The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
Animals ; Autoimmune Diseases/pathology* ; Cell Count ; Epididymis/pathology* ; Epididymitis/pathology* ; Histamine H1 Antagonists/pharmacology* ; Hypersensitivity, Delayed ; Immunity, Cellular/drug effects* ; Ketotifen/pharmacology* ; Male ; Mast Cells/pathology* ; Orchitis/pathology* ; Rats ; Severity of Illness Index ; Spermatic Cord Torsion/pathology* ; Testis/pathology* ; Vaccination

Chlorpheniramine maleate is commonly used antihistamine. Since antihistamines are the main therapeutic agents for symptomatic treatment of urticaria, anaphylaxis to antihistamines may lead to errors in diagnosis and treatment. We report a case of anaphylaxis induced by chlorpheniramine maleate confirmed by intradermal test. A 35-year-old female experienced history of anaphylaxis after intramuscular injection of chlorpheniramine maleate. Skin prick test was negative, but intradermal test was positive. Patient also experienced mild dizziness after intradermal test and refused to perform any further evaluation such as oral challenge test. Anaphylaxis for chlorpheniramine maleate is very rare but should be considered.
Adult ; Anaphylaxis ; Chlorpheniramine ; Diagnosis ; Dizziness ; Female ; Histamine Antagonists ; Humans ; Injections, Intramuscular ; Intradermal Tests ; Skin ; Urticaria

BACKGROUND: Although oral antihistamines (H1-histamine receptor antagonists) are the main treatment option for pruritus in general skin dermatosis, their effect in treating pruritus of atopic dermatitis (AD) has not yet been established. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the effectiveness of combined therapy of H1-antihistamines and topical steroids. METHODS: We systematically searched MEDLINE, Embase, and CENTRAL databases for articles published from 1967 to 2015. We identified 1,206 studies and assessed their titles, abstract, and full-text. Random effects meta-analysis was used to calculate mean differences (MD) with 95% confidence intervals (CI). RESULTS: Two studies satisfying the inclusion criteria of antihistamine therapy with mandatory topical steroid use were selected. Comparing antihistamine monotherapy with combination therapy, patients treated with the addition of antihistamine to topical corticosteroids showed a statistically significant clinical improvement (standard MD, −0.24; 95% CI, −0.42 to −0.05; p=0.01). CONCLUSION: H1-antihistamines may have a synergistic effect when combined with topical steroids by influencing various associative factors of chronic pruritus in AD.
Adrenal Cortex Hormones ; Dermatitis ; Dermatitis, Atopic ; Histamine Antagonists ; Histamine H1 Antagonists ; Humans ; Pruritus ; Skin ; Skin Diseases ; Steroids

PURPOSE: This study aimed to investigate the characteristics of poisoning drug ingested by younger children, and to compare the clinical outcome by drug forms.METHODS: This was a retrospective analysis based on medical records from the Emergency Department based Injury In-depth Surveillance (EDIIS) registry in Korea from January to December 2015. Patients aged 7 years or younger visiting the emergency department (ED) with drug poisoning were included. We classified the forms of drugs as tablets or syrup, and analyzed the characteristics by size, color, and shape. In addition, clinical outcomes and ED length of stay were compared according to the drug forms.RESULTS: A total of 308 cases were collected, and 202 patients finally were analyzed. Tablets and capsules (TACs) were more common than syrup (67.3% vs. 32.7%). Regarding clinical outcomes, patients who took TACs had higher admission rate (17.6% vs. 7.6%, P = 0.040) without a significant difference in ED length of stay compared to those who took syrups. While commonly ingested drugs in TACs were hormones, sedative and analgesics, frequent drugs in syrup were antihistamines and cold drugs. In 136 case of TACs, median long and short axes were 0.85 cm (interquartile range [IQR], 0.7–1.1 cm) and 0.72 cm (IQR, 0.59–0.82 cm), respectively. Chromatic TACs were 80 cases (58.8%) and more common than achromatic TACs. Round shapes were preferred than angular ones (96.3% vs. 3.7%).CONCLUSION: In younger children poisonings, the TACs showed higher incidence and admission rate compared to syrups. Especially, chromatic TACs and round shapes were preferred. Therefore, drugs with these characteristics need to be stored more carefully.
Analgesics ; Capsules ; Child ; Dosage Forms ; Drug Compounding ; Emergency Service, Hospital ; Histamine Antagonists ; Humans ; Incidence ; Korea ; Length of Stay ; Medical Records ; Poisoning ; Retrospective Studies ; Tablets

Urticaria multiforme is a cutaneous condition observed in children. This self-limited condition is characterized by well-circumscribed, annular, and erythematous wheals, which spontaneously disappear within a few days. Patients commonly present with acral edema and show a favorable response to antihistamines. It is frequently misdiagnosed as erythema multiforme or serum sickness-like reaction owing to distinctive annular wheals with an ecchymotic center observed in patients. This condition was previously known as acute annular urticaria. The term urticaria multiforme was introduced in 2007 to highlight this specific variant of urticaria. We describe 2 patients with acral edema and transient annular wheals with dusky red centers, which were diagnosed as urticaria multiforme lesions. To our knowledge, the Korean literature includes only a single case report describing acute annular urticaria. However, the report does not use the term ‘urticaria multiforme’ to describe this condition.
Child ; Edema ; Erythema Multiforme ; Histamine Antagonists ; Humans ; Pigmentation* ; Urticaria*

Chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria, is a common chronic inflammatory skin disorder that has a prevalence of 0.5% to 1% in the general population. It affects daily normal life and work productivity, with significant impacts on quality of life. Generally, the management of CSU uses a step-wise approach. Although second-generation H1 antihistamines are an effective mainstay of CSU, approximately 20% of patients are resistant to conventional antihistamine monotherapy. Evidence-based and expert consensus-based treatment guidelines of CSU can be a useful resource for primary care physicians and specialists. This review presents diverse information to support decision-making for individualized treatment plans in this special population. Several major therapeutic advances have occurred in recent years. Omalizumab, an immunoglobulin G humanized monoclonal anti-immunoglobulin E antibody that prevents binding of immunoglobulin E to the high-affinity immunoglobulin E receptor has shown safety and efficacy in patients with intractable CSU. In well-controlled clinical trials in patients with refractory CSU who received add-on therapy with subcutaneous omalizumab (300 mg every 4 weeks for 12 or 24 weeks), the rates of complete response were significantly higher in the omalizumab group (relative risk, 4.55; P < 0.0001). The introduction of omalizumab as an add-on therapy to H1 antihistamines as a management option has markedly improved the therapeutic possibilities for CSU and the quality of life of CSU patients. Nevertheless, many patients still do not tolerate or benefit from existing therapies, including omalizumab. There are ongoing studies investigating the treatment potential of novel therapeutic targets in CSU.
Efficiency ; Histamine Antagonists ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Omalizumab ; Physicians, Primary Care ; Prevalence ; Quality of Life ; Receptors, IgE ; Skin ; Specialization ; Urticaria

Although rare, antihistamines can cause adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after administration of antihistamines, (e.g., ucerax [hydroxyzine] or leptizine [levocetirizine]), for cholinergic rashes; he did not have pruritus. Skin prick, intradermal, and drug provocation tests were performed to determine the relationship between the antihistamines and eruptions. Levocetirizine induced wheals in the skin prick test and a rash in the oral drug provocation test. In contrast, ketotifen induced no reaction in the skin prick test but showed a positive reaction in the oral provocation test. Our case report highlights that children can experience the same types of adverse reactions as seen in adults, and cross-reactivity between various antihistamines can occur.
Adult ; Anaphylaxis ; Child ; Child, Preschool ; Drug Eruptions ; Exanthema ; Histamine Antagonists ; Humans ; Ketotifen ; Pruritus ; Skin ; Urticaria

Scombroid fish poisoning (SFP) is a form of histamine food poisoning caused by the ingestion of improperly stored fish. The term “scombroid” derives from the family name of the fish family first implicated, such as tuna and mackerel. On the other hand, non-scombroid fish species, such as sardine and herring, can also cause histamine poisoning. The histamine is converted from histidine by a bacterial enzyme in the causative fish. Because the symptoms of SFP can easily be confused with food allergies, it is believed to have been significantly under-reported. In 2016, an outbreak of SFP occurred among primary school students who had eaten yellowtail steak in Korea. The most common findings consisted of a rapid onset of flushing of the face and trunk, erythematous and urticarial rash, diarrhea, and headache occurring soon after consuming the spoiled fish. Usually, the course is self-limiting and antihistamines can be used successfully to relieve symptoms, but several life-threatening SFP cases have been reported. Clinical toxicologists should be familiar with SFP and have competency to make a differential diagnosis between fish allergy and histamine poisoning. SFP is a histamine-induced reaction caused by the ingestion of histamine-contaminated fish, whereas a fish allergy is an IgE-mediated reaction. This review discusses the epidemiology, pathophysiology, diagnosis, treatment, and preventive measures of SFP.
Diagnosis ; Diagnosis, Differential ; Diarrhea ; Eating ; Epidemiology ; Exanthema ; Flushing ; Food Hypersensitivity ; Foodborne Diseases ; Hand ; Headache ; Histamine Antagonists ; Histamine ; Histidine ; Humans ; Hypersensitivity ; Korea ; Perciformes ; Poisoning ; Tuna

To investigate the relationship between single nucleotide polymorphisms (SNPs) of CACNA1C (SNPs rs58619945, rs7316246 and rs216008) and susceptibility of chronic spontaneous urticaria (CSU) as well as the curative effect of non-sedating antihistamine drugs.
 Methods: Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI) changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs (rs58619945, rs7316246 and rs216008) of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs (desloratadine, mizolastine, fisofenadine) in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.
 Results: Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR(95%CI)=0.660(0.470-0.925), P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls. Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs (rs58619945: OR=0.843, P=0.454; rs7316246: OR=2.103, P=0.102; rs216008: OR=0.237, P=0.363). There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR(95%CI)=0.480(0.247-0.933), P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine.
 Conclusion: The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.
Calcium Channels, L-Type ; genetics ; Chronic Disease ; Genetic Predisposition to Disease ; Histamine H1 Antagonists, Non-Sedating ; therapeutic use ; Humans ; Loratadine ; analogs & derivatives ; therapeutic use ; Polymorphism, Single Nucleotide ; Prognosis ; Retrospective Studies ; Urticaria ; drug therapy ; genetics

Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.
Animals ; Cyproheptadine ; pharmacology ; Female ; Histamine H1 Antagonists ; pharmacology ; Membrane Potentials ; drug effects ; physiology ; Mice, Inbred C57BL ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Prefrontal Cortex ; drug effects ; physiology ; Pyramidal Cells ; drug effects ; physiology ; Receptors, sigma ; agonists ; metabolism ; Tetraethylammonium ; pharmacology ; Tissue Culture Techniques