Palpable purpura: an algorithmic approach

Author: Gary L. Stevens, Paul M. Wallach
Date: Oct, 1995

Palpable purpura is a cutaneous manifestation of several diseases. Although palpable purpura is the classic skin lesion of cutaneous vasculitis (Figure 1), it may also result from infection, malignancy or embolic disease. Conversely, vasculitis may be manifested as various skin lesions other than palpable purpura. Cutaneous vasculitis itself may result from various diseases that have a poorly understood pathogenesis, making classification of palpable purpura difficult.

Pathogenesis

The proposed mechanism of cutaneous vasculitis involves the deposition of soluble antigen-antibody complexes on or between the endothelial cells of blood vessel walls. Complement proteins are activated, most notably C3 and C5, which serve as chemotactic factors for leukocytes. Leukocytes release lysozymes that destroy the blood vessel wall, resulting in extravasation of red blood cells. The inflammatory cell infiltrate, along with necrosis and fibrin deposition in the blood vessel wall, results in palpable purpura.

A variety of processes are associated with the initiation of immune complex formation, such as collagen vascular disease, malignancy, infection and drug reactions. Cutaneous vasculitis may be localized or may be accompanied by systemic vasculitis. Many different clinical and laboratory features are possible. The classification of vasculitis is difficult since the range of features varies so widely, but it is usually based on vessel size.[1]

The vasculitides presenting with palpable purpura are those involving small vessels (mainly postcapillary venules) and are characterized histologically by the term "leukocytoclastic vasculitis" (destruction of neutrophils with nuclear debris). This type of vasculitis may be referred to as "small-vessel vasculitis," "cutaneous vasculitis" or "hypersensitivity vasculitis." Combinations occur, as in polyarteritis nodosa and Wegener's granulomatosis, with both small- and medium-sized arteries involved. These diseases also may present with leukocytoclastic vasculitis and palpable purpura.

SYSTEMIC INVOLVEMENT IN CUTANEOUS VASCULITIS

Transient or chronic glomerulonephritis and/or renal vasculitis may coexist with cutaneous vasculitis. In one series,[2] 10 of 82 patients (12 percent) with cutaneous vasculitis had renal involvement. Hematuria with red cell casts, azotemia, proteinuria and hypertension may occur. Musculoskeletal complaints were common (43 percent) in the same series of patients and included migratory arthralgias and arthritis. Gastrointestinal signs and symptoms, which are particularly common in patients with Henoch-Schonlein purpura (Figure 2), include abdominal pain, nausea, vomiting and intestinal bleeding. Lesions affecting the nervous system may cause peripheral neuropathy or central nervous system symptoms, including seizures.

The granulomatous vasculitides, such as Wegener's granulomatosis and Churg-Strauss syndrome (a rare vasculitis characterized by adult-onset asthma, peripheral eosinophilia and recurrent pneumonia) may or may not involve the skin, although pulmonary disease is common. Pulmonary findings include dyspnea, cough, hemoptysis, infiltrates and pleuritis with effusion. Cardiac lesions are uncommon, but coronary angiitis may result in arrhythmia, myocardial infarction or congestive heart failure.

Approach to the Patient with Palpable Purpulra

CLASSIFICATION AND DIFFERENTIAL DIAGNOSIS

All forms of purpura involve microvascular disruption leading to extravasation of erythrocytes into the surrounding dermis. Consequently, purpuric lesions do not blanch with pressure as do telangiectasias and erythema. Different descriptive terms based on size are used to describe purpura. Petechiae are areas of hemorrhage 3 mm or less, ecchymoses are purpuric lesions larger than 3 mm and contusions are purpuric lesions associated with soft tissue swelling, usually due to trauma.

The causes of purpura may be divided into three categories (Table 1). Intravascular causes are the result of platelet defects or coagulopathies, most of which present as nonpalpable purpura. The vascular causes include the palpable forms. Palpable purpura is usually caused by vasculitis but may have other causes, including trauma, emboli from endocarditis or cholesterol emboli. Extravascular (miscellaneous) causes of purpura are usually nonpalpable and include actinic (senile) purpura, corticosteroid reactions and scurvy.[3]

TABLE 1Etiology of PurpuraIntravascular (usually nonpalpable)Alterations in platelet formation, destruction or function Drugs (aspirin, methyldopa [Aldomet]) Idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura Disseminated intravascular coagulation Infection (especially Neisseria, Rickettsia, Staphylococcus) Splenic sequestration Radiation therapy Myelofibrosis Myeloproliferative disorders Vascular (usually palpable) Inflammatory vascular causes Cutaneous vasculitis Purely cutaneous vasculitis (e.g., secondary to medications) Henoch-Schonlein purpura Polyarteritis nodosa Granulomatous vasculitis (Wegener's granulomatosis, Churg-Strauss vasculitis) Cutaneous vasculitis associated with a collagen vascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) Giant cell arteritis Mixed cryoglobulinemia Hyperglobulinemic purpuraNoninflammatory vascular causes Trauma Subacute bacterial endocarditis Other embolic diseases AmyloidosisExtravascular and miscellaneous (may be palpable or nonpalpable)CorticosteroidsToxins and venomsSenile purpuraScurvyValsalva's maneuverPseudopurpura (Sweet's syndrome, cherry angiomas, angiokeratoma, Kaposi's sarcoma)Derived from Schreiner DT. Purpura. Dermatol Clin1989;7(3):481-90.

Pseudopurpura presents with red papules or plaques on the skin that may be mistaken for palpable purpura. One such entity, Sweet's syndrome (acute febrile neutrophilic dermatosis), is characterized by painful, plaque-forming papules associated with fever, arthralgia and peripheral leukocytosis. Histologically, the papillary dermis is densely infiltrated by neutrophils without vasculitis. Clinically, however, Sweet's syndrome may be confused with vasculitis. The lesions of Kaposi's sarcoma may present as nodules or plaques and may be mistakenly diagnosed as vasculitis.

The differential diagnosis of palpable purpura includes both vascular and miscellaneous causes (Table 2). However, one of the most likely causes of palpable purpura is small-vessel vasculitis.[4,5] It must be emphasized that vasculitis may be manifested as skin lesions other than palpable purpura, especially recurrent urticaria, ulcers, nodules and livedo reticularis.[2] These various skin lesions may provide a useful starting point in helping to identify the size of the vessel involved and the specific vasculitis. For example, vasculitis of venules and post-capillary venules often manifests as palpable purpura or urticaria. Vasculitis involving small and medium-sized muscular arteries, however, is more likely to present as nodules, ecchymosis or ulceration.[6]

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Symptoms associated with palpable purpura include pruritus, burning and, less often, pain. Lesions may be asymptomatic, however, so the presence or absence of these symptoms is not particularly helpful in the differential diagnosis.

PATIENT EVALUATION

The principal challenge to the clinician is to distinguish between vasculitis and the many other causes of palpable purpura. Specifically, the physician must search for an underlying cause, determine whether the condition is a local or systemic disorder and, in most cases, confirm the diagnosis histologically. The most productive initial step is a thorough history and physical examination (Table 3).

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Knowledge of the key features of the various processes that can cause palpable purpura (Table 2) and the most common causes of vasculitis[2,7-14] will allow the clinician to focus the history and physical examination. For example, one of the most common causes of cutaneous vasculitis is a drug reaction. If a patient has recently started pharmacotherapy, discontinuing the drug or switching to a different drug may provide both an etiology and a treatment for the vasculitis, obviating the need for a skin biopsy. Likewise, palpable purpura in a patient with longstanding, erosive, classic rheumatoid arthritis with a high-titer rheumatoid factor will usually not require a biopsy, unless there is a clinical suspicion that a new process has developed.[15]

[1.] Jorizzo JL. Classification of vasculitis. J Invest Dermatol 1993;100:106S-10S. [2.] af Ekenstam E, Callen JP. Cutaneous leukocytoclastic vasculitis. Clinical and laboratory features of 82 patients seen in private practice. Arch Dermatol 1984;120:484-9. [3.] Adelman HM, Wallach PM, Gutierrez F, Kreitzer SM, Seleznick MJ, Espinoza CG, et al. Scurvy resembling cutaneous vasculitis. Cuhs 1994;54:111-4. [4.] Lightfoot RW. Palpable purpura: identifying the cause. Hosp Pract [Off Ed] 1992;27:39-47. [5.] Fox IH, Altman RO, Bennett RM, et al. Vasculitis. In: Medical knowledge self-assessment program VIII. Philadelphia: American College of Physicians, 1988:598-600. [6.] Habif TP. Hypersensitivity syndromes and vasculitis. In: Habif TP. Clinical dermatology: a color guide to diagnosis and therapy. 2d ed. St. Louis: Mosby, 1990:461-71. [7.] Kurzrock R, Cohen PR, Markowitz A. Clinical manifestations of vasculitis in patients with solid tumors. A case report and review of the literature. Arch Intern Med 1994;154:334-40. [8.] Sanchez NP, Van Hale HM, Su WP. Clinical and histopathologic spectrum of necrotizing vasculitis. Report of findings in 101 cases. Arch Dermatol 1985;121:220-4. [9.] Mackel SE, Jordon RE. Leukocytoclastic vasculitis. A cutaneous expression of immune complex disease. Arch Dermatol 1982;118:296-301. [10.] Jain KK. Drug-induced cutaneous vasculitis. Adverse Drug React Toxicol Rev 1993;12:263-76. [11.] Callen JP. Cutaneous vasculitis and other neutrophilic dermatoses. Curr Opin Rheumatol 1993;5:33-40. [12.] Puavilai S, Timpatanapong P, Rajatanavin N, Charuwichitratana S, Polnikorn N. Cutaneous leukocytoclastic vasculitis: clinical and laboratory features of 45 patients seen in Ramathibodi Hospital. J Med Assoc Thai 1990;73:269-73. [13.] Vollertsen RS, Conn DL. Vasculitis associated with rheumatoid arthritis. Rheum Dis Clin North Am 1990;16:445-61. [14.] Callen JP, af Ekenstam E. Cutaneous leukocytoclastic vasculitis: clinical experience in 44 patients. South Med J 1987;80:848-51. [15.] Gray RG, Poppo MJ. Necrotlzing vasculitis as the initial manifestation of rheumatoid arthritis. J Rheumatol 1983;10:326-8. [16.] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. (Case 44-1993). A 39-year-old man with fever, polyarthralgia, and purpuric skin lesions. N Engl J Med 1993;329:1411-6. [17.] Jennette JC, Falk RJ. Disease associations and pathogenic role of antineutrophil cytoplasmic antibodies in vasculitis. Curr Opin Rheumatol 1992;4:9-15. [18.] Dahlberg PJ, Lockhart JM, Overholt EL. Diagnostic studies for systemic necrotizing vasculitis. Sensitivity, specificity, and predictive value in patients with multisystem disease. Arch Intern Med 1989;149:161-5. [19.] Zax RH, Hodge SJ, Callen JP. Cutaneous leukocytoclastic vasculitis. Serial histopathologic evaluation demonstrates the dynamic nature of the infiltrate. Arch Dermatol 1990;126:69-72. [20.] Uetrecht J. Dapsone and sulfapyridine. Clin Dermatol 1989;7:111-20. [21.] Taylor HG, Samanta A. Treatment of vasculitis. Br J Clin Pharmacol 1993;35:93-104. [22.] Sams WM Jr. Hypersensitivity angiitis. J Invest Dermatol 1989;93(2 Suppl):78S-81S. 23. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983;98:76-85. [24.] Ledermann JA, Hoffbrand BI. Dapsone in allergic vasculitis: its use in Henoch-Schonlein disease following vaccmation. J R Soc Med 1983;76:613-4. [25.] Misiani R, Bellavita P, Fenili D, Vicari O, Marchesi D, Sironi PL, et al. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994;330:751-6.

The Authors

GARY L. STEVENS, M.D. is currently serving a residency in dermatology at the University of Texas Southwestern Medical Center at Dallas. Dr. Stevens is a graduate of the University of South Florida College of Medicine, Tampa. He served an internship in internal medicine at the University of South Florida Health Sciences Center, Tampa.

HAROLD M. ADELMAN, M.D. is professor of medicine in the Division of Rheumatology at the University of South Florida Health Sciences Center and assistant chief of the medical service at the James A. Haley Veterans, Hospital, Tampa. Dr. Adelman is a graduate of the University of Bologna College of Medicine in Italy. He completed a residency in general internal medicine at the Brookdale Hospital Medical Center in Brooklyn, N.Y., and a fellowship in rheumatology at the Albert Einstein College of Medicine, Bronx, N.Y.

PAUL M. WALLACH, M.D. is associate professor of internal medicine and internal medicine clerkship director at the University of South Florida Health Sciences Center. He is a graduate of the University of South Florida College of Medicine, where he completed a residency in general internal medicine.

Address correspondence to Harold M. Adelman, M.D., lames A. Haley Veterans, Hospital, 13000 Bruce B. Downs Blvd., Area 111, Tampa, FL 33612.

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