Strongyloidiasis-Related IRIS

Abstract

Helminthic infection and HIV have been reported to coexist, particularly in sub-Saharan African patients living with HIV. Strongyloidiasis is one of the most common helminths, usually leading to cutaneous and gastrointestinal (GI) symptoms. In the immunocompromised host, this infection can lead to strongyloidiasis hyperinfection syndrome (SHS), not common in HIV-infected patients. Immune reconstitution inflammatory syndrome (IRIS) can follow the initiation of antiretroviral therapy (ART), with a variety of presentations. The authors present here a 32-year-old HIV-infected female who was recently diagnosed with AIDS, started ART, and recovered from SHS. Her upper endoscopy revealed severe duodenitis but no causal agent per biopsy or stool examination. After receiving symptomatic therapy, she showed improvement, a course of events that fit the diagnosis of GI-related IRIS.

Case Presentation

A 32-year-old female, immigrant from a sub-Saharan African country, with past medical history of spherocytosis and chronic anemia, presented to the hospital with complaints of epigastric abdominal pain, nonretractable vomiting, anorexia, and weight loss of 5 kg in the last 2 weeks. Emesis was postprandial and was triggered by both fluids and solids. The patient also complained about a new diffuse rash and pruritus. She denied any complaints of fever, chills, change in bowel habits, or other systemic symptoms. She was recently diagnosed with AIDS in another hospital, 2 months prior to her admission. On her admission then, she had arrived with the same complaints combined with a productive cough and hemoptysis. On physical examination, she was hemodynamically stable, with no finding other than thrush and was admitted for a workup. Blood counts revealed pancytopenia with leukocytes of 2210 cell/µL, hemoglobin level 9.4 g/dL, platelets 152 000 cell/µL, CD4 counts of 40 cells/mm³, and HIV viral load of more than 2 million copies/mL. Upper endoscopy revealed gastritis and duodenitis with Strongyloides (Figure 1). No evidence of cytomegalovirus (CMV) or candida on hematoxylin and eosin staining or immunohistochemistry was found. Bronchoscopy revealed Strongyloides parasites in the sputum, and stool microscopy was positive for Strongyloides stercoralis. Polymerase chain reaction for blood CMV detected a viral load of 14 000 copies/mL. She was diagnosed with AIDS, complicated pulmonary and gastrointestinal Strongyloides hyperinfection with suspected CMV involvement, and was started with antiretroviral (ARV) medication (including—darunavir, ritonavir, tenofovir, and emtricitabine), preventive sulfamethoxazole–trimethoprim and azithromycin, ivermectin with albendazole, and valganciclovir. After receiving this treatment, her condition improved, and she started eating and gaining weight, her vomiting and hemoptysis ceased, and her cytopenias resolved (other than chronic anemia). A month later, her CD4 counts increased to 170 cells/mm³ and HIV viral load decreased to 1000 copies/mL. Five weeks later, on her current admission to our hospital, the patient was drowsy, her viral signs were within normal limits, abdomen was soft and nontender, and no remarkable physical finding were noted other than a diffuse scaly rash on both torso and extremities with an edematous border, fitting the clinical diagnosis of tinea corporis. Laboratory findings included leukocytes of 1600 cell/µL, hemoglobin level 8.4 g/dL, and platelets 46 000 cell/µL. Hypoalbuminemia of 1.2 g/dL and hypomagnesemia of 1 mEq/L were also noted (other electrolytes was in the lower border of the normal range), reflecting her malnourished state, concurrent with low creatinine and blood urea nitrogen levels. No abnormal cells or signs of hematological malignancy were noted on the peripheral blood smear. She was admitted to the medical ward and treated with antiemetic medication, proton pump inhibitors, and fluids and electrolytes replenishment. Due to her low intake and low nutritional status, total parenteral nutrition (TPN) and thiamine were started. Given her clinical presentation and her recent history, a high suspicion for recurrent/unresolved Strongyloides infection was suspected and she was retreated with ivermectin 9 mg daily for a week. All medications other than ARV drugs were stopped (at that time, she was not receiving valganciclovir, finishing 6 weeks of therapy prior to her admission). Upper endoscopy revealed severe duodenitis in the first and second part, and biopsies showed signs of acute inflammation but was negative for Strongyloides or inclusion bodies (Figure 2). Stool for parasites was also negative. Mycologic culture from the skin grew Trichophyton. The polymerase chain reaction (PCR) for CMV in the blood was negative, and mycobacterial blood culture was sterile. Under symptomatic treatment and TPN, the patient slowly recovered and resumed eating. Leukopenia, thrombocytopenia, and hypoalbuminemia slowly resolved, while no further electrolytes abnormalities were noted. Two weeks after admission to our hospital, she was discharged to her home in a good medical condition, asymptomatic. The patient continued her follow-up 6 months later in our HIV outpatient clinic. Her CD4 count increased to 250 cells/mm³, HIV viral load was under 20 copies/mL under her ARV therapy.

Figure 1.

Duodenal biopsy showing Strongyloides stercoralis eggs in crypts and a larva (Hematoxylin and Eosin [H&E] ×400).

Figure 2.

Duodenal biopsy showing neutrophilic infiltrates in the lamina propria and duodenal epithelium. A marked increase in lamina propria eosinophils is also seen. No evidence of Strongyloides stercoralis.

Discussion and Review of the Literature

Strongyloidiasis, caused by Strongyloides stercoralis (Ss), is a parasitic infection, common in the developing world. The helminth enters the body through the skin and initially migrates through the venous peripheral blood system to the lung parenchyma, ascending the bronchotracheal tree, and is subsequently swallowed to gain access to the small intestine. After initial infection, mature females in the duodenum produce rhabditiform larvae that can develop into infective filariform larvae and reinfect the host through penetration of intestinal mucosa. This autoinfection cycle allows Ss to persist for decades inside a human host. Infection can be asymptomatic or can present as cutaneous and/or abdominal symptoms. Pulmonary symptoms are less common but can occur.

The prevalence of HIV and Strongyloides coinfection differs in the cohorts that were published in the literature so far. A cohort from an urban HIV clinic in the United States found 25% of 103 HIV-infected patients to carry positive serology for Ss. ¹ Another cohort from Georgia reported 33 (26%) of 128 coinfected patients. ² In another cohort of 700 HIV-positive patients who reside in Entebbe, Uganda, Ss-positive stool culture was positive in 12% of the patients. ³ In a cohort from Iran, 2 of 781 HIV-positive patients had positive stool for Ss. ⁴ Feitosa et al report that 20 (5.5%) of 365 of HIV-positive patients had positive stool for Ss in Brazil. ⁵ In a cohort of HIV-positive immigrants in Italy, 15 (11%) of 138 patients were Ss positive. ⁶ Only 2 of 90 HIV-positive immigrants in Ireland had Ss infection. ⁷ Diagnostics (serology, stool culture, biopsy etc) seem to impact reported prevalence and so the real prevalence of this coinfection remains to be determined.

Strongyloidiasis hyperinfection syndrome (SHS) is one of the manifestations in immunocompromised host (mostly chronic steroid users and HTLV-infected individuals) and might involve multiple organs (disseminated disease) and extensive GI involvement (SHS) that can lead to severe malnutrition. Surprisingly, in HIV-infected patients, this syndrome is not common, with only sparse repots in the literature in the last decades. ⁸ Viney et al hypothesized that in HIV-positive patients, unlike other patients in other immunosuppressive state (ie, steroid therapy), the life circle promotes indirect larvae development over direct larvae development. ³ Progressive HIV-associated CD4 lymphocytopenia lowered chances for larvae maturation within the gut, which led to decreased risk of autoinfection—a process required in the development of SHS. Hence, HIV-related immunosuppression is paradoxically associated with lower SHS risk.

Although Ss is listed as an immune reconstitution inflammatory syndrome (IRIS)-related pathogen, ⁹ this condition is scarcely reported in the literature. The IRIS after initiation of ART in patients with chronic strongyloidiasis (the so-called “unmasking IRIS”) was reported in 4 cases so far. ^{10 -13} The IRIS in these patients might increase replication of larvae and promote typical symptoms of chronic strongyloidiasis (diarrhea, vomiting, constipation, etc) On the other hand, documented IRIS development after resolution of SHS (“paradoxical IRIS”) has not been reported in the literature so far. This case report describes one of the many forms IRIS can present with and highlights the need for comprehensive follow-up in HIV-positive patients after the initiation of ART.

Whether the start of antiretroviral therapy (ART) should be postponed due to SHS could not be determined due to the lack of evidence. Guidelines recommend ART and antiparasitic treatment be started together when parasitic infections are diagnosed in HIV-positive patients. So far, not enough cases were reported to generate a clear recommendation for ART timing in Ss-infected HIV-positive patients. Further research is needed to clarify this.