascular disease workup revealed positive ANA with speckled pattern and rheumatoid factor in 3 (6%) patients each, while it was observed in 28.5 and 26.4% patients, respectively, by Sais et al. [8] In addition, c-ANCA, HCV and serum cryoglobulins [dx.doi.org]

• Arthralgia

  We describe 4 patients who presented with palpable purpura, arthralgia or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA) positivity most likely as a result of a hypersensitivity reaction to cocaine-levamisole induced vasculopathy [ncbi.nlm.nih.gov]

  A few days after the initiation of treatment, the patient developed persistent arthralgia in the upper and lower limbs. [scielo.br]

• Ankle Pain

  Purpuric, pustular lesions surrounded by an erythematous halo in a 26-year-old man; the rash was associated with ankle pain but no other symptoms. The appearance was similar to that of folliculitis. [rheumatologyadvisor.com]

• Purpura

  Abstract Palpable purpura tends to indicate involvement of small vessel vasculitis in the upper dermis. [ncbi.nlm.nih.gov]

  A concomitant biopsy for direct immunofluorescence evaluation is useful to distinguish between IgA-associated vasculitis (Henoch-Schönlein purpura) and IgG-/IgM-associated vasculitis. [symptoma.com]

• Palpable Purpura

  We describe 4 patients who presented with palpable purpura, arthralgia or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA) positivity most likely as a result of a hypersensitivity reaction to cocaine-levamisole induced vasculopathy [ncbi.nlm.nih.gov]

• Ulcer

  A 43-year old man with DM developed refractory multiple cutaneous ulcers which were revealed as vasculitis by skin biopsy. [ncbi.nlm.nih.gov]

  Practice Points Hydralazine-induced small vessel vasculitis has a characteristic pattern of acral pseudoembolic vesiculopustules with necrosis and ulceration, along with involvement of the aerodigestive tract. [mdedge.com]

  Livedo reticularis, nodules, and deep ulcers are usually caused by vasculitis of deeper, medium or large vessels. [msdmanuals.com]

• Skin Lesion

  The skin lesions were gradually healed in several months OUTCOMES:: This patient was followed up at 1-month, 5-month, and 10-month after discharged, the skin lessons was gradually healed and never occurred. [ncbi.nlm.nih.gov]

• Cutaneous Manifestation

  Most of the cutaneous manifestations of APS have been found to be thrombotic on histopathology without evidence of perivascular inflammation. Vasculitis is usually seen in APS patients with coexistent Systemic Lupus Erythematosus (SLE). [ncbi.nlm.nih.gov]

  Dear Sir, Crohn's disease is associated with a variety of cutaneous manifestations many of which parallel disease activity. [academic.oup.com]

• Seizure

  […] uneasiness with cause difficult to identify Weight loss Arthritis Black discoloration of skin primarily on the extremities Severe inadequate blood supply to the extremities Ischemic stroke, hemorrhages and a progressive encephalopathy with or without seizures [en.wikipedia.org]

The diagnosis of CV can be challenging due to its variable clinical presentation. The physician has to not only diagnose the vasculitis but should also identify the underlying condition leading to the vasculitis, order the appropriate laboratory workup, treat the patient and follow-up carefully. After eliciting a detailed history and performing a multi-system physical examination, routine laboratory tests like complete blood count, erythrocyte sedimentation rate, C-reactive protein, renal function tests, and urinalysis are ordered. Specific tests like antinuclear antibody, anti-neutrophil cytoplasmic antibodies (ANCA), perinuclear ANCA (pANCA), rheumatoid factor, and complement levels should be obtained in CV patients despite the absence of clinical features of connective tissue disorders or rheumatoid arthritis or systemic lupus erythematosus. Adult patients with HSP have been reported to have immunoglobulin (Ig)A-type antiphospholipid antibodies [7] and should be tested for it.

If the etiology of CV has been identified then laboratory tests like serum protein electrophoresis (for paraproteinemia), cryoglobulins, hepatitis C antibody and, HIV should be performed. Bone marrow biopsy is indicated in patients with abnormal peripheral blood smears [8]. Although testing for malignancies is not routinely recommended, it should be performed if the clinical presentation in CV is indicative of it [9]. Blood culture and echocardiography may be indicated in patients with endocarditis.

Skin biopsy of the lesion is the mainstay of CV diagnosis as it differentiates between authentic versus pseudo-vasculitis. The timing of the biopsy, multiple biopsies taken from the most reddish, tender and purpuric cutaneous lesions and extending into the subcutaneously help improve identification of the lesion [2]. Almost all biopsies can detect immunoglobulins in the first 48 hours, although complement can still be detected in a majority of cases after 72 hours [10]. Histology demonstrating pan-dermal small-vessel vasculitis as well as subcutaneous muscular-vessel vasculitis is indicative of a connective tissue disorder, ANCA-associated vasculitis, Behçet disease, or malignancy-associated vasculitis. A concomitant biopsy for direct immunofluorescence evaluation is useful to distinguish between IgA-associated vasculitis (Henoch-Schönlein purpura) and IgG-/IgM-associated vasculitis.

There is no general treatment strategy and the effects of various treatments have never been confirmed histopathologically. A 43-year old man with DM developed refractory multiple cutaneous ulcers which were revealed as vasculitis by skin biopsy. [ncbi.nlm.nih.gov]

The diagnosis of gut vasculitis infers a poor prognosis necessitating aggressive therapy. We describe a case with predominant features of a skin-limited vasculitis but atypical debilitating abdominal symptoms. [ncbi.nlm.nih.gov]

For example, a patient with cutaneous leucocytoclastic angiitis and moderate nephritis as component of Henoch-Schonlein purpura has a much better prognosis than a patient with these same findings as a component of Wegener's granulomatosis Reference: [gpnotebook.co.uk]

The prognosis of systemic vasculitis is dependent upon the severity of involvement of other organs. If vasculitis affects the kidneys, lungs or brain it can be life-threatening. [dermnetnz.org]

OBJECTIVE: To determine the clinical profile, etiologic factors, disease associations, and the laboratory profile of adult patients with cutaneous leukocytoclastic vasculitis (LV) presenting to the Dermatology Department at Farwaniya Hospital, Kuwait. [ncbi.nlm.nih.gov]

Although vasculitis can be classified by etiology, many cases have no identifiable cause, and a single etiologic agent can elicit several distinct clinicopathologic expressions of vasculitis. [pdfs.journals.lww.com]

Object: We studied the etiological factors and clinico-pathological spectrum of patients with cutaneous vasculitis at a tertiary referral centre of north India. [ijcbr.com]

It is important to investigate etiological possibilities. 50% or more of cases appear to be idiopathic. Pathophysiology Pathogenesis. The most commonly accepted mechanism of vasculitis is type III hypersensitivity. [vetstream.com]

Penny K, Fleming M, Kazmierczak D, et al. : An epidemiological study of Henoch-Schönlein purpura. Paediatr Nurs. 2010; 22 (10): 30–35. PubMed Abstract | Publisher Full Text 11. [f1000research.com]

A number of patients with cutaneous vasculitis may also have an underlying bacterial infection, according to researchers from the Hospital Universitario Marqués de Valdecilla and the rheumatology division of the Epidemiology, Genetics and Atherosclerosis [healio.com]

Herein, we review cutaneous vasculitis focusing on diagnostic criteria, classification, epidemiology, etiology, pathogenesis, and evaluation of the cutaneous vasculitis patient. [pdfs.journals.lww.com]

Secondary Raynaud's phenomenon and cutaneous vasculitis associated with the use of interferon Cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis. [medical-dictionary.thefreedictionary.com]

Pathophysiology Pathogenesis. The most commonly accepted mechanism of vasculitis is type III hypersensitivity. Soluble circulating antigen-antibody immune complexes (formed in antigen excess) become blocked in blood vessel endothelium. [vetstream.com]

Pathophysiology The pathophysiology of cutaneous vasculitis is thought to revolve around the actual deposition of immune complexes in blood vessels at risk in the skin. [clinicaladvisor.com]

Pathophysiology Immune complex deposition, with resultant neutrophil chemotaxis and release of proteolytic enzymes and free oxygen radicals, is a key component in the pathophysiology of LCV. [10, 11] In addition, other autoantibodies, such as antineutrophil [emedicine.medscape.com]

This finding on histological examination is termed “leukocytoclastic vasculitis”. [5] Considering the wide range of potential causes leading to cutaneous small vessel vasculitis, there are subtle variations in the underlying pathophysiology for each cause [en.wikipedia.org]

It occurs more frequently in small blood vessels, and the pathophysiological mechanism involved is the deposition of immune complexes, usually immunoglobulin M and G, that activate the complement pathways, leading to the production of chemotactic factors [scielo.br]

Moreover we give a short review of the recurrence of IgA nephropathy and HSP after renal transplantation followed by possible strategies for prevention and therapy of recurrent disease. [ncbi.nlm.nih.gov]

Diagnosis This article is available in full to registered subscribers Sign up now to purchase a 30 day trial, or Login Treatment This article is available in full to registered subscribers Sign up now to purchase a 30 day trial, or Login Prevention This [vetstream.com]

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