Reguiaï Z, Tchen T, Perceau G, Bernard P
Service de dermatologie, hôpital Robert-Debré, CHU de Reims, 51092 Reims cedex, France.
Ann Dermatol Venereol. 2009 May;136(5):431-4. doi: 10.1016/j.annder.2008.10.038. Epub 2009 Feb 26.
The mainstay in the treatment of bullous pemphigoid (BP) is corticosteroids. Immunosuppressive agents might be used for steroid-sparing effect. We report the case of a patient with refractory BP successfully treated with rituximab.
An 83-year-old woman was hospitalized in January 2005 for severe BP. She was initially treated with 30 g/day of clobetasol propionate 0.05% and methotrexate (20 mg/week), with partial remission. However, every attempt to reduce topical corticosteroids resulted in a relapse of the patient's BP. Subsequently, mycophenolate mofetil, azathioprine, dapsone, intravenous immunoglobulins, topical tacrolimus and systemic glucocorticoids (steroid-dependency at 20 mg/day) failed to induce complete remission. In December 2005, we decided to treat the patient with four infusions of rituximab 375 mg/m(2) at 1-week intervals, and this led to a dramatic reduction of the severity of BP. In May 2006, a second course of rituximab was given. One month later, for the first time in 18 months, complete clinical and immunological remission of BP was noted. The patient remains in complete remission, without treatment, 2 years after the last infusion of rituximab.
The B cell-modulating effect of rituximab has encouraged its use in a variety of autoimmune diseases including pemphigus. Only five cases of refractory BP, treated with rituximab (including two paediatric cases), have so far been reported. In three of these cases, follow-up was too short to allow detection of any relapse and the other two patients had lymphocytic leukaemia requiring rituximab infusions every 2 months. In our case, the two courses of rituximab were well tolerated, induced complete clinical and immunological remission and enabled discontinuation of local and systemic corticosteroids.
Rituximab could offer a safe and effective therapeutic alternative for refractory BP.
大疱性类天疱疮（BP）治疗的主要手段是使用皮质类固醇。免疫抑制剂可用于减少类固醇用量。我们报告了1例用利妥昔单抗成功治疗的难治性BP患者。
一名83岁女性于2005年1月因严重BP住院。她最初接受0.05%丙酸氯倍他索30 g/天和甲氨蝶呤（20 mg/周）治疗，病情部分缓解。然而，每次尝试减少外用皮质类固醇都会导致患者BP复发。随后，霉酚酸酯、硫唑嘌呤、氨苯砜、静脉注射免疫球蛋白、外用他克莫司和全身糖皮质激素（类固醇依赖剂量为20 mg/天）均未能诱导完全缓解。2005年12月，我们决定给患者静脉输注4次利妥昔单抗，剂量为375 mg/m²，间隔1周，这使得BP严重程度显著降低。2006年5月，给予第二个疗程的利妥昔单抗。1个月后，18个月来首次出现BP临床和免疫完全缓解。最后一次输注利妥昔单抗2年后，患者未经治疗仍处于完全缓解状态。
利妥昔单抗对B细胞的调节作用促使其被用于包括天疱疮在内的多种自身免疫性疾病。目前仅有5例难治性BP患者接受利妥昔单抗治疗的报道（包括2例儿科病例）。其中3例随访时间过短，无法检测到复发情况，另外2例患者患有淋巴细胞白血病，需要每2个月输注1次利妥昔单抗。在我们的病例中，两个疗程的利妥昔单抗耐受性良好，诱导了临床和免疫完全缓解，并使局部和全身皮质类固醇停用。
利妥昔单抗可为难治性BP提供一种安全有效的治疗选择。
