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Small vasculitis. Leukocytoclastic Vasculitis: Causes, Symptoms, and Treatment of Small Vessel Inflammation

by alexxlab

What is leukocytoclastic vasculitis. How is it diagnosed. What are the main causes and triggers of this condition. What are the key clinical features and symptoms. How is leukocytoclastic vasculitis treated.

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Understanding Leukocytoclastic Vasculitis: An Overview of Small Vessel Inflammation

Leukocytoclastic vasculitis (LCV) is a form of small vessel vasculitis characterized by inflammation of the dermal capillaries and venules. This condition falls under the broader category of cutaneous small-vessel vasculitis and can be either idiopathic or associated with various underlying factors. To fully grasp the nature of this condition, it’s essential to understand its key features, causes, and management approaches.

What Defines Leukocytoclastic Vasculitis?

LCV is primarily defined by its histopathological features, which include:

  • Immune complex-mediated inflammation of small blood vessels in the skin
  • Involvement of dermal capillaries and venules
  • Presence of leukocytoclasis (nuclear debris from fragmented neutrophils)

Is LCV limited to the skin? While cutaneous involvement is the hallmark of LCV, extracutaneous manifestations can occur in approximately 30% of cases, highlighting the potential for systemic involvement in some patients.

Etiology and Triggers of Leukocytoclastic Vasculitis

The causes of leukocytoclastic vasculitis are diverse, with up to 50% of cases being idiopathic. However, several triggers and associated conditions have been identified:

Infectious Triggers

Infections are among the most common causes of secondary LCV. These include:

  • Streptococcal upper respiratory tract infections (most common)
  • Mycobacterium and Staphylococcus aureus infections
  • Viral infections, including HIV
  • Chronic infections such as hepatitis B, hepatitis C, and syphilis

Drug-Induced Leukocytoclastic Vasculitis

Numerous medications can trigger LCV, typically within 1 to 3 weeks of initiation. Some examples include:

  • Antibiotics (beta-lactams, erythromycin, clindamycin, vancomycin, sulfonamides)
  • Diuretics (furosemide, thiazides)
  • NSAIDs and allopurinol
  • Cardiovascular drugs (amiodarone, beta-blockers)
  • Anticonvulsants (phenytoin, valproic acid)
  • Newer agents like TNF-alpha inhibitors and selective serotonin reuptake inhibitors

Autoimmune and Systemic Disorders

LCV can be associated with various autoimmune and systemic conditions, including:

  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Sjögren’s syndrome
  • ANCA-associated vasculitis
  • Behçet’s disease
  • Cryoglobulinemic vasculitis

Malignancy-Associated LCV

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

Clinical Presentation and Diagnostic Features of Leukocytoclastic Vasculitis

Recognizing the clinical presentation of LCV is crucial for prompt diagnosis and management. The key features include:

Cutaneous Manifestations

  • Palpable purpura: The most characteristic skin finding
  • Predilection for the lower extremities
  • Other possible skin lesions: petechiae, pustules, urticaria, livedo reticularis, or ulcers

Why do lesions predominantly affect the lower extremities? This distribution is likely due to gravitational dependency and increased hydrostatic pressure in these areas.

Extracutaneous Symptoms

While less common, systemic involvement can manifest as:

  • Joint pain or arthritis
  • Gastrointestinal symptoms (abdominal pain, bleeding)
  • Renal involvement (hematuria, proteinuria)
  • Neurological symptoms (peripheral neuropathy)

Diagnostic Approach to Leukocytoclastic Vasculitis

Diagnosing LCV requires a combination of clinical assessment, laboratory tests, and histopathological examination:

Skin Biopsy

A punch biopsy of affected skin is essential for diagnosis. Key histopathological findings include:

  • Neutrophilic infiltration of vessel walls
  • Fibrinoid necrosis of blood vessels
  • Leukocytoclasis (nuclear debris)
  • Extravasation of red blood cells

Direct immunofluorescence studies can help identify immune complex deposition, further aiding in diagnosis and classification.

Laboratory Investigations

Initial laboratory tests for suspected LCV include:

  • Complete blood count (CBC)
  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
  • Basic metabolic panel and liver function tests
  • Urinalysis

In cases with suspected systemic involvement or to identify underlying causes, additional tests may be necessary:

  • Antineutrophil cytoplasmic antibodies (ANCA)
  • Antinuclear antibodies (ANA)
  • Complement levels
  • Hepatitis B and C serologies
  • Cryoglobulins
  • Blood cultures if infection is suspected

Treatment Strategies for Leukocytoclastic Vasculitis

The management of LCV depends on the severity of the disease and the presence of any underlying conditions. Treatment approaches include:

Conservative Management

For mild, localized cutaneous disease:

  • Removal of potential triggers (e.g., discontinuation of offending medications)
  • Leg elevation and compression stockings to reduce edema
  • Symptomatic treatment with antihistamines for pruritus

Pharmacological Interventions

For more severe or persistent cases:

  • Oral corticosteroids: Often the first-line treatment for moderate to severe disease
  • Colchicine: Can be effective in some cases, particularly for recurrent disease
  • Dapsone: Useful in chronic or recurrent cutaneous vasculitis
  • Immunosuppressive agents: For refractory cases or those with significant organ involvement (e.g., azathioprine, methotrexate, mycophenolate mofetil)
  • Rituximab: Considered in severe, refractory cases

Treatment of Underlying Conditions

Addressing any identified underlying causes is crucial:

  • Antibiotic therapy for infectious triggers
  • Management of associated autoimmune diseases
  • Treatment of underlying malignancies if present

Prognosis and Long-term Outlook for Patients with Leukocytoclastic Vasculitis

Understanding the prognosis of LCV is important for both healthcare providers and patients. Several factors influence the course and outcome of the disease:

Natural History of LCV

  • Idiopathic cases: Approximately 90% resolve within weeks to months
  • Chronic or recurrent disease: Occurs in about 10% of cases
  • Extracutaneous involvement: Present in up to 30% of patients, potentially impacting prognosis

What factors influence the likelihood of chronic or recurrent disease? Persistent underlying triggers, systemic involvement, and certain associated conditions (e.g., autoimmune diseases) may contribute to a more prolonged course.

Monitoring and Follow-up

Regular follow-up is essential to:

  • Assess treatment response
  • Monitor for potential complications
  • Identify and manage any emerging systemic involvement
  • Adjust treatment as necessary

Long-term Considerations

Patients with LCV should be aware of:

  • Potential for disease recurrence
  • Importance of avoiding identified triggers
  • Need for ongoing surveillance, especially in cases associated with systemic disorders or malignancies

Emerging Research and Future Directions in Leukocytoclastic Vasculitis

As our understanding of LCV continues to evolve, several areas of research and development are showing promise:

Biomarker Discovery

Ongoing research aims to identify specific biomarkers that could:

  • Improve diagnostic accuracy
  • Predict disease severity and prognosis
  • Guide treatment decisions

Targeted Therapies

Investigation into more targeted therapeutic approaches includes:

  • Biologics targeting specific inflammatory pathways
  • Personalized medicine approaches based on individual patient characteristics and disease mechanisms

Genetic Studies

Research into the genetic factors influencing LCV susceptibility and progression may lead to:

  • Better understanding of disease pathogenesis
  • Identification of high-risk individuals
  • Development of preventive strategies

How might advances in genetic research impact the management of LCV? Genetic profiling could potentially help predict disease course, guide treatment choices, and even prevent disease onset in susceptible individuals.

The Role of the Interprofessional Team in Managing Leukocytoclastic Vasculitis

Effective management of LCV often requires a collaborative approach involving various healthcare professionals:

Key Team Members

  • Dermatologists: Often lead the diagnosis and management of cutaneous manifestations
  • Rheumatologists: Provide expertise in systemic vasculitis and associated autoimmune conditions
  • Internists or Primary Care Physicians: Coordinate overall care and manage comorbidities
  • Pathologists: Essential for accurate histopathological diagnosis
  • Immunologists: Assist in complex cases or those requiring advanced immunological testing
  • Specialists (e.g., nephrologists, gastroenterologists): Involved in cases with specific organ involvement

Collaborative Approach Benefits

An interprofessional team approach offers several advantages:

  • Comprehensive assessment of the patient’s condition
  • Coordinated treatment planning
  • Improved management of complex or refractory cases
  • Enhanced patient education and support

How does interprofessional collaboration improve outcomes in LCV management? By combining expertise from various specialties, teams can provide more personalized, efficient, and effective care, potentially leading to better disease control and quality of life for patients.

Communication and Coordination

Effective team functioning relies on:

  • Regular case discussions and treatment plan reviews
  • Clear communication channels between team members
  • Shared decision-making involving the patient
  • Continuous education and updates on latest research and guidelines

Leukocytoclastic vasculitis presents a complex challenge in dermatology and rheumatology. Its varied etiology, potential for systemic involvement, and range of clinical presentations necessitate a thorough understanding and a multifaceted approach to management. By recognizing the key features, employing appropriate diagnostic strategies, and implementing tailored treatment plans, healthcare providers can effectively manage this condition and improve outcomes for affected patients. The ongoing research in this field promises to further enhance our ability to diagnose, treat, and potentially prevent LCV in the future.

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

Who treat Vasculitis

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To make an appointment with the clinic, you can contact the single contact center:
+7 (495) 6-171-171

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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.