BACKGROUND

Lithium has been known as a second-line treatment for hyperthyroidism. However, it has a narrow therapeutic range especially in patients with impaired renal function. Toxicity can cause neurological, gastrointestinal, cardiovascular, and renal symptoms, including rare cases of renal failure needing renal replacement therapy. This case report highlights a rare instance of acute lithium toxicity in a patient with multinodular goiter and chronic kidney disease, following methimazole-induced agranulocytosis.

A 55-year-old Filipino woman with chronic kidney disease and multinodular toxic goiter who developed methimazole-induced agranulocytosis presented with altered mental status after pre-treatment with lithium. Laboratory tests confirmed elevated lithium levels, consistent with acute lithium toxicity. She developed acute kidney injury, necessitating urgent hemodialysis with hemoperfusion. After two sessions, her neurological status and renal function improved. The patient resumed pre-treatment with carbimazole and subsequently underwent successful RAI then maintained on levothyroxine for long-term thyroid management

Lithium toxicity is rare but can cause life-threatening complications, particularly in patients with pre-existing kidney disease. Hemodialysis remains the treatment of choice for severe toxicity, significantly improving patient outcomes. Lithium toxicity can occur even within therapeutic levels, emphasizing the need for careful monitoring. This case highlights the importance of clinical vigilance when using lithium.

Introduction: Autoimmune thyroid disease is frequently associated with other immune-mediated disorders; however, clinically significant pancytopenia is rare. In patients with Graves’ disease receiving antithyroid therapy, leukopenia raises concern for drug-induced agranulocytosis, a rare but potentially life-threatening complication characterized by severe neutropenia requiring immediate drug withdrawal. The coexistence of hemolytic anemia and thrombocytopenia may instead suggest Evans syndrome, defined by autoimmune hemolytic anemia with immune thrombocytopenia, with or without neutropenia. Importantly, uncontrolled thyrotoxicosis itself may cause immunemediated cytopenias, creating a diagnostic challenge. Case: We report a 55-year-old female with thyroid receptor antibody-positive Graves’ disease who presented with jaundice and pancytopenia while receiving carbimazole therapy. Laboratory evaluation demonstrated anemia with reticulocytosis and a positive direct antiglobulin test, thrombocytopenia and leukopenia. Complement testing revealed reduced C3 with normal C4, consistent with immune-mediated hemolysis. Peripheral blood film showed no blast cells or marrow infiltration, and autoimmune screening, including antinuclear antibodies and anti–double stranded DNA, was negative. The coexistence of Coombs-positive hemolysis and thrombocytopenia initially raised suspicion for Evans syndrome, while leukopenia during carbimazole therapy prompted concern for drug-induced agranulocytosis. However, neutropenia was not severe, and the absence of marrow infiltration or systemic autoimmune disease made alternative causes of pancytopenia less likely. Importantly, blood counts progressively improved following the optimization of thyroid control despite continuation of carbimazole at a reduced dose, without the use of immunosuppressive therapy. This clinical course supported the interpretation of thyrotoxicosis-associated immune cytopenia rather than primary Evans syndrome or carbimazole-induced agranulocytosis. Conclusion This case highlights thyrotoxicosis-associated immune cytopenia as an important mimic of Evans syndrome and carbimazole-related hematological toxicity. Recognizing this entity is essential to avoid unnecessary discontinuation of antithyroid therapy or inappropriate immunosuppressive treatment.
Evans Syndrome ; Carbimazole ; Pancytopenia ; Agranulocytosis ; Graves Disease

Introduction: Severe thyrotoxicosis is particularly difficult to manage when antithyroid drugs are contraindicated. Therapeutic plasma exchange (TPE) is an adjunctive option in complicated hyperthyroidism, including thyroid storm and refractory thyrotoxicosis, through the rapid removal of circulating thyroid hormones, hormone-binding proteins, cytokines, and thyroid autoantibodies. However, its precise role and indications remain incompletely defined. We report two patients with Graves’ disease complicated by carbimazole-induced agranulocytosis in whom TPE was used as bridging therapy before total thyroidectomy. Cases: The first patient was a 32-year-old female who developed carbimazole-induced agranulocytosis 1 month after the diagnosis of hyperthyroidism. Biochemical control remained unsatisfactory despite second-line therapy with high-dose lithium, cholestyramine, propranolol, corticosteroids, and 5 days of Lugol’s iodine. Over 8 days, free thyroxine (fT4) increased by 13%, necessitating TPE for preoperative stabilization. Following three cycles over 4 days, fT4 decreased by 20%, from 52 to 41 pmol/L, enabling successful total thyroidectomy. The second patient was a 26-year-old female who presented with neutropenic sepsis and severe agranulocytosis 2 months after being diagnosed with Graves’ disease. She received second-line therapy, and neutrophil recovery occurred only after 7 days of granulocyte colony-stimulating factor. TPE, together with Lugol’s iodine, was then initiated as bridging therapy before surgery. After 5 days of Lugol’s iodine and three TPE cycles, fT4 decreased by 43%, from 58 to 33 pmol/L, permitting total thyroidectomy. Conclusion These cases highlight TPE as a useful bridging strategy in Graves’ thyrotoxicosis when antithyroid drugs are precluded by agranulocytosis, and conventional secondline therapy fails to achieve adequate biochemical control. TPE may facilitate timely stabilization and safe progression to definitive surgical treatment.
Plasma Exchange ; Agranulocytosis ; Graves Disease

OBJECTIVE: To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children. METHODS: The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared. RESULTS: A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G⁺), the most common multi-drug resistant G⁺ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G^- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011). CONCLUSIONS The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.
Humans ; Child ; Shock, Septic ; Retrospective Studies ; Sepsis ; Risk Factors ; Bacteria ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Escherichia coli ; Anti-Infective Agents ; Agranulocytosis

OBJECTIVES: To study the application value of metagenomic next-generation sequencing (mNGS) for pathogen detection in childhood agranulocytosis with fever. METHODS: A retrospective analysis was performed on the mNGS results of pathogen detection of 116 children with agranulocytosis with fever who were treated from January 2020 to December 2021. Among these children, 38 children with negative mNGS results were enrolled as the negative group, and 78 children with positive results were divided into a bacteria group (n=22), a fungal group (n=23), and a viral group (n=31). Clinical data were compared between groups. RESULTS: For the 116 children with agranulocytosis and fever, the median age was 8 years at diagnosis, the median turnaround time of mNGS results was 2 days, and the positive rate of mNGS testing was 67.2% (78/116). Compared with the negative group, the bacterial group had a higher procalcitonin level (P<0.05), the fungal group had higher level of C-reactive protein and positive rate of (1,3)-β-D glucan test/galactomannan test (P<0.05), and the fungal group had a longer duration of fever (P<0.05). Among the 22 positive microbial culture specimens, 9 (41%) were consistent with the mNGS results. Among the 17 positive blood culture specimens, 8 (47%) were consistent with the mNGS results. Treatment was adjusted for 28 children (36%) with the mNGS results, among whom 26 were cured and discharged. CONCLUSIONS The mNGS technique has a shorter turnaround time and a higher sensitivity for pathogen detection and can provide evidence for the pathogenic diagnosis of children with agranulocytosis and fever.
Agranulocytosis/diagnosis* ; Bacteria ; Child ; Fever/diagnosis* ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Metagenomics/methods* ; Retrospective Studies ; Sensitivity and Specificity

OBJECTIVE: To explore the intervention effect of recombinant human interleukin-11 (rhIL-11) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the duration and severity of agranulocytosis in patients with hematological malignancies after chemotherapy, and to analyze the influencing factors. METHODS: The data of hematological malignancy patients treated with rhIL-11 and rhG-CSF after chemotherapy in the hematology department of The First Hospital of Lanzhou University from July 2017 to July 2020 were collected retrospectively. The duration and differences of agranulocytosis in differeent groups were compared by univariate analysis, and the influencing factors of agranulocytosis duration were further analyzed by multiple regression analysis. RESULTS: The duration of agranulocytosis in 97 patients was 6.47±2.93 days. The results of univariate analysis showed that there were no statistical differences in the duration of agranulocytosis among patients with different sex, age, height, weight, body surface area, body mass index (BMI), dose of rhG-CSF, dose of rhIL-11, spontaneous bleeding after administration of rhG-CSF and rhIL-11, and the duration of agranulocytosis in patients with different red blood cell count (RBC), hemoglobin(HGB) level, platelet count (PLT) and absolute neutrophil count (ANC), before administration of rhG-CSF and rhIL-11. There were significant differences in agranulocytosis time among patients with different disease types, chemotherapy cycle, fever after rhG-CSF and rhIL-11 administration, and different white blood cell count (WBC) baseline level before rhG-CSF and rhIL-11 administration (P＜0.05). Compared with patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), patients with acute myeloid leukemia (AML) had the longest duration of agranulocytosis, which was 7.07±3.05 d. Compared with patients with chemotherapy cycles of 4－6 and ≥7, patients with total chemotherapy cycle of 1－3 had the shortest duration of agranulocytosis, which was 5.25±2.48 d. Compared with patients without fever, patients with fever within 1 day after administration of cytokines and patients with fever within 2-5 days after administration of cytokines, the duration of agranulocytosis was the longest in patients with fever 6 days after administration of cytokines, which was 8.85±2.85 d. Compared with patients with WBC baseline <1.0×10⁹/L, (1.0－1.9)×10⁹/L and (2.0－3.9)×10⁹/L, patients with WBC baseline ≥4.0×10⁹/L had the shortest duration of agranulocytosis, which was 4.50±2.56 d. Multiple linear regression analysis showed that chemotherapy cycle, different fever after administration of rhG-CSF and rhIL-11, diagnosis of ALL and NHL, and WBC baseline level before administration of rhG-CSF and rhIL-11 were the influencing factors of the duration of agranulocytosis (P＜0.001). CONCLUSION The risk of prolonged agranulocytosis is higher in patients diagnosed with AML, with more chemotherapy cycles, lower WBC baseline before cytokines administration and fever later after cytokines administration, which should be paid more attention to.
Agranulocytosis ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematologic Neoplasms/drug therapy* ; Humans ; Interleukin-11 ; Lymphoma, Non-Hodgkin/drug therapy* ; Recombinant Proteins/therapeutic use* ; Retrospective Studies

Agranulocytosis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; China ; Fever ; Humans ; Pharmaceutical Preparations

A 34-year-old Filipino with Graves' disease on methimazole came in due to fever, sore throat and jaundice. Patient was initially diagnosed with methimazole induced agranulocytosis and drug induced liver injury. She was treated with intravenous broad spectrum antibiotic and granulocyte colony stimulating factor. On day 4 of admission, patient had pancytopenia and was managed as methimazole induced aplastic anemia and was started on steroid therapy and 1 unit of packed red blood cell was transfused. The jaundice also increased hence she was given ursodeoxycholic acid. On day 9 of admission, with the consideration of "lineage steal phenomenon," biopsy was done and eltrompobag was started. Patient was discharged stable at 12th day of hospital admission. This case presents the 3 rarest, life threatening complication of methimazole: agranulocytosis, aplastic anemia and hepatitis. 

Autoimmune hemolytic anemia is a disease characterized with destruction of erythrocytes as a result of antibody produce against patient's own erythrocytes and anemia. Autoimmune hemolytic anemia can be roughly stratified into two groups according to serological features and secondary causes including drugs induced hemolytic anemia. Drugs induced autoimmune hemolytic anemia is very rare in pediatric patients. Even though hematological side effects such as leucopenia, agranulocytosis, eosinophilia, thrombocytopenic purpura and aplastic anemia might occur due to psychotropic drug use; to the best of our knowledge there is no autoimmune hemolytic anemia case due to quetiapine, an atypical antipsychotics, in literature. We hereby describe the first child case of autoimmune hemolytic anemia during quetiapine treatment.We also are pointing out that one should keep in mind serious hematological side effects with atypical antipsychotic drug use with this case report.
Agranulocytosis ; Anemia ; Anemia, Aplastic ; Anemia, Hemolytic ; Anemia, Hemolytic, Autoimmune* ; Antipsychotic Agents ; Child* ; Eosinophilia ; Erythrocytes ; Humans ; Purpura, Thrombocytopenic ; Quetiapine Fumarate*

Ecthyma gangrenosum (EG) is a rare skin manifestation which starts with a maculopapular eruption and followed by a necrotic ulcer covered with black eschar. EG usually occurs in immunosuppressed patients with Pseudomonas aeruginosa sepsis. We present a previously healthy 12-month-old girl with EG by P. aeruginosa and agranulocytosis due to influenza A and then rhinovirus infection, without bacteremia. It is important for allergists to culture wound and differentiate EG from other skin disorders including Tsutsugamushi disease and initiate appropriate empiric antipseudomonal antibiotic treatment, and to evaluate for possible immunodeficiency, even in a healthy child.
Agranulocytosis* ; Bacteremia ; Child ; Ecthyma* ; Female* ; Humans ; Infant* ; Influenza, Human ; Pseudomonas aeruginosa ; Rhinovirus ; Scrub Typhus ; Sepsis ; Skin ; Skin Manifestations ; Ulcer ; Wounds and Injuries