Iron-Related Pseudomelanosis Duodeni in a Patient with Gastrointestinal Bleeding: A Case Report

Introduction

Pseudomelanosis duodeni (PD) is a rare incidental endoscopic finding characterized by flat, discrete speckles of dark pigment, usually found in the proximal duodenum [1]. It was first documented incidently in 1976 by Bisordi and Kleinman [2] as “melanosis duodeni”, since the dark pigment detected was thought to be composed of melanin. This pigment was then found to be formed mainly by ferrous sulfide accumulation in macrophages located in the lamina propria [1]. PD occurs primarily in middle-aged or older adults, particularly females, but pediatric cases have been also reported [3]. According to the literature, PD was associated with chronic conditions like end-stage renal disease, hypertension, or diabetes and with certain medications like oral iron supplements and sulfur-containing antihypertensives [4]. To date, PD is considered benign and has not been associated with any malignancy. We herein present the case of a middle-aged female patient on oral iron supplements who was found to have PD on endoscopy.

Case Report

A 56-year-old female patient was admitted with lower abdominal pain and intermittent rectorragia. Her past medical history was positive for peptic ulcer disease and iron-deficiency anemia, treated with oral iron supplements. The patient’s home medications consisted solely of proton pump inhibitors and oral iron supplements, and she did not take any sulfur-containing medications. Laboratory test results were pertinent for microcytic anemia, with a hemoglobin level of 8 g/dL (reference range 12–16 g/dL) and a mean corpuscular volume of 73 fL (reference range 80–100 fL). On physical examination, vital signs were stable, with no hypotension or tachycardia, and the rectal examination showed prolapsed internal hemorrhoids, with a small amount of brown stools, which were guaiac-positive. Given the patient’s clinical presentation, a colonoscopy was performed to identify the source of the bleeding and to rule out any possible underlying malignancy or other chronic disorders, such as inflammatory bowel disease. Colonoscopy showed large internal hemorrhoids. One pocket was severely congested and with stigmata of recent bleeding. Esophagogastroduodenoscopy showed no active or stigmata of recent gastrointestinal bleeding. Examination of the duodenal bulb and the descending part (D2) of the duodenum showed abnormal mucosa with multiple pinpointed and punctate black spots and speckled pigmentation (Figure 1). The pigmentation was permanent and did not change with water irrigation. Biopsies from the duodenum showed edematous villosities and large clusters of pigmented macrophages, with golden-brown cytoplasm positively stained with Perl’s Prussian blue stain, indicating the presence of iron inside the macrophages. These findings confirmed the diagnosis of PD. The patient underwent a closed hemorrhoidectomy procedure during the same admission, in which hemorrhoids were excised using a sharp scalpel, and closure of the wound then subsequently ensued.

Discussion

PD is a rare endoscopic finding of the duodenum characterized by multiple pigmented black-dotted mucosa along the apex of the duodenal villi [4]. The pigment in PD is composed primarily of iron and sulfur, and varying amounts of other components, including magnesium, silver, aluminum, and calcium, with iron being the main component, as seen in Perl’s Prussian blue stain [4,5]. Hirai et al [3] reported a case of PD in a patient with chronic renal disease and hypertension before and after 2 years of oral iron therapy. This was the first case to report on the endoscopic appearance of PD before and after oral iron therapy [5]. Lopez et al [4] suggested that iron alone is not sufficient for pigmentation, but rather an interplay between sulfur and iron is needed. The proposed explanation for this hypothesis is that coupling of iron and sulfur causes difficulty in iron transportation and results in their accumulation in macrophages, leading to pigment formation [3]. The presence of sulfur in patients with hypertension appears to arise from using sulfur-containing antihypertensive drugs [3]. Moreover, Deliwala et al [6] reported a case of PD in a patient with end-stage renal disease after dialysis. This is due to renal functional impairment and decreased clearance, leading to the accumulation of sulfur or iron [4].

This case is unique as it presents a finding of PD along with lower gastrointestinal bleeding manifesting as hemorrhoids. PD has been reported in cases of gastrointestinal bleeding but not in cases of hemorrhoids, as observed in our patient. The hypothesis behind these findings is related to iron accumulation in the duodenum secondary to chronic bleeding and excessive iron release. However, given the anatomical nature of hemorrhoids, it is less likely that bleeding from this site would lead to iron accumulation and deposition in the duodenum. The fact that our patient was on oral iron therapy in the absence of chronic renal disease or the use of antihypertensive drugs rendered oral iron the most likely culprit in the development of PD. The diagnosis of PD is based on the endoscopic findings of discrete pigmentation in the duodenum along with histological findings. On histology, those black specks appear as pigment-laden macrophages in the lamina propria of duodenal villi [7]. To minimize the financial burden of unnecessary tests, physicians should be familiar with the diagnosis of pseudomelanosis.

Apart from in the duodenum, pseudomelanosis has also been reported in the esophagus and stomach. Regardless of its location, the etiology remains consistently the same. Issac et al [8] reported a case of pseudomelanosis esophagi complicated by pseudoachalasia. In this case, the etiology was attributed to the drug hydrazaline.

Melanosis coli is another pigmentation disorder that can present similarly to PD but affects the colon rather than the duodenum and is typically caused by chronic laxative intake [4]. Histologically, the pigment in PD is composed mainly of iron and varying amounts of other components, including magnesium, silver, aluminum, sulfur, and calcium [5]. On the other hand, pigments in melanosis coli are secondary to lipofuscin accumulation in macrophages [5]. Moreover, unlike PD, which has no clinical significance, melanosis coli has been observed in patients with colon cancer.

PD is generally considered a benign condition with no subsequent complications or reported death cases or any link to malignancy [6]. To date, withdrawing oral iron therapy or hypertensive drugs in patients with PD is not indicated, as this clinical feature is asymptomatic and requires no treatment. Thus, further prospective studies and observations are needed to assess the long-term outcomes of this disorder.

Conclusions

PD is a benign disorder of the duodenum associated with oral iron therapy, end-stage renal disease, and sulfur-containing antihypertensive drugs. To date, no known complications or deaths related to PD have been reported. Recognizing PD on endoscopy and biopsy is crucial to distinguish it from other more serious pathologies that might look similar, such as gastrointestinal bleeding. Further studies with large sample sizes and long follow-up periods are needed to investigate the long-term outcomes and grave consequences resulting from chronic iron accumulation in the gastrointestinal system and to formulate optimal management strategies.