S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV)
Authors: Antiga Emiliano , Bech Rikke , Maglie Roberto , Genovese Giovanni , Borradori Luca , Bockle Barbara , Caproni Marzia , Caux Frédéric , Chandran Nisha Suyien , Corrà Alberto , D'Amore Francesco , Daneshpazhooh Maryam , De Dipankar , Didona Dario , Dmochowski Marian , Drenovska Kossara , Ehrchen Jan , Feliciani Claudio , Goebeler Matthias , Groves Richard , Günther Claudia , Handa Sanjeev , Hofmann Silke C. , Horvath Barbara , Ioannidis Dimitrios , Jedlickova Hana , Kowalewski Cezary , Kridin Khalaf , Joly Pascal , Lim Yen Loo , Marinovic Branka , Maverakis Emanual , Meijer Joost , Patsatsi Aikaterini , Pincelli Carlo , Prost Catherine , Setterfield Jane , Sprecher Eli , Skiljevic Dusan , Tasanen Kaisa , Uzun Soner , Van Beek Nina , Vassileva Snejina , Vorobyev Artem , Vujic Igor , Wang Gang , Wang Mingyue , Wozniak Katarzyna , Yayli Savas , Zambruno Giovanna , Hashimoto Takashi , Schmidt Enno , Mascarò José Manuel , Marzano Angelo Valerio 
Published: March 2023

Background

Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi‐organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease‐associated complications, such as bronchiolitis obliterans.

Objectives

These guidelines summarize evidence‐based and expert‐based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included.

Results

Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti‐envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first‐line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco‐haematologists is recommended for optimal management of the patients.

Conclusions

These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.