A causal role for parvovirus B19 infection in adult dermatomyositis and other autoimmune syndromes

Background: Infection with parvovirus B19 (B19) has been associated with co nnective tissue disease (CTD) stigmata, namely, a systemic lupus erythemato sus (SLE)-like illness, seronegative polyarthritis resembling rheumatoid ar thritis, and vasculitis. The dermatopathology and pathogenetic basis of suc h B19-associated CTD-like syndromes have not been elucidated. Objective: We attempted to document persistence of the B19 genome in skin l esions of 7 patients with CTD-like symptomatology following B19 infection a nd to correlate systemic manifestations to dermatopathological findings. Method: In 7 prospectively encountered patients in whom history, clinical s igns and/or serology supported a diagnosis of CTD in the setting of B19 inf ection, dermatopathological and clinical features were correlated. Parvovir us B19 viral genome was sought in skin tissue using the polymerase chain re action (PCR). Results: Two patients had clinical features diagnostic of myopathic dermato myositis (DM), 1 of whom is still symptomatic 1.5 years after the onset of her illness, and the other has had typical clinical features of DM for a du ration of 3.5 years. A 3rd patient with SLE remains symptomatic 4 years aft er the onset of her illness. A 4th patient has persistent seronegative symm etrical polyarthritis of 6 years' duration and cutaneous lesions of granulo ma annulare (GA). The 5th patient has a 1.5-year history of debilitating po lyarthritis and cutaneous lesions with overlap features of DM and subacute cutaneous LE (SCLE). The Gth patient has had a persistent folliculocentric necrotizing vasculitis for 3 years. The 7th patient has a 1-year history of microscopic polyarteritis nodosa (PAN) with cutaneous vasculitis and persi stent active renal disease. In 4 patients, exposure to children with fifth disease immediately preceded the onset of their CTD. Parvovirus B19 infecti on was documented serologically in 6 patients with antibodies of IgG subcla ss in 6 and of IgM subclass in 1. Four of 6 patients questioned had a histo ry of atopy. Skin biopsies from patients with clinical features of SLE or D M demonstrated an interface dermatitis with dermal mucinosis. A necrotizing vasculitis with epithelial pustulation was seen in 2 patients. Interstitia l GA-like infiltrates were seen in 5 cases. Immunofluorescent (IF) testing revealed a positive lupus band test (LBT) and epidermal nuclear and vascula r staining for IgG and C5b-9 in the SLE patient. One DM patient had a negat ive LET in concert with C5b-9 deposition along the dermoepidermal junction (DEJ) and within blood vessels while the other showed endomysial vascular C 5b-9 deposition. In all patients, skin biopsy material contained B19 genome , which was absent in the serum of 4 patients analyzed. Symptomatic relief followed immunosuppressive and immunomodulatory therapy with agents includi ng prednisone, cyclophosphamide, hydroxychloroquine, non-steroidal anti-inf lammatory drugs and etanercept, but no patient has had complete symptom res olution. Conclusions: Persistent B19 infection may be of pathogenetic importance in certain prototypic CTD syndromes, to which underlying immune dysregulation associated with a blunted IgM response to viral antigen may predispose. Ant i-viral therapy might be worthy of consideration since traditional immunosu ppressive therapy was unsuccessful in our cases. (C) Munksgaard 2000.