Dapsone Hypersensitivity Syndrome-related Lung Injury without Eosinophilia in the Bronchoalveolar Lavage Fluid

Abstract

A 73-year-old man was admitted in respiratory failure that had subacutely progressed after five weeks of dapsone treatment for a skin rash. He also presented with fever, systemic erythroderma and liver dysfunction. Chest computed tomography showed diffuse reticular shadows with ground-glass opacity and bilateral mediastinal lymphadenopathy. Lymphocytes, but not eosinophils, were increased in the bronchoalveolar lavage fluid. Moreover, reactivation of human herpes virus-6 was confirmed on a paired serum test. Finally, we diagnosed the patient with dapsone hypersensitivity syndrome (DHS), a rare adverse event of this drug. Lung injury unaccompanied by eosinophilia in the bronchoalveolar lavage fluid is even more rare as a DHS-related lung manifestation.

Dapsone hypersensitivity syndrome

“…HLA-B * 13:01 has been found to be a strong risk factor for DHS, according to a genome-wide association study (odds ratio, 20.53; P = 6.84 Â 10 À25 ) [5] and major histocompatibility complex (MHC) I region typing (odds ratio, 69.6; P = 1.96 Â 10 À11 ) [6] in the Chinese population. The same HLA association has been verified in Taiwan (China), [7] Japan, [8] Thailand, [9] Malaysia, [10] India, [11] Korea, [12] and Indonesia. [13] In addition, the HLA-B * 13:01 allele is significantly associated with DDSinduced Stevens-Johnson syndrome and toxic epidermal necrolysis.…”

Bronchoscopic Investigation of Atypical Drug-induced Hypersensitivity Syndrome Showing Viral Lung Involvement

“…There have been at least eight case reports of DIHS/ DRESS in the English literature showing pulmonary manifestations (12)(13)(14)(15)(16)(17)(18)(19) (Table), however, a histopathological evaluation was not performed in most cases. Six cases (cases 1-6) showed lung involvement as one of the initial manifestations of DIHS/DRESS within 0-2 weeks after the disease onset.…”

Transplante De Fígado Por Falência Hepática Fulminante Secundária a Tratamento De Hanseníase: Relato De Caso

“…Um mecanismo proposto envolve a formação de haptenos a partir de metabólitos da dapsona, que subsequentemente produzem anticorpos anti-dapsona, induzindo diferentes respostas adversas. 17 Esses metabólitos tóxicos são produzidos como resultado do metabolismo oxidativo pelo citocromo P450, mieloperoxidases e peroxidases da tireóide e, geralmente, são ainda mais biotransformados e desintoxicados pela epóxido-hidroxilase. Pacientes que não possuem essa enzima ou têm mutações disfuncionais em seu gene são mais propensos a desenvolver a síndrome.…”

“…Metabólitos oxidativos também podem causar a liberação de citocinas que alertam o sistema imunológico do estresse e dano celular. 17 O paciente em questão apresentou a SHD com quadro de anemia, dermatite esfoliativa, icterícia progressiva, elevação importante das enzimas hepáticas, alargamento do INR e aumento das bilirrubinas. Ao quadro, somou-se o diagnóstico de FHF, já que apresentou encefalopatia hepática severa em adição à queda da função do órgão.…”