Paraneoplastic pemphigus: insight into the autoimmune pathogenesis, clinical features and therapy

Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed "paraneoplastic pemphigus". We included also papers in French, German, and Spanish. We found 613 papers for "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed “paraneoplastic pemphigus”. We included also papers in French, German, and Spanish. We found 613 papers for “paraneoplastic pemphigus”. Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL

Paraneoplastic pemphigus with clinical features of lichen planus associated with low-grade B cell lymphoma

BACKGROUND: Neoplasia-induced lichen planus is described as a cell-mediated reaction to unknown epithelial antigens. Paraneoplastic pemphigus (PNP), characterized by the presence of a specific array of autoantibodies, probably represents a different form of presentation of the same autoimmune syndrome where the mucocutaneous expression depends on the dominant pathologic mechanism. METHODS: The authors report a case of PNP with predominant lichen planus-like lesions and review the relevant literature. We observed a 74-year-old female with vesico-bullous, erosive, target-shaped and flat papular lichenoid lesions on the lower legs, palms and soles, evolving for 3 weeks. Histopathology revealed a lichenoid dermatitis. Direct immunofluorescence showed C3 deposition around keratinocytes and epidermal IgG intranuclear deposition. Indirect immunofluorescence revealed circulating IgG with intercellular staining on rat bladder substrate. Immunoblotting demonstrated bands of 130, 190, 210 and 250 kDa antigens. A pararenal B cell lymphoma was found. RESULTS: Oral corticotherapy with 40 mg prednisolone daily was initiated with a good cutaneous response. Four months later, cyclophosphamide (50 mg/day) was introduced because of a discrete enlargement of the pararenal mass. The patient died on the seventh month of follow up as a result of respiratory insufficiency. CONCLUSION: PNP has different forms of presentation and the lack of a consensus about diagnostic criteria may contribute to underdiagnosed cases. Advances on the knowledge of the sensitivity and specificity of diagnostic criteria have allowed a better accuracy of diagnosis

Direct and indirect immunofluorescence

A imunofluorescência é um valioso instrumento auxiliar no diagnóstico das dermatoses bolhosas autoimunes e desordens inflamatórias, uma vez que seus achados clínicos e histopatológicos podem não ser determinantes. Consiste em um método laboratorial factível, que requer profissionais técnicos experientes, e detecta imunocomplexos in situ e/ou circulantes, que podem estar envolvidos na patogênese de tais enfermidades cutâneas.Immunofluorescence is a valuable auxiliary diagnostic tool for autoimmune bullous diseases and inflammatory disorders, since their clinical and histopathologic findings may be inconclusive. It is a feasible laboratory method that requires experienced technicians and detects in situ and circulating immune deposits that may be involved in the pathogenesis of such skin diseases.CNP

Paraneoplastiline autoimmuunsus

Paraneoplastilist autoimmuunsust on täheldatud peaaegu kõikide kasvajate korral, kuid selle väljendused ning patogenees on väga varieeruvad. Autoimmuunne kahjustus võib tabada eri elundisüsteeme: tuntakse neuroloogilisi, dermatoloogilisi, hematoloogilisi, reumatoloogilisi ja süsteemseid sündroome. Tekkemehhanismidest eristatakse neoplastilisi tsentraalse immuuntolerantsuse häireid, perifeerse immuuntolerantsuse iseärasusi ning antigeenide avaldumishäireid. Paraneoplastilised sündroomid võivad nii eelneda kui ka järgneda kasvaja diagnoosile või koguni viidata veel avastamata kasvaja paikmele. Autoimmuunsed nähud võivad kaduda või taandareneda põhihaiguse ravi järel, kuid mõnedel juhtudel peab kiiresti alustama immuunsupresseerivat ravi, et vältida pöördumatute kahjustuste teket. Paraneoplastilise autoimmuunsusega patsientidel on kirjeldatud paremat prognoosi võrreldes nendega, kellel sama kasvaja esineb isoleeritult. Arvatavasti peegeldab autoimmuunsus sel puhul tugevamat immuunvastust ka kasvaja enese vastu.Eesti Arst 2017; 96(5):259–26

Thymic Carcinoma Associated with Cerebellar Degeneration

We present the case of a 57-year-old man with ataxia and clinical and radiological features of cerebellar degeneration. A computed tomography showed a mediastinal mass. The patient was diagnosed of thymic carcinoma. paraneoplastic cerebellar degeneration is an unfrequent disorder, and its association with thymic carcinoma is very rare

Nickel - Induced Oral Pemphigus Vulgaris -Like Lesions

U literaturi je zabilježen samo jedan slučaj oralnog pemfigusa za koji se kao uzrok navodi nikal. U ovom prikazu opisali smo deskvamativni gingivitis kod 49-godišnjeg muškarca. Lezija se nalazila u prednjoj regiji mandibule koja je bila u kontaktu s keramičkim krunicama i mostovima. Osim tog oštećenja pronađene su i opsežne ulceracije u području lijeve i desne obrazne sluznice. Nakon godine dana liječenja lezije se nisu povukle. Uklanjanjem krunica i mostova te jakim topikalnim kortikosteroidima postignut je zadovoljavajući rezultat. Dentalna legura ispitivala se nakon toga metalurgijskim tehnikama. Rezultati su pokazali da je njezin glavni sastojak nikal. Patohistološki test i test imunofluorescencije potvrdili su dijagnozu pemphigus vulgaris. To nas je navelo na zaključak da pacijent boluje od lezija nalik na pemphigus vulgaris izazvanih niklom.So far, only a single case of nickel-induced pemphigus has been reported in the literature. We present a case of a 49-year-old male who had experienced a desquamative gingivitis on the anterior mandibular region which was in contact with porcelain crowns and bridges and severe ulcerations on the right and left buccal mucosa. The lesions did not respond to any medications for a year. After removal of those crowns and bridges with the treatment of potent topical steroids, the lesions responded dramatically. The dental alloy used as the core of crowns and bridges was further investigated using metallurgy techniques. The results showed that the dental alloy mainly contained nickel. Histopathologic and direct immunofluorescence evaluations confirmed a diagnosis of pemphigus vulgaris. We concluded that the patient had experienced nickel-induced pemphigus vulgaris-like lesions on the oral mucosa