Severe immune neutropenia/immune agranulocytosis (neutrophils < 0.5 × 109 /L) is a rare condition with limited treatment options 1. We recently described the first case of refractory immune neutropenia treated with the JAK inhibitor ruxolitinib 2. Here, we describe the second case of steroid and G-CSF-refractory immune neutropenia successfully treated with ruxolitinib. A 21-year-old woman presented with a 3-week history of gingivitis, 2-week history of otitis externa, 8-day history of abdominal pain and nausea, and a new onset history of fever. She had iron deficiency but was otherwise healthy. She had received trimethoprim sulfamethoxazole and cefuroxime prior to presentation, but these had been discontinued. Blood tests showed a white blood cell (WBC) count of 1.41 × 109/L (ref. 4.5–11), absolute neutrophil count (ANC) of 0.0 × 109/L (ref. 2–7.5), and lymphocytes 0.83 × 109/L (ref. 1.5–3), which was a dramatic change from bloodwork done 5 months earlier, showing WBC 6.7 × 109/L, neutrophils 3.9 × 109/L and lymphocytes 1.91 (Table 1). G-CSF 300 mcg continued, prednisone stopped Ruxolitinib 10 mg bid G-CSF 300 mcg Ruxolitinib 20 mg BID G-CSF 300 mcg stopped Ruxolitinib 20 mg bid Physical examination showed gingival hyperplasia without any ulcerations in her mouth and a 1.5 cm soft, mobile, non-tender lymph node in the left mid-anterior cervical area; the rest of the exam was unremarkable. Her hemoglobin was 99 g/L (ref. 120–160), platelets 211 × 109/L (ref. 150–350). Blood film showed agranulocytosis with otherwise unremarkable morphology. Creatinine was 68 µmol/L (ref. 49–90), lactate dehydrogenase (LDH) 142 U/L, and C-reactive protein (CRP) 84 mg/L (ref. < 8). Hepatitis B/C, HIV, parvovirus B19, Epstein–Barr virus, CMV, and ANA/ANCA were negative, and vitamin B12 and serum protein electrophoresis were normal. Computed tomography (CT) of the chest, abdomen, and pelvis showed mild splenomegaly (13 cm), mildly enlarged (up to 1.2 cm) mesenteric lymph nodes, and mild right side sacroiliitis. Bone marrow aspirate and biopsy showed a hypocellular marrow with agranulocytosis (Figure 1). Flow cytometry was negative for T-LGL leukemia. The working diagnosis was immune neutropenia versus drug-induced agranulocytosis from recent antibiotics. Due to the lack of antecedent bloodwork, it was impossible to distinguish whether the neutropenia arose before or after the ear infection and antibiotic exposure, although gingival swelling is a classic symptom of neutropenia. She was started on 30 mg of prednisone daily and 300 mcg of G-CSF sc daily. On September 26, 2025, her ANC remained 0.03 × 109/L. Ruxolitinib 10 mg BID was started. On September 27, her ANC was 0.02 × 109/L and lymphocytes 1.90 × 109/L. On September 28, her ANC was 0.0 × 109/L, but lymphocytes rose to 3.87 × 109/L, and ruxolitinib was increased to 20 mg BID. Her ANC was 0.60 × 109/L on September 29, 8.9 × 109/L on September 30, 28.6 × 109/L on October 1. Her blood film showed mature neutrophils, reactive lymphocytes, and immature granulocytes, consistent with marrow recovery (Figure 1). Ruxolitinib was discontinued, and she was discharged home on October 1. Over the next 2 weeks, her CBC returned to normal. Severe immune neutropenia is diagnosed after ruling out other causes such as medications, infections, and lymphoproliferative disorders 1. Severe immune neutropenia is a rare but serious disorder, and treatments are lacking; 3 the last significant drug for immune neutropenia was G-CSF over 30 years ago 2, 4. Ruxolitinib is very effective for immune neutropenia due to T-LGLL 5. We recently published the first case of immune neutropenia responsive to ruxolitinib in a 77-year-old male. That patient remains in remission but requires ongoing ruxolitinib. The present case represents the second patient with immune neutropenia responsive to ruxolitinib. Like the first case, she also required a higher dose, 20 mg BID, but only needed the medication for 5 days and has maintained a remission for nearly 4 months off all medications. As in T-LGLL, ruxolitinib is emerging as a significant treatment option for other causes of immune neutropenia refractory to steroids and G-CSF 6. In this case, drug-induced agranulocytosis cannot be ruled out, and she was on G-CSF during her neutrophil recovery, but the clear temporal association between the introduction of ruxolitinib and dramatic improvement in lymphocyte and neutrophil count demonstrates that JAK inhibition can be quite effective in the resolution of severe immune-mediated neutropenia. Her profound neutrophilia after initiation of ruxolitinib may have been influenced impart by G-CSF, but the rapid recovery in lymphocyte and neutrophil counts after initiation of ruxolitinib, strongly suggests that the JAK inhibitor was the main cause of her recovery. This clinical observation supports further study of JAK inhibition as a potential treatment for immune neutropenia. Luke Chen's research is supported by a philanthropic gift from the Hsu & Taylor family through the VGH & UBC Hospital Foundation and Nova Scotia Health. The authors have nothing to report. We have written patient consent on file. The authors declare no conflicts of interest. The authors have nothing to report.
Schwarzkopf et al. (Wed,) studied this question.