Urticarial Leukocytoclastic Vasculitis

Urticarial leukocytoclastic vasculitis is a clinicopathologic form of cutaneous small-vessel vasculitis characterized by recurrent urticarial or hive-like lesions with histologic evidence of vascular injury. In contrast to conventional urticaria, individual lesions typically persist for more than 24 hours and may be associated with burning or pain, purpura, or residual hyperpigmentation. Histologically, there is a predominantly neutrophilic perivascular and interstitial infiltrate with leukocytoclasia, erythrocyte extravasation, endothelial and vessel wall injury, and variable fibrin deposition. Urticarial vasculitis may be classified as normocomplementemic or hypocomplementemic according to serum complement levels; hypocomplementemic disease is more frequently associated with systemic involvement and may be associated with anti-C1q antibodies. Urticarial vasculitis may be idiopathic or occur in association with medications, infections, autoimmune disorders, and hematologic diseases or malignancies.

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Slide 1: Figure 1. 57-year-old man with JAK2 V617F–positive essential thrombocythemia presenting with recurrent pruritic, hive-like lesions involving the face, neck, and upper extremities. The eruption initially developed after ropeginterferon alfa-2b therapy but persisted following discontinuation, raising the possibility that interferon exposure initiated or unmasked a vasculitic process subsequently sustained by the proinflammatory milieu of the underlying JAK2-mutated myeloproliferative neoplasm. JAK2-associated inflammatory signaling, including increased IL-6 and TNF-α, may promote endothelial activation, neutrophil recruitment, and vascular injury.

Slide 2: Figure 2. H&E shows a neutrophilic urticarial reaction with a predominantly perivascular and interstitial neutrophilic infiltrate. Leukocytoclasia, erythrocyte extravasation, and perivascular fibrin deposition indicate associated small-vessel injury, supporting urticarial leukocytoclastic vasculitis rather than uncomplicated neutrophilic urticaria (200×).

Slide 3: Figure 3. Higher-power H&E highlights leukocytoclasia, erythrocyte extravasation, and perivascular fibrin deposition associated with the neutrophilic infiltrate, confirming leukocytoclastic vascular injury (400×).

Slide 4: Figure 4. H&E shows cytoid bodies associated with accelerated keratinocyte apoptosis, which may contribute to the secondary keratinocyte-derived amyloid deposition identified in this biopsy (400×).

Slide 5: Figure 5. H&E shows globular pink amyloid deposits within the papillary dermis immediately subjacent to the epidermis. The distribution favors secondary localized keratinocyte-derived cutaneous amyloidosis, likely reflecting accelerated keratinocyte apoptosis (400×).

Slide 6: Figure 6. C3d and C4d immunohistochemistry show no significant microvascular complement deposition, suggesting that complement activation was not a dominant mechanism of vascular injury at the time of biopsy. Both stains highlight the papillary dermal amyloid deposits, likely reflecting complement binding or entrapment within the amyloid rather than primary complement-mediated vascular injury (200×).

Slide 7: Figure 7. C5b-9 immunohistochemistry similarly shows no significant microvascular deposition but highlights the papillary dermal amyloid deposits. MxA is negative, indicating no significant ongoing cutaneous type I interferon response at the time of biopsy; however, this does not exclude an earlier initiating effect of ropeginterferon alfa-2b (200×).