Antipruritic Research Articles

Management of Severe Allergic Conjunctivitis With Topical Cyclosporin A 0.05% Eyedrops

To evaluate the efficacy of topical cyclosporin A 0.05% in the management of severe allergic conjunctivitis. Seven patients with severe allergic conjunctivitis who were not responding to topical steroids, antihistamines, and mast cell stabilizers were given topical cyclosporin A 0.05%. All patients had an active disease when they were included in the study. Signs and symptoms were recorded before and after treatment. Seven patients, 6 boys and 1 girl, 6-14 years old, 6 with vernal keratoconjunctivitis and 1 with atopic keratoconjunctivitis, were enrolled in the study. Treatment with topical cyclosporin A 0.05% decreased the severity of symptoms and clinical signs significantly after 6 months (P < 0.05, Wilcoxon signed rank test). In addition, the need for steroids was reduced or even stopped. The patients experienced no side effects during the follow-up periods (mean, 14.0 +/- 2.1 months; range, 8-18 months). Topical cyclosporin A is an effective treatment in the management of severe allergic conjunctivitis with a benefit as a steroid-sparing agent.

Rare coincidence of eosinophilic esophagitis with esophageal stenosis and intramural pseudodiverticulosis

We describe the first detailed case of eosinophilic esophagitis associated with esophageal intramural pseudodiverticulosis and gastro-esophageal reflux disease in a 24-year-old man, who suffered from recurrent dysphagia since the age of 3 years. He presented with symptoms of dysphagia, food impaction and malnutrition. An esophagogram revealed a high-grade stenosis in the proximal part of the esophagus. Histological evaluation of esophageal mucosal biopsies demonstrated more than 20 eosinophil granulocytes per high power field, indicative of eosinophilic esophagitis. Additionally, esophago-gastro-duodenoscopy showed pseudodiverticulosis in the distal portion of the esophagus. A therapeutic regimen consisting of topical steroid intake, antihistamines, proton-pump-inhibition and specific food avoidance led to significant clinical improvement within 6 weeks.

The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis

Patients with allergic rhinitis demonstrate hyperreactive response in distilled water nasal provocation, shown by significant increase in nasal airway resistance (NAR). Antihistamines, including topical antihistamine, levocabastine, reduce response in non-specific nasal provocation tests. Furosemide is a diuretic which reduces hyperreactivity in lower airways, but the mode of its action is not yet fully understood. In this study, we hypothesized that either levocabastine or furosemide pre-treatment in allergic rhinitis patients reduced response to nasal challenge with non-isotonic aerosol. To test the hypothesis, we measured the effect of pre-treatment with levocabastine and furosemide in topical application on suppression of hyperreactive response to distilled water nasal inhalation. Nasal resistance was measured, prior to and after the provocation, by active anterior rhinomanometry in two randomized groups of patients, according to pre-treatment, either by levocabastine or furosemide, 20 patients in each group, respectively. Nasal airflow resistance and level of hyperreactive response considering nasal eosinophilia were tested. Significant increase in nasal resistance following provocation was found at baseline conditions (without pre-medication); pre-treatment with levocabastine and furosemide has suppressed such response. Patients with positive nasal eosinophilia showed a significantly higher increase in nasal resistance compared to those with negative smears. Furosemide has shown significantly better protective effect on nasal resistance increase in patients with positive eosinophils nasal smears. Levocabastine and furosemide pre-treatment suppress hyperreactive response to distilled water nasal provocation. Comparison of resistances (pre-treatment vs. without) showed more protective effect of furosemide, measured on both better and worse patent side of nose, in contrast to levocabastine group for which it was shown only on better patent side prior to provocation. Protection of furosemide was significantly more pronounced in patients with significant nasal eosinophilia.

A case report of remote cutaneous metastasis from male breast carcinoma

A 66-year-old man, who had been diagnosed with vasculitis 1 year previously, presented at our hospital with edema of the left leg and erythema of more than 1 year's duration (Fig. 1). He had been diagnosed with dermatitis and vasculitis in another hospital without being biopsied, and had been treated with topical steroids, oral antihistamines, antibacterials, hydrochlorothiazide, and Radix Salviae Miltiorrhizae, which provided some temporary benefit. He had no other complaints and denied any family history of breast cancer. No history of radiation therapy to the chest or hormone therapy was elicited. After biopsy of the skin lesion in our hospital, a breast mass was found, followed by lumpectomy for pathologic examination. The results of a physical examination showed a well-developed and well-nourished man. There was a 2-cm, palpable subareolar mass in the left breast with inguinal lymph node and axillary lymph node swelling; no discharge or tenderness was evident on breast mass palpation. The skin and nipple overlying the breast mass were normal. The right breast was unremarkable. Examination revealed solitary, nonpitting edema of the left thigh and buttock with erythema. Laboratory tests showed normal plasma alpha-l-fucosidase (AFU) and alpha-fetoprotein (AFP) and a carcinoembryonic antigen (CEA) level of 145.9 microg/L. Ultrasonography showed normal resonance in the prostate, bladder, liver, spleen, pancreas, and kidney, but abnormal resonance beside the aorta. Computed tomography (CT) showed lymph node swelling in the mediastina. The skin biopsy from the erythema of the left thigh revealed metastatic carcinoma (atypical cells in the lymphatic vessel). Pathologic examination of the breast mass revealed intraductal carcinoma (Figs 2 and 3). The breast mass was positive for presenilin-2 (PS2), c-erbB-2, and cytokeratin (CK), but negative for estrogen receptor (ER) and progesterone receptor (PR). The cutaneous metastasis was positive for CK but negative for PR, ER, PS2, and c-erbB-2.

Outbreak of Tropical Rat Mite (Ornithonyssus bacoti) Dermatitis in a Home for Disabled Persons

Five mentally handicapped individuals living in a home for disabled persons in Southern Germany were seen in our outpatient department with pruritic, red papules predominantly located in groups on the upper extremities, neck, upper trunk and face. Over several weeks 40 inhabitants and 5 caretakers were affected by the same rash. Inspection of their home and the sheds nearby disclosed infestation with rat populations and mites. Finally the diagnosis of tropical rat mite dermatitis was made by the identification of the arthropod Ornithonyssus bacoti or so-called tropical rat mite. The patients were treated with topical corticosteroids and antihistamines. After elimination of the rats and disinfection of the rooms by a professional exterminator no new cases of rat mite dermatitis occurred. The tropical rat mite is an external parasite occurring on rats, mice, gerbils, hamstersand various other small mammals. When the principal animal host is not available, human beings can become the victim of mite infestation.

Pruritus bei atopischer Dermatitis: Mechanismen und Therapie

Die Inzidenz der atopischen Dermatitis bei Kindern hat in den letzten Jahren stark zugenommen. Chronischer Pruritus ist hierbei eine schwer therapierbare Begleiterscheinung, der bei Kindern vornehmlich mit verschiedenen Topika zu behandeln ist. Konventionelle Therapien wie topische Antihistaminika sind in den meisten Fällen unwirksam und prolongieren den Pruritus. Dadurch kann der Pruritus weiter chronifizieren, zu sekundären Kratzläsionen führen und die Lebensqualität erheblich verschlechtern. Aktuell stehen neue antipruritische Substanzen zur Verfügung, die in unterschiedliche, pruritogene Mechanismen eingreifen und auch bei Kindern angewandt werden können. Eingesetzt werden Substanzen, die die kutane Pruritusentstehung blockieren bzw. die Weiterleitung von Pruritus an das zentrale Nervensystem hemmen. Wichtig ist auch eine Durchbrechung peripherer Sensibilisierungsprozesse. Leider stehen bei Kindern derzeit keine zugelassenen Substanzen zur Verfügung, die die Weiterleitung von Pruritus im zentralen Nervensystem oder die zentrale Sensibilisierung unterbinden. Wichtig ist es daher, bei Kindern möglichst früh Pruritus zu behandeln, um Sensibilisierungs- und Chronifizierungsprozessen vorzubeugen.

Resultados y evaluación del fotoparche en España: hacia una nueva batería estándar de fotoalergenos

Introduction While the standardization of exploration with photoallergy tests or photopatch testing runs its course in Europe, we have carried out an epidemiological study about the current situation of photoallergy in our country. Material and methods We have gathered the results of photopatch testing in seven hospital centres of Madrid, Cataluña, Galicia and Comunidad Valenciana during the years 2004 and 2005. The exploration has included, at least, the standard set of the Spanish Photobiology Group (GEF), with 16 (photo) allergens, that have been irradiated with 10 joules/cm 2. We have assessed the total number of explored patients, their sex, present, past or unknown relevance of positive photopatch testing, cross reactions, and allergens responsible for photosensitization. Results Of 224 patients explored by photopatch testing, 39.3 % show one or more positive tests. Seventy-one percent (103) were considered relevant with respect to clinical history, 14 cases (9.6 %) were cross reactions, and 28 (19.3 %) were considered of unknown relevance. The most prevalent allergens were nonsteroidal antiinflammatory drugs, specially ketoprophen (43 patients), followed by bencydamine (7 patients) and etofenamate (5 patients). The mixture of four sunscreens from the standard set of the GEF only detected 10 of 16 patients with photoallergy to sunscreens. Photopatch testing of unknown relevance was mainly due to antiseptics (fenticlor) and topical antihistamines. Conclusions We propose the modification of the standard set of photoallergens from the GEF, that should include the majority of nonsteroidal antiinflammatory drugs and sunscreens available in Spain. Ketoprophen continues to be the most frequent photoallergen in our country. It is also important for the cross sensitizations that may present. Sunscreens should be explored separately and not in form of a mixture.

Results and Assessment of Photopatch Testing in Spain: Towards a New Standard Set of Photoallergens

Introduction While the standardization of exploration with photoallergy tests or photopatch testing runs its course in Europe, we have carried out an epidemiological study about the current situation of photoallergy in our country. Material and methods We have gathered the results of photopatch testing in seven hospital centres of Madrid, Cataluña, Galicia and Comunidad Valenciana during the years 2004 and 2005. The exploration has included, at least, the standard set of the Spanish Photobiology Group (GEF), with 16 (photo) allergens, that have been irradiated with 10 J/cm 2. We have assessed the total number of explored patients, their sex, present, past or unknown relevance of positive photopatch testing, cross reactions, and allergens responsible for photosensitization. Results Of 224 patients explored by photopatch testing, 39.3% show one or more positive tests. Seventyone percent (103) were considered relevant with respect to clinical history, 14 cases (9.6%) were cross reactions, and 28 (19.3%) were considered of unknown relevance. The most prevalent allergens were nonsteroidal antiinflammatory drugs, specially ketoprophen (43 patients), followed by bencydamine (7 patients) and etofenamate (5 patients). The mixture of four sunscreens from the standard set of the GEF only detected 10 of 16 patients with photoallergy to sunscreens. Photopatch testing of unknown relevance was mainly due to antiseptics (fenticlor) and topical antihistamines. Conclusions We propose the modification of the standard set of photoallergens from the GEF, that should include the majority of nonsteroidal antiinflammatory drugs and sunscreens available in Spain. Ketoprophen continues to be the most frequent photoallergen in our country. It is also important for the cross sensitizations that may present. Sunscreens should be explored separately and not in form of a mixture.

Prospective, randomized controlled trial onLactobacillus rhamnosusin infants with moderate to severe atopic dermatitis

A reduction of symptoms of atopic dermatitis (AD) in small infants by the administration of Lactobacillus rhamnosus has been reported in a few studies. One study with older children and adolescents failed to show any effect. We conducted a prospective study to reassess the efficacy of orally administered L. rhamnosus strain GG (LGG) in infants with AD. In a randomized, double-blind, placebo-controlled study, 54 infants aged 1-55 months with moderate to severe AD were randomized to daily 10 x 10(9) colony-forming units of LGG or to placebo during an 8-week intervention phase. Emollients, class I-II topical corticosteroids and antihistamines were permitted. The treatment with LGG was well tolerated. At the end of treatment there were no significant differences between the groups with respect to clinical symptoms (SCORAD, pruritus, sleep loss), the use of topical corticosteroids and antihistamines, immunological parameters, or health-related quality of life of the parents. Our results could not confirm LGG as an effective treatment of AD in infancy.

Montelukast in allergic rhinitis: a systematic review and meta‐analysis

Allergic rhinitis is common. This systematic review outlines the evidence regarding montelukast in allergic rhinitis and provides a meta-analysis of its efficacy. The evidence suggests that montelukast does reduce nasal symptom score by 3.4% (95% CI: 2.5% to 4.2%) when compared with placebo. Montelukast is not as effective as topical nasal steroids or antihistamines and should therefore be regarded as second line therapy. When used, montelukast should be used in combination with an antihistamine.

Characteristics of diagnosed polymorphous light eruption

The characteristics of polymorphous light eruption (PMLE) have been described in patients evaluated and diagnosed at specialized photodermatology centers. Our goal was to describe the characteristics of PMLE diagnosed in a general clinic setting. We used electronic medical records to identify patients diagnosed with PMLE from 2000 to 2002 within a large group practice. We then collected additional information from medical records about patient demographics, lesion morphology, diagnostic testing, and therapies for the selected patients. We identified 142 patients with diagnosed PMLE. After manual chart review, we excluded 18 patients with other forms of photosensitivity, eczema, or collagen vascular disease. Eighty-percent of the remaining 124 patients were diagnosed by a dermatologist during the study period. Females predominated in our patient series and the mean age of PMLE onset was 37.8 years. Lesions were commonly described as papular, edematous papulare, papulo-vesicular, eczematous, and plaque-like. Few skin biopsies were performed, and no patient had phototesting or photopatch testing. Topical corticosteroids and antihistamines were the most commonly prescribed therapies. Only four patients were treated with phototherapy. Patient demographics and lesion morphology in our cohort were similar to other reports, but patterns of diagnostic testing and treatment were somewhat different than those observed in photodermatology clinics.

Vulvar Syringomas in a 9‐year‐old Child with Review of the Literature

Syringomas are benign tumors of the eccrine sweat gland that are most common to the periorbital location. Less common and under-recognized is their potential involvement of the vulvar skin, where they may cause significant pruritus. In this location, lesions often develop just prior to or during puberty, with symptoms of pruritus sometimes correlating with pregnancy or menstruation. A hormonal influence has thus been postulated. Reported treatments for symptomatic patients include topical corticosteroids, systemic and topical antihistamines, laser and excisional surgery, cryotherapy, and topical atropine, with variable results. We report a 9-year-old girl who had severe pruritus secondary to syringomas of the vaginal labia, and review the literature on this unusual disorder. Awareness of this condition is important in order that patients receive appropriate evaluation and management of their symptoms.

Étude clinique des compresses supranettes dans le traitement de l’allergie oculaire saisonnière ou per-annuelle de l’enfant

Ocular allergy is a common disease that is on the rise. Seasonal and perennial conjunctivitis are the most common forms of ocular allergy. Itching, hyperemia, foreign body sensation, irritation, blurred vision or ocular dryness sensations, tearing, and photophobia are the clinical signs observed in patients. A topical antiallergic treatment is prescribed associated with ocular cleaning to contribute to an antigen washing of the ocular surface. Our study aimed to evaluate the use of Supranettes pads as supplementation treatment in children for seasonal or perennial conjunctivitis. Our prospective study was done in children with a diagnosis of seasonal or perennial clinical ocular allergy. Every symptom was rated from 0 to 4 according to the intensity described by the children and their parents. Twenty children (range, 4-10 years) presenting an ocular allergy were included in the study. A topical antiallergic treatment membrane stabilizer or antihistamine and Supranettes pads were prescribed for ocular cleaning of one randomized selected eye four times a day. Patients were seen in consultation 1 month later to evaluate the treatment. The ocular comfort of each eye, one treated with Supranettes pads and the other not treated by Supranettes pads, was evaluated by the child helped by parents on a graduated self-evaluation scale (range, 0-10). The Mann-Whitney statistical test was used to differentiate the two groups. Of the 20 patients, eleven presented seasonal conjunctivitis and nine perennial conjunctivitis. Six of them presented conjunctivitis with a slight to moderate superficial punctuate keratitis. At the consultation on day 28+/-3, patients who were first treated showed clear improvement of clinical signs with the prescribed treatment. The statistical comparison of the two groups confirmed a significant difference (p<0.05) to the advantage of the group using the Supranettes pads. Ocular washing is essential in the treatment of allergic conjunctivitis. The new galenic form of ocular cleaning by physiological serum-impregnated pads is simple to use for children. An objective significant difference is difficult to observe in 1 month. This study underlines the importance of the comfort of Supranettes pads evaluated in the treatment of children's conjunctivitis. It confirms the advantage of developing evaluation studies including patient satisfaction and quality of life in ophthalmology.

A randomized comparative clinical trial of recombinant canine interferon‐γ (KT‐100) in atopic dogs using antihistamine as control

Recombinant canine interferon-gamma (KT-100) or topical antihistamine (diphenhydramine: DH) was administered to dogs with atopic dermatitis (AD) for 4 weeks and their efficacies were compared using pruritus, excoriation, erythema and alopecia as evaluation criteria. Clinical studies on 92 atopic dogs (KT-100 group: 63, DH group: 29) were conducted at 18 animal hospitals in Japan. KT-100 was administered subcutaneously once a day three times a week on alternating days for 4 weeks. DH was administered topically twice daily for 4 weeks. The efficacy rates of the KT-100 group on day 28 were 72.1% for pruritus, 73.8% for excoriation, 75.4% for erythema and 60.7% for alopecia, which were significantly higher than those of the DH group (20.7% for pruritus, 27.6% for excoriation, 24.1% for erythema and 24.1% for alopecia).

Die allergische Rhinitis: Besonderheiten von Diagnostik und Therapie im Kindes- und Jugendalter

Allergic rhinitis (AR) has a life prevalence of about 24% and, thereby, AR is the most common immune disease and one of the most common chronic diseases. It often develops in childhood or adolescence and there is a continuing trend towards increasing numbers in most industrialized countries in this age group, thus, diagnosis and therapy are of major importance. AR has a high impact on social living, school performance and mental and physical development of those children. In addition, it is accompanied by comorbidities such as conjunctivitis, bronchial asthma, food allergies, atopic dermatitis, sinusitis and others. E.g., the risk to develop bronchial asthma is approximately 4 times higher in children with AR if compared with a matched control group. In the drug treatment of AR, α-sympathomimetics, anticholinergic agents, nasal rinsing methods, topical and systemic antihistamines, topical glucocorticosteroids, and leukotrien rezeptorantagonists are used. Spezific immuntherapy (hyposensitization) is the only causal treatment option in AR besides allergen avoidance and should be used early in disease. Efficacy of subcutaneous immuntherapy is well-documented. Besides therapy, the efficiacy of specific immunotherapy to prevent new sensitizations and to avoid the allergic march should be taken into account.

Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy (EPPER) in a patient with breast cancer

Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy (EPPER) in a patient with breast cancer

Onset of action of a topical antihistamine as assessed by histamine challenge-induced plasma exudation responses

Although usually administered orally, antihistamines are available also for topical use in allergic rhinitis. Information on onset of action of these drugs is incomplete. To examine onset of action of topical cetirizine-dinitrate on plasma exudation evoked by repeated nasal histamine challenges. A liposome formulation of cetirizine-dinitrate (2.44 mg per nasal cavity) was delivered via a nasal spray device as 2 consecutive actuations per nasal cavity in a placebo-controlled design. The nasal mucosal surface was challenged and lavaged with a histamine solution (100 microg/mL) 5, 15, 25, and 55 minutes after each treatment. In addition, the mucosa was lavaged with saline before each treatment. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation (luminal entry) of plasma. Histamine produced significant increases in nasal lavage fluid levels of alpha2-macroglobulin at all observation points (5 through 55 minutes after treatment). Nasal cetirizine-dinitrate significantly inhibited this response at 5 and 15 minutes after treatment. The effect of topical cetirizine-dinitrate, as established by histamine challenge-induced mucosal exudation of plasma, has an early onset (ie, within 5 to 10 minutes).

Vernal Keratoconjunctivitis Presenting Unilaterally

A 7-year-old boy had itching, foreign body sensation, and redness in his right eye. Unilateral cobblestone papillae and a shield ulcer were found. Topical antihistamines, mast cell stabilizers, and steroids led to marked improvement. Unilateral vernal keratoconjunctivitis should be included in the differential diagnosis of unilateral giant papillary conjunctivitis.

The Role of Antihistamines in the Management of Allergic Rhinitis

Allergic rhinitis is a common disease worldwide and antihistamines remain the mainstay of pharmacotherapy for allergic rhinitis. Histamine is one of main mediators involved in the disease pathophysiology. The primary mechanism of antihistamine action is believed to be competitive antagonism of histamine receptors, specifically the H1-receptors. These receptors are present on nerve endings, smooth muscles, and glandular cells. However, H1- antagonism may not be their sole mechanism of action. Antihistamines have been used in two forms; oral and topical, in the management of allergic rhinitis. The use of the first-generation oral antihistamines (chlorpheniramine, diphenhydramine, promethazine, tripolidine, clemastine, and tripelennamine) is considerably limited by their sedative and anticholinergic effects. The secondgeneration antihistamines (acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine, mizolastine, and terfenadine) are effective in reducing nasal symptoms, and have no sedative effects. However, terfenadine, astemizole and recently, loratadine, have been found to cause prolongation of the QT interval on electrocardiogram, and can increase the risk for development of potentially lethal ventricular tachyarrhythmias, or torsades de pointes. The next-generation antihistamines (fexofenadine, desloratadine, tecastemizole, and levocetirizine) are typically the structurally modified, active metabolites or isomers of second-generation antihistamines. These agents retain the non-sedating properties of second- generation antihistamines while eliminating or limiting the cardiac risks. Topical antihistamines (azelastine and levocabastine), delivered by nasal spray, avoid or minimize systemic adverse effects. They have a rapid onset of action (less than 15 min) at low drug dosage, but their action is limited to the treated organ. Keywords: allergic rhinitis, antihistamine, h-receptor antagonist

Histamine receptors and the conjunctiva

The purpose of this review is to evaluate the effect of histamine on various receptors in the conjunctiva. A Medline search from 1980 was performed on the histamine receptor subtypes H1, H2 and H3 in the human conjunctiva. In the conjunctiva, histamine has been shown to induce various physiological and immunological changes through both H1 and H2 receptor stimulation. Histamine binding to conjunctival H1 receptors through the phospholipase C-dependent inositol phosphate pathway leads to the symptom of pruritus while histamine stimulation of the conjunctival H2 receptors has been indirectly shown to cause vasodilation. The effect of histamine on conjunctival H1 receptors appears to be the primary target for ocular allergy treatment as it is primarily involved in ocular pruritus. The exact interaction of the conjunctival H2 receptors appears to work in a complementary fashion to the H1 receptor in controlling other features of ocular allergy such as vasodilation and injection. Thus, oral and topical antihistamines with multiple histamine receptor binding activities may provide an improved treatment paradigm for the various signs and symptoms of ocular allergy. The histamine H1, H2 and H3 receptor affinities of ketotifen, pyrilamine, and epinastine appear to have the strongest H1 and H2 affinities.