OBJECTIVES: To investigate the clinical manifestations and laboratory examination results of children with Kawasaki disease complicated by macrophage activation syndrome (KD-MAS), and to provide a basis for identifying early warning indicators for the early diagnosis and treatment of KD-MAS. METHODS: A retrospective study was performed on 27 children with KD-MAS (KD-MAS group) and 110 children with KD (KD group) who were admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2014 to January 2022. Clinical and laboratory data were compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of laboratory markers with statistical significance in the diagnosis of KD-MAS. RESULTS: Compared with the KD group, the KD-MAS group had significantly higher incidence rates of hepatomegaly, splenomegaly, incomplete KD, no response to intravenous immunoglobulin, coronary artery damage, multiple organ damage, and KD recurrence, as well as a significantly longer length of hospital stay (P<0.05). Compared with the KD group, the KD-MAS group had significantly lower levels of white blood cell count, absolute neutrophil count, hemoglobin, platelet count (PLT), erythrocyte sedimentation rate, serum albumin, serum sodium, prealbumin, and fibrinogen (FIB), a significantly lower incidence rate of non-exudative conjunctiva, and significantly higher levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and serum ferritin (SF) (P<0.05). The ROC curve analysis showed that SF, PLT, FIB, and LDH had high value in the diagnosis of KD-MAS, with areas under the curve (AUC) of 0.989, 0.966, 0.932, and 0.897, respectively (P<0.001), and optimal cut-off values of 349.95 μg/L, 159×10⁹/L, 3.85 g/L, and 403.50 U/L, respectively. The combination of SF, PLT, FIB, and LDH had a larger AUC than PLT, FIB, and LDH alone in the diagnosis of KD-MAS (P<0.05), but there was no significant difference in the AUC between the combination of SF, PLT, FIB, and LDH and SF alone (P>0.05). CONCLUSIONS KD-MAS should be considered when children with KD have hepatosplenomegaly, no response to intravenous immunoglobulin, coronary artery damage, and KD recurrence during treatment. SF, PLT, FIB, and LDH are of high value in the diagnosis of KD-MAS, especially SF is of great significance in the diagnosis of KD-MAS.
Child ; Humans ; Immunoglobulins, Intravenous ; Macrophage Activation Syndrome/etiology* ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Retrospective Studies ; Blood Sedimentation ; Hepatomegaly

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.
Humans ; Female ; Adult ; Rituximab/therapeutic use* ; Macrophage Activation Syndrome/etiology* ; Retrospective Studies ; Lupus Erythematosus, Systemic/drug therapy* ; Methylprednisolone/therapeutic use* ; Lupus Vasculitis, Central Nervous System ; Fever/drug therapy* ; Erythema/drug therapy* ; Hormones/therapeutic use* ; Anemia ; Alopecia/drug therapy* ; Triglycerides/therapeutic use* ; Ferritins/therapeutic use*

Child ; Humans ; Arthritis, Juvenile/drug therapy* ; Macrophage Activation Syndrome/etiology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Anemia, Hemolytic, Autoimmune ; etiology ; Child, Preschool ; Humans ; Macrophage Activation Syndrome ; etiology ; Male ; Mucocutaneous Lymph Node Syndrome ; complications

Child ; Child, Preschool ; Humans ; Macrophage Activation Syndrome ; etiology ; pathology ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; pathology

Humans ; Macrophage Activation Syndrome ; etiology ; Rheumatic Diseases ; complications

OBJECTIVETo study the clinical manifestations of rheumatic disorders with macrophage activation syndrome (MAS) in children.

METHODSThe authors characterized MAS by carrying out a retrospective study on patients who were identified during the past 12 years in Tianjin Children's Hospital.

RESULTSSix cases (4 females, 2 males) were studied. Four had typical systemic onset juvenile idiopathic arthritis (SOJIA), two had systemic lupus erythematosus (SLE) with lupus nephritis. Clinical manifestations at diagnosis, which occurred in the lower activity state of these primary diseases, included high spiking fever (in 5 cases) or high fever (in 1), hepatosplenomegaly (in 6), lymphadenopathy (in 6), profound decrease of all 3 blood cell lines (in 6), significant injury of liver (in 6), diseminated intravascular coagulation (DIC)-like picture (in 2), and central nervous system dysfunction (in 3). Hypofibrinogenemia, elevated liver enzymes and hypertriglyceridemia were found consistently. The phagocytic histiocytes with plasmacytosis were found in 3 bone marrow smears (not done in others). MAS was presumed to have been precipitated by viral infections in 3 patients, two had evidences for herpes simplex virus infection and one for hepatitis A virus infection. The treatment regimen was tailored to each patient, as the clinical course was variable.

CONCLUSIONSMAS may not only be most frequently seen in children with SOJIA, but also in those with other rheumatic diseases, and may be a syndrome that is more common than previously thought. Infection may be main trigger factor for MAS. The immunoapheresis combined with immunochemotherapy may be optimal for severe injury of the liver in patients with MAS.

Adolescent ; Arthritis, Juvenile ; complications ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Lupus Erythematosus, Systemic ; complications ; pathology ; Macrophage Activation Syndrome ; etiology ; pathology ; Male ; Retrospective Studies

OBJECTIVEMacrophage activation syndrome (MAS) is a rare but life-threatening complication in children with rheumatic diseases, particularly systemic-onset juvenile idiopathic arthritis (SOJIA). Because of the potential fatality of this condition, prompt recognition and immediate therapeutic intervention are important. This study reviewed the data of MAS in 13 cases with SOJIA.

METHODSRetrospective review was performed on the precipitating events, clinical manifestations, laboratory data, treatment, and outcome of macrophage activation syndrome in 13 children with SOJIA seen from 1996 to 2005.

RESULTSOver the past 10 years the unit has had 90 new patients with SOJIA. Thirteen of those patients (14.4%) developed MAS during the course of their primary SOJIA, of whom ten were male. All patients were noted to have active SOJIA prior to developing MAS; 3 patients had medications, which were considered as trigger factors; 8 had infections prior to MAS, in two of them the infections were possible triggers. All the patients had high grade fever; 12 cases (92.3%) had hepatomegaly; 10 patients (76.9%) had coagulopathy, and eight patients (61.5%) had central nervous system dysfunction. The counts of platelet, white blood cells and the mean erythrocyte sedimentation rate fell dramatically in all patients; hyperferritinemia was identified in 8 patients, in 5 of whom serum ferritin (SF) was >or= 10,000 microg/L; in 8 (72.7%) of 11 cases fibrinogen was or= 2.5 mmol/L in 9 (69.2%) of 13 cases.

CONCLUSIONMAS is a rare and potentially fatal complication of children with SOJIA. Primary disease activity, medications and infections preceding MAS were all important triggers. The strongest clinical discriminators were hepatomegaly, hemorrhages and central nervous system dysfunction. The strongest laboratory tests were decreased counts of platelet and white blood cells, decreased ESR and fibrinogen, dramatically increased SF and TG. It calls for the immediate treatments, particularly with cyclosporin A, which are often effective.

Arthritis, Juvenile ; complications ; drug therapy ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Macrophage Activation Syndrome ; drug therapy ; etiology ; pathology ; Male ; Retrospective Studies

OBJECTIVETo review and analyze the clinical features, treatment, and outcome of macrophage activation syndrome (MAS) in children with systemic onset juvennil rheumatoid arthritis (SOJRA).

METHODRetrospective review and analysis were performed on cases with MAS from a prospectively collected database of children with SOJRA from the year of 2003 to 2006 in the Hospital.

RESULTSTwenty four patients (21 boys, 3 girls) were diagnosed as having MAS with SOJRA. Mean age of the patients with MAS at diagnosis was 7 years, and the duration prior to diagnosis of MAS was 12 months. No trigger factors were found except in one case whose MAS was triggered by use of methotrexate and in another by parvovirus B19 infection. High grade fever, new onset hepatosplenomegaly and lymphadenopathy, pancytopenia, liver dysfunction were common clinical features in all the 24 cases (100%). Bleeding from skin, mucous membrane and gastrointestinal tract were noted in 9 cases (38%). Twelve (50%) cases had CNS dysfunction (high intracranial pressure, seizure and coma). Six cases (25%) developed ARDS. One patient suffered from renal damage. The laboratory test revealed elevated live enzymes and ferritin, decreased value of ESR, albumin, complete blood count and fibrinogen in all the 24 cases. Bone marrow examination supported the diagnosis of definite hemophagocytosis in the 24 cases. Lymph node biopsy was done for one case and histopathological examination showed that the node was full of activated macrophage. As to treatment, five cases only received high dose steroids (three of them died), 14 cases were treated with high dose steroids plus cyclosporine (one died), two were treated with steroids plus cyclosporine and etoposide (none died). The causes of deaths were ARDS and CNS involvement. In three of the cases who died, treatment was given up by their parents.

CONCLUSIONSMAS is a rare and potentially fatal complication of SOJRA. Most of our patients were male. Bone marrow studies support the diagnosis. CNS involvement and ARDS were poor prognostic signs. Early diagnosis and aggressive therapy are essential.

Adolescent ; Arthritis, Juvenile ; complications ; drug therapy ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Macrophage Activation Syndrome ; drug therapy ; etiology ; pathology ; Male ; Retrospective Studies

Macrophage activation syndrome (MAS) is a rare and potentially fatal complication of rheumatic disorders in children. We describe a 13-month-old boy in whom MAS developed as a complication of systemic juvenile rheumatoid arthritis (S-JRA). He suffered from fever and generalized rash followed by multiple joints swelling for four months before admission. Physical examination revealed cervical lymphadenopathy and hepatosplenomegaly. Laboratory findings were: abnormal liver enzymes, increased triglyceride and ferritin levels, coagulopathies resembling disseminated intravascular coagulation, anemia and thrombocytopenia. Hyperplasia of hemophagocytic macrophages was remarkable in his bone marrow. Methylprednisolone and cyclosporin therapy resulted in clinical and laboratory improvements. This is the third case of MAS associated with S-JRA in Koreans, and the first one, in which hemophagocytic macrophages were proven in bone marrow.
Alanine Transaminase/metabolism ; Alkaline Phosphatase/metabolism ; Antigens, CD/blood ; Antigens, Differentiation, Myelomonocytic/blood ; Arthritis, Juvenile Rheumatoid/blood/*complications/pathology ; Aspartate Aminotransferases/metabolism ; Blood Cell Count ; Hepatomegaly/*etiology/pathology ; Humans ; Infant ; Liver/enzymology/pathology ; *Macrophage Activation ; Male ; Partial Thromboplastin Time ; Prothrombin Time ; Splenomegaly/*etiology/pathology ; Syndrome ; gamma-Glutamyltransferase/metabolism