Cutaneous small-vessel vasculitis (CSVV) is

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

of small

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s, usually accompanied by small lumps beneath the skin. The condition is also known as hypersensitivity vasculitis, cutaneous leukocytoclastic vasculitis, hypersensitivity angiitis, cutaneous leukocytoclastic angiitis, cutaneous necrotizing vasculitis and cutaneous necrotizing venulitis, It is the most common form of

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...

seen in clinical practice, usually caused by inflammation of post-capillary

venules A venule is a very small vein in the microcirculation that allows blood to return from the capillary beds to drain into the venous system via increasingly larger veins. Post-capillary venules are the smallest of the veins with a diameter of bet ...

in the

dermis The dermis or corium is a layer of skin between the epidermis (skin), epidermis (with which it makes up the cutis (anatomy), cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from s ...

). "Leukocytoclastic" (literally meaning '

leukocyte White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

-destroying') refers to the damage caused by nuclear debris from infiltrating

neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...

s in and around the vessels.

Signs and symptoms

Skin lesions

Initially red to pink, flat spots (formally, "macules") and raised bumps (formally, "papules") may be seen on the skin. Once fully developed, the classic appearance is "non-blanching, palpable purpura". This appears as deep red to purple spots that feel raised to the touch. Purpura refers to the red-purple discolored spots, while palpable implies that these spots can be felt as raised from the surrounding skin. Additionally, when gently pressed, the color does not fade to a lighter color ("non-blanching"). The red-purple color of the lesions is due to the inflammation in the blood vessels causing red blood cells to escape into the

skin layer. Small fluid-filled blisters (or "vesicles"), pus-filled bumps resembling a pimple (or "pustules"), or shallow

ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing ...

may also develop but are less common. The location of skin lesions varies but are most commonly found symmetrically below the waist, primarily on the buttocks and legs. Other distributions include localized areas on the upper body or over several areas of the body. With treatment, the lesions typically resolve in weeks to months and leave behind flat spots that are darker than the surrounding skin (see "Postinflammatory hyperpigmentation" on "

Hyperpigmentation Hyperpigmentation, also known as the dark spots or circles on the skin, is the darkening of an area of Human skin, skin or nail (anatomy), nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or ...

"). A portion of cases may be persistent or recurrent. This tends to occur when the vasculitis is associated with chronic conditions such as

connective tissue diseases Connective tissue diseases (also termed connective tissue disorders, or collagen vascular diseases), are medical conditions that affect connective tissue. Connective tissues protect, support, and provide structure for the body's other tissues a ...

Associated symptoms

In most cases skin lesions do not cause symptoms, however itching, burning, or pain may occur. Frequently reported symptoms include mild fever, muscle pain, joint pain, or an overall feeling of discomfort. Additional symptoms depend on the cause of the vasculitis and if other organ systems are involved. For example, if the vasculitis is a manifestation of

Henoch–Schönlein purpura IgA vasculitis (HSP), previously known as Henoch–Schönlein purpura, is an autoimmune disease that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of bleeding underneath the skin), often wi ...

, individuals may also experience abdominal pain or blood in the urine.

Cause

Cutaneous vasculitis can have various causes including but not limited to medications, bacterial and viral infections or allergens. It is estimated that 45–55% of cases are idiopathic, meaning the cause is unknown. In cases where a cause can be determined, medications and infectious pathogens are most common in adults, while IgA vasculitis (Henoch–Schönlein purpura) frequently affects children. Other etiologies include autoimmune conditions and malignancies, usually hematologic (related to the blood). The small vessels in the skin affected are located in the superficial dermis and include arterioles (small arteries carrying blood to capillaries), capillaries, and venules (small veins receiving blood from capillaries). In general,

immune complex An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen of ...

es deposit in vessel walls leading to activation of the

complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...

. C3a and C5a, proteins produced from the complement system, attract

s to the vessels. Once activated, neutrophils then release preformed substances, including enzymes causing damage to vessel tissue. Evidence of this process can be seen with a sample of removed skin tissue, or biopsy, viewed under a microscope. Neutrophils are seen surrounding blood vessels and their debris within vessel walls, causing

fibrinoid necrosis Fibrinoid necrosis is a pathological lesion that affects blood vessels, and is characterized by the occurrence of endothelial damage, followed by leakage of plasma proteins, including fibrinogen, from the vessel lumen; these proteins infiltrate and ...

. This finding on histological examination is termed "leukocytoclastic vasculitis". Considering the wide range of potential causes leading to cutaneous small vessel vasculitis, there are subtle variations in the underlying pathophysiology for each cause. For example, medications are metabolized to smaller molecules that can attach to proteins in the blood or vessel walls. The immune system senses these altered proteins as foreign and produces antibodies in efforts to eliminate them from the body. A similar process occurs with infectious agents, such as bacteria, in which antibodies target microbial components.

Diagnosis

Micrograph of cutaneous small-vessel vasculitis

The diagnostic testing for vasculitis should be guided by the patient's history and physical exam. The clinician should ask about the duration, onset, and presence any associated symptoms such as weight loss or fatigue (that would indicate a systemic cause). It is important to distinguish between IgA and non-IgA vasculitis. IgA vasculitis is more likely to present with abdominal pain, bloody urine, and joint pain. In the case that the cause is not obvious, a reasonable initial workup would include a complete blood count, urinalysis, basic metabolic panel, fecal occult blood testing,

erythrocyte sedimentation rate The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of in ...

(ESR), and

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...

level. Small vessel cutaneous vasculitis is a diagnosis of exclusion and requires ruling out systemic causes of the skin findings. Skin biopsy (punch or excisional) is the most definitive diagnostic test and should be performed with 48 hours of appearance of the vasculitis. A skin biopsy will be able to determine if the clinical findings are truly due to a vasculitis or due to some other cause.

Classification

Subtypes of small-vessel vasculitis include: :*

IgA vasculitis IGA or IgA may refer to: Businesses and organizations * IGA (supermarkets) (initially Independent Grocers Alliance), a name used by many independent supermarkets throughout the world ** IGA (Australian supermarket group), the local Australian va ...

(Henoch-Schönlein purpura) :* Acute hemorrhagic edema of infancy :*

Urticarial vasculitis Urticarial vasculitis (also known as "chronic urticaria as a manifestation of venulitis", "hypocomplementemic urticarial vasculitis syndrome", "hypocomplementemic vasculitis" and "unusual lupus-like syndrome") is a skin condition characterized by f ...

Cryoglobulinemic vasculitis Cryoglobulinemic vasculitis is a form of inflammation affecting the blood vessels (vasculitis) caused by the deposition of abnormal proteins called cryoglobulins. These immunoglobulin proteins are soluble at normal body temperatures, but become i ...

Erythema elevatum diutinum Erythema elevatum diutinum is a form of vasculitis. It has been described as a paraneoplastic syndrome. See also * Cutaneous small-vessel vasculitis * List of cutaneous conditions Many skin conditions affect the human integumentary system ...

Granuloma faciale Granuloma faciale is an uncommon benign chronic skin disease of unknown origin characterized by single or multiple cutaneous nodules, usually occurring over the face. Diagnosis Differential diagnosis Treatment History GF was first desc ...

ANCA-associated vasculitis Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of autoantibodies, mainly of the IgG type, against antigens in the cytoplasm of neutrophils (the most common type of white blood cell) and monocytes. They are detected as a blood test ...

:* Arthropod bites :* Platelet dysfunction or deficiency :* Cholesterol emboli :* Septic emboli :*

Livedoid vasculopathy Livedoid vasculopathy (LV) is an uncommon Thrombosis, thrombotic dermal Vasculitis, vasculopathy that is characterized by excruciating, recurrent Ulcer (dermatology), ulcers on the lower limbs. Livedo racemosa, along with painful ulceration in th ...

Treatment

Treatment should be directed towards the specific underlying cause of the vasculitis. If no underlying cause is found and the vasculitis is truly limited to the skin then treatment is primarily supportive. Such treatment involves measures such as leg elevation, stockings, and topical steroids to relieve itching/burning. If the vasculitis does not self-resolve within 3–4 weeks, more aggressive treatment may be warranted.Small Vessel Vasculitis of the Skin, Rheumatic Disease Clinics of North America, 2015-02-01, Volume 41, Issue 1, Pages 21-32 Oral

colchicine Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...

dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment an ...

are often used for this purpose. If rapid control of symptoms is needed, a short course of high-dose oral steroids may be given. Immunosuppressive agents such as

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

and

azathioprine Azathioprine, sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus er ...

may be used in truly refractory cases not responsive to colchicine or dapsone.

Additional images

Image:LV1,2010.JPG, Image:LV22010.JPG, Image:Leukocytoclastic vasculitis caused by reaction to minocycline.jpg, Image:LV4.JPG

References

External links

{{Hypersensitivity and autoimmune diseases Systemic connective tissue disorders Vascular-related cutaneous conditions Immune system disorders