Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte–Mediated Bullous Skin Disorders

Chen, Chun‐Bing; Kuo, Kang-Ling; Wang, Chuang‐Wei; Lu, Chun‐Wei; Hui, Rosaline Chung‐Yee; Lu, Kun-Lin; Chang, Wen Han; Chen, Wei-Ti; Fu, Yao‐Shi; Teng, Yu-Chuan; Lee, Hua-En; Lin, Jingyi; Ho, Hung‐Yao; Chi, Min‐Hui; Yang, Lin; Chang, Chee Jen; Lin, Yu Hui; Ku, Cheng‐Lung; Hung, Shuen‐Iu; Chang, Ya‐Ching; Chung, Wen‐Hung

doi:10.1016/j.jaip.2020.09.048

Cited by 24 publications

(25 citation statements)

References 38 publications

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“…Both diseases are mediated by cytolytic factors such as perforin/granzyme B and granulysin. 6,7 A recent publication analysed lesional granulysin levels in bullous skin diseases and observed high levels of granulysin in TEN and, to a lower amount, in bullous GvHD. 7 Regarding therapeutic strategies, first-line treatment in acute severe GvHD is systemic methylprednisolone (2 mg/kg BW/day).…”

mentioning

confidence: 99%

“…6,7 A recent publication analysed lesional granulysin levels in bullous skin diseases and observed high levels of granulysin in TEN and, to a lower amount, in bullous GvHD. 7 Regarding therapeutic strategies, first-line treatment in acute severe GvHD is systemic methylprednisolone (2 mg/kg BW/day). 8 In TEN, cessation of the causing agent, high-dose intravenous immunoglobulins together with systemic steroids are recommended.…”

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confidence: 99%

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Toxic epidermal necrolysis‐like acute cutaneous graft‐versus‐host disease in a stem cell recipient – a diagnostic dilemma

Klein¹,

Kolm

Nair

et al. 2021

Acad Dermatol Venereol

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confidence: 99%

Toxic epidermal necrolysis‐like acute cutaneous graft‐versus‐host disease in a stem cell recipient – a diagnostic dilemma

Klein¹,

Kolm

Nair

et al. 2021

Acad Dermatol Venereol

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“…However, the percentage of GBFDE patients who would test positive with this assay has not been studied. The level of granulysin expressed in blister fluid in cytotoxic T cell-mediated disorders, including SJS/TEN and both generalized and localized bullous FDE, has been found to be significantly higher than in non-cytotoxic T cell-mediated blistering disorders such as bullous lupus erythematosus, pemphigus vulgaris, and bullous pemphigoid [ 49 ]. Moreover, blister granulysin levels in SJS/TEN have recently been shown to be significantly higher than in bullous FDE, although the comparison did not differentiate between localized and generalized bullous FDE [ 49 ].…”

Section: Generalized Bullous Fixed Drug Eruption (Gbfde)mentioning

confidence: 99%

“…The level of granulysin expressed in blister fluid in cytotoxic T cell-mediated disorders, including SJS/TEN and both generalized and localized bullous FDE, has been found to be significantly higher than in non-cytotoxic T cell-mediated blistering disorders such as bullous lupus erythematosus, pemphigus vulgaris, and bullous pemphigoid [ 49 ]. Moreover, blister granulysin levels in SJS/TEN have recently been shown to be significantly higher than in bullous FDE, although the comparison did not differentiate between localized and generalized bullous FDE [ 49 ]. Further studies will be necessary to determine if lesional granulysin levels within blister fluid can help to differentiate SJS/TEN and GBFDE; however, these entities are ultimately clinical diagnoses based on consistent history and physical exam findings.…”

Section: Generalized Bullous Fixed Drug Eruption (Gbfde)mentioning

confidence: 99%

A Review of Fixed Drug Eruption with a Special Focus on Generalized Bullous Fixed Drug Eruption

Anderson

Lee

2021

Medicina

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Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is ingested. With each recurrence, the eruption can involve additional sites. Lesions can have overlying vesicles and/or bullae, and when they cover a significant percentage of body surface area, the eruption is referred to as generalized bullous fixed drug eruption (GBFDE). Due to the widespread skin denudation that can be seen in this condition, GBFDE may be confused clinically with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). While treatments described for GBFDE include supportive care, topical and/or systemic steroids, and, recently, cyclosporine, the mainstay of management involves identifying and discontinuing the causative drug. This review article will provide an overview of FDE with an emphasis on its generalized bullous variant.

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“…Granulysin has been identified as an important effector molecule in bullous skin disorders mediated by cytotoxic T cells [27][28][29], including EMM [27,28]. CD4 + CD8 + T cells in BF in our patient expressed high levels of granulysin, along with perforin, and the frequency of cells expressing these cytotoxic markers among CD4 + CD8 + was higher than among CD4 + or CD8 + single positive T cells (37,6% of cells among vs. 10,8% among CD4 − CD8 + and 0,02% among CD4 + CD8 − T cells, Fig.…”

Section: Case Descriptionmentioning

confidence: 99%

Clonal expansion of CD4+CD8+ T cells in an adult patient with Mycoplasma pneumoniae-associated Erythema multiforme majus

Volkers

Meisel

Terhorst‐Molawi

et al. 2021

Allergy Asthma Clin Immunol

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Background Erythema multiforme (EM) is an acute, immune-mediated mucocutaneous disease, most often preceded by herpes simplex virus (HSV) infection or reactivation. Mycoplasma pneumoniae (Mp) is considered the second major trigger of EM and is often associated with an atypical and more severe presentation of disease, characterized by prominent mucosal involvement. However, contrary to HSV-associated Erythema multiforme (HAEM), immunological mechanisms of Mp-associated EM remain unclear. Case presentation We present the case of a 50-year-old male patient presenting with community-acquired pneumonia (CAP) and erythema multiforme majus (EMM). Acute Mp infection was diagnosed by seroconversion, with no evidence of HSV infection as a cause of EMM. We performed immune phenotyping of blister fluid (BF) and peripheral blood (PB) T cells and detected a clonally expanded TCRVβ2+ T cell population that was double positive for CD4 and CD8, and expressed the cytotoxic markers granulysin and perforin. This CD4+CD8+ population comprised up to 50.7% of BF T cells and 24.9% of PB T cells. Two years prior to the onset of disease, the frequency of PB CD4+CD8+T cells had been within normal range and it gradually returned to baseline levels with the resolution of symptoms, suggesting an involvement of this population in EMM disease pathophysiology. Conclusions This report is the first to provide a phenotypic description of lesional T cells in Mp-associated EMM. Characterizing the local immune response might help to address pathophysiological questions and warrants further systematic research.

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Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte–Mediated Bullous Skin Disorders

Cited by 24 publications

References 38 publications

Toxic epidermal necrolysis‐like acute cutaneous graft‐versus‐host disease in a stem cell recipient – a diagnostic dilemma

Toxic epidermal necrolysis‐like acute cutaneous graft‐versus‐host disease in a stem cell recipient – a diagnostic dilemma

A Review of Fixed Drug Eruption with a Special Focus on Generalized Bullous Fixed Drug Eruption

Clonal expansion of CD4+CD8+ T cells in an adult patient with Mycoplasma pneumoniae-associated Erythema multiforme majus

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