tacrolimus and Urticaria

Topics: Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Autoimmune Diseases; Chronic Disease; Cyclosporine; Disease Management; Female; Histamine Antagonists; Humans; Immunosuppressive Agents; Male; Omalizumab; Prevalence; Tacrolimus; Urticaria

The purpose of the review is to review the pathophysiology, available data, and our current recommendations for calcineurin inhibitor (cyclosporine and tacrolimus) treatment in antihistamine refractory chronic idiopathic urticaria (CIU) patients.. Low-dose cyclosporine (<5  mg/kg per day) may have unique immunological modulating properties beyond mast cell and basophil stabilization in CIU. Starting CIU treatment with very low cyclosporine dosages (1 mg/kg per day) and titrating based on response and side-effects may decrease adverse events while preserving efficacy. In cyclosporine responsive patients failing cyclosporine taper, case series data support the safety and efficacy of long-term (5-10 years), very low dose (1-2 mg/kg per day) cyclosporine treatment with appropriate clinical monitoring.. For CIU patients refractory to antihistamines, low-dose cyclosporine therapy (<3 mg/kg per day) with appropriate laboratory monitoring provides an alternative with an acceptable side-effect profile. Long-term (>12 months) moderate-dose (2.5-5 mg/kg per day) cyclosporine treatment may cause longitudinal increases in serum creatinine. However, decreasing or stopping cyclosporine dosing reverses measured nephrotoxicity in the vast majority of patients, and some patients with careful monitoring can tolerate very low-dose cyclosporine (<2 mg/kg per day) for longer periods. Tacrolimus is an alternative to cyclosporine with a slightly different adverse effect profile. Minimal data are available on its use in chronic urticaria.

Topics: Calcineurin Inhibitors; Chronic Disease; Cyclosporine; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Male; Tacrolimus; Time Factors; Urticaria

Urticaria is a rash, that typically involves skin and mucosa, and is characterized by lesions known as hives or wheals. In some cases there is an involvement of deep dermis and subcutaneous tissue that causes a skin/mucosa manifestation called angioedema. Urticaria and angioedema are very often associated: urticaria-angioedema syndrome. The acute episodic form is the most prevalent in the pediatric population, and it is often a recurrent phenomenon (recurrent urticaria). Acute episodic urticaria it is usually triggered by viruses, allergic reactions to foods and drugs, contact with chemicals and irritants, or physical stimuli. In many instances it is not possible to identify a specific cause (idiopathic urticaria). Chronic urticaria is a condition that can be very disambling when severe. In children is caused by physical factors in 5-10% of cases. Other trigger factors are infections, foods, additives, aeroallergens and drugs. The causative factor for chronic urticaria is identified in about 20% of cases. About one-third of children with chronic urticaria have circulating functional autoantibodies against the high affinity IgE receptor or against IgE. (chronic urticaria with autoantibodies or "autoimmune" urticaria). It is not known why such antibodies are produced, or if the presence of these antibodies alter the course of the disease or influence the response to treatment. Urticaria and angioedema can be symptoms of systemic diseases (collagenopathies, endocrinopathies, tumors, hemolytic diseases, celiachia) or can be congenital (cold induced familiar urticaria, hereditary angioedema). The diagnosis is based on patient personal history and it is very important to spend time documenting this in detail. Different urticaria clinical features must guide the diagnostic work-up and there is no need to use the same blood tests for all cases of urticaria. The urticaria treatment includes identification of the triggering agent and its removal, reduction of aspecific factors that may contribute to the urticaria or can increase the itch, and use of anti-H1 antihistamines (and/or steroids for short periods if antihistamines are not effective). In some instances an anti-H2 antihistamine can be added to the anti-H1 antihistamines, even if the benefits of such practice are not clear. The antileucotriens can be beneficial in a small subgroup of patients with chronic urticaria. In case of chronic urticaria resistant to all the aforementioned treatments, cyclosporine and

Topics: Autoantibodies; Child; Chronic Disease; Cyclosporine; Epinephrine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Receptors, IgE; Tacrolimus; Urticaria

During the past year there have been significant advances in our understanding of the mechanisms underlying allergic skin diseases. This article reviews some of these advances in atopic dermatitis and urticaria. The introduction of a new class of topical anti-inflammatory medications, topical calcineurin inhibitors, has significantly increased our treatment options and led to a rethinking of potential management approaches in atopic dermatitis.

Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Calcineurin Inhibitors; Dermatitis, Atopic; Humans; Immunosuppressive Agents; T-Lymphocytes; Tacrolimus; Urticaria

We report the result of a pilot study of low-dose tacrolimus for the treatment of patients with severe chronic idiopathic urticaria (CIU). Nineteen patients with severe CIU were treated with tacrolimus for 12 weeks. Two patients dropped out after 1 week of treatment because of side effects. Following 3 months of treatment, 12 of 17 patients (70.5%) had a clinical response to tacrolimus. In 9 patients, the urticaria had been improved significantly (urticarial score 0-1), enabling them to discontinue antihistamines and, in the case of two patients, corticosteroids. The remaining 3 patients had moderate improvement (urticarial score 2). Three months after the discontinuation of tacrolimus, 3 of 10 responders had a complete resolution of their urticaria (urticarial score 0), 3 had mild deterioration (urticarial score 1-2) controllable by antihistamines alone, and 4 patients had a full relapse (urticarial score 3). Our preliminary results suggest tacrolimus as a treatment option for patients with severe CIU.

Topics: Adult; Chronic Disease; Female; Humans; Immunosuppressive Agents; Male; Prospective Studies; Tacrolimus; Urticaria

Hemophagocytic syndrome (HPS) is an unusual disorder associated with systemic lupus erythematosus (SLE). A 64-year-old woman was admitted because of fever and urticarial vasculitis. Laboratory data revealed pancytopenia and immunological abnormalities, suggesting elevated disease activity. Prednisolone monotherapy failed to improve the pancytopenia despite the amelioration of other clinical findings. Because her condition was suggestive of HPS, tacrolimus at 2-3 mg/day was added to the prednisolone regimen. Eventually, the pancytopenia improved and prednisolone could be effectively tapered. Tacrolimus could be an additional or alternative modality for treating refractory HPS.

Topics: Bone Marrow; Dose-Response Relationship, Drug; Female; Fever; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Pancytopenia; Prednisolone; Remission Induction; Tacrolimus; Treatment Failure; Treatment Outcome; Urticaria; Vasculitis

Topics: Arthritis, Rheumatoid; Female; Humans; Immunosuppressive Agents; Middle Aged; Tacrolimus; Treatment Outcome; Urticaria

Chronic urticaria is a common skin disorder, which causes considerable morbidity. In approximately 40% of cases, patients have an autoimmune disorder in which functional antibodies cause degranulation of mast cells and basophils, and C5a complement augments this in varying amounts from patient to patient. Since the calcineurin inhibitor ciclosporin has been used in chronic autoimmune urticaria, we examined the effect of ciclosporin and other drugs on the release of histamine from basophils when stimulated by sera from patients with chronic autoimmune urticaria.. Leucocytes from healthy donors were isolated and incubated in varying concentrations of ciclosporin, ascomycin, methotrexate, diphenhydramine or hydroxyzine for 30 min prior to stimulation with serum from urticaria patients known to have functional immunoglobulin (Ig)G antibodies directed against the alpha subunit of the IgE receptor. Histamine release was then measured.. Pre-incubating cells with ciclosporin and ascomycin produced dose-dependent inhibition of histamine release when cells were stimulated by sera of urticaria patients, by purified IgG from these sera, but not by C5a. Inhibition was not prevented by C5a receptor blocking antibodies. No inhibition was seen with methotrexate, diphenhydramine or hydroxyzine.. This is the first demonstration of inhibition of histamine release by calcineurin inhibitors employing sera of patients with chronic autoimmune urticaria. These drugs may work by interfering with intracellular signalling in cells following cross-linking of the IgE receptor, but not following stimulation of the C5a receptor.

Topics: Basophils; Calcineurin Inhibitors; Cells, Cultured; Chronic Disease; Complement C5a; Cyclosporine; Diphenhydramine; Dose-Response Relationship, Immunologic; Histamine H1 Antagonists; Histamine Release; Humans; Hydroxyzine; Immunoglobulin G; Immunosuppressive Agents; Leukocytes; Methotrexate; Recurrence; Tacrolimus; Urticaria

Topics: Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Immunosuppressive Agents; Infant; Neurodermatitis; Tacrolimus; Urticaria