Leukocytoclastic Vasculitis - Causes, Symptoms, Diagnosis and Treatment

What Is Leukocytoclastic Vasculitis?

Leukocytoclastic vasculitis is an inflammatory disorder of the small blood vessels characterized by immune complex-mediated damage of the blood vessels. Leukocytoclastic vasculitis is usually confined to the superficial sites on the skin, with rare chances of occurring at extracutaneous sites in less than 30 % of the cases.

The term“leukocytoclastic” comes from the word leukocytoclasia, which is described as a process where the infiltrating neutrophils disintegrate and release debris. “Vasculitis” is the inflammation of the blood vessels.

What Are the Causes of Leukocytoclastic Vasculitis?

The cause of Leukocytoclastic vasculitis is numerous and also idiopathic.

• Drugs are one of the most common causes of triggering leukocytoclastic vasculitis. The onset of the reaction is typically seen one to three weeks after the administration of the drug.

  • Pharmacological Drugs: Some pharmacological drugs associated with the disease include the following:

    • Beta-lactams.

    • Erythromycin.

    • Clindamycin.

    • Vancomycin.

    • Sulfonamides.

    • Furosemide.

    • Allopurinol.

    • Nonsteroidal anti-inflammatory drugs (NSAIDs).

    • TNF-alpha inhibitors.

    • Beta-blockers.

    • Amiodarone.

    • Selective serotonin reuptake inhibitors.

    • Metformin.

    • Valproic acid.

    • Warfarin.

• Allergic foods can also trigger the disease if the affected person is allergic to the exposed food.

• Infections play a major role in triggering inflammatory reactions. All bacterial, viral, and parasitic infections can pose a serious threat to trigger the reaction.

• Most commonly, it occurs due to exposure to a streptococcal infection of the upper respiratory tract.

• Other infective agents that can cause the disease include

  • Mycobacterium species.

  • Hepatitis B.

  • Hepatitis C.

  • Staphylococcus aureus.

  • Neisseria gonorrhoeae.

  • Human immunodeficiency virus.

• Autoimmune diseases have also been found to be associated with leukocytoclastic vasculitis.

• The following autoimmune diseases can cause small vessel vasculitis:

  • Rheumatoid arthritis (a disorder marked by inflammation of the joints).

  • Systemic lupus erythematosus (an autoimmune disease causing widespread organ damage).

  • Sjogren’s syndrome (a condition marked by dry eyes and dry mouth).

• Inflammatory bowel diseases like Crohn’s disease and ulcerative colitis have also been associated with leukocytoclastic vasculitis.

• Malignant conditions are less commonly related to Leukocytoclastic vasculitis. These may include

• Solid neoplastic tumors (cancers).

• Lymphomas (cancer of the lymphatic system).

• Leukemias (a type of blood cancer of white blood cells).

• Myleoproliferative disorders.

• Myeloplastic disorders.

Is Leukocytoclastic Vasculitis a Malignant Condition?

Leukocytoclastic vasculitis is an inflammation of the blood capillaries and small venules. It is not a malignant condition. However, it can be considered a marker of underlying malignancy. Leukocytoclastic vasculitis is the most common form of vasculitis that is frequently linked with cancer. It is commonly associated with cancers originating in the blood, like lymphomas and leukemias. Leukocytoclastic vasculitis is more likely to be related to cancer in individuals older than 50 years of age.

• Paraneoplastic Cutaneous Leukocytoclastic Vasculitis Syndrome: The pathogenesis of the paraneoplastic variant of leukocytoclastic vasculitis is not known. It has been suggested that tumor cells release certain immunogenic factors into the blood circulation, leading to the deposition of immune complexes within vessel walls and the subsequent development of vasculitis. The prognosis of this type of cutaneous vasculitis is very poor.

What Is the Frequency of Occurrence of Leukocytoclastic Vasculitis?

The average incidence rate of leukocytoclastic vasculitis cases reported yearly is approximately 45 per million individuals. The disease occurs in all ages but is most commonly found in adults. Both males and females are equally affected by the disease.

What Is the Pathophysiology of the Disease?

The etiopathogenesis of leukocytoclastic vasculitis involves the deposition of immune complexes in the walls of the blood vessels. This leads to the activation of the complement system, whereby the activated neutrophils come into action. Injury to vessel walls results in dead red blood cells, fibrin, and plasma serum exudated. Lysosomal enzymes cause the fibrinoid necrosis of small vessel walls. There is increased venous pressure in the lower extremities, due to which it is common to find the purpura on the legs of the affected patients.

What Are the Symptoms of Leukocytoclastic Vasculitis?

The most significant clinical symptoms of leukocytoclastic vasculitis appear cutaneously. Usually, a rash appears that is characterized by the following:

• Palpable reddish-purple purpura (purpura is a raised spot).

• Tenderness and burning, stingy sensation.

• Itchy and pruritic.

• Bullae, pustules or nodules.

• Ulcers.

• Mottled skin.

Generalized Symptoms:

• Fever that is low grade.

• Weight loss.

• Muscle pain.

• Joint pain.

• Blood in urine or stool.

• Pain in the abdomen.

• Nausea and vomiting.

• Cough.

• Lethargy and weakness.

What Is the Histopathology of Leukocytoclastic Vasculitis?

• Leukocytoclastic vasculitis is a histopathologic term. Therefore, it is important to know the histology of the lesion.

• Biopsy of the lesion on a light microscope reveals the destruction of the blood vessel wall by intense inflammatory cell infiltration within and around the vessel wall.

• Classically, the histologic section reveals the infiltration of neutrophils in the walls of the blood vessel.

• These neutrophils then undergo disintegration and degeneration, known as the process of leukocytoclasis, thereby releasing nuclear dust.

• Fibrinoid necrosis of the vessel walls can also be seen.

• Eosinophils are observed in the connective tissue in drug-related cases.

• Lymphocytic inflammatory cell infiltration can also be seen in some cases.

What Are the Diagnostic Tests Done for Leukocytoclastic Vasculitis?

A healthcare provider should perform several tests to diagnose the disease, which include:

• Medical Examination: Physical examination of the cutaneous lesion to check for tenderness, swelling, redness, and inflammation.

• Medical History: Medical or drug history to determine if any specific drug or medical condition triggered the symptoms.

• Blood Tests: Hematologic tests include a complete blood count and liver and kidney functions to identify any underlying infection.

• Urine Examination: Urine analysis to look for any underlying signs of the disease.

• Biopsy: Punch biopsy includes deeper layers of the skin to confirm the diagnosis.

What Is the Treatment of Leukocytoclastic Vasculitis?

• Most cases of cutaneous leukocytoclastic vasculitis are idiopathic and resolve with supportive measures such as raising the legs, rest, ice packs, compression stockings, and administration of antihistamines.

• In more chronic and severe cases, corticosteroids are prescribed for approximately four to six weeks.

• Immunosuppressive agents may also be prescribed in rare cases.

• Withdrawal of the drug is necessary to resolve the vasculitis in case the offending drug causes inflammation.

• NSAIDs (nonsteroidal anti-inflammatory drugs) help treat muscle and joint pain if the lesion has become chronic.

Conclusion

Leukocytoclastic vasculitis is a clinicopathological entity where the mortality rate of patients is low, with approximately 90 % of patients showing spontaneous resolution of their cutaneous lesions within four to eight weeks. Leukocytoclastic vasculitis is synonymous with cutaneous vasculitis, or small vessel cutaneous vasculitis generating confusion. Therefore, the confirmed diagnosis should be made with the help of a punch biopsy to comprehend if it is a skin-limited or systemic disease to identify the correct course of medical treatment.