来源:pifuke_zhouxun    发布时间:2019-06-11 19:31:40




B. IgG4相关性皮肤病



活检标本示大量淋巴细胞混合浆细胞和嗜酸性粒细胞结节性浸润整个真皮层(图B和C)。免疫球蛋白和T细胞受体基因重排分析未见淋巴细胞非典型形态或单克隆性增殖。免疫组化染色示真皮内多数浆细胞IgG4(图D)呈阳性。IgG(3743mg / dL;正常值为870-1700 mg / dL)和IgG4(2140 mg / dL;正常值<70 mg / dL)血清浓度明显升高。血清白细胞介素(IL)-6值在正常范围内。IgG4阳性细胞计数为每高倍视野78个,IgG4阳性/ IgG阳性细胞比率为87%。真皮纤维化并不明显。局部应用0.05%丙酸氯倍他索,丘疹和斑块逐渐变平。对患者进行随访,一年两次CT扫描,注意内部器官纤维团形成和检测血清IgG4。


IgG4相关性疾病是近期公认的纤维炎性疾病,病因尚不明确,主要见于中年男性。尽管该疾病与血清IgG4水平升高有关,但这些评价指标对确诊即不够敏感又不具有特异性。 IgG4相关疾病确诊需结合临床、影像学、实验室和组织病理学检查结果。该疾病的临床特征为内脏器官纤维团形成和淋巴结肿大。组织病理学检查应可见IgG4阳性细胞高度浸润;确诊可见受累区域IgG4阳性细胞比率与总的IgG阳性细胞比值大于40%,和/或浸润的IgG4阳性细胞(每高倍视野10-200个细胞)数量增加。席纹状纤维化是IgG4相关性疾病的另一组织病理学特征,但在皮损中不常见并且仅表现为轻微至中等程度。


本病例需与Castleman病、原发性皮肤边缘区淋巴瘤(PCMZL)和假性淋巴瘤进行鉴别诊断。 Castleman病特征为C 反应蛋白质和血清IL-6水平升高,多克隆丙种球蛋白缺乏。 PCMZL表现常见相对年轻个体(中位年龄55岁)的躯干和双臂,单克隆性B淋巴细胞增殖异常。基于IgG4阳性细胞显著浸润,本病例被诊断为IgG4相关性皮肤病比假性淋巴瘤更合适。由于未发现抗Ro/ SS-A和抗La/ SS-B抗体,可基本排除干燥综合征。

IgG4相关性皮肤病的正确诊断对临床正确处理是至关重要的。对活动性、症状性IgG4相关性疾病状态,需紧急全身应用糖皮质激素(30-60 mg /天)治疗,尤其累及主动脉、肾、胆道系统、胰腺、或其它内部器官。如果治疗不充分,可出现慢性器官功能障碍,随后出现严重和不可逆的组织改变。因为有人提出皮损能有效预测全身性疾病,因而应密切监视IgG4相关性皮肤病患者其他受累器官。


Microscopic Findings and Clinical Course

The biopsy specimen demonstrated nodular infiltration of numerous lymphocytes admixed with plasma cells and eosinophils throughout the dermis (Figure, B and C). The lymphocytes did not show atypical morphology or monoclonal proliferation in analysis for immunoglobulin and T-cell receptor gene rearrangements. Immunohistochemical staining revealed that most of plasma cells in the dermis were positive for IgG4(Figure,D). Both IgG(3743mg/dL;normal, 870-1700 mg/dL) and IgG4 (2140 mg/dL; normal, <70 mg/dL) serum concentrations were markedly elevated. The serum interleukin(IL)-6 value was with in normal range. The IgG4-positive cell count was 78 per high-power field, and the IgG4-positive/IgG-positive cell ratio was 87%. Fibrosis was not evident in the dermis. The papules and plaques gradually flattened with topical application of 0.05% clobetasol propionate. The patient has since followed up with biannual CT scanning with attention to fibrous mass formation in internal organs and monitoring of serum IgG4.


A recently recognized fibroinflammatory condition, IgG4-related disease is of uncertain etiology and is characterized by a middle-aged male predominance. Although the disease is associated with an elevation in serum IgG4 level, this measure is neither sufficiently sensitive nor specific for diagnosis. The identification of IgG4-related disease draws on a combination of clinical, imaging, laboratory, and histopathological findings. The condition is clinically characterized by fibrous mass formation in internal organs and lymphadenopathy. Histopathologically, a high degree of IgG4-positive cell infiltration is necessary; a ratio of IgG4-positive cells to total IgG-positive cells of greater than 40% and/or an elevated number of infiltrating IgG4-positive cells (10-200 cells per high-power field) in the affected tissue is required for diagnosis. Storiform fibrosis is another histopathological feature of IgG4-related disease but is uncommon in skin lesions and only manifests to a slight to moderate degree.

Frequently, IgG4-related disease involves skin lesions that appear as nonspecific patches, plaques, or papulonodules, or as palpable swelling. It is noteworthy that some patients have presented with skin manifestations as the solitary and antecedent symptom of IgG4-related disease. Recently, Tokura et al  proposed the categorization of IgG4-related skin disease induced by direct infiltration of IgG4-positive plasma cells into 3 types: (1) cutaneous plasmacytosis, (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia,and (3)Mikulicz disease. The present case matches the characteristics of type 2.

Differential diagnoses in the present case included Castleman disease, primary cutaneous marginal zone lymphoma (PCMZL), and pseudolymphoma. Castleman disease is characterized by elevated C-reactive protein and serum IL-6 levels in addition to polyclonal gammaglobulinemia. The manifestation of PCMZL is predominantly on the trunk and arms of relatively younger individuals (median age, 55 years), wherein abnormal B lymphocytes proliferate in a monoclonal pattern. In the present case, The diagnosis of IgG related skin disease was deemed more appropriate than that of pseudolymphoma based on the prominent infiltration of IgG4-positive cells. Sjögren syndrome could be ruled out largely due to the absence of anti-Ro/SS-A and anti-La/SS-B antibodies.

The correct diagnosis of IgG4-related skin disease is critical for proper clinical management. An active, symptomatic IgG4-related disease state requires urgent treatment with systemic glucocorticoids (30-60 mg/d), especially when the aorta, kidney, biliary tree, pancreas, or other internal organs are involved. If therapy is insufficient, severe and irreversible tissue alteration may be followed by chronic organ dysfunction. As skin lesions have also been proposed as effective predictors of systemic disease, careful surveillance for other organ involvement is recommended for patients with IgG4-related skin disease.


原文来自:JAMA Dermatology May 2016 Volume 152, Number 5