滤泡树突状细胞肉瘤并发副肿瘤性天疱疮

报告1例滤泡树突状细胞肉瘤并发副肿瘤性天疱疮.患者男,49岁.因全身红色风团反复发作5个月、口腔黏膜疼痛性溃疡2个月、间擦部位水疱并进行性加重1个月就诊.皮肤科检查:全身散在红色风团,口腔黏膜溃疡,间擦部位水疱.皮损组织病理检查显示表皮内角质形成细胞灶性坏死、棘层松解、基底细胞液化变性.皮损直接免疫荧光显示基膜带及棘细胞间IgG沉积.患者血清以大鼠膀胱为底物间接免疫荧光显示移行上皮细胞间荧光阳性.腹部B超及CT检查示腹膜后占位性病变.手术切除肿瘤后经组织病理学及免疫组织化学证实为滤泡树突状细胞肉瘤.手术切除肿瘤20 d后患者死于呼吸衰竭.     

滤泡树突状细胞肉瘤相关的副肿瘤天疱疮

报告1例滤泡树突状细胞肉瘤相关的副肿瘤天疱疮。患者男,16岁。因口腔、外阴溃疡伴发热2个月余,全身糜烂20d入院。临床表现为口腔、生殖器溃疡,全身水疱、糜烂及结痂,皮损组织病理改变符合副肿瘤天疱疮。腹部CT示右肾上腺占位性病变,手术切除并经组织病理证实为滤泡树突状细胞肉瘤。经大剂量静脉注射用人免疫球蛋白及口服、静脉滴注糖皮质激素和免疫抑制剂治疗后,采用手术切除肿瘤,术后7周躯干皮损基本愈合,遗留黏膜损害及肢端皮损。     

罕见副肿瘤性天疱疮合并滤泡树突状细胞肉瘤患者的护理

副肿瘤性天疱疮(paraneoplastic pemphigus,PNP)是一种严重的、罕见的自身免疫性疾病,死亡率高,以疼痛的口腔炎和多形性皮疹为临床表现,与非霍奇金淋巴瘤和Castleman病等肿瘤有明确相关性[1]。滤泡树突状细胞肉瘤(follicular dendritic cell sarcoma,FDCS)是罕见的肿瘤,由Monda等[2]在1986年首次提出,2018年一篇文献[3]提及,截至2012年7月全世界范围内英文文献共报道了343例患者。副肿瘤性天疱疮合并滤泡树突状细胞肉瘤极为罕见,仅零散文献报道[4,5],临床主要通过手术治疗肿瘤,术后予化疗、糖皮质激素、免疫抑制剂等综合治疗,但因其皮损广泛及大剂量糖皮质激素、免疫抑制剂等治疗使机体潜在风险增加,感染、阻塞性细支气管炎等并发症为该病主要死亡原因[6,7],所以在临床护理中对潜在风险因素的评估与防治显得尤为重要,而国内外文献中较少提及。我科于2019年7月31日收治1例副肿瘤性天疱疮合并滤泡树突状细胞肉瘤患者,现报道如下。     

Autoantibody production from a thymoma and a follicular dendritic cell sarcoma associated with paraneoplastic pemphigus

BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease. We previously reported that B cells in a Castleman tumour associated with PNP produced autoantibodies. However, it is uncertain whether the production of autoantibodies from the associated tumour is a common mechanism in PNP. OBJECTIVES: To investigate autoantibody production in a thymoma and a follicular dendritic cell sarcoma that were excised from two patients with PNP. METHODS: Tumour cells were cultured, and their surface markers were identified. Indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA) using culture media from the tumours were used to detect PNP autoantibodies. RESULTS: B cells with markers (CD22+, surface membrane IgG+ and surface membrane IgM+) of mature B lymphocytes constituted a proportion of cultured tumour cells in both tumours. Western blot showed that the medium from both the thymoma and the follicular dendritic cell sarcoma cells recognized 190-kDa periplakin and 210-kDa envoplakin bands of human epithelial proteins as well as recombinant linker regions of periplakin, envoplakin, desmoplakin and bullous pemphigoid antigen 1. ELISA was positive for antidesmoglein 3 antibody. CONCLUSIONS: The presence and localization in tumours of B-lymphocyte clones against proteins of the plakin family and desmoglein 3 in skin may not be confined to PNP with Castleman disease, but is possibly a common mechanism in PNP associated with various tumours.     

Coexistence of IgA antibodies to desmogleins 1 and 3 in pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus

BACKGROUND: Pemphigus is a bullous mucocutaneous autoimmune disease characterized by IgG autoantibodies to desmoglein (Dsg) 1 and/or Dsg3. Occasionally direct immunofluorescence of pemphigus skin reveals IgA depositions with an intraepidermal intercellular pattern in addition to the IgG deposition. OBJECTIVES: To investigate if pemphigus patients, in addition to having IgG autoantibodies, also generate IgA antibodies to Dsg1 and/or Dsg3. PATIENTS/METHODS: Sera of 100 pemphigus patients and 36 bullous pemphigoid controls were tested by IgA enzyme-linked immunosorbent assay (ELISA) to the recombinant extracellular domains of Dsg1 and Dsg3. The patients were selected on clinical grounds and positive IgG ELISA index values for Dsg1 and/or Dsg3. They were divided into four groups: patients having IgG to only Dsg1 (n=34), patients having IgG to both Dsg1 and Dsg3 (n=31), patients having IgG to only Dsg3 (n=27) and patients who had paraneoplastic pemphigus (PNP) (n=8). RESULTS: IgA antibodies to Dsg1 were found in 13 (38%) of the patients with IgG to Dsg1, in five (16%) of the patients with IgG to both Dsg1 and Dsg3, in four (15%) of the patients with IgG to Dsg3 and in none of the PNP patients. IgA antibodies to Dsg3 were found in one (3%) of the patients with IgG to Dsg1, in 18 (58%) of the patients with IgG to both Dsg1 and 3, in 18 (67%) of the patients with IgG to Dsg3, and in four (50%) of the PNP patients. Immunofluorescence analysis demonstrated intraepidermal intercellular staining IgA antibodies in serum and intercellular IgA deposits in skin of IgA ELISA-positive patients, although to a lesser extent than by ELISA. CONCLUSIONS: This study shows that in a considerable number of supposedly IgG-mediated pemphigus patients IgA to Dsg1 and Dsg3 is also present. In most cases the antigen specificity of the IgA follows the antigen specificity of the IgG, although in a small number of cases IgA is present against the Dsg not recognized by IgG.     

Bilateral corneal melting in a patient with paraneoplastic pemphigus

An 80-year-old man, with a solid abdominal tumor and multiple skin lesions, was admitted to the hospital because of a perforated right cornea and an impending perforation of the left. The clinical, histological, immunohistological and immunoprecipitation findings of the skin lesions were consistent with Anhalt's criteria for paraneoplastic pemphigus (PNP). The underlying malignancy proved to be an incurable peripheral neuronal shaft tumor. Both conjunctivae appeared normal. The right eye revealed a flat anterior chamber, due to a spontaneous, central corneal perforation. The central part of the left cornea had severely thinned, resulting in a descemetocele, which eventually perforated. Multiple surgical interventions were needed to restore the anterior chamber in both eyes. Although a causative association between PNP and corneal perforation could not be demonstrated, we think that corneal melting should be added to the list of ocular complications in patients with PNP.     

Fatal paraneoplastic pemphigus associated with a mediastinal tumor

Paraneoplastic pemphigus (PNP) is a rare life‐threatening autoimmune bullous skin disease which is an obligate paraneoplasma. A 34‐year‐old woman presented with recalcitrant stomatitis and a generalized lichenoid rash. A diagnosis of PNP was established based on clinical findings, immunofluorescence, histopathology and biochemistry. A localized mediastinal mass was found with CT imaging and excised. The histologic diagnosis was dendritic cell sarcoma. Despite removal of tumor and immunosuppressive therapy, the PNP progressed rapidly and the patient died of septic multiorgan failure.     

Follicular dendritic cell sarcoma aggravated by hyaline-vascular Castleman's disease in association with paraneoplastic pemphigus: study of the tumor and successful treatment

The authors have successfully treated and monitored a case of paraneoplastic pemphigus in association with follicular dendritic cell sarcoma aggravated by hyaline-vascular Castleman's disease. The patient was a 56-year-old female who presented with recalcitrant erosive lichen planus of the oral cavity, tongue, and genital mucosa, along with polymorphous eruptions throughout her body. Histological examination of the cutaneous lesions, indirect immunofluorescence on rat bladder epithelium, and western blot of human keratinocyte proteins identified anti-epidermal antibodies in the patient's serum. Positron emission tomography and computed tomography scans found a mass in her retroperitoneal region. Pathology and immunohistochemistry investigation further corroborated the diagnosis of follicular dendritic cell sarcoma originated from hyaline-vascular Castleman's disease. Complete remission was achieved and the patient has been monitored for four years.     

Localized mucosal involvement and severe pulmonary involvement in a young patient with paraneoplastic pemphigus associated with Castleman's tumour

We describe a 19-year-old female patient who developed recurrent ulcerations limited to the orogenital mucosa for the last 3 years. She also developed dyspnoea 5 months after the onset of the orogenital lesions. Castleman's tumour of the retroperitoneum was found incidentally during routine physical examination. The diagnosis of paraneoplastic pemphigus (PNP) was made by pathological and immunological studies. The orogenital ulceration responded well to corticosteroid therapy, but severe bronchiolitis obliterans progressed despite intensive care. The patient eventually died from respiratory failure. This case demonstrates the diversity of clinical features of paraneoplastic pemphigus.     

Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3

BACKGROUND: Pemphigus is an antidesmoglein (Dsg) autoimmune disease that is divided into two major subtypes: pemphigus foliaceus (PF) and pemphigus vulgaris (PV). We previously developed enzyme-linked immunosorbent assays (ELISAs) using recombinant Dsg1 and Dsg3 to detect IgG autoantibodies in patients with pemphigus. The protocol for the ELISAs was optimized for serological diagnosis, but under the conditions used, these assays were not particularly useful for monitoring disease activity in certain patients. That is, the sera from some patients with high-titre antibodies continued to show high index values in the ELISA after clinical improvement. OBJECTIVES: In the study reported here, we modified the ELISA protocol to obtain 'true' index values that exhibit a better correlation with disease activity. METHODS: We tested two cases of pemphigus foliaceus (PF) and four cases of pemphigus vulgaris (PV), each with ELISA index values greater than 150 for Dsg1 or Dsg3. We ran an ELISA with sera from these patients serially diluted from 1 : 100 to 1 : 12,800. We then performed ELISA with a series of PV No. 1 sera diluted to 1 : 800 and PV No. 2-4 and PF No. 1-2 sera diluted to 1 : 1600, after which we plotted the ELISA index values against the time course of disease activity. RESULTS: In each of these cases, there was no apparent decline, over the course of the disease activity, in the ELISA index values at a serum dilution of 1 : 100, probably because the antigen-antibody reaction was saturated at that dilution. After running an ELISA with sera serially diluted from 1 : 100 to 1 : 12,800 we found that a linear dose-dependency between the dilution value and the index value was only observed when sera were diluted to 1 : 800 or more in one case (PV No.1) and to 1 : 1600 or more in the other five cases (PV No. 2-4, PF No. 1-2). After performing ELISA with these series as outlined above we plotted the ELISA index values against the time course of disease activity and found that the index values obtained from these appropriately diluted sera fluctuated in parallel with disease activity, and declined with clinical improvement. CONCLUSIONS: These findings indicate that when appropriate dilutions are used in Dsg1 and Dsg3 ELISA, these assays can provide useful serological information for assessing disease activity in PF and PV.