Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis)


Article Author:
Dana Baigrie


Article Editor:
Jonathan Crane


Editors In Chief:
Jessica Snowden
Asif Noor
H Davies


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
6/4/2019 5:41:25 PM

Introduction

Leukocytoclastic vasculitis, also known as “hypersensitivity vasculitis” is a histopathologic diagnosis given to cutaneous, small vessel vasculitis, specifically a vasculitis of the dermal post-capillary venules. The vasculitis is most often idiopathic. However, there are many other triggers including, but not limited to, infections, neoplasms, inflammatory disorders, and drug-induced vasculitis. Key clinical features of leukocytoclastic vasculitis include palpable purpura, lower extremity location, small vessel involvement, and extracutaneous involvement in approximately 30% of patients.[1][2][3]

If leukocytoclastic vasculitis is suspected, a punch biopsy should be performed with direct immunofluorescence studies. If no systemic symptoms are present, laboratory testing including ESR, 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 can be performed.

Most cases of cutaneous, small vessel vasculitis are self-limited with 90% 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 agents.[4][5]

Etiology

Leukocytoclastic vasculitis may be triggered by a variety of different factors, though approximately half of cases are idiopathic. The triggering factors include infections, certain drugs or chemicals, systemic disease, or neoplastic disease. Aside from idiopathic etiology, infections and drugs are the most common triggers. [6]

Of the infectious triggers, streptococcal upper respiratory tract infection is the most common. Other infectious triggers include, but are not limited to, Mycobacterium, hepatitis B and C, Staphylococcus aureus, Chlamydia, Neisseria, and HIV. 

There are many drug etiologies of cutaneous small vessel 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 (lupus, dermatomyositis, and Sjogren), inflammatory bowel disease, Behcet disease, and rheumatoid arthritis have been implicated in leukocytoclastic vasculitis.

Thrombotic, embolic, and cryoglobulinemia are also documented triggers of cutaneous small vessel vasculitis.[7]

Epidemiology

Leukocytoclastic vasculitis occurs in all ages and both genders; however, it typically presents in adults. The annual incidence of biopsy-proven leukocytoclastic vasculitis is approximately 45 per million individuals. Henoch-Schonlein purpura (HSP) is the most common form of vasculitis in children, with an incidence of up to 270 cases per million children per year. Children affected by HSP average 6 years of age and have 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.[8][9][10]

Histopathology

The histopathologic features of leukocytoclastic vasculitis will vary based on the time frame of the vasculitis. To observe the most diagnostic findings is best to biopsy a lesion in the first 18 to 24 hours of onset. In this stage, classically leukocytoclastic vasculitis demonstrates neutrophil infiltration into small venule vessel walls. The neutrophils will undergo degeneration, known as leukocytoclasis with nuclear dust (karyorrhexis). Fibrinoid necrosis of the vessel walls will be apparent around the vasculature. Extravasation of red blood cells will be present in the dermis as well. In drug-related cases, eosinophils are often noted in the dermis.

While some studies suggest that direct immunofluorescence is not useful in diagnosis unless performed on fresh lesions less than 6 hours old, more recent studies indicate that C3, fibrinogen, and IgM may be noted in a granular pattern within vessel walls. If IgA is noted on direct immunofluorescence, this strongly predicts renal disease.

History and Physical

The cutaneous manifestations of leukocytoclastic vasculitis usually appear about a week after the triggering event. Leukocytoclastic vasculitis presents as erythematous macules with palpable purpura bilaterally on dependent areas of the body like the lower extremities. 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 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 not uncommon. 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.

Henoch-Schonlein purpura is a specific form of cutaneous small vessel vasculitis that typically affects children and proceeds an upper respiratory tract infection. This disease involves vascular IgA deposition. The clinical features include palpable purpura, abdominal pain, hematuria/renal disease, and arthritis.

Evaluation

If leukocytoclastic vasculitis is suspected, a punch biopsy should be performed preferably in the first 24 to 48 hours of lesion onset when the diagnostic yield of the biopsy is greatest. Also, direct immunofluorescence should be performed to evaluate for the presence of immunoglobulins, as this may have an impact on disease course.

A general workup, if there is no concern systemic involvement, should include ESR, CBC, and basic metabolic panel to rule out renal disease, liver function tests, and urinalysis to check for hematuria and proteinuria. A more extensive workup can be completed if systemic involvement is a concern including a hepatitis panel, HIV testing, ASO titer (if a streptococcal infection is the suspected trigger, chest x-ray, ANA, rheumatoid factor, serum complement, SPEP/UPEP, and cryoglobulins.

Treatment / Management

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. 

Mild cases can be treated with supportive measures such as leg elevation, rest, compression stockings, and antihistamines. Systemic corticosteroids may be used in chronic or more severe cases related to medications to ameliorate the disease progression and help improve the vasculitis. A tapering high-dose of 1 mg/kg per day is recommended over 4 to 6 weeks.

In idiopathic or chronic cases, certain steroid-sparing medications such as dapsone, methotrexate, mycophenolate mofetil, azathioprine, cyclophosphamide, and intravenous immunoglobulin (IVIG) may be indicated. 

Drug and infection-induced vasculitis respond to discontinuation of the offending medication and treatment of the infection.

Enhancing Healthcare Team Outcomes

The management of leukocytoclastic vasculitis is with a multidisciplinary team including nurse practitioners and pharmacists. In all cases, the key is to stop the offending drug or remove the trigger. The recovery is slow and may take weeks or months. About 90% of patients do have a complete recovery but about 10% of patients may require immunosuppresive or biological therapy.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis) - Questions

Take a quiz of the questions on this article.

Take Quiz
A patient with hepatitis C presents with palpable purpura on his lower extremities. He also complains of malaise and low-grade fevers. Examination reveals petechiae and purpura with some ulcerated lesions. What is the most likely diagnosis?

(Move Mouse on Image to Enlarge)
  • Image 290 Not availableImage 290 Not available
    Contributed by DermNetNZ
Attributed To: Contributed by DermNetNZ



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A hospitalized patient presents with fever, arthralgias, and weight loss as well as a palpable purpuric eruption on his lower extremities. What is the next best step in management?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most common trigger for leukocytoclastic (cutaneous small vessel) vasculitis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is not a characteristic feature of leukocytoclastic vasculitis on histology?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 5-year-old male presents with a history of upper respiratory infection and bilateral rash on his buttocks and both thighs. The rash consists of palpable purpura ranging from 2 to 10 mm in diameter and appeared approximately 1 week after the upper respiratory infection. He also complains of arthralgias and abdominal pain. Which of the following ancillary tests is most appropriate to order for this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis) - References

References

Piubelli MLM,Felipe-Silva A,Kanegae MY,Ferraz de Campos FP, Fatal necrotizing {i}Candida{/i} esophagitis in a patient with leukocytoclastic cutaneous vasculitis and ankylosing spondylitis. Autopsy     [PubMed]
Younger DS,Carlson A, Dermatologic Aspects of Systemic Vasculitis. Neurologic clinics. 2019 May;     [PubMed]
Alquorain NAA,Aljabr ASH,Alghamdi NJ, Cutaneous Polyarteritis Nodosa Treated with Pentoxifylline and Clobetasol Propionate: A Case Report. Saudi journal of medicine     [PubMed]
Wick MR,Patterson JW, Cutaneous paraneoplastic syndromes. Seminars in diagnostic pathology. 2019 Jan 31;     [PubMed]
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. Respiratory medicine case reports. 2019;     [PubMed]
Fekete GL,Fekete L, Cutaneous leukocytoclastic vasculitis associated with erlotinib treatment: A case report and review of the literature. Experimental and therapeutic medicine. 2019 Feb;     [PubMed]
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. Journal of cutaneous pathology. 2019 May;     [PubMed]
Shavit E,Alavi A,Sibbald RG, Vasculitis-What Do We Have to Know? A Review of Literature. The international journal of lower extremity wounds. 2018 Dec;     [PubMed]
Nakamura T,Wakiguchi H,Okazaki F,Asano N,Hoshii Y,Hasegawa S, Purpuric drug eruption without leukocytoclastic vasculitis associated with vancomycin. Asian Pacific journal of allergy and immunology. 2018 Oct 15;     [PubMed]
Younis AA, Urticarial vasculitis as an initial manifestation of colonic carcinoma: a case report and review of the literature. Reumatismo. 2018 Dec 20;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pediatric-Infectious Diseases. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pediatric-Infectious Diseases, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pediatric-Infectious Diseases, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pediatric-Infectious Diseases. When it is time for the Pediatric-Infectious Diseases board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pediatric-Infectious Diseases.