Small-Vessel Vasculitis (Leukocytoclastic Vasculitis)

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Practice Essentials

Vasculitis may involve any organ system in the body, and may involve small, medium, or large blood vessels. Cutaneous vasculitis can present in several forms, as follows[1] :

This article focuses on small-vessel vasculitis (SVV) that affects the skin. This includes cutaneous small-vessel vasculitis (CSVV), which is a single-organ vasculitis affecting the small vessels of the skin, previously termed hypersensitivity vasculitis. Leukocytoclastic vasculitis (LCV) is a histopathologic finding that is characterized by neutrophilic inflammation of the small postcapillary venules of the dermis leading to leukocytoclasis (vascular damage caused by nuclear debris from the infiltrating neutrophils). LCV is the common histologic finding of SVV in the skin, regardless of whether the vasculitis is skin-predominant or systemic (see the image below).[2]



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Histopathology of leukocytoclastic vasculitis.

Classically, small-vessel vasculitis in the skin presents as palpable purpura (see the image below). The primary lesion is palpable due to inflammation, and purpuric due to extravasation of red blood cells, indicative of the underlying vascular damage. Less common morphologies include urticarial lesions, inflammatory retiform purpura,[3]  (shallow) erosions and ulcers, as well as hemorrhagic vesicles, bullae, and pustules. Deep ulcers, large areas of necrosis or retiform purpura, nodules, and livedo reticularis or racemosa are clinical signs that medium or large vessels may be involved. The internal organs most commonly affected in SVV are the joints, gastrointestinal (GI) tract, and kidneys.

 



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Palpable purpura in a patient with small-vessel vasculitis.

Cases of SVV affecting the skin may be idiopathic or may be secondary to systemic vasculitis, infections, medications, or other identifiable causes. See Etiology.

Typically, SVV with cutaneous involvement is acute and self-limited. However, approximately 10% of patients will have persistent or recurrent disease.[2, 4]  Complications include ulceration and post-inflammatory changes in the skin, as well as end-organ damage in cases associated with systemic involvement. Overall, however, patients have a favorable prognosis, particularly those without internal involvement.

Patients with SVV that primarily involves the skin should be treated with nontoxic modalities whenever possible. Elevation of the legs or use of compression stockings may be helpful because the disease often affects dependent areas. NSAIDs, analgesics, or antihistamines can be used for symptomatic relief of burning, pain, and pruritus. Treatment of the underlying trigger or cause may speed improvement. See Treatment for details.

Henoch-Schönlein purpura (HSP), a specific subtype of cutaneous vasculitis warranting separate discussion, is characterized by IgA-mediated vessel injury. The classic clinical finding of palpable purpura in HSP is often preceded by viral respiratory illness. HSP is more common in children but can also occur in adults and is currently better identified as IgA vasculitis.[1]  Children may develop systemic disease with GI, joint, and/or kidney involvement.[5]  In adults, arthritis and kidney disease occur more frequently.[6] HSP in adults, especially older men, may be associated with malignancy.[7] For full discussion of HSP, see IgA Vasculitis (Henoch-Schönlein purpura).

A newer classification category, IgM/IgG vasculitis (non-IgA), is yet to be fully delineated but was noted in the 2017 dermatologic addendum to the 2012 Revised International Chapel Hill Consensus Conference.[1, 8]

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 cutaneous small-vessel vasculitis.[9, 10]  When systemic disease is present (such as in vasculitis associated with antineutrophil cytoplasmic antibodies [ANCA]), other mechanisms may contribute.[11]

Etiology

Approximately 70-80% of adult patients presenting with biopsy-proven LCV have skin-limited disease (cutaneous small vessel vasculitis).[12, 13, 4]  In a recent series, about 12% had IgA vasculitis (according to the classic HSP definition, with palpable purpura, nephritis, and GI involvement). Approximately 8% had other systemic vasculitides (such as cryoglobulinemic vasculitis, connective tissue disease, ANCA-associated vasculitis, polyarteritis nodosa, or Behcet disease).[13] In an older series, of 120 adult patients with primary cutaneous vasculitis, 39 (33%) had HSP and 11 had essential mixed cryoglobulinemia; 25% of patients had a systemic vasculitis (eg, polyarteritis nodosa [PAN], granulomatosis with polyangiitis [GPA], eosinophilic granulomatosis with polyangiitis [EGPA], connective tissue disease).[12]  

In skin-limited cases of LCV, about 50-60% are idiopathic, about 25% are thought to be secondary to medications, and upwards of 10% of cases are post-infectious. Other causes may be attributed to underlying connective tissue diseases, illicit drug use, systemic vasculitis (such as ANCA-associated vasculitis presenting with LCV), and malignancy.[14, 13, 15, 16, 17] Sporadic reports of vaccine-induced LCV exist.[18, 19]

Virtually any medication may lead to development of LCV. Antibiotics, particularly beta-lactam drugs, are most commonly implicated and in these cases identifying whether the medication or infection is primarily responsible for development of LCV may be impossible.[16] NSAIDs, allopurinol, and immune checkpoint inhibitors are also notable triggers.[20]  Monoclonal antibody therapy, such as with rituximab, is associated with serum sickness, which may present clinically with vasculitis.[21]

Levamisole, an immunomodulatory and anti-helminthic agent withdrawn from the United States market, is present in a high percentage of cocaine in the US. Levamisole-adulterated cocaine may lead to retiform purpura and mimic ANCA-associated vasculitis, particularly GPA. Often, patients with levamisole-induced vasculitis/vasculopathy present with both MPO and PR3 antibodies, and 70% of patients in a recent review tested positive for antiphospholipid antibodies.[22]  Early biopsies of levamisole-induced lesions tend to show vasculopathy/microvasculiar occlusion, suggesting this as the primary etiology, with vasculitis develping in more established lesions.

Infections that may be associated with vasculitis include the following:

LCV with cutaneous involvement may also be a sign of systemic disease. Collagen vascular diseases, in particular rheumatoid arthritis, Sjögren syndrome, and systemic lupus erythematosus, may have an associated vasculitis, as may dermatomyositis and sarcoidosis. Inflammatory bowel disease (IBD; ulcerative colitis and Crohn disease[28] ) may be associated with SVV. Treatments for IBD, in particular tumor necrosis factor alpha inhibitors, have also been associated with vasculitis in these patients.[29, 20]

Cutaneous vasculitis with LCV may be the presenting sign of systemic vasculitidies such as IgA vasculitis (formerly HSP); cryoglobulinemic vasculitis; and ANCA-associated vasculitis, including granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis.  Polyarteritis nodosa may present with systemic disease or as a more limited cutaneous form, and is generally thought of as a predominantly medium-vessel vasculitis; histologically, vasculitis may affect small arteries in the subcutaneous fat and extend to arterioles at the dermal subcutaneous junction (but not post-capillary venules).[30]

SVV presenting in the skin may be associated with underlying solid-organ or hematologic malignancy, though overall numbers are low (around 2-4%).[16, 13, 25, 31, 32]  Lymphoproliferative diseases, such as multiple myeloma and myelodysplastic syndrome, may be more common culprits.[33, 34]  In one series, paraneoplastic SVV was found more commonly in older patients with constitutional symptoms and in those with anemia and immature cells on peripheral blood smears.[31]  

Epidemiology

SVV with skin predominance (LCV) is reported to occur in 10-30 persons per million annually. Many of the estimates come from Spanish cohorts.[35, 36, 37, 16, 13, 38] Cutaneous LCV has been reported more frequently in males.[16, 13]

Prognosis

Typically, SVV with cutaneous involvement is acute and self-limited. However, approximately 10% of patients will have persistent or recurrent disease.[2, 4]  One series noted recurrent or chronic disease in 36 of 82 patients (44%).[17]  Complications include ulceration and post-inflammatory changes in the skin as well as end-organ damage in cases with associated systemic involvement.

A review from Germany of prognostic markers in 28 inpatients with non-IgA single-organ cutaneous SVV found that disease manifestation on the upper extremities strongly predicted the absence of severe disease.[39]

The overall prognosis in patients with cutaneous vasculitis depends primarily on the underlying syndrome and/or the presence of end-organ dysfunction. In many patients with isolated cutaneous SVV the condition will be self limited, and treatment may be primarily supportive (see Treatment). Prognosis will be greatly affected by the presence of systemic disease (additional end-organ involvement beyond the skin) and/or the underlying trigger. In the case of infections, mortality may be more likely related to infectious complications than the vasculitis itself.[25]

History

In patients who present with skin signs suggesting small-vessel vasculitis (SVV), it is important to assess for signs and symptoms of extracutaneous disease. Specific evaluation of the following is necessary:

The internal organs most commonly affected in SVV are the kidneys, joints, and gastrointestinal (GI) tract (particularly in IgA vasculitis). Additional history should focus on possible triggers, including a thorough review of medications, evidence of infection, or signs and symptoms of associated inflammatory conditions (eg, connective tissue disease, inflammatory bowel disease) and malignancy.

Physical Examination

Classically, small-vessel vasculitis in the skin presents with palpable purpura (see the image below). The primary lesion is palpable due to inflammation and purpuric due to extravasation of red blood cells, indicative of the underlying vascular damage. Less common cutaneous lesions include urticarial lesions, inflammatory retiform purpura,[3]  (shallow) erosions and ulcers as well as hemorrhagic vesicles, bullae, and pustules. Lesions tend to develop in dependent areas or in areas of trauma or pressure. Deep ulcers, large areas of necrosis or retiform purpura, nodules, and livedo reticularis or racemosa are clinical signs that medium or large vessels may be involved.



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Palpable purpura in a patient with small-vessel vasculitis.

In one series of 82 patients, the morphologic type of skin lesions most commonly found were palpable purpura (51 patients), urticarial-like lesions (17 patients), ulcers (eight patients), erythematous plaques (five patients), and/or nodules (five patients)[17] .

Features of palpable purpura include the following:

When urticarial lesions develop, one must evaluate for urticarial vasculitis (see the image below).



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Urticarial vasculitis. Lesions differ from routine urticaria (hives) in that they last longer (often >24 h), are less pruritic, and often resolve with....

Approach Considerations

The evaluation of a patient with small-vessel vasculitis (SVV) serves two purposes. The first is determining whether systemic vasculitis is present. The second is identifying an associated disorder, which can provide prognostic information. For a practical algorithmic approach to the workup and diagnosis of SVV, see the review article by Micheletti.[44]

In all adult patients, basic blood and urine studies are appropriate. A skin biopsy of a relatively new lesion should be performed in most adult patients with suspected SVV.

Imaging is generally indicated only when extracutaneous involvement is suspected, with study selection based on the patient's signs/symptoms. Electromyography and nerve conduction studies are indicated if neuropathy (motor or sensory) is present.

Laboratory Studies

Although no standard protocol has been established, testing in all adult patients presenting with SVV in the skin should include the following:

When the diagnosis of skin-limited cutaneous SVV is clear-cut (namely, when a reasonable trigger has been identified and there is low concern for systemic or end-organ involvement beyond the skin), no further diagnositic testing may be necessary. However, for patients presenting with additional systemic signs/symptoms or recurrent disease, the following work-up should be considered (not every patient will need every test):

Imaging Studies

In patients with small-vessel vasculitis in the skin, imaging is generally indicated only when extracutaneous involvement is suspected; it is not recommended for routine screening of patients.[45]  In those with concerning signs/symptoms, the following may be considered:

Procedures

A skin biopsy of a relatively new lesion should be performed in most adult patients with suspected SVV. The diagnostic yield is higher when performed on a fresh skin lesion, in the first 24 to 48 hours of development.[46]  Direct immunofluorescence (DIF) microscopy should be performed to assess for perivascular deposition of IgA; this is best done on lesions within 24 hours of development.[47, 4]

Histologic Findings

Skin biopsy reveals the presence of vascular and perivascular infiltration of polymorphonuclear leukocytes with formation of nuclear dust (leukocytoclasis), extravasation of erythrocytes, and fibrinoid necrosis of the vessel walls (see image below). This process is dynamic, and biopsy of a lesion performed too early or too late in the evolution may not reveal the classic findings.[48]  Neutrophilia is common in skin biopsies of patients with cutaneous vasculitis associated with severe bacterial infection.[49]  



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Histopathology of leukocytoclastic vasculitis.

Leukocytoclastic vasculitis (LCV) is a histologic pattern that can occur in any vasculitic syndrome but may also occur in nonvasculitic diseases such as neutrophilic dermatoses, at the base of an ulcer, or in some insect bite reactions. Careful clinical-pathologic correlation is therefore necessary, and one should avoid using "LCV" as a diagnosis in and .of itself.

Immunofluorescent staining may reveal immunoglobulins (eg, immunoglobulin G, immunoglobulin M) and complement components (eg, C3, C4) deposited on the skin basement membrane, suggesting immune complex deposition. In Henoch-Schönlein purpura, IgA-predominant deposits may be found.

Medical Care

Once a diagnosis of cutaneous small-vessel vasculitis is established and the patient is fully evaluated (ie, systemic disease has been ruled out), treatment is generally based on the severity of the disease, as well as patient-specific factors. Any identifiable cause should be treated (in the case of infection or malignancy) or removed (in the case of medication or other trigger). Topical steroids may provide some symptomatic relief, and nonsteroidal anti-inflammatory drugs (NSAIDs) may be beneficial for associated pain or arthralgias.[44]  For patients with severe disease at initial presentation, systemic corticosteroids may be necessary to gain rapid control of the disease but should not be used for long-term management owing to the risk of adverse effects.

For patients with severe, recurrent or chronic disease, first-line treatments may include the following:

Second-line treatments include traditional steroid-sparing agents, especially for patients with severe disease that flares with taper of systemic glucocorticoids:

Adjunctive therapies, or as monotherapy in select patients, may include:

It should be noted that data for all therapies are very limited. Currently, an international, multicenter, randomized trial enrolling patients with isolated skin vasculitis (ARAMIS; NCT02939573) is investigating colchicine, dapsone, and azathioprine as first-line therapies. The only completed randomized controlled trial in cutaneous vasculitis suggested that colchicine had no significant therapeutic effect.[62]  However, this study was limited by short treatment duration (1 month) and relapse upon cessation of the medication in 3 complete responders (suggesting the medication was helpful in a subset of the patients studied).

Additional medications that have been reported in isolated patients with cutaneous small-vessel vasculitis include infliximab and cyclosporine.

Surgical Care

Surgical care is rarely needed in patients with vasculitis. However, surgery may be appropriate in any of the following circumstances:

Consultations

The following specialty consultations may be indicated:

Diet and Activity

No specific diet is required in patients with SVV. In select patients, an elimination diet could be considered.[63]

Supportive measures, such as rest and leg elevation, may be all that are necessary for treatment in patients with mild, self-limiting cutaneous small vessel vasculitis.

Complications

Complications of skin involvement include pain, ulceration, and post-inflammatory changes. Systemic complications may include those from therapy (such as systemic corticosteroids or immunosuppressives) or systemic vasculitis (such as kidney dysfunction) when present.

Long-Term Monitoring

Care should be taken to monitor kidney function in patients with small-vessel vasculitis that affects the skin, particularly in patients with recurrent disease. For patients requiring long-term therapy, appropriate medication monitoring is necessary.

Medication Summary

No effective therapy has been established for all patients with small-vessel vasculitis (SVV). Few therapies for SVV have been tested in controlled trials, and data is based largely on expert opinion and anecdotal evidence.

Colchicine or dapsone are often used as first-line options in patients with cutaneous-predominant SVV, possibly with the addition of pentoxifylline. Methotrexate, azathioprine, and mycophenolate mofetil provide additional options. Systemic corticosteroids can be used for short-term control. Hydroxychloroquine and antihistamines may be considered, particularly for urticarial lesions. In rare cases of severe and refractory cutaneous vasculitis, intravenous immunoglobulin (IVIg) or rituximab may be considered. Janus kinase (JAK) inhibitors may have a role to play in the treatment of cutaneous vasculitis, and provide an exciting new potential treatment for refractory disease.[60, 61]

Colchicine (Colcrys, Gloperba, Lodoco)

Clinical Context:  Has effects against neutrophils, which are involved in the pathogenesis of cutaneous vasculitis. It remains a widely used medication for cutaneous vasculitis.

Class Summary

These agents inhibit key events involved in the inflammatory process.

Dapsone

Clinical Context:  Small, open-label studies or single case reports have suggested that dapsone is effective in some patients with cutaneous vasculitis.

Class Summary

Some types of antimicrobials (eg, dapsone) have anti-inflammatory properties.

Prednisone (Deltasone, Prednisone Intensol, Rayos)

Clinical Context:  Should be used sparingly for skin-limited cutaneous vasculitis; it is not considered an acceptible long-term treatment option for those with chronic or relapsing disease

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Cyclophosphamide (Cytoxan)

Clinical Context:  Alkylating agent that depresses T-cell and B-cell function. Has largely been supplanted by Rituximab in cases of systemic vasculitis (especially ANCA-associated), but may be used in cases of life-threatening vasculitis

Azathioprine (Azasan, Imuran)

Clinical Context:  Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Methotrexate (Jylamvo, Otrexup, Rasuvo)

Clinical Context:  Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response.

Mycophenolate (CellCept, MMF, Myfortic)

Clinical Context:  Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.

Two formulations are available and are not interchangeable. The original formulation, mycophenolate mofetil (MMF, CellCept) is a prodrug that, once hydrolyzed in vivo, releases the active moiety mycophenolic acid. A newer formulation, mycophenolic acid (MPA, Myfortic) is an enteric-coated product that delivers the active moiety. The latter is often associated with less gastrointestinal disturbance.

Rituximab (Riabni, Rituxan, Rituximab-abbs)

Clinical Context:  Antibody genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Antibody is an IgG1-kappa immunoglobulin that contains murine light- and heavy-chain variable region sequences and human constant region sequences. Generally used in cases of systemic vasculitis, but may be indicated in patients with cutaneous vasculitis who have severe, relapsing disease and have failed or cannot tolerate first or second-line agents

Class Summary

These agents inhibit cell growth and proliferation, decreasing immune reactions.

Hydroxychloroquine sulfate (Plaquenil)

Clinical Context:  Not often used as monotherapy, but may be helpful in particular in cases associated with connective tissue disease, such as systemic lupus erythematosus.

What is leukocytoclastic vasculitis (LCV)?What is Henoch-Schönlein purpura (HSP)?How frequently is leukocytoclastic vasculitis (LCV) idiopathic?Where in the body does leukocytoclastic vasculitis (LCV) manifest?What is the prognosis of leukocytoclastic vasculitis (LCV)?What are the forms of leukocytoclastic vasculitis (LCV)?What is the pathophysiology of leukocytoclastic vasculitis (LCV)?What is the incidence of leukocytoclastic vasculitis (LCV) in the US?What is the global incidence of leukocytoclastic vasculitis (LCV)?What is the prognosis of leukocytoclastic vasculitis (LCV)?What are the racial predilections of leukocytoclastic vasculitis (LCV)?How does the prevalence of leukocytoclastic vasculitis (LCV) vary by sex?How does the prevalence of leukocytoclastic vasculitis (LCV) vary by age?What are the signs and symptoms of leukocytoclastic vasculitis (LCV)?Which disorders may be comorbid with leukocytoclastic vasculitis (LCV)?What should be the focus of the medical history in suspected leukocytoclastic vasculitis (LCV)?Why is consideration of the underlying disorder required in the evaluation of leukocytoclastic vasculitis (LCV)?What is the most common manifestation of leukocytoclastic vasculitis (LCV)?Which types of lesions may develop in patients with leukocytoclastic vasculitis (LCV)?How is urticarial vasculitis differentiated from leukocytoclastic vasculitis (LCV) during the physical exam?How is the duration of individual leukocytoclastic vasculitis (LCV) lesions determined?How is hypocomplementemic urticarial vasculitis differentiated from leukocytoclastic vasculitis (LCV) during physical exam?What should be included in the physical exam of suspected leukocytoclastic vasculitis (LCV)?What are the causes of leukocytoclastic vasculitis (LCV)?What are the most common drugs that cause leukocytoclastic vasculitis (LCV)?Which infections may cause leukocytoclastic vasculitis (LCV)?How often is can an infectious etiology be differentiated for a drug-related cause of leukocytoclastic vasculitis (LCV)?What is the prevalence of a collagen-vascular disease etiology of leukocytoclastic vasculitis (LCV)?What are the GI causes of leukocytoclastic vasculitis (LCV)?What is the role of malignancy in the etiology of leukocytoclastic vasculitis (LCV)?What are the signs and symptoms of a malignant etiology for leukocytoclastic vasculitis (LCV)?Which larger-vessel vasculitis conditions are associated with leukocytoclastic vasculitis (LCV)?Which conditions should be included in the differential diagnoses of leukocytoclastic vasculitis (LCV)?What are the differential diagnoses for Small-Vessel Vasculitis (Leukocytoclastic Vasculitis)?What are the goals of evaluation of a patient with leukocytoclastic vasculitis (LCV)?What is the role of lab testing in the evaluation of leukocytoclastic vasculitis (LCV)?When are serologic studies indicated for the evaluation of leukocytoclastic vasculitis (LCV)?When should complement levels be obtained in the evaluation of leukocytoclastic vasculitis (LCV)?Which lab studies are indicated in the evaluation of leukocytoclastic vasculitis (LCV) without an identified etiology?Which additional studies may be useful in the diagnosis of leukocytoclastic vasculitis (LCV)?When is testing for malignancy indicated in the evaluation of leukocytoclastic vasculitis (LCV)?What is the role of imaging studies in the evaluation of leukocytoclastic vasculitis (LCV)?What are some other tests used for the diagnosis of hypocomplementemic urticarial vasculitis syndrome (HUVS)What is the purpose of direct immunofluorescence (DIF) microscopy in the diagnosis of leukocytoclastic vasculitis (LCV)?What is the role of skin biopsy in the evaluation of leukocytoclastic vasculitis (LCV)?What is the role of muscle, nerve, or visceral organ biopsy in the evaluation of leukocytoclastic vasculitis (LCV)?Which biopsy findings are characteristic of leukocytoclastic vasculitis (LCV)?Which histologic findings are characteristic of leukocytoclastic vasculitis (LCV)?What does immunofluorescent staining reveal in patients with leukocytoclastic vasculitis (LCV)?What are treatment options for leukocytoclastic vasculitis (LCV)?How are the urticarial lesions of leukocytoclastic vasculitis (LCV) treated?What are the treatment options for severe visceral involvement in leukocytoclastic vasculitis (LCV)?What are the treatment options for chronic leukocytoclastic vasculitis (LCV)?What are the treatment options for severe or debilitating leukocytoclastic vasculitis (LCV)?What is the role of rituximab in the treatment of leukocytoclastic vasculitis (LCV)?When is surgery indicated in the treatment of leukocytoclastic vasculitis (LCV)?Which specialists should be consulted for the management of leukocytoclastic vasculitis (LCV)?Which diet modifications helpful in the treatment of leukocytoclastic vasculitis (LCV)?What is the role of medication in the treatment of leukocytoclastic vasculitis (LCV)?Which medications in the drug class Cytotoxic/Immunosuppressive Agents are used in the treatment of Small-Vessel Vasculitis (Leukocytoclastic Vasculitis)?Which medications in the drug class Corticosteroids are used in the treatment of Small-Vessel Vasculitis (Leukocytoclastic Vasculitis)?Which medications in the drug class Antibiotics are used in the treatment of Small-Vessel Vasculitis (Leukocytoclastic Vasculitis)?Which medications in the drug class Anti-inflammatory Agents are used in the treatment of Small-Vessel Vasculitis (Leukocytoclastic Vasculitis)?

Author

Evan W Piette, MD, FAAD, Director, Cutaneous Vasculitis Clinic, Instructor, Department of Dermatology, Harvard Medical School

Disclosure: Nothing to disclose.

Coauthor(s)

A Brooke W Eastham, MD, Board Certified Dermatologist, Nashville Skin and Cancer

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD, Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Biogen US (Adjudicator for study entry cutaneous lupus erythematosus); Priovant (Adjudicator for entry into a dermatomyositis study); IQVIA (Serono - adjudicator for a study of cutaneous LE) <br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts for: Stocks held in various trust accounts: Allergen; Amgen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble;; Celgene; Gilead; CVS; Walgreens; Bristol-Myers Squibb.

Ruth Ann Vleugels, MD, MPH, Assistant Professor of Dermatology, Harvard Medical School; Associate Physician, Department of Dermatology, Brigham and Women's Hospital; Associate Physician, Department of Immunology and Allergy, Children's Hospital Boston

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD, Associate Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Disclosure: Stock ownership for: Johnson & Johnson.

Additional Contributors

Bryan L Martin, DO, Associate Dean for Graduate Medical Education, Designated Institutional Official, Associate Medical Director, Director, Allergy Immunology Program, Professor of Medicine and Pediatrics, Ohio State University College of Medicine

Disclosure: Nothing to disclose.

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Histopathology of leukocytoclastic vasculitis.

Palpable purpura in a patient with small-vessel vasculitis.

Palpable purpura in a patient with small-vessel vasculitis.

Urticarial vasculitis. Lesions differ from routine urticaria (hives) in that they last longer (often >24 h), are less pruritic, and often resolve with a bruise or residual pigmentation.

Histopathology of leukocytoclastic vasculitis.

Palpable purpura in a patient with small-vessel vasculitis.

Henoch-Schönlein purpura.

Histopathology of leukocytoclastic vasculitis.

Urticarial vasculitis. Lesions differ from routine urticaria (hives) in that they last longer (often >24 h), are less pruritic, and often resolve with a bruise or residual pigmentation.

Erythema elevatum diutinum, a rare cutaneous vasculitis.