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AUTHOR AND EDITOR INFORMATION

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Author: Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Editors: Michelle Pelle, MD, Clinical Assistant Professor, Division of Dermatology, Department of Medicine, University of California at San Diego; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

Author and Editor Disclosure

Synonyms and related keywords: LCV, allergic angiitis, small-vessel vasculitis, small vessel vasculitis, Henoch-Schönlein purpura, acute hemorrhagic edema, hypocomplementemic urticarial vasculitis, livedo reticularis, cutaneous vasculitis, upper respiratory tract infections, beta-hemolytic streptococcal infection, viral hepatitis, HIV infection, hepatitis B, hepatitis C, collagen vascular disease, rheumatoid arthritis, Sjögren syndrome, lupus erythematosus, inflammatory bowel disease, ulcerative colitis, Crohn colitis

INTRODUCTION

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Background

Leukocytoclastic vasculitis (LCV) is a histopathologic term commonly used to denote a small-vessel vasculitis. Many possible causes exist for this condition, but a cause is not found in as many as 50% of patients.

The disorder may be localized to the skin, or it may manifest in other organs. The internal organs most commonly affected are the gastrointestinal tract and the kidneys. Joints are also commonly affected. The prognosis is good when no internal involvement is present. The disorder may be acute or chronic.

Pathophysiology

In the past, circulating immune complexes were believed to cause LCV. Although immune complexes are involved in the pathogenesis of LCV, other autoantibodies cause disease manifestations, such as antineutrophil cytoplasmic antibody (ANCA), other inflammatory mediators, and local factors that involve the endothelial cells and other adhesion molecules. The exact mechanisms remain to be elucidated.

Frequency

United States

The incidence is unknown, but the condition is presumed to be rare.

International

Several studies from Spain have been conducted.1, 2, 3, 4, 5 Hypersensitivity vasculitis reportedly has an incidence of 10-30 cases per million people per year. Henoch-Schönlein purpura reportedly has an incidence of 14 cases per million people per year.

Mortality/Morbidity

  • The prognosis of LCV is generally good, but mortality is possible if the kidneys, the gastrointestinal tract, the lungs, the heart, or the central nervous system is involved.
  • Chronic cutaneous disease may involve ulceration or painful bouts of purpura. Some patients alter their lives because of recurrent purpuric eruptions.

Race

LCV is reported most often in the white population.

Sex

LCV affects men and women in approximately equal proportions. Some of the studies from Spain suggest that LCV is slightly more common in men than in women.

Age

  • LCV may occur at any age.
  • In children, LCV may be called Henoch-Schönlein purpura. This condition may also occur in adults. Another form of vasculitis that is reported in infancy is acute hemorrhagic edema.


CLINICAL

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History

  • Patients with vasculitis of their skin may complain of itching, a burning sensation, or pain, or they may have asymptomatic lesions.
  • Vasculitis of the skin may occur in the absence of any systemic disease.
  • Vasculitis may manifest as an eruption only, or it may occur in conjunction with collagen vascular disorders, paraproteinemia, ingestants (drugs or foods), infections, or malignancy (rare).
  • Elicit information about possible systemic manifestations from patients. Inquire about the presence or the absence of fever, arthralgia, arthritis, myalgia, abdominal pain, diarrhea, hematochezia, cough, hemoptysis, sinusitis, paresthesia, weakness, and hematuria.
  • Obtain information about symptoms of an associated disorder. Determine the patient's history of intravenous drug use, hepatitis, transfusion, and travel, along with symptoms or a history of inflammatory bowel disease and collagen vascular disorder, particularly rheumatoid arthritis, lupus erythematosus, or Sjögren syndrome.

Physical

Palpable purpura is the most common manifestation of cutaneous vasculitis, but other manifestations may occur.

  • Palpable purpura is the most frequent presentation of small-vessel vasculitis.
    • Lesions are usually round and 1-3 mm in diameter.
    • Lesions may coalesce to form plaques; they may ulcerate in some instances.
    • Retiform lesions were associated with immunoglobulin A (IgA)–related immune complex disease in one study; however, this result has not been validated in subsequent studies.
    • Palpable purpura is most frequently observed on the legs, but any surface can be involved. Purpuric lesions are sometimes barely palpable.
  • Urticarial lesions may occur in some patients; rarely, this type of lesion can predate purpuric lesions.
    • Urticarial lesions are of a different character than routine urticaria, tending to be of longer duration (often >24 h) and tending to resolve with some residual pigmentation or ecchymosis. Patients complain of a burning sensation rather than itching.
    • To determine the duration of individual lesions, encircle several lesions and ask the patient to observe them periodically and note when they resolve or when they change shape and when a lesion is outside the encircled area.
  • Patients with hypocomplementemic urticarial vasculitis may develop chronic obstructive pulmonary disease; carefully examine the heart and the lungs.6, 7
  • Livedo reticularis is a rare manifestation of small-vessel vasculitis. It is more frequent in patients with occlusive or inflammatory disease of medium-sized vessels.
  • Nodular lesions may occur in some patients with small-vessel vasculitis.
  • Ulceration is more common in vasculitis that affects larger vessels, but it may complicate intense purpura.
  • Perform a careful physical examination in patients with vasculitis, including specific observation of cardiopulmonary, musculoskeletal, and gastrointestinal systems.

Causes

  • Between one third and one half of cutaneous vasculitis cases are idiopathic; the remainder have a variety of causes.
  • Antibiotics are the most common drugs that can cause cutaneous vasculitis, particularly beta-lactams. Nonsteroidal anti-inflammatory drugs and diuretics also frequently cause vasculitis. However, almost all drugs are potential causes.
  • Various infections may be associated with vasculitis. Upper respiratory tract infections (particularly beta-hemolytic streptococcal infection) and viral hepatitis, particularly hepatitis C, are most often implicated. HIV infection may also be associated with some cases of cutaneous vasculitis. Ascertaining whether a drug (eg, antibiotic) or an infection (eg, upper respiratory infection) is responsible for the disease is impossible because the occurrence of vasculitis postdates infection and the drug used to treat the infection.
  • Foods or food additives may cause vasculitis.
  • Hepatitis C is a regularly recognized cause of vasculitis, probably through the presence of cryoglobulins. However, of 1614 patients with hepatitis C, vasculitis occurred in only 12 patients (9 with cryoglobulinemia, 3 without). Interestingly, cryoglobulins were present in roughly 40% of those tested; many patients with cryoglobulins (98%) did not have vasculitis despite an abnormal circulating paraprotein. Hepatitis B was implicated in some cases of vasculitis in the past.
  • Collagen vascular diseases account for 10-15% of cases of vasculitis.
    • In particular, rheumatoid arthritis, Sjögren syndrome, and lupus erythematosus may have an associated vasculitis.
    • The presence of vasculitis often denotes active disease and possibly a poorer prognosis.
  • Inflammatory bowel disease, ulcerative colitis, or Crohn colitis may be associated with cutaneous vasculitis.
  • Malignancy accounts for less than 1% of cases of cutaneous vasculitis.
    • Perhaps lymphoproliferative diseases are more common (particularly hairy cell leukemia); however, any type of tumor at any site may possibly be related to cutaneous vasculitis.
    • Effective tumor therapy in some patients has led to resolution of the vasculitis.
  • Small-vessel cutaneous vasculitis may be seen uncommonly in patients with a larger vessel vasculitis, such as Wegener granulomatosis, polyarteritis nodosa, or Churg-Strauss syndrome.


DIFFERENTIALS

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Churg-Strauss Syndrome (Allergic Granulomatosis)
Cutaneous Manifestations of Cholesterol Embolism
Meningococcemia
Rocky Mountain Spotted Fever
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Wegener Granulomatosis

Other Problems to be Considered

Amyloidosis
Buerger disease (thromboangiitis obliterans)
Infective endocarditis
Gonococcal infections
Polyarteritis nodosa
Thrombotic thrombocytopenic purpura (TTP)
Urticaria
Waldenström hypergammaglobulinemia
Idiopathic thrombocytopenia purpura
Polyangiitis overlap syndrome
Thrombocytopenia


WORKUP

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Lab Studies

  • Evaluation of patients with vasculitis serves 2 purposes: to determine the presence of systemic disease and to identify an associated disorder, which aids in predicting the patient's prognosis.
  • No established routine exists, but testing for all adult patients includes a complete blood count, an erythrocyte sedimentation rate, a urinalysis, and a blood chemistry panel.
  • Obtain stool guaiac or Hematest for patients with bowel symptoms even though these tests are not particularly reliable.
  • Obtain serologic studies (eg, antinuclear antibody, ANCA [ie, circulating ANCA, perinuclear ANCA, atypical ANCA], rheumatoid factor) for patients without an obvious disease cause. In children and perhaps in some adults, serologic testing for a possible streptococcal infection should be considered (Streptozyme or ASO titer).
  • Complement levels, including total hemolytic complement (CH100 or CH50), C3 levels, and C4 levels, may be obtained for patients suspected of having lupus erythematosus or patients who have urticarial vasculitis.
  • Include serum protein electrophoresis, cryoglobulins, and hepatitis C antibody in tests for paraproteins for patients without otherwise identified disease.
    • Hepatitis B was associated with vasculitis in the past; however, it appears that the association may have occurred by virtue of co-infection with hepatitis C (previously termed non-A, non-B).
    • The measurement of hepatitis B surface antigen may not be required in all cases.
    • Cryoglobulins are often not obtained properly; a positive rheumatoid factor should suggest the presence of cryoglobulins.
  • Perform HIV testing for patients at high risk for infection and possibly for those with otherwise unidentifiable cause of disease.
  • Consider obtaining direct immunofluorescence microscopy for selected patients. The presence of IgA occurs in Henoch-Schönlein purpura.

Imaging Studies

  • Chest radiography is part of the routine evaluation.
  • Consider performing visceral angiography for patients with a severe vasculitic syndrome.
  • Perform cardiac ultrasonography and blood cultures for patients with fever and/or a heart murmur.

Other Tests

  • Obtain pulmonary function tests for patients with hypocomplementemic urticarial vasculitis.

Procedures

  • Perform a skin biopsy of a relatively fresh lesion in most, if not all, adult patients. For humanitarian reasons, biopsies are often not performed in children with suspected vasculitis.
  • Consider performing a biopsy of muscle or a biopsy of visceral organs in patients with severe vasculitic syndromes; however, most patients with leukocytoclastic vasculitis of the skin do not require such tests.
  • Obtaining a bone marrow sample may be useful if the peripheral smear is abnormal.

Histologic Findings

A skin biopsy sample reveals the presence of vascular and perivascular infiltration of polymorphonuclear leukocytes with formation of nuclear dust (leukocytoclasis), extravasation of erythrocytes, and fibrinoid necrosis of the vessel walls. This process is dynamic; a biopsy sample of a lesion too early or too late in its evolution may not reveal these findings.

The picture of leukocytoclastic vasculitis is a pattern that can occur in any vasculitic syndrome but may also occur in nonvasculitic diseases (eg, neutrophilic dermatoses), at the base of a biopsy sample of a leg ulceration, or in some insect bite reactions. Careful clinical-pathologic correlation is necessary.


TREATMENT

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Medical Care

  • Once a diagnosis of cutaneous small-vessel vasculitis is established and the patient is fully evaluated, specific or nonspecific management options may be used.
  • Elevation of the legs or compression stockings may be useful because the disease often affects dependent areas.
  • Treat the cause in patients with an identifiable cause. Removal of a drug thought to be causing the vasculitis may result in rapid clearing of the process in up to 2 weeks.
  • Treat chronic disease that primarily involves the skin with nontoxic modalities whenever possible; avoid using systemic corticosteroids and/or immunosuppressive agents. Colchicine8, 9 or dapsone may be administered for patients with disease of the skin with or without joint manifestations.
  • Patients with urticarial lesions may be treated with antihistamines (both soporific ones and less sedating agents). Sometimes, a combination of these agents is needed to control disease manifestations. Some patients have responded to nonsteroidal anti-inflammatory agents.
  • Patients with severe visceral involvement may require high doses of corticosteroids (1-2 mg/kg/d) with or without an immunosuppressive agent (eg, cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil).
  • Rituximab has been reported in various subsets of vasculitis including several patients with chronic cutaneous small vessel vasculitis.10
  • Consider a restrictive diet for patients with chronic cutaneous vasculitis without other identifiable causes.11

Surgical Care

  • Surgical care for patients with vasculitis is rarely needed.
    • Surgical care may be appropriate if a tumor is identified as a cause of the process.
    • Surgical care may be appropriate if recalcitrant ulceration occurs after control of active disease.

Consultations

  • Rheumatologist
  • Dermatologist
  • Nephrologist
  • Gastroenterologist/hepatologist

Diet

No specific diet is required. A restrictive diet may be used for up to 2 weeks for diagnostic and therapeutic purposes.11

Activity

No specific restrictions on activity are recommended.


MEDICATION

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No established, effective therapy is available for all patients. Few of the therapies have been tested in controlled trials.

Drug Category: Anti-inflammatories

These agents decrease inflammatory responses and systemically interfere with events leading to inflammation.

Drug NameColchicine
DescriptionHas effects against neutrophils, which are probably involved in expression of cutaneous vasculitis; has been demonstrated to be steroid-sparing in open-label studies. The only double-blinded placebo-controlled trial failed to demonstrate its efficacy; however, several methodological errors occurred in this study. Not FDA approved in children.
Adult Dose0.5-0.6 mg PO bid
Pediatric DoseInitial: 0.5 mg/d PO
Maintenance
<5 years: 0.5 mg/d PO; not exceed 2 mg/d
>5 years: 0.5 mg PO bid; not to exceed 2 mg/d
ContraindicationsDocumented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias
InteractionsSympathomimetic agent toxicity and effect of CNS and bone marrow depressants are significantly increased with colchicine; clarithromycin may cause significant increases in colchicine serum concentrations; may increase cyclosporine levels when concomitantly administered with colchicine
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsRisk of renal failure, hepatic failure, permanent hair loss, bone marrow suppression, numbness or tingling in hands and feet, disseminated intravascular coagulopathy, and decreased sperm count; may cause nausea, diarrhea, vomiting, or abdominal pain approximately 8-12 h after PO administration in 80% of patients, especially when maximal doses used (discontinue use at onset of gastrointestinal intolerance); may cause myopathy and myoneuropathy

Drug NameDapsone (Avlosulfon)
DescriptionSmall open-label studies or single case reports have suggested that dapsone is effective in some patients with cutaneous vasculitis. Used in hypersensitivity vasculitis not for its antimicrobial activity but for its modulatory effect on neutrophil activity.
Adult Dose150-200 mg PO qd
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; known G-6-PD deficiency
InteractionsMay inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine) monitor for agranulocytosis during the second and third months of therapy; probenecid increases dapsone toxicity; trimethoprim with dapsone may increase toxicity of both drugs; because of increased renal clearance, levels may significantly decrease when administered concurrently with rifampin
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsPerform weekly blood counts (first mo), then perform WBC counts monthly (6 mo), then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is noted; caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; excreted in breast milk and may cause toxic effects in infants; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Drug NamePrednisone (Deltasone)
DescriptionIndicated for vasculitis affecting internal organs (eg, kidneys, lungs, CNS). Patients whose skin involvement results in ulceration may require corticosteroid therapy.
Adult Dose0.05-2 mg/kg/d PO divided bid/qid; not to exceed 80 mg/d qd or divided bid/qid; taper over 1-2 wk as symptoms resolve
Pediatric Dose4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
ContraindicationsDocumented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; active infection, particularly deep fungal infections or tuberculosis
InteractionsCoadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with concurrent use of diuretics
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsTake measures to assess infection, particularly tuberculosis, at the onset of therapy; patients on long-term therapy require monitoring of bone density, blood pressure, vision, and blood sugar level; skin changes may include atrophy, acneiform eruptions, poor wound healing, purpura, striae, and hirsutism; acute toxicity includes aseptic necrosis of bones, particularly the hip, and psychosis

Drug Category: Cytotoxic/immunosuppressives

These agents inhibit cell growth and proliferation.

Drug NameCyclophosphamide (Cytoxan, Neosar)
DescriptionUseful in life-threatening cases of vasculitis. Patients with only skin disease generally should not be treated with this agent. Useful in patients with polyarteritis nodosa, Wegener granulomatosis, and Churg-Strauss syndrome. Agent is an alkylating agent that depresses T- and B-cell function.
Adult Dose1-2 mg/kg/d PO; may also be given in pulsed doses IV every mo
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; severely depressed bone marrow function
InteractionsAllopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsRegularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis (can be prevented by early administration of dose and hydration); long-term use can increase risk of bladder cancer, leukemia, and other lymphoproliferative neoplasia; bone marrow suppression is frequent and is dose related; nausea and vomiting are possible; oral aphthae can occur; alopecia or anagen effluvium is possible; anovulation and azoospermia may occur and may be irreversible

Drug NameAzathioprine (Imuran)
DescriptionAntagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult Dose1-2 mg/kg/d PO
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)
InteractionsToxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsIncreases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated

Drug NameMethotrexate (Folex, Rheumatrex)
DescriptionUnknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).
Adjust dose gradually to attain satisfactory response.
Adult Dose10-50 mg qwk PO/IV/IM
Pediatric Dose10-25 mg qwk PO/IV/IM
ContraindicationsDocumented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
InteractionsOral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) may increase effects and toxicity; may increase plasma levels of thiopurines
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsMonitor CBC counts monthly, and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant decrease in blood counts occurs; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased methotrexate toxicity with NSAIDs, including salicylates, should result in careful monitoring of renal function and blood counts)

Drug NameRituximab (Rituxan)
DescriptionGenetically engineered human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.
Immunomodulates response against malignant cells.
Adult Dose60-75 mg/m2 IV as a single dose; repeat q21d
Alternatively: 20-30 mg/m2/d for 2-3 d; repeat in 4 wk
Additional alternative: 4 weekly infusions at 375 mg/m2 with prednisone at 1 mg/kg/d (according to Keough et al, 2006)
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsConcurrent administration of cisplatin and rituximab may increase risk of severe renal toxicity, including acute renal failure (not approved treatment regimen); coadministration with disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis may increase risk of severe infections
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsHypotension, bronchospasm, and angioedema may occur
Patients with preexisting cardiac or pulmonary conditions, prior clinically significant cardiopulmonary events, or a high level of malignant circulating cells (>25,000/µL), regardless of the tumor burden, require close monitoring during infusions; hypersensitivity reactions may be severe; may respond to adjustments in infusion rate; discontinue infusions in event of serious or life-threatening cardiac arrhythmias
Hepatitis B infection (risk for hepatitis B virus reactivation); human antichimeric antibodies (<1%); safety of immunization with any vaccine, particularly live viral vaccines, following rituximab has not been studied
Severe mucocutaneous reactions may include vasculitis, vesiculobullous drug reaction, drug-induced pemphigus, lichenoid dermatitis, Stevens-Johnson syndrome/toxic epidermal necrolysis
Tumor lysis syndrome; history of allergies; sensitivity to medications (enhanced risk of hypersensitivity)
Severe infusion-related reactions, typically occurring during the first infusion, sometimes fatal, have been reported
Patients with hemolytic anemia, aplastic anemia, thrombocytopenic disorder, lymphocytopenia, or neutropenia have increased infection/sepsis risk
Caution in persons with obliterative bronchiolitis or pneumonitis
Risk of progressive multifocal leukoencephalopathy reported (stop use if this occurs)

Drug NameMycophenolate (CellCept)
DescriptionInhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.
Adult Dose1-1.5 g PO bid
Pediatric DoseNot established; 400-600 mg/m2 bid, not to exceed 2 g/d suggested
ContraindicationsDocumented hypersensitivity; hypersensitivity to polysorbate 80 (IV formulation)
InteractionsMay elevate levels of acyclovir and ganciclovir; antacids and cholestyramine decreases absorption, reducing levels (do not administer together); probenecid may increase levels of mycophenolate; salicylates may increase toxicity of mycophenolate
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsIncreases risk for infection; increases toxicity in patients with renal impairment; caution in active peptic ulcer disease
Bone marrow suppression may occur, including severe neutropenia; due to increased risk of skin cancer, limit exposure to sunlight and UV light; increased risk for developing lymphomas or other malignancies; concomitant use with azathioprine is not recommended; oral susp contains aspartame so should be used with caution in patients with phenylketonuria; use cautiously in elderly patient and with drugs that affect enterohepatic recirculation; live attenuated vaccines should not be used during treatment and other vaccines may be less effective; avoid in patients with hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase
Avoid in pregnant women unless benefit clearly outweighs risk; negative pregnancy test should be obtained in women of childbearing potential; contraception should be used during treatment and for 6 wk after stopping treatment
Serious adverse effects may include confusion, GI hemorrhage, hypertension, increased frequency of cough, infectious disease, myelosuppression, peripheral edema, sepsis, and tremor


FOLLOW-UP

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Further Inpatient Care

  • Inpatient care is needed for patients who have severe vasculitic syndromes with multiple organ dysfunction.
  • Most patients with cutaneous vasculitis are treated on an outpatient basis.

Further Outpatient Care

  • Design of a follow-up program depends on the vasculitic syndrome, its chronicity, and the organ systems affected.
  • Further follow-up care may not be needed once the process is inactive in a patient with hypersensitivity vasculitis.
  • Patients with Henoch-Schönlein purpura may develop impairment of renal function or hypertension; regular follow-up care, even after complete clearing of disease, is needed.

In/Out Patient Meds

  • Management of patients with chronic cutaneous vasculitis is a challenge.
    • Dietary restriction may be tried in absence of an identifiable cause.
    • Colchicine (0.6 mg bid) and/or dapsone (100-200 mg/d) may control disease.
    • Other agents (including immunosuppressive/cytotoxic agents) may be administered in patients with unresponsive or poorly responsive conditions.

Transfer

  • Consider transfer to a tertiary care facility for patients with severe visceral disease.
  • Patients with chronic cutaneous disease are often referred to a tertiary care center for specialty care.

Complications

  • Vasculitis may be complicated by ulceration of skin or by end-organ dysfunction.

Prognosis

  • The prognosis of patients with cutaneous vasculitis depends on the underlying syndrome or the presence of end-organ dysfunction.
  • Patients with disease that primarily affects the skin and/or the joints have a good prognosis.
  • Patients with Wegener granulomatosis, polyarteritis nodosa, Churg-Strauss syndrome, or severe necrotizing vasculitis have a potentially fatal disease. Treatments with corticosteroids and/or immunosuppressive/cytotoxic agents often save the patient's life.


MISCELLANEOUS

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Medical/Legal Pitfalls

  • Misdiagnosis of vasculitis in patients with a nonvasculitic disorder (eg, insect bite reaction)
  • Failure to recognize serious systemic disease
  • Failure to inform patients of the risks associated with therapy (eg, corticosteroid-induced avascular necrosis)
  • Overaggressive treatment of patients with chronic, but mild disease may cause complications
  • Undertreatment of patients with severe systemic disease may cause complications


MULTIMEDIA

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Media file 1:  Hypersensitivity vasculitis.
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Media type:  Photo

Media file 2:  Henoch-Schönlein purpura.
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Media type:  Photo

Media file 3:  Histopathologic features of leukocytoclastic vasculitis.
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Media type:  Photo

Media file 4:  Urticarial vasculitis. These lesions differ from routine hives by lasting longer (often >24 h), being less pruritic, and often resolving with a bruise or residual pigmentation.
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Media type:  Photo

Media file 5:  Erythema elevatum diutinum, a rare cutaneous vasculitis.
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Media type:  Photo


REFERENCES

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  1. Blanco R, Martínez-Taboada VM, Rodríguez-Valverde V, García-Fuentes M. Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients. Medicine (Baltimore). Nov 1998;77(6):403-18. [Medline].
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Hypersensitivity Vasculitis (Leukocytoclastic Vasculitis) excerpt

Article Last Updated: May 15, 2007