Cutaneous vasculitis: insights into pathogenesis and histopathological features

Abstract

The mechanisms underlying the onset and progression of vasculitis remain poorly understood. This condition is characterized by damage to the vascular wall, recruitment of inflammatory cells, and subsequent structural remodeling, which are hallmarks of vasculitis. The histopathological classification of vasculitis relies on the size of the affected vessel and the predominant type of inflammatory cell involved - neutrophils in acute cases, lymphocytes in chronic conditions, and histiocytes in granulomatous forms. Pathological changes progress in every context, and a single vasculitic pattern can be associated with various systemic conditions. Conversely, a single causative agent may lead to multiple distinct clinical and pathological manifestations of vasculitis. Moreover, many cases of vasculitis have no identifiable cause. A foundational understanding of the normal structure of the cutaneous vascular network is crucial. Similarly, identifying the cellular and molecular participants and their roles in forming the "dermal microvascular unit" is propedeutical.

This review aims to elucidate the complex mechanisms involved in the initiation and progression of vasculitis, offering a comprehensive overview of its histopathological classification, underlying causes, and the significant role of the cutaneous vascular network and cellular dynamics. By integrating the latest insights from studies on NETosis and the implications of lymphocytic infiltration in autoimmune diseases, we seek to bridge gaps in current knowledge and highlight areas for future research. Our discussion extends to the clinical implications of vasculitis, emphasizing the importance of identifying etiological agents and understanding the diverse histopathological manifestations to improve diagnostic accuracy and treatment outcomes.

Keywords: NETosis; dermal microvascular unit; leukocytoclastic; vasculitis histopathology; vasculitis pathogenesis.

Figure 1.

Leukocytoclastic vasculitis: a postcapillary venule in the mid dermis present degenerative changes of endothelial cells. A subtle rim of fibrin is visible. Neutrophils infiltrating the vessel wall and the perivascular stroma are associated with nuclear dust (leukocytoclasis).

Figure 2.

Leukocytoclastic vasculitis: in late lesion neutrophils are barely visible. Histiocytes with intracytoplasmic nuclear fragments can be documented. Insert: perivascular dermis gains a “busy” aspect.

Figure 3.

The presence of eosinophils may suggest a drug-induced case.

Figure 4.

Neutrophilic urticarial dermatosis.

Figure 5.

A necrotic vessel is present in the deep dermis. The lumen is obliterated by fibrin cellular debris and nuclear dust. A V shaped ulcer with granulation tissue is present downstream as the result of ischemia. A septicaemic state was documented clinically in this case.

Figure 6.

Erythema elevatum diutinum: concentric fibrosis predominates in late lesion. A careful search for nuclear dust (insert) must be done.

Figure 7.

Necrotizing vasculitis in the upper hypodermis associated with subendothelial fibrin deposition in a smaller vessel in deep dermis in a MPO-ANCA+ patient.

Figure 8.

Polyartheritis nodosa: an arteriole in the deep dermis is involved. A complete fibrin ring push endothelial lining narrowing the lumen. Mononuclear cells infiltrate arterial wall and periarterial space. Some nuclear dust is visible.

Figure 9.

Macular artheritis: more limited vessel wall damage than in polyarthritis nodosa.

Figure 10.

Lupus tumidus. Lymphocytic vasculitis is defined by a heavy sleeve shaped perivascular lymphocytic infiltrate involving the superficial and deep plexus. Lymphocytes are present trough the vessel wall and in contact with plump endothelial cells. Subtle involvement of perieccrine connective and interstitial mucin are diagnostic clues (inserts).

Figure 11.

Lymphocytic vasculitis in lichen sclerosus: intramural lymphocytic infiltrates in large muscular vessels associated with classic pathological changes at the junctional level.

Figure 12.

Leukemia cutis with a lymphocytic vasculitis-like pattern. Co-expression of CD20 and CD5 in small lymphocytes is a diagnostic clue for chronic lymphocitic leukemia.