Cyclophosphamide immunomodulation of TB-associated cerebral vasculitis

Celotti, A.; Vianello, Fabrizio; Sattin, Andrea; Malipiero, Giacomo; Faggin, Roberto; Cattelan, Anna María

doi:10.1080/23744235.2018.1467038

“…Cyclophosphamide, an alkylating cytotoxic drug is an effective drug in the treatment of primary cerebral vasculitis. Two case reports have described clinical improvement with the use of cyclophosphamide in TBM associated cerebral vasculitis 57 , 58 ; however, its role as an effective treatment in this context needs further investigation particularly due to concerns over its potential adverse activity as a potent immunosuppressive drug. Table 2 summarises cases within the published literature where these agents have been used in the context of TBM; however, pre-clinical and clinical studies to systematically investigate the therapeutic effectiveness is required before they can be used more widely as adjunctive therapies in TBM.…”

Section: Promising Host Directed Therapies For Tuberculous Meningitismentioning

confidence: 99%

Host Directed Therapies for Tuberculous Meningitis

Davis

¹

,

Donovan

²

,

Bremer

³

et al. 2021

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A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.

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“…Cyclophosphamide, an alkylating cytotoxic drug is an effective drug in the treatment of primary cerebral vasculitis. Two case reports have described clinical improvement with the use of cyclophosphamide in TBM associated cerebral vasculitis 54,55 ; however, its role as an effective treatment in this context needs further investigation, particularly due to concerns over its potential adverse activity as a potent immunosuppressive drug. Table 2 summarises cases within the published literature where these agents have been used in the context of TBM; however, pre-clinical and clinical studies to systematically investigate the therapeutic effectiveness are required before they can be used more widely as adjunctive therapies in TBM.…”

Section: Immunomodulatory Therapiesmentioning

confidence: 99%

Host Directed Therapies for Tuberculous Meningitis

Davis

¹

,

Donovan

²

,

Bremer

³

et al. 2020

View full text Add to dashboard Cite

A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.

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“…Celotti et al, 2018 [10] Brain A patient diagnosed with tuberculous meningitis and started the anti-TB therapy and dexamethasone. On second attempt to taper steroid the patient had cognitive impairment with decreased level of consciousness.…”

Section: Site Of Paradoxical Reaction Conclusion and Manifestationsmentioning

confidence: 99%

Multifocal Tuberculosis with Prolonged Paradoxical Reaction

Al-Ebrahim

¹

,

Madani

²

2019

JKAU Med Sci

0

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This is a case report describing successful treatment of a challenging case of an 18-year old previously healthy high school male student with multifocal tuberculosis involving the spleen and mediastinal and abdominal lymph nodes confirmed by histopathology of splenectomy tissue. The patient initially responded well to antituberculosis therapy with complete resolution of fever and improvement in his general health and weight. However, two months after initiation of anti-tuberculosis therapy, the patient developed paradoxical reaction manifest as recurrence of fever that persisted for five months and was associated with enlargement of lymph nodes. The fever failed to abate with continuation of the same antituberculosis therapy. Despite reassurance that the fever was due to a prolonged paradoxical reaction, a decision was made by the family to seek advice in another hospital where lymphoma was excluded again by histopathological examination of an excisional lymph node biopsy that revealed caseating granulomatous lymphadenitis and negative tuberculosis stain, culture, and polymerase chain reaction. The patient was continued on anti-tuberculosis therapy and treated with corticosteroids that resulted in complete resolution of fever and subsequent full recovery from his tuberculosis.

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Cyclophosphamide immunomodulation of TB-associated cerebral vasculitis

Cited by 6 publications

References 9 publications

Host Directed Therapies for Tuberculous Meningitis

Host Directed Therapies for Tuberculous Meningitis

Host Directed Therapies for Tuberculous Meningitis

Multifocal Tuberculosis with Prolonged Paradoxical Reaction

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