Bougacha Marwa, Blibech Hana, Bouchabou Bouchra, Jouini Raja, Helal Imen, Snene Houda, Belkhir Donia, Mehiri Nadia, Ennaifer Rim, Chedly Achraf, Ben Salah Nozha, Louzir Bechir
Pulmonology Department, Mongi Slim Hospital, Tunis, Tunisia.
University of Tunis El Manar, Faculty of Medicine of Tunis, Tunis, Tunisia.
Heliyon. 2024 Feb 3;10(4):e25826. doi: 10.1016/j.heliyon.2024.e25826. eCollection 2024 Feb 29.
Sarcoidosis and the overlap syndrome of autoimmune hepatitis and primary biliary cholangitis (PBC) share common clinical, biological, and histological features. The simultaneous occurrence of these diseases have been reported in few cases and suggests that a common pathway which may contribute to granuloma formation in both conditions. We report the cases of two female patients having an association of sarcoidosis and inflammatory liver diseases. The first case is of a 61-year-old woman had been monitored for an overlap syndrome of PBC and autoimmune hepatitis (AIH). Therefore, treatment with azathiprine has been initiated associated with ursodeoxycholic acid (UDCA). Azathioprine had to be discontinued due to digestive intolerance, specifically chronic diarrhea and abdominal pain. The patient remained clinically stable on UDCA and her liver function tests were stable for years, until she developed symptoms of progressive dyspnea without any other associated signs. Chest computed tomography (CT) revealed mediastinal enlargement, bilateral pulmonary nodules, and symmetrical adenomegalies in the mediastinum. The bronchoalveolar lavage (BAL) revealed increased cellularity, with a notable elevation in lymphocyte count (48 %) and a CD4/CD8 ratio of 4. The patient underwent mediastinoscopy; a biopsy of the right laterotracheal (4R) adenomegaly was performed. Histological examination of the lymph node showed epithelioid and giant-cell tuberculoid lymphadenitis without necrosis, compatible with sarcoidosis. Ophthalmological and cardiac assessments were normal. Plethysmography test was normal and there was no need for corticosteroid treatment; a surveillance was planned. Treatment with UDCA was pursued. The second case is of a 50-year-old woman with no medical history presented symptoms including dry eyes and mouth, inflammatory-type polyarthralgia affecting knees and wrists, bilateral Raynaud's phenomenon, right hypochondrium pain, and worsening dyspnea over six months. Liver analysis showed elevation of alkaline phosphatase (ALP) to three times upper limit of normal (ULN) and gamma-glutamyltransferase (GGT) to 5 times ULN. This cholestasis was associated with an increase in transaminase activity to 5 times ULN for over six months. Immunological tests revealed positive anti-nuclear antibodies (ANA), anti-Ro52, anti-M23E, and anti-centromere antibodies. Chest-CT showed multiple bilateral bronchiolar parenchymal micronodules mostly in the upper and posterior regions without any mediastinal adenomegaly. Bronchial endoscopy was normal, and biopsies indicated chronic inflammation. The BAL revealed increased cellularity, characterized by a high lymphocyte count (51.7 %) and a CD4/CD8 ratio of 2.8. Biopsy of minor salivary gland revealed grade 4 lymphocytic sialadenitis. Skin biopsy revealed an epithelioid granuloma without caseous necrosis. Liver biopsy performed in the presence of cytolysis and moderate hepatic insufficiency, revealed granulomatous hepatitis and cholangitis lesions along with septal fibrosis suggestive of PBC. The diagnosis of cutaneous and pulmonary sarcoidosis with PBC and Sjögren's syndrome was retained. The spirometry and diffusing capacity for carbon monoxide value were normal. Treatment involved UDCA, corticosteroids, and azathioprine, leading to clinical and biological improvement. Sarcoidosis shares some clinical manifestations with autoimmune liver diseases, primarily PBC. A hepatic granuloma with a different appearance and location can guide the diagnosis. Early diagnosis and appropriate management can avoid serious complications and improve prognosis.
结节病与自身免疫性肝炎和原发性胆汁性胆管炎(PBC)的重叠综合征具有共同的临床、生物学和组织学特征。这些疾病同时发生的情况鲜有报道,提示可能存在一条共同的通路,在这两种情况下都可能促成肉芽肿的形成。我们报告了两例患有结节病与炎症性肝病关联的女性患者病例。第一例是一名61岁女性,一直在接受PBC与自身免疫性肝炎(AIH)重叠综合征的监测。因此,已开始使用硫唑嘌呤联合熊去氧胆酸(UDCA)进行治疗。由于消化不耐受,特别是慢性腹泻和腹痛,硫唑嘌呤不得不停用。患者在UDCA治疗下临床症状保持稳定,其肝功能检查多年来也一直稳定,直到她出现进行性呼吸困难症状且无任何其他相关体征。胸部计算机断层扫描(CT)显示纵隔增宽、双侧肺结节以及纵隔内对称性淋巴结肿大。支气管肺泡灌洗(BAL)显示细胞数增加,淋巴细胞计数显著升高(48%),CD4/CD8比值为4。患者接受了纵隔镜检查;对右侧气管旁(4R)淋巴结肿大进行了活检。淋巴结的组织学检查显示上皮样和巨细胞结核样淋巴结炎,无坏死,符合结节病表现。眼科和心脏评估均正常。体积描记法测试正常,无需使用皮质类固醇治疗;计划进行监测。继续使用UDCA治疗。第二例是一名50岁女性,无病史,出现包括眼干、口干、累及双膝和双腕的炎症性多关节痛、双侧雷诺现象、右季肋部疼痛以及六个月来逐渐加重的呼吸困难等症状。肝脏分析显示碱性磷酸酶(ALP)升高至正常上限(ULN)的三倍,γ-谷氨酰转移酶(GGT)升高至ULN的5倍。这种胆汁淤积伴有转氨酶活性升高至ULN的5倍并持续超过六个月。免疫检测显示抗核抗体(ANA)、抗Ro52、抗M23E和抗着丝点抗体呈阳性。胸部CT显示双侧多个细支气管周围实质微小结节,主要位于上叶和后叶区域,无纵隔淋巴结肿大。支气管内镜检查正常,活检提示慢性炎症。BAL显示细胞数增加,其特征为淋巴细胞计数高(51.7%),CD4/CD8比值为2.8。小唾液腺活检显示4级淋巴细胞性涎腺炎。皮肤活检显示上皮样肉芽肿,无干酪样坏死。在存在细胞溶解和中度肝功能不全的情况下进行的肝脏活检显示肉芽肿性肝炎和胆管炎病变以及提示PBC的间隔纤维化。最终确诊为皮肤和肺部结节病合并PBC和干燥综合征。肺活量测定和一氧化碳弥散量值正常。治疗包括UDCA、皮质类固醇和硫唑嘌呤,使临床症状和生物学指标得到改善。结节病与自身免疫性肝病,主要是PBC,有一些共同的临床表现。具有不同外观和位置的肝脏肉芽肿可指导诊断。早期诊断和适当管理可避免严重并发症并改善预后。