| Abstract|| |
Strongyloides stercoralis (S. stercoralis) is a soil transmitted intestinal roundworm that has a unique ability to multiply within the human host and reinfect the human carrier by a process of autoinfection. By this property, S. stercoralis can persist as an occult infection for many decades. In situations of immunosuppression or other permissive gastrointestinal conditions, there occurs a massive increase in parasite multiplication. The parasites penetrate through the intestinal mucosa and are carried in circulation and can cause multisystem involvement. We report a case of a 76-year-old Columbian male who presented with intractable vomiting and hyponatremia who was then diagnosed to have syndrome of inappropriate antidiuretic hormone (SIADH). The patient's symptoms improved after treatment with two doses of ivermectin and his serum sodium levels returned to normal. S. stercoralis infection should be suspected in patients from endemic regions who present with gastrointestinal symptoms and unexplained hyponatremia.
Keywords: Disseminated strongyloidiasis, Hyponatremia, Parasite, Strongyloides hyperinfection, Strongyloides stercoralis, Syndrome of inappropriate antidiuretic hormone secretion
|How to cite this article:|
Chowdhury DN, Dhadham GC, Shah A, Baddoura W. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in Strongyloides stercoralis hyperinfection. J Global Infect Dis 2014;6:23-7
|How to cite this URL:|
Chowdhury DN, Dhadham GC, Shah A, Baddoura W. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in Strongyloides stercoralis hyperinfection. J Global Infect Dis [serial online] 2014 [cited 2020 Aug 7];6:23-7. Available from: http://www.jgid.org/text.asp?2014/6/1/23/127945
| Introduction|| |
S. stercoralis is an intestinal nematode or roundworm which causes an infection that can manifest as an asymptomatic eosinophilia in the immunocompetent host to fatal disseminated disease in the immunocompromised host. An unusual characteristic of S. stercoralis is its ability to multiply within the human host. ,, By this unique property, this parasite can persist for many decades as occult infection through an autoinfection cycle where mature rhabditiform larvae transform into infective filariform larvae within the intestinal tract.  Humans acquire S. stercoralis when infective filariform larvae found in fecally contaminated soil penetrate skin or mucus membranes. Prior reports state up to 50% of infected individuals remain asymptomatic , or may have symptoms such as abdominal pain; nausea; vomiting; and diarrhea; or pulmonary symptoms such as dry cough, dyspnea, or wheezing. Massive multiplication of parasites within the gastrointestinal tract, known as hyperinfection, can occur in situations of immunosuppression or local gastrointestinal conditions such as achlorhydria, blind loops, and diverticulosis. Disseminated strongyloidiasis occurs when these infective filariform larvae invade through the gastrointestinal tract and migrate to other organs and cause multisystem involvement. Bacteremia and septicemia occur due to migration of bowel organisms through damaged intestinal epithelium.  Features of dissemination include severe abdominal pain, nausea, vomiting, diffuse rash, pulmonary infiltrates, ileus, gram negative sepsis, meningitis, and protein losing enteropathy. , Majority of patients with disseminated strongyloidiasis (83-87%) have a fatal outcome. 
We report a case of a 76-year-old Colombian male patient presenting with gastrointestinal symptoms, hyponatremia, and S. stercoralis hyperinfection after being recently treated with corticosteroids. SIADH associated with S. stercoralis infection is vastly under-reported though it may be a common occurrence. There are only four previously reported cases in literature of SIADH being associated with disseminated strongyloidiasis.
It is therefore important to acknowledge this clinical entity in order to recognize the various manifestations of disseminated strongyloidiasis and institute appropriate treatment early to prevent fatal complications.
| Case Report|| |
A 76-year-old Hispanic male presented to our hospital with a 2-month history of fatigue, nausea, intractable vomiting and a 30-pound weight loss. Past medical history was significant for idiopathic thrombocytic purpura (ITP) diagnosed 4 months ago, which was treated with steroids for 3 weeks. The patient had immigrated to the United States from Columbia 17 years ago and had travelled to Venezuela a month prior to presentation. He had a history of smoking 1 pack per day for 40 years.
On physical examination there was nonpalpable purpurae. Abdominal examination revealed a soft nondistended abdomen with mild epigastric tenderness, with no associated guarding, rigidity, rebound tenderness, or organomegaly.
Laboratory examination revealed elevated white cell count of 11,400/μl, with a normal eosinophil count of 1%. Biochemistry revealed sodium of 122 meq/l. Other significant laboratory abnormalities were a total protein level of 4.5 g/dl and albumin level of 1.7 g/dl. The rest of laboratory examination was normal [Table 1]. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain were unremarkable. The patient tested negative for both HIV and human T-lymphotropic virus (HTLV).
The patient was initially treated with 0.9 normal saline infusions suspecting hypovolemic hyponatremia due to persistent vomiting, but showed only minimal improvement in serum sodium levels. A diagnosis of SIADH was then made based on his high urine osmolality, 564 mOsm/kg and low plasma osmolality 261 mOsm/kg. Fluid restriction increased his serum sodium to 133 meq/l.
To evaluate his symptoms of intractable vomiting, an esophagogastroduodenoscopy (EGD) was performed which showed erythema in the stomach and duodenum. Histopathology showed acute and chronic duodenitis, with marked blunting of villi and reactive cellular changes, active gastritis, and presence of parasites consistent with S. stercoralis [Figure 1] and [Figure 2]. Stool examination showed many S. stercoralis larvae.
|Figure 1: Hematoxylin and eosin stain of a duodenal biopsy specimen showing inflammatory cell infiltrate, marked blunting of villi and Strongyloides stercoralis larvae (×100)|
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|Figure 2: Longitudinal and cross-sectional view of a duodenal biopsy specimen stained with hematoxylin and eosin showing several S. stercoralis larvae lying within a crypt (×40)|
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The patient was treated with two doses of ivermectin 12 mg (calculated at 200 μg/kilogram) following which his nausea and vomiting improved and serum sodium increased to 139 meq/l. Repeat stool examination after 2 weeks of ivermectin therapy did not show any S. stercoralis larvae.
| Discussion|| |
S. stercoralis is a soil transmitted intestinal nematode that is endemic to many humid, tropical parts of the world including south eastern United States, south Asia, Latin America, and sub-Saharan Africa.  In the United States, it is found most commonly among immigrants from endemic areas.  It affects 30 to 100 million people worldwide.  It is uncommon in regions with temperate climate. The highest noted prevalence in USA is among residents of south eastern states and in individuals who have resided at or travelled to endemic areas. ,,, Our patient had migrated to the USA 17 years ago from South America, an endemic region for S. stercoralis infections and had also recently travelled to Venezuela. Life cycle of S. stercoralis is more complex than other nematodes in the same class with its ability to alternate between free living and parasitic cycles and its capacity to autoinfect and multiply within the host. ,, In the gastrointestinal tract of the human host, the infective stage of S. stercoralis, the filariform larva matures into the adult worm, which then lives within the mucosa of the duodenum or jejunum. The adult worm produces eggs from which develop the rhabtidiform larvae, which are either passed in stool or mature into infective filariform larvae. These infective filariform larvae cause internal autoinfection by penetrating through the intestinal mucosa or external autoinfection by penetrating the skin of the perianal region. ,
Autoinfection is usually restricted by an intact immune response and a low level of autoinfection may allow the organism to persist for decades. , However, in the setting of a depressed immune system, the autoinfection process can lead to a large increase in the parasite burden, causing a hyperinfection syndrome, which can then result in massive dissemination of filariform larvae into heart, lungs, central nervous system (CNS), liver, and endocrine organs ensuing in disseminated strongyloidiasis. , Immunocompromised conditions which have been noted to predispose to S. stercoralis hyperinfection and dissemination include disorders such as protein-calorie malnutrition,  hematologic malignancies (especially lymphoma) , immunosuppressive therapy (particularly steroids),  kidney transplantation,  and viral infections such as human T-cell lymphotropic virus type 1 (HTLV-I). 
S. stercoralis hyperinfection has also been reported with chronic variable immunodeficiency, chronic renal failure,  burns, , and diabetes.  Local factors such as impaired bowel motility,  constipation, and diverticulosis as well as achlorhydria  can all cause an unrestricted increase in parasitic multiplication and maturation. Furthermore, severe disseminated strongyloidiasis may develop in immunocompromised patients leading to sepsis, respiratory failure, and death. Our patient was treated with oral corticosteroids for ITP which could have predisposed him to develop disseminated strongyloidiasis.
In patients with decreased cell mediated immunity, the case fatality rate of disseminated disease has been reported to range between 50 and 86%.  Interestingly there are only a few cases reported of S. stercoralis hyperinfection in patients infected with HIV-1.  Prior case reports mentioning the association of disseminated strongyloidiasis and SIADH consisted of patients who were on steroid therapy for various conditions. Their laboratory examination results are compared for review [Table 2].
|Table 2: Comparison of laboratory examination results of patients in previously reported cases|
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Peripheral eosinophilia, which is known to be an important clinical marker for helminthic infection, is very nonspecific and is seen in only 5-15% of infected patients. ,, Eosinophilia may be absent in disseminated S. stercoralis infection and also after corticosteroid therapy,  as seen in our patient who had an eosinophil count of 1% or 1,000/mm 3 . Absence of eosinophilia is a poor prognostic sign. 
Hypoproteinemia in S. stercoralis hyperinfection may occur as a result of hemorrhage, edema, and capillary leaks in the intestinal mucosa causing a protein losing enteropathy  which was also noted in our patient who had a total protein of 4.5 g/dl and albumin of 1.7 g/dl.
Skin lesions such as nonpalpable purpura, seen in our patient, resemble vasculitis and have been attributed to a hypersensitivity reaction to S. stercoralis larvae in the dermis. ,
SIADH is thought to occur by various dysfunctions and infections, particularly virus infections, which may cause meningoencephalitis by virus dissemination. SIADH has been associated with systemic strongyloidiasis; the mechanism is unknown, although it has been attributed to CNS or pulmonary involvement. ,,,, In one report, diffuse pulmonary interstitial infiltrates was reported to be responsible for the development of SIADH;  while another report identified anorexia, as a result of chronic S. stercoralis infection to be responsible for increased ADH secretion.  However, our patient did not have CNS features or pulmonary infiltration, and the mechanism by which S. stercoralis causes SIADH remains unclear.
Definitive diagnosis of strongyloidiasis is usually made on direct visualization of larvae in stool or in clinical specimens such as duodenal or jejunal aspirates and/or biopsies obtained via endoscopy. However, these may be negative in approximately 25% of infected patients. A low parasite burden or intermittent excretion , in stool may be responsible for a large percentage of false negative results. Specialized testing of the stool sample with the Baermann concentration technique or a modified agar plate method may increase the yield. Considering the possibility of intermittent excretion, repeated examinations with up to 3-7 stool samples may increase sensitivity. , Diagnosis can also be made with serological testing.  In disseminated strongyloidiasis, filariform larvae can also be found in sputum, pleural and peritoneal fluid, and bronchoalveolar lavage fluid in addition to stool. ,,,, We diagnosed strongyloidiasis in our patient by means of esophagogastroduodenoscopy and biopsy of gastric and duodenal mucosa which showed many S. Stercoralis larvae. S. stercoralis larvae was also directly visualized on stool examination.
Treatment with ivermectin has shown good results in this condition, including patients who did not respond adequately to thiabendazole. Ivermectin is highly effective when given orally (200 μg/kg per day for 1-2 days) for complicated intestinal strongyloidiasis. In one study, complete parasitological cure was obtained in 24 of the 29 patients treated with ivermectin 200 μg/kg as a single dose (83%) and in nine of the 24 patients who were given albendazole 400 mg/day for 3 days (38%). Both treatment groups suffered from minimal clinical or biological adverse effects.  Our patient achieved cure after two doses of ivermectin verified by a stool testing.
Ivermectin also appears to be devoid of the side effects seen with thiabendazole therapy, and achieves cure rates of up to 88% in immunocompetent patients.  Immunocompromised patients with systemic disease may require multiple dose regimens.  Patients who experience frequent relapses may benefit from monthly treatment regimens. 
| Conclusion|| |
Ill-defined gastrointestinal symptoms, obscure hyponatremia, hypoproteinemia, and purpuric rash in immunocompromised patients who have lived in an endemic region for S. stercoralis should prompt the suspicion of strongyloidiasis as one of the differential diagnoses. All patients who possess risk factors for the development of S. stercoralis infection must be screened for the presence of the parasite before starting any immunosuppressive therapy even if exposure was many decades ago. SIADH may occur in patients with disseminated strongyloidiasis and is a frequently unrecognized complication of the disease. Healthcare professionals need to be aware of this fatal complication to institute early and appropriate treatment.
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Deepshikha Nag Chowdhury
Department of Internal Medicine, St. Joseph's Regional Medical Center, Paterson, New Jersey
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2]