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IgG4-related skin disease pathology

Author: Dr Priyam Sobarun, Dermatology Registrar, Green Lane Hospital, Auckland, New Zealand. October 2015.



IgG4-related disease is a recently described entity. It is characterised by:

  • High levels of circulating IgG4 (>135 mg/dL) in 60–70% of patients
  • Tissue infiltration of IgG4+ plasma cells
  • Fibroinflammatory change in various organs such as the pancreas, salivary, lacrimal, etc
  • Striking histological similarities across organs.

Histology of IgG4-related skin disease

  • Dense lymphoplasmacytic infiltrate (figures 1,2)
  • Storiform fibrosis (fibrosis in a cart-wheel pattern, figure 3)
  • Modest-to-moderate tissue eosinophilia (figure 4)

Generally, the minimum for making the diagnosis for most tissues is from 30 to 50 IgG4-positive cells per high power field. However, in some organs or tissues e.g kidney, only 10 IgG4-positive plasma cells per high power field may be sufficient.

IgG4-related skin disease pathology

Special stains of IgG4-related skin disease

  • The CD3 stain illustrates the dense population of T lymphocytes (figure 5)
  • The CD20 stain illustrate the population of plasma cells/ B cells (figure 6)
  • The anti IgG4 stain which looks brown shows an impressive >250 IgG4 +B cells on high power field (figure 7)

IgG4-related skin disease – special stains

Classification of IgG4-related skin disease

Yokura et al (2014) proposed a classification of IgG4-related skin disease which divides it into primary, mass-forming lesions due to the direct infiltration of plasma cells and secondary lesions which are due to IgG4-mediated inflammation through secondary mechanisms.

Primary lesions include:

  • Cutaneous plasmacytosis
  • Pseudolymphoma and angiolymphoid hyperplasia with eosinophilia
  • Mikulicz disease (inflammation of lacrimal and salivary glands).

Secondary lesions include:

  • Psoriasis-like lesions
  • Unspecified maculopapular or erythematous lesions
  • Hypergammaglobulinaemia, purpura and urticarial vasculitis.
  • Ischaemic digit

The diagnostic criteria on histology proposed for skin disease are the following:

  • Primary IgG4 related skin disease
  • Marked lymphocyte and plasmacyte infiltration, IgG4+/IgG+ >40%
  • No of IgG4+ cells per high power field >10.

Secondary IgG4-related skin disease

  • Plasmacyte infiltration with IgG4+/IgG+ >40% and/or perivascular IgG4 deposition

Differential diagnosis of IgG4-related skin disease

The differential diagnosis of immunoglobulin G4-related disease (IgG4-RD) is broad and depends upon the specific site of involvement and clinical presentation.



  • Tokura Y, Yagi H, Yanaguchi H et al. IgG4‐related skin disease. Br J Dermatol. 2014; 171: 959–67. PubMed.
  • Masaki Y, kurose N, Umehara H.IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century. Journal of clinical and experimental hematopathology 2011; 51(1): 13–20. PubMed.
  • Haralampos MM, Fragoulis GE, Stone JH. Overview of IgG4-related diseases. Retrieved from UptoDate on 17/09/15.

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