tacrolimus and Pruritus

New topical agents have been developed for the treatment of atopic dermatitis (AD) in recent years. This systematic review is intended to synthesize the clinical trial literature and concisely report the updated safety and adverse effects of topical medications used to treat atopic dermatitis in children.. A systematic search of Cochrane Library, Embase, PubMed and ClinicalTrials.gov from inception to March 2022 was conducted for trials of topical medications used to treat AD in patients <18 years (PROSPERO #CRD42022315355). Included records were limited to English-language publications and studies of ≥3 weeks duration. Phase 1 studies and those that lacked separate paediatric safety reporting were excluded.. A total of 5005 records were screened; 75 records met inclusion criteria with 15 845 paediatric patients treated with tacrolimus, 12 851 treated with pimecrolimus, 3539 with topical corticosteroid (TCS), 700 with crisaborole and 202 with delgocitinib. Safety data was well reported in tacrolimus trials with the most frequently reported adverse events being burning sensation, pruritus and cutaneous infections. Two longitudinal cohort studies were included, one for tacrolimus and one for pimecrolimus, which found no significant increased risk of malignancy with topical calcineurin inhibitor (TCI) use in children. Skin atrophy was identified as an adverse event in TCS trials, which other medications did not. Systemic adverse events for the medications were largely common childhood ailments.. Data discussed here support the use of steroid-sparing medications (tacrolimus, pimecrolimus, crisaborole, delgocitinib) as safe options with minimal adverse events for managing paediatric AD, although a larger number of TCI studies reported burning and pruritus compared to TCS studies. TCS was the only medication class associated with reports of skin atrophy in this review. The tolerability of these adverse events should be considered when treating young children. This review was limited to English-language publications and the variable safety reporting of trial investigators. Many newer medications were not included due to pooled adult and paediatric safety data that did not meet inclusion criteria.

Topics: Adult; Calcineurin Inhibitors; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Humans; Longitudinal Studies; Pruritus; Tacrolimus; Treatment Outcome

More than 15 years have passed since the clinical launch of topical tacrolimus for the treatment of atopic dermatitis. Its efficacy and safety have been clearly demonstrated in many global and domestic short-term and long-term clinical trials. Although the prolonged external application of steroids causes many adverse reactions including cutaneous atrophy, no such reactions occur with the use of topical tacrolimus. Therefore, the therapeutic guidelines recommend a combined topical treatment with tacrolimus and steroids. Tacrolimus is a potent immunosuppressant. However, recent studies have revealed its diverse action on the cardinal pathomechanisms of atopic dermatitis. In this review, we summarize the mechanistic role of tacrolimus in various aspects of allergic inflammation including mast cell activation, innate allergic response, pruritus, sensory nerve activation, and skin barrier dysfunction.

Topics: Administration, Topical; Animals; Cytokines; Dermatitis, Atopic; Humans; Immunosuppressive Agents; Pruritus; Skin; Tacrolimus; Treatment Outcome

Neurologic itch is defined as pruritus resulting from any dysfunction of the nervous system. Itch arising due to a neuroanatomic pathology is seen to be neuropathic. Causes of neuropathic itch range from localized entrapment of a peripheral nerve to generalized degeneration of small nerve fibers. Antipruritic medications commonly used for other types of itch such as antihistamines and corticosteroids lack efficacy in neuropathic itch. Currently there are no therapeutic options that offer relief in all types of neuropathic pruritus, and treatment strategies vary according to etiology. It is best to decide on the appropriate tests and procedures in collaboration with a neurologist during the initial work-up. Treatment of neuropathic itch includes general antipruritic measures, local or systemic pharmacotherapy, various physical modalities, and surgery. Surgical intervention is the obvious choice of therapy in cases of spinal or cerebral mass, abscess, or hemorrhagic stroke, and may provide decompression in entrapment neuropathies. Symptomatic treatment is needed in the vast majority of patients. General antipruritic measures should be encouraged. Local treatment agents with at least some antipruritic effect include capsaicin, local anesthetics, doxepin, tacrolimus, and botulinum toxin A. Current systemic therapy relies on anticonvulsants such as gabapentin and pregabalin. Phototherapy, transcutaneous electrical nerve stimulation, and physical therapy have also been of value in selected cases. Among the avenues to be explored are transcranial magnetic stimulation of the brain, new topical cannabinoid receptor agonists, various modes of acupuncture, a holistic approach with healing touch, and cell transplantation to the spinal cord.

Topics: Acupuncture Therapy; Amines; Anesthetics, Local; Anticonvulsants; Antipruritics; Botulinum Toxins, Type A; Calcineurin Inhibitors; Cannabinoid Receptor Agonists; Capsaicin; Cyclohexanecarboxylic Acids; Doxepin; Gabapentin; gamma-Aminobutyric Acid; Humans; Neuromuscular Agents; Peripheral Nervous System Diseases; Phototherapy; Physical Therapy Modalities; Pregabalin; Pruritus; Tacrolimus; Transcranial Magnetic Stimulation; Transcutaneous Electric Nerve Stimulation

Uremic itch is a frequent and sometimes very tormenting symptom in patients with advanced or end-stage renal failure, with a strong negative impact on the quality of life. According to a representative study, the point prevalence of chronic itch is 25% in hemodialysis patients but may reach more than 50% in single cohorts depending on the country and dialysis efficacy. Not much is known regarding the pathogenesis of uremic itch. Besides parathyroid hormone, histamine, tryptase, and alteration of the calcium-phosphate metabolism have been suspected. More recently, derangements in the opioid system and an inflammatory condition have been investigated as suspected players in the pathogenesis of uremic itch, but remain unproven so far. Treatment of chronic itch in dialysis patients remains difficult. Besides topical application of rehydrating or immunomodulating compounds, such as γ-linolenic acid or tacrolimus treatment with nalfurafine may be helpful. Apart from that, gabapentin and pregabalin are promising drugs to alleviate uremic itch. In many cases, UVB phototherapy is effective in reducing the intensity of itch. When treating patients, one should take into account that most of the drugs available are not licensed for the treatment of itch. Therefore, a deliberate use of therapeutic options aiming for a good risk-benefit relation should be adopted. In very severe and refractory cases, patients suitable for renal transplantation might be switched to 'high urgency' status, as successful renal transplantation cures uremic pruritus in most of the cases.

Topics: Acupuncture Therapy; Amines; Analgesics, Opioid; Anticonvulsants; Calcineurin Inhibitors; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; gamma-Linolenic Acid; Humans; Kidney Failure, Chronic; Morphinans; Narcotic Antagonists; Pregabalin; Pruritus; Receptors, Opioid, kappa; Receptors, Opioid, mu; Renal Dialysis; Spiro Compounds; Tacrolimus; Ultraviolet Therapy; Uremia

Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and compromising symptom in patients with advanced or end-stage renal disease, strongly reducing the patient's quality of life. More than 40% of patients undergoing hemodialysis suffer from chronic pruritus; half of them complain about generalized pruritus. The pathogenesis of CKD-aP remains obscure. Parathormone and histamine as well as calcium and magnesium salts have been suspected as pathogenetic factors. Newer hypotheses are focusing on opioid-receptor derangements and microinflammation as possible causes of CKD-aP, although until now this could not be proven. Pruritus may be extremely difficult to control, as therapeutic options are limited. The most consequential approaches to treatment are: topical treatment with or without anti-inflammatory compounds or systemic treatment with (a) gabapentin, (b) μ-opioid receptor antagonists and κ-agonists, (c) drugs with an anti-inflammatory action, (d) phototherapy, or (e) acupuncture. A stepwise approach is suggested starting with emollients and gabapentin or phototherapy as first-line treatments. In refractory cases, more experimental options as μ-opioid-receptor-antagonists (i.e., naltrexone) or κ-opioid-receptor agonist (nalfurafine) may be chosen. In desperate cases, patients suitable for transplantation might be set on 'high urgency'-status, as successful kidney transplantation will relieve patients from CKD-aP.

Topics: Acupuncture Therapy; Amines; Anti-Inflammatory Agents; Calcium Channel Blockers; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; gamma-Linolenic Acid; Humans; Morphinans; Naltrexone; Narcotic Antagonists; Pentoxifylline; Phototherapy; Pregabalin; Pruritus; Receptors, Opioid, kappa; Renal Insufficiency, Chronic; Spiro Compounds; Tacrolimus; Thalidomide; Uremia

Topics: Administration, Topical; Adrenal Cortex Hormones; Anti-Allergic Agents; Baths; Cholestasis, Intrahepatic; Cyclosporins; Dermatitis, Atopic; Diagnosis, Differential; Female; Histamine Antagonists; Humans; Immunosuppressive Agents; Pemphigoid Gestationis; Pregnancy; Pregnancy Complications; Prurigo; Pruritus; Skin; Tacrolimus

Atopic dermatitis, also known as atopic eczema, is a chronic pruritic skin condition affecting approximately 17.8 million persons in the United States. It can lead to significant morbidity. A simplified version of the U.K. Working Party's Diagnostic Criteria can help make the diagnosis. Asking about the presence and frequency of symptoms can allow physicians to grade the severity of the disease and response to treatment. Management consists of relieving symptoms and lengthening time between flare-ups. Regular, liberal use of emollients is recommended. The primary pharmacologic treatment is topical corticosteroids. Twice-daily or more frequent application has not been shown to be more effective than once-daily application. A maintenance regimen of topical corticosteroids may reduce relapse rates in patients who have recurrent moderate to severe atopic dermatitis. Pimecrolimus and tacrolimus are calcineurin inhibitors that are recommended as second-line treatment for persons with moderate to severe atopic dermatitis and who are at risk of atrophy from topical corticosteroids. Although the U.S. Food and Drug Administration has issued a boxed warning about a possible link between these medications and skin malignancies and lymphoma, studies have not demonstrated a clear link. Topical and oral antibiotics may be used to treat secondary bacterial infections, but are not effective in preventing atopic dermatitis flare-ups. The effectiveness of alternative therapies, such as Chinese herbal preparations, homeopathy, hypnotherapy/biofeedback, and massage therapy, has not been established.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Bacterial Infections; Calcineurin Inhibitors; Cicatrix; Complementary Therapies; Dermatitis, Atopic; Dermatologic Agents; Diagnosis, Differential; Dose-Response Relationship, Drug; Emollients; Histamine Antagonists; Humans; Phototherapy; Pruritus; Skin; Tacrolimus

Persistent pruritus, or itch, is one of the earliest symptoms of atopic dermatitis (AD). When pruritus is untreated, the incessant scratching response by the patient can increase the inflammatory response, resulting in aggravation of disease symptoms and severity, increasing flares and worsening patient quality of life. Therefore, it is essential that pruritus be treated effectively, rapidly and safely for optimal management of AD. In this article, the authors review clinical trials using tacrolimus ointment, a topical calcineurin inhibitor, to treat adult and pediatric patients with AD over a wide range of disease severity focusing on its efficacy in rapidly reducing pruritus. Furthermore, the authors evaluate trials in which tacrolimus ointment was directly compared with topical corticosteroids, the mainstay of AD treatment, and pimecrolimus cream, another topical calcineurin inhibitor, as well as long-term safety trials in which patients applied tacrolimus ointment for extended periods.

Topics: Administration, Cutaneous; Adolescent; Adult; Calcineurin Inhibitors; Child; Child, Preschool; Clinical Trials as Topic; Dermatitis, Atopic; Humans; Immunosuppressive Agents; Ointments; Pruritus; Quality of Life; Severity of Illness Index; Tacrolimus

The uremic pruritus is a very painful symptom suffered by chronic haemodialysis patients and is observed in 22 to 74% of the subjects. The causes of uremic pruritus have not yet been clarified. During the last 20 to 30 years it has been focused on altogether 5 different pathophysiological hypotheses: stimulating influences (e.g. calcium phosphate deposits in the epidermis), stimuli (e.g. secondary hyperparathyroidism), neuropathic injuries (e.g. disturbance of the cutaneous innervation in patients with uremic peripheral neuropathy), and central nervous changes (e.g. accumulation of endorphins in uremic patients which is associated with increasing pruritus), and immunologic conditions. The last mentioned immunological hypothesis has increasing importance, not at least based on the fact that the application of a topical calcineurin inhibitor (tacrolimus) improves the uremic pruritus. However, this fact could not be confirmed in a recent prospective placebo-controlled study from the USA. Only after kidney transplantation with a functioning transplant the uremic pruritus is stopped. That is why no causal therapy exists so far. Actually, the uremic pruritus has to be treated by topical and systemic means in a symptomatic and polypragmatic way only. Urea represents one of the most important "natural moisturizing factors" which are responsible for the hydration of the skin. It has been demonstrated that older patients have decreased urea levels within the stratum corneum of the epidermis, whereas in patients with terminal kidney insufficiency - despite dryness of the skin - as a paradox finding elevated levels of urea have been assessed in the stratum corneum. Because of this reason, the meaning of urea as part of the "natural moisturizing factors" system is not understood, until now. However, there are very promising results of clinical phase II studies showing a significant effect of topical application of 2.5% L-arginine hydrochlorid ointment - a semi-essential amino acid - on improvement of dryness and, in particular, on improvement of pruritus in haemodialysis patients.

Topics: Antipruritics; Arginine; Calcineurin Inhibitors; Capsaicin; Controlled Clinical Trials as Topic; Humans; Ichthyosis; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Ointments; Prospective Studies; Pruritus; Renal Dialysis; Skin; Tacrolimus; Urea; Uremia

Topical treatment with tacrolimus is more effective than the placebo and the low potency corticosteroids in the treatment of atopic dermatitis (AD) in both adults and children while it has a similar potency as some topical corticosteroids of medium potency. Since it was put on the market, more evidence has been accumulating to make our previous statements and it has been demonstrated to have greater effectivity than topical pimecrolimus and oral cyclosporine. It is a safe drug and its side effects are of little importance. Specifically no side effects have been demonstrated due to its systemic absorption nor has there been any increase in skin infections. The most frequent side effect is burning sensation or increased pruritus in the area where the product is applied. It is more frequent if the lesions treated are very acute and is generally transitory, not causing the treatment to be discontinued. Furthermore, with the current information, it cannot be associated to an increase of any type of neoplasms.

Topics: Adrenal Cortex Hormones; Adult; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Cyclosporine; Dermatitis, Atopic; Humans; Immunosuppressive Agents; Meta-Analysis as Topic; Middle Aged; Neoplasms; Pruritus; Retrospective Studies; Spain; Tacrolimus; Young Adult

In this article there were regarded the most frequent side effects that appear in the patients who have been treated with topical tacrolimus, and the association between topical tacrolimus and the development of tumors is unfolded. The irritation in the site of application of the tacrolimus can manifiest as pruritus, sensation of burning and/or eritema located to the area of the application. It is the most frequent side effect, independently of the duration of the study. The cutaneous infections, especially the viral ones, tend to be more numerous in patients with atopic dermatitis that receive topic tacrolimus. After reviewing the medical literature one concludes that nowadays there doesn t exist scientific evidence of an increase of skin cancer, lymphomas or systemic immunosuppression in those patients that use or have used topical tacrolimus. Nevertheless, it is not possible to exclude the possibility that there appear cutaneous and/or systemic long-term side effects.

Topics: Administration, Cutaneous; Animals; Calcineurin Inhibitors; Clinical Trials as Topic; Dermatitis, Atopic; Flushing; Humans; Immunosuppressive Agents; Neoplasms; Neoplasms, Experimental; Organ Transplantation; Postoperative Complications; Pruritus; Retrospective Studies; Skin Absorption; Skin Diseases, Viral; Spain; Tacrolimus

Topical tacrolimus is an immunosuppressant that acts through the inhibition of calcineurin and thus of the T cells. This causes a decrease in the production of interleukins, the granulocyte colony stimulating factor, alpha interferon and tumor necrosis factor. Although the use of topical tacrolimus is only indicated for the treatment of moderate or severe atopic dermatitis, its immunosuppressant effect and fewer side effects regarding topical corticosteroids have lead to the increase of its use in other types of inflammatory skin diseases. The purpose of this article is to review the use of tacrolimus in this group of diseases other than atopic dermatitis, this use not being authorized within the data sheet of the drug.

Topics: Adult; Autoimmune Diseases; Child; Clinical Trials as Topic; Dermatitis; Graft vs Host Disease; Humans; Immunosuppressive Agents; Lichenoid Eruptions; Multicenter Studies as Topic; Off-Label Use; Pruritus; Psoriasis; Pyoderma Gangrenosum; Skin Diseases; Tacrolimus; Uremia; Vitiligo

The prevalence of atopic dermatitis is increasing, and more than 50% of children with atopic dermatitis go on to develop asthma and allergies. A better understanding of the underlying immune abnormalities of this complex chronic relapsing skin disease is needed. Although the optimal treatment approach remains to be defined, several recent studies suggest a rationale for using topical calcineurin inhibitors as early intervention and adding topical corticosteroids as rescue therapy if needed.

Topics: Adrenal Cortex Hormones; Bacterial Toxins; Child; Child, Preschool; Dermatitis, Atopic; Exanthema; Humans; Ointments; Pruritus; Tacrolimus

Atopic dermatitis (AD) is a common eczematous skin condition; as many as 10-17 percent of all children are affected, and 35-60 percent of affected patients manifest symptoms manifest during the first year of life. Treatment principles for AD in young children involve conservative measures such as avoidance of hot water and environmental irritants, combined with liberal use of emollients after bathing. Low potency topical corticosteroids (TCS) are the current standard of therapy for AD in young children, reserving mid- and high-potency TCS for severe disease. However, complications of long-term use of TCS include skin atrophy, stria formation, telangiectasia, hypopigmentation, secondary infections, steroid acne, allergic contact dermatitis, and miliaria. The pediatric population is also at increased risk for systemic absorption because of their high ratio of skin surface to body mass. Systemic absorption may result in hypothalamic-pituitary-adrenal axis suppression and ultimately growth retardation. Although most topical and systemic corticosteroids are not approved by the Food and Drug Administration for use in children less than 2 years of age, conservative treatment often fails in this age group and frequently patients are treated with TCS, antibiotics, and antihistamines.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Anti-Bacterial Agents; Dermatitis, Atopic; Dose-Response Relationship, Drug; Drug Evaluation; Drug Utilization Review; Emollients; Female; Histamine H1 Antagonists; Humans; Immunosuppressive Agents; Infant; Male; Ointments; Pain; Pruritus; Retrospective Studies; Tacrolimus; Treatment Outcome

Topics: Humans; Naltrexone; Peritoneal Dialysis, Continuous Ambulatory; Prevalence; Pruritus; Renal Dialysis; Tacrolimus; Uremia

Tacrolimus, a macrolide immunomodulator, is believed to control atopic dermatitis by inhibiting T lymphocyte activation, altering cell surface expression on antigen-presenting dendritic cells and modulating the release of inflammatory mediators from skin mast cells and basophils. Tacrolimus ointment penetrates human skin with no systemic accumulation after repeated applications; systemic absorption is generally low, with most patients in clinical trials having blood concentrations of the drug below the limit of quantification. Moderate to severe atopic dermatitis significantly improved (measured using multiple end-points, including > or = 90% improvement in Physician's Global Evaluation of Clinical Response) with tacrolimus 0.03 and 0.1% ointment compared with vehicle in both adult (n = 304 and 328) and pediatric (n = 351) patients in three 12-week, double-blind, randomized, phase III trials. In adults, tacrolimus ointment was effective therapy for the treatment of atopic dermatitis on all skin regions, including the head and neck. The 0.1% concentration was more effective than the 0.03% concentration. Clinical improvement in moderate to severe atopic dermatitis in adult (n = 316) or pediatric (n = 255) patients was seen as early as week 1, and improvement continued and/or was maintained for up to 6 and/or 12 months in long-term studies. The 0.1% formulation was also effective and well tolerated for up to 2 years. Tacrolimus 0.03 and 0.1% ointment was associated with significant quality-of-life benefit in adults, children (aged 5 to 15 years) and toddlers (aged 2 to 4 years) with atopic dermatitis in 12-week phase III trials (n = 985). Skin burning and pruritus were the most common application site adverse events in adult and pediatric patients in short-term and long-term trials. These events were generally of short duration and mild or moderate severity. Cutaneous infections occurred with a similar incidence after treatment with tacrolimus ointment to that seen after vehicle in short-term trials.. Both short- and long-term monotherapy with tacrolimus 0.03 and 0.1% ointment improves moderate to severe atopic dermatitis in adult and pediatric patients. Topical tacrolimus ointment is well tolerated, with the majority of adverse events being localized, transient in nature and of mild or moderate severity. Tacrolimus ointment provides a promising addition to the currently available treatments for atopic dermatitis; it can be used as a short- or long-term intermittent therapy for moderate to severe disease, including disease on the head or neck, in adult (0.1 and 0.03% formulations) and pediatric (0.03% formulation) patients who are not adequately responsive to or are intolerant of conventional treatments.

Topics: Administration, Topical; Age Factors; Dermatitis, Atopic; Humans; Immunosuppressive Agents; Ointments; Pruritus; Quality of Life; Tacrolimus

Treatment of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) with ursodeoxycholic acid (UDCA) has been in common use since 1985. In PBC, treatment with UDCA improves laboratory data, liver histology, enables a longer transplantation-free interval and prolongs disease survival. Because UDCA is unable to cure the disease newer drugs or combination therapies are still needed. Studies with UDCA and immunosuppressants such as prednisone, budesonide and azathioprine have shown that in selected patients combination therapy may be superior to UDCA monotherapy. PSC is treated successfully with UDCA and endoscopic dilatation of the bile duct strictures. Treatment of extrahepatic manifestations of cholestatic liver disease such as pruritus, fatigue, osteoporosis and steatorrhea can be problematic and time-consuming.

Topics: Azathioprine; Celiac Disease; Cholagogues and Choleretics; Cholangitis, Sclerosing; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Osteoporosis; Prednisolone; Pruritus; Tacrolimus; Ursodeoxycholic Acid

The calcineurin pathway is often activated in mycosis fungoides. We aimed to assess the activity and safety of topical pimecrolimus, a calcineurin inhibitor, in patients with early mycosis fungoides.. PimTo-MF was a single-arm, multicentre, phase 2 trial done at six medical centres in Spain. Patients (aged ≥18 years) had histologically confirmed early mycosis fungoides (stages IA-IIA) and an Eastern Cooperative Oncology Group performance status of 0-1. Key exclusion criteria included the use of concurrent treatments for mycosis fungoides, including sunbathing, topical or systemic corticosteroids, and other calcineurin inhibitors. Patients applied topical pimecrolimus 1% cream on their skin lesions twice daily for 16 weeks (1 g per 2% of body surface), with subsequent follow-up of 12 months. Dosage modifications were not allowed. To evaluate adherence to the treatment, patients were instructed to return all empty tubes to the hospital (as per drug accountability protocols). The primary endpoint was the overall response ratein the intention-to-treat population. PimTo-MF is registered with EudraCT, 2014-001377-14, and is complete.. Between March 1, 2015, and Sept 30, 2016, 39 patients were enrolled. All patients were assessable, with a median age of 51·5 years (IQR 45-62), and the population was predominantly male (24 male [62%], 15 female [38%]). Median follow-up after baseline was 5·7 years (IQR 5·7-6·2). 22 (56%) of 39 patients had an overall response (one complete response, 21 partial responses). Responses were observed across IA (14 [54%] of 26 patients) and IB (eight [73%] of 11 patients) clinical stages, but not IIA. Topical pimecrolimus was well tolerated and no patient required a dose reduction or discontinued treatment because of unacceptable drug-related toxicity. No patients were lost to follow-up or discontinued treatment. 13 (33%) of 39 patients reported adverse events; transitory mild burning or pruritus (grade 1) was the most common, seen in eight (21%) patients. In three (8%) of these patients, the burning or pruritus was considered related to treatment. No grade 4 or 5 adverse events were observed.. Pimecrolimus 1% cream seems active and safe in patients with early stage mycosis fungoides. Our findings should be taken with caution until long-term follow-up data are obtained that confirm the safety of this treatment. Further controlled clinical trials are warranted to confirm these results.. Instituto de Salud Carlos III and the European Regional Development Fund.. For the Spanish translation of the abstract see Supplementary Materials section.

Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Pruritus; Skin Neoplasms; Tacrolimus

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare infiltrative vascular tumors. Currently, no standard treatment regimens exist for KHE/TA. The purpose of our study was to evaluate the efficacy and safety of topical application of tacrolimus for superficial KHE/TA. We examined six patients with superficial KHE/TA. All patients were treated with tacrolimus 0.1% ointment twice daily for at least 12 months. The response rate was 100%, including three nearly complete remissions. Only one patient experienced local pruritus during treatment. The data constituted an intriguing rationale for clinical trials of topical tacrolimus in the treatment of superficial KHE/TA.

Topics: Administration, Cutaneous; Biopsy; Child, Preschool; Female; Hemangioendothelioma; Hemangioma; Humans; Infant; Kasabach-Merritt Syndrome; Male; Off-Label Use; Ointments; Photography; Pruritus; Sarcoma, Kaposi; Skin; Skin Neoplasms; Tacrolimus; Treatment Outcome

In the treatment of atopic dermatitis, pimecrolimus has high antipruritic effects.. To investigate the efficacy of 1% pimecrolimus cream in comparison to 1% hydrocortisone cream in non-atopic prurigo nodularis (PN).. A randomized, controlled, double-blind study with intraindividual randomization was done in 30 patients (17 females, 13 males; mean age 58.5 years) with PN.. Pruritus intensity decreased significantly (p < 0.001) on both treated sides as early as after 10 days of treatment; scratch lesions improved (p < 0.001). Quality of life as assessed by the Dermatology Life Quality Index improved significantly. However, a significant advantage of pimecrolimus over hydrocortisone was not found.. The results suggest that the non-steroid pimecrolimus is an effective alternative for PN treatment.

Topics: Administration, Cutaneous; Adult; Aged; Anti-Inflammatory Agents; Biomarkers; Calcitonin Gene-Related Peptide; Dermatologic Agents; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Neuropeptides; Prurigo; Pruritus; Quality of Life; Tacrolimus

The purpose of this study was to investigate the clinical effect of a supplementary diet containing heat-killed lactic acid bacterium Lactobacillus paracasei K71 (LAB diet) on adult patients with atopic dermatitis (AD). A randomized, double-blind, placebo-controlled study was conducted in 34 adult type AD subjects who were treated with conventional topical corticosteroid and tacrolimus. LAB diet or placebo was added over 12 weeks. The primary end-point was the clinical severity of AD which was evaluated by a severity scoring system proposed by the guideline of the Japanese Dermatological Association. The effect was also secondarily evaluated by itch scores of visual analog scales (VAS), quality-of-life (QOL) impairment scores of Skindex 16 and consumption amounts of topical therapeutics. Data on these four assessment variables were collected at baseline and at week 4, 8 and 12. Within the study population, the skin severity scores were significantly decreased from baseline at week 8 (P<0.05) and at week 12 (P<0.01) in the LAB diet group but not in the placebo group. Influence of LAB diet on itch scores or QOL impairment scores was not evident. The consumption of topical therapeutics in the placebo group was 1.9-times greater in total amount compared with the corresponding value in the LAB diet group during the intervention period, although there was no significant difference. No LAB diet- or placebo-related adverse events were observed. We concluded that the LAB diet may have some benefits as a complementary therapy for adult AD patients who are managed with the conventional treatment.

Topics: Adrenal Cortex Hormones; Adult; Aged; Complementary Therapies; Dermatitis, Atopic; Double-Blind Method; Female; Hot Temperature; Humans; Lactobacillus; Male; Middle Aged; Practice Guidelines as Topic; Probiotics; Pruritus; Quality of Life; Severity of Illness Index; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Adult; Calcineurin Inhibitors; Double-Blind Method; Humans; Immunosuppressive Agents; Pruritus; Severity of Illness Index; Tacrolimus; Treatment Outcome; Uremia

Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2-15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of >or=60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was -11.8%, exceeding the non-inferiority limit of -15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 +/- 5.0 and 8.6 +/- 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep.

Topics: Adolescent; Androstadienes; Calcineurin Inhibitors; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Female; Fluticasone; Humans; Male; Ointments; Pruritus; Recurrence; Sleep Wake Disorders; Tacrolimus; Treatment Outcome

We aimed to compare the efficacy of topical pimecrolimus versus hydrocortisone in treating external auditory canal pruritus, using the Modified Itch Severity Scale as an assessment tool.. We included in the study 40 patients with isolated itching of the external auditory canal who had not received any benefit from previous topical and systemic treatments. Topical 1 per cent pimecrolimus or topical hydrocortisone was applied to each patient's external auditory canal for three months. A Modified Itch Severity Scale was developed and used to assess treatment response.. Compared with itching scores on initial assessment, the scores of patients receiving topical pimecrolimus had decreased by 52.3 per cent by the third week of treatment and by 77.6 per cent by the third month, whereas the scores of patients receiving topical hydrocortisone had decreased by 34.4 per cent by the third week and by 64.2 per cent by the third month.. Topical pimecrolimus appears to be as effective as topical hydrocortisone in relieving external auditory canal pruritus. We used a novel scoring system, the Modified Itch Severity Scale, to evaluate external auditory canal pruritus; this is the first self-reporting questionnaire for the quantification of external auditory canal pruritus severity. Further studies are needed to validate this scoring system.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Ear Canal; Ear Diseases; Female; Humans; Hydrocortisone; Immunosuppressive Agents; Male; Middle Aged; Pruritus; Severity of Illness Index; Surveys and Questionnaires; Tacrolimus; Treatment Outcome

Chronic hand dermatitis is common and difficult to treat.. Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis.. Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators' Global Assessment of prospectively selected 'target hand' as treatment success (Investigators' Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed.. Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase.. The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Dermatologic Agents; Double-Blind Method; Emollients; Female; Hand Dermatoses; Humans; Male; Middle Aged; Pruritus; Severity of Illness Index; Tacrolimus; Treatment Outcome; Young Adult

Atopic dermatitis (AD) is most prevalent in areas of reduced skin barrier reserve, like face and neck, especially in children. Treatment with topical corticosteroids (TCS) is limited due to heightened risk of treatment-associated side-effects, thus necessitating alternative AD therapies.. The primary study objective was to determine the efficacy of pimecrolimus cream 1% in children with mild-moderate facial AD dependent on/intolerant of TCS. Secondary objectives included effects on overall Eczema Area and Severity Index (EASI), head/neck EASI, pruritus severity and time to clearance of facial AD.. A multicentre, double-blind (DB) study of < or = 6 weeks, followed by a 6-week, open-label (OL) phase was conducted. Two hundred patients (aged 2-11 years) were randomized 1:1 to pimecrolimus cream 1% (n = 99) or vehicle (n = 101) twice daily until clearance of facial AD or for a maximum of 6 weeks (DB phase). Sixteen patients receiving vehicle were allowed to switch to the OL phase at day 22.. Significantly more pimecrolimus-treated vs. vehicle-treated patients were cleared/almost cleared of facial AD (Investigators' Global Assessment 0/1): 74.5% vs. 51.0%, P < 0.001 (day 43) [57.1% vs. 36.0%, P = 0.004 (day 22)]. Median time to clearance was 22.0 vs. 43.0 days (pimecrolimus vs. vehicle, respectively). Statistically significant differences for pimecrolimus vs. vehicle were also seen on head/neck EASI, overall EASI, and head/neck pruritus scores. Adverse events were mainly mild-moderate, occurring with similar frequency in both treatment groups.. In children with facial dermatitis intolerant of/dependent on TCS, pimecrolimus cream 1% effectively controls eczema and pruritus and is well tolerated.

Topics: Adrenal Cortex Hormones; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Double-Blind Method; Eczema; Facial Dermatoses; Female; Humans; Male; Pharmaceutical Vehicles; Pruritus; Severity of Illness Index; Tacrolimus; Treatment Outcome

This study compared topical pimecrolimus with betamethasone in the treatment of pruritus and chronic skin lesions due to sulfur mustard exposure. Seventy male chemical-injured war veterans participated in this investigator-blinded clinical trial. They were randomized to receive pimecrolimus cream 1% (n = 35) or betamethasone cream 0.1% (n = 35) two times a day for 6 weeks. Dermatological examination and assessment of pruritus severity by a pruritic score questionnaire and visual analogue scale were done before and after the treatment course. A significant decrease (P < 0.05) in pruritus, burning sensation, and skin dryness was shown in both groups after the treatment. However, the severity of hyper- and hypopigmentation, vesicle, erythema, fissure, lichenification and excoriation did not decrease significantly in either group (P > 0.05). Mean (+/- standard deviation) pruritic scores at baseline for the pimecrolimus and betamethasone groups were 30.4 (+/- 8.0) and 33.6 (+/- 7.2), respectively (P = 0.103). These scores decreased to 18.8 (+/- 4.8) in the pimecrolimus and 20.8 (+/- 4.0) in the betamethasone groups after treatment; both showed a statistically significant decrease (P < 0.001). Change of pruritus score from baseline to after the treatment course was not statistically different between the two groups (P = 0.502). No serious side-effects were reported during the course of the treatment. Topical pimecrolimus 1% was as effective as betamethasone cream 0.1% in controlling pruritus, burning sensation and skin dryness of sulfur mustard-exposed patients.

Topics: Administration, Cutaneous; Adult; Aged; Anti-Inflammatory Agents; Betamethasone; Chemical Warfare Agents; Chronic Disease; Drug Administration Schedule; Humans; Male; Middle Aged; Mustard Gas; Ointments; Pruritus; Severity of Illness Index; Single-Blind Method; Tacrolimus; Treatment Outcome

Pimecrolimus was found to be effective for the treatment of seborrheic dermatitis in several studies and its off-label use is increasing gradually.. This study was conducted to obtain more detailed information concerning the daily use of pimecrolimus in seborrheic dermatitis and it also aims to contribute to data for the future construction of guidelines.. A total of 52 patients with seborrheic dermatitis enrolled in the study. Pimecrolimus 1% cream was applied twice daily. The mean cure and remission times, detailed responses of each clinical finding and side effects were investigated.. The mean cure and mean remission times were 13.34 and 47.98 days, respectively. Disease severity improved by 50% in between the third and seventh days. Pruritus responded first to pimecrolimus. The drug was equally effective for erythema and scaling. The most frequent side effect was the burning-tingling sensation. After the seventh day of the study, there was no side effect.. Pimecrolimus applications for the treatment of seborrheic dermatitis provide a complete cure in a short period of time and a sustained symptom-free period with low and self-limited side effects.

Topics: Adult; Dermatitis, Seborrheic; Dermatologic Agents; Female; Humans; Male; Pruritus; Tacrolimus

To investigate the antipruritic mechanisms of pimecrolimus cream for women facial dermatitis.. Topical pimecrolimus cream 1% was applied in 52 women patients with facial dermatitis. The Investigators Global Assessment (IGA) score, severity of pruritus (SP) scores, and a basic syntax and molecular substrate (molecular psychophysics) of nociception and pruriception established by temperature-sensitive transient receptor potential (TRP) channels were used to evaluate the clinical signs, severity of pruritus, and skin sensory phenomenon.. The IGA scores at day 1 and 4 of treatment and the SP score at day 1, 4, and 11 of treatment were significantly lower than the baseline scores before treatment (P < 0.05). Among these 52 patients, 28 (53.8%) showed positive capsaicin-like response (i.e., burning with consequent rapid amelioration of pruritus) at the application sites, 12 (23.1%) showed camphor-like response (i.e., warming with consequent rapid amelioration of pruritus), and 12 (23.1%) showed negative capsaicin-like response or negative camphor-like response.. Treatment with pimecrolimus cream 1% can rapidly and effectively improve the signs and symptoms of facial dermatitis in adult women patients. Pimecrolimus cream 1% may act on the transient potential vanilloid 1 (TRPV1) receptor in the skin sensory afferents to induce capsaicin-like response or camphor-like response and then desensitizes TRPV1 and rapidly inhibits or alleviate itching.

Topics: Administration, Topical; Adolescent; Adult; Antipruritics; Dermatitis; Face; Female; Humans; Middle Aged; Pruritus; Tacrolimus; Young Adult

Pimecrolimus cream 1% has been shown to effectively control atopic eczema (AE) when applied twice daily from the first signs or symptoms of AE until clearance. Moreover, pimecrolimus cream 1% has a favourable safety profile, lacking topical corticosteroid-related side-effects such as skin atrophy, making it particularly useful to treat delicate body regions (e.g. the face).. The objective of this naturalistic study was to monitor the safety, tolerability and efficacy of pimecrolimus when used in the long-term management of AE in a real-life setting.. A multicentre, open-label study was conducted in 2034 patients aged >or= 3 months with mild to moderate AE for up to 12 months' duration. Patients applied pimecrolimus cream twice daily, initiating treatment at first signs or symptoms of AE, continuing until clearance.. Patients (n= 1847; 91%) completed 3 months of the study. Treatment success (clear or almost clear AE) after 3 months of treatment was observed on the whole body in 59% of patients and on the face in 81% of patients. Disease improvement of whole body and face was seen in 77% and 63% of patients, respectively. Pruritus was absent or mild in 79% of patients. Pimecrolimus cream was well tolerated throughout the study.. In a daily practice setting, pimecrolimus cream 1% effectively and safely controls AE.

Topics: Adolescent; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infant; Male; Ointments; Pruritus; Tacrolimus; Treatment Outcome

The objective of this study was to assess time to onset of pruritus improvement in a pediatric population treated with pimecrolimus cream 1%. This 8-day, double-blinded, vehicle-controlled study randomized 174 children and adolescents (aged 2-17 years) with mild to moderate atopic dermatitis (AD) and moderate to severe pruritus to twice-daily applications of pimecrolimus cream 1% or vehicle. There were no significant between-group differences in demographics or baseline disease characteristics. Pruritus was assessed by subjects using a 4-point pruritus severity scale (0-3). The primary efficacy variable was time to a 1 point or more improvement in pruritus score from baseline. The 2 treatment groups were compared using log-rank testing of the time-to-event data. In the per-protocol (PP) population, median times to a 1 point or more improvement in pruritus score were 48 and 72 hours for pimecrolimus and vehicle groups, respectively (P = .038). From day 3 onward, significantly more subjects (P = .023) in the pimecrolimus group versus the vehicle group reported complete pruritus resolution. Pimecrolimus cream 1% improved pruritus within 48 hours in children and adolescents with mild to moderate AD and achieved complete resolution of pruritus in a significantly greater number of subjects in the pimecrolimus group versus the vehicle group by the end of the 7-day treatment period (P = .008).

Topics: Adolescent; Calcineurin Inhibitors; Case-Control Studies; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Double-Blind Method; Drug Administration Schedule; Emollients; Follow-Up Studies; Humans; Immunosuppressive Agents; Peptidylprolyl Isomerase; Pharmaceutical Vehicles; Placebos; Pruritus; Severity of Illness Index; Tacrolimus; Time Factors; Treatment Outcome

To evaluate the efficacy of the novel topical immune modulator tacrolimus in chronic uninfectious otherwise therapy-resistant external otitis (EO).. Prospective clinical study.. There were 53 patients aged 5 to 83 years. An ear wick containing 0.1% tacrolimus ointment (Protopic) was inserted into the external auditory canal every 2nd to 3rd day. Altogether, the wick was changed three times. The pre-, intra- and posttherapeutic state of the clinical parameters otalgia, edema, otorrhea, erythema, pruritus, and desquamation was rated by means of a 6-point score system. Treatment efficiency was evaluated on the basis of follow-up investigations at 3-month intervals, a standardized findings sheet, and photograph documentation.. The short-term results showed a clear improvement in 85% of the patients and significant reductions of the severity levels for all clinical parameters investigated (P < .001). Concerning the long-term results, a one-time treatment cycle led to complete healing in 46% of the patients throughout a follow-up of 10 to 22 months. Of the patients, 54% had recurrent EO events with significantly extended mean symptom-free intervals. Reapplied tacrolimus treatment patterns attenuated the relapsing course of disease and significantly reduced the number of EO episodes. Within the observation period, no relevant side effects were observed, except for a local feeling of heat, occasional skin burning, and itching.. The topical application of 0.1% tacrolimus ointment in the outer ear canal appears to be an effective and well-tolerated new option in corticosteroid-free treatment of chronic therapy-resistant EO.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cerebrospinal Fluid Otorrhea; Child; Child, Preschool; Drug Resistance, Bacterial; Earache; Edema; Erythema; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Otitis Externa; Otoscopy; Prospective Studies; Pruritus; Tacrolimus; Treatment Outcome

Use of topical corticosteroids for the treatment of pityriasis alba is limited by their potential side-effects, such as skin atrophy especially with long-term use on the face. Pimecrolimus cream 1% is a topical calcineurin inhibitor that has anti-inflammatory properties, lacks the cutaneous side-effects associated with steroids, and provide a potential benefit for the treatment of pityriasis alba.. This 10-patient, prospective, single-arm, open-label, single-center, 12-week, investigator-initiated proof of concept study assessed the efficacy, safety, and patient acceptance of pimecrolimus cream 1% twice daily. In addition to pimecrolimus cream, patients used facial emollient containing SPF 15 sunscreen and mild soap-free cleanser. Efficacy assessments were Investigator Global Assessment (IGA) of disease severity and evaluation of uneven skin color, scaling, eczema, follicular keratosis, and pruritus. All efficacy assessments were reported on a 4-point scale (0 = none to 3 = severe).. Of the 10 patients enrolled (aged: 12-35 years), all had intensive sun-exposure, 90% had skin type IV-V, and 80% completed the 12-week treatment. At baseline, mean IGA was 1.20 (mild-moderate), uneven skin color was 2.3 (moderate-severe) and scaling was 1.2 (mild). IGA decreased to 0.25 by week 12, uneven skin color improved by week 3 with near complete resolution by week 12 (mean = 0.38) and scaling resolved at week 3. Pruritus, eczema, and follicular keratosis remained at low levels from baseline throughout the course of the study. Patients consistently reported satisfaction with the treatment ("satisfied" or "very satisfied"). No adverse events were reported.. Pimecrolimus cream 1% may represent an alternative for the treatment of pityriasis alba.

Topics: Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Drug Administration Schedule; Eczema; Female; Humans; Hypopigmentation; Male; Pityriasis; Prospective Studies; Pruritus; Severity of Illness Index; Skin; Tacrolimus; Treatment Outcome

Pimecrolimus cream 1% (Elidel, Novartis Pharmaceuticals AG) effectively improves/relieves pruritus associated with atopic dermatitis (AD), but few data are available regarding the timing of relief. The purpose of this study was to investigate the timing of pruritus relief produced with pimecrolimus in adults with mild/moderate AD and moderate/severe pruritus.. Patients were randomized to 7 days of treatment with pimecrolimus (n = 100) or vehicle (n = 98). Pruritus severity was assessed daily on a 4-point scale (0 = absent, 3 = severe), reflecting the previous 24 h experience. Patients who completed this core study were eligible to enter a voluntary 5-week, open-label extension study.. A significant effect was noted within 48 h of treatment, with pruritus improving in 56% of pimecrolimus-treated patients and 34% of vehicle-treated patients (P = 0.003). Pruritus relief was maintained during the remainder of the core and extension phases, and was accompanied by an improvement in the Investigator's Global Assessment score.. Pimecrolimus cream 1% significantly reduced pruritus within 48 h.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Atopic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ointments; Probability; Pruritus; Reference Values; Severity of Illness Index; Tacrolimus; Treatment Outcome

Topical pimecrolimus and narrowband ultraviolet B (UVB) are both known to be effective in treating atopic dermatitis. We compared the clinical efficacy of monotherapy with either twice daily topical 1% pimecrolimus cream or twice weekly narrowband UVB, and combination therapy in 26 children and adolescents with moderate to severe atopic dermatitis in a half-side manner for 6 weeks. Twenty-four patients completed the study. Monotherapy and combination therapy notably reduced the scores of the Eczema Area and Severity Index ( p = 0.002) and the severity of pruritus ( p < or = 0.004). There was no significant difference in therapeutic efficacy among the treatment regimens at week 6. In conclusion, because of the lack of short-term additive therapeutic efficacy, concomitant use of pimecrolimus and narrowband UVB is inadvisable in treating moderate to severe atopic dermatitis in children and adolescents.

Topics: Administration, Topical; Adolescent; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Female; Humans; Male; Ointments; Prospective Studies; Pruritus; Severity of Illness Index; Tacrolimus; Treatment Outcome; Ultraviolet Therapy

Pityriasis alba (PA) is a frequent reason for dermatological consultation because of its chronic course, tendency to relapse and aesthetic impact.. In view of its strong association with atopic dermatitis, the objective of this open-label study was to assess the efficacy and safety of tacrolimus ointment in the treatment of PA compared with the efficacy of moisturizers.. The study population consisted of 60 individuals of phototype III or IV according to Fitzpatrick's classification, aged 6-21 years. Patients were randomly assigned to one of two groups. Subjects in group A were instructed to apply tacrolimus ointment 0.1% twice daily, 12 h apart, on all hypopigmented macules. Standard moisturizers with SPF 20 sunscreen were used on all lesions applied at least 30 min apart from the tacrolimus ointment. Subjects in group B used solely the same moisturizers with sunscreen. Hypopigmented areas were evaluated at baseline and weeks 0, 3, 6 and 9 by investigators for scaling, hypopigmentation and pruritus on a scale of 0-3. Patient satisfaction was also recorded on a scale of 0-3. All adverse effects were recorded.. A statistically significant improvement through time, in hypopigmentation, pruritus and scaling was observed in both groups during the course of 9 weeks. Hypopigmentation resolved from a baseline score of 2.38+/-0.64 to 1.15+/-0.54 at week 3, 0.46+/-0.51 at week 6 and 0.00+/-0.00 at week 9 for the group applying tacrolimus ointment 0.1%. The difference in improvement between the two groups was statistically significant on all three assessments for hypopigmentation (P<0.001), and for pruritus on week 6 and 9 assessments (P<0.05). Three patients (11.5%) in the tacrolimus group reported a mild transient sensation of burning. All patients in the tacrolimus group reported they were completely satisfied or just satisfied with the treatment compared with only 50% of patients using the placebo.. Tacrolimus ointment 0.1% appears to be an effective and safe treatment for PA.

Topics: Adolescent; Adult; Analysis of Variance; Child; Dermatologic Agents; Double-Blind Method; Female; Humans; Hypopigmentation; Immunosuppressive Agents; Male; Pityriasis; Pruritus; Skin; Statistics, Nonparametric; Sunscreening Agents; Tacrolimus

Pruritus is a common and disabling symptom for patients undergoing hemodialysis. Many topical and systemic treatments have been used for uremic pruritus, mostly in anecdotal reports. A recent case series demonstrated that topical tacrolimus ointment 0.03% had a significant antipruritic effect for patients with uremia. In an attempt to confirm these findings, we conducted a randomized, double-blind, vehicle-controlled study to assess the efficacy of tacrolimus ointment 0.1% for the treatment of hemodialysis-related pruritus. The results of this study do not demonstrate that tacrolimus ointment 0.1% is more effective than vehicle in relieving uremic pruritus.

Topics: Administration, Topical; Aged; Double-Blind Method; Humans; Immunosuppressive Agents; Middle Aged; Ointments; Pruritus; Renal Dialysis; Tacrolimus; Uremia

Uraemic pruritus (UP) is a serious symptom of chronic dialysis patients and patients with end-stage renal disease. UP causes skin damage, discomfort, sleeping disorders and diminished quality of life. Since UP is considered to be in part an immune-mediated inflammatory process, immunosuppressive drugs like tacrolimus may be beneficial.. We conducted a prospective study on the effect of 6 weeks treatment with two sequential concentrations of tacrolimus ointment on the severity of UP in chronic dialysis patients and again after 2 weeks wash-out. Twenty-five patients with UP were enrolled in the study; 21 patients completed the study. UP was measured using a validated modified pruritus assessment score and a Visual Analogue Scale (VAS).. The modified pruritus assessment score decreased significantly by 81.8% after 6 weeks treatment from [median score 11 (interquartile range: IQR 6-16) on day 0 to median score 2 (IQR 0-5.25) at week 6: P<0.0001]. After 2 weeks wash-out, the median score returned to 72.7% of baseline levels [8 (IQR 2-16)]. Using the VAS score an identical evolution could be demonstrated. Tacrolimus ointment was well tolerated and no serious adverse events were noted. Transient stinging and burning sensation was reported by four patients in the first weeks of the trial, one patient suffered a mild skin rash. No systemic exposure to tacrolimus was detected.. This prospective study has shown that 6 weeks treatment with tacrolimus ointment significantly reduces the severity of UP in chronic dialysis patients and is well tolerated. Randomized placebo-controlled studies are necessary to confirm these encouraging preliminary results.

Topics: Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Pruritus; Renal Dialysis; Tacrolimus

To evaluate pimecrolimus cream 1% and tacrolimus ointment 0.03% in pediatric patients with moderate atopic dermatitis (AD).. 141 patients (aged 2-17 years) were randomized to treatment with pimecrolimus cream 1% (n=71) or tacrolimus ointment 0.03% (n=70) twice daily for 6 weeks.. At day 4, local, application-site reactions were less common and of shorter duration with pimecrolimus than with tacrolimus. Incidence of erythema/irritation was 8% (6/71) with pimecrolimus compared with 19% (13/70) with tacrolimus (P=.039). Fewer patients receiving pimecrolimus (0%, 0/6) experienced erythema/irritation lasting >30 minutes, compared with those receiving tacrolimus (85%, 11/13; P <.001). Fewer patients reported itching with pimecrolimus (8%; 6/71) than with tacrolimus (20%; 14/70; P=.073). Incidence of warmth, stinging, and burning was similar in both groups; however, reactions lasting >30 minutes were fewer with pimecrolimus (0%, 0/14) than with tacrolimus (67%, 8/12; P <.001). More patients receiving pimecrolimus rated ease of application as 'excellent' or 'very good', compared with tacrolimus (76% vs 59%, respectively; P <.020). Efficacy was similar in both groups at day 43. Both treatments were generally well tolerated with no unexpected adverse events.. Pimecrolimus cream 1% had better formulation attributes and local tolerability than tacrolimus ointment 0.03% while providing similar efficacy and overall safety in pediatric patients with moderate AD.

Topics: Adolescent; Child; Child, Preschool; Dermatitis, Atopic; Dermatitis, Irritant; Dermatologic Agents; Drug Administration Schedule; Drug Combinations; Erythema; Female; Humans; Male; Ointments; Patient Satisfaction; Pruritus; Tacrolimus

Topics: Administration, Topical; Adolescent; Child; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Male; Pruritus; Skin; Sleep Wake Disorders; Tacrolimus; Treatment Outcome

Seborrhoeic dermatitis is a chronic inflammatory disease with remissions and exacerbations, characterized by erythema, scaling and pruritus primarily on the face, scalp and chest. Corticosteroids and antifungals are the mainstay of therapy. However, chronic use of corticosteroids is associated with side-effects such as skin atrophy and telangiectasia. Pimecrolimus, an inhibitor of calcineurin, has been used successfully in one patient with seborrhoeic dermatitis.. The objective of this randomized open-label clinical trial was to compare the efficacy and tolerability of pimecrolimus in comparison with a potent corticosteroid (betamethasone 17-valerate) in the treatment of seborrhoeic dermatitis.. Twenty patients with seborrhoeic dermatitis were included in this study, 11 patients in the pimecrolimus 1% cream group and nine patients in the betamethasone 17-valerate 0.1% cream group. Patients were instructed to use a thin layer of the study products twice daily at the lesional area and to discontinue treatment as soon as symptoms were absent. Clinical measures assessed were erythema, scaling and pruritus which were evaluated using a four-point scale (0-3).. Both pimecrolimus and betamethasone were highly effective in the treatment of seborrhoeic dermatitis. Betamethasone reduced all three parameters, erythema, scaling and pruritus, faster than pimecrolimus, but the differences in reduction were not statistically significant. Relapses were observed more frequently and were more severe with betamethasone than with pimecrolimus. Moreover, pruritus was not observed after discontinuation of treatment from day 15 and beyond in the pimecrolimus group, whereas it was reported in most patients of the betamethasone group. This difference was statistically significant.. It appears that pimecrolimus, a nonsteroidal topical treatment, may be an excellent alternative therapeutic modality for treating seborrhoeic dermatitis.

Topics: Administration, Cutaneous; Adult; Betamethasone; Calcineurin Inhibitors; Dermatitis, Seborrheic; Dermatologic Agents; Erythema; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pruritus; Recurrence; Severity of Illness Index; Tacrolimus; Treatment Outcome

Contact dermatitis is a common clinical problem, with prevalent sensitizers being cosmetics, metals, medicines, and plants. Plants of the Toxicodendron species cause allergic contact dermatitis (ACD) in 50% to 70% of the population. Pimecrolimus is an ascomycin macrolactam developed for the treatment of inflammatory skin diseases and approved by the US Food and Drug Administration for atopic dermatitis. There are studies supporting the effectiveness of macrolactams when administered before antigen challenge, but there are no studies describing the effectiveness of these drugs in the treatment of established human ACD.. To investigate the effect of topical pimecrolimus in the treatment of Toxicodendron-induced ACD once rash is evident.. Poison ivy tincture was applied to the bilateral anterior forearms of 12 subjects with Finn Chambers (Allerderm Diagnostic Products, Petaluma, CA). After dermatitis was evident, volunteers treated each arm twice daily with either 1% topical pimecrolimus cream or placebo in a blinded fashion. Outcomes measured were a dermatitis grading score and time to rash and itch resolution.. The median +/- SEM time for rash resolution was 16.55 +/- 1.59 days in the treatment group and 16.27 +/- 1.82 days in the placebo group (P = 0.601). The median time for itch resolution was 4.73 +/- 1.56 days in the treatment group and 4.91 +/- 1.59 days in the placebo group (P = 0.167). The average dermatitis score was 2.26 +/- 0.17 in the treatment group and 2.32 +/- 0.15 in the placebo group (P = 0.62).. The application of topical pimecrolimus is ineffective in the treatment of ongoing Toxicodendron-induced ACD.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Allergic Contact; Dermatitis, Toxicodendron; Dermatologic Agents; Exanthema; Female; Humans; Male; Middle Aged; Pruritus; Severity of Illness Index; Tacrolimus; Time Factors; Treatment Outcome

Tacrolimus (formerly FK 506) is an immunosuppressive drug that works by inhibiting calcineurin, a calcium-dependent protein phosphatase required for immune function. Tacrolimus has been shown to be effective topically in atopic dermatitis and systemically in psoriasis and graft-vs-host disease (GVHD). However, its efficacy in treating cutaneous GVHD when applied topically has not been reported.. To assess the therapeutic efficacy of 0.1% tacrolimus ointment on chronic cutaneous GVHD in patients with symptoms refractory to systemic corticosteroid therapy.. Tacrolimus ointment effectively treated pruritus and/or erythema in 13 (72%) of 18 patients with chronic GVHD. Responding patients had a rapid effect within several hours to days. Effectiveness was measured by means of patient report, results of physical examination, side-by-side comparisons of tacrolimus vs a vehicle control, and temporal flares of the cutaneous symptoms of the disease in the context of stopping tacrolimus ointment therapy. Because of the progression of GVHD and in 2 cases, loss of drug efficacy, all patients eventually went on to receive more aggressive treatment, including increases in steroid dosage, psoralen-UV-A therapy, and extracorporeal photopheresis.. This case series suggests that tacrolimus ointment has efficacy in treating the erythema and pruritus of steroid-refractory, chronic cutaneous GVHD in most patients. The rapid response of tacrolimus ointment may provide a useful therapeutic bridge to systemic therapies that have slower onset, such as psoralen-UV-A therapy or extracorporeal photopheresis.

Topics: Adult; Bone Marrow Transplantation; Chronic Disease; Erythema; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Pruritus; Skin Diseases; Tacrolimus; Treatment Outcome

To evaluate the role of tacrolimus ointment in the management of patients on dupilumab therapy for severe atopic dermatitis, in a real-life setting.. Consecutive patients with severe AD treated with dupilumab were enrolled. Topical treatment was associated according to the clinical practice. Eczema Area and Severity Index (EASI), itching and sleep Numerical Rating Scale (NRS) and Dermatologic quality of Life (DLQI) were recorded at baseline and after 4, 16 and 52 weeks of treatment with dupilumab.. Overall, 342 patients were enrolled, and 307 were evaluable. Tacrolimus was used by 6.5% (n=20) of patients at baseline, 11%, 13.5%, and 11.3% after 1, 4 and 12 months, respectively; the mean time to introduce tacrolimus after initiation of dupilumab was 8.3 ± 0.3 months. Low EASI score (<7; mild disease) after 1 month of systemic therapy was more frequent in patients who applied tacrolimus at baseline than in patients who did not (72.2% vs. 55.8%, p=0.027). Female sex, low DLQI scores, low age at dupilumab initiation, and non-generalized AD were correlated with an increased probability to start tacrolimus at any time during the study.. Data suggested that early treatment of localized areas with tacrolimus improves systemic treatment efficacy.

Topics: Dermatitis, Atopic; Eczema; Female; Humans; Pruritus; Quality of Life; Severity of Illness Index; Tacrolimus; Treatment Outcome

Topics: Eczema; Humans; Immunosuppressive Agents; Keratosis; Pruritus; Tacrolimus

Atopic dermatitis (AD) has a severe impact on quality of life (QoL).. To analyze the impact of AD on QoL of small children with moderate-to-severe AD in a tertiary health care hospital in Helsinki, Finland.. Based on interim analysis of this longitudinal follow-up study, we investigated treatment response (topical corticosteroids vs. tacrolimus) and QoL of 152 small children with moderate-to-severe AD.. The tacrolimus group had a significantly better treatment response at 12 months visit, but thereafter no differences were observed (p = 0.029; Mann-Whitney U test). The odds ratio for group comparisons was 2.258 (CI: 1.151-4.431). There was a significant improvement in QoL during follow-up in both treatment groups. Our study showed substantial improvements in disease severity and QoL based on active management and effective treatments in small children with AD. The main improvement was seen during the first year in both treatment groups with a lasting response.. Effective treatment has a significant positive impact on the QoL of small children with AD and their families.

Topics: Administration, Topical; Dermatitis, Atopic; Dermatologic Agents; Family; Female; Follow-Up Studies; Humans; Hydrocortisone; Immunosuppressive Agents; Infant; Longitudinal Studies; Male; Ointments; Pruritus; Quality of Life; Severity of Illness Index; Tacrolimus

Epidermolytic acanthomas (EA) are rare benign tumors of unclear etiology that present as flat, sometimes slightly keratotic, pale or whitish papules that are usually asymptomatic. Not uncommonly, their clinical appearance in the anogenital area might lead to misdiagnosis as other lesions that commonly develop at this site, such as condylomata acuminata. Though mainly asymptomatic, there are also reports of EA presenting with persistent genital pruritus. We describe the first reported case of pruritic scrotal EA successfully treated with topical pimecrolimus.

Topics: Acanthoma; Dermatologic Agents; Dosage Forms; Humans; Male; Middle Aged; Pruritus; Scrotum; Skin Neoplasms; Tacrolimus; Treatment Outcome

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Topics: Adult; Anti-Inflammatory Agents; Calcineurin Inhibitors; Child; Dermatitis, Atopic; Eczema; Humans; Pruritus; Tacrolimus

Bullous scabies is an uncommon subtype of scabies that frequently mimics other blistering skin diseases. Nocturnal pruritus is a hallmark symptom of bullous scabies. We report an unusual case of bullous scabies presenting in the absence of pruritus in an immunosuppressed pediatric patient. It is critical that clinicians consider the diagnosis of bullous scabies in any patient with bullae, irrespective of pruritus symptoms.

Topics: Adolescent; Alagille Syndrome; Diagnosis, Differential; Exanthema; Follow-Up Studies; Humans; Immunocompromised Host; Ivermectin; Liver Transplantation; Male; Pemphigoid, Bullous; Pruritus; Risk Assessment; Scabies; Tacrolimus

Topics: Administration, Cutaneous; Animals; Aprepitant; Behavior, Animal; Calcineurin Inhibitors; Dermatitis, Contact; Disease Models, Animal; Filaggrin Proteins; Ganglia, Spinal; Humans; Intermediate Filament Proteins; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ointments; Oxazolone; Oximes; Pruritus; Skin; Substance P; Tacrolimus; TRPA1 Cation Channel

Transient erythema after alcohol consumption is a side effect of topical tacrolimus use. The clinical picture is characterised by itching, a burning sensation and erythema, often at the site where tacrolimus is applied. The erythema develops shortly after alcohol consumption and disappears after approximately 1 hour.. We are describing a patient who used a 0.1% tacrolimus ointment for periocular eczema and in whom transient erythema developed around the eyes after alcohol consumption.. The symptoms may be caused by the capsaicin-like effects of both tacrolimus and ethanol. Potential inhibition of aldehyde dehydrogenase by tacrolimus may also play a role. Prophylactic treatment with acetylsalicylic acid before alcohol consumption reduces the symptoms.

Topics: Administration, Topical; Alcohol Drinking; Eczema; Erythema; Humans; Immunosuppressive Agents; Ointments; Pruritus; Tacrolimus

Topics: Administration, Cutaneous; Adolescent; Adult; Dermatitis, Atopic; Emollients; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pain; Pain Measurement; Prospective Studies; Pruritus; Skin; Tacrolimus; Treatment Outcome; Water Loss, Insensible; Young Adult

Topical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood.. This study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms.. AD-like dermatitis was induced in the dorsal skin of NC/Nga mice by repeated topical application of Dermatophagoides farinae body (Dfb) ointment twice weekly for three weeks. Mice with dermatitis scores over 5 were divided into five groups with equal dermatitis scores and treated with BMV, CBP, TAC, or Vaseline (Vas) once daily for two consecutive days, or were not treated (NT). Scratching behavior was analyzed using a SCLABA. After the second treatment, dermatitis showed significantly greater improvement in the CBP and TAC-treated groups than in the Vas-treated and NT groups. The numbers of scratching bouts were significantly lower in CBP and TAC-treated mice than in Vas-treated mice. TEWL was significantly lower in TAC-, but not in CBP-, treated mice than in Vas-treated mice. Immunohistochemical examination showed that BMV, CBP and TAC did not reduce the increased densities of epidermal protein gene product 9.5- and substance P-immunoreactive fibers. The numbers of dermal CD4-immunoreactive T cells were significantly lower in BMV and CBP-treated mice than in Vas-treated and NT mice. The numbers of dermal eosinophils were significantly lower in BMV, CBP and TAC-treated mice than in Vas-treated and NT mice, with CBP showing the strongest effect. CBP significantly reduced epidermal thickness compared with Vas and NT. There were no significant differences in the numbers of interleukin-31-immunoreactive cells and mast cells, or in expression of epidermal thymic stromal lymphopoietin among all five groups.. The therapeutic potency of TAC against AD-like symptoms, including pruritus, is equal to that of the corticosteroid CBP. Epidermal innervation of sensory nerves itself might not be related to the therapeutic effects of topical tacrolimus and corticosteroids in its early phase.

Topics: Administration, Topical; Adrenal Cortex Hormones; Animals; Betamethasone Valerate; Clobetasol; Cytokines; Dermatitis, Atopic; Dermatophagoides farinae; Disease Models, Animal; Emollients; Epidermis; Humans; Immunosuppressive Agents; Male; Mast Cells; Mice; Ointments; Petrolatum; Pruritus; Tacrolimus; Thymic Stromal Lymphopoietin; Treatment Outcome; Ubiquitin Thiolesterase

We have designed and efficiently synthesized novel 1-phenyl-6-aminouracils by replacing the chroman moiety in CX-659S, a nonsteroidal dermatologic candidate, with dimethyldihydrobenzofuranol to cancel CX-659S asymmetric center. Medicinal chemistry effort culminated in the discovery of 13d bearing a 3-methyl group at the 1-phenyl group as a promising compound. Compound 13d, having good in vitro ADME profile and moderate oral bioavailability in mice, showed potent anti-inflammatory activity against hapten-induced contact hypersensitivity reaction in mice following topical and oral administration. The effects of 13d were equipotent to that of tacrolimus or prednisolone. In addition, compound 13d, having potent hydroxyl radical-scavenging activity, showed more potent suppressive effect on substance P-induced pruritus in mice than oxatomide.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Benzofurans; Cell Line, Tumor; Cell Membrane Permeability; Dermatitis, Atopic; Half-Life; Humans; Mice; Microsomes; Pruritus; Rats; Uracil

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pruritus; Skin; Tacrolimus

Topics: Administration, Topical; Bariatric Surgery; Drug Administration Schedule; Female; Femoral Neuropathy; Follow-Up Studies; Humans; Hypertension; Middle Aged; Nerve Compression Syndromes; Obesity, Morbid; Pain; Postoperative Period; Pruritus; Tacrolimus; Treatment Outcome

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. Most patients have an atopic predisposition. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution of the eczema; and (iii) chronic and chronically relapsing course. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Topics: Administration, Cutaneous; Administration, Oral; Anti-Inflammatory Agents; Dermatitis, Atopic; Dermatologic Agents; Diet Therapy; Evidence-Based Medicine; Glucocorticoids; Histamine Antagonists; Humans; Immunosuppressive Agents; Japan; Ointments; Patient Compliance; Patient Education as Topic; Pruritus; Quality of Life; Severity of Illness Index; Tacrolimus; Ultraviolet Therapy

Topics: Activities of Daily Living; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antipruritics; Child; Dermatitis, Atopic; Emollients; Female; Histamine Antagonists; Humans; Internet; Male; Middle Aged; Pruritus; Surveys and Questionnaires; Tacrolimus; Young Adult

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease, currently considered a benign vascular proliferation of unknown etiology, and whose treatment is still unclear and challenging.. Two women in their thirties consulted for itchy lesions of the right ear. Both presented with a reddish bleeding papulonodular infiltration of the auricle, with a nodule at the entrance to the external auditory canal in the first patient. Laboratory tests showed no abnormalities and in particular no hypereosinophilia or elevated serum immunoglobulin E. In both cases, histology of lesional skin showed vascular proliferation with thick-walled vessels lined by plump endothelial cells, protruding into the lumen, together with a mixed dermal inflammatory infiltrate consisting primarily of eosinophils and lymphocytes. A diagnosis of ALHE was made in both patients based on clinical and histological features. MRA revealed no underlying vascular malformation in both cases. Patients started treatment with 0.1% tacrolimus ointment twice daily. The pruritic sensation and bleeding had completely subsided within two weeks and the reddish infiltration and nodules had practically disappeared after two months of topical tacrolimus. Continuous application resulted in no recurrence at 6 months of follow-up.. Treatment of ALHE is still poorly standardized due to doubts concerning the pathophysiology of this rare condition and the small number of available studies. Topical tacrolimus was originally developed for the treatment of moderate to severe atopic dermatitis because of its anti-inflammatory and immunomodulatory properties. Recent studies suggest that this drug may be effective in treating other forms of inflammatory dermatosis. Our two observations suggest that tacrolimus ointment also represents potentially valuable treatment in AHLE.

Topics: Administration, Topical; Adult; Angiolymphoid Hyperplasia with Eosinophilia; Female; Humans; Immunosuppressive Agents; Pruritus; Tacrolimus

Topics: Administration, Oral; Adult; Antipruritics; Female; Humans; Immunosuppressive Agents; Prurigo; Pruritus; Remission Induction; Tacrolimus; Treatment Outcome

Topics: Animals; Anti-Allergic Agents; Dermatitis, Atopic; Dibenzoxepins; Disease Models, Animal; Immunosuppressive Agents; Interleukins; Mice; Olopatadine Hydrochloride; Pruritus; Tacrolimus

To assess the efficacy of clobetasol propionate 0.05% cream in male patients suffering from genital lichen sclerosus (GLS), as well as the efficacy of methylprednisolone aceponate 0.1% cream and tacrolimus 0.1% ointment as maintenance therapy.. The study was conducted retrospectively. At baseline, male patients with GLS (n = 41) were treated with clobetasol propionate 0.05% cream applied twice daily for 8 weeks. Visual Analog Scale (VAS) score for pruritus, Investigator's Global Assessment (IGA) score and Dermatology Life Quality Index (DLQI) were recorded at baseline, week 8 and week 20. At week 8, patients responsive to treatment (n = 37) were further treated with methylprednisolone aceponate 0.1% cream twice weekly (n = 17) or tacrolimus 0.1% ointment once daily (n = 20), as maintenance therapy until week 20.. VAS, IGA and DLQI median scores were significantly decreased from baseline to week 8 (p < 0.001). At week 20, patients treated with methylprednisolone aceponate 0.1% cream presented no significant difference in median IGA score (p = 0.865), median DLQI score (p = 0.853) or median VAS score (p = 0.474) compared with patients treated with tacrolimus 0.1% ointment.. Clobetasol propionate 0.05% cream is effective as first-line treatment in male GLS. The data suggest that there is no difference between methylprednisolone aceponate 0.1% cream and tacrolimus 0.1% ointment in preventing the relapses.

Topics: Adult; Clobetasol; Genital Diseases, Male; Humans; Lichen Sclerosus et Atrophicus; Maintenance Chemotherapy; Male; Methylprednisolone; Pruritus; Quality of Life; Retrospective Studies; Secondary Prevention; Skin Cream; Tacrolimus

To date, no study has compared the clinical characteristics, malignancy associations, and treatment of dermatomyositis in predominantly Caucasian vs. Asian populations.. This prospective study was conducted to compare clinical characteristics of dermatomyositis, its relationship to malignancy, and treatment between two tertiary medical centers in the USA and Singapore. A total of 19 newly-diagnosed patients in the USA and 15 patients in Singapore were enrolled. Dermatomyositis or amyopathic dermatomyositis were diagnosed based on clinical assessment, skin and muscle biopsies, and muscle testing.. Ninety-five percent of patients in the USA group were of Caucasian descent, while 93% of patients in the Singapore group were of Chinese descent. Both groups were predominantly female. Pruritus was the most common initial symptom reported in both groups, while periungual erythema and Gottron's papules were the most common skin presentations. Heliotrope eruption was more common in the Singapore group, occurring in 80% of patients vs. 32% of patients in the USA group (P = 0.007). Three patients in the Singapore group developed a malignancy, with two of these patients having nasopharyngeal carcinoma. None of the USA patients developed malignancies in a follow- up period of 2-5 years. Immunosuppressive steroid sparing therapy with hydroxychloroquine was more frequently used in Singapore, while topical tacrolimus was more frequently used in the USA.. The clinical presentations of dermatomyositis vary among different ethnic populations. Chinese patients with dermatomyositis have a significant risk for nasopharyngeal carcinoma.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Asian People; Bone Density Conservation Agents; Calcium Compounds; Carcinoma; Dermatomyositis; Dietary Supplements; Diphosphonates; Erythema; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Nasopharyngeal Neoplasms; Oxides; Prospective Studies; Pruritus; Rituximab; Singapore; Tacrolimus; Tertiary Care Centers; United States; Vitamin D; White People

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Child; Drug Therapy, Combination; Female; Histamine Antagonists; Humans; Immunosuppressive Agents; Lichen Planus; Obesity; Pruritus; Remission Induction; Tacrolimus

Epidermal hyperinnervation in atopic dermatitis (AD) is activated directly by various external stimuli, causing enhanced itching. Nerve density is regulated by the nerve repulsion factor semaphorin 3A (Sema3A), along with nerve elongation factors.. To investigate the effects of Sema3A ointment in the NC/Nga mouse model of AD.. An AD-like phenotype was induced by repeated application of Dermatophagoides farinae body (Dfb) ointment to the dorsal skin of NC/Nga mice. Vaseline, heparinoid, betamethasone, tacrolimus and recombinant Sema3A ointments were applied to the lesional skin once a day for 4 days. Transepidermal water loss (TEWL) was measured before and after each treatment. We also scored the degree of dermatitis and recorded videos to observe scratching behavior. Subsequently, we collected skin samples from these mice for histological analyses.. Topical application of Sema3A, betamethasone and tacrolimus ointments significantly inhibited scratching behavior and improved dermatitis scores in Dfb-treated mice compared with control mice, whereas vaseline and heparinoid had no effects. A significant improvement of TEWL was observed only in Sema3A ointment-treated mice. Moreover, Sema3A ointment reduced the densities of PGP9.5- and substance P-immunoreactive nerve fibers in the epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T cells and eosinophils, and improved acanthosis in the Dfb-treated mice compared with controls.. Sem3A ointment may have therapeutic efficacy in patients with pruritus and dermatitis of AD.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Behavior, Animal; Betamethasone; Dermatitis, Atopic; Dermatophagoides farinae; Drug Therapy, Combination; Epidermis; Immunosuppressive Agents; Male; Mice; Mice, Inbred Strains; Nerve Endings; Ointments; Pruritus; Semaphorin-3A; Specific Pathogen-Free Organisms; Tacrolimus

Effects of probiotics on the prevention of atopic diseases have been proposed recently. Although we have already reported the suppressive effects of the probiotic, ImmuBalance™, on a mouse model for peanuts allergy, its influence on atopic diseases remains unclear.. Potential efficacy of ImmuBalance™, which is the fermented soy product, on treatment of atopic dermatitis (AD) was investigated using a mouse model for human AD, NC/Tnd mice.. For in vivo study, ImmuBalance containing chow or a control diet were fed to NC/Tnd mice with moderate dermatitis for 2 weeks. Topical application of FK506 ointment was used as a positive control. Clinical skin severity scores, scratching behaviors, trans-epidermal water loss (TEWL), and histological features were analyzed. For in vitro study, suppressive effect of ImmuBalance™ on nerve growth factor (NGF)-activated neurite outgrowth of PC12 cells was examined.. Clinical skin severity scores of the mice fed with ImmuBalance containing chow were gradually reduced as well as the mice treated with FK506. Feeding with ImmuBalance completely inhibited the increase in scratching behavior of NC/Tnd mice. The value of TEWL of NC/Tnd mice fed with ImmuBalance was significantly decreased. In addition, histological examination revealed that application of ImmuBalance decreased the number of PGP9.5-positive neuronal fibers in the lesional skin. When ImmuBalance extract was added to the culture, NGF-activated neurite outgrowth of PC12 cells was diminished through the inhibition of the phosphatidylinositol 3-kinase phosphorylation.. ImmuBalance could exhibit favorable alterations on AD symptoms, particularly through down regulation of the itch sensation.

Topics: Administration, Oral; Administration, Topical; Animals; Dermatitis; Dermatitis, Atopic; Down-Regulation; Fermentation; Glycine max; Hydrolysis; Male; Mice; Nerve Growth Factor; PC12 Cells; Phosphatidylinositol 3-Kinases; Phosphorylation; Pruritus; Rats; Skin; Tacrolimus; Time Factors; Water

To investigate the effectiveness of pimecrolimus cream 1% for sensitive skin in adult women and its underlying mechanisms.. The changes of subjective symptoms and signs were evaluated before and after the application of pimecrolimus cream 1% based on the severity of pruritus (SP) and severity of burning sensation (SB) scores, and on a basic syntax and molecular substrate (molecular psychophysics) of nociception and proprioception established by temperature-sensitive transient receptor potential (TRP) channels.. The SP and SB scores were significantly decreased in 32 patients with sensitive skin after using topical pimecrolimus cream 1% (P<0.05). Twenty (62.5%) patients showed positive capsaicin-like response (i.e. burning with consequent rapid amelioration of pruritus or burning sensation) and 6 (18.8%) showed positive camphor-like response (i.e. warming with consequent rapid amelioration of pruritus) on application sites after using the topical pimecrolimus cream 1%, and 6 (18.8%) showed negative capsaicin-like response and/or negative camphor-like response.. Pimecrolimus may rapidly inhibit or alleviate itch or burning sensation of patients with sensitive skin. The therapeutic effect of pimecrolimus is relevant to the mechanisms that activate or sensitize transient receptor potential vanilloid 1 (TRPV1) and desensitizes TRPV1 in the skin sensory afferents.

Topics: Adolescent; Adult; Dermatitis, Atopic; Female; Humans; Male; Middle Aged; Pruritus; Skin; Tacrolimus; TRPV Cation Channels; Young Adult

Itching is the most important problem in atopic dermatitis and tacrolimus has been suggested to attenuate the itching by topical application. However, the anti-itch mechanism of tacrolimus has not been well elucidated. In the present study, an allergic dermatitis accompanied by frequent scratching behaviors was induced by repeated paintings with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse ear and the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior were comparatively examined. Repeated DNFB paintings caused a typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behaviors. Both tacrolimus and dexamethasone given topically for 10 days before the final challenge significantly inhibited the ear swelling and reduced the expression of interferon-gamma mRNA. Dexamethasone inhibited the accumulation of eosinophils completely, although tacrolimus did not. Both drugs did not affect the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior, whereas dexamethasone failed to affect it. Repeated DNFB challenge depleted substance P in the dermis. Treatment with tacrolimus before the final challenge completely inhibited the recovery of substance P content, whereas dexamethasone facilitated the recovery. DNFB-induced ear swelling and scratching behavior were significantly inhibited by FK888, a tachykinin NK(1) receptor antagonist. Therefore, substance P seems to participate in the induction of ear swelling and scratching behavior upon final challenge with DNFB, and depletion of substance P by tacrolimus in the dermis contributes to its inhibition of ear swelling and scratching behavior at least in part.

Topics: Animals; Behavior, Animal; Dermatitis, Atopic; Dexamethasone; Ear; Male; Mice; Mice, Inbred BALB C; Pruritus; Substance P; Tacrolimus

Topics: Chronic Disease; Drug Resistance, Bacterial; Ethics, Research; Humans; Immunosuppressive Agents; Otitis Externa; Pruritus; Tacrolimus

Tacrolimus (FK506) and cyclosporine A (Cys A) are immunosuppressive drugs used in the treatment of inflammatory diseases and for preventing rejection of allogeneic transplants. Tacrolimus forms a complex with FK506 binding protein (FKBP), and Cys A forms a complex with cyclophilin. These tacrolimus-FKBP and Cys A-cyclophilin complexes interact with calcineurin (CaN), thereby suppressing activation of T cells. In contrast, steroidal anti-inflammatory drugs suppress the immune system mainly via inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and the activating protein-1 (AP-1) pathway. Previously, we reported that tacrolimus, but not dexamethasone, reduced scratching behavior in a murine model of atopic dermatitis. To elucidate the mechanism involved in the inhibition of scratching behavior, we used a mouse model of allergic dermatitis to compare the characteristics of tacrolimus and Cys A treatment. We found that Cys A suppressed scratching behavior induced by application of 2,4-dinitrofluorobenzene, as did tacrolimus. In addition, both drugs attenuated increases in vascular permeability and scratching behavior induced by passive cutaneous anaphylaxis. These results indicate that inhibition of the CaN pathway plays an important role in tacrolimus- and Cys A-induced inhibition of scratching behavior in mice. Furthermore, we observed that CaN inhibitors suppressed mast cell-dependent allergic reaction.

Topics: Animals; Antipruritics; Behavior, Animal; Calcineurin Inhibitors; Capillary Permeability; Cyclosporine; Dermatitis, Atopic; Dinitrofluorobenzene; Disease Models, Animal; Immunosuppressive Agents; Male; Mice; Mice, Inbred BALB C; Passive Cutaneous Anaphylaxis; Pruritus; Tacrolimus

Mycophenolate mofetil (MMF) is a cornerstone immunosuppressive drug after liver transplantation (OLT). The aim of this study was to evaluate the long term results of the addition of MMF in maintenance OLT recipients.. From 1996 to 2006, MMF was introduced because of (1) histologic features of rejection or (2) calcineurin inhibitor (CNI) toxicity in order to reduce CNI dosage.. The study population included 208 patients (median, age 54 ± 9 years), with a median delay between OLT and MMF introduction of 54 ± 43 months. The median dosage of MMF was 1180 mg/d at the end of follow-up. After a median follow-up of 50 ± 26 months, 26.4% of the patients taking MMF did present ≥1 side effect and MMF discontinuation rate was 13.8% (transient in 3.8%). The main side effects were digestive disorders (45%), pruritus ± rash ± mucitis (12.7%), and myelosuppression (16.4%). MMF was withdrawn because of digestive disorders (17.2%), pruritus ± rash ± mucitis (17.2%), and myelosuppression (24.1%). The mean glomerular filtration rate as calculated by the Cockcroft-Gault formula value significantly increased after the introduction of MMF (58.1 vs 71.4 mL/min; paired t-test; P < .01). Improvement of renal function was significantly associated with initial association with tacrolimus (vs cyclosporine), initial trough level of cyclosporine (not tacrolimus), delay between OLT and MMF introduction, and age of renal impairment.. Our results suggest that the introduction of MMF in OLT maintenance recipients is efficient and well-tolerated (one quarter of the patients presented significant side effects, leading to treatment discontinuation in 10% of the patients).

Topics: Adult; Azathioprine; Cyclosporine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Tolerance; Exanthema; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Function Tests; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Pruritus; Tacrolimus; Time Factors; Treatment Outcome

Topics: Administration, Cutaneous; Amines; Analgesics; Antipruritics; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Immunosuppressive Agents; Middle Aged; Pruritus; Tacrolimus; Treatment Outcome; Trigeminal Neuralgia

Proteinase-activated receptor-2 (PAR2) may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity. However, little is known of the role of PAR2 in allergic pruritus, because mast cells, which are thought to be responsible for this symptom, can release a number of different pruritogens. In the present study, we investigated the effects of several agents on passive cutaneous anaphylaxis-induced scratching behavior in ICR mice. As a result, cetirizine and ketanserin produced dose-dependent inhibition of scratching behavior induced by passive cutaneous anaphylaxis. Combined cetirizine with ketanserin exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Pretreatment of the experimental animals with PAR2-neutralizing antibody and protease inhibitor leupeptin significantly inhibited passive cutaneous anaphylaxis-induced scratching behavior. Furthermore, we found that topical application of tacrolimus significantly reduced the number of scratching behavior induced by passive cutaneous anaphylaxis in a dose-dependent manner. Combined cetirizine with tacrolimus also exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Tacrolimus in doses of 3% and 10% significantly inhibited tryptase-induced scratching behavior. These results suggest that PAR2 may be involved in passive cutaneous anaphylaxis-induced scratching behavior and tacrolimus produces an anti-allergic pruritus effect in ICR mice.

Topics: Animals; Antibodies, Monoclonal; Antipruritics; Behavior, Animal; Cetirizine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Ketanserin; Mice; Mice, Inbred ICR; Passive Cutaneous Anaphylaxis; Pruritus; Receptor, PAR-2; Tacrolimus

Protease-activated receptor-2 (PAR2) has been shown to play a key role in the pathophysiology of itch. However, the precise mechanism of PAR2-mediated itch remains largely unknown. In the present study, we investigated the effects of several agents on the scratching behavior induced by PAR2-activating peptide (SLIGRL-NH2). Pretreatment of experimental animals with tacrolimus or the 5-lipoxygenase inhibitor zileuton significantly reduced SLIGRL-NH2-induced scratching behavior, whereas histamine H(1) receptor antagonist cetirizine or the cyclooxygenase inhibitor indomethacin had little effect. Furthermore, intradermal injection of SLIGRL-NH2 increased cutaneous levels of LTB(4) and PGE(2). In vitro, SLIGRL-NH2 treatment enhanced LTB(4) and PGE(2) release from primary keratinocytes in a concentration-dependent manner. Preincubation of keratinocytes with zileuton resulted in a significant decrease of LTB(4) release and treatment of indomethacin led to a significant decrease of PGE(2) in response to SLIGRL-NH2 stimulation. In addition, SLIGRL-NH2-induced secretion of LTB(4) and PGE(2) was significantly inhibited by tacrolimus, whereas cetirizine had no effect. These results indicate that SLIGRL-NH2 stimulates LTB(4) and PGE(2) release from mouse keratinocytes and that enhancement of LTB(4) and PGE(2) secretion contributes to SLIGRL-NH2-induced scratching behavior in ICR mice.

Topics: Animals; Cetirizine; Dinoprostone; Dose-Response Relationship, Drug; Drug Interactions; Hydroxyurea; Indomethacin; Injections, Intradermal; Keratinocytes; Leukotriene B4; Male; Mice; Mice, Inbred ICR; Oligopeptides; Pruritus; Skin; Tacrolimus

Topics: Administration, Topical; Aged; Antipruritics; Female; Genital Diseases, Male; Humans; Immunosuppressive Agents; Male; Pruritus; Pruritus Vulvae; Scrotum; Tacrolimus

Using mice, we examined whether the topical application of tacrolimus would produce an acute anti-pruritic effect. An itch-related response, scratching, was elicited by intradermal injections of mosquito allergen (10 microg/site) in sensitized mice and SLIGRL-NH2 (protease-activated receptor-2 agonist, 50 nmol/site), histamine (100 nmol/site), serotonin (100 nmol/site) and substance P (100 nmol/site) in naive ones. Topical application of 1%, but neither 0.1% nor 0.3%, tacrolimus to the skin 1 h before injection inhibited scratching induced by mosquito allergen and SLIGRL-NH2, without effects on scratching induced by histamine, serotonin, and substance P. Topical tacrolimus also inhibited licking induced by an intraplantar injection of capsaicin (0.1 microg/site). These results suggest that topical tacrolimus exerts acute inhibitory effects on allergic and protease-activated receptor-2-mediated itching. Though precise mechanisms remain unclear, the action on sensory neurons expressing protease-activated receptor-2 and transient receptor potential vanilloid-1 capsaicin receptor may be involved in the inhibitory effects of tacrolimus.

Topics: Administration, Topical; Aedes; Animals; Antipruritics; Behavior, Animal; Capsaicin; Female; Histamine; Immunosuppressive Agents; Male; Mice; Mice, Inbred ICR; Pruritus; Serotonin; Substance P; Tacrolimus

TS-022, {4-[(1R, 2S, 3R, 5R)-5-Chloro-2-((S)-3-cyclohexyl-3-hydroxyprop-1-ynyl)-3-hydroxycyclopentyl] butylthio} acetic acid monohydrate, inhibits ADP-induced platelet aggregation, an effect significantly antagonized, as in the case of prostaglandin D(2) by the prostanoid DP(1) receptor antagonist (BW A868C). TS-022 is a prostanoid DP(1) receptor agonist, originally developed as a novel anti-pruritic drug for patients with atopic dermatitis. We examined the effects of TS-022 on experimental pruritus, cutaneous barrier disruption, and atopic dermatitis and in in vitro immune function tests. Topically applied TS-022 significantly suppressed scratching in skin-lesioned NC/Nga mice from a concentration of 2.5 nM, and this scratch-suppressive activity was significantly antagonized by BW A868C. Tacrolimus (FK-506) and dexamethasone, used as reference drugs for atopic dermatitis, also exhibited suppressive effects against scratching, but only at concentrations of 125 and 25,000 microM. TS-022 applied topically, once a day for 2 days, significantly accelerated repair of the cutaneous barrier disruption caused by mechanical scratching, from concentrations of 2.5 nM. This acceleration of repair of the disrupted cutaneous barrier by this drug was also significantly antagonized by BW A868C. FK-506 and dexamethasone showed no beneficial effects on the repair of the disrupted cutaneous barrier. Repeated topical application of 2.5 microM of TS-022 and 12.5 microM of FK-506 once a day for 6 weeks significantly improved the skin inflammation scores in the NC/Nga mice. In regard to the effects of TS-022 in vitro, the inhibitory activity of TS-022 against concanavalin A-induced cytokine production by splenocytes was marginal as compared with that of FK-506 or dexamethasone. These results suggest that the beneficial therapeutic effects of TS-022 in NC/Nga mice with atopic dermatitis are mediated by its suppressive effect on scratching and its effect of accelerating repair of the disrupted cutaneous barrier, both effects being attributable to its prostanoid DP(1) receptor agonistic activity.

Topics: Acetates; Animals; Antipruritics; Concanavalin A; Cyclohexanes; Cytokines; Dermatitis, Atopic; Dexamethasone; Humans; Hydantoins; Immunosuppressive Agents; Inflammation; Male; Mice; Platelet Aggregation; Prostaglandin D2; Pruritus; Receptors, Immunologic; Receptors, Prostaglandin; Skin; Sulfhydryl Compounds; Tacrolimus; Wound Healing

Female NC/Jic mice were sensitized and challenged repeatedly at 48 h intervals for 10 and 30 days by painting 1% 2,4,6-trinitrochlorobenzene (TNCB) on both ears. Mice challenged with TNCB for 30 days developed an inflammatory dermatitis with high immunoglobulin E (IgE) titer. Histological analysis with acidic Toluidine Blue staining revealed that dermal mast cells markedly differentiated and intensely degranulated, consistent with a dramatic increase in scratching behavior. A significant increase in total scratching events could be observed in mice treated with TNCB for a short period of 10 days. Extending the term of TNCB application to 30 days, the IgE titer and number of mast cells elevated significantly, and thus various drugs were evaluated pharmacologically by using the mice treated with TNCB for 30 days. Terfenadine and cyproheptadine attenuated the chronic scratching behavior. Tacrolimus and dexamethasone were less effective and cromolyn showed no effect. In addition, terfenadine and tacrolimus suppressed the degranulation of mast cells. The present chronic scratching model could be suitable to evaluate drugs effective for suppression of mast cell differentiation and degranulation by irritation, and may represent a promising tool to develop new drugs for inflammatory pruritus associated with, for example, atopic dermatitis.

Topics: Animals; Antipruritics; Cell Degranulation; Chronic Disease; Cromolyn Sodium; Cyproheptadine; Dermatitis, Atopic; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Immunoglobulin E; Mast Cells; Mice; Picryl Chloride; Pruritus; Tacrolimus; Terfenadine; Time Factors

Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Ear, External; Humans; Pruritus; Tacrolimus

Several factors may contribute to post-transplant cholestatic complications after liver transplantation. These include ischemic reperfusion injury, hypoperfusion, bile duct strictures, and hepatotoxic drugs. Up to now, there have been no publications on tacrolimus cholestatic toxicity in clinical transplantation when the drug was used in therapeutic doses. We describe six pediatric liver graft recipients in whom cholestatic complications developed under a tacrolimus-based immunosuppression following liver transplantation and all of them suffered from previous steroid-resistant graft rejection. The overall incidence of cholestatic syndrome was 5.4% in children receiving tacrolimus. The immunosuppression was switched back to cyclosporine and prednisolone in all six patients resulting in completely resolved clinical signs and laboratory findings. We conclude from our observations that a cholestatic syndrome following pediatric liver transplantation may be caused by tacrolimus therapy following steroid-resistant graft rejection, even if given in therapeutic doses.

Topics: Adolescent; Child; Cholestasis; Cyclosporine; Graft Rejection; Humans; Immunosuppressive Agents; Infant; Liver; Liver Transplantation; Postoperative Complications; Pruritus; Retrospective Studies; Tacrolimus

Topics: Animals; Dermatitis, Atopic; Dexamethasone; Disease Models, Animal; Drug Evaluation; Haptens; Humans; Mice; Pruritus; Tacrolimus

Atopic eczema is one of the most common diseases in dermatology. Patients suffer from both the chronic relapsing skin disease and the associated emotional stress. Itching and visible lesions on the face and hands are the most unpleasant features for many often young patients, seriously reducing their quality of life. New therapeutic approaches have changed the management of atopic eczema in recent years. Relatively potent new drugs with fewer side effects than corticosteroids help to control the disease. This review focuses on the basic principles of modern atopic eczema treatment, emphasizing basic emollient therapy and topical therapy with calcineurin inhibitors.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Calcineurin Inhibitors; Child; Combined Modality Therapy; Dermatitis, Atopic; Dose-Response Relationship, Drug; Emollients; Humans; Immunoglobulin E; Immunosuppressive Agents; Infant; Pruritus; Quality of Life; Tacrolimus; Urea

JTE-907, N-(benzo[1,3]dioxol-5-ylmethyl)-7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxamide, is a selective cannabinoid CB2 receptor antagonist/inverse agonist. The anti-pruritic activity of JTE-907 was studied in NC mice with chronic dermatitis, a model of atopic dermatitis. The oral dose of JTE-907 (1 and 10 mg/kg/day), an immunosuppressant agent tacrolimus (1 mg/kg/day) and a glucocorticoid betamethasone 17-valerate (1 mg/kg/day) for 20 days suppressed the spontaneous scratching and cutaneous nerve activity of NC mice. JTE-907 (10, but not 1, mg/kg) and tacrolimus, but not betamethasone, tended to alleviate the dermatitis. Betamethasone inhibited the body weight gain. These results suggest that JTE-907 suppresses spontaneous itch-associated responses of NC mice without adverse effects such as weight loss.

Topics: Administration, Oral; Animals; Behavior, Animal; Betamethasone Valerate; Body Weight; Dermatitis, Atopic; Dioxoles; Disease Models, Animal; Dose-Response Relationship, Drug; Glucocorticoids; Immunosuppressive Agents; Male; Mice; Mice, Inbred Strains; Pruritus; Quinolones; Receptor, Cannabinoid, CB2; Severity of Illness Index; Skin; Tacrolimus

Itching is the most important problem in many allergic and inflammatory skin diseases especially in atopic dermatitis. However, animal models for allergic dermatitis useful for the study of itching have rarely been established. We established a mouse allergic dermatitis model involving frequent scratching behavior by repeated painting with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse skin, and comparatively examined the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior. Repeated DNFB painting caused typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behavior. An apparent thickening of the epidermis and dermis, and the significant accumulation of inflammatory cells were observed. Increased interferon (IFN)-gamma mRNA expression and the induction of interleukin (IL)-4 and IL-5 mRNA expression were also observed in the skin lesion. The scratching behavior was inhibited by dibucaine and naloxone. Although tacrolimus reduced the increased expression of IFN-gamma and IL-4 mRNA, dexamethasone potently depressed that of IFN-gamma, IL-4 and IL-5 mRNA. Dexamethasone inhibited the accumulation of lymphocytes and eosinophils, although tacrolimus did not. Both drugs failed to inhibit the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior that was associated with the inhibition of nerve fiber extension into the epidermis, whereas dexamethasone failed to have any effect. The mouse dermatitis model seems to be beneficial for the study of itching associated with allergic dermatitis, such as atopic dermatitis, and tacrolimus seems to exhibit an anti-itch effect through the inhibition of nerve fiber extension at least in part.

Topics: Allergens; Anesthetics, Local; Animals; Antipruritics; Behavior, Animal; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dexamethasone; Dibucaine; Dinitrofluorobenzene; Disease Models, Animal; Glucocorticoids; Immunoglobulin E; Interferon-gamma; Interleukin-4; Interleukin-5; Male; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Pruritus; RNA, Messenger; Skin; Tacrolimus

To understand the role and efficacy of topical pimecrolimus in the treatment of refractory pruritus of the external auditory canals (EACs).. Retrospective chart review.. Thirty-six patients with pruritic EACs who had failed conventional therapy with topical and systemic medications were treated with topical pimecrolimus 1% for a period of 3 months. Baseline and follow-up evaluation of the degree of pruritus among other variables was performed. A control group of 19 patients was instructed on aural toilet alone and was not treated with topical pimecrolimus 1%.. Of the 36 patients who were treated with topical pimecrolimus for their pruritic EACs, 34 patients had resolution of their symptoms. There was evidence of return of cerumen production in 86% of patients. In the control group, 16% of patients had improvement of their symptoms with aural toilet. This difference was statistically significant (chi, P < .0001).. Topical pimecrolimus appears to be more efficacious than aural toilet in the treatment of pruritic ears for chronic use without side effects.

Topics: Administration, Topical; Calcineurin Inhibitors; Cerumen; Cohort Studies; Dermatologic Agents; Ear Canal; Ear Diseases; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Ointments; Pruritus; Retrospective Studies; Tacrolimus

Sterile eosinophilic folliculitis, a clinical entity first described by Ofuji in 1970, is a rather rare skin disorder, in particular in the non-Asian population. We report the first case of eosinophilic folliculitis associated with toxocariasis in a Caucasian patient. Topical and systemic anti-inflammatory and antiphlogistic therapy along with systemic antihelminthic treatment resulted in complete remission of the skin lesions. In addition, there was a marked decrease of antibodies to Toxocara antigens in the patient's serum following antihelminthic therapy. Given that (I) some cases of eosinophilic folliculitis have been reported which were associated with infestation with metazoan parasites; (2) infestations with the roundworm Toxocara canis are known to induce eosinophilic reactions in some tissues; and (3) therapy-induced remission of eosinophilic folliculitis was accompanied by a decrease of Toxocara-directed antibodies in the patient's serum, we propose that there is an aetiopathogenic link between toxocariasis and eosinophilic folliculitis in this patient.

Topics: Albendazole; Animals; Anthelmintics; Eosinophilia; Female; Folliculitis; Humans; Immunosuppressive Agents; Middle Aged; Pruritus; Tacrolimus; Toxocara canis; Toxocariasis; White People

Topics: Administration, Topical; Aged; Female; Humans; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Pruritus; Tacrolimus; Treatment Outcome

The action of tacrolimus ointment on pruritus in atopic dermatitis is still unclear. In this open study we investigated both the relationship between the severity of eruptions and the degree of itch and scratching in patients with atopic dermatitis and the effects of topical tacrolimus on these symptoms. Seventy adults with moderate to severe atopic dermatitis with facial eruptions that were recalcitrant to topical steroids applied a 0.1% tacrolimus ointment twice per day after discontinuation of topical steroid. The eruption scores and an assessment of the itch and scratching were recorded for 12 weeks. Oral antihistamine was prescribed at least one month before the study and continued unchanged during the study in each patient. The percentage reduction in the score of itch and scratching after two weeks (n=59) was significantly higher than in the score of eruption. Although there was no significant relationship between the severity of the eruptions and the degree of itch and scratching during steroid application, a relationship became significant after four weeks (n=59) of tacrolimus use by a one-factor ANOVA analysis. This suggests that tacrolimus ointment is effective for the itch and scratching in cases where degrees might be discrepant from the severity of eruptions in patients with recalcitrant facial eruptions of AD.

Topics: Administration, Topical; Analysis of Variance; Dermatitis, Atopic; Facial Dermatoses; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Ointments; Probability; Prospective Studies; Pruritus; Severity of Illness Index; Tacrolimus; Treatment Outcome

(1) Drug therapy for exacerbations of atopic dermatitis (atopic eczema) should only be considered when simple measures and emollients are inadequate. The first-line option is a topical corticosteroid with a level of potency appropriate for the affected site and the patient's age. (2) Tacrolimus, an immunosuppressant used orally or parenterally to prevent graft rejection, is now marketed in France as an ointment, in two dose strengths, for the treatment of atopic dermatitis. It is approved for use when topical corticosteroids fail, in patients aged at least two years. (3) According to a comparative trial in adults, tacrolimus, when used as a first-line treatment, is no more effective than a class II (strong) topical corticosteroid. Several clinical trials show that it is better than the excipient in both adults and children. The 0.1% strength seems to be slightly more active than the 0.03% strength in adults. (4) It is not known whether tacrolimus is effective after topical corticosteroid failure. (5) In comparative trials the main systemic adverse events in patients using tacrolimus ointment were flu-like syndromes and headache. Local adverse events included burning or pruritus at the site of application in about 50% of patients. These local effects are due to both the excipient and tacrolimus. (6) Severe skin infections and skin cancer cannot be ruled out as serious side effects. (7) Tacrolimus uptake through the skin exposes patients to systemic adverse effects and drug interactions. (8) In practice, patients with atopic dermatitis, however severe, have no reason to use tacrolimus, at least pending studies showing it is effective after topical corticosteroid failure.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Adult; Child; Clinical Trials as Topic; Contraindications; Dermatitis, Atopic; Drug Approval; Drug Interactions; France; Humans; Immunosuppressive Agents; Ointments; Pruritus; Quality of Life; Randomized Controlled Trials as Topic; Tacrolimus

We investigated the effects of several agents on the established itching model in NC/Nga mice, model of atopic dermatitis-like disease, to elucidate related characteristics. The number of spontaneous scratching behaviors (the duration time is over 1.5 s) by NC/Nga mice with severe skin lesions was measured before and after administration of agents for 24 h. The scratching behavior by NC/Nga mice was significantly suppressed by administration of dexamethasone or tacrolimus, but not by chlorpheniramine maleate or cyproheptadine hydrochloride. These results suggest that this method shows a good correlation with the effectiveness of drugs prescribed for itching in humans with atopic dermatitis, and histamine and serotonin do not play an important role in causing the scratching behavior seen by NC/Nga mice. The scratching behavior was also significantly suppressed by naloxone hydrochloride, dibucaine or capsaicin. These results suggest that the scratching behavior seen in this model is caused by itching signal transmission through neural system. Furthermore, we found that theophylline, pinacidil or limaprost had scratching suppression effects in this model.

Topics: Alprostadil; Animals; Antipruritics; Behavior, Animal; Capsaicin; Chlorpheniramine; Cyproheptadine; Dermatitis, Atopic; Dexamethasone; Dibucaine; Male; Mice; Mice, Inbred Strains; Naloxone; Pinacidil; Pruritus; Tacrolimus; Theophylline; Time Factors

Topics: Administration, Cutaneous; Diagnosis, Differential; Epidermolysis Bullosa; Extremities; Female; Humans; Immunosuppressive Agents; Middle Aged; Pruritus; Tacrolimus

We investigated the effects of 1-4% ointments of metronidazole and tinidazole (derivatives of nitroimidazole) on models of inflammatory dermatitis evoked by antigen, hapten and monoclonal anti-dinitrophenol (DNP) IgE antibody in mice. Metronidazole and tinidazole ointments (1) suppressed the late-phase reaction (LPR) of biphasic ear edema in mice sensitized with ovalbumin (OA), (2) suppressed trinitrochlorobenzene-induced inflammatory dermatitis, (3) suppressed the immediate phase reactions and LPR in mice passively sensitized with anti-DNP IgE mAb, and (4) enhanced vascular permeability and the number of scratching reactions, presumably due to itching, in passively sensitized mice. These results strongly indicate that metronidazole and tinidazole 1-4% ointments possess antiinflammatory, immunosuppressive and anti-itching effects, and have the potential for clinical use in the treatment of human inflammatory skin diseases including atopic dermatitis in addition to rosacea and acne vulgaris.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Antipruritics; Capillary Permeability; Dermatitis; Dermatologic Agents; Disease Models, Animal; Edema; Humans; Immunosuppressive Agents; Male; Metronidazole; Mice; Ointments; Ovalbumin; Picryl Chloride; Pruritus; Tacrolimus; Tinidazole

The development of topical calcineurin inhibitors resulted in a significant improvement in the treatment of inflammatory skin diseases such as atopic dermatitis. In addition, an excellent amelioration of pruritus could be observed. Other itchy dermatoses such as chronic irritative hand dermatitis, rosacea, graft-versus-host-disease, renal pruritus, lichen sclerosus, prurigo simplex, prurigo nodularis, scrotal eczema, and inverse psoriasis also have been treated successfully with pimecrolimus and tacrolimus. The antipruritic effect currently is believed to be related to the inhibition of inflammatory cytokines. Furthermore, recent investigations indicate a release of neuropeptides from sensory nerve fibers and degranulation of mast cells mediated by pimecrolimus and tacrolimus. Similar effects have been observed during capsaicin treatment. These findings may provide a possible explanation for initially observed calcineurin inhibitors related side-effects such as burning and pruritus. Moreover, the antipruritic potency may be related to a direct effect on nerve fibers leading to suppression of itch mediated by unknown mechanisms.

Topics: Administration, Topical; Animals; Antipruritics; Calcineurin Inhibitors; Dermatitis, Allergic Contact; Humans; Immunosuppressive Agents; Mast Cells; Microscopy, Fluorescence; Neuropeptides; Pruritus; Skin; Substance P; Tacrolimus; Treatment Outcome

To report a case of elevated blood tacrolimus concentration after application of topical tacrolimus ointment in an erythrodermic patient.. A 44-year-old man developed generalized erythroderma and itching due to infection with human T-cell lymphotropic virus. Despite application of strong glucocorticosteroid ointments, the symptoms and area of erythroderma were not alleviated. Daily topical application of tacrolimus 0.1% ointment was added and therapeutic drug monitoring was started. The dose and applied area of tacrolimus were gradually increased from 2.5 to 12.5 g/d and from 10% to 90% of body surface area, respectively. Because the trough concentration of tacrolimus in whole blood increased from 7.5 ng/mL on treatment day 9 to 15.4 ng/mL on day 13, the dose was reduced to 10 g/d. However, the concentration further elevated to 16.5 ng/mL. Therefore, the applied area was reduced to 20% of body surface area, and the tacrolimus concentration decreased gradually thereafter. Although the transient increase of blood tacrolimus concentration was observed on day 23, treatment with 20% applied area and 5 g/d were maintained.. Topically applied tacrolimus was substantially absorbed with the expansion of its applied area and dose. Increased tacrolimus concentrations may have a tendency to depend on the increase of the percent of body surface area per dose. Our findings showing the elevation of blood tacrolimus concentration after application of the ointment to a large area of the body suggest that the applied area should be as narrow as possible in a barrier-disrupted condition such as erythroderma. However, the safety of tacrolimus ointment has not been established in patients with generalized erythroderma.. Tacrolimus concentrations in whole blood should be carefully monitored to prevent nephrotoxicity. Based on the results of that monitoring, the application area and dose of tacrolimus ointment should be closely adjusted, especially in generalized erythrodermic cases.

Topics: Administration, Topical; Adult; Deltaretrovirus Infections; Dermatitis, Exfoliative; Humans; Leukemia, T-Cell; Male; Ointments; Pruritus; Skin Absorption; Tacrolimus; Time Factors

Topics: Administration, Topical; Adult; Antibody Formation; Child; Dermatitis, Atopic; Dose-Response Relationship, Drug; Erythema; Humans; Immunity, Cellular; Pruritus; Randomized Controlled Trials as Topic; Tacrolimus