P006 Use of baricitinib in an human immunodeficiency virus-positive patient who developed refractory haemophagocytic lymphohistiocytosis with an unknown trigger: was it worth the risk?

Background/Aims We present the case of a 64-year-old lady Zimbabwean female with a background of HIV, who developed haemophagocytic lymphohistiocytosis (HLH) due to an unknown trigger, and required the use of baracitinib to gain control of the refractory cytokine storm. Methods Her initial presentation of a 7-day history of flu-like symptoms and fever was managed as a viral infection. Considering her background of HIV and previous cerebral toxoplasmosis, she was admitted for further investigations when she re-presented with facial swelling and widespread rash. Bloods demonstrated a neutrophilic leucocytosis, CRP 141.8mg/L, CK 220 IU/L, undetectable HIV viral load, past infection with hepatitis B, an indeterminate IGRA, but a positive HSV-1 DNA (IV aciclovir was commenced). CT thorax, abdomen and pelvis showed no lymphadenopathy or evidence of superior vena cava obstruction. Skin biopsy was non-specific and myositis immunoblot was negative. Persistent fevers, hyperferritinaemia (32,621 mcg/L) and hypertriglyceridaemia led to calculation of an H score (164 points). Bone marrow aspirate confirmed features of haemophagocytosis (H score 199 points). Corticosteroid treatment was commenced but quickly weaned and replaced with IV anakinra (2mg/kg à 4mg/kg à 8mg/kg) due to concerns about masking of an HIV-related lymphoma. No evidence of a malignancy was found on deep skin and excision lymph node biopsies and CT PET scans. An inadequate response to anakinra led to a switch to baricitinib with guidance from the national HLH MDT and local medicine management and therapeutics committee approval; initially for 2 weeks but extended to a total of 6 months as the patient responded well to treatment both clinically and biochemically. Latest ferritin is 66 mcg/L and CRP 1.2 mg/L. Methotrexate has now replaced baricitinib. Results Refractory HLH, particularly when there is no clear trigger but concern about steroid use masking lymphoma, continues to pose management challenges. This case was further complicated by HIV positivity; whilst viral load was suppressed, chronic HIV infection can cause persistent immune activation and dysregulated cytokine signalling. In the absence of an alternative trigger, it is possible that HIV-associated immune dysregulation itself contributed to the development of HLH. Immune regulation inflammatory syndrome was an unlikely trigger as HIV therapy had not been recently modified. With close multidisciplinary oversight, baricitinib was used as salvage therapy for six months without HIV reactivation, highlighting that Janus kinase inhibitors (JAK-i) may be an option in refractory HLH even in immunocompromised HIV patients. Controlled data is lacking but case reports suggest that combined JAK-1 and 2 (e.g. baracitinib and ruxolitinib) may be superior to JAK-1 inhibition alone. Conclusion This case posed challenges due to refractory HLH with no clear trigger in an HIV-positive patient. It supports cautious use of baracitinib, even in immunocompromised patients, where standard cytokine blockade agents have failed. Disclosure U. Ahmed: None. K. Sharma: None. M. Iftikhar: None. A. Ahmed: None.