title: IgG4-related skin disease successfully treated by thalidomide: a report of 2 cases with emphasis on pathological aspects.
abstract: OBJECTIVE
  In IgG4-related disease (IgG4-RD), skin involvement is rare and associated especially with systemic disease. We report 2 cases of isolated skin IgG4-RD successfully treated with thalidomide and investigated their phenotypic characteristics.
  
  
  METHODS
  Two men had cephalic nodules. Skin biopsies revealed dense lymphocytic infiltrates with numerous plasma cells and fibrosis. IgG4-RD was confirmed by very high IgG4+ to IgG+ plasma cells ratios of 76% (patient 1) and 100% (patient 2). The serum IgG4 level was normal. There was no other organ involvement. Thalidomide therapy was introduced. After 6 months, lesions were in remission. Patient 1 required long-term, low-dose thalidomide, whereas patient 2 stopped treatment and showed no relapse. Immunostaining revealed numerous FoxP3+ cells in the interfollicular areas, which decreased with treatment in patient 2, and numerous follicular helper T lymphocytes (TFH) within the follicular germinal centers. There were numerous mast cells; some stained for interleukin (IL)-6, and expression of phospho-Smad2/3 was demonstrated.
  
  
  CONCLUSIONS
  IgG4-RD may be skin limited. Cutaneous infiltrates comprise numerous FoxP3+ cells that may interact with mast cells to produce IL-6 and stimulate fibrosis synthesis via the transforming growth factor β/phospho-Smad2/3 pathway. The role of TFH cells remains to be studied. IgG4-RD should be added to the causes of cutaneous pseudolymphomas. Thalidomide could be considered as a therapeutic option in IgG4-RD.
authors.affiliation: Department of Dermatology, Henri Mondor Hospital, 51 avenue du Marechal de Lattre de Tassigny, 94000 Creteil, France. saskia.oro@hmn.aphp.fr
authors.forename: Saskia
authors.initials: S
authors.lastname: Ingen-Housz-Oro
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.forename: Muriel
authors.initials: M
authors.lastname: Elhai
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.forename: Pierre
authors.initials: P
authors.lastname: Aucouturier
authors.forename: Olivier
authors.initials: O
authors.lastname: Chosidow
mesh_terms: D000328:Adult; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction / Q000379:methods; D055502:Secondary Prevention; D012871:Skin Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013792:Thalidomide