SKIN MANIFESTATION OF ACUTE GRAFT-VERSUS-HOST DISEASE MIMICKING DENGUE FEVER RASH: A CASE REPORT

Abstract

The impact of dengue on Hematopoietic Stem Cell Transplantation (HSCT) patients is poorly understood, with few case reports from endemic areas and no prospective studies. It is known that various manifestations of dengue, such as fever, rash, and thrombocytopenia, can occur during the evolution of post-HSCT, often delaying the diagnosis of the arbovirus or HSCT-related complications, such as Graft-Versus-Host Disease (GVHD) or other infections. Here, we present a case report of a patient with severe acute skin GVHD concurrent with dengue fever, mimicking the rash secondary to dengue. A 43-year-old female patient underwent a myeloablative allogeneic HSCT for not responding to three lines of treatment for chronic myeloid leukemia in December 2023, with her sibling as an identical HLA donor with a peripheral blood cell source. GvHD prophylaxis was ATG, methotrexate, and tacrolimus, and the patient was discharged without GvHD disease or active infections. Neutrophil engraftment occurred on D+12. She developed symptoms of dengue fever, including a skin rash, and tested positive for dengue. Her condition worsened, and she had a pruritic, erythematous papular rash on the trunk and upper limbs. Despite initiating topical steroids and adjusting the tacrolimus level, the skin lesions became confluent and diffuse, involving 100% of the body surface area. A skin biopsy was performed, and systemic steroid therapy was initiated (2 mg/kg/day). As the skin lesions worsened and the biopsy was compatible with the diagnosis of GvHD, second-line treatment with ruxolitinib at a dose of 20 mg daily was initiated. After ten days, there was a remarkable improvement in the skin lesions, and the corticosteroid gradually tapered off. However, she had other virus infections, including mild COVID-19 and hemorrhagic cystitis due to BK virus reactivation. She also evolved with chronic GvHD of skin and mucosas. GvHD affects 30%‒50% of transplant patients and is caused by donor T-cell reactivation against the recipient cell surface antigens. HLA class I/II molecules, various cytokines, and costimulatory molecules are associated with the risk of developing acute GvHD. Inflammatory triggers can drive immune responses, and tissue lesions caused by infections can exacerbate acute GvHD. Viral infections can lead to increased activation of donor T-cells, causing a dysfunctional balance between tolerance and immune response, predisposing to developing GvHD. This case report describes a scenario where the medical team promptly diagnosed dengue fever despite symptoms that could be mistaken for other common conditions in post-HSCT patients. A rash appeared within the expected timeframe for dengue, but due to its severity and worsening condition, treatment for severe acute GvHD was initiated. A skin biopsy was necessary to confirm the diagnosis and determine the next steps, as the disease did not respond to steroids. The patient developed severe acute GvHD and later moderate chronic GvHD, affecting her quality of life and posing a significant risk of non-relapse mortality. This case highlights the importance of taking preventive measures against dengue in patients who have undergone HSCT, as they may be at risk of experiencing complications not typically seen in the general population. It also underscores the need to remain vigilant during dengue epidemics and emphasizes the value of conducting skin biopsies for accurate differential diagnosis.