Angioedema and transient acquired C1 inhibitor functional deficiency in HIV infection: case report

A 25-year-old man was referred to our outpatient clinic because of urticaria episodes for the past 5 months. For the past 3 months he had also suffered from eyelid or labial angioedema attacks not associated with the urticaria symptoms. A physical examination revealed soft and painful cervical and inguinal lymphadenopathies. Skin-prick tests were negative to inhalants (pollens, mites, moulds and animals), foods, latex and Anisakis simplex. Serum analysis was performed: his cell count revealed slight lymphocytosis, and his erythrocyte sedimentation rate was increased (45 mm/h). Serum biochemistry was normal. A proteinogram showed a polyclonal increase in betaglobulin and gammaglobulin. This polyclonal increase was 2510 mg/ml for IgG, 246 mg/ml for IgM, and 754 mg/ml for IgA. Hepatitis B and C serology were negative. HIV-1 serology was positive using enzyme-linked immunosorbent assay and Western blot techniques. The percentages of CD4 and CD8 cells were 9 and 68%, respectively, and the viraemia count in the diagnosis was 192 000 viral copies, using the polymerase chain reaction technique. Total IgE was normal (56 KU/l) and specific IgE (CAP Pharmacia) was negative to several parasites (Echinococcus, Ascaris and Toxoplasma). In the complement study, C3 (107 mg/dl) and CH50 (312 U/ml) were normal, but the C4 level was low (8.9 mg/ml; normal range 14–47 mg/ml), and the antigenic C1 inhibitor was normal (30 mg/ml). Plasma functional C1 inhibitor was low (10.4 mg/ml; 30%) when it was measured using an enzyme-linked immunosorbent assay technique with the C1 inhibitor marked with biotin [1]. The assay was repeated on several occasions with the same results. Control samples were normal in the same assay. C1q was low (60 μg/ml). Autoantibodies to C1 inhibitor were negative. A positive control was included in the assay. The patient was diagnosed with AIDS stage A2, angioedema caused by acquired functional deficiency of C1 inhibitor, possibly in relation to the HIV primary infection, and acute recidivating urticaria. During the following months, the patient showed clinically evident improvement, the angioedema episodes remitted slowly and spontaneously before antiretroviral therapy was initiated, and the urticaria episodes reduced in intensity and frequency. Although C4 persisted at a low level (6.35 mg/dl), a normalization of the C1q level (126 μg/ml) and of the functional C1 inhibitor occurred before starting antiretroviral therapy. One year after the patient started antiretroviral therapy, he had not suffered any episodes of angioedema. In his last analysis C4 persisted at a low level (7.81 mg/ml), with a normal level of C1q and functional C1 inhibitor. Other authors have previously described C1 inhibitor deficiencies in patients with HIV infection [2]. They showed a decrease in functional C1 inhibitor without clinical expression. On the other hand, Beretta et al. [3] did not find antigenic or functional C1 inhibitor deficiencies in patients with HIV infection, and attributed the results of Gerencer et al. [2] to possible contact activation and cleavage of C1 inhibitor during sample storage. Therefore, we present a patient with a transient alteration in C1 inhibitor function during HIV primary infection, which produced several episodes of angioedema. M. Rechea T. Caballeroa M. López-Trascasab J. R. Arribasc M. C. López Serranoa