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retroperitoneal fibrosis ( rf ) is a rare disease characterized by the development of peritoneal inflammation and fibrosis , which often cause entrapment of the ureters .
the recently advocated concept of immunoglobulin g4 ( igg4)-related disease , derived from research on autoimmune pancreatitis ( aip ) , and the associated diagnostic criteria have led to the widespread recognition of rf as a condition caused by igg4-related disease .
rf can occur for other reasons or with other igg4-related diseases , including aip [ 2 , 3 ] .
the first line of treatment for rf , regardless of its cause , is standard steroid therapy as used for aip [ 1 , 4 ] .
however , steroid - related complications often occur because of the 1- to 3-year treatment duration .
we present the first case of rf treated with hochuekkito maintenance treatment , a kampo ( i.e. traditional japanese herbal ) medicine , selected because of the side effects of steroid therapy ( such as impaired glucose tolerance ) . in this case ,
complete remission occurred and the patient has not relapsed in the 3 years since initially starting steroid therapy .
a 62-year - old japanese man was admitted to our hospital for left back pain in november 2010 . he had no medical history of allergic or autoimmune diseases .
serum biochemistry showed elevated levels of creatinine ( 1.47 mg / dl , normal range 0.601.10 ) , soluble interleukin-2 receptor ( 1,130.0 u / ml , normal range 145.0519.0 ) , and igg-4 ( 290 mg / dl , normal range 4.8105.0 ) .
abdominal computed tomography ( ct ) indicated a solitary soft tissue density mass of 4.5  6.0  11.0 cm in diameter located in the retroperitoneal space around the abdominal aorta ; the mass involved the left ureter and was associated with left hydronephrosis ( fig .
the patient first underwent the insertion of a ureteral stent for treatment of the left hydronephrosis .
for the definite diagnosis of this lesion , we performed a biopsy by laparotomy through a small incision in december 2010 .
histopathology revealed that the lesion was composed of abundant fibrosis with infiltrating lymphocytes and plasma cells not exhibiting nuclear atypia ( fig .
many igg4-positive plasma cells ( > 70 counts per high power field ) were observed with immunohistochemistry ( fig .
the ratio of igg4-positive to igg - positive cells was 41:100 ( fig . 2c ,
the initial dose of oral prednisolone was 30 mg / day , and the dose was tapered by 5 mg every 2 weeks ; the maintenance dose was 5 mg .
six months following his initial administration , the patient experienced steroid - related complications including impaired glucose tolerance and edema , and oral antidiabetic medication was initiated .
ct revealed a gradual decrease in the size of the lesion , with disappearance after 7 months of steroid therapy ( fig .
maintenance steroid treatment was also stopped at this time because the patient hoped to escape the steroid - related complications in addition to obtaining complete remission . after consulting with our hospital 's department of japanese oriental medicine ,
we started a 1.5-year course of hochuekkito , a kampo medicine , as an alternate maintenance treatment . at 3 years following the initiation of medical treatment , the patient was doing well ,
his steroid - related complications had improved , and he had not experienced a relapse .
rf was first reported by ormond in 1948 and has since been widely documented . when all identifiable causes are excluded , the condition is labeled idiopathic rf . some cases of idiopathic rf involve other idiopathic sclerosing lesions , a condition that has been referred to as multifocal fibrosclerosis in the past . based on recent studies of aip ,
a new entity of igg4-related systematic disease has been proposed [ 3 , 7 , 8 ] .
accordingly , multifocal fibrosclerosis is now considered an igg4-related disease . some individual cases and several case series of rf without obvious manifestations of aip
only the retroperitoneal space was observed to be affected , and no other sclerosing lesions were identified .
currently , a definitive diagnosis of igg4-related rf is based on the fulfillment of the following 3 criteria : ( 1 ) soft tissue masses surrounding the aorta and/or adjacent tissues on ct and/or magnetic resonance imaging , ( 2 ) elevation of serum igg4 levels ( 135 mg / dl ) , and ( 3 ) infiltration with igg4-positive plasma cells ( > 10 igg4-positive plasma cells per high power field and a ratio of igg4-positive to igg - positive cells of > 40:100 ) .
with regard to the radiological criterion , soft tissue masses located in the renal hilus frequently involve the ureter .
with regard to the histological criterion , histological findings from sites other than the retroperitoneal mass can be used , as performing biopsies of such masses is usually difficult .
although our patient 's mass was confined to the retroperitoneal space , we were able to biopsy the mass via minimal laparotomy and confirm the histological criterion .
the indications for steroid use are symptoms such as obstructive jaundice due to sclerosing cholangitis , abdominal pain , and hydronephrosis due to associated rf .
standard steroid treatment consists of an initial dose of 0.6 mg / kg / day of oral prednisolone , which is reduced to a maintenance dose ( 5 mg / day ) over a period of 36 months . to prevent relapse , maintenance treatment for 6 months to 3 years is recommended . in most cases ,
our patient received standard steroid treatment resulting in complete remission 7 months after starting medication .
however , maintenance treatment was stopped because of steroid - related complications such as impaired glucose tolerance . as an alternative to standard maintenance treatment
, we treated this patient with hochuekkito , which potentiated the immunomodulatory effect for 1.5 years , resulting in maintenance of remission for 3 years after medication was first initiated .
hochuekkito is a type of kampo ( i.e. traditional japanese herbal ) medicine , and it has been used to improve the weakened physical condition of patients with various chronic diseases .
moreover , hochuekkito has been reported to exhibit beneficial pharmacological immune activity [ 12 , 13 ] while suppressing the inflammatory response .
a recent study suggests that the preoperative administration of hochuekkito can prevent an excessive postoperative inflammatory response and prolonged postoperative immunosuppression .
we used hochuekkito in this patient with igg4-related rf as an alternative maintenance treatment to suppress the inflammatory response with fewer side effects than steroids . however , numerous questions remain regarding the details of hochuekkito 's mechanism of action on the immune system . in conclusion , we report a rare case of igg4-related rf with complete remission after steroid therapy .
hochuekkito , a kampo medicine associated with immunomodulation , was used as a maintenance treatment with few side effects , allowing the patient to escape steroid - related complications .
however , prospective studies are needed to clarify the details of the effect of hochuekkito on igg4-related disease .
we report a case of immunoglobulin g4 ( igg4)-related retroperitoneal fibrosis ( rf ) with complete remission and no relapses after therapy with steroids and hochuekkito , a kampo ( i.e. traditional japanese herbal ) medicine . 
 a 62-year - old japanese man was admitted to our hospital for treatment of a retroperitoneal mass detected by computed tomography . the mass had a maximum diameter of 11.0 cm 
 ; it involved the left ureter and was associated with left hydronephrosis . after inserting a ureteral stent , we performed a biopsy by laparotomy . 
 histopathology revealed igg4-related rf . 
 the lesion disappeared after 7 months of steroid therapy . 
 we subsequently used hochuekkito as an alternative maintenance treatment because of steroid - related complications . 
 the patient has not relapsed in the 3 years since starting the medication . to the best of our knowledge , 
 this is the first case of igg4-related rf treated with hochuekkito as a maintenance treatment .