Management of urticarial vasculitis: A worldwide physician perspective

Abstract

Background: Urticarial vasculitis (UV) is a rare type of leukocytoclastic vasculitis characterized by long lasting urticarial skin lesions and poor response to treatment. As of yet, no clinical guidelines, diagnostic criteria, or treatment algorithms exist, and the approaches to the diagnostic workup and treatment of UV patients may differ globally. We conducted an online survey to examine how UV patients are diagnosed and treated by international specialists and to reveal the greatest challenges in managing UV patients worldwide.Methods: Distribution of the questionnaire included an email to individuals in the World Allergy Organization (WAO) database, with no restrictions applied to the specialty, affiliation, or nationality of the participants (November 2018). The email contained a link (Internet address) to the online questionnaire. Responses were anonymous. The link to the questionnaire was further sent to the network of Urticaria Centers of Reference and Excellence (UCARE) in the Global Allergy and Asthma European Network (GA 2 LEN) as well as to the Turkish Dermatology Society and the Japanese Society of Allergology, who distributed the link to their members. In addition, the survey link was posted online in the group of the Russian Society of Allergologists and Immunologists. Results:We received 883 completed surveys from physicians in 92 countries. UV was reported to be rare in clinical practice, with an average of 5 patients per physician per year. More than twothirds of physicians reported wheals, burning of the skin, and residual hyperpigmentation in 60-100% of UV patients. The most frequently reported reason for receiving referrals of patients with UV was to establish the diagnosis. The most important features for establishing the diagnosis of UV were wheals of longer than 24 hours duration (72%), the results of skin biopsy (63%), and postinflammatory hyperpigmentation (46%). The most common tests ordered in UV patients were complete blood count, erythrocyte sedimentation rate, C-reactive protein, complement components, antinuclear antibodies, and skin biopsy. Physicians considered UV to be of unknown cause in most patients, and drugs and systemic lupus erythematosus to be the most common identifiable causes. Two of 3 physicians reported that they use second-generation antihistamines in standard dose as the first-line therapy in patients with UV. The greatest perceived challenges in the management of UV were the limited efficacy of drugs and the absence of clinical guidelines and treatment algorithms.

Histopathology of chronic spontaneous urticaria with occasional bruising lesions is not significantly different from urticaria with typical wheals

“…Recent publications seldom refer to leukocytoclastic vasculitis, 21,27 but report nuclear dust and blurring of capillaries in a few cases of CU 18 . In the very few cases of UV evaluated in the present study, as this is a relatively rare disease, 7 neutrophilic infiltration, and karyorrhexis were more prominent, but frank fibrinoid necrosis of vessel walls was not apparent in one of the cases. As fibrinoid necrosis may be subtle or focal in UV, it might have been overlooked also in cases classified as CSU.…”

“…Long‐lasting and bruising lesions may suggest the clinical diagnosis of UV, and in two of these cases we observed concomitant incipient fibrinoid necrosis and minor karyorrhexis, which might be classified as early aspects of vasculitis, but not the full‐blown leukocytoclastic vasculitis characteristic of UV, according to the Chapel Hill classification 4 . Also, these patients have never had systemic symptoms, one of them was actually a fast and complete responder to omalizumab and, in the other patient, CSU resolved in a few months after changing H1‐antihistamines, which are not common findings in UV 7 . Moreover, in two other cases without bruising, we also observed either incipient fibrinoid necrosis of vessel walls or minor leukocyte karyorrhexis.…”

“…The diagnosis of CSU is mostly clinical but there may be difficulties in distinguishing urticarial lesions in CSU from those that occur in urticarial vasculitis (UV) or autoinflammatory syndromes 2,5 . Clinical and laboratory signs (absence of pruritus, concomitant fever, high C‐reactive protein [CRP]) and histopathology with a predominantly neutrophilic infiltrate support the diagnosis of autoinflammatory urticarial syndromes, whereas nonpruritic urticarial lesions that last more than 24 hours, have a transient bruising phase and show vasculitis on histopathology (fibrinoid necrosis of vessel walls and leukocytoclasis) are characteristic of UV 6,7 . The latter can be hypocomplementemic, with low C3, C4, and C1q, anti‐C1q autoantibodies, leukocytoclastic vasculitis and systemic manifestations (arthralgia, kidney, and pulmonary involvement), 8,9 but there is a less well‐defined subtype of normocomplementemic UV, where complement levels are within the normal range and there is usually no associated systemic disease 8 .…”

“…The latter can be hypocomplementemic, with low C3, C4, and C1q, anti‐C1q autoantibodies, leukocytoclastic vasculitis and systemic manifestations (arthralgia, kidney, and pulmonary involvement), 8,9 but there is a less well‐defined subtype of normocomplementemic UV, where complement levels are within the normal range and there is usually no associated systemic disease 8 . This subtype of UV may be particularly difficult to distinguish from CSU that occasionally exhibits urticarial lesions that last more than 24 hours and leave transient bruising before fading out, but have no systemic symptoms and generally behave clinically as CSU 3,7,10 . There is some controversy as to whether these cases represent severe forms of CSU, UV or if CSU and UV belong to a common disease spectrum 4 …”

A case report of hypocomplementemic urticarial vasculitis presenting with membranoproliferative glomerulonephritis

“…Constitutional symptoms, such as fever, fatigue and malaise are rather rare, while arthralgias and arthritis are frequent. Common manifestations further include uveitis and abdominal pain, as well as renal and pulmonary involvement, each of them affecting 20-50% of patients [1,6,7]. Involvement of the heart, mainly pericarditis and valvular disease, is unusual, though possibly life threatening [8,9].…”