Reactive macrophage activation syndrome in a patient with parvovirus B19 infection, lymphocytic lichenoid vasculitis, urticaria and angioedema.

Abstract

47-year-old woman had a history of episodic acute intermittent angioedema and urticaria with moderate pruritus for one month. She was on 10 mg of loratadine daily. She had a fever of 39oC, arthralgia, fatigue, and angioedema of the upper respiratory tract. Laboratory results are shown in [Table 1]. She had elevated IgE (206 kU/L). The immunoassay for C1-esterase inhibitor was normal. She was treated with H1- and H2-blocking antihistamines, and methylprednisolone intravenously (1 mg/kg/day). Culture results and viral titers were negative except for a high positive titer of specific IgG antibody to parvovirus B19 of 11.1 (positive titer >1). On the third week of hospitalization, she deteriorated rapidly and developed a macular rash on the trunk and extremities with generalised lymphadenpathy, liver dysfunction and disseminated intravascular coagulopathy (DIC) [Figure 1]. A skin biopsy specimen was compatible with lymphocytic lichenoid vasculitis. An inflammatory pattern centered on the basal layer of the epidermis and upper dermis in a dense band-like distribution. Direct immunofluorescence showed no IgG, IgA, IgM, C3, C1q and fibrinogen deposits. A bone marrow aspirate showed hemophagocytosis [Figure 2]. Parvovirus B19 DNA was detected by the polymerase chain reaction (PCR) in bone marrow [Figure 3]. Macrophage activation syndrome was confirmed. The patient was treated with methylprednisolone 250 mg/day intravenously and intravenous immunoglobulin (IVIG) 0.55 g/kg BW/day for five consecutive days, followed by methylprednisolone 1 mg/kg daily. Fresh frozen plasma and enoxaparin were administered. Two days after treatment, she improved. Monthly infusions of IVIG were continued for 6 months. Corticosteroids were tapered gradually to 8 mg of methylprednisolone daily. On periodic follow-up, the patient was quite well without episodes of angioedema and no new skin lesions were seen. Our patient met all criteria for reactive macrophage activation syndrome (rMAS) outlined by Imashuku. [1] Acute parvovirus B19 infection can be diagnosed by demonstrating a four-fold rise in serum B19-specific IgG antibody titers, as in our case. B19 specific DNA or antigens can be detected for months or even years after infection. [2], [3] We speculate that the presence of acute parvovirus B19 infection was a trigger for rMAS. [4] Lymphocytic vasculitis is a reactive process. [5], [6] Purpura pigmentosa chronica, fixed drug eruption, urticarial vasculitis, allergic vasculitis, and the vasculitis of Sjogren syndrome are known to have lymphocytic vasculitis. We conclude that rMAS might represent a subgroup of patients with systemic inflammatory response amenable to IVIG treatment. Given early, IVIG may interrupt the processes that lead to macrophage overactivation.