Small-vessel Vasculitis Conceptually
The term “small-vessel vasculitis” refers to histopathologic findings of deposits of fibrin in the wall of venules (and uncommonly of arterioles) or thrombi in lumen of those vessels, or of both of those findings concurrently, in the context of an infiltrate of inflammatory cells. Small-vessel vasculitis may be divided according to the type of vessel affected (venules or arterioles) and the type of inflammatory cells (neutrophils or lymphocytes) that predominate.
The three most common expressions of small-vessel vasculitis associated with predominance of neutrophils are leukocytoclastic, septic, and livedo. Leukocytoclastic vasculitis is characterized histopathologically by the presence of leukocytoclasis, i.e., nuclear “dust” of neutrophils in company with intact neutrophils and, in fully- developed lesions, with fibrin in the wall of venules. In septic vasculitis, neutrophils predominate, but they are unaccompanied by nuclear “dust” of neutrophils or fibrin in the wall of venules; they are joined, however, by a thrombus in the lumen of some venules. In livedo vasculitis, there is no nuclear “dust” of neutrophils, but fibrin is present in the wall of venules and a thrombus within the lumen of some of them.
The different types of neutrophilic vasculitis can be recognized for what they are both clinically and histopathologically. The quintessential example of leukocytoclastic vasculitis is Henoch-Schönlein purpura, of septic vasculitis gonococcemia, and of livedo vasculitis atrophie blanche. When tissue sections of biopsy specimens of the three major types of neutrophilic vasculitis are examined by conventional microscopy, many blood vessels, often most of them, are seen to be affected by the vasculitic process, i.e., by either fibrin or thrombi, or both.
"Lymphocytic Vasculitis" an Epiphenomenon
Lymphocytic vasculitis is defined as an infiltrate of lymphocytes (that usually is perivascular only, and both superficial and deep) in company with fibrin in the wall or a thrombus within the lumen of venules. The phenomenon is rare. In a section of a biopsy specimen that exhibits lymphocytic vasculitis, very few vessels, often only a single one, show fibrin in a wall or a thrombus in a lumen. Furthermore, in contrast to vasculitis with preponderance of neutrophils, it usually is not possible, clinically or histopathologically, to assign a name of a specific disease to it. In vasculitis with a predominance of neutrophils, a diagnosis can be made clinically even before a biopsy specimen has been obtained, e.g., Finkelstein’s disease, ecthyma gangrenosum, or atrophie blanche. That clinical judgment can be confirmed by study of tissue sections that in the case of Finkelstein’s disease reveals leukocytoclastic vasculitis, of ecthyma gangrenosum septic vasculitis, and of atrophie blanche livedo vasculitis. That is not the situation for vasculitis in which lymphocytes monopolize. Furthermore, no disease of the skin shows findings of lymphocytic vasculitis consistently. Predominance of lymphocytes in the context of vasculitis is observable episodically in conditions as disparate as Mucha-Habermann disease, response to an arthropod assault, and lupus erythematosus. In short, in contrast to small-vessel vasculitis with predominance of neutrophils, lymphocytic vasculitis has no diagnostic significance to a histopathologist or a clinician.
Some authors, like Carlson et al., have tried to confer histopathologic importance on “lymphocytic vasculitis” by proposing a classification of it that includes diseases like lymphomatoid papulosis and mycosis fungoides on one hand and Behçet’s disease and Mucha-Habermann disease on the other. They were obliged to admit, however, that Behçet’s disease displays a “leukocytoclastic rather than a lymphocytic vasculitis,” and that only 5-10% of all specimens of Mucha-Habermann disease display a vasculitis in which lymphocytes are dominant. The authors failed to identify a single disease that is associated repeatedly with lymphocytic vasculitis. That supports the results of Massa and Su who reviewed sections from 71 biopsy specimens in which lymphocytes were preponderant in the context of small-vessel vasculitis. They concluded that lymphocytic vasculitis is not associated with any disease in which clinical features can be wedded consistently with histopathologic findings.
In sum, we think that lymphocytic vasculitis is a mere epiphenomenon, i.e., a happenstance secondary to a basic pathologic process, never a fundamental pathologic process itself. Whereas types of neutrophilic vasculitis have diagnostic importance for clinicians and histopathologists, lymphocytic vasculitis does not.
Dr. Graefe did this work while a Visiting Fellow in dermatopathology. He is now on the faculty of the University of Jena in Germany. Dr. Ackerman is director of the Ackerman Academy of Dermatopathology in New York City.
“Lymphocytic vasculitis can be inferred unequivocally if there are infiltrates of lymphocytes in and around the walls of venules accompanied by fibrin deposition in their walls or lumens, or both.” Carlson JA, Mihm MC, LeBoit PE. Cutaneous lymphocytic vasculitis: a definition, a review, and a proposed classification. Sem Diagn Pathol 1996;13(1):72-90.
“Lymphocytic vasculitis is not a disease sui generis, but rather a group term for a number of clinically heterogenous diseases which on histopathological examination have evidence of a lymphocytic vasculitis; that is, there is a predominately lymphocytic infiltrate involving and surrounding the walls of small vessels in the dermis.” Weedon D. Skin pathology. New York: Churchill Livingstone, 1997:206.
“A histologic diagnosis of a lymphocytic vasculitis may be made if there is sufficient evidence of vascular change and the inflammatory infiltrate is predominately lymphocytic.” Elder D, Elsenitas R, Jaworsky C, Johnson B. Lever’s histopathology of the skin. 8th ed. Philadelphia: Lippincott-Raven, 1997:198.
“Lymphocytic vasculitis is a lymphocytic inflammation of the small vessels of the upper dermis, resulting in vessel change and hemorrhage. There are two main idiopathic categories: pityriasis lichenoides and purpura pigmentosa chronica. Many other entities, including erythema multiforme and drug reactions may show lymphocytic vasculitis.” Okun M, Edelstein LM, Fisher BK. Gross and microscopic pathology of the skin. 2nd ed. Canton, MA: Dermatology Foundation Press, 1988:146.
“Lymphocytic vasculitis, unlike neutrophilic vasculitis, is exceptionally rare . . .” Ackerman AB. Histologic diagnosis of inflammatory skin diseases. Philadelphia: Lea & Febiger, 1978:369.
“Lymphocytic vasculitis, in itself, does not seem to be indicative of a specific disease or even of a class of diseases. In brief, it seems to be a wholly nonspecific, secondary phenomenon.” Ackerman AB. Histologic diagnosis of inflammatory skin diseases. Baltimore: Williams & Wilkins, 1997:129.
“In lesions more than 24 to 48 hours old, a lymphocytic vasculitis may represent a resolving phase of an immune complex-mediated neutrophilic vasculitis.” Smoller BR, McNutt NS, Contreras F. The natural history of vasculitis. Arch Dermatol 1990;126:84-9.
“Lymphocytic vasculitis is not widely accepted as a pathologic mechanism by dermatopathologists, and a comprehensive list of its causes cannot be found in the literature. This state of affairs stems largely from the lack of a rigorous definition.” Carlson JA, Mihm MC, LeBoit PE. Cutaneous lymphocytic vasculitis: a definition, a review, and a proposed classification. Sem Diagn Pathol 1996;13(1):72-90.
“We conclude that lymphocytic vasculitis is not a specific pathologic entity but is a reactive process secondary to severe lymphocytic inflammation around and within the blood vessels.” Massa MC, Su WPD. Lymphocytic vasculitis: is it a specific clinicopathologic entity? J Cutan Pathol 1984;11:132-9.
“Lymphocytic vasculitis is a reaction pattern . . .” Murphy. Dermatopathology. A practical guide to common disorders. Philadelphia: Saunders, 1995:134-5.