Predominately small vessel

Isolated Cutaneous Leukocytoclastic Vasculitis

  • What is it?
    • Hypersensitivity Vasculitis is a rare form of vasculitis that is far less common in children compared to adults. As described in earlier in different parts of this website, vasculitis involves the swelling (inflammation) of blood vessels in the body that lead to different symptoms depending on the blood vessels’ locations. This particular condition involves the small vessels in the body, and is often a reaction that occurs after an immune system response or hypersensitivity reactions (such as allergies). This first immune system activity is often caused by a substance that originates from outside the body and is often hard to identify.
    • Hypersensitivity Vasculitis shares similar symptoms with serum sickness, which is an allergic reaction caused by an injection of serum (liquid in the blood). Both of these illnesses are often seen as skin rashes and fevers. However, the biggest difference is that hypersensitivity vasculitis actually involves vasculitis-related swelling (inflammation).
    • It should be noted that his condition often has many different names, some of which include drug-induced vasculitis, allergic vasculitis, and serum sickness.
    • Another name used very often is “Isolated Cutaneous Leukocytoclastic Vasculitis”. In this term, “cutaneous” refers to the involvement of the skin in this disease, while “leukocytoclastic” describes the involvement of the death of white blood cells.
  • How does it happen?
    • Hypersensitivity vasculitis involves an immune system response that is caused by a substance that affects that body. This response involves an increase in immune cells in the blood, which are meant to find and remove this harmful substance. Eventually, the death of white blood cells, in combination with other factors, can come together and lead to the thickening and weakening of the blood vessel walls. It is thought that this occurs because of these immune cells depositing in the blood vessels, which can lead to thickening, weakening and scarring of vessel walls. This is often reflected in the body as symptoms such as raised spots (that can be felt) and rashes on the skin, in combinations with other symptoms.
  • In most cases, Hypersensitivity Vasculitis is triggered by particular drug interactions (medications). This is what leads to the initial immune system response. This response can also be caused by allergic reactions (hypersensitivity reactions) or by other infections and viruses. It can also be triggered by a combination of drugs and particular infections or diseases. However, there are also cases where a precise cause cannot be identified.
    • Drugs
      • These are the most common causes in cases of Hypersensitivity Vasculitis, which are sometimes called drug-induced vasculitis. However, this disease is very difficult to define because it is hard to prove that drugs are truly responsible for the illness.
      • There are a few types of medications that are often discussed as causing Hypersensitivity Vasculitis; antibiotics, diuretics, anticonvulsants, and anti-inflammatory drugs (not steroids).
      • In a 1996 study, it was suggested that drug-induced vasculitis can be classified using certain characteristics. These include a precipitating agent, organs being involved, and a description of pathology.
    • Infection (caused by viruses or bacteria)
      • Certain types associated with Hypersensitivity Vasculitis include hepatitis B or C, Mycobacterium tuberculosis, HIV and streptococcal agents.
    • Food
      • There have been cases in children where this illness was caused by consuming cow’s milk, chocolate or other cocoa-containing products.
  • Hypersensitivity Vasculitis is a rare disease that is seen far more in adults than in children. Because of this, there is far less data available amongst the childhood population.
  • Children can be diagnosed with Hypersensitivity Vasculitis based on their skin-related symptoms, which are by far the most obvious features of this disease.
  • Click here for more detailed information on classifying and diagnosing Hypersensitivity Vasculitis.
  • The treatment of patients with Hypersensitivty Vasculitis is usually focused on removing the cause of this disease, which can often lead to the person feeling better within days or weeks. In other cases, drugs can be used in the treatment as well.
    • Click here for more detailed information on suggested treatment protocols.

Blanco, R., Martinez-Taboada, V. M., Rodríguez-Valverde, V., & García-Fuentes, M. (1998). Cutaneous vasculitis in children and adults: associated diseases and etiologic factors in 303 patients. Medicine, 77(6), 403-418.

Blanco, R., Martinez-Taboada, V. M., Rodríguez-Valverde, V., & García-Fuentes, M. (1998). Cutaneous vasculitis in children and adults: associated diseases and etiologic factors in 303 patients. Medicine, 77(6), 403-418.

Businco, L., Falconieri, P., Bellioni‐Businco, B., & Bahna, S. L. (2002). Severe food‐induced vasculitis in two children. Pediatric allergy and immunology, 13(1), 68-71.

Cabral, D. & Morishita, K., Hypersensitivity vasculitis in children. In: UpToDate, TePas E. (Ed), UpToDate. Retrieved from https://www.uptodate.com/contents/hypersensitivity-vasculitis-in-children (Accessed on October 9, 2016.)

Calabrese, L. H., & Duna, G. F. (1996). Drug-induced vasculitis. Current opinion in rheumatology, 8(1), 34-40.

Calabrese, L. H., Michel, B. A., Bloch, D. A., Arend, W. P., Edworthy, S. M., Fauci, A. S., … & Lightfoot, R. W. (1990). The American College of Rheumatology 1990 criteria for the classification of hypersensitivity vasculitis. Arthritis & Rheumatism, 33(8), 1108-1113.

Lunardi, C., Bambara, L. M., Biasi, D., Zagni, P., Caramaschi, P., & Pacor, M. L. (1991). Elimination diet in the treatment of selected patients with hypersensitivity vasculitis. Clinical and experimental rheumatology, 10(2), 131-135.

Martinez-Taboada, V. M., Blanco, R., Miguel Garcia-Fuentes, M. D., & Vicente Rodriguez-Valverde, M. D. (1997). Clinical features and outcome of 95 patients with hypersensitivity vasculitis. The American journal of medicine, 102(2), 186-191.

Ozen, S., Ruperto, N., Dillon, M. J., Bagga, A., Barron, K., Davin, J. C., … & Ravelli, A. (2006). EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Annals of the rheumatic diseases,65(7), 936-941.

Sais, G., Vidaller, A., Jucgla, A., Gallardo, F., & Peyri, J. (1995). Colchicine in the treatment of cutaneous leukocytoclastic vasculitis: results of a prospective, randomized controlled trial. Archives of dermatology, 131(12), 1399-1402.

Watts, R., About Vasculitis: Hypersensitivity Vasculitis. In: Vasculitis UK. Retrieved from http://www.vasculitis.org.uk/about-vasculitis/hypersensitivity-vasculitis (Accessed on October 9, 2016.)

Wint, C. (2015, December). Hypersensitivity (Allergic) Vasculitis. Retrieved from http://www.healthline.com/health/allergic-vasculitis#Triggers2 (Accessed on October 8, 2016.)

    • Note that unlike many of the major forms of systemic vasculitis, such as Kawasaki Disease and Takayasu arteritis, Hypersensitivity Vasculitis does not have specific classification criteria for the childhood population. Since there are no EULAR/PRINTO/PRES criteria, the American College of Rheumatology (ACR) criteria based on adult data is used for children.
    • According to the ACR criteria, the presence of 3 of more of the following criteria point towards Hypersensitivity Vasculitis:
    • Age >16 years
    • Use of a possible offending drug in temporal relation to the symptoms
    • Palpable purpura
    • Maculopapular rash
    • Biopsy of a skin lesion showing neutrophils around an arteriole or venule
    • It is also very important to note that these criteria do not help distinguish between this disease and Henoch-Schönlein purpura (IgA Vasculitis); a disease that involves immunoglobulin A (IgA) complexes that deposit in skin lesions.

    Diagnosis:

    In order to reach a diagnosis, it is important to consider a combination of clinical features, laboratory tests, along with biopsy results. For more details view the diagnostic algorithm for Hypersensitivity Vasculitis.

    • The most common symptoms involved in Hypersensitivity Vasculitis are described in this section. By far, the main system involved in this illness is the skin. Symptoms have been seen to appear within 7 to 10 days after the particular substance comes in contact with the body. They appear quickly, but can be resolved within weeks or even days (certain disease-causing agents and clinical features take longer than others to resolve).
      • Skin
        • Such as in Henoch–Schönlein purpura (HSP), the main feature of this disease of palpable purpura and/or petechiae. Other skin symptoms include edema, papules, ulcers, subcutaneous nodules, macules and utricaria.
        • These are usually seen in the lower extremities (i.e. legs and feet), and under tight clothing areas.
          • Palpable purpura
            • Main symptom
            • Purple-red spots which can be distinctly felt, and do not disappear when pressure is applied (non-blanching).
            • Spots are raised and can be touched.

     

    • Petechiae
      • Bleeding in the skin that leads to small red or purple spots (not large like palpable purpura so cannot be felt)
    • Edema
      • Swelling caused by fluid collecting in the body’s tissues
    • Papule
      • Small, raised swelling that is often a part of a rash
    • Ulcer
      • An open sore of the skin that is caused by a skin break and doesn’t heal fully.
    • Subcutaneous nodules
      • Small swelling of cells that is underneath the surface skin layers
    • Macules
      • Spots or blotches seen on the skin that may have changed colors
    • Utricaria
      • Known as “hives”, which are itchy, raised bumps. They can be red, and often turn white when pressure is applied (known as blanching).
    • Additional Symptoms:
      • Fever
      • Malaise
      • Myalgias (muscle pain)/ arthralgias (joint pain)
      • Arthritis (inflammation and stiffness of joints)
      • Abdominal pain
      • Lymphadenopathy (disease of lymph nodes, for example, affecting their size or number)
    • Other organ involvement: There is much less information available on the involvement of other organs in children with Hypersensitivity Vasculitis.
      • In adults, patients with Hypersensitivity Vasculitis have also reported the involvement of the:
        • Kidney
        • Liver
        • Less commonly: lung, heart and central nervous system
  • Diagnostic Purposes
    • No particular laboratory tests exist to help diagnose Hypersensitivity Vasculitis
    • The following are findings that are often seen in patient with this illness:
      • Increased levels of white blood cells (leukocytosis)
      • Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
      • Hematuria (blood in urine), proteinuria (protein in urine), cellular casts in cases of renal involvement
      • Low levels of C3 and C4 serum compliment levels
      • Positive results that show the presence of a virus or bacteria that is associated with Hypersensitivity Vasculitis (e.g. Hepatitis C)
  • There aren’t any significant imaging tests that are done for patients with Hypersensitivity Vasculitis.
  • The diagnosis of HSP is often done using mainly clinical features such as the clear sign of palpable purpura in the lower limbs and buttocks. However, when this is not obvious and a diagnosis is more difficult, then a biopsy of the skin or kidney can be done. These cases include where there is no rash, an unusual rash, or in cases of significant kidney disease.
  • Skin
    • Sample blood vessels in skin to make diagnosis
    • Shows inflammation (swelling) of the small blood vessels in the skin
    • Show the immune cells (neutrophils) that are present in this area and death of the tissues (fibrinoid necrosis).
      • It is this particular feature that is described as “leukocytoclastic vasculitis”
    • Kidney
      • This is only done in patients with clear renal involvement.
      • Results often show deposits composed of immunoglobulin G (IgG) and C3/C4 complements in the glomerular capillary wall (small blood vessels in the kidneys).

 

Boyer, T. D., Sun, N., & Reynolds, T. B. (1977). Allopurinol-hypersensitivity vasculitis and liver damage. Western Journal of Medicine, 126(2), 143.

Cabral, D. & Morishita, K., Hypersensitivity vasculitis in children. In: UpToDate, TePas E. (Ed), UpToDate. Retrieved from https://www.uptodate.com/contents/hypersensitivity-vasculitis-in-children (Accessed on October 9, 2016.)

Calabrese, L. H., & Duna, G. F. (1996). Drug-induced vasculitis. Current opinion in rheumatology, 8(1), 34-40.

DE LA PAVA, S. A. M. U. E. L., NIGOGOSYAN, G., & PICKREN, J. W. (1962). Fatal glomerulonephritis after receiving horse anti-human-cancer serum: report of three cases. Archives of internal medicine, 109(4), 391-399.

Dubost, J. J., Souteyrand, P., & Sauvezie, B. (1991). Drug-induced vasculitides. Baillière’s clinical rheumatology, 5(1), 119-138.

García-Porrúa, C., & González-Gay, M. A. (1999, June). Comparative clinical and epidemiological study of hypersensitivity vasculitis versus Henoch-Schönlein purpura in adults. In Seminars in arthritis and rheumatism(Vol. 28, No. 6, pp. 404-412). WB Saunders.

Khetan, P., Sethuraman, G., Khaitan, B. K., Sharma, V. K., Gupta, R., Dinda, A. K., … & Singh, M. K. (2012). An aetiological & clinicopathological study on cutaneous vasculitis. The Indian journal of medical research,135(1), 107.

Martinez-Taboada, V. M., Blanco, R., Miguel Garcia-Fuentes, M. D., & Vicente Rodriguez-Valverde, M. D. (1997). Clinical features and outcome of 95 patients with hypersensitivity vasculitis. The American journal of medicine, 102(2), 186-191.

Parker, C. W. (1982). Allergic reactions in man. Pharmacological Reviews,34(1), 85-104.

Starkebaum, G. A., (2015, April). Hypersensitivity Vasculitis. Retrieved from https://medlineplus.gov/ency/article/000874.htm

Watts, R., (2016, August). Hypersensitivity Vasculitis. Retrieved from http://www.vasculitis.org.uk/about-vasculitis/hypersensitivity-vasculitis

General First Step

  • The most important step in the treatment of Hypersensitivity Vasculitis involves removing the triggering agent. For example, if it is a particular drug that is causing this illness, then the removal of that drug is extremely important. In many cases, this removal can lead to the healing of lesions and recovery within a period of days or weeks. However, patients whose illness is related to an infection (Hepatitis C for example), usually take longer in terms of treatment of the longer time it takes to deal with those infections. Infection-associated Hypersensitivity Vasculitis cases are given treatments that are focused on resolving the infection.

Different Cases

  • Mild cases that are limited to the skin
    • The symptoms of this disease usually are resolved on their own, without any particular treatment.
  • Severe/Persistent cutaneous (skin-related) disease
    • In these more serious cases, some of the following drugs have been discussed for having positive benefits:
      • Colchicine
      • Antihistamines
      • Anti-inflammatory drugs (non-steroidal)
      • Dapsone
    • Sudden or progressive disease, or with serious organ involvement
      • Immunosuppressive therapy with Glucocorticoids (ex. prednisone) or cytotoxic agents

Below you can find downloadable PDF files of suggested treatment protocols for patients with Hypersensitivity Vasculitis.

Suggested Treatment Protocols:

  1. (These numbers depend on the types of treatment protocols provided for Hypersensitivity Vasculitis)
  2. (These numbers depend on the types of treatment protocols provided for Hypersensitivity Vasculitis)
  3. (These numbers depend on the types of treatment protocols provided for Hypersensitivity Vasculitis)

Cabral, D. & Morishita, K., Hypersensitivity vasculitis in children. In: UpToDate, TePas E. (Ed), UpToDate. Retrieved from https://www.uptodate.com/contents/hypersensitivity-vasculitis-in-children (Accessed on October 9, 2016.)

Callen, J. P., & Af Ekenstam, E. (1987). Cutaneous leukocytoclastic vasculitis: clinical experience in 44 patients. Southern medical journal, 80(7), 848-851.

Cohen, M. G., & Prowse, M. V. (1989). Drug-induced rheumatic syndromes.Medical toxicology and adverse drug experience, 4(3), 199-218.

Jennette, J. C., Falk, R. J., Andrassy, K., Bacon, P. A., Churg, J., Gross, W. L., … & Mccluskey, R. T. (1994). Nomenclature of systemic vasculitides.Arthritis & Rheumatism, 37(2), 187-192.

Sais, G., Vidaller, A., Jucgla, A., Gallardo, F., & Peyri, J. (1995). Colchicine in the treatment of cutaneous leukocytoclastic vasculitis: results of a prospective, randomized controlled trial. Archives of dermatology, 131(12), 1399-1402.

Starkebaum, G. A., (2015, April). Hypersensitivity Vasculitis. Retrieved from https://medlineplus.gov/ency/article/000874.htm

Watts, R., (2016, August). Hypersensitivity Vasculitis. Retrieved from http://www.vasculitis.org.uk/about-vasculitis/hypersensitivity-vasculitis

Wint, C. (2015, December). Hypersensitivity (Allergic) Vasculitis. Retrieved from http://www.healthline.com/health/allergic-vasculitis#Triggers2 (Accessed on October 8, 2016.)