Clinicopathologic analysis of IgG4-related skin disease

Abstract

IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions with lymphoplasmacytic infiltration, increase in the number of IgG4 þ cells in affected tissues and elevation of serum IgG4 levels. In 2009, we were the first to report skin lesions in patients with IgG4-related disease, but no large case series has been reported and clinicopathological findings remain unclear. To clarify these features, we herein report 10 patients (9 men and 1 woman; median age, 64 years; age range, 46-81 years) with IgG4-related skin disease. All patients had erythematous and itchy plaques or subcutaneous nodules on the skin of the head and neck, particularly in the periauricular, cheek, and mandible regions, except for one patient, whose forearm and waist skin were affected. In addition, eight patients had extracutaneous lesions: these were found on the lymph nodes in six patients, the lacrimal glands in three patients, the parotid glands in three patients, and the kidney in one patient. Histologically examined extracutaneous lesions were consistent with IgG4-related disease; five of six lymph node lesions showed progressively transformed germinal centers-type IgG4-related lymphadenopathy. Cases of IgG4-related skin disease were classified into two histological patterns: those exhibiting a nodular dermatitis pattern and those with a subcutaneous nodule pattern. The infiltrate was rich in plasma cells, small lymphocytes, and eosinophils; the majority of the plasma cells were IgG4 þ . The IgG4 þ cell count was 49-396 per high-power field (mean±s.d., 172±129), with an IgG4 þ /IgG þ cell ratio ranging from 62 to 92%. Serum IgG4 levels were elevated in all examined patients. In conclusion, patients with IgG4-related skin disease had uniform clinicopathology. Lesions were frequently present on the skin of the periauricular, cheek, and mandible regions, and were frequently accompanied by IgG4-related lymphadenopathy.

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

“…[24][25][26][27][28][29] In the largest and bestcharacterized published series of 10 patients with IgG4-related skin disease, 24 8/10 patients were 450 years old, in 8/10 patients extracutaneous manifestations of IgG4-related disease could be proven (lymph node, lacrimal and/or salivary gland, and kidney), and all 10 patients showed an elevated serum IgG4 level. Regarding the localization of IgG4-related skin disease that generally present on the head and neck, particularly cheek, periauricular, and mandible regions, our cases of IgG4 þ primary cutaneous marginal zone lymphomas in contrast showed preferential manifestations on the back, shoulders, and upper extremities.…”

“…In addition, typical histopathological characteristics of IgG4-related disease, such as fibrosclerosis, obliterative phlebitis, or an increased Although IgG4-related disease is a polyclonal disease, IgG4 þ primary cutaneous marginal zone lymphomas are clonal proliferations with light chain restriction. Clonality and/or light chain restriction have not been detected so far in four recent publications [24][25][26]30 dealing with IgG4-related skin disease.…”

Increased Immunoglobulin (Ig) G4–Positive Plasma Cell Density and IgG4/IgG Ratio Are Not Specific for IgG4-Related Disease in the Skin

“…22 The largest study of patients with IgG4-related skin disease to date (n = 10) reported an IgG4+ plasma cell density of 49 to 396 cells per hpf, with an IgG4/IgG ratio of 0.62 to 0.92. 14 Another study of five patients with cutaneous manifestations of IgG4-RD reported an IgG4+ density of 23 to 128.6 per hpf. 15 Our data indicate that moderately elevated IgG4+ plasma cell density and IgG4/IgG ratio are not specific to IgG4-RD.…”

“…1,6,[8][9][10][11][12] Although cutaneous manifestations of IgG4-RD appear to be rare, they may produce nonspecific erythematous papules, nodules, and plaques. [13][14][15][16][17] Therefore, it would follow that evidence for IgG4-RD in the skin (an organ readily accessible for biopsy) may be of diagnostic utility, particularly in patients with nondiagnostic biopsy specimens from visceral organs. Investigators have defined cutoff values for IgG4+ tissue densities for the diagnosis of IgG4-RD for extracutaneous organs, 18 and a recent pathology consensus statement recommended that the IgG4 density for skin should exceed 200 cells per hpf 6 on the basis of anecdotal evidence.…”

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

“…[1][2][3][4] Histological examination of IgG4-related disease has shown diffuse lymphoplasmacytic infiltration, interstitial fibrosis, obliterative phlebitis, and eosinophilic infiltration. Additionally, numerous IgG4-positive plasma cells are observed and the IgG4-positive/IgG-positive cell ratio is elevated above 40% in affected tissues.…”