Secondary hemophagocytic lymphohistiocytosis in a 5-month-old infant with IBD post-COVID-19: a case report

Abstract

Background: COVID-19 is known to induce cytokine storms and inappropriate cytotoxic immune responses. Hemophagocytic lymphohistiocytosis (HLH) is an underrecognized condition due to a hyperinflammatory syndrome characterized by fulminant hypercytokinemia with a high mortality burden. Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced secondary HLH during and post-infection have been sparsely reported in children. Inflammatory bowel disease (IBD) is a chronic, relapsing disorder of the gastrointestinal tract with a multifactorial etiology involving genetic, environmental, and immunological factors. To date, secondary HLH associated with COVID-19 in very early-onset inflammatory bowel disease (VEO-IBD) has not been reported. This case report aims to enhance understanding of the clinical manifestations of VEO-IBD and HLH, thereby facilitating the timely diagnosis and management of this rare condition.

Case presentation: We present the case of a 5-month-old Chinese female infant diagnosed with HLH following COVID-19 infection. The patient presented with hemophagocytic syndrome, which included recurrent fever, hepatosplenomegaly, cytopenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia, after exposure to her mother, who had been diagnosed with COVID-19. Whole-exome sequencing(WES) identified heterozygous mutations in the IL-10RA gene: c.537 G > A (inherited from her mother) and c.301 C > T (inherited from her father), who was ultimately identified as having VEO-IBD. Despite receiving nutritional support, intravenous immunoglobulin (IVIG), and dexamethasone therapy, the patient continued to experience anemia, diarrhea, and refractory gastrointestinal bleeding. Following a brief improvement after interventional treatment, the parents declined further medical interventions, signed for discharge, and the infant sadly passed away three months later.

Conclusion: Rare genetic variants play a pivotal role in the pathogenesis of VEO-IBD, particularly in infants diagnosed before the age of one. These cases often demonstrate resistance to various immunosuppressive therapies and have a poor prognosis with conventional treatments. Our findings highlight the potential increased risk of severe HLH in patients with VEO-IBD and concurrent COVID-19, underscoring the need for comprehensive and vigilant differential diagnosis when patients exhibit symptoms suggestive of multi-organ damage.

Keywords: COVID-19; IL-10RA; child; hemophagocytic lymphohistiocytosis; inflammatory bowel diseases.

Figure 1

The timeline information of this patient.

Figure 2

Imagines of CT and MRI. (A–D) Brain MRI showed asymmetric signals in the midbrain, pontine, bilateral lateral ventricle triangle and posterior horn. (E–H) Abdominal CT revealed thickening and strengthening of the intestinal wall and thickening of the vessels in the colon's hepatocele wall.

Figure 3

(A) Bone marrow smear show hemophagocytic. (B) Gastrointestinal angiography and vascular embolization interventional surgery, multiple branch bleeding signs of the inferior mesenteric artery.

Figure 4

Sanger sequencing validation of this patient and her parents. (A) chr11: 117989554. (B) chr11: 117993410.