Alopecia areata with ophiasis has a worldwide prevalence of only 0.02%. In the last ten years, only 10 cases have been reported in the Philippines. This variant is often resistant to treatment. Novel therapeutic options are being explored, although these are frequently limited to case reports due to the rarity of the disease. Newer therapies, such as JAKSTAT inhibitors and monoclonal antibodies, show promise as effective options for ophiasis-type alopecia areata.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia affecting children 2-5 years old. The clinical presentation ranges from self-resolving localized disease to fulminant, fatal disseminated disease. While the most common presentation of LCH are small, translucent crusted papules on the trunk, intertriginous areas, and scalp, it may present as crusted plaques and alopecia. A 3-year-old male presented with a 4-month history of solitary, well-defined, hyperpigmented plaque with yellow-brown crust on the left parieto-occipital area of the scalp measuring 1.5 x 1.5 cm and a solitary, well-defined, hairless patch with areas of erythema on the left parieto-occipital area measuring 5.0 x 6.0 cm. Scalp biopsy revealed diffuse collection of lymphohistiocytes interspersed with distinct kidney bean-shaped cells. CD1a is positive for cells of interest. Skeletal survey revealed lytic lesions involving the skull, thoracic cage, spine, pelvis, and upper and lower extremities. The rest of the physical examination findings revealed lymphadenopathy, crackles, globular abdomen with right and left upper quadrant dullness. The patient had episodes of fever, difficulty of breathing, and abdominal pain. The patient received chemotherapy as multisystem LCH based on prednisone and vinblastine. Following 3 courses of chemotherapy, there is noted hair regrowth and sloughing off of crust.

Alopecia resulting from radiation exposure occurs 2-8 weeks after exposure. It can be temporary or permanent depending on the dose of exposure. Alopecia following fluoroscopy-guided procedures are increasing in frequency. We report the case of a 22-year-old female who underwent fluoroscopically-guided embolization of an arteriovenous malformation. Twelve days after embolization, significant hair shedding was noted, resulting in a large rectangular hairless patch with no erythema or pain on the irradiated site. Hair pull test was positive and the hair mount showed dystrophic anagen hairs. Hair tug test was negative. Trichoscopy showed yellow dots, black dots, vellus hairs, and flame hairs. Histopathologic examination showed an increase in catagen and telogen hairs. On review of the procedure, she received a total peak skin dose of 4.67 Gray from the procedure. The diagnosis of radiation-induced alopecia was made and topical minoxidil was started, resulting in complete hair growth after six months. Patients undergoing fluoroscopy-guided procedures should have adequate follow-up weeks to months post-procedure to monitor for skin and hair reactions. Physicians should also consider delayed radiation reactions in patients with a history of radiation exposure. Safety protocols must be in place, and measures should be done to minimize the dose delivered.

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

OBJECTIVE: To determine the expression level of Sonic hedgehog (Shh) in the passage of hair follicle stem cells (HFSCs), analyze the effect of Shh overexpression on the proliferation activity of HFSCs, and explore the survival of HFSCs after Shh overexpression and its effect on hair follicle regeneration. METHODS: Hair follicles from the normal area (H1 group) and alopecia area (H2 group) of the scalp donated by 20 female alopecia patients aged 40-50 years old were taken, and the middle part of the hair follicle was cut under the microscope to culture, and the primary HFSCs were obtained and passaged; the positive markers (CD29, CD71) and negative marker (CD34) on the surface of the fourth generation HFSCs were identified by flow cytometry. The two groups of HFSCs were transfected with Shh-overexpressed lentivirus. Flow cytometry and cell counting kit 8 assay were used to detect the cell cycle changes and cell proliferation of HFSCs before and after transfection, respectively. Then the HFSCs transfected with Shh lentivirus were transplanted subcutaneously into the back of nude mice as the experimental group, and the same amount of saline was injected as the control group. At 5 weeks after cell transplantation, the expression of Shh protein in the back skin tissue of nude mice was detected by Western blot. HE staining and immunofluorescence staining were used to compare the number of hair follicles and the survival of HFSCs between groups. RESULTS: The isolated and cultured cells were fusiform and firmly attached to the wall; flow cytometry showed that CD29 and CD71 were highly expressed on the surface of the cells, while CD34 was lowly expressed, suggesting that the cultured cells were HFSCs. The results of real-time fluorescence quantitative PCR and Western blot showed that the expression levels of Shh protein and gene in the 4th, 7th, and 10th passages of cells in H1 and H2 groups decreased gradually with the prolongation of culture time in vitro. After overexpression of Shh, the proliferation activity of HFSCs in the two groups was significantly higher than that in the blank group (not transfected with lentivirus) and the negative control group (transfected with negative control lentivirus), and the proliferation activity of HFSCs in H1 group was significantly higher than that in H2 group before and after transfection, showing significant differences ( P<0.05). At 5 weeks after cell transplantation, Shh protein was stably expressed in the dorsal skin of each experimental group; the number of hair follicles and the expression levels of HFSCs markers (CD71, cytokeratin 15) in each experimental group were significantly higher than those in the control group, and the number of hair follicles and the expression levels of HFSCs markers in H1 group were significantly higher than those in H2 group, and the differences were significant ( P<0.05). CONCLUSION Lentivirus-mediated Shh can be successfully transfected into HFSCs, the proliferation activity of HFSCs significantly increase after overexpression of Shh, which can secrete and express Shh continuously and stably, and promote hair follicle regeneration by combining the advantages of stem cells and Shh.
Animals ; Female ; Mice ; Alopecia/surgery* ; Hair Follicle ; Hedgehog Proteins/genetics* ; Mice, Nude ; Regeneration ; Stem Cells

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 summarize the clinical and imaging features of linear scleroderma en coup de saber (LSCS) with central nervous system involvement in children. Methods: The clinical data(clinical manifestations and imaging features) of 6 children diagnosed with LSCS with central nervous system involvement who were admitted to Beijing Children's Hospital Affiliated to Capital Medical University from May 2019 to November 2021 were retrospectively analyzed. Results: The 6 patients were all female, aged 6.8 (3.3, 11.0) years at the time of diagnosis, and aged 3.0 (1.7, 4.1) years at the time of discovery of facial skin lesions. Facial skin lesions appeared before neurological symptoms in 5 cases, and neurological symptoms appeared 2 months before skin lesions in 1 case. All the patients had "sword wound" skin lesions on the forehead with alopecia. Neurological manifestations included epileptic seizures in 6 cases, focal neurological defects in 5 cases, and headaches in 2 cases. The intracranial lesions were all ipsilateral to the skin lesions. The magnetic resonance imaging (MRI) of 6 cases showed abnormal signals mainly involving white matter in 1 hemisphere, and 3 cases showed local encephalomalacia. The scattered low signal was observed in 5 cases on susceptibility weighted imaging. Localized brain parenchyma or leptomeninges enhancement was seen on Gadolinium-enhanced sequences in 5 cases. Scattered foci of calcification on the affected side were seen on cranial CT in 4 cases. Skin biopsy was performed in 2 cases. Part of the lesion of the brain was removed in 1 case, and the pathological findings suggested small vasculitis, which was consistent with skin pathological changes. All patients received symptomatic treatment with antiepileptic drugs. Oral prednisone combined with methotrexate was given in 4 cases, and 1 case was given oral prednisone only. One case was presumed to be in the resting stage of the disease due to significant cerebral atrophy in half of the brain, and only antiepileptic drugs were added. The patients were followed up for 6-36 months. The skin lesions of scleroderma and alopecia did not progress in 5 cases, and hemifacial atrophy was developed in 1 case, which was considered to be combined with Parry-Romberg syndrome. The seizures were controlled in 4 cases. One case had reduced seizure frequency but left hemiplegia. One patient still had intractable epilepsy and paroxysmal headache. Conclusions: LSCS with central nervous system involvement is more common in girls, with seizures and neurological defects as the main manifestations. Intracranial lesions are mostly ipsilateral to the skin lesions. Cerebral microbleeds, calcification, and encephalomalacia foci are common, and the pathological changes in skin and intracranial lesions are consistent with small-vessel vasculitis. Prednisone combined with methotrexate treatment has shown some efficacy, but some children remain with refractory epilepsy and neurological deficit symptoms.
Child ; Humans ; Female ; Scleroderma, Localized ; Anticonvulsants ; Methotrexate ; Prednisone ; Retrospective Studies ; Seizures ; Drug Resistant Epilepsy ; Calcinosis ; Alopecia ; Brain ; Encephalomalacia ; Headache

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*