A woman in her early 60s with non-ischemic cardiomyopathy leading to end-stage heart failure and a history of Hodgkin's lymphoma (treated with radiation therapy many years ago) underwent a heart transplant. Several months post-transplant, she presented with progressively worsening abdominal symptoms (nausea, vomiting, abdominal pain) and rash.

Nonischemic cardiomyopathy and heart failure reduced ejection fraction secondary to chemotherapy for Hodgkin’s lymphoma.

Tacrolimus, Mycophenolate mofetil, prednisone, trimethoprim-sulfamethoxazole, valganciclovir.

Born in and raised in the United States; has resided in the Midwest for the past 25 years. No current pets, but previously owned dogs and cats and had a bird many years ago. Never smoker, social alcohol use, no illicit substances.

The patient appeared well. The blood pressure was 128/78, pulse 97 beats per minute, temperature 97.8F (36.5C), and respirations 18 breaths per minute. Exam was remarkable for pruritic maculopapular rash on her trunk and buttocks. Abdomen was soft, non-distended, and tender to palpation in epigastrium. No rebound or guarding. The examination was otherwise normal.

Figure 1. Abdominal skin rash

Hemoglobin 10.3 g/dL (reference range 11.5-15.5), hematocrit 31.4% (reference range 36-46%), platelets 314 k/uL (reference range 150-400), white cell count 3.7 k/uL (reference range 3.7-11.0), with 29% neutrophils, 14% lymphocytes, 43% eosinophils. Serum electrolytes and chemistries were normal except for a creatinine of 1.46 mg/dL (reference 0.58-0.96). C-reactive protein 3.4 mg/dL (reference range < 0.9).

Computed tomography (CT) Abdomen/Pelvis demonstrated borderline to mildly dilated loops of small bowel in the lower abdomen with suggestion of wall thickening, possibly enteritis. No pneumatosis, portal venous gas, or free intraperitoneal air. CT Chest showed new diffuse lung opacities, differential including including pulmonary edema, atypical pneumonia, or alveolar hemorrhage.

Figure 5. Labs

Pre-transplant screening was unremarkable, including negative Strongyloides IgG. The patient received standard immunizations. She had minimal travel history outside of the U.S., with a past trip to Mexico over 20 years prior. Post-transplant she was placed on standard immunosuppressive therapy with tacrolimus, mycophenolate mofetil, and prednisone. She was also on valganciclovir and trimethoprim-sulfamethoxazole prophylaxis. She had undergone esophagogastroduodenoscopy (EGD) approximately 2 weeks post-transplant for dysphagia and odynophagia with evidence of many superficial esophageal ulcers. Pathology demonstrated active esophagitis with granulation tissue, with special stains negative for herpes simplex virus (HSV), cytomegalovirus (CMV) and PAS/D. She was discharged with pantoprazole which was continued until re-admission 2 months later.

Initial workup, including stool pathogen panel, blood cultures, and CMV and EBV DNA levels, was negative. On hospital day 4, an EGD revealed erosive gastropathy and a CT A/P raised concern for ileus. Empiric ganciclovir was started due to concern for tissue invasive CMV infection. That evening, the patient became confused and developed hypoxia, necessitating transfer to the ICU and intubation with mechanical ventilation. Blood cultures obtained at this time were positive for gram negative rods, which were subsequently identified as Enterobacter cloacae.

EGD (esophagogastroduodenoscopy)

• Small bowel, duodenum, biopsy: Acute duodenitis with Strongyloides organisms. CMV, HSV and adenovirus immunohistochemistry negative (Figure 3)
• Stomach, antrum, biopsy: Positive for Strongyloides organisms. Portions of oxyntic and antral type gastric mucosa with chronic inactive gastritis. Negative for Helicobacter pylori organisms on routine staining. Negative for intestinal metaplasia or dysplasia

 Skin abdomen punch biopsy (Figure 2)

• Orthokeratosis overlying an essentially unremarkable epidermis. Within the superficial and deep dermis, there is a mildly dense perivascular lymphohistiocytic infiltrate with numerous admixed eosinophils. Additionally, there are basophilic exogenous structures, consistent with nematode larvae, percolating between collagen bundles within the dermis and subcutaneous tissues.

Bronchoscopy with BAL (bronchoalveolar lavage):

• Cell count and differential:  13,350 RBCs, 48 nucleated cells with 33% neutrophils, 19% lymphocytes, 5% monocytes, 37% macrophages and 6% eosinophils.
•  BAL O&P: rare Strongyloides stercoralis

Lumbar puncture:

• Cell count and differential: 9 RBCs, 3 nucleated cells (7% neutrophils, 92% lymphocytes, 1% monocytes)
• Protein 41, glucose 169
• Bacterial Culture: Vancomycin resistant Enterococcus faecium

 Right ventricle, endomyocardial biopsy:

• Foci of interstitial mononuclear cell infiltrates with numerous eosinophils.  There is one biopsy fragment with a granuloma containing an elongated wrinkled eosinophilic structure with numerous faint blue nuclei. In the setting of disseminated Strongyloides infestation, the morphology of this structure is consistent with a degenerated Strongyloides larva. 

Figure 3. Small bowel, duodenum, biopsy. Acute duodenitis with strongyloides organisms.

Figure 6. Stool Ova & Parasite test

Figure 2. Skin, abdomen punch biopsy

Figure 4. CT Chest

Strongyloides was identified on duodenal biopsy, prompting immediate initiation of oral ivermectin. Because pre-transplant screening of the patient for Strongyloides IgG was negative, there was concern for donor-derived infection which was later confirmed in another recipient from the same donor. A stool O&P confirmed presence of Strongyloides.

Prednisone dosing was reduced and ESBL Enterobacter cloacae bacteremia was treated with meropenem. Despite initial therapy, the patient’s condition worsened, requiring intensive care unit admission for respiratory failure and intubation. Bronchoscopy with BAL demonstrated diffuse alveolar hemorrhage (DAH) and O&P of BAL fluid confirmed presence of Strongyloides larvae, leading to the diagnosis of hyperinfection syndrome. Due to persistent encephalopathy, a lumbar puncture was obtained, with E. faecium on culture which was treated with linezolid.

The abdominal maculopapular rash noted on admission became progressively more purpuric and spread to involve her periumbilical region, bilateral flanks and bilateral proximal anterior thighs (Figure 1). Dermatology was consulted due to high suspicion of cutaneous strongyloidiasis. A punch skin biopsy was obtained and histological examination showed basophilic exogenous structures, consistent with nematode larvae, percolating between collagen bundles within the dermis and subcutaneous tissues (Figure 2).

Patient was initiated on oral ivermectin 200 mcg/kg/day the same day that the EGD results were reported.  Due to the development of ileus with concern for impaired enteric absorption, an Investigational New Drug (IND) application was submitted and approved by the FDA for subcutaneous administration of a veterinary preparation of ivermectin, which was started on hospital day 9, at which point her PO ivermectin was discontinued. She finished a course of meropenem for ESBL Enterobacter bacteremia. Stool O&Ps were performed every 3 days while on subcutaneously administered ivermectin. O&P became negative after 12 days of ivermectin (9 days of subcutaneous ivermectin) and she was transitioned back to oral ivermectin once bowel function returned.

This case highlights the potential for donor-derived Strongyloides infection in heart transplant recipients, underscoring the need for vigilant screening in high-risk populations. Early recognition and treatment with ivermectin are critical in preventing progression to hyperinfection syndrome.

Additionally, this case demonstrates both disseminated disease in which there is spread of organism to organs outside of the normal life cycle as well as hyperinfection syndrome, characterized by an accelerated autoinfection.

Treatment challenges exist and include ileus or poor gastrointestinal absorption of ivermectin. In this case, it prompted an IND application for subcutaneous administration of ivermectin.

Cutaneous manifestation of disseminated strongyloidiasis are rare, but periumbilical purpura resembling thumbprints can be a pathognomonic physical exam finding to aid in early diagnosis.

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IDWeek 2025- Fellows’ Day

Ana Khazan, MD, MPH – Cleveland Clinic Foundation

Contributors: Dr. Chroistopher Kovacs, Dr. Amanda Vest, Dr. Mohamed El Hag, Dr. Martan Rothschild, Dr. Omar Mehkri, Andrea Pallota PharmD

Case #25001: When the Past Resurfaces: An Infectious Complication After Heart Transplant [Internet]. Partners Infectious Disease Images. Available from: http://www.idimages.org/idreview/case/caseid=620.

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