A Wasting Syndrome and Malnutrition Caused by Small Intestine Fungal Overgrowth: Case Report and Review of the Literature

Abstract

Only a handful of case reports in the literature describe presence of Candida albicans in the gut of otherwise healthy subjects who were older adults and presented with gastrointestinal (GI) symptoms. In this article, the authors describe an interesting case report of a 48-y-old female with Sjogren’s syndrome and stage II cervical cancer complicated by a rectovaginal fistulae postradiation therapy requiring a colectomy and ileostomy, who presented with a wasting syndrome consisting of unresolving watery diarrhea and a 40-pound (18.14 kg) weight loss in the course of 5 mo. On physical exam, she appeared to be a thin, fragile female with wasting in the subscapular and sternocleidomastoid area with benign GI exam. An upper endoscopy was unremarkable for any significant pathological entity. A small bowel fluid aspirate was positive for overgrowth of Candida tropicalis and also was found to have anti-Candida immunoglobulin A. The patient was begun on central parenteral nutrition and she completed a 3-wk course of fluconazole. She was gradually weaned off total parenteral nutrition during the next 3 mo, with slow reintroduction of healthy whole foods and had appropriate weight gain and resolution of her GI symptoms. This case shows how important dietary interventions can be in managing malnutrition. Adding proper nutrients and slowly eradicating the dysbiotic fungi in the small intestine can help in resolution of GI symptoms and return to functional status.

The gastrointestinal (GI) microbiome is consequently composed of viruses, bacteria, and fungi in order of magnitude. The small intestine’s microbiome has a paucity of bacteria less than 10 000 microbes per milliliter of fluid with scantily detectable fungi by the culture of fewer than 100 fungi per milliliter.¹ Overgrowth of small intestine bacteria is also known as SIBO, which can be asymptomatic, have mild symptoms, or present as a full-blown malabsorption.² Small intestine fungal overgrowth (SIFO) occurs when excessive amounts of fungus populate the small bowel.³ SIFO is usually seen as part of an immunodeficiency syndrome with other GI manifestations such as oral and or esophageal candidiasis.⁴ Candida causing diarrhea has been frequently described in neonates, undernourished children, older patients, the severely or chronically ill, in intensive care units, or in patients on chronic antibiotic therapy.¹

Case Presentation

A 48-year-old female with Sjogren’s syndrome and stage II cervical cancer complicated by a rectovaginal fistulae post radiation therapy requiring a colectomy and ileostomy presented to the clinic with a wasting syndrome consisting of watery diarrhea and a 40-pound (18.14 kg) weight loss in the course of 5 months. She was seen by her primary care physician and was advised to increase the calorie intake and high-protein diet. She did not notice any improvement in her weight. Her diarrhea was also bothersome as it did not resolve. She was referred to gastroenterologist who assessed her condition thoroughly and recomended admission to the hospital for further management of her condition by not just treating her symptoms but also finding the root cause of her severe malnourishment.

Timeline.

On physical examination, she appeared to be a thin, fragile female with wasting in the subscapular and sternocleidomastoid area. Nontender, nondistended abdomen with colostomy bag was present without surrounding erythema, or discharge.

An upper endoscopy showed duodenal scalloping; however, biopsies were unremarkable for any pathological entity. A small bowel fluid aspirate was negative for bacterial overgrowth but positive for overgrowth of Candida tropicalis and also was found to have anti-Candida immunoglobulin A 2.7 times the upper limit of normal. The patient was begun on central parenteral nutrition (CPN) and closely monitored for refeeding syndrome and antifungals. She completed a 3-week course of fluconazole and her symptoms slowly improved and she started gaining weight. She was gradually weaned off total parenteral nutrition during the next 3 months, with slow reintroduction of healthy whole foods and returned to work by the fourth month postdischarge. She has regular follow ups and her weight increased up to 11 pounds (4.99 kg) with improvement of her diarrhea and malnutrition.

Discussion

Microbial colonization starts in the GI tract, since birth. Microbiota is established in the course of time in series of stages. It comprises of various types of microorganism. More than 99% of this microbiota consists of bacterial and Candida yeasts are detectable in 96% of neonates by the end of the first month of life.¹ The overgrowth of these microbes occur under various circumstances and cause GI symptoms. The amount of microorganisms increases as we proceed toward the colon with highest number in colon. Gastric acid secretion and intestinal clearance provide the qualitative and quantitative partitioning of intestinal bacteria; small intestinal bacteria overgrowth (SIBO) occurs when these barrier mechanisms fail.² The mechanism by which Candida overgrowth causes diarrhea is unknown. There are multiple theories but none has substantial evidence to validate itself. The patient was without an intact ileocecal valve, which may explain the colonization of the small bowel with a colonic commensal fungus. The therapeutic approach to SIBO is oriented toward resolving predisposing conditions and is supported by antibiotic treatment to restore the normal small intestinal microflora and by modifications of dietary habits for symptomatic relief.²

Our patient did not have gross or histological evidence of a fungal infection; however, the small bowel aspirate demonstrated hyphae and cultures confirmed the diagnosis of SIFO, which was appropriately treated with antifungal medication. Incidence of invasive fungal infections increases in time with the rise in at-risk populations (in particular, patients with acquired immunodeficiencies due to immunosuppressive therapies).⁵ Fungal infection, particularly candidiasis, is well known to cause GI symptoms in patients with underlying diseases such as cancer.⁵

There are only rare case reports in the literature regarding the presence of Candida albicans, in the gut of otherwise healthy subjects who were older adults.^6,7 Overall, those who present with GI candidiasis have prompt resolution of symptoms after antifungal treatment with azole antifungals, especially fluconazole for 2 to 3 weeks.⁴ The clinical presentation of Candida-induced diarrhea is similar to the presentation of other types of intestinal infection and physical examination findings are also not very helpful in differentiating it from other forms of infectious diarrhea.⁷ Rao and colleagues⁸ present an intriguing case series of patients who presented with unexplained SIBO-like symptoms with dyspepsia, gas, bloating, diarrhea and had positive jejunal fluids for microbial dysbiosis.

A total of 150 subjects were evaluated via nasojejunal fluid aspirates for culture with 94/150 or 63% having a small intestine microbial overgrowth, of which 38/94 (40%) had SIBO, 24/94 (26%) had SIFO, and 32/94 (34%) had mixed SIBO/SIFO. These investigators reported that use of proton pump inhibitors and GI dysmotility were independent risk factors for both SIBO and SIFO. Our patient did not appear to have an underlying connective tissue disease associated with dysmotility and her gastric pH was 2.0 on testing.

Intestinal candidiasis has been linked to a myriad of systemic symptoms that overlap with SIBO, such as migraines, fatigue, depression, bloating and more.⁹ If aspiration of small bowel fluids is not available, many are now using urinary organic acids such as D-arabinitol to confirm that fungal overgrowth may be responsible.¹⁰ Once thought commensual, GI fungi such as C tropicalis may play a causative role in autoimmunity.^11,12 Interestingly, in a study, analysis of the gut bacteriome and mycobiome in patients with Crohn’s disease, among hundreds of bacterial and fungal species residing in the gut, large-scale sequencing and bioinformatics showed the association between a fungal species (C tropicalis) and 2 bacterial species (Serratia marcescens and Escherichia coli).¹¹

Our patient is a unique example of how important dietary and lifestyle interventions can be in managing malnutrition. Adding proper nutrients and slowly eradicating the dysbiotic fungi in the small intestine helped her in restoring small bowel absorptive capacity leading her to adequate weight gain and return to functional status. Currently, most of the SIFO cases and studies in the literature have reported C albicans but only a handful of them reports C tropicalis. Further studies are needed to establish more concrete guidelines for diagnosing and managing SIFO.

Patient Perspective

“My odyssey started in 2008 when I began wasting away due to excessive weight loss and malnutrition. I was prescribed a high protein diet, calorie filled foods and was advised to eat more. I still was losing weight and had lost hope. Then after meeting Dr Mullin I had the confidence that he was the doctor who could save my life. He wanted to find the root cause of my problems instead of jumping to simply treat my symptoms. He wanted to do further testing, therefore he recommended getting admitted to the hospital. Dr Mullin’s willingness to communicate at every step and taking into account my impressions and thoughts on what was happening to my body made aware of his thought process. After running few tests Dr Mullin had answers to my questions. He worked with me to map out a plan for my recovery and talked extensively about diet and lifestyle changes that would aid in my overall health. I was stunned that a doctor would take such a huge amount of time with me to ensure that I had only the best care.

Today I am amazingly healthy and my weight is up where it belongs, and Dr Mullin continues to consult with me and check in on my health and condition. At last I would say that a doctor’s wisdom and patience while working on my condition saved my life.”

Biographies

Rajdeep Singh, MD, is gastroenterologist at Sinai Hospital of Baltimore in Baltimore, Maryland

Gerard E. Mullin, MD, is an associate professor of medicine at Johns Hopkins School of Medicine and Sinai Hospital of Baltimore in Baltimore, Maryland.