The clinical spectrum and therapeutic management of hypocomplementemic urticarial vasculitis: data from a French nationwide study of fifty-seven patients.

OBJECTIVE: Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV. METHODS: We conducted a French nationwide retrospective study that included 57 patients with chronic urticaria, histologic leukocytoclastic vasculitis, and hypocomplementemia. We assessed clinical and laboratory data and evaluated the patients' cutaneous and immunologic responses to therapy. We evaluated treatment efficacy by measuring the time to treatment failure. RESULTS: Urticarial lesions were typically more pruritic than painful and were associated with angioedema in 51% of patients, purpura in 35%, and livedo reticularis in 14%. Extracutaneous manifestations included constitutional symptoms (in 56% of patients) as well as musculoskeletal involvement (in 82%), ocular involvement (in 56%), pulmonary involvement (in 19%), gastrointestinal involvement (in 18%), and kidney involvement (in 14%). Patients with HUV typically presented with low C1q levels and normal C1 inhibitor levels, in association with anti-C1q antibodies in 55% of patients. Hydroxychloroquine or colchicine seemed to be as effective as corticosteroids as first-line therapy. In patients with relapsing and/or refractory disease, rates of cutaneous and immunologic response to therapy seemed to be higher with conventional immunosuppressive agents, in particular, azathioprine, mycophenolate mofetil, or cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy. Finally, a cutaneous response to therapy was strongly associated with an immunologic response to therapy. CONCLUSION: HUV represents an uncommon systemic and relapsing vasculitis with various manifestations, mainly, musculoskeletal and ocular involvement associated with anti-C1q antibodies, which were found in approximately half of the patients. The best strategy for treating HUV has yet to be defined.

Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro.

Aberrant expression of master phenotype regulators or alterations in their downstream pathways in lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF fibroblasts compared with normal fibroblasts (mRNA: +44%, protein: +77%). Immunohistochemistry showed FOXF1 expression in nuclei of bronchial smooth muscle cells, endothelial cells, and lung fibroblasts including fibroblastic foci of IPF lungs. In normal lung fibroblasts, FOXF1 repressed cell growth and expression of collagen-1 (COL1) and actin-related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown inhibited cell growth and COL1 expression, consistent with FOXF1 acting in part through ARPC2 repression. In IPF fibroblasts, COL1 and ARPC2 repression by FOXF1 was blunted, and FOXF1 did not repress growth. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 and repressed by the profibrotic cytokine transforming growth factor-ß1 in both normal and IPF lung fibroblasts. Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant in uninjured mouse lungs. In conclusion, FOXF1 functions and regulation were consistent with participation in antifibrotic pathways. Alterations of pathways downstream of FOXF1 may participate to fibrogenesis in IPF fibroblasts.

Rationale and efficacy of CD52 targeting in HTLV-1-associated myositis.

We retrospectively analysed two selected patients, referred to our Haematology Department for refractory HTLV-1 associated myositis with circulating pathologic T-cell population with ATL phenotype. They respectively presented also HTLV-1 associated Crohn-like disease and myelopathy. Muscle biopsy of both patients was analysed to determine the pathologic infiltrate. Alemtuzumab was proposed as salvage therapy. Targeting CD52 with alemtuzumab showed good efficacy on myopathy of both patients for respectively 11 and 10 months. Interestingly, this treatment showed also efficacy on circulating pathologic T-cell population and on concomitant digestive and neurological diseases. The double infected cells ablation and immunosuppressive propriety of alemtuzumab probably explains its interest in this infectious and dysimmunitary disorder. Even though alemtuzumab probably remains a suspensive treatment, its place should be assessed in controlled trial in this difficult to treat rare disease.

Prolonged paradoxical response to anti-tuberculous treatment after infliximab.

A 56-year-old woman with ankylosing spondylitis, treated for 3 months with infliximab, developed miliary tuberculosis with mediastinal lymphadenopathies and brain and splenic lesions. After initial improvement under anti-tuberculous therapy, she suffered an unexpectedly prolonged paradoxical worsening with several episodes of lymphadenopathy, including life-threatening ones, over a period of more than 14 months of follow-up. The outcome was favorable as a result of corticosteroid and surgical treatments. This phenomenon reflects a paradoxical reaction precipitated by infliximab withdrawal.