Severe graft‐versus‐host disease‐like enterocolitis accompanied with cytomegalovirus‐reactivation in drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms

Abstract

Drug‐induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug adverse reaction with skin eruption and visceral organ involvement. The characteristic clinical features of DIHS/DRESS are reactivation of human herpesviruses (HHV) and the development of autoimmune diseases, but their pathogenesis and associations are not yet understood. Here, we report a 66‐year‐old man who presented with fever, generalized erythema, diffuse lymphadenopathy, and diarrhea after 3 weeks of treatment with zonisamide. Reactivation of HHV‐6 and cytomegalovirus (CMV) was detected during the clinical course. The patient was diagnosed with DIHS/DRESS and treated with systemic prednisolone, i.v. immunoglobulin therapy, and ganciclovir. However, severe enterocolitis persisted for 6 months. A series of examinations revealed features of both CMV enterocolitis, as indicated by identification of a few CMV‐positive cells on immunohistochemical analysis, and graft‐versus‐host disease (GVHD)‐like enterocolitis indicated by orange‐peel appearance on endoscopic examination and histopathological loss of goblet cells. Intractable enterocolitis continued and the patient finally died of pneumonia. An autoimmune predisposition in DIHS/DRESS patients in combination with CMV reactivation was considered to trigger the severe enterocolitis of this case that showed GVHD‐like features of the gastrointestinal tract. GVHD‐like organ damage is a pathological condition rarely observed in DIHS/DRESS but should be recognized as one of the most severe complications of the disease.

Immunopathogenic Insights on Preferential Human Herpesvirus-6 Reactivation in Drug Rash With Eosinophilia and Systemic Symptoms: A Scoping Review

“…Multi-organ system involvement have been reported with evidence of HHV-6 reactivation within specific organ parenchyma or in serum, sometimes leading to fatal sequelae related to the liver, 12 - 19 kidney, 7 , 12 , 20 - 23 gastrointestinal tract, 24 , 25 bone marrow, 12 , 26 - 28 lymph nodes, 12 , 29 , 30 peripheral and central nervous system, 7 , 31 - 34 heart, 13 , 35 and lung. 36 , 37 There have been many reports of new-onset autoimmune disease, as well.…”

“…The possibility of HHV-6 playing an exacerbating role in both conditions has not been ruled out, as demonstrated by a case of DRESS complicated by GVHD enterocolitis. 25 …”

Comprehensive analyses identify potential biomarkers for encephalitis in HIV infection

“…In the present study, STAT1 , ISG15 , and SCN2B were found to interact with garcinol and ipriflavone, as well as irinotecan and zonisamide, respectively. Interestingly, recent studies have shown that garcinol and ipriflavone have anti-inflammatory effects, especially in the inflammation of the brain 35 – 38 , while irinotecan and zonisamide can induce inflammation 39 – 42 . Therefore, STAT1 , ISG15 , and SCN2B may be new targets for HIVE drug therapy.…”

How to recognize and manage challenging DRESS cases: Two case reports and a review of the literature

“…Herpesviridae reactivation has also been reported in the progression of the disease 15 . However, whether the viral reactivation is a cause or solely a consequence of DRESS syndrome has yet to be elucidated 16,17 . HHV‐6 is the most common virus associated with DRESS, with reactivation reported in 16 to 60% of cases 3,15 …”

“…15 However, whether the viral reactivation is a cause or solely a consequence of DRESS syndrome has yet to be elucidated. 16,17 HHV-6 is the most common virus associated with DRESS, with reactivation reported in 16 to 60% of cases. particular features distinguish this syndrome from others.…”