Immunoglobulin G4-related kidney diseases: An updated review

Table 1 Representative organ manifestations in IgG4-related disease

Organs adopted at the 1st International symposium in Boston in 2011
Pancreas	Lymphoplasmacytic sclerosing pancreatitis
Eye/orbit/lacrimal glands	Dacryadenitis/orbital inflammation/pseudotumour
Salivary glands	Sialoadenitis/Mikulicz disease/Kuttner’s tumor
Aorta/arteries	Aortitis/periaortitis/arteritis
Mediastinum/retroperitoneum	Mediastinitis/retroperitoneal fibrosis/mesenteritis
Kidney	Tubulointerstitial nephritis/renal pyelitis
Pachimeninges/hypophysis	Pachimeningitis/hypophysitis
Lung	Lung disease/inflammatory pseudotumor
Pleura/pericardium	Pleuritis/pericarditis
Breast	Mastitis
Bile ducts/gall bladder/ liver	Sclerosing cholangitis/cholecystitis/hepatopathy
Prostate	Prostatitis
Skin	Skin disease/pseudolymphoma
Limph node	Lymphadenopathy
Organs newly recognized after the Boston meeting
Nerve	Infraorbital nerve swelling
Paranasal sinus	Chronic rhinosinusitis
Testis/paratestis	Paratesticular pseudotumour
Ureter	Ureteritis
Urethra	Urethritis
Urinary bladder	Interstitial cystitis

Table 2 Conditions once regarded as individual disorders now recognized to be part of IgG4-related disease

Autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis)

Eosinophilic angiocentric fibrosis (affecting the orbits and upper respiratory tract)

Fibrosing mediastinitis

Hypertrophic pachymeningitis

Idiopathic hypocomplementemic tubulointerstitial nephritis with extensive tubulointerstitial deposits

Inflammatory pseudotumour (affecting the orbits, lungs, kidneys, and other organs)

Küttner’s tumor (affecting the submandibular glands)

Mikulicz’s disease (affecting the salivary and lacrimal glands)

Multifocal fibrosclerosis (commonly affecting the orbits, thyroid gland, retroperitoneum, mediastinum, and other tissues and organs)

Periaortitis and periarteritis

Inflammatory aortic aneurysm

Retroperitoneal fibrosis (Ormond’s disease)

Riedel’s thyroiditis

Sclerosing mesenteritis

Table 3 Mimickers of immunoglobulin G4-related disease

Autoimmune	Malignancy	Other
Antineutrophil cytoplasmic antibody-associated vasculitis	Adenocarcinoma and squamous cell carcinoma	Castleman’s disease
Granulomatosis with polyangiitis	Extranodal marginal zone lymphoma	Cutaneous plasmocytosis
Eosinophilic granulomatosis with polyangiitis	Inflammatory myofibroblastic tumor	Erdheim-Chester disease
Microscopic polyangiitis	Lymphoplasmacytic lymphoma	Inflammatory bowel disease
Sarcoidosis	Lymphoproliferative disease	Perforating collagenosis
Sjogren’s disease	Follicular lymphoma	Primary sclerosing cholangitis
		Rhinosinusitis
		Rosai-Dorfman disease
		Splenic sclerosing angiomatoid nodular transformation
		Xanthogranuloma

Table 4 Clinical presentation of immunoglobulin G4-related disease per site of involvement

Organ system	Nomenclature	Clinical features
Orbit	IgG4-related ophthalmic disease IgG4-related orbital inflammatory pseudo-tumor IgG4-related pan-orbital inflammation IgG4-related orbital myositis	Swelling of orbital tissue and proptosis
Lacrimal gland	IgG4-related dacryadenitis	Bilateral swelling of the glands and impaired production of secretion
Salivary gland	IgG4-related sialoadenitis IgG4-related parotitis IgG4-related submandibular gland disease	Bilateral swelling of the glands and impaired production of secretion
Thyroid	IgG4-related thyroid disease	Hypothyroidism, neck pain, dysphagia, dyspnea
Liver	IgG4-related hepatopathy	Jaundice, right upper quadrant mass
Biliary tract and gall bladder	IgG4-related sclerosing cholangitis IgG4-related cholecystitis	Jaundice, pruritus, cholestasis
Blood vessels	IgG4-related aortitis/periaortitis IgG4-related periarteritis	Chest pain, dyspnea
Retroperitoneal fibrosis	IgG4-related retroperitoneal fibrosis	Flank pain, obstructive symptoms, peripheral edema
Kidneys	IgG4-related kidney disease Tubulo-interstitial nephritis secondary to IgG4-related disease	Hematuria, proteinuria, hypocomplementemia, chronic renal failure
Skin	IgG4-related skin disease	Papulonodular lesions, plaques, purpura

Table 5 Major histopathological features associated with immunoglobulin G4-related disease

Dense lymphoplasmacytic infiltrate

Fibrosis, arranged at least focally in a storiform pattern

Obliterative phlebitis

Phlebitis without obliteration of the lumen

Increased number of eosinophils

Table 6 Two proposed criteria for IgG4-TIN by the Mayo Clinic and the Japanese Society of Nephrology

Criterion	The Mayo Clinic criteria	JSN criteria
Histology	Plasma cell-rich TIN with > 10 IgG4+ plasma cells/HPF in the most concentrated field (mandatory criterion) TBM immune complex deposits by immunofluorescence, immunochemistry, and/or electron microscopy	Dense lymphoplasmacytic infiltrate with > 10 IgG4+ plasma cells/HPF and/or IgG4/IgG+ plasma cell ratio of > 40%; Characteristic storiform fibrosis
Imaging	Small peripheral low-attenuation cortical nodules, round or wedge-shaped lesions, or diffuse patchy involvement	Multiple low-density lesions or enhanced CT, diffuse kidney enlargement, hypovascular solitary nodule, hypertrophic lesion of the renal pelvic wall
Serology	Elevated serum IgG4 or total IgG level	Elevated serum IgG4 or total IgG level
Clinical features	None	Clinical or laboratory evidence of kidney damage
Other organ involvement	Characteristic findings of IgG4-RD in other organs	Characteristic findings of IgG4-RD in other organs
Definite IgG4-TIN	The histologic feature and at least one other feature from imaging, serology or other organ involvement	The histologic feature (a and b) and at least two of other features from imaging, serology or other organ involvement

IgG4-RD: Immunoglobulin G4-related disease; IgG4-TIN: Immunoglobulin G4-related tubulointerstitial nephritis; CT: Computed tomography.