Successful Treatment of Non-Langerhans Cell Histiocytosis With Topical Rapamycin in Two Pediatric Cases

Effendi, Raden Mohamad Rendy Ariezal; Rizqandaru, Trustia; Yuliasari, Renata; Gondokaryono, Srie Prihianti; Diana, Inne Arline; Dwiyana, Reiva Farah

doi:10.2147/ccid.s375995

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…Translationally, our data strongly encourage one to next probe in a clinical trial whether topical rapamycin can significantly retard the graying process or even repigment graying/white hair, namely in younger individuals with recent onset of hair graying, and whether this indeed prolongs anagen duration in vivo . That topical rapamycin is already frequently used in daily dermatological practice (Mercurio et al , 2021; Balestri et al , 2022; Effendi et al , 2022) facilitates its repurposing for canities and poliosis management, provided that a sufficient level of rapamycin reaches the HFPU of graying/white human anagen HFs.…”

Section: Resultsmentioning

confidence: 99%

mTORC1 activity negatively regulates human hair follicle growth and pigmentation

et al. 2023

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Dysregulation of the activity of the mechanistic target of rapamycin complex 1 (mTORC1) is commonly linked to aging, cancer, and genetic disorders such as tuberous sclerosis (TS), a rare neurodevelopmental multisystemic disease characterized by benign tumors, seizures, and intellectual disability. Although patches of white hair on the scalp (poliosis) are considered as early signs of TS, the underlying molecular mechanisms and potential involvement of mTORC1 in hair depigmentation remain unclear. Here, we have used healthy, organ‐cultured human scalp hair follicles (HFs) to interrogate the role of mTORC1 in a prototypic human (mini‐)organ. Gray/white HFs exhibit high mTORC1 activity, while mTORC1 inhibition by rapamycin stimulated HF growth and pigmentation, even in gray/white HFs that still contained some surviving melanocytes. Mechanistically, this occurred via increased intrafollicular production of the melanotropic hormone, α‐MSH. In contrast, knockdown of intrafollicular TSC2, a negative regulator of mTORC1, significantly reduced HF pigmentation. Our findings introduce mTORC1 activity as an important negative regulator of human HF growth and pigmentation and suggest that pharmacological mTORC1 inhibition could become a novel strategy in the management of hair loss and depigmentation disorders.

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Section: Resultsmentioning

confidence: 99%

mTORC1 activity negatively regulates human hair follicle growth and pigmentation

et al. 2023

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“…27 Topical rapamycin, which targets the PI3K/mTOR pathway, was successfully administered to the JXG lesions. 28 Our commentary highlights the importance of complete genomic profiling, including mutant signal pathways and translocations involved in cell proliferation. This reveals the novel pathogenesis of SJXG and guides the use of targeted agents, particularly for patients who fail to respond to conventional therapies.…”

Section: The Treatment Modalities In Sjxgmentioning

confidence: 98%

“…Another report showed a rapid clinical response to dasatinib in a child with SJXG with MRC1‐PDGFRB translocation 27 . Topical rapamycin, which targets the PI3K/mTOR pathway, was successfully administered to the JXG lesions 28 …”

Section: The Treatment Modalities In Sjxgmentioning

confidence: 99%

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Frequent detection of genetic aberrations reveals novel pathogenesis and treatment modalities in systemic juvenile xanthogranuloma

Xu,

Ma,

Yao

et al. 2023

Pediatric Investigation

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Frequent detection of genetic aberrations reveals novel pathogenesis and treatment modalities in systemic juvenile xanthogranulomaJuvenile xanthogranuloma (JXG), the most common form of non-Langerhans cell histiocytosis (non-LCH), is generally confined to the skin during infancy and early childhood. 1 JXG rarely involves extracutaneous tissues or systemic organs, resulting in high morbidity and mortality rates. Clonality in JXG has been verified by histopathological and genetic analyses, which have shown it to be tumorous rather than a reactive disorder of JXG. 2 However, the exact etiopathogenesis of JXG remains unclear.Diverse organs and systems can be involved in systemic JXG (SJXG). The most common extracutaneous sites include the eyes, central nervous system (CNS), liver, and lungs. Compared with cutaneous JXG, SJXG usually requires more aggressive treatment. Conventionally, the first-line treatment for SJXG is based on chemotherapy used in Langerhans cell histiocytosis (LCH), such as corticosteroids and vinblastine, with various responses. 3 Alternative regimens include methotrexate, cladribine, and cytarabine when initial chemotherapy fails.In the past decade, genomic studies have been conducted on histiocytosis, including JXG, and distinctive genetic abnormalities have been discovered (e.g., BRAFV600E mutations and ALK translocations). 4,5 These novel genetic discoveries further confirmed the tumorigenesis of JXG and highlighted the possibility of therapeutic targets in refractory or severe cases. GENETIC ABERRATIONS IN THE PATHOGENESIS OF SJXGJXG is involved in the clonal proliferation of histiocytes by human androgen receptor assay (HUMARA). 2 However, the drivers of cell proliferation in JXG remain to be elucidated. Several cases of JXG have been reported

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Yellow papules on the face and scalp

Ashworth

Oliveira

Ferreira

et al. 2023

Anales de Pediatría (English Edition)

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Successful Treatment of Non-Langerhans Cell Histiocytosis With Topical Rapamycin in Two Pediatric Cases

Cited by 8 publications

References 23 publications

mTORC1 activity negatively regulates human hair follicle growth and pigmentation

mTORC1 activity negatively regulates human hair follicle growth and pigmentation

Frequent detection of genetic aberrations reveals novel pathogenesis and treatment modalities in systemic juvenile xanthogranuloma

Yellow papules on the face and scalp

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