HISTOPLASMA ASSOCIATED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN KIDNEY TRANSPLANT RECIPIENT

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HISTOPLASMA ASSOCIATED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN KIDNEY TRANSPLANT RECIPIENT
Walaa
Dabbas
Walaa Dabbas wdabba2@uic.edu University of Illinois Chicago Medicine/Nephrology Chicago
Ruchi Naik rnaik@uic.ed University of Illinois Chicago Medicine/Nephrology Chicago
Nawaf Al-Hashemi nawaf.alhashemi.md@gmail.com Gulf medical university Medicine Ajman
Ignatius Tang iytang@uic.edu University of Illinois Chicago Medicine/Nephrology Chicago
 
 
 
 
 
 
 
 
 
 
 

Kidney transplant recipients are at risk of infectious complications due to chronic immunosuppressive state. While histoplasmosis is the most prevalent mycosis in the united states, histoplasma associated hemophagocytic lymphohistiocytosis (HLH) is rare and frequently underdiagnosed.

Case

Our patient is a 42 ‐year‐old female with a history of end stage kidney disease due to hypertension, she is 18 months post deceased donor kidney transplant. Her maintenance immunosuppression included mycophenolic acid 360 mg, 4 times a day, prednisone 10 mg daily and monthly belatacept infusion. she had an episode of antibody mediated rejection for which she received IV methylprednisone, plasma exchange, high dose IVIG with improvement of allograft function 1 year post transplant.

Patient presented to the emergency room with abdominal pain, chills, and dysuria of 1 week duration. Vital signs were within normal limits. On examination, she had mild epigastric tenderness and splenomegaly. Laboratory studies were significant for leucopenia with, WBC of 2000 k/uL, elevated liver enzymes including AST 97 U/L, ALT 150 U/L, ALP 302 iu/l, ferritin of 11792 ng/ml and triglyceride 449 mg/dL.

CT scan of the abdomen and pelvis without contrast showed splenomegaly and hepatic steatosis. Viral hepatitis studies were negative. Based on the clinical presentation, HLH was suspected. CT chest without contrast showed tree-in-bud opacities in the right lower lobe and

Scattered pulmonary nodules measuring up to 0.6 cm.

Bone marrow biopsy was done on day 4 that showed cellular marrow with active trilineage hematopoiesis with no evidence of a hemophagocytosis and no evidence of histoplasmosis or other infections. At this time, patient was empirically started on dexamethasone 40 mg daily and posaconazole 300 mg orally twice a day.

Soluble serum IL-2R, was 4806 pg/ml and CXCL9 was 7,244 pg/ml,. both of which markedly elevated (>20 ng/ml),that is consistent with the diagnosis of HLH.

On day 7 of admission, urine histoplasma antigen returned at a level above the limit of quantification, consistent with disseminated histoplasmosis as the culprit agent precipitating her HLH syndrome. At this point, patient was treated with IV liposomal amphotericin 3 mg/kg for 7 days then switched to itraconazole 2.5mg/kg orally three times daily for 3 days as loading dose, then transitioned to itraconazole 200mg orally twice a day for 12 months. Immunosuppressive regimen was changed to cyclosporine and prednisone. Belatacept and mycophenolic acid were stopped. 

Repeat urine histoplasma antigen was down to 8.35 ng/ml after 1 month. Three months later, patient was asymptomatic, had normal WBC, platelets count, creatinine, AST, ATL, stable hemoglobin of 8.4 g/dL, ferritin was down to 2454 ng/ml. Urine histoplasma antigen was down to 6.6 ng/ml. patient had recovery of splenomegaly.


HLH is characterized by an extensive inflammatory response to a variety of infections or immune system abnormalities. Histoplasma associated HLH has high mortality. Timely diagnosis and treatment is associated with positive outcomes. This is first reported case of histoplasma associated HLL without evidence of yeast and/or hemphagocytosis on bone marrow biopsy.

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