Intestinal giardiasis and spirochetosis causing unintentional weight loss in a 40-year-old man

Key points

• The differential diagnosis for unintentional weight loss is wide, and infectious causes should be considered in the appropriate clinical setting.

• Taking a comprehensive history is important when evaluating weight loss, particularly a detailed travel, exposure, and sexual history.

• Infections with enteric pathogens, such as giardiasis and spirochetosis, may occur through exposure to contaminated water or food, and direct or indirect oral–anal sexual contact.

• A high index of suspicion for enteric infection should be maintained among those with unintentional weight loss and associated relevant risk behaviours or exposures, and dedicated testing should be pursued accordingly.

A 40-year-old man was referred to our internal medicine clinic for assessment of a 3-month history of unintentional weight loss and daily night sweats with subjective fevers. He had been treated for rectal chlamydia infection 1 month prior. He had lost about 6 kg, from a baseline weight of 75 kg to 69 kg (8% body weight loss). He had chronic low back stiffness, but no ocular, skin, or other autoimmune symptoms. His review of systems was negative, including no gastrointestinal symptoms, mood changes, or dietary modifications. He had a family history pertinent for Crohn disease. His only regular medication was pre-exposure prophylaxis therapy for HIV prevention. He reported use of alcohol, cannabis, amyl nitrite, and MDMA (3,4-methylenedioxymethamphetamine), and he did not use intravenous drugs. His sexual history was pertinent for oral–anal sexual activity with multiple male partners.

When we saw the patient in clinic, his physical examination was unremarkable, including a normal rectal examination. The results of his initial laboratory tests, microbiology, and imaging were normal (Table 1). As the diagnosis remained unclear, we subsequently ordered laboratory autoimmune tests and lumbar radiography, given his low back stiffness, to assess for an inflammatory arthritis. These investigations had normal results (Table 1). We also ordered computed tomography (CT), with contrast enhancement, of the chest, abdomen, and pelvis to assess for malignancy, which showed evidence of proctitis (Table 1).

Table 1:

Results of the initial workup for unintentional weight loss in a 40-year-old man

Test	Result
Laboratory
Hemoglobin, g/L	136 (normal 115–155)
Leukocyte count, × 109/L	5.7 (normal 3.5–10.5)
Platelet count, × 109/L	170 (normal 125–400)
Thyroid-stimulating hormone, mIU/L	1.13 (normal 0.4–4.8)
Hemoglobin A1c, %	5.3 (normal < 6.0)
Erythrocyte sedimentation rate, mm/h	2 (normal 0–15)
C-reactive protein, mg/L	1.5 (normal < 11.0)
Electrolytes and extended electrolytes
Sodium, mmol/L	144 (normal 135–145)
Potassium, mmol/L	4.5 (normal 3.5–5)
Calcium, mmol/L	2.19 (normal 2.1–2.5)
Albumin, g/L	43 (normal 35–50)
Magnesium, mmol/L	0.92 (normal 0.65–1.05)
Phosphate, mmol/L	0.91 (normal 1–1.5)
Renal function
Serum creatinine, μmol/L	89 (normal 50–110)
Liver enzymes
Aspartate transaminase, IU/L	14 (normal 7–40)
Alanine transaminase, IU/L	16 (normal 5–35)
Alkaline phosphatase, IU/L	73 (normal 40–160)
Total bilirubin, μmol/L	6 (normal 3–22)
Antinuclear antibody, rheumatoid factor, and complement levels	Negative
Microbiology
Gonorrhea and chlamydia	Negative (urine, rectal, and pharyngeal testing)
HIV	Negative
Syphilis	Negative
Hepatitis B and C	Negative
Imaging
Chest radiography	Normal
Lumbar radiography	Normal (no erosive or inflammatory sacroiliitis)
CT chest	No evidence of thoracic malignancy or infection
CT abdomen and pelvis	Evidence of proctitis

Note: CT = computed tomography.

Given the patient’s symptoms, CT findings of proctitis, and risk factors (prior rectal chlamydia infection and ongoing anal intercourse), we made a presumptive diagnosis of lymphogranuloma venereum (LGV) as the cause for his ongoing weight loss. About 1 month after his initial presentation, results from repeat urine and rectal chlamydia and gonorrhea testing were negative, but we prescribed a 3-week course of empiric oral doxycycline 100 mg twice daily and also referred him to a gastroenterologist for endoscopic evaluation because of his persistent symptoms. Given the presence of proctitis, the gastroenterologist completed a bidirectional endoscopic evaluation about 8 weeks after his initial presentation to assess for inflammatory bowel disease and enteric infections, as well as sexually transmitted infections (STIs). Gastrointestinal malignancy and malabsorption related to celiac disease were also considerations, given the patient’s weight loss, but suspicion for these was low. With the exception of a 5-mm rectal aphthous ulcer and surrounding erythema, his endoscopies were normal. Tissue samples of the rectal ulcer and normal mucosa throughout the gastrointestinal tract were obtained for biopsy. In light of the initial endoscopic findings, the gastroenterologist considered the patient’s presentation to be most consistent with an STI (LGV), with a low likelihood for gastrointestinal disease.

However, the duodenal histology results eventually showed giardiasis, and the colonic and rectal histology results showed spirochetosis (Figure 1). At that point, further history revealed that he had consumed unfiltered water during a trip to the Caribbean 2 months before the onset of his weight loss. The gastroenterologist prescribed a 7-day course of oral metronidazole 500 mg twice daily. With completion of antimicrobial therapy, the patient’s night sweats and subjective fevers resolved, and his weight increased to about 71 kg, which has been stable during a year of follow-up.

Figure 1:

(A) Duodenal mucosa of a 40-year-old man with pear- and sickle-shaped trophozoites loosely floating at the epithelial surface (yellow arrows) (immunohistochemical stain). (B) Colonic mucosa with a dense colonization of spirochetes at the epithelial surface forming a “false brush border” appearance (red arrow) (colon Warthin–Starry stain).

Discussion

Unintentional weight loss is frequently seen in both inpatient and ambulatory care settings, and is clinically important when a decline of at least 5% in total body weight has occurred.^1,2 The differential diagnosis for unintentional weight loss is broad and can be categorized into several different causes (Box 1).^1,3 A comprehensive diagnostic workup is indicated to assess for underlying disease. Although ruling out malignancy is of high priority, additional investigations should be guided by the clinical presentation and risk factors.

Box 1: Causes of unintentional weight loss .

• Neoplasm (e.g., solid tumour and hematologic)

• Gastrointestinal diseases (e.g., inflammatory bowel disease, peptic ulcer disease, and malabsorption related to celiac disease)

• Endocrine disorders (e.g., diabetes, hyperthyroidism, and adrenal insufficiency)

• Infections (e.g., viral, bacterial, fungal, and parasitic)

• Connective tissue diseases (e.g., acute and chronic autoimmune diseases)

• Neurologic disorders (e.g., Parkinson disease, dementia, stroke, and multiple sclerosis)

• Cachexia in the setting of advanced chronic diseases (e.g., severe chronic obstructive pulmonary disease, severe congestive heart failure, and progressive renal disease requiring dialysis)

• Psychiatric disorders (e.g., depression)

• Substance use or medication side effects

• Social factors (e.g., poor socioeconomic status and food insecurity)

Among organic, nonmalignant causes, gastroenterological disorders are the most common etiology for unintentional weight loss, but occult infections are also an important cause.³ Giardia lamblia (Giardia intestinalis or Giardia duodenalis) is the intestinal protozoal organism implicated in human giardiasis. Giardiasis is commonly seen in those with exposure to endemic areas — usually resource-limited regions — as well as to contaminated water or food.⁴ Once contracted, it is associated with a spectrum of manifestations, varying from minimal-to-no symptoms, gastrointestinal symptoms such as diarrhea, and systemic symptoms such as weight loss.

Brachyspira species (Brachyspira aalborgi or Brachyspira pilosicoli) are the organisms implicated in human intestinal spirochetosis, which commonly occurs in resource-limited regions (given the increased risk for consumption of contaminated water or food), but can also be found in individuals residing in high-income countries (particularly among men who have sex with men).^5,6 Similar to G. lamblia, human intestinal spirochetosis is associated with varying clinical presentations, ranging from asymptomatic colonization, to diarrhea, to rectal bleeding, and to weight loss. Although it is often asymptomatic and an incidental finding observed during colonoscopy, its symptoms can be serious, regardless of the severity of pathology noted on biopsy (Box 2).⁸

Box 2: Evaluation of giardiasis and human intestinal spirochetosis .

• Risk factors

  • Exposure to endemic areas (area of residence or via travel)

  • Exposure to contaminated water or food

  • Direct or indirect oral–anal sexual contact

• Clinical presentation

  • Asymptomatic

  • Gastrointestinal symptoms (e.g., diarrhea)

  • Systemic symptoms (e.g., weight loss)

• Diagnosis

  • Human giardiasis: stool antigen assay or NAAT, or endoscopy with biopsy (which shows trophozoites at the surface of or invading through intestinal mucosa⁷)

  • Human intestinal spirochetosis: endoscopy with biopsy (which shows a diffuse fringe of spirochetes along the intercryptal epithelial layer)⁸

  • In both infections, pathology typically contributes to diagnosis more than endoscopic appearance, as endoscopic findings may be minimal

• Management

  • Nitroimidazoles (e.g., metronidazole) if treatment is indicated (e.g., if symptoms are present)

Enteric pathogens such as Giardia and Brachyspira should be considered as a cause for unintentional weight loss, even in the absence of gastrointestinal symptoms, when relevant risk factors are present. Such organisms can be transmitted through exposure to contaminated water or food, or they can be sexually transmitted. Most STIs are caused by viral and bacterial organisms; however, enteric pathogens are also accounting for a growing number of STIs, particularly through direct or indirect oral–anal sexual contact.^9,10 Existing studies show the sexual transmission of various enteric infections among men who have sex with men, including giardiasis and spirochetosis.^6,9–11 The risk for infection through sexual activity in this population is increased by several factors, including the frequency of exposure to the infected host and the frequency of sexual practices enabling transmission.⁹ Thus, among those with unintentional weight loss who have associated enteritis, proctitis, or proctocolitis and specific risk behaviours or exposures, clinicians should maintain a high index of suspicion for food-borne, waterborne, and sexual transmission of enteric pathogens and pursue relevant testing accordingly.⁹

The diagnosis of giardiasis is generally made through direct immunofluorescent stool antigen assays or nucleic acid amplification tests (NAATs). However, endoscopic assessment with biopsies should be pursued in cases in which stool testing is negative and clinical suspicion for giardiasis remains high. In contrast, the diagnosis of human intestinal spirochetosis is made through histopathologic staining of colonic mucosal biopsies.

In this case, an enteric infection presented as an unusual cause of a common medical problem. The fact that symptom improvement and stability in weight were achieved after completion of antimicrobial therapy supports that the enteric pathogens noted on pathology were the true cause for our patient’s symptoms, as opposed to incidental colonization. Despite repeat negative results from rectal chlamydia testing, we made a presumptive diagnosis of LGV and prescribed empiric treatment, because false negative results can occur in up to 50% of patients with LGV.¹² Ultimately, however, we deemed the endoscopic findings to be inconsistent with LGV and revised the working diagnosis.

The challenge with the evaluation of unintentional weight loss is its nonspecific nature and wide range of associated causes. A careful history can therefore aid clinicians in their decision-making and allow them to home in on potential contributing causes. Our patient had several risk factors for an enteric infection (including exposure to contaminated water and oral–anal sexual contact) that warranted further testing, but diagnostic consideration was not given to this initially. A detailed travel and exposure history was obtained only following diagnosis by pathology, which highlights the importance of taking a comprehensive history in the evaluation of weight loss. Although there is no one-size-fits-all diagnostic approach, certain aspects must be explored in the history-taking for any patient with weight loss to appropriately guide additional investigations and to allow for a timely diagnosis and subsequent management (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.241507/tab-related-content, and Box 3).³ Moreover, although a standard set of investigations is pursued in the evaluation of weight loss, additional diagnostic studies may be completed depending on the clinical context, including on the basis of history and physical examination.³ For instance, chest radiography is considered part of the standard workup for weight loss, but we expanded our investigations in a stepwise manner with CT of the chest, abdomen, and pelvis to evaluate for malignancy, and bidirectional endoscopic assessment to evaluate for gastrointestinal disease, when the cause remained unclear. The diagnosis in this case remained elusive until a correlation between travel and exposure history and pathology was ultimately made.

Box 3: Evaluation of unintentional weight loss Approach to investigations^* .

• Investigations should be guided by history and physical examination.

• There is a standard set of tests that should be completed in all cases, which include the following:

  • Laboratory investigations: complete blood count, electrolytes, extended electrolytes, creatinine, and liver enzymes

  • Endocrine laboratory tests: thyroid-stimulating hormone and hemoglobin A_1c

  • Inflammatory markers: erythrocyte sedimentation rate and C-reactive protein

  • Imaging: chest radiography

  • Other: age-appropriate cancer screening

  • Additional investigations that can be pursued based on the clinical presentation and risk factors (especially if the diagnosis remains unclear) include the following:

  • Autoimmune laboratory tests: antinuclear antibody, extractable nuclear antigen, rheumatoid factor, and complement levels

  • Microbiology: HIV, syphilis, chlamydia, gonorrhea, hepatitis B and C, and stool for bacterial culture and sensitivity, and ova and parasites

  • Imaging: computed tomography of the chest, abdomen, and pelvis (to exclude malignancy or occult infections)

  • Endoscopy: esophagogastroduodenoscopy and colonoscopy with biopsies

We report a case of duodenal giardiasis and colonic spirochetosis in a man who experienced unintentional weight loss in the setting of untreated water consumption and high-risk sexual practices. This case highlights the importance of engaging in a thorough history and maintaining a broad differential diagnosis for patients with undifferentiated presentations such as weight loss. Although giardiasis and spirochetosis are rare causes for weight loss, it is important to consider such enteric infections as a cause for systemic symptoms, especially among those with relevant risk factors for disease transmission.

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