Background: Adult hemophagocytic syndrome is a critical condition that is often difficult to diagnose and results in a bad prognosis because of the lack of effective and unified treatment. Aim: To investigate the clinical, diagnosis and treatment of hemophagocytic syndrome. Case Presentation: A 22-year-old female patient received a splenectomy, and the spleen was sent to the King Med Center of Medical Inspection. The results confirmed the diagnosis of hemophagocytic syndrome related to EB (Epstein-Barr) virus infection. Conclusion: Early diagnosis and early intervention are important factors for affecting the progression of the disease and improving its prognosis.
Hemophagocytic syndrome (HS) is a clinically rare autoimmune disease that is characterized in clinical practice by fever, hepatomegaly, splenomegaly, pancytopenia, and hemophagocytosis in the bone marrow, liver, spleen, and lymph nodes. Scott and Rob-Smith have reported a neoplastic disorder, showing hemophagocytosing histiocytes and systemic proliferation of the precursors of histiocytes in 1939.
The diagnosis of HS includes a spectrum of inherited or acquired defects in cytotoxic lymphocyte function, often with uncontrolled infections. HS may also arise as the result of persistent antigen stimulation due to autoimmune disease or malignancy. HS is often described in binary terms as “primary,” indicating Mendelian inheritance of gene mutations resulting in cytotoxic lymphocyte dys- function, or “secondary” indicating an acquired reactive disorder. Increasing evidence describes HS as more complex phenomenon, resulting from specific immune challenges in patients with a susceptible genetic background. Early recognition of HS and evaluation of potential causes is critically important, as survival generally requires urgent treatment with immune suppression and resolution of the activating antigen. However, the diagnosis of HS is challenged by the myriad of pathways that lead to pathologic inflammation and the clinical overlap with other conditions. Further improvements in therapy will require prospective trials to define optimal strategies for each patient based on the individual paths that lead to pathologic inflammation. This paper is a case and literature review that focuses on one HS patient who was admitted to and treated in the First central hospital of Tianjin.
A 22-year-old female patient presented at the local hospital on June 30, 2013, with an intermittent fever accompanied by pancytopenia for >1.0 month. The patient’s fever of 38.5˚C began without obvious inducement; she experienced a slight intolerance to cold. After taking ibuprofen, the patient’s body temperature somewhat decreased; however, the fever returned without obvious chills and reached a high of 39.5˚C. Local treatment with infusion of antibiotics, such as penicillin, had some therapeutic effect; however, the fever returned without pha- ryngalgia, cough, phlegm, headache, nausea, vomiting, urodynia, diarrhea, abdominal pain, urgent urination, or frequent micturition.
On May 24, 2013, a bone marrow aspiration procedure and physical examinations and tests, such as a positron emission tomography-computed tomography (Graph 1), were performed on the patient in the Second People’s Hospital of Huaian; a malignant lymphoma was not excluded. On June 16, 2013, the patient
Graph 1. Positron emission tomography-computed tomography.
had diagnostic chemotherapy with a regimen comprising Cytoxan® (cyclophosphamide), Adriamycin® (hydroxy doxorubicin), vincristine (Oncovin®), and Prednisone (CHOP). On the second day of chemotherapy, the patient’s body temperature was under control; however, the fever returned 2.0 d later and a regimen of cefepime with peroral Voriconazole did not relieve the condition. The patient was given imipenem combined with vancomycin, acyclovir, and foscarnet sodium therapy for 1.0 week, but there was no obvious improvement and she was admitted into the hospital for further treatment.
On admission, the patient received a full physical examination. She appeared to have mild anemia with pale skin and mucosae, but no yellow staining, rash, or hemorrhagic spots. There were several movable, swollen lymph nodes with a maximum diameter of ~1.0 cm in the middle on the neck and under the armpit but no tenderness. The sclera was not yellow. The abdomen was flat without tenderness or rebound tenderness. The liver was felt 7.0 cm below the subcostal margin and the spleen was felt 11 cm below the subcostal margin.
Routine blood tests showed the following data: white blood cell count, 2.98 × 109/L, hemoglobin (Hb), 74.00/L, platelet count (PLT), 23.00 × 109/L, C-reactive protein, 7.57 mg/dL, plasma thromboplastin antecedent, 73%, thrombin time, 23.00 s, fibrinogen, 1.17 g/L, D-dimer 4004.16 μg/L. The bone marrow examination showed the presence of was erythrocytosis, guanulocytosis, and thrombocytosis accompanied by unidentifiable cells that were further inspected. Epstein- Barr (EB) virus DNA 4.63 × 105 copies/ml.
The results from pathological examinations showed that hyperplasia of the hemopoietic tissue was active and guanulocytosis was obvious (Graph 2). The
Graph 2. The results from pathological examinations.
patient’s anemia was corrected by an infusion of red blood cells. After receiving hormonotherapy for 1.0 week, the blood platelet count became normal and the spleen obviously retracted. After the condition was stable, a splenectomy was performed under general anesthesia on August 2, 2013. The extracted tissue was sent to the King Med Center of Medical Inspection. The results from the pathology tests indicated that hemophagocytic syndrome related to EB virus infection was the first consideration, and a T-cell receptor (TCR) examination was recommended to check for extranodal lymphoma, which was later ruled out from the TCR results.
The diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) from the International Tissue and Cell Society drafted in 2004 are as follows [
HS, also known as HLH, is reactive histiocytosis [
HS is divided into either the primary and acquired condition [
The progression of HS is swift and violent, is often misdiagnosed, and has fatality rates. In particular, it is difficult to distinguish primary from acquired HS. The initial diagnosis of primary HS requires a complete patient history, including childhood diseases and any family members who tested positive for the condition; however, in recent years with continuous improvement of diagnostic criteria these requirements have changed. Individual cases of primary adult HS are regularly reported. The oldest patient on record is a 62-year-old male reported by Nagafuji et al. [
There is no effective treatment for HS. It is dormant in its early stages, but critical in the acute stages with a bad prognosis. About one-half of HS patients die mainly from hemorrhage, infection, multiple organ failure, and disseminated intravascular coagulation. The key to HS treatment is early diagnosis and early inhibition of the uncontrollable activity of lymphocytes and macrophages. Janka et al. [
Code | Disease type | Genetic locus | Relevant genes |
---|---|---|---|
#267700: | FHL1 | 9q21.3-q22 | Not clear yet |
#603553: | FHL2 | 10q22 | PRF1 |
#608898: | FHL3 | 17q25.1 | UNC13D |
#603552: | FHL4 | 6q24 | STX11 |
#613101: | FHL5 | 19p13 | STXBP2 |
FHL: familial hemophagocytic lymphohistiocytosis; OMIM: online Mendelian inheritance in man.
can be injected into the spinal column [
Adult HLH is a critical condition that is often difficult to diagnose and results in a bad prognosis because of the lack of effective and unified treatment. Early diagnosis and early intervention are important factors for affecting the progression of the disease and improving its prognosis. In clinical practice, when children or adults have a fever, hepatosplenomegaly, lymphadenectasis, and a significantly abnormal ferritin level, this disease should be considered.
Liu, X.L., Zhang, Y.M., Cui, Z.L., Tian, Q. and Duan, D.M. (2016) One Hemophagocytic Syndrome Re- lating to Adult Epstein-Barr Virus Infection and a Literature Review. Case Reports in Clinical Medicine, 5, 511-517. http://dx.doi.org/10.4236/crcm.2016.512065