What is leukocytoclastic vasculitis. How is it diagnosed. What are the main causes and symptoms of this small vessel inflammation. How is leukocytoclastic vasculitis treated. What is the prognosis for patients with this condition.

Understanding Leukocytoclastic Vasculitis: An Overview of Small Vessel Inflammation

Leukocytoclastic vasculitis (LCV) is a form of small vessel vasculitis characterized by inflammation of dermal capillaries and venules. This condition involves immune complex-mediated damage to blood vessel walls, leading to tissue destruction and potential organ involvement. LCV primarily affects the skin but can occasionally manifest with extracutaneous symptoms in up to 30% of cases.

The hallmark clinical feature of LCV is palpable purpura, typically presenting on the lower extremities. While often idiopathic, LCV can be associated with various underlying conditions, including infections, medications, autoimmune disorders, and malignancies.

Key Features of Leukocytoclastic Vasculitis

• Small vessel involvement
• Palpable purpura on lower extremities
• Immune complex-mediated inflammation
• Potential for extracutaneous manifestations
• Often self-limited, resolving within weeks to months

Etiology and Triggers of Leukocytoclastic Vasculitis

The etiology of leukocytoclastic vasculitis is diverse, with up to 50% of cases being idiopathic. However, several factors have been identified as potential triggers for this condition:

Infectious Causes

Infections are among the most common triggers for secondary LCV. Post-infectious LCV is frequently observed following streptococcal upper respiratory tract infections. Other infectious agents associated with LCV include:

• Mycobacterium species
• Staphylococcus aureus
• Chlamydia
• Neisseria
• HIV
• Hepatitis B and C
• Syphilis

Drug-Induced Leukocytoclastic Vasculitis

Numerous medications have been implicated in the development of LCV, typically occurring 1 to 3 weeks after drug initiation. Some common culprits include:

• Beta-lactam antibiotics
• Erythromycin and clindamycin
• Vancomycin
• Sulfonamides
• Furosemide
• Allopurinol
• NSAIDs
• Amiodarone
• Gold compounds
• Thiazide diuretics
• Phenytoin
• Beta-blockers
• TNF-alpha inhibitors
• Selective serotonin reuptake inhibitors (SSRIs)
• Metformin
• Warfarin
• Valproic acid

Autoimmune and Systemic Disorders

LCV can occur secondary to various autoimmune and systemic conditions, including:

• Rheumatoid arthritis
• Systemic lupus erythematosus
• Sjögren’s syndrome
• Henoch-Schönlein purpura
• Cryoglobulinemic vasculitis
• Hypocomplementemic urticarial vasculitis
• Behçet’s disease
• ANCA-associated vasculitides (e.g., microscopic polyangiitis, granulomatosis with polyangiitis)

Malignancy-Associated Leukocytoclastic Vasculitis

In some cases, LCV can be a paraneoplastic manifestation of underlying malignancies, particularly hematologic disorders.

Clinical Presentation and Diagnosis of Leukocytoclastic Vasculitis

The diagnosis of leukocytoclastic vasculitis relies on a combination of clinical presentation, histopathological findings, and laboratory investigations. Understanding the typical features and diagnostic approach is crucial for timely and accurate identification of this condition.

Key Clinical Features

The most characteristic clinical manifestation of LCV is palpable purpura, which typically appears on the lower extremities. Other cutaneous signs may include:

• Petechiae
• Pustules
• Urticaria
• Livedo reticularis
• Ulcerations (in severe cases)

Extracutaneous symptoms, while less common, may involve:

• Joint pain and arthritis
• Gastrointestinal symptoms (abdominal pain, bleeding)
• Renal involvement (hematuria, proteinuria)
• Peripheral neuropathy

Diagnostic Approach

When LCV is suspected, the following diagnostic steps are typically undertaken:

1. Skin biopsy: A punch biopsy of affected skin is essential for histopathological examination and direct immunofluorescence studies.
2. Laboratory testing: Initial tests include C-reactive protein, complete blood count, basic metabolic panel, liver function tests, and urinalysis.
3. Additional workup: If systemic involvement is suspected, more extensive investigations may be necessary, such as ANCA testing, complement levels, cryoglobulins, and viral serologies.

Histopathological Features of Leukocytoclastic Vasculitis

The histopathological examination of skin biopsies is crucial for confirming the diagnosis of LCV. Characteristic findings include:

• Neutrophilic infiltration of small vessel walls
• Fibrinoid necrosis of vessel walls
• Leukocytoclasis (nuclear debris from fragmented neutrophils)
• Extravasation of erythrocytes
• Endothelial cell swelling

Direct immunofluorescence studies may reveal deposits of immunoglobulins (IgM, IgG, or IgA) and complement components (C3) within vessel walls, supporting the immune complex-mediated nature of the inflammation.

Treatment Strategies for Leukocytoclastic Vasculitis

The management of leukocytoclastic vasculitis depends on the severity of the disease, underlying causes, and the presence of systemic involvement. Treatment approaches range from conservative measures to immunosuppressive therapies.

Conservative Management

For mild, localized cutaneous LCV without systemic involvement, conservative measures may be sufficient:

• Leg elevation and compression stockings to reduce edema
• Avoidance of prolonged standing or sitting
• Discontinuation of potential triggering medications
• Treatment of underlying infections, if present

Pharmacological Interventions

When more aggressive treatment is necessary, the following options may be considered:

1. Corticosteroids:
   • Oral prednisone for moderate cases
   • Pulse methylprednisolone for severe or refractory cases
2. Colchicine: Often used as a steroid-sparing agent for chronic or recurrent LCV
3. Dapsone: Effective in some cases, particularly those associated with neutrophilic inflammation
4. Hydroxychloroquine: May be beneficial in mild to moderate cases
5. Immunosuppressive agents: For severe or refractory cases, options include:
   • Azathioprine
   • Mycophenolate mofetil
   • Methotrexate
   • Cyclophosphamide (for life-threatening cases)
6. Biological agents: In select cases, drugs such as rituximab or TNF-alpha inhibitors may be considered

Treatment of Underlying Conditions

Addressing any underlying triggers or associated conditions is crucial for effective management of LCV. This may involve:

• Antibiotic therapy for infectious causes
• Treatment of autoimmune disorders
• Management of malignancies, if present

Prognosis and Long-Term Outlook for Patients with Leukocytoclastic Vasculitis

The prognosis for patients with leukocytoclastic vasculitis is generally favorable, particularly for those with isolated cutaneous involvement. Understanding the factors influencing outcomes and potential complications is essential for patient management and counseling.

Factors Affecting Prognosis

Several factors can influence the prognosis of LCV:

• Extent of organ involvement
• Underlying etiology (idiopathic vs. secondary)
• Presence of systemic symptoms
• Timeliness of diagnosis and treatment
• Response to initial therapy

Course of Disease

The typical course of leukocytoclastic vasculitis varies:

• Acute cases: Often self-limited, resolving within weeks to months
• Chronic cases: May persist for months to years, requiring long-term management
• Recurrent cases: Some patients experience periodic flares, necessitating intermittent treatment

Approximately 90% of idiopathic cutaneous small-vessel vasculitis cases resolve within weeks to months of onset. However, a small percentage of patients may develop chronic or recurrent disease.

Potential Complications

While most cases of LCV are limited to the skin, potential complications can occur, especially in cases with systemic involvement:

• Skin ulceration and scarring
• Chronic edema of affected limbs
• Renal insufficiency (in cases with significant kidney involvement)
• Gastrointestinal bleeding or perforation
• Peripheral neuropathy

Long-Term Management

For patients with chronic or recurrent LCV, long-term management strategies may include:

• Regular follow-up with a rheumatologist or dermatologist
• Periodic laboratory monitoring for disease activity and medication side effects
• Adjustment of immunosuppressive therapies as needed
• Vigilance for potential triggers and prompt treatment of infections
• Patient education on disease management and when to seek medical attention

Recent Advances and Future Directions in Leukocytoclastic Vasculitis Research

As our understanding of the pathophysiology of leukocytoclastic vasculitis continues to evolve, new therapeutic approaches and diagnostic tools are emerging. Recent advances in immunology and molecular biology have opened up exciting avenues for research and potential treatment options.

Emerging Therapeutic Approaches

Several novel therapies are being investigated for the treatment of LCV and other small vessel vasculitides:

• Targeted biologic agents: Newer monoclonal antibodies targeting specific inflammatory pathways are under study.
• JAK inhibitors: These drugs, which modulate immune responses, show promise in treating various autoimmune and inflammatory conditions, including some forms of vasculitis.
• Complement inhibitors: Given the role of complement activation in LCV, drugs targeting the complement system are being explored.
• Nanoparticle-based drug delivery: This approach aims to improve the efficacy and reduce side effects of existing therapies.

Advances in Diagnostic Techniques

Improving diagnostic accuracy and early detection of LCV is an area of active research:

• Biomarker discovery: Identification of specific biomarkers may help in early diagnosis and monitoring of disease activity.
• Advanced imaging techniques: Novel imaging modalities may allow for non-invasive assessment of small vessel inflammation.
• Genetic profiling: Understanding genetic susceptibilities may aid in predicting disease course and treatment response.

Future Research Directions

Several key areas are likely to shape the future of LCV research and management:

1. Personalized medicine approaches: Tailoring treatments based on individual patient characteristics and disease subtypes.
2. Immunomodulatory strategies: Developing therapies that can selectively target pathogenic immune responses while preserving protective immunity.
3. Long-term outcome studies: Better understanding of the natural history and long-term consequences of LCV to inform management strategies.
4. Prevention strategies: Identifying and mitigating risk factors for the development of LCV in susceptible individuals.

As research in these areas progresses, it is hoped that more effective and targeted therapies will become available, improving outcomes for patients with leukocytoclastic vasculitis and related small vessel inflammatory disorders.

Leukocytoclastic Vasculitis – StatPearls – NCBI Bookshelf

Continuing Education Activity

Leukocytoclastic vasculitis is a cutaneous, small-vessel vasculitis of the dermal capillaries and venules. This condition can be idiopathic or can be associated with infections, neoplasms, autoimmune disorders, and drugs. Key clinical features of leukocytoclastic vasculitis include palpable purpura on the lower extremity, small vessel involvement, and, in about 30 percent of individuals, extracutaneous involvement. Most cases of idiopathic cutaneous, small vessel vasculitis are self-limited with 90 percent of cases resolving in weeks to months of onset. Otherwise, treatment depends on the severity of disease and can range from an oral corticosteroid taper to various steroid-sparing immunosuppressive agents. This activity describes the evaluation and management of leukocytoclastic vasculitis and highlights the role of the interprofessional team in the care of affected patients.

Objectives:

• Describe the etiology of leukocytoclastic vasculitis.

• Review the typical presentation of leukocytoclastic vasculitis.

• Outline the management options available for leukocytoclastic vasculitis.

• Explain interprofessional team strategies for improving care coordination and communication to advance the treatment of leukocytoclastic vasculitis and improve outcomes.

Access free multiple choice questions on this topic.

Introduction

Vasculitis refers to inflammation of the blood vessels leading to tissue destruction with or without organ damage. Vasculitis is classified as small vessel, medium vessel or large vessel vasculitis[1] and maybe either idiopathic or associated with an underlying pathology/disease.  Small vessel vasculitis can be seen secondary to systemic vasculitides such as Anti-neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (Microscopic polyangiitis, Granulomatosis with polyangiitis or Eosinophilic granulomatosis with polyangiitis), Behçet’s disease, and Cogan’s syndrome. Immune complex-mediated small vessel vasculitis can be seen in rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, Henoch-Schönlein purpura, cryoglobulinemic vasculitis, Hypocomplementemic urticarial vasculitis, Erythema elevatum diutinum, and cutaneous leukocytoclastic angiitis, formerly known as hypersensitivity vasculitis.  Other causes of small vessel vasculitis or leukocytoclastic vasculitis include drug-induced vasculitis, paraneoplastic vasculitis, and infection associated vasculitis (hepatitis B, hepatitis C, syphilis).

Leukocytoclastic vasculitis is a small vessel vasculitis characterized histopathologically by immune complex-mediated vasculitis of the dermal capillaries and venules. Cutaneous leukocytoclastic vasculitis is usually confined to skin with rare extracutaneous manifestations in less than 30% of the cases. Key clinical features of cutaneous leukocytoclastic angiitis include palpable purpura, lower extremity location, small vessel involvement. [2][3][4] If leukocytoclastic vasculitis is suspected, a punch biopsy should be performed with direct immunofluorescence studies. If no systemic symptoms are present, laboratory testing including C-reactive protein, complete blood count (CBC), basic metabolic panel, liver function tests, and urinalysis should be done as well. If there is a concern for systemic involvement, a more extensive workup needs to be performed. Most cases of idiopathic cutaneous small-vessel vasculitis cases are self-limited with 90% resolving in weeks to months of onset. In persistent vasculitis, treatment depends on the severity of disease and can range from oral corticosteroids to various steroid-sparing agents.[5][6]

Etiology

Leukocytoclastic vasculitis is idiopathic up to 50% of the cases.  Infections and drugs are the most common triggers for secondary leukocytoclastic vasculitis.[7] It can be seen secondary to underlying systemic autoimmune diseases, chronic infections, and malignancies as well.  Post-infectious leukocytoclastic vasculitis is most commonly seen after streptococcal upper respiratory tract infection. Other infectious triggers include, but are not limited to, Mycobacterium, Staphylococcus aureus, Chlamydia, Neisseria, and HIV.  Chronic infections with hepatitis B, hepatitis C, and syphilis can be associated with leukocytoclastic vasculitis as well. Several drugs have been associated with leukocytoclastic vasculitis. The onset is typically 1 to 3 weeks after drug initiation. These include, but are not limited to, beta-lactams, erythromycin, clindamycin, vancomycin, sulfonamides, furosemide, allopurinol, NSAIDs, amiodarone, gold, thiazides, phenytoin, beta-blockers, TNF-alpha inhibitors, selective serotonin reuptake inhibitors, metformin, warfarin, valproic acid, among many others. Neoplastic or hematologic triggers of leukocytoclastic vasculitis include, but are not limited to lymphomas, leukemias, visceral tumors such as intestinal adenocarcinoma and lung cancer.   Systemic diseases including connective tissue diseases (systemic lupus erythematosus, Sjogren syndrome), inflammatory bowel disease, Behcet disease, and rheumatoid arthritis cryoglobulinemic vasculitis, Henoch-Schönlein purpura (HSP), Hypocomplementemic urticarial vasculitis, and Erythema elevatum diutinum are also associated with leukocytoclastic vasculitis.[8]

Epidemiology

The annual incidence of biopsy-proven leukocytoclastic vasculitis is approximately 45 per million individuals. The epidemiology of leukocytoclastic vasculitis varies with the underlying etiology. Leukocytoclastic vasculitis occurs in all ages and both genders; however, it typically presents in adults. However, HSP is usually seen in children and young adults with an incidence of up to 270 cases per million children per year with a slight male predominance. 

Pathophysiology

The pathogenesis of leukocytoclastic vasculitis involves immune complex deposition in small vessel walls in addition to activation of the complement system. Neutrophils are recruited, and injury to vessel walls ensues with secondary exudation of erythrocytes, fibrin, and serum. Fibrinoid necrosis of small vessel walls will be noted secondary to lysosomal enzymes such as collagenases and elastases as well as reactive oxygen species. Lymphokines aid in the evolution of the clinical findings as well. IL-1, IL-6, IL-8, and tumor necrosis factor are increased in circulation. Turbulence and increased venous pressure present in the lower extremities can elucidate why leukocytoclastic vasculitis commonly tends to occur on the legs.[9][10][11]

Histopathology

The histopathologic features of leukocytoclastic vasculitis will vary based on the time frame of the vasculitis.  Fresh lesions biopsied within the 1st 18-24 hours of onset, from a nonulcerated site have the highest yield with most diagnostic findings.  On light microscopy, findings of vessel wall destruction by the infiltration of inflammatory cells within and around the vessel wall can be seen.  Classically leukocytoclastic vasculitis demonstrates neutrophil infiltration in the small vessel walls. The neutrophils undergo degeneration, known as leukocytoclasis with nuclear dust (karyorrhexis). Fibrinoid necrosis of the vessel walls can be apparent around the vasculature. Extravasation of red blood cells can be present in the dermis as well. In drug-related cases, eosinophils are often noted in the dermis.  Older lesions especially those more than 48 hours old can demonstrate lymphocytic infiltration.

Direct immunofluorescence is strongly recommended in cases of new-onset leukocytoclastic vasculitis.  While a negative result carries a low yield, a positive result can sometimes be diagnostic of an underlying disease and can provide insight into the underlying disease pathophysiology.  Further, light microscopy and histopathological features of leukocytoclastic vasculitis may not be sufficient in differentiating pauci-immune vasculitis from immune complex-mediated vasculitis.   Immunofluorescence shall be performed with fluorescein-labeled antibodies against IgG, IgM, IgA, and C3.  Strong IgA deposition without other antibody deposition is indicative of HSP.  Leukocytoclastic vasculitis associated with underlying systemic lupus erythematosus can show diffusely positive immunofluorescence in addition to increased dermal mucin.

History and Physical

The cutaneous manifestations of leukocytoclastic vasculitis usually appear about 1-3 weeks after the triggering event. Leukocytoclastic vasculitis presents as erythematous macules with palpable purpura bilaterally on dependent areas of the body like the lower extremities and buttocks. Unilateral presentations and localized lesions are rare. Hemorrhagic vesicles and bulla, pustules, nodules, crusted ulcers, or livedo reticularis may also be present on physical exam. The lesions can range in size from 1 mm to 1 cm in diameter. The lesions can appear at once in crops, or various crops may cycle and produce lesions with different stages of evolution. Koebnerization, the appearance of lesions at areas of trauma, is uncommon with this vasculitis. In fact, reverse koebnerization has been described with the disappearance of the lesions with pressure bandage application after the biopsy. The lesions are asymptomatic but may itch, burn, or sting.

Extracutaneous manifestations with leukocytoclastic vasculitis are less common. Systemic symptoms noted with leukocytoclastic vasculitis may include low-grade fevers, malaise, weight loss, myalgias, and arthralgias. These findings have been noted in approximately 30% of affected patients, with arthralgias compromising the most common manifestation. Other less common manifestations include renal, gastrointestinal, pulmonary, or neurological symptoms, and these entities may be better classified as microscopic polyangiitis/polyarteritis.  Other features of the underlying disease associated with leukocytoclastic vasculitis can give a clue to the underlying diagnosis.  Leukocytoclastic vasculitis in children along with symptoms of inflammatory arthritis, abdominal pain, edema and hematuria/renal disease is characteristic of Henoch-Schoenlein purpura.   Leukocytoclastic vasculitis is unlikely to be the presenting complaint in rheumatoid arthritis and Sjogren syndrome and usually, these patients already have a well-established diagnosis for several years before they developed leukocytoclastic vasculitis.  In systemic lupus erythematosus, leukocytoclastic vasculitis is less likely to be the presenting initial complaint but it can be seen as the initial complaint.  These patients will likely have other associated features of systemic lupus erythematosus as well.

Evaluation

Skin biopsy with direct immunofluorescence is the cornerstone for the diagnosis of leukocytoclastic vasculitis. Workup for an underlying disease should be undertaken based on clinical suspicion.  Complete blood counts, liver function test and renal function tests along with urinalysis are recommended at least once at baseline. A more extensive workup shall be pursued if systemic involvement is a concern including a viral hepatitis panel, HIV testing, ASO titer (if a streptococcal infection is the suspected trigger), antinuclear antibody and more specific antibodies for systemic lupus erythematosus and Sjogren syndrome, rheumatoid factor, anti-CCP antibody, serum complements, serum protein electrophoresis and cryoglobulins.

Treatment / Management

Most cases of idiopathic cutaneous leukocytoclastic vasculitis are mild and resolve with supportive measures such as leg elevation, rest, compression stockings, and antihistamines. In more chronic or resistant cases, a 4-6 week tapering dose of corticosteroids can be used.  Rarely, immunosuppressive steroid-sparing agents such as methotrexate, azathioprine, mycophenolate mofetil, dapsone, cyclophosphamide, and intravenous immunoglobulin may be needed.

If an offending drug has been identified, withdrawal of the drug is crucial in the resolution of the vasculitis.  In cases of leukocytoclastic vasculitis associated with an infection, treatment of the infection usually results in the resolution of the vasculitis. Similarly, malignancy-associated leukocytoclastic vasculitis improves with treatment of the malignancy.  When leukocytoclastic vasculitis is associated with an underlying connective tissue disease or an autoimmune disease such as systemic lupus erythematosus or rheumatoid arthritis, better control of the underlying disease by an escalation of the immunosuppressive therapy may be needed to treat the leukocytoclastic vasculitis and prevent relapses.   Mild cases of HSP usually do not require corticosteroids or immunosuppressive agents, and skin rash and arthralgia usually respond to NSAIDs.  High-dose corticosteroids and/or immunosuppressive agents may be indicated in cases of severe renal involvement or systemic involvement.

Differential Diagnosis

The differential diagnosis includes:

• Thrombocytopenic purpura

• Benign pigmented purpura

• Schamberg disease

  • This is an idiopathic phenomenon, which results from erythrocyte extravasation into the dermis in the lower extremities due to capillary fragility or leaky blood vessels, venous stasis or exercise.  Hyperpigmentation in the lower extremities is frequently present. 

Skin biopsy can easily differentiate benign pigmented purpura from leukocytoclastic vasculitis given the lack of features of vasculitis such as fibrinoid necrosis and vessel wall disruption by the inflammatory infiltrates.[12]

Prognosis

The mortality rate of leukocytoclastic vasculitis is low (about 2%), and related to systemic involvement versus strictly cutaneous involvement. Approximately 90% of patients experience spontaneous resolution of their skin lesions within weeks to months, with the remaining 10% continuing to chronic disease averaging 2 to 4 years. Arthralgias without fever may portend chronicity. 

Complications

Rare complications of cutaneous leukocytoclastic vasculitis include skin ulcerations which may get secondarily infected.  While wound care is crucial in the management of these skin ulcers, they usually do not resolve unless immunosuppressive therapy such as corticosteroids is used to treat the underlying vasculitic insult.

Deterrence and Patient Education

Early identification, especially in drug-induced leukocytoclastic vasculitis, is crucial and patients should be educated about this potential adverse effect of the medications before initiating the medication.  Patients with idiopathic cutaneous leukocytoclastic vasculitis usually carry a favorable prognosis, however, if there is a secondary etiology, close follow-up is needed and patients should be educated about the importance of compliance and regular monitoring.   Further, patients should be educated about the course of the leukocytoclastic vasculitis as it may take several weeks to months for it to resolve.

Enhancing Healthcare Team Outcomes

The involvement of an interprofessional team including physicians, nurse practitioners, nurses, and pharmacists is needed to manage leukocytoclastic vasculitis.  Pharmacists can assist in identifying potential drug triggers and removing them.  The involvement of the nursing team is crucial in maintaining close follow-up and monitoring of the patient.  The involvement of specialists including rheumatologists may be needed in some cases especially when secondary etiologies are suspected.  Finally, patient education and reassurance about the benign course of the idiopathic cutaneous leukocytoclastic vasculitis as in most cases can help prevent undue anxiety in the patients.  Close communication among the team members can significantly enhance patient-centered care. [Level V]

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Figure

Leukocytoclastic Vasculitis. Contributed by DermNetNZ

References

1.

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. [PubMed: 23045170]

2.

Piubelli MLM, Felipe-Silva A, Kanegae MY, Ferraz de Campos FP. Fatal necrotizing Candida esophagitis in a patient with leukocytoclastic cutaneous vasculitis and ankylosing spondylitis. Autops Case Rep. 2019 Apr-Jun;9(2):e2018070. [PMC free article: PMC6433139] [PubMed: 30963052]

3.

Younger DS, Carlson A. Dermatologic Aspects of Systemic Vasculitis. Neurol Clin. 2019 May;37(2):465-473. [PubMed: 30952419]

4.

Alquorain NAA, Aljabr ASH, Alghamdi NJ. Cutaneous Polyarteritis Nodosa Treated with Pentoxifylline and Clobetasol Propionate: A Case Report. Saudi J Med Med Sci. 2018 May-Aug;6(2):104-107. [PMC free article: PMC6196709] [PubMed: 30787830]

5.

Wick MR, Patterson JW. Cutaneous paraneoplastic syndromes. Semin Diagn Pathol. 2019 Jul;36(4):211-228. [PubMed: 30736994]

6.

Lee HL, Kim L, Kim CW, Kim JS, Nam HS, Ryu JS. Case of both rivaroxaban- and dabigatran-induced leukocytoclastic vasculitis, during management of pulmonary thromboembolism. Respir Med Case Rep. 2019;26:219-222. [PMC free article: PMC6356047] [PubMed: 30740299]

7.

Fekete GL, Fekete L. Cutaneous leukocytoclastic vasculitis associated with erlotinib treatment: A case report and review of the literature. Exp Ther Med. 2019 Feb;17(2):1128-1131. [PMC free article: PMC6327513] [PubMed: 30679984]

8.

Li X, Xia J, Padma M, Ma Z, Tian Y. Cutaneous leukocytoclastic vasculitis as the first manifestation of malignant syphilis coinfected with human immunodeficiency virus. J Cutan Pathol. 2019 May;46(5):393-395. [PubMed: 30632201]

9.

Shavit E, Alavi A, Sibbald RG. Vasculitis-What Do We Have to Know? A Review of Literature. Int J Low Extrem Wounds. 2018 Dec;17(4):218-226. [PubMed: 30501545]

10.

Nakamura T, Wakiguchi H, Okazaki F, Asano N, Hoshii Y, Hasegawa S. Purpuric drug eruption without leukocytoclastic vasculitis associated with vancomycin. Asian Pac J Allergy Immunol. 2020 Mar;38(1):47-51. [PubMed: 30447655]

11.

Younis AA. Urticarial vasculitis as an initial manifestation of colonic carcinoma: a case report and review of the literature. Reumatismo. 2018 Dec 20;70(4):259-263. [PubMed: 30570245]

12.

Tolaymat L, Hall MR. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Apr 17, 2023. Pigmented Purpuric Dermatitis. [PubMed: 30137846]

Disclosure: Dana Baigrie declares no relevant financial relationships with ineligible companies.

Disclosure: Amandeep Goyal declares no relevant financial relationships with ineligible companies.

Disclosure: Jonathan Crane declares no relevant financial relationships with ineligible companies.

Cutaneous small vessel vasculitis | DermNet

Author: Based on Dr Amy Stanway’s article on Cutaneous Vasculitis, 2003. Revised by A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, January 2016.

What is vasculitis?

Vasculitis is a disorder in which there are inflamed blood vessels. These may include capillaries, arterioles, venules and lymphatics.

• There are a wide variety of clinical presentations.
• There are several types of cutaneous vasculitis.
• Cutaneous vasculitis is associated with systemic vasculitis in a minority of patients.

What is a small vessel vasculitis?

Small vessel vasculitis is the most common form of vasculitis affecting arterioles and venules.

• In the skin, small vessel vasculitis presents with palpable purpura.
• Cutaneous small-vessel vasculitis can be idiopathic/primary, or secondary to infection, drug or disease.
• It may be neutrophilic, lymphocytic or granulomatous on histopathology.

Small vessel vasculitis is also called immune complex small vessel vasculitis. The term hypersensitivity vasculitis is used for cutaneous small vessel vasculitis due to known drug or infection.

There are particular types of small vessel vasculitis that present with similar cutaneous signs and should be considered in the differential diagnosis.

• Henoch-Schönlein purpura
• Acute haemorrhagic oedema of infancy
• Urticarial vasculitis
• Exercise-induced vasculitis
• Polyarteritis nodosa (which also affects medium-sized vessels)
• Erythema elevatum diutinum
• Malignant atrophic papulosis (Degos disease)
• Recurrent cutaneous necrotising eosinophilic vasculitis
• ANCA-associated vasculitis:
  • Microscopic polyangiitis
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
  • Granulomatosis with polyangiitis
  • Lymphomatoid granulomatosis

Who gets cutaneous small vessel vasculitis?

Cutaneous small vessel vasculitis mainly affects adults of all races over the age of 16. Children are more likely to have Henoch-Schönlein purpura, a distinctive vasculitic syndrome associated with deposits of IgA in the skin and kidneys.

Secondary cutaneous small vessel vasculitis often affects older people, because they are more likely to have diseases and medications (alone or in combination) that are potential causes of vasculitis.

What causes small vessel vasculitis?

Many different insults may cause an identical inflammatory response within the blood vessel wall. Three main mechanisms are proposed.

• Direct injury to the vessel wall by bacteria or viruses
• Indirect injury by activation of antibodies
• Indirect injury through activation of complement, a group of proteins in the blood and tissue fluids that attack infection and foreign bodies.

Vasculitis can be triggered by one or more factors. In the past, it was frequently seen with administration of antisera (serum sickness) but is now more often due to drugs, infections and disease. In most cases, an underlying cause is not found

Drugs

Drugs are frequently responsible for cutaneous small vessel vasculitis, particularly in association with infection, malignancy or autoimmune disorders. The onset of vasculitis is often 7–10 days after the introduction of new medicine, such as:

• Antibiotics
• Thiazide diuretics
• Phenytoin
• Allopurinol
• Oral anticoagulants, such as warfarin and coumarin.
• Non-steroidal anti-inflammatory drugs (NSAIDs).

Foods and food additives, for example, tartrazine, are rare causes of vasculitis.

Infection

Examples of infections associated with cutaneous small vessel vasculitis include:

• Bacterial infection: Streptococcus pyogenes, bacterial endocarditis
• Viral infection: hepatitis B, hepatitis C (by causing cryoglobulinaemia), human immunodeficiency virus (HIV) and haemorrhagic fever (eg, dengue).

Diseases

Cancer is found in fewer than 5% of patients with cutaneous small vessel vasculitis. It is thought that malignancy leads to more circulating antibodies and viscous proteins that may sludge within small blood vessels.

Autoimmune disorders such as systemic lupus erythematosus (SLE), dermatomyositis, and rheumatoid arthritis are characterised by circulating antibodies that target the individual’s tissues. Some of these antibodies can target blood vessels, resulting in vasculitis.

Why does small vessel vasculitis favour the lower legs?

The main reason that vasculitis affects the lower leg is reduced blood flow because this leads to the deposition of mediators of inflammation on the blood vessel wall. Contributing factors include:

• Stasis: gravity pooling and slowing blood flow in the lower legs
• The high-fat content of thighs and buttocks relative to leaner areas
• Vasoconstrictor drugs, such as beta-blockers
• Varicose veins
• Inadequate arterial blood supply to the legs (peripheral vascular disease)
• Cold weather
• High blood viscosity causing sedimentation of the blood cells
• Precipitation of cryoglobulins
• Fibrin deposition blocking the blood vessels.

What are the clinical features of small vessel vasculitis?

The clinical features of hypersensitivity vasculitis include:

• Prominent involvement of lower legs with fewer lesions on proximal sites
• Palpable purpura (purple, non-blanching papules and plaques)
• Sometimes, petechiae and ecchymoses
• Non-purpuric erythematous or urticaria-like weals, macules and papules
• Haemorrhagic bullae, necrosis and superficial ulceration
• Local pruritus, burning pain and swelling
• Variable systemic symptoms with fever, joint aches, lymphadenopathy and gastrointestinal upset.

The initial acute rash of small vessel vasculitis usually subsides within 2–3 weeks, but crops of lesions may recur over weeks to several months, and hypersensitivity vasculitis may rarely become relapsing or chronic.

Cutaneous small vessel vasculitis

Cutaneous vasculitis

Cutaneous vasculitis

Hypersensitivity vasculitis

Complications of small vessel vasculitis

The most severe complications of small vessel vasculitis are seen with its systemic forms, such as kidney disease associated with Henoch-Schönlein purpura.

Local ulceration from cutaneous small vessel vasculitis can lead to:

• Wound infection or cellulitis
• Chronic leg ulceration
• Scar formation.

How is cutaneous small vessel vasculitis diagnosed?

The clinical diagnosis of an acute cutaneous small vessel vasculitis is generally straightforward.

Thorough history and examination are essential to determine if symptoms and signs are confined to the skin, or if there may be systemic involvement, and to establish a cause.

Cutaneous small vessel vasculitis is confirmed by 4-mm punch biopsy of an early purpuric papule, ideally present for 24–48 hours. Histopathology reveals neutrophils around arterioles and venules, and fibrinoid necrosis (fibrin within or inside the vessel wall). There may be extravasated red cells, leukocytoclasis (broken-up neutrophils within the vessel wall) and signs of an underlying disease.

Direct immunofluorescence (DIF) of a lesion less than 24 hours old often reveals immunoglobulins and complement.

• Perivascular IgA is characteristic of Henoch-Schönlein purpura
• Perivascular IgM suggests cryoglobulinaemia or rheumatoid arthritis
• Interface immunoglobulins may be a sign of systemic lupus erythematosus
• DIF is often negative in cutaneous polyarteritis nodosa and ANCA-positive vasculitis

Screening tests are requested to identify any underlying cause and to determine the extent of involvement of internal organs. The history and symptoms may suggest these. Patients should have:

• Urinalysis, looking for protein, blood and glomerular casts
• Full blood count, liver and kidney function

Additional tests may include:

• Anti-nuclear antibodies (ANA), extractable nuclear antigen profile (ENA)
• Anti-streptococcal antibodies, human immunodeficiency virus (HIV), hepatitis B and C serology
• Serum complement levels
• Protein and immunoglobulin electrophoresis
• Cryoglobulins
• Antineutrophil cytoplasmic antibody (ANCA)
• Chest X-ray if symptoms suggest lung disease

If an initial screen indicates an abnormality or there is clinical suspicion of a more widespread vasculitic process, further investigations will be requested. The majority of patients presenting with palpable purpura have primary cutaneous small vessel vasculitis, and no underlying cause is found in spite of extensive investigations.

What is the treatment for cutaneous small vessel vasculitis?

In most patients presenting with the first episode of acute cutaneous small vessel vasculitis, general measures are all that is required to keep the patient comfortable until the rash spontaneously resolves.

• If an underlying cause is found, remove the trigger (for example, stop the drug) and treat associated disease(s)
• Rest — exercise often induces new lesions
• Apply compression and elevate the affected limb(s)
• Use simple analgesics and NSAIDs for pain
• Protect fragile skin from injury
• Apply emollients to relieve dryness and itch
• Dress ulcers
• Treat secondary bacterial infection

Severe, recurrent or chronic cutaneous small vessel vasculitis

Medications used to control cutaneous vasculitis have not been subjected to randomised trials. They are recommended in acute vasculitis when ulcerated and in symptomatic relapsing or chronic disease. They include:

• Corticosteroids: prednisone 0.5 mg/kg/day for 1–2 weeks, tapered over 3–6 weeks
• Colchicine: 0.5 or 0.6 mg bd
• Dapsone: 50–100 mg daily.

Other treatments reported to be helpful in at least some cases include:

• Hydroxychloroquine
• Minocycline
• Immune modulators: methotrexate, azathioprine, mycophenolate, cyclosporin
• Rituximab
• Intravenous immunoglobulin.

If cutaneous vasculitis is a manifestation of systemic vasculitis, treatment of the systemic disorder is required.

How can cutaneous small vessel vasculitis be prevented?

Flares of cutaneous small vessel vasculitis can be minimised by rest, compression and elevation of lower legs.

Once a drug is identified as the cause of small vessel vasculitis, the patient should avoid it lifelong. It is not usually possible to prevent other forms of vasculitis.

What is the outlook for small vessel vasculitis?

Idiopathic/primary cutaneous small vessel vasculitis is self-limiting. Most cases resolve within a period of weeks to months. When the cause is an underlying disease, the vasculitis may recur at variable intervals after the initial episode.

It is common for an orange-brown discolouration of the skin due to haemosiderin deposition to persist for weeks or months after the inflammatory disease has settled.

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.

Vasculitis: causes, types, symptoms, diagnosis and treatment of vasculitis in Moscow

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• Published: January 22, 2016

• Article updated: March 15, 2023

Author of the publication: Aleksey Vladimirovich Zaitsev, Dermatovenerologist (children), Dermatovenereologist (adult)
Editor: Krizmanich Maria Pavlovna, Dermatovenereologist (adult), Dermatovenereologist (children)

Content of the article:
Forms, varieties, and symptoms
Skin 900 11 Allergic
Systemic
Cryoglobulinemic
Urticarial vasculitis
Vasculitis in children
Kawasaki syndrome
Hemorrhagic vasculitis
Diagnosis and treatment at NEARMEDIC

An autoimmune inflammation of the walls of blood vessels is called vasculitis. A disturbed immune system affects the vessels located on the surface – in the dermis, as well as in deeper layers and internal organs.

The causes of vasculitis are long-term allergic agents (drugs, fluff and pollen, house and book dust) and chronic infectious diseases (affected teeth, otitis media, tonsillitis, mycoses). The disease in children can be caused by an allergy to the vaccine.

Also, the reason may be a hereditary immunodeficiency condition of the body, which is not always diagnosed at an early stage of development, but manifests itself with a long-term effect of the agent on the immune system and causes aggression towards the walls of blood vessels.

Vasculitis is an inflammatory disease of the walls of blood vessels that can present with red patches or rashes on the skin, muscle and joint pain, fever, and general malaise. The causes of vasculitis can be varied, including infections, allergic reactions, autoimmune diseases, and other factors. To diagnose vasculitis, you need to contact a dermatovenerologist, who will conduct an examination and prescribe the necessary studies. Treatment may include medications such as steroids or immunosuppressants, as well as physical therapy. It is important to see a doctor at the first sign of vasculitis in order to avoid complications and start treatment faster.

Cosmetologist (adult), Dermatovenereologist (adult)

Forms, varieties, and symptoms

Symptoms of the disease depend on the form of vasculitis and variety. Early symptoms are similar to the manifestation of most infectious and inflammatory diseases: fever, weakness, headache, fatigue, pain in the muscles.

With the development of the process, symptoms of the primary and secondary forms of the disease appear. The primary form is an independent disease, which consists in inflammation of the vessel of immune origin, autoimmune vasculitis. The secondary form is a consequence and symptom of a systemic disease, as well as a consequence of infections, infection with helminths, exposure to toxins, chemicals, and radiation. Among the systemic diseases, the symptoms of which can be vasculitis are diabetes mellitus, lupus erythematosus, sarcoidosis.

Cutaneous

Cutaneous vasculitis affects vessels of the dermis of small or medium diameter, but does not affect the vessels of the internal organs. Diagnosed by biopsy, since skin vasculitis is similar in external symptoms to some diseases:

• capillary effusions of the skin – purpura;
• damage to skin capillaries – petechiae;
• urticaria, nodules;
• net levedo due to stagnation of blood in the capillaries.

Vasculitis of the skin can develop against the background of systemic diseases, and then the symptoms are supplemented by fever, pain in the joints.

Allergic

Manifested by the following symptoms:

• nodules, hemorrhagic, erythematous spots and rashes;
• skin infarction – the formation of a black crust in the area of ​​​​rashes;
• hemorrhages under toenails;
• pain in joints and muscles;
• burning, squeezing pain or itching at the eruption;

Allergic vasculitis is most often manifested by a rash on the thighs, legs, feet, and in the generalized form, rashes are added on the forearms and trunk.

The group of allergic vasculitis includes Bazin’s indurative erythema, acute and chronic erythema nodosum, Behcet’s disease, temporal angiitis, which have specific symptoms.

Acute erythema nodosum is characterized by large nodes and discoloration of the skin underneath from red to greenish.

Behcet’s disease affects mainly the mucous membranes of the eyes, mouth and skin with the formation of erosions and ulcers.

With temporal or senile angiitis, older women suffer from severe and prolonged pain in the temples.

Systemic

Occurs when immune mechanisms are impaired in various systemic diseases, which are characterized by connective tissue damage (rheumatism, granulomatosis, lupus erythematosus, etc.)

In Wegener’s granulomatosis, the disease manifests itself with the following symptoms:

• destructive changes in the walls of the vessels of the respiratory tract and kidneys;
• ulcerated granulomas on the mucous membrane of the nose, mouth, bronchi;
• glomerulonephritis;
• severe complications on internal organs, skin, nervous system, organs of vision.

In rheumatism, it spreads to the whole body and manifests itself depending on the stage of development of the disease. In addition to the skin, the vessels of the internal organs and the brain are affected with the risk of internal bleeding.

Cryoglobulinemic

One of the systemic varieties of the disease is cryoglobulinemic vasculitis, in which cryoglobulin proteins appear in blood cells, which are deposited on the walls of blood vessels and destroy them.

The disease has a progressive course, and its characteristic symptom (except for those common to all types of disease) is damage to the peripheral nerves and impaired sensitivity. If not adequately treated, cryoglobulinemic vasculitis can cause speech loss and motor paralysis.

Urticarial vasculitis

Urticarial vasculitis, or angiitis, is one of the varieties of the allergic form of the disease, which is characterized by chronic inflammation of the superficial vessels of the skin.

At the initial stage of development, it is often diagnosed as chronic urticaria. The disease is characterized by the following symptoms:

• undulating course;
• appearance on the skin of hemorrhagic spots, nodules, blisters;
• burning sensation in affected areas;
• headache, pain in joints, waist, muscles, abdomen;
• fever;
• glomerulonephritis.

Diagnosed by immunofluorescence and histological examination of the affected areas of the dermis.

Vasculitis in children

Vasculitis in children is quite rare, but all varieties have characteristic features of the course that are characteristic only in childhood.

Kawasaki syndrome

Systemic form of the disease in children under 7 years of age with damage to the vessels of the heart, lymph nodes, and respiratory mucosa. The clinical picture is characterized by a rapid, acute onset with a temperature of 38 to 41 degrees and the following symptoms (in order of gradual appearance):

• debilitating fever;
• skin lesions with scarlatina-like rash with erythematous plaques;
• damage to the mucous membrane of the respiratory tract, nose, eyes;
• thickening and redness of the skin on the soles and palms;
• enlargement of the lymph nodes of the neck;
• crimson tongue;
• peeling of the skin around the nails, on the phalanges of the fingers of the extremities;
• damage to the cardiovascular system in the acute phase, aneurysm.

Kawasaki syndrome is curable with timely diagnosis, the consequences are eliminated after 5-8 years.

Hemorrhagic vasculitis

While hemorrhagic vasculitis in adults can be caused by pathologies during pregnancy, diabetic nephropathy, cirrhosis of the liver, malignant neoplasms, this form of the disease in children is most often caused by infections of the upper respiratory tract, measles, paratyphoid, drug or food allergies.

Hemorrhagic vasculitis in children is subdivided into the following forms: cutaneous, cutaneous-articular, abdominal, renal, and cutaneous-renal. Specific symptoms are inherent in each of them:

• skin form – pronounced edema against the background of cold urticaria, purpura, rashes with localization on the feet, shins, gradually spreading to the thighs, joint pain;
• abdominal form: severe course with severe pain in the abdomen, localized near the navel;
• renal form – the presence of proteins, globulins in the urine.

Hemorrhagic vasculitis is dangerous due to complications, relapses and a tendency to generalization – spread to the vessels of internal organs.

Diagnostics and treatment in NEARMEDIC

Diagnostics in the NEARMEDIC network of clinics is carried out in our own clinical diagnostic laboratory using modern, informative and effective methods, using diagnostic tests that allow us to exclude the misinterpretation of external symptoms.

The laboratory performs:

• histopathological examination;
• immunoassay;
• allergy testing;
• PCR test;
• immunogram examination;
• multiple urine and blood tests;
• regular examination of the cardiovascular and respiratory systems.

When vasculitis is diagnosed, treatment is prescribed depending on the form and variety. Drug therapy includes prescription:

• glucocorticosteroids in severe pathological conditions;
• medications for the treatment of the underlying disease in secondary forms;
• treatment of foci of infection;
• non-steroidal anti-inflammatory drugs;
• medications to restore the strength and elasticity of vessel walls;
• antioxidants;
• painkillers;
• corticosteroids for the diagnosis of hemorrhagic vasculitis.

Treatment includes physiotherapy and diet therapy.

At the first appearance of symptoms of the disease, contact your nearest NEARMEDIC clinic or call our contact center at the phone number listed on the website. You can also make an appointment with a dermatologist through feedback services.

Doctors

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Allergic skin vasculitis: symptoms, diagnosis, treatment of allergic skin vasculitis

Allergic vasculitis is an inflammatory disease of the walls of blood vessels that occurs as a result of an allergic reaction. Allergic vasculitis can have a lot of varieties, some of which damage individual organs, while others spread to their entire systems. In allergic skin vasculitis, the inflammatory process affects the vessels that are in the subcutaneous tissue (as a rule, without involving the vessels of the internal organs in the process).

Both adults and children are susceptible to it, regardless of age.

Causes of allergic skin vasculitis.

• Drug or food allergy
• Infections or viruses in the body
• Prolonged sun exposure
• Genetic predisposition
• Hypothermia, etc.

Symptoms of the disease.

Allergic vasculitis of the skin (depending on the depth of the damaging process) is divided into:

• Surface
• Deep

Symptoms of allergic skin vasculitis:

• Purpura – vascular spots in areas with hemorrhage
• Ulcers
• Vascular spots
• Papules – pink nodules of the skin
• Vesicles greater than 5 mm in diameter
• Hypodermic nodes
• Chronic urticaria
• Rash

All of the above symptoms are usually accompanied by general malaise, loss of appetite, itching and burning of the skin, fever and fever.

The danger of this disease to humans.

With allergic vasculitis, the walls of blood vessels weaken and become thinner, which can lead to complete blockage of blood circulation and more serious consequences for the patient.

Diagnosis of allergic vasculitis.

After a detailed examination of the patient and studying his anamnesis, the doctor prescribes the necessary examinations:

• urine and blood tests, biochemical analysis of blood serum;
• analysis of blood serum for immunoglobulin;
• cardiogram of the heart;
• biopsy of the affected area of ​​the skin;
• X-ray of internal organs;
• determination of the general state of immunity, etc.

Specialists.

List of specialists to contact for the diagnosis and treatment of allergic vasculitis:

• Allergist
• Immunologist
• Therapist

Additionally, the doctor can refer the patient for a consultation with narrow specialists: a dermatologist, a vascular surgeon, a venereologist, a rheumatologist, etc.

For the diagnosis, treatment and prevention of this disease, we invite you to the NCC Clinic No. 2 (Central Clinical Hospital of the Russian Academy of Sciences), where you can undergo all the necessary examinations.

Treatment.

Allergic vasculitis must be treated comprehensively.

• It is necessary to identify the allergen and exclude its effect on the body (stop taking the drug, some product, etc.)
• Take antihistamines.
• In the acute course of the disease, bed rest should be observed.
• Drink plenty of water and follow a strict diet that includes the required amount of vegetables, protein foods and fruits, with the exception of those that can cause allergies (nuts, red fish, chocolate, citrus fruits, honey, etc.).
• If a chronic infection is detected, antibacterial drugs are prescribed.
• Vascular protectors are prescribed to strengthen the walls of blood vessels.
• For the treatment of allergic vasculitis of the skin, topical drugs (creams and ointments as prescribed by a doctor) can be used.