intestinal pseudomelanosis is a condition characterized by dark pigmentation of the intestinal mucosa , such as colon , small bowel , and stomach . among intestinal pseudomelanosis ,
melanosis coli is the most common and a well known condition , which occurs with the laxative use , especially anthraquinone containing laxatives .
the dark brown pigmentation of melanosis coli is actually lipofuscin in macrophages and not melanin ( 1 ) .
interestingly , extracolonic pseudomelanosis has also been rarely reported in the literature ( 2 , 3 ) and several etiologies have been suggested for the development of extracolonic pseudomelanosis .
most commonly reported location of extracolonic pseudomelanosis is the duodenum , although it can also be found on the mucosa of the stomach , jejum or ileum ( 2 - 4 ) .
in addition , few reports on pseudomelanosis ilei have attributed its cause to chronic oral iron therapy , but the association is still unclear ( 2 , 5 ) .
few reports showed that there are considerable association with end stage renal disease and hypertension ( 3 ) .
herein , we describe 6 cases of the small bowel pseudomelanosis with possible etiology being chronic iron intake .
the cases included one man and 5 women , with a mean age of 62 yr ( median 69.5 , range 34 - 73 ) .
summary on endoscopic findings , associated medical conditions , and concurrent medications of the subjects are shown in table 1 .
five ( 83% ) patients had chronic kidney disease , 2 of whom were undergoing peritoneal dialysis , 5 ( 83% ) patients had hypertension , and 3 ( 50% ) patients had diabetes mellitus .
various classes of antihypertensive medication including beta blockers , thiazides , angiotensin receptor blockers , and calcium channel blockers were being taken by the hypertensive patients .
other common medications included statin ( hmg - coa reductase inhibitor ) and potassium binder .
all patients had been taking iron sulfate for an average of 32.8 months ( 13 - 66 months ) .
four patients underwent both upper and lower endoscopy , and the remaining two underwent upper endoscopy or colonoscopy .
numerous brown spots were observed on the mucosa of terminal ileum in 3 patients , duodenum in 1 patient , jejunum in 1 patient , and both duodenum and terminal ileum in 1 patient ( fig .
the patient had undergone subtotal gastrectomy with billroth ii reconstruction due to early gastric cancer .
biopsies were taken during endoscopy and specimens were stained with hematoxylin and eosin and also stained for iron .
histology revealed pigment deposition within macrophages of the lamina propria and a positive prussian blue stain indicated hemosiderin deposition ( fig .
the cases included one man and 5 women , with a mean age of 62 yr ( median 69.5 , range 34 - 73 ) .
summary on endoscopic findings , associated medical conditions , and concurrent medications of the subjects are shown in table 1 .
five ( 83% ) patients had chronic kidney disease , 2 of whom were undergoing peritoneal dialysis , 5 ( 83% ) patients had hypertension , and 3 ( 50% ) patients had diabetes mellitus .
various classes of antihypertensive medication including beta blockers , thiazides , angiotensin receptor blockers , and calcium channel blockers were being taken by the hypertensive patients .
other common medications included statin ( hmg - coa reductase inhibitor ) and potassium binder .
all patients had been taking iron sulfate for an average of 32.8 months ( 13 - 66 months ) .
four patients underwent both upper and lower endoscopy , and the remaining two underwent upper endoscopy or colonoscopy .
numerous brown spots were observed on the mucosa of terminal ileum in 3 patients , duodenum in 1 patient , jejunum in 1 patient , and both duodenum and terminal ileum in 1 patient ( fig .
the patient had undergone subtotal gastrectomy with billroth ii reconstruction due to early gastric cancer .
biopsies were taken during endoscopy and specimens were stained with hematoxylin and eosin and also stained for iron .
histology revealed pigment deposition within macrophages of the lamina propria and a positive prussian blue stain indicated hemosiderin deposition ( fig .
small bowel pseudomelanosis is a finding that is rarely encountered during endoscopy and its etiology is still not fully understood ( 3 , 5 ) . whereas melanosis coli is relatively common condition occurring in more than 70% of persons who use anthraquinone containing laxatives , pseudomelanosis of
although examination of the small bowel has been facilitated with the introduction of capsule endoscopy ( ce ) or double balloon endoscopy ( dbe ) , pseudomelanosis of the small bowel is still a rare finding . a portuguese center with experience of more than 600 ce and 100 dbe reported only two cases of small bowel pseudomelanosis ( 2 ) ; one case showed pigmentation in the entire small bowel and the other case in the ileum ( 6 ) . in korea ,
pseudomelanosis duodeni or ilei has been reported sporadically in 7 cases in patients taking oral iron ( 7 - 9 ) .
interestingly , 6 cases of pseudomelanosis ilei associated with charcoal ingestion have been reported only in korea ( 10 - 14 ) . in our case series ,
all patients had been taking oral iron at the time of upper or lower endoscopy . of the 6 cases ,
3 had undergone upper and lower endoscopy before initiating iron therapy , which revealed normal mucosa without pigmentation on duodenum and terminal ileum .
therefore , the cause of pseudomelanosis of small bowel in these patients could be attributed to oral iron therapy .
apart from oral iron therapy , other possible causes of small bowel pseudomelanosis include chronic kidney disease , hypertension , and certain medications like antihypertensive drugs ( 3 , 15 ) .
it has been hypothesized that coupling of absorbed iron with a sulfur moiety from antihypertensive medications could be the underlying mechanism for pigment accumulation in macrophages of small bowel mucosa ( 2 ) .
fernando ( 16 ) demonstrated that absorbed iron coupled with sulfur in pseudomelanosis duodeni , using electron probe x - ray analysis of epithelial cells and macrophages at different levels of the intestine .
he proposed that this coupling results in impaired iron transport that leads to the accumulation of ferrous sulfates .
as for the source of sulfur , antihypertensive medications such as furosemide and hydrochlorothiazide which contain sulfur moiety have been implicated ( 17 , 18 ) . typically , the biopsy specimen shows dark brown to black granular deposits in the lamina propria of the tips of intestinal villi , and the deposits often contain iron as hemosiderin in ferric or ferrous form ( 19 ) .
a recent retrospective study showed that pigment - laden macrophages were sometimes observed even when it was not apparent during endoscopy ( 3 ) . in another case of pseudomelanosis
in which there were pigmentations from stomach to jejunum , review of previous histopathology slides from antral ulcer two years earlier revealed granular pigment in the lamina propria with positive stain for iron ; however , pigmentation was not evident endoscopically at that time ( 20 ) .
it could be postulated that duration of iron therapy is associated with the development of pseudomelanosis in the small bowel and determines its extent , but this association could not be validated possibly due to the small sample size .
although the causes of pseudomelanosis of the small bowel and its underlying mechanism are still unknown , our case series with a relatively large number of patients suggests that there could be a likely association between pseudomelanosis of the small bowel and chronic oral iron therapy .
 an accumulation of pigment deposits on mucosa , called melanosis or pseudomelanosis , of the small bowel is observed infrequently during endoscopic examination . 
 we describe 6 cases of small bowel pseudomelanosis ; the possible etiology of which was chronic iron intake . 
 we observed numerous brown spots in duodenum , jejunum , and terminal ileum during upper and lower endoscopy . 
 interestingly , all patients have been taking oral iron for several years . 
 histology showed pigment depositions within macrophages of the lamina propria and a positive prussian blue stain indicating hemosiderin deposition . 
 herein , we demonstrate that long term iron therapy may result in pseudomelanosis of small bowel , such as duodenum , jejunum , and ileum . 
INTRODUCTION
CASE DESCRIPTION
Clinical findings
Endoscopic findings
Pathologic findings
DISCUSSION