A Case of Paraneoplastic Pemphigus with Malignant Thymoma and Obliterated Bronchiolitis / 罕见病研究

Paraneoplastic pemphigus (PNP) is a rare and life-threatening autoimmune blistering disease characterized by severe mucosal erosions and polymorphous cutaneous eruptions associated with lymphoproliferative neoplasmas. Castleman's disease, non-Hodgkin's lymphoma, thymoma, follicular dendritic cell sarcoma and chronic lymphocytic leukemia are the commonly associated neoplasmas in PNP, whereas malignant thymoma is rare. The prognosis of PNP is poor due to severe infections during immunosuppressive treatment, underlying malignancies and bronchiolitis obliterans mediated by autoimmunity. A 58-year-old woman who experienced recurrent oral erosive ulcer for 3 years, systemic erythema for 10 months, and dyspnea for 3 months was diagnosed with PNP with malignant thymoma and obliterated bronchiolitis by clinical, radiological, histopathological, and immunological examinations. She died of respiratory failure 3 weeks after resection of the malignant thymoma.

Analysis of skin and mucosal infections and their management after primary tumor resection in patients with paraneoplastic pemphigus / 中华皮肤科杂志

Objective:To analyze the occurrence of and risk factors for skin and mucosal infections after primary tumor resection in patients with paraneoplastic pemphigus, and to summarize relevant nursing experience.Methods:Clinical characteristics and postoperative skin and mucosal infections were retrospectively analyzed in patients with confirmed paraneoplastic pemphigus, who underwent primary tumor resection in Department of Dermatology, Peking University First Hospital between January 1999 and January 2021. Common infectious agents were analyzed, and infection-related risk factors were identified by logistic regression analysis.Results:A total of 44 patients with paraneoplastic pemphigus were included in this study, including 25 (56.8%) males and 19 (43.2%) females, and their age were 33.8 ± 15.4 years. Postoperatively, 21 (47.73%) patients developed skin and mucosal infections, and their postoperative hospital stay (median [ Q1, Q3]) was 38 (25, 60) days, which was significantly longer than that in patients without skin and mucosal infections (21 [12, 23] days, Z = -4.08, P < 0.001) . The most common pathogen was methicillin-resistant Staphylococcus aureus (15 cases, 34.09%) . High glucocorticoid dosage per kilogram of body weight ( OR = 1.21, 95% CI: 1.00 - 1.46, P = 0.047) and receiving assisted ventilation therapy ( OR = 9.20, 95% CI: 2.01 - 42.13, P = 0.004) were independent risk factors for postoperative skin and mucosal infections. After active treatment and care, 37 (84.1%) patients recovered well at discharge. Conclusion:Skin and mucosal infections are a common postoperative complication in patients with paraneoplastic pemphigus, and the pathogens are mostly drug-resistant bacteria, which can lead to prolonged hospital stay, so attention should be paid to postoperative skin care; high postoperative glucocorticoid dosage per body weight and respiratory support may be associated with postoperative skin and mucosal infections.

Efficacy of combined lymphoplasma exchange for the treatment of severe refractory immune-related skin diseases: a clinical observation / 中华皮肤科杂志

Objective To evaluate the clinical efficacy of lymphoplasma exchange (LPE) for the treatment of severe refractory immune-related skin diseases.Methods From May 2013 to October 2015,8 patients with toxic epidermal necrolysis,drug-induced hypersensitivity syndrome (DIHS),pemphigus vulgaris,pemphigoid or paraneoplastic pemphigus were enrolled from Department of Dermatology,Xiangya Hospital,Central South University,who showed no response to conventional therapy or presented with multiple organ dysfunction.After the treatment with LPE,the efficacy was evaluated,and adverse reactions were observed.Results After one session of LPE therapy,6 patients received marked improvement,and were cured at last.In 1 patient with pemphigus vulgaris who was resistant to the treatment with high doses of glucocorticoids and immunosuppressive agents,the rashes regressed during the treatment with LPE,but recurred after the end of treatment.One patient with bullous pemphigoid presented with eruptive blisters on the next day after the treatment with LPE,which were considered as allergic reactions to allogeneic plasma.There were no obvious differences in white blood cell count,lymphocyte count,neutrophil count and blood platelet count in the peripheral blood of 8 patients before and after the treatment with LPE.During the follow-up of 3-5 years,all of the patients were recovered without recurrence,except 1 patient with bullous pemphigoid who died of disseminated tuberculosis after 1 year.Conclusion LPE is effective for the treatment of severe immune-related skin diseases,but attention should be paid to potential transfusion reaction and allergic reactions.

Paraneoplastic Pemphigus Associated with Hepatocellular Carcinoma / 대한피부과학회지

PNP is a rare autoimmune mucocutaneous blistering disease associated with neoplasms, most frequently of the lymphoproliferative type. As PNP is clinically characterized by polymorphous mucosal lesions and cutaneous eruptions, it is important to differentiate it from erythema multiforme, Stevens-Johnson syndrome, lichen planus, and other bullous diseases. A diagnosis of PNP can be confirmed by immunologic studies such as direct and indirect immunofluorescence, immunoblotting, immunoprecipitation. Rare PNP cases related to nonhematological solid tumors have been reported. A 54-year-old male visited us with generalized pruritic scaly lichenoid lesions on the whole body from 5 weeks prior to his first visit. He also presented with extensive painful ulcers and erosions on the oral mucosa and lips for 2 months. Histopathologic findings showed lichenoid infiltration with vacuolar interface change, lichenoid interface dermatitis, keratinocyte apoptosis, and suprabasal acantholysis with cleft. Indirect immunofluorescence using normal human skin showed IgG deposition at the intercellular space. Immunoblotting using normal epidermal extracts in the serum of patient detected antibody to the 190 kDa (envoplakin), 210 kDa (periplakin) molecules polypeptides. He also had a hepatocellular carcinoma and chemoradiotherapy done before. The diagnosis of paraneoplastic pemphigus (PNP) was made. To our knowledge, there are only two reports of PNP associated with hepatocellular carcinoma worldwide, yet no report in Korean literature. Herein, we report the first case of PNP associated with hepatocellular carcinoma in Korea.

Castleman's disease with secondary paraneoplastic pemphigus and systemic lupus erythematosus: a case report / 中华皮肤科杂志

A 47-year-old man presented with recurrent oral ulcerations for more than 1 year and generalized vesicles for 9 months.Physical examination revealed multiple oral ulcers,patchy labial erosions with yellow or dark brown crusts,maceration and blanching of the angle of mouth resulting in difficulty in mouth opening.Cinnamomeous crusts were seen on the nasal limen,palpebral margin and coronary sulcus of penis,with pale red macules after decrustation.Diffuse erythematous patches and bullae were present on the trunk and extremities.The walls of bullae tightly clung to the skin,and some bullae were ruptured,leaving an erythematous and moist surface and giving an erythema multiforme-like appearance; some bullae were turbid and covered with adherent drugcontaining white crusts or black crusts.Nikolsky's sign was negative.Shrinking,edematous dark-red patches were seen in periungual regions of all the fingers and toes.Histologic biopsy and direct immunofluorescence examination of bullous lesions confirmed a diagnosis of paraneoplastic pemphigus (PNP).Histopathological and immunohistochemical findings from the mediastinal tumor were consistent with Castleman's disease (hyalinevascular type) with proliferation of follicular dendritic cells.Laboratory examination revealed a decrease in serum complement C3 and the presence of antinuclear,anti-nucleosome and anti-dsDNA antibodies.The final diagnosis included Castleman's disease,PNP and systemic lupus erythematosus.After 2 months of treatment with low-dose prednisone and azathioprine,skin lesions completely regressed.Then,the dose of prednisone and azathioprine was tapered.Six months later,the patient himself suddenly withdrew prednisone and azathioprine,and began to take traditional Chinese medicine; thereafter,the lesions developed into toxic epidermal necrolysis (TEN),and the patient died finally.This case demonstrates that immunosuppressive therapy should be maintained for a long period of time in patients with Castleman's disease after tumor removal,otherwise,skin lesions may recur or get worse.

Analysis of the reactivity of indirect immunofluorescence in patients with pemphigus foliaceus and pemphigus vulgaris using rat bladder epithelium as a substrate

OBJECTIVES: To evaluate the reactivity of indirect immunofluorescence using rat bladder epithelium as a substrate in patients with pemphigus foliaceus and pemphigus vulgaris from the Department of Dermatology, University of São Paulo Medical School, Brazil. METHODS: Thirty-two patients (8 male and 24 female) from the Department of Dermatology, University of São Paulo Medical School, were selected. Three had mucosal pemphigus vulgaris, 20 had mucocutaneous pemphigus vulgaris, and 9 had pemphigus foliaceus. Patients’ sera were tested by indirect immunofluorescence performed on human foreskin and rat bladder epithelium and by ELISA assays utilizing baculovirus-expressed recombinant desmoglein 3 and desmoglein 1. RESULTS: No patients with mucosal pemphigus vulgaris, 5 of 20 patients with mucocutaneous pemphigus vulgaris (25 percent) and 4 of 9 patients with pemphigus foliaceus (44 percent) had positive indirect immunofluorescence using rat bladder epithelium as a substrate. CONCLUSION: Indirect immunofluorescence using rat bladder epithelium as a substrate is recommended whenever a diagnosis of paraneoplastic pemphigus is considered. The identification of a subset of pemphigus foliaceus and pemphigus vulgaris patients that recognizes desmoplakins by this laboratory tool is critical to avoid the misdiagnosis of paraneoplastic pemphigus.

A Case of Paraneoplastic Autoimmune Multiorgan Syndrome (PAMS) / 대한피부과학회지

Paraneoplastic autoimmune multiorgan syndrome (PAMS) is also known as paraneoplastic pemphigus, and this is a heterogenous autoimmune syndrome involving the skin, mucosa and internal organs and it is caused by autoantibodies related to the underlying neoplasm. Painful stomatitis is the earliest and most constant feature. The cutaneous lesions of this disease are polymorphic. The majority of cases of this syndrome are associated with a lymphoproliferative disorder such as non-Hodgkin lymphoma, chronic lymphocytic leukemia and Castleman disease. A 40-year-old woman presented with a 1-month history of a pruritic erythematous papulomacular rash on the trunk and extremities. She also had a 4-month history of painful oral stomatitis that had failed to respond to steroid therapy. Despite the vigorous treatment, the skin lesions progressed to generalized polymorphic lesions with persistent oral lesions. The histopathologic findings of these lesions revealed polymorphous characteristics according to the clinical features, and they mimicked erythema multiforme, graft-versus-host disease, lichen planus and pemphigus vegetans. Finally, a mass of lymphatic tissue 7.2 cm in diameter and that was diagnosed as Castleman disease was found in her retroperitoneal pelvic cavity. With removal of the lymphatic mass, her skin lesions subsided except for the glossal lesion.

Giant lymph node hyperlasia and its combined paraneoplastic pemphigus: the clinical, histo-pathology and CT findings / 肿瘤研究与临床

Objective To explore the CT findings, the clinicopathological features of giant lymph node hyperlasia and its combined paraneoplastic pemphigus. Methods The clinical features,the imaging and the follow-up data of 19 patients surgically confirmed as giant lymph node hyperlasia were analyzed. Results Clinically, the majority of patients not accompanied with paraneoplastic pemphigus abnormal pulmonary,showed asymptomatic, and only a very small number had lower abdominal discomfort or pain.The patients associated with paraneoplastic pemphigus and abnormal pulmonary manifested the special clinical manifestations, CT finding, pathological characteristics. Histopathologically, the hyaline-vascular type was found in 18 cases and mixed type in 1 case. CT scanning showed that the lesions in 18 patients appeared as larger(2.5-15 cm in diameter), solitary, cylindrical soft-tissue masses with marked enhancement. One case was presented as multiple enlarge lymph node at left neck (1.5-5 cm in diameter). Seventeen of 19 cases were smooth at the edge, and ten cases were uniform in density. The calcification was characterized of an arborizing and (or) flocculent pattern and central location in 7 cases, of which, 1 case circumferential distribution and 5 cases scattered with multiple spots or strip. Shapes were cylindrical and spherical or elliptical. All patients with giant lymph node hyperlasia showed marked enhancement after contrast administration at arterial phase and delay scan. Conclusion CT scanning is an effective method in diagnosis, guiding surgery and evaluating prognosis of giant lymph node hyperlasia, especially dynamic contrast-enhanced and delayed CT scanning. It is the critical way for patients complicated with paraneoplastic pemphigus and abnormal pulmonary cases, to diagnose early and resect tumor-like lesions in vivo.

A Case of Paraneoplastic Pemphigus Presenting with Generalized Exfoliative Dermatitis / 대한피부과학회지

We describe a 56-year-old Korean man with paraneoplastic pemphigus (PNP) associated with persistent generalized exfoliative dermatitis (GED). He developed multiple scattered flaccid bullae on the erythematous base with scales over his face, upper trunk and extremities, with mucosal involvement for 4 months. Due to myasthenia gravis he also suffered from ptosis, general weakness, and weight loss of 10 kg for a month. A computed tomography and histopathological examination of the chest revealed a mass in the anterior mediastinum which was confirmed as thymoma. During the course of disease, his erythematous patch with crust lesions became confluent, and then GED developed. After total thymectomy, GED waxed and waned for 2-years and eventually disappeared. Herein, we report an interesting case of PNP associated with persistent GED for at least 2 years, even though the patient had been treated with surgery and medication.

Inflammatory Myofibroblastic Tumor on Intercostal Nerve Presenting as Paraneoplastic Pemphigus with Fatal Pulmonary Involvement

Inflammatory myofibroblastic tumors (IMTs) are benign neoplasms that can occur at different anatomic sites with nonspecific clinical symptoms. A 48-yr-old woman presented with a 2-month history of a relapsed oral ulcer, progressive dyspnea, and a thoracic pain induced by breathing. A tumorous mass was noticed in the right costodiaphragmatic recess on chest computed tomography and magnetic resonance imaging, and the patient underwent a right costotransversectomy with excision of the tumor, which originated from the 12th intercostal nerve. Histology and immunohistochemistry showed that the tumor was an IMT of the intercostal nerve. The patient's postoperative course was not favorable; dyspnea persisted after surgery, and a progressive pulmonary compromise developed. The cause of the respiratory failure was found to be bronchiolitis obliterans, which in this case proved to be a fatal complication of paraneoplastic pemphigus associated with an IMT. This case of IMT of the spinal nerve in the paravertebral region is unique in terms of its location and presentation in combination with paraneoplastic pemphigus, which is rare. A brief review of the heterogeneous theories concerning the pathogenesis, clinicopathological features, and differential diagnosis of this disease entity is presented.

Castleman Tumor in Association with Paraneopiastic Pemphigus-A Report of 10 Cases / 中华皮肤科杂志

Objective To obtain a better understaning of the clinical features of Castleman tumor associated paraneoplastic pemphigus. Methods The clinical features and therapy of 10 cases of this disease, diagnosed in the Department of Dermatology of Peking University First Hospital were analyzed. Results Castleman tumor was shown to be the most common neoplasm associated with paraneoplastic pemphigus in China. The clinical presentations, histopathologic characteristics, CT scan findings, and immunologic features were all unique. The early diagnosis and removal of the Castleman tumor are crucial for the treatment of this tumor-associated autoimmune disease. Conclusions Because Castleman tumor is directly related to the induction of autoimmunity, early diagnosis and prompt removal of the tumor are essential to the management of this disease.

The Pathogenesis of Paraneoplastic Pemphigus Associated with Castleman′s Disease / 中华皮肤科杂志

Objective To investigate the role of Castleman′s disease in the pathogenesis of paraneoplastic pemphigus (PNP). Methods In six PNP patients associated with Castleman′s disease, routine immunohistochemistry was performed on tumor tissue. Reverse transcription - PCR, DNA sequencing of cloned PCR product and in situ hybridization (ISH) were used to estimate the clonality of the B-cells in the tumors. The expression of the specific tumor B-cell clones was evaluated by Northern blot. Six patients with Castleman′s disease without mucocutaneous lesion and 3 patients with reactive lymphadenopathy were used as the controls. Results Immunohistochemistry showed that CD20-positive B-cells in high density located in lymphoid follicles. The PCR produced one discrete band of about 128 bp in every paraneoplastic pemphigus patients. After sequencing the cloned PCR product, only two kinds of highly homologous sequences were found in all of the PNP patients. The 128 bp sequences were the major clones seen in all patients, and the 122 bp sequences were the relatively minor one seen in 4 patients. Anti-sense RNA probe transcribed from a clone of 128 bp was used in ISH. Signals of ISH located in cytoplasm of the cells in follicles of the tumors. Furthermore, this probe was also used for Northern blot and showed a strong signal in PNP patients. Conclusions Castleman′s disease associated with PNP share a major B-cell clone. The B-cell clone is expressed and maybe produces functional antibody initiating the mucocutaneous immune injury.

Paraneoplastic Pemphigus: A Report of Two Cases / 中华皮肤科杂志

Paraneoplastic pemphigus(PNP) is a clinically, histologically, and immunopathologically distinct autoimmune bullous disease characterized by severe painful mucosal erosions and polymorphous skin lesions. Histopathology shows acantholysis with lichenoid dermatitis or keratinocyte necrosis, and there are autoantibodies to various epidermal proteins with underlying neoplasia. We report two cases of paraneoplastic pemphigus in China firstly. The clinical, histologic, and immunopathologic findings of both cases strongly suggest the diagnosis of paraneoplastic pemphigus associated with Castleman′ s tumor.

A Preliminary Study on the Antibody Secreted in Castleman's Disease Associated with Paraneoplastic Pemphigus / 中华皮肤科杂志

Objective To identify features of antibodies in the supernatants of cultured Castleman's disease cells.Methods Lymphocytes of Castleman's disease were isolated and cultured.Immunofluorescence and immunoblot assays were performed with IgG extracted from culture supernatants.The immunoglobulin heavy chaingene of cultured tumor B cells was analyzed by RT-PCR,cloning and sequencing.ResultsIg Gextracted from culture supernatant scouldattachtotheepithelialcellsurfacesofmousebladdertissues.Theantibodycouldalsoidentifytwoantigencomponents,210000and190000,ofnormalhumanepidermaltis-sues.ThesequencesimilaritywasfoundinimmunoglobulinheavychaingeneofculturedtumorBcellscom-paredwiththatof6patientswithCastleman'sdiseasepreviouslyreported.Conclusions Castleman's tumor associated with paraneoplastic pemphigus can secret autoantibody with similar features to that found in patients'sera.