Gastroduodenal Strongyloidiasis Diagnosed during Iron Deficiency Anemia Workup Open Access

The Strongyloidae family includes at least fifty species of intestinal nematode worms, and Strongyloides stercoralis is the most prevalent nematode among humans, causing strongyloidiasis [1, 2]. This infestation is more prevalent in tropical and temperate climates, including Eastern, Southern, and Central Europe, Southeast Asia, sub-Saharan Africa, Caribbean Islands, and Latin America [3]. Nevertheless, immigration from endemic areas has contributed to its spread to developed countries [4‒7]. In immunocompetent individuals, the infestation is commonly undiagnosed as infect patients are generally asymptomatic for decades. On the other hand, in immunodeficient patients, such as those with a history of allograft transplants, cancer, or acquired immunodeficiency syndrome, and those receiving long-term corticosteroid therapy, the subclinical dormant infestation can progress to the hyperinfection stage [8]. As part of this stage, the dormant rhabditiform larvae in the duodenal submucosa evolve into filariform larvae that migrate through different organs and transfer with them enteric organisms, culminating in life-threatening sequelae, including gram-negative bacteremia [9].

In this case report, we describe the case of an asymptomatic and immunocompetent Liberian patient with gastroduodenal strongyloidiasis whose diagnosis was made based on histologic findings during the endoscopic evaluation of chronic iron deficiency anemia. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000539769).

The patient was a 53-year-old African American male patient who was born in Liberia and who moved to the USA at 18 years of age. He was seen at the gastroenterology clinic for evaluation of iron deficiency anemia. His past medical history was significant for uncontrolled type II diabetes mellitus hypertension, beta thalassemia minor, and chronic iron deficiency anemia. He had no pertinent social or family history.

On presentation, the patient had no fatigue, abdominal discomfort, nausea, vomiting, change in appetite, weight loss, or change in bowel movements (constipation, diarrhea, melena, or hematochezia). Physical exam including a digital rectal exam was unremarkable. Complete blood count (CBC) from a recent visit to the primary care physician’s office revealed microcytic anemia with an Hb of 10.5 g/dL (normal = 12.0–16.0 g/dL) and a mean corpuscular volume of 70 fL (normal = 80–100 fL). No previous iron studies were present in the chart. The white blood cell count was normal at 6,580 cells/μL, but there was evidence of peripheral eosinophilia with an eosinophil count of 2,060 cells/μL (31.3%; n = 0.3–5.9%). Three years ago, CBC was significant for microcytic anemia, with Hb of 10.0 g/dL, a white blood cell count of 7,130 cells/μL, and an eosinophil count of 1,850 cells/μL (26%). All other CBC findings were unremarkable including a platelet count (352 K/μL). No prior human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV) testing was performed.

Given his chronic iron deficiency anemia, the patient was scheduled for a colonoscopy and an esophageal gastroduodenoscopy (EGD) to rule out any organic pathology. EGD revealed diffuse erythema and mucosal atrophy but was otherwise unremarkable (Fig. 1a, 2a). Histopathology of biopsies taken from the stomach and duodenum revealed fragments of gastric and duodenal mucosa with many cross-sections of S. stercoralis, eosinophilic inflammatory infiltrate, and marked reactive changes (Fig. 1b, 2b).

The colonoscopy revealed granular lesions along the cecum and the ascending colon. The granularity was very subtle and was not easily discernible with white light and better visualized under narrow band imaging (Fig. 3a). Biopsies revealed an eosinophilic inflammatory infiltrates, chronic inflammation, and tissue reactive changes. There were hyperplastic changes in the cecum and lymphoid aggregates in the ascending colon. These findings are nonspecific findings that support the diagnosis of a parasitic infestation.

After the diagnosis of strongyloidiasis was confirmed, the patient completed a 2-day course of ivermectin. On 3-month follow up, his Hb improved to 12.4 g/dL. Additionally, his hyper-eosinophilia improved to eosinophilia as his eosinophilic counts dropped from 2,340 eos/mL (37.6%) before treatment to 890 eos/μL (15.9%) (normal range <500 eos/μL). Iron studies were checked and revealed a ferritin of 100 ng/mL, a total iron of 64 μg/dL, a transferrin saturation of 20%, and a total iron-binding capacity of 285 μg/dL. Unfortunately, there were no prior iron studies to compare the pre- and post-treatment results.

S. stercoralis has a unique and complex lifecycle composed of free-living, parasitic, and autoinfection cycles. After the rhabditiform larvae in stool mature into filariform larvae, they infect human hosts by penetrating their skin from the soil. The larvae then migrate via the bloodstream to the lungs and the tracheobronchial tree to end up in the duodenal submucosa after being swallowed by the host. The filariform larvae mature into female adults in the intestines where they lay eggs that hatch into rhabditiform larvae. The latter end up being shed in feces to either turn into free-living adults in soil (free-living cycle) or to reinvade the human host through the perianal skin or intestinal mucosa (autoinfection). In this way, rhabditiform larvae can turn into infective filariform larvae and complete their formation in the intestines without an exogenous host (autoinfection). They can then migrate through the intestines into the lungs and the tracheobronchial tree to repeat their life cycle and replicate in their host. If left untreated, this can result in persistent infestation, even after the host resides in a non-endemic area without exogenous exposure for several years [10].

Our patient was born in Liberia and had diabetes mellitus type II. He was infested with S. stercoralis and remained clinically asymptomatic, despite iron deficiency anemia and eosinophilia being suggestive of an underlying parasitic infestation. In healthy individuals, infestation can remain clinically dormant for years. Immunocompromised patients, such as those with HIV and HTLV infections or those requiring immunosuppressive medications, can be affected by Strongyloides hyperinfection syndrome [5‒7, 11, 12]. The dormant rhabditiform larvae in the duodenal submucosa can evolve into filariform larvae. These migrate through different organs including the intestines, lungs, the meninges, the myocardium, and the urinary tract, resulting in pneumonia [13], meningitis [14], and polymicrobial gram-negative sepsis [15] as they carry and transfer enteric organisms with them from the intestines [9].

Larval identification in stool remains the gold standard for diagnosing strongyloidiasis. The larval output in stool samples is very low due to the intermittent shedding; hence, the sensitivity is low. There are techniques to improve larval detection in stool including the use of formalin-ethyl acetate concentration, saline-Lugol iodine stain, and nutrient agar plate cultures. Diagnostic serological antibody assays are sensitive but not specific because of their cross-reaction with other parasitic organisms, such as Ascaris, and are generally of limited utility due to their inability to distinguish an acute infestation from a chronic one. Newly emerging serological tests now utilize recombinant antigens which have proven to be more sensitive and specific than previously used assays [16]. In our patient, no relevant stool studies were performed prior to endoscopic evaluation.

Peripheral eosinophilia is useful in suggesting a parasitic infestation but has not proven to be a consistent finding in chronic strongyloidiasis. Although it is considered as a good marker of S. stercoralis infestation, it is not sensitive enough to be used as a screening test for strongyloidiasis [17, 18]. In a study by Koczka et al. [12], seventeen out of twenty-two confirmed strongyloidiasis cases had peripheral eosinophilia. The fact that our patient comes from an endemic country and has had chronic eosinophilia and iron deficiency anemia for years should have raised the concern for a helminthic infestation years ago. Strong consideration for the possibility of underlying strongyloidiasis should be taken in such cases. Aggressive intervention should be implemented in cases immunosuppressive therapy is to be initiated (example: steroid or anti-tumor necrosis factor therapy in inflammatory bowel disease, tocilizumab, or steroids for COVID-19 infection treatment).

Endoscopic findings in strongyloidiasis are usually nonspecific. When the stomach is involved, gastric fold thickening and mucosal erosions and ulcerations might be noted. When the duodenum is involved, endoscopic findings might include erythematous spots, ulcerations, swelling, and megaduodenum [19, 20]. In addition to gastritis with lymphocytic, eosinophilic, and plasma cell infiltration in the lamina propria, histopathology may reveal parts of the adult worms, larvae, or eggs [21‒23]. While the adult female worm measures 2–3 mm × 30–60 μm, the rhabditiform larva measures 200–300 μm × 10–20 μm and the filariform larva measures 300–600 μm × 10–20 μm. Identification of the worm in gastric biopsies is very rare. Interestingly, our patient’s most unusual finding was the granular tissue in the colon which did not reveal any confirmatory pathologic findings, while the nonspecific EGD findings were associated with organisms on pathology. Ivermectin is the current treatment of choice for strongyloidiasis [24‒26]. The recommended treatment regimen consists of 200 mg/kg of ivermectin for two consecutive days [16, 23]. A negative stool sample or serology after 6 months of treatment usually helps confirm the eradication of the infestation [27]. Although not very reliable, the presence of eosinophilia after the completion of treatment might imply persistence or recurrence of the infestation.

In the case of disseminated strongyloidiasis, the mortality rate can be as high as 90% despite aggressive therapy [28]. The combination of ivermectin and antibiotics with gram-negative coverage can be administered for at least 2 weeks until the patient becomes asymptomatic and daily stool samples fail to show evidence of the parasite for at least 2 weeks. All patients should be screened for an underlying immunosuppressive condition, such as HIV or HTLV infection [8].

In conclusion, we described a case of gastroduodenal strongyloidiasis diagnosed histologically on gastric and duodenal biopsies. Pathology showed the strongyloides nematode and eosinophilic inflammatory infiltrates. From this respect, this case sheds light on the importance of suspecting the diagnosis of disseminated strongyloidiasis in high-risk individuals with iron deficiency anemia in combination with peripheral eosinophilia.

The completion of this research paper was done without the help of artificial intelligence-assisted technologies or nonauthor contributors.

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

The authors declare no conflicts of interest.

The authors declare no grants or financial support for the research, authorship, and publication of this article.

J.M.C., S.A., N.M., and H.A.M. managed the patient at the hospital. M.K., J.M.C., S.A., N.M., L.K., and H.A.M. performed the literature review and carried out the drafting of the manuscript and its critical revision. R.C. provided the pathology slides and incorporated them into the manuscript.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.