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*

OBJECTIVE: To investigate the effect of acute graft-versus-host disease (aGVHD) mouse models established respectively by total body irradiation (TBI) and busulfan combined with cyclophosphamide (BU/CY) conditioning regimens after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Bone marrow cells and splenic mononuclear cells were isolated respectively from femur, tibia, and spleen of C57BL/6 male mice (H-2Kb) which were selected as donors. After TBI pretreatment, BALB/c female mice (H-2Kd) were injected with donor bone marrow cells 1×10⁷/50 μl and splenic mononuclear cells 2×10⁷/100 μl through caudal vein, while CB6F1 female mice (H-2Kd/b) with donor bone marrow cells 2×10⁷/100 μl and splenic mononuclear cells 1×10⁸/500 μl after BU/CY pretreatment. The successful establishment of the aGVHD models were determined by post-transplant manifestations, rate of chimerism, target organ damage, etc. Results: After transplantation, mice of both groups showed listlessness, low activity, continued weight loss, and typical manifestations of aGVHD such as alopecia, hunched posture, diarrhea, and anal swelling. and died within 4 weeks. Flow cytometry detection showed complete chimerism in all the mice. Pathological examination of skin, intestines, liver, lung, and spleen tissues showed obvious aGVHD pathological changes. However, the weight loss, ruffled fur, and alopecia combined with severe scurf on those hair-free areas were significantly apparent in TBI group than BU/CY group, as well as higher aGVHD score, and the differences were statistically significant (P<0.05). CONCLUSION Both TBI and BU/CY as conditioning regimens can successfully establish stable mouse models of aGVHD after fully allo-HSCT and haploidentical HSCT for further research about mechanism of aGVHD. BU/CY conditioning regimen can more truly simulate physiological status in vivo of patients with chemotherapy based conditioning regimen, while TBI conditioning regimen shows significantly more typical aGVHD symptoms and easier to operate.
Alopecia/drug therapy* ; Animals ; Busulfan/therapeutic use* ; Cyclophosphamide ; Female ; Graft vs Host Disease/drug therapy* ; Hematopoietic Stem Cell Transplantation ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation Conditioning ; Transplantation, Homologous ; Weight Loss ; Whole-Body Irradiation

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab in patients with unresectable locally advanced or metastatic squamous cell carcinoma of penis. Methods: A total of 33 patients with unresectable squamous cell carcinoma of penis undergoing neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab at Sun Yat-sen University Cancer Center from May 2015 to June 2021 were enrolled retrospectively. All the patients were male, with a median age (M(IQR))of 49.0 (13.5) years (range: 30 to 70 years). According to the therapy protocols, patients were divided into the chemotherapy group (16 cases) and the triple combination group (17 cases). Log-rank test was used to compare the progression-free survival and overall survival. χ² test or Fisher exact method was used to compare the objective response rate, pathological down-stage rate and adverse events between these two groups. Results: The follow-up time was 28.1(19.2) months (range: 1.5 to 33.4 months). Patients of triple combination group were observed significantly longer progression-free survival (30.0 months vs. 8.2 months, χ²=3.998, P=0.046) than those of chemotherapy group. The median overall survival of the triple combination group and chemotherapy group were not reached and 15.2 months (χ²=3.298, P=0.069), respectively. Although there was no significant difference in the subsequent surgical resection rate between these two groups (12/17 vs.11/16, P=1), the objective response rate and the pathological complete response rate in triple combination group were significantly higher than in chemotherapy group (13/17 vs. 6/16, χ²=5.125, P=0.024; 6/7 vs. 0, P=0.001). The main common grade 1 to 2 adverse events in the triple combination group were alopecia (16 cases), anemia (15 cases), and nausea (14 cases). The main common grade 1 to 2 adverse events in the chemotherapy group were anemia (14 cases), alopecia (12 cases), decreased appetite (12 cases), and nausea (11 cases). The incidence of adverse events ≥grade 3 was similar in the triple combination group and chemotherapy group (8/17 vs. 6/16, χ²=0.308, P=0.579). There was no grade 3 adverse event in both groups. Conclusion: Compared with traditional chemotherapy alone, chemotherapy combined with toripalimab and nimotuzumab provides longer progression-free survival and similar toxicity for unresectable stage Ⅳ squamous cell carcinoma of penis.
Humans ; Male ; Female ; Neoadjuvant Therapy ; Retrospective Studies ; Carcinoma, Squamous Cell/drug therapy* ; Alopecia ; Anemia

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533
Alopecia ; Carboplatin ; Cohort Studies ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Hand-Foot Syndrome ; Humans ; Korea ; Ovarian Neoplasms ; Paclitaxel ; Peripheral Nervous System Diseases ; Platinum ; Prognosis ; Recurrence ; Retrospective Studies

Administration, Topical ; Alopecia/drug therapy* ; China ; Double-Blind Method ; Fibroblast Growth Factors/therapeutic use* ; Hair ; Humans ; Male ; Minoxidil/therapeutic use* ; Treatment Outcome

PURPOSE: Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent meta-analysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. MATERIALS AND METHODS: Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. RESULTS: Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). CONCLUSION: Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.
Abdominal Pain ; Alopecia ; Anorexia ; Appointments and Schedules ; Breast Neoplasms ; Breast ; Cyclophosphamide ; Diarrhea ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Dyspepsia ; Febrile Neutropenia ; Headache ; Humans ; Incidence ; Mucositis ; Muscle Weakness ; Myalgia ; Nausea

Anagen effluvium is an abrupt loss of hair in its growing phase due to an event that impairs the mitotic or metabolic activity of the hair follicle. Anagen effluvium is commonly associated with the administration of chemotherapy, radiation, and drugs as well as exposure to toxic chemicals. However, alopecia due to the administration of anti-tuberculosis drugs has rarely been reported in the literature. A 50-year-old female was diagnosed with intestinal tuberculosis and was started on anti-tuberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide. After starting the treatment, erythematous to brown patches appeared all over her body, which was followed by diffuse hair loss on the scalp and body. Hair examination showed intact inner and outer root sheaths with fully pigmented hair bulbs, and histopathological examination of a scalp biopsy showed vacuolar degeneration in the interfollicular epidermis and perifollicular infiltration of mononuclear cells and eosinophils. The condition was diagnosed as anagen effluvium with drug eruption, and a potent corticosteroid lotion was prescribed for scalp application twice a day. After complete hair loss, the anti-tuberculosis medications were withdrawn, and hair regrowth started 4 months later. Here, we report a rare case of anagen effluvium with generalized drug eruption due to anti-tuberculosis medication.
Alopecia ; Biopsy ; Drug Eruptions* ; Drug Therapy ; Eosinophils ; Epidermis ; Ethambutol ; Female ; Hair ; Hair Follicle ; Humans ; Isoniazid ; Middle Aged ; Pyrazinamide ; Rifampin ; Scalp ; Tuberculosis

Alopecia ; chemically induced ; diagnosis ; Antirheumatic Agents ; administration & dosage ; adverse effects ; Arthritis, Rheumatoid ; drug therapy ; Biopsy ; methods ; Cyclosporine ; administration & dosage ; Dermatologic Agents ; administration & dosage ; Drug Hypersensitivity Syndrome ; diagnosis ; etiology ; physiopathology ; therapy ; Humans ; Male ; Middle Aged ; Prednisolone ; administration & dosage ; Skin ; pathology ; Sulfasalazine ; administration & dosage ; adverse effects ; Symptom Flare Up ; Treatment Outcome ; Vitiligo ; chemically induced ; diagnosis

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.
Alanine Transaminase/analysis ; Alopecia/etiology ; Antibiotics, Antineoplastic/*therapeutic use ; Aspartate Aminotransferases/analysis ; Azathioprine/adverse effects ; Female ; Hepatitis, Autoimmune/*drug therapy/pathology ; Humans ; Liver/enzymology/pathology ; Middle Aged ; Mycophenolic Acid/*therapeutic use ; Pancytopenia/etiology ; Prednisolone/therapeutic use