IgG4-related skin disease pathology

Introduction

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.

Figure 1

Figure 2

Figure 3

Figure 4

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)

Figure 5

Figure 6

Figure 7

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.