International archives of allergy and immunology · 2026
A Narrative Review of Drug-Induced Haemophagocytic Lymphohistiocytosis: A Rare but Relevant Differential Diagnosis.
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Ali Syed B, King Jovanka, Lucas Michaela
Аннотация
INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening, multisystemic, hyperinflammatory disease. There is a trend towards increased reports of drug-induced HLH (diHLH), an entity that has some features akin to severe cutaneous adverse reactions (SCARs). A narrative review was conducted to summarise the literature on reported cases of diHLH.
METHODS: All published cases of diHLH between January 1993 and August 2023 on PubMed database were reviewed, and those with ≥5 HLH-2004 criteria and/or Hscore ≥169 were included. All potential confounding secondary causes of HLH, as well as cases attributed to immune checkpoint inhibitors, chimeric antigen receptor T-cell immunotherapy, and vaccines, were excluded from the analysis.
RESULTS: There were 39 cases identified, with a median age of 28.0 years (IQR = 7-46) and a predominance of males (57.9%). Anticonvulsants (n = 15, 38.4%), particularly lamotrigine (n = 10, 66.7%), and antimicrobials (n = 15, 38.4%) were most frequently implicated. Among the antimicrobials, beta-lactam antibiotics were the most common (n = 12, 80%). Time to latency for presentation of diHLH was 14 days (IQR = 8-21); anticonvulsants had a significantly longer latency (17 days) than antimicrobials (12.5 days; p = 0.0180). The median HLH-1994/2004 diagnostic criteria and Hscore were 5 and 227, respectively. Ten patients (25.6%) also had SCAR features at initial presentation (DRESS syndrome: n = 7 and Stevens-Johnson syndrome and/or toxic epidermal necrolysis: n = 3). Nine patients (23.1%) succumbed to the disease, who were significantly older (median age of 56 years) compared to those achieving remission (median age of 27.5 years, p = 0.0092).
CONCLUSION: Drug induced HLH is a rare but important diagnosis sharing some similarities in its initial presentation with SCAR, including anticonvulsants and antimicrobials as culprit drugs. As diHLH mortality parallels that in other forms of secondary HLH, prompt recognition is required for culprit drug cessation and initiation of immunosuppressive treatment.
METHODS: All published cases of diHLH between January 1993 and August 2023 on PubMed database were reviewed, and those with ≥5 HLH-2004 criteria and/or Hscore ≥169 were included. All potential confounding secondary causes of HLH, as well as cases attributed to immune checkpoint inhibitors, chimeric antigen receptor T-cell immunotherapy, and vaccines, were excluded from the analysis.
RESULTS: There were 39 cases identified, with a median age of 28.0 years (IQR = 7-46) and a predominance of males (57.9%). Anticonvulsants (n = 15, 38.4%), particularly lamotrigine (n = 10, 66.7%), and antimicrobials (n = 15, 38.4%) were most frequently implicated. Among the antimicrobials, beta-lactam antibiotics were the most common (n = 12, 80%). Time to latency for presentation of diHLH was 14 days (IQR = 8-21); anticonvulsants had a significantly longer latency (17 days) than antimicrobials (12.5 days; p = 0.0180). The median HLH-1994/2004 diagnostic criteria and Hscore were 5 and 227, respectively. Ten patients (25.6%) also had SCAR features at initial presentation (DRESS syndrome: n = 7 and Stevens-Johnson syndrome and/or toxic epidermal necrolysis: n = 3). Nine patients (23.1%) succumbed to the disease, who were significantly older (median age of 56 years) compared to those achieving remission (median age of 27.5 years, p = 0.0092).
CONCLUSION: Drug induced HLH is a rare but important diagnosis sharing some similarities in its initial presentation with SCAR, including anticonvulsants and antimicrobials as culprit drugs. As diHLH mortality parallels that in other forms of secondary HLH, prompt recognition is required for culprit drug cessation and initiation of immunosuppressive treatment.