Omalizumab is effective and safe in chronic inducible urticaria (CIndU): Real-world data from a large multi-national UCARE study.

BACKGROUND: Long-term data on the effectiveness and safety of omalizumab for chronic inducible urticaria (CIndU) in large populations are lacking. OBJECTIVE: To evaluate the effectiveness, safety, estimated omalizumab treatment duration and its predictors, as well as differences between CIndU subtypes, in a large long-term CIndU cohort. METHODS: A multinational multicenter study was conducted at 14 specialized urticaria centres (UCAREs), including all CIndU patients ever treated with omalizumab from 2009 until July 2022. Kaplan-Meier survival and regression analyses were performed. RESULTS: Across 234 CIndU patients (55% female; mean age 37 years), 76% (n = 178) had standalone CIndU and 24% (n = 56) had predominant CIndU plus minor CSU, with an observation period up to 13 years. Most CIndU patients (73%, n = 145/200 with available data on response) had complete/good response to omalizumab treatment, without significant differences between CIndU subtypes. Sixty-two (26%) patients discontinued omalizumab; due to well-controlled disease (47%, n = 29), ineffectiveness (34%, n = 21), side effects (3%, n = 2), combination of ineffectiveness and side effects (3%, n = 2) and other reasons (13%, n = 8). The median estimated omalizumab treatment duration exceeded 5 years (54% drug survival at 5 years) and was mostly determined by well-controlled disease. Higher age predicted a lower chance to discontinue omalizumab due to well-controlled disease (HR 0.969, 95%CI 0.945-0.995). CIndU subtype and presence of minor CSU were not related to response and time until omalizumab discontinuation for any reason. CONCLUSION: Omalizumab is highly effective and safe in CIndU patients, with long estimated treatment duration mainly reflecting long disease duration. Our data show omalizumab's high potential as treatment in any subtype of CIndU and support its clinical use for these patients.

Evaluation of skin perfusion pressure to assess refractory foot ulcers.

OBJECTIVE: The number of patients with foot gangrene caused by critical ischaemia and severe infection is increasing significantly in developed countries. The measurement of perilesional skin blood flow by skin perfusion pressure (SPP) is useful to select the appropriate treatment of gangrenous lesions, in that it is not affected by calcifications of blood vessels. However, the prognosis of a foot ulcer may also be affected by the level of blood sugar and infections. This study aimed to validate the use of SPP in cases of foot gangrene and ulcers in patients with and without diabetes mellitus (DM) and infection. METHOD: Clinical symptoms, ankle-brachial pressure index (ABPI) and SPP were assessed to evaluate the condition of each foot ulcer. Every foot ulcer was treated as independent, even if a participant had multiple ulcers. All ulcers for which we measured SPP were subject to the analysis. All ulcers were purely ischaemic in nature and were exclusively located on the foot or toes. RESULTS: Data were collected from 117 foot ulcers on 91 toes and feet from 65 patients. Almost all SPP values in healed cases were > 27 mmHg. There were three patients whose ulcers failed to heal by conservative treatments were complicated with severe infection. However, no effect of DM on the relationship between SPP values and prognosis was observed. Logistic regression analysis of all ulcers except for the 5 cases complicated with infection revealed that those with 30 mmHg or lower SPP values are likely to heal by conservative treatment with 23% or lower probability, whereas any ulcer with more than 50 mmHg SPP value and without severe infection may heal without the need for further operations with 80% or higher probability. CONCLUSION: The combination of SPP and careful evaluation of infection may be a good parameter to decide the appropriate treatment for ischaemic skin ulcers, regardless of the complication of DM.

Contact urticaria syndrome with IgE antibody against a cefotiam-unique structure, evoked by nonapparent exposure to cefotiam.

A 26-year-old woman presented with recurrent attacks of widespread urticaria and systemic symptoms. The patient was a nurse, and the attacks occurred only in her workplace, without an apparent trigger. A patch test to cefotiam (CTM) induced an immediate skin reaction. ELISA detected the patient's serum IgE antibody binding to CTM conjugated with human serum albumin (CTM-HSA), and her basophils released histamine in response to CTM-HSA in a histamine release assay (HRA). Both reactions in ELISA and HRA were inhibited by pretreatment of the patient's serum or basophils with cefotiam. No crossreactivity in skin tests or in vitro assays was observed against other antibiotics, even those containing a beta-lactam ring and/or side chains similar to CTM. Certain antibiotics including CTM may cause extremely sensitive and specific contact urticaria syndrome, which is mediated by IgE and evoked even without apparent skin contact with the culprit drug and in the absence of any history of an allergic reaction against other antibiotics with similar structures.

Increase of coagulation potential in chronic spontaneous urticaria.

BACKGROUND: The pathogenesis of chronic spontaneous urticaria (CU) has recently been conceived to be associated with thrombin generation through the extrinsic coagulation pathway. However, little is known about the components of the intrinsic coagulation pathway potentially involved. METHODS: To investigate the whole process of coagulation, both classical coagulation assays and a global coagulation test, the intrinsic coagulation pathway-dependent activated partial thromboplastin time (APTT) clot waveform analysis, were performed using plasma of 36 patients with CU who had various severities. RESULTS: Classical coagulation assays revealed that levels of fibrinogen, D-dimer, and fibrin and fibrinogen degradation products (FDP), and positive rates of soluble fibrin monomer complex (SFMC) were significantly elevated in patients with CU, whereas the elevation of prothrombin fragment 1 + 2 was not statistically significant. On the other hand, all parameters of a global coagulation test, APTT clot waveform analysis, evidently showed a hypercoagulable pattern and were significantly correlated to disease severity of CU. CONCLUSIONS: CU is characterized by elevated blood coagulation potential with involvement of the intrinsic coagulation factors, which may contribute in vivo to the generation of fibrin even by small amounts of thrombin.

Coagulation/fibrinolysis and inflammation markers are associated with disease activity in patients with chronic urticaria.

BACKGROUND: The evaluation of disease severity and activity of chronic urticaria (CU) is essential for the adequate treatment of patients. However, there is no reliable biomarker for such evaluations. Recently, markers of blood coagulation and fibrinolysis have been revealed to be elevated in severe cases of CU. In this article, we studied the coagulation/fibrinolysis and inflammation markers and their relationship to disease activity in patients with CU. METHODS: Plasma fibrin degradation products (FDP), d-dimer and serum C-reactive protein (CRP) were measured with the assessment of disease severity and skin reaction to autologous serum in 82 patients with CU and 37 patients with acute urticaria, idiopathic angioedema (AE) or inducible types of urticaria (IU). RESULTS: The levels of FDP in patients with CU were significantly higher than those in patients with IU, but no other differences in FDP, d-dimer and CRP were observed among patients with different types of urticaria. These markers of patients with CU were well correlated with each other and significantly associated with disease severity of CU, but not with skin reactions to autologous serum. In 37 patients with CU, levels of all these parameters reduced as their disease condition improved, while they increased when the disease became aggravated. Regarding FDP, this relationship was observed even if FDP concentrations were within normal range throughout the study. CONCLUSIONS: The measurement of plasma FDP, d-dimer and serum CRP may be useful for the assessment of disease activity of CU.

Sweat antigen induces histamine release from basophils of patients with cholinergic urticaria associated with atopic diathesis.

BACKGROUND: We previously demonstrated that the semipurified human sweat antigen causes skin reactions and histamine release from basophils via specific IgE in patients with atopic dermatitis (AD). Patients with cholinergic urticaria (ChU) also develop skin reactions and histamine release of basophils in response to autologous sweat. OBJECTIVES: To study whether or not patients with ChU share sensitivity for the sweat antigen with patients with AD and to study the clinical characteristics among patients with ChU and the relationship with histamine-release activity of basophils. METHODS: The sweat antigen that induces histamine release from basophils of patients with AD was prepared by Con-A, anion-exchange and reverse-phase chromatography. Relationships between histamine-release activity against the sweat antigen and clinical features of patients with ChU were analysed. RESULTS: Twenty-three of 35 patients with ChU showed > 5% net histamine release in response to the semipurified sweat antigen, whereas none of healthy controls did so. In patients with ChU, histamine release in response to semipurified sweat antigen significantly correlated with the level of serum IgE and eosinophil numbers in peripheral blood. Incidence of each atopic disease in patients with ChU tended to be higher than in the general Japanese population. When the patients were categorized according to their responses in the histamine release test, the positive group tended to show a higher incidence of AD and bronchial asthma compared with the negative group. CONCLUSIONS: ChU and AD may share hypersensitivity to common antigens in sweat. The sweat allergy and atopic diathesis are associated with each other.

Cervical fast spin echo three-dimensional magnetic resonance myelography.

A technique of fast spin echo three-dimensional magnetic resonance (MR) myelography with flow compensation was developed for the evaluation of the cervical spinal lesions. The whole spinal cord and roots in the spinal canal can be visualized non-invasively on voxel images by the maximum intensity projection process to achieve the best static contrast of the cerebrospinal fluid. This method of MR myelography is applicable as a screening test for the patients with cervical spinal lesions.

[Bilateral carotid endarterectomy for patients with bilateral carotid artery stenosis].

In a couple of recent randomized trials, the benefits of unilateral carotid endarterectomy (CEA) have been reevaluated in symptomatic patients with severe stenosis. In contrast, the operative indication, procedure, and perioperative management of bilateral CEAs for patients with bilateral carotid artery stenosis are still controversial. In this report, we reviewed 7 patients who underwent bilateral CEAs at out institute during the last 10 years, with regard to the clinical feature, angiographical findings, operative procedure, surgical results and long-term prognosis. The patients ranged from 52 to 73 years in age, and included six males and one female. Clinical symptoms were asymptomatic in 1 patient, transient ischemic attack in 2, reversible ischemic neurological deficits in 2, minor completed stroke in 1, and major completed stroke in 1. The angiographical carotid artery stenosis in the dominant side of symptomatic cases was 50% in 3, 70% in 1, 90% in 2, and ulceration in 4 cases. The stenosis in the non-dominant side of symptomatic cases was 60% in 1, 70% in 3, 90% in 2, and 4 cases with ulceration. One case among the asymptomatic cases had bilateral 80-90% stenosis. We staged bilateral CEAs, in the dominant side first except in one case among the symptomatic cases and on the more severely stenotic side first in the asymptomatic cases. During CEA, an external shunt was placed in 1 case, but no internal shunt was used in any of the cases. Perioperative complications were found in 2 patients, transient bilateral hypoglossal nerve palsy and local hemorrhage in the other case. Totally, all of 7 cases (14 consecutive CEAs) have been performed with satisfactory results. No mortality and no permanent morbidity has resulted. In the follow-up period (mean: 38.3 month), 1 patient was found to have developed cerebral infarction in the ipsilateral carotid artery territory. From our own small experience and from that in the literature, CEAs for bilateral carotid artery stenosis should be performed in the dominant side first. Then, after a certain period, from 2 to 6 weeks, the CEA should be performed in the non-dominant side.

[Chronic subdural hematoma with bleeding tendency; clinical analysis of 11 surgical cases].

Eleven patients with chronic subdural hematoma (CSDH) with bleeding tendency (BT) were surgically treated in the last 12 years. To study the clinical problem of CSDH with BT, 11 surgical cases were divided into 3 groups, Group A; CSDH with primary BT (1 case of hemophilia A), Group B; CSDH with BT secondary to a basic disease (3 cases of leukemia, 2 cases of malignant tumor with DIC, 1 case of chronic renal failure and 1 case of liver cirrhosis), Group C; CSDH with BT by anticoagulants (warfarin) (2 cases of replacement of mitral valve, 1 case of A-C bypass). Evacuation of the hematoma was performed by means of one or two burr holes with irrigation of the hematoma cavity and a drainage tube was placed in the subdural space. The outcome was excellent in Groups A and C. In Group B, two patients with DIC due to gastric cancer and prostatic cancer died, and 3 patients with leukemia recovered dramatically from CSDH, but the poor course of the disease itself resulted in death. The outcome of other patients in Group B was excellent. Since CSDH with BT is often fatal, those patient had usually been treated conservatively. However, from this analysis, we stress that CSDH with BT should be surgically treated after checking the blood conditions carefully to determine whether or not the patient has need for surgery.