Drug-induced hypersensitivity syndrome caused by minodronic acid hydrate

Abstract

Background Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings. Case presentation An 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test. Conclusions We described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

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. 7 , 9 , 26 , 38 , 39 However, association of HHV-6 with severe, organ-specific sequelae are mostly limited to case reports, which precludes the formation of strong conclusions.…”

“… 45 As such, reports of negative HHV-6 assessed only once immediately or shortly after DRESS onset may have missed later reactivation. 8 , 11 , 44 , 46 - 50 While there are many reports of delayed seroconversion or reactivation, 9 , 15 , 33 , 37 , 51 - 54 sometimes with initially undetectable viral loads, 21 , 27 , 55 , 56 HHV-6 reactivation at the onset of DRESS is possible, as well. 8 , 28 , 32 , 57 , 58 It should be noted that HHV-6 reactivation has not been reported before DRESS onset, which suggests that HHV-6 reactivation likely does not cause DRESS.…”

Chronic and Acute Drug-Induced Hypersensitivity Syndrome in a Rural Patient With Cytomegalovirus Infection: A Case Report

“…The limited availability and delayed results of DLST in rural settings pose a challenge, highlighting the need for increased accessibility to specialized diagnostic services in these areas [ 18 ]. In addition, the cutoff of DLST can differ in countries, which may confuse medical professionals in assessing type four allergies to medications [ 19 ]. Even if DLST is negative, there is a possibility that one medicine can be a cause of DIHS.…”

Multidisciplinary approach to diagnosis and management of fever of unknown origin: A case report

“…The skin biopsy report suggested possible follicular eczema, which is a common finding in DIHS. [ 16 , 17 ] Therefore, the possibility of DIHS could not be completely ruled out.…”