Idiopathic angioedema and urticarial vasculitis in a patient with a history of acquired haemophilia.

Angioedema is a potentially life-threatening disease cate-gorised into several forms such as allergic, hereditary, acquired autoimmune and idiopathic. Allergic angioedema is dependent on histamine release, whereas mutations in the C1-inhibitor and factor XII genes have been described in hereditary angioedema (1, 2). Bradykinin-induced acquired angioedema is often caused by antibodies to C1-inhibitor, increased consumption of C1-inhibitor in cases of malignancies or autoimmune diseases (2, 3). Angioedema may also be idiopathic (4). Bradykinin, released during activation of the kallikrein-kinin system, is the main mediator of oedema in hereditary angioedema. It is assumed that the kallikrein-kinin system, linked to the coagulation system via factor XI and factor XII, is also activated in cases of idiopathic angioedema (5, 6). Here, we report an unusual case of therapy resistant idiopathic angioedema, normocomplementaemic urticarial vasculitis and a history of autoimmune acquired haemophilia. Emerging evidence suggests that coagulation and inflammatory responses are interlinked (7–9), as illustrated by this case. A 71-year-old man was, apart from a history of hypertension and a minor stroke without sequelae, healthy until he developed a peri-/myocarditis of unknown cause. One year later he developed autoimmune haemophilia with antibodies to factor VIII (10). The patient had no other autoimmune disease at the time of diagnosis, but had a high titre of anti-nuclear antibodies (ANA; ≥ 54 IU/ ml), speckled pattern. Following treatment with high-dose glu-cocorticoids, anti-factor VIII autoantibodies could no longer be detected. However, while the patient was still on prednisolone 10 mg/day (less than 5 months after the diagnosis of autoimmune haemophilia), bruises were gradually replaced by non-pruritic erythematous urticarial lesions that remained for more than 24 h and healed with hyperpigmentation (Fig. 1a and b). Skin biopsies showed leucocytoclastic vasculitis and the patient was diagnosed with urticarial vasculitis. Immunofluorescence analysis showed fibrinogen deposits around blood vessels. Subsequently, severe episodes of angioedema (Fig. 1c), including the face, extremities and upper airways, occurred on multiple occasions and the patient underwent emergency coniotomy on one occasion. Angioedema and urticarial vasculitis always occurred concurrently. Treatment with antihistamines, hydroxychloroquine, tranexamic acid or prednisolone (≤ 80 mg/day) had no effect. A combination of azathioprine 100 mg and dapsone 150 mg daily finally rendered complete recovery from skin lesions and angioedema, but due to side effects, dapsone was discontinued after a few weeks. For almost 3 years the patient was successfully treated with azathioprine. About a month after azathioprine was tapered down, urticarial vasculitis and angioedema reappeared …