[Crohn's disease affecting only vulvoperineal area]. / Maladie de Crohn à expression vulvopérinéale exclusive.

INTRODUCTION: Vulvar involvement in Crohn's disease is uncommon. We report here a rare case of Crohn's disease affecting only the vulva and perineum. CASE: A 55-year-old women had been followed at another hospital since 1995 for histology-proved Crohn's disease affecting only the vulvoperineal area. Treatment with infliximab led to a relapse in 2001. The patient was hospitalized because of a new vulvar and perineal flare-up, with major vulvar edema, aphthoid vulvar and perineal erosions and fissures. Findings from upper endoscopy and colonoscopy were normal. A biopsy sample of the ulcerated tissue showed inflammatory infiltration including histiocytes and macrophages. No microorganisms were found. The initial course was favorable, with systemic corticosteroid therapy and azathioprine. Clinical relapse during the corticosteroid tapering necessitated infliximab. DISCUSSION: Vulvar localizations of Crohn's disease are uncommon. They may precede gastrointestinal involvement by many years or very rarely be isolated, as here. Typical clinical appearance includes edema and ulcerations. Other causes of granulomatous vulvar and perineal lesions must be ruled out. There is no consensus for its treatment. This case indicates that infliximab, which is used in fistulized Crohn's disease, can be useful for vulvar and perineal involvement. Physicians must recognize that on rare occasions vulvar involvement is possible without any gastrointestinal localization.

Superficial venous thrombophlebitis as the initial manifestation of hypereosinophilic syndrome: study of the first 3 cases.

BACKGROUND: Superficial venous thrombophlebitis (SVT), often perceived as benign, can coexist with hypercoagulable states. Predisposing risk factors for SVT are similar to those observed for deep venous thrombosis. Association of eosinophilia with SVT is a rare situation that can reveal neoplasia, malignant blood disorders, or vasculitis, but it has never been described in hypereosinophilic syndrome (HES). We herein describe the clinical and biological features, outcome, and response to therapy of 3 patients with SVT associated with eosinophilia that revealed HES. OBSERVATIONS: Superficial venous thrombophlebitis was the initial manifestation of HES in all 3 patients. The mean eosinophil count at diagnosis was 2.4 x 10(3)/muL. All patients received corticosteroids and anticoagulants as the initial treatment, with marked improvement of SVT and return of the eosinophil count to reference limits. All patients experienced relapse and remained dependent on corticosteroid therapy. Two patients received interferon alfa with dramatic regression of SVT, allowing a decrease in the dose of corticosteroids. CONCLUSIONS: We report, to our knowledge, the first 3 cases of SVT related to HES. Superficial venous thrombophlebitis was difficult to treat, with dependence on corticosteroid therapy and partial efficacy of anticoagulant and antiplatelet therapy. Interferon alfa was effective in preventing relapse of SVT related to HES. Mechanisms implied in this thrombogenesis are multiple and remain speculative.

Takayasu's arteritis: An update on physiopathology.

Takayasu's arteritis (TA) is a chronic large vessel vasculitis. The physiopathology of TA has not been completely elucidated, but it appears to be multifactorial and to mainly involve cellular immunity. The pathologic sequence could implicate stimulation from an antigen that triggers heat shock protein (HSP)-65 expression in aortic tissue which, in turn, induces MHC class I-related chain A (MICA). T-cells and natural killer (NK) cells expressing NKG2D receptors could recognize MICA, resulting in acute inflammation. Pro-inflammatory cytokines released from these infiltrating cells induce matrix metalloproteinases and amplify the inflammatory response, inducing more MHC antigen and costimulatory molecule expression on vascular cells and, thus, recruiting more mononuclear cells. Alpha-beta T-cells then infiltrate and specifically recognize one or a few autoantigens presented by a shared epitope associated with specific MHC on the dendritic cells (DC). These DC simultaneously cooperate to some extent with B-cells and determine a humoral immunity mainly constituted by anti-endothelial cell autoantibodies that could trigger complement-dependent cytotoxicity against endothelial cells. The use of corticosteroids and of other immunosuppressive agents can bring TA into remission in most patients. A better understanding of the immunological mechanisms responsible for the vascular injury has led to trials of anti-TNF-alpha agents with encouraging results. In the near future, new drugs specifically designed to target some of the mechanisms described above may be able to expand the physician's therapeutic arsenal in TA.

Kinetic profiles and management of hepatitis B virus reactivation in patients with immune-mediated inflammatory diseases.

OBJECTIVE: Immunosuppressive therapy may trigger hepatitis B virus (HBV) reactivation for increased morbidity and mortality. We aimed to describe HBV reactivation in patients receiving treatment for immune-mediated inflammatory diseases (IMIDs) and to evaluate a predefined algorithm for its prevention. METHODS: Physicians submitted data for patients receiving treatment for IMIDs and exhibiting HBV reactivation, defined as an increase of >1 log10 IU/ml of HBV DNA levels or DNA reappearance. We systematically reviewed cases in the literature. RESULTS: The 35 physician-collected patients had rheumatoid arthritis (n = 14), connective tissue disease (n = 7), vasculitis (n = 5), and other diseases (n = 9). At baseline, 65.7% of patients were positive for hepatitis B surface antigen (HBsAg), 31.4% had a history of HBV infection, and 2.9% had occult HBV infection. Reactivation occurred a median of 35 weeks (range 2-397 weeks) after the start of corticosteroid and/or immunosuppressive therapy. In all, 88.6% of patients were clinically asymptomatic, but 25.7% had severe hepatitis; none had fulminant hepatitis. Management was antiviral therapy for 91.4%, with discontinuation or decrease of immunosuppressive therapy for 45.7%. In pooling these 35 cases and 103 patients from the literature, 73.9% of patients were clinically asymptomatic, 33.3% had severe hepatitis, and 12.3% died and/or had fulminant hepatitis. Reactivation occurred early with rituximab or cyclophosphamide therapy and in HBsAg-positive/HBV DNA-positive patients. Using the predefined algorithm, 78% of patients with reactivation would have received preemptive antiviral therapy. CONCLUSION: We provide new insights into HBV reactivation in patients receiving treatment for IMIDs. A predefined algorithm may be effective in reducing the risk of HBV reactivation in this population.

Vasculitides associated with malignancies: analysis of sixty patients.

OBJECTIVE: To describe characteristics and outcomes of vasculitides associated with malignancies. METHODS: The requirement for inclusion in this retrospective, 10-year study was development of vasculitis in patients with a progressing malignancy. Malignancies secondary to immunosuppressants used to treat vasculitis were excluded. The main characteristics of vasculitides were analyzed and compared according to the type of malignancy. RESULTS: Sixty patients were included (male/female sex ratio 2.53, mean age 62.4 years). Mean followup duration was 45.2 months. Vasculitides were cutaneous leukocytoclastic (45%), polyarteritis nodosa (36.7%), Wegener's granulomatosis (6.7%), microscopic polyangiitis (5%), and Henoch-Schönlein purpura (5%). Malignancies were distributed as follows: hematologic in 63.1%, myelodysplastic syndrome (MDS) in 32.3%, lymphoid in 29.2%, and solid tumor in 36.9%. Vasculitides were diagnosed concurrently with malignancy in 38% of the cases. Manifestations of vasculitides were fever (41.7%), cutaneous involvement (78.3%), arthralgias (46.7%), peripheral neuropathy (31.7%), renal involvement (23.3%; 11.7% glomerulonephritis, 11.7% microaneurysms, 6.7% renal insufficiency), and antineutrophil cytoplasmic antibody (20.4%). Vasculitis treatments were corticosteroids (78.3%) and immunosuppressant(s) (41.7%). Vasculitis was cured in 65% of patients, but 58.3% died, with 1 death secondary to vasculitis. Independent of subtype, patients with vasculitides associated with MDS more frequently had renal manifestations (P = 0.02) and steroid dependence (P = 0.04) and achieved complete remission less often (P = 0.04) than patients with vasculitides associated with other malignancies. Patients with vasculitides associated with a solid tumor more frequently had peripheral neurologic involvement (P = 0.05). Patients with vasculitides associated with lymphoid malignancy had less frequent arthralgias (P = 0.01) and renal involvement (P = 0.02). CONCLUSION: Vasculitides occurring during malignancies present distinctive features according to the vasculitis subtype and nature of the malignancy.

Primary chronic interstitial nephritis in Crohn's disease.

BACKGROUND & AIMS: In Crohn's disease, cases of interstitial nephritis with renal failure have been reported in connection with the use of mesalamine. METHODS: We observed 4 patients with severe interstitial nephritis proven by examination of kidney biopsy specimens. Renal failure was discovered before or simultaneously with the diagnosis of Crohn's disease, and patients were not treated with mesalamine. Impairment of renal function progressed to end-stage renal failure in 3 of the 4 patients. RESULTS: Our results show that the kidney can be an extraintestinal target of Crohn's disease. CONCLUSIONS: Several unanswered questions remain concerning the frequency of interstitial nephritis in patients with Crohn's disease, as well as the exact role of mesalamine in the development of chronic interstitial nephritis.

Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review.

OBJECTIVE: To analyze specific clinical findings, underlying disorders, treatments, outcomes, and prognostic factors for reactive hemophagocytic syndrome (RHS) in systemic disease. METHODS: Data were collected using standardized forms as part of a French national survey. Adult cases without an underlying malignancy, diagnosed on bone marrow or lymph node biopsy, were included. RESULTS: Twenty-six cases (7 men, 19 women, mean age 47.4 +/- 17.7 years) were studied. Systemic diseases included systemic lupus erythematosus (n = 14), rheumatoid arthritis (n = 2), adult onset systemic Still's disease (n = 4), polyarteritis nodosa (n = 2), mixed connective tissue disease (n = 1), pulmonary sarcoidosis (n = 1), systemic sclerosis (n = 1), and Sjögren's syndrome (n = 1). RHS occurred in 2 distinct clinical settings in the course of systemic disease. RHS was associated with an active infection in 15 patients (bacterial infections, 10 cases; viral, 3 cases; tuberculosis, 1 case; and aspergillosis, 1 case) and with the onset of a systemic disease alone in 9 cases. Isolated RHS occurred in 2 cases. The overall mortality rate was 38.5%. Two factors were associated with mortality: corticosteroid treatment at the time of RHS diagnosis, and thrombocytopenia (odds ratio = 28, 95% confidence interval = 13.3-238.9). CONCLUSIONS: When RHS occurs in the course of an active systemic disease (situation only reported in cases of systemic lupus or adult Still's disease), immunosuppressive therapy should be used. In contrast, when RHS is present concomitantly with an active infection, immunosuppressive therapy needs to be lowered and antibiotic therapy should be instituted.