mycophenolic-acid and Dermatitis--Atopic

With the increasing number of options for the treatment of moderate-to-severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein.

Topics: Aged; Asthma; Cyclosporine; Dermatitis, Atopic; Female; Humans; Methotrexate; Mycophenolic Acid

Topics: Adolescent; Adult; Analysis of Variance; Dermatitis, Atopic; Enzyme Inhibitors; Female; Humans; IMP Dehydrogenase; Male; Mycophenolic Acid; Off-Label Use; Remission Induction

Many patients with mild to moderate atopic dermatitis (AD) are managed by identifying and avoiding allergens and irritants, ensuring skin moisturization, and graded use of topical corticosteroids and/or calcineurin inhibitors. There is little consensus on the next step. Most systemic therapies are "off label" in the United States and include phototherapy, cyclosporine, mycophenolic acid precursors, azathioprine, and methotrexate. The decision to use these therapies should be based on efficacy and safety readouts from well designed, long-term trials. This article reviews the long-term randomized, controlled trials examining safety and/or efficacy of interventions recommended for patients with mild to severe AD.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Azathioprine; Baths; Calcineurin Inhibitors; Cyclosporine; Dermatitis, Atopic; Glucocorticoids; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Phototherapy; Randomized Controlled Trials as Topic; Skin Cream; Time Factors

Itch, or pruritus, is a hallmark feature of atopic dermatitis (AD). The impact of AD-related pruritus can range from mildly distressing or distracting to completely disabling. Traditionally, management of itch in AD patients has focused on restoring the altered skin barrier with topical emollients and/or reducing inflammation. A growing emphasis has been placed on directly targeting the neural transmission pathways that mediate itch signaling. Off-label use of neuromodulatory agents has helped reduce this aggravating symptom in atopic patients. This article reviews the current literature on the use of neuromodulatory agents and nonpharmacologic alternative therapies used to treat AD-related pruritus.

Topics: Acupuncture Therapy; Administration, Cutaneous; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Calcineurin Inhibitors; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Dietary Supplements; Emollients; Enzyme Inhibitors; Histamine Antagonists; Humans; Immunosuppressive Agents; Mycophenolic Acid; Neurotransmitter Agents; Plant Oils; Pruritus; Ultraviolet Therapy

The majority of atopic dermatitis (AD) patients respond satisfactorily to gentle bathing, frequent moisturizing, and topical medications. Second-line therapies for AD should be used in recalcitrant cases or in patients with uncontrolled disease despite compliance with first-line measures and avoidance of allergens. Recommended advanced therapies include phototherapy, especially narrowband ultraviolet B, systemic immunosuppressants, and a new biologic agent. Few studies have compared head-to-head efficacy of the different immunosuppressant therapies such as cyclosporine, methotrexate, azathioprine and mycophenolate mofetil. Therefore, the agent used is based on provider and patient preferences and can be decided on a case-by-case basis.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Humans; Immunosuppressive Agents; Interleukin-13; Interleukin-4; Methotrexate; Mycophenolic Acid; Phototherapy

Atopic dermatitis (AD) is a common chronic, pruritic skin disease in children. As the incidence of AD increases, especially in high-income countries, paediatricians may see an increasing number of recalcitrant AD cases in their practice. Although these cases are principally managed by paediatric dermatologists, it is important for paediatricians to be aware of the use and side effects of non-topical treatment like phototherapy and systemic agents as well as the evidence for alternative treatment, which caregivers may ask about. This review presents paediatric evidence for the practical use of phototherapy and certain oral immunosuppressants for paediatric AD including doses, duration of use and monitoring of adverse effects. The use of alternative therapy including traditional medicine, probiotics and the role of nutrition are also discussed. Narrow band ultraviolet B phototherapy is effective in recalcitrant paediatric AD. When phototherapy is ineffective or contraindicated, systemic drugs may be administered cautiously with close surveillance of side effects. The use of azathioprine, ciclosporin, methotrexate and mycophenolate mofetil is generally safe in the short term under close monitoring and can be effective alongside compliance to topical treatment. Alternative complementary treatment is not known to be effective. Holistic management including therapeutic patient education is important. Good quality paediatric studies for non-topical AD treatment are needed for definitive guidelines.

Topics: Azathioprine; Child; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Humans; Immunosuppressive Agents; Medicine, Chinese Traditional; Methotrexate; Mycophenolic Acid; Phototherapy; Prebiotics; Probiotics; Recurrence; Ultraviolet Therapy

Atopic Dermatitis (AD) is a chronic inflammatory skin disease that is a significant cause of morbidity, quality-of-life impairment and health-care costs. Although many patients can be treated satisfactorily with topical medications and phototherapy, a smaller subset requires more aggressive systemic therapies. Multiple studies have shown promise for the use of mycophenolate mofetil (MMF) to treat refractory AD. This report summarizes the evidence for use of MMF in the treatment of recalcitrant AD for both children and adults. Familiarity with these studies on the benefits and risks of MMF will enable the clinician and patient to select the most appropriate therapy.

J Drugs Dermatol. 2016;15(6):715-718.

Topics: Dermatitis, Atopic; Enzyme Inhibitors; Gastrointestinal Diseases; Humans; Mycophenolic Acid; Severity of Illness Index

Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition characterized by relapsing pruritic, scaly, erythematous papules and plaques frequently associated with superinfection. The lifelong prevalence of AD is over 20 % in affluent countries. When a child with severe AD is not responding to optimized topical therapy including phototherapy, and relevant triggers cannot be identified or avoided, systemic therapy should be considered. If studies show early aggressive intervention can prevent one from advancing along the atopic march, and relevant triggers such as food allergies cannot be either identified or avoided, systemic therapy may also play a prophylactic role. Though the majority of evidence exists in adult populations, four systemic non-specific immunosuppressive or immunomodulatory drugs have demonstrated efficacy in AD and are used in most patients requiring this level of intervention regardless of age: cyclosporine, mycophenolate mofetil, methotrexate, and azathioprine. This article reviews the use of these medications as well as several promising targeted therapies currently in development including dupilumab and apremilast. We briefly cover several other systemic interventions that have been studied in children with atopic dermatitis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Child; Cyclosporine; Dermatitis, Atopic; Drug Administration Routes; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Severity of Illness Index; Thalidomide

Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control.. We sought to systematically evaluate the efficacy and safety of systemic treatments for moderate-to-severe AD.. A systematic literature search was performed in MEDLINE, EMBASE, and CENTRAL (until June 2012). Randomized controlled trials (RCTs) evaluating systemic immunomodulating treatments for moderate-to-severe AD were included. Selection, data extraction, quality assessment, and generation of treatment recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed independently by 2 reviewers. Efficacy outcomes were clinical signs, symptoms, quality of life, and the course of AD. Safety data were compared by calculating the weekly incidence rates (as percentages) for adverse events.. Thirty-four RCTs with 12 different systemic treatments and totaling 1653 patients were included. Fourteen trials consistently indicate that cyclosporin A efficaciously improves clinical signs of AD. Cyclosporin A is recommended as first-line treatment for short-term use. A second-line treatment option is azathioprine, but efficacy is lower, and evidence is weaker. Methotrexate can be considered a third-line treatment option. Recommendations are impossible for mycophenolate, montelukast, intravenous immunoglobulins, and systemic glucocorticosteroids because of limited evidence. A meta-analysis was not performed because of a lack of standardization in outcome measures.. Although 12 different interventions for moderate-to-severe AD have been studied in 34 RCTs, strong recommendations are only possible for the short-term use of cyclosporin A. Methodological limitations in the majority of trials prevent evidence-based conclusions. Large head-to-head trials evaluating long-term treatments are required.

Topics: Azathioprine; Cyclosporine; Dermatitis, Atopic; Glucocorticoids; Humans; Immunosuppressive Agents; Interferon-gamma; Methotrexate; Mycophenolic Acid

Topics: Administration, Cutaneous; Administration, Oral; Adrenal Cortex Hormones; Adult; Age of Onset; Antibodies, Monoclonal; Biological Availability; Clinical Trials as Topic; Dermatitis, Atopic; Dermatologic Agents; Disease Management; Filaggrin Proteins; Genetic Predisposition to Disease; Histamine Antagonists; Humans; Immunosuppressive Agents; Intermediate Filament Proteins; Mycophenolic Acid

Although many atopic dermatitis patients can be treated satisfactorily with topical medications and systemic anti-itch approaches, a smaller subset require more aggressive systemic therapies. Familiarity with the latest literature on the benefits and risks of these treatments will enable the clinician and patient to select the most appropriate therapy based on the patient's lifestyle, assessments of risks and comorbidities.. Additional data have come to light altering the risk and benefit ratio of certain systemic atopic dermatitis therapies. In 2011, we saw several head-to-head, randomized controlled trials of established systemic medications for the treatment of atopic dermatitis. A few new systemic atopic dermatitis treatments have highlighted how targeted therapies may inform us about disease pathogenesis.. In light of the risk of hepatosplenic T-cell lymphomas, a greater degree of caution is warranted in the use of azathioprine. NBUVB, mycophenolate, and methotrexate remain the reasonable first-line systemic treatment options for atopic dermatitis. A brief run-in with high-dose cyclosporine to clear atopic dermatitis followed by maintenance with low-dose cyclosporine or cellcept - both of which have better risk and benefit ratios is a reasonable approach. Interferon gamma and intravenous immunoglobulin, although expensive, are potential options, and possibly most ideal for atopic dermatitis patients plagued by significant viral skin infections such as eczema herpeticum. A better understanding of the immunopathogenesis of atopic dermatitis will come with the exploration of novel targeted therapies.

Topics: Azathioprine; Cyclosporine; Dermatitis, Atopic; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Kaposi Varicelliform Eruption; Male; Methotrexate; Mycophenolic Acid; Randomized Controlled Trials as Topic; Risk Factors

Severe childhood atopic dermatitis refers to the presence of recurrent, widespread, eczematous dermatitis that significantly interferes with the daily activities and/or the quality of life of the affected child and family. The vast majority of children with severe, long-standing atopic dermatitis can be managed with the appropriate use of topical treatments, including long-term maintenance therapy and adjunctive treatments. In the recalcitrant patient, second line therapies such as narrowband ultraviolet light therapy and systemic immunosuppressants such as cyclosporine, azathioprine, mycophenolate moefetil, and methotrexate have been shown to be safe and effective in children with severe atopic dermatitis and can lead to sustained clinical improvement. To date, biologic therapy has not been uniformly effective in childhood atopic dermatitis. Management of severe childhood atopic dermatitis, including topical and adjunctive treatments and second-line therapies including systemic immunosuppressants will be reviewed here.

Topics: Administration, Cutaneous; Adolescent; Adrenal Cortex Hormones; Antibodies, Monoclonal; Azathioprine; Baths; Child; Child, Preschool; Cyclosporine; Dermatitis, Atopic; Disinfectants; Humans; Immunosuppressive Agents; Infant; Methotrexate; Mycophenolic Acid; Sodium Hypochlorite; Ultraviolet Therapy

Systemic therapy is required in patients with severe atopic dermatitis (AD) refractory to adequate topical therapy. The aim of a systemic therapy is the rapid and efficient improvement of skin symptoms and pruritus in acute exacerbation and/or the long-term control of severe chronic disease. A number of immunosuppressive and immunomodulating substances are available that may efficiently reduce skin inflammation and thus lead to a relief of symptoms including pruritus. The excellent effects of cyclosporine as short-term as well as maintenance therapy have been documented in several studies in children and adults. Furthermore, other immunosuppressive substances such as azathioprine, mycophenolate mofetil and methotrexate are effective in patients with moderate to severe AD. Intravenous immunoglobulins and γ-interferon exert immunomodulatory effects and thus may improve severe AD. Biological agents are a new approach in AD therapy since they may specifically target cells, cytokines or mediators involved in the pathogenesis of AD.

Topics: Adrenal Cortex Hormones; Adult; Alitretinoin; Antibodies, Monoclonal; Azathioprine; Child; Cyclosporine; Dermatitis, Atopic; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Interferon-gamma; Methotrexate; Mycophenolic Acid; Recombinant Proteins; Tretinoin

Topics: Algorithms; Anti-Bacterial Agents; Antiviral Agents; Azathioprine; Child; Child, Preschool; Cyclosporine; Dermatitis, Atopic; Emollients; Glucocorticoids; Histamine Antagonists; Humans; Immunoglobulins; Immunologic Factors; Infant; Infusions, Intravenous; Interferon-gamma; Methotrexate; Mycophenolic Acid; Phototherapy; Primary Health Care; Severity of Illness Index; Treatment Outcome

Atopic dermatitis is a chronically relapsing eczematous disease of the skin. A wide range of therapeutic regimens has been used for atopic dermatitis. A better understanding of its pathogenesis will also lead to the development of novel approaches to treating this disease. This article reviews the recent advances in allergen-specific sublingual immunotherapy and therapy with antileukotriene drugs, probiotics, mycophenolate mofetil, leflunomide, and intermittent fluticasone propionate ointment, which the authors expect will be clinically useful therapies in the near future.

Topics: Androstadienes; Animals; Dermatitis, Atopic; Desensitization, Immunologic; Fluticasone; Histamine H1 Antagonists; Humans; Immunosuppressive Agents; Isoxazoles; Leflunomide; Leukotriene Antagonists; Mycophenolic Acid; T-Lymphocytes, Regulatory

Mycophenolate mofetil (MMF) is an immunosuppressive drug the efficiency of which has been established in renal transplantation. Recent studies suggest that it may also be effective in the treatment of variant skin diseases especially if the skin lesions are triggered by lymphocytes. Studies have shown efficacy in autoimmune bullous dermatoses, atopic dermatitis and psoriasis. However, there are no placebo-controlled trials that support the use of MMF as first line therapy in these skin diseases.

Topics: Dermatitis, Atopic; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Mycophenolic Acid; Psoriasis; Pyoderma Gangrenosum; Skin Diseases, Vesiculobullous

Severe atopic dermatitis in children is rare. When prescribing exceptional treatments (because of failure with classical drugs such as topical corticosteroids or topical immunosuppressors), it is important to ensure that the child is not suffering from an atopic dermatitis that has not been handled correctly. This assessment may require short hospitalisation. When the severity and rebellious nature of the atopic dermatitis with regard to routine treatment has been confirmed, exceptional treatment is envisaged. Currently, the treatment that is mastered in children remains cyclosporine, although marketing authorisation has not been granted in this indication. The side effects and notably nephrotoxicity justify the careful prescription of this drug with regular controls, and the opinion of a paediatric nephrologist. Other immunosuppressive treatments such as azathioprine, mycophenolate mofetil or even interferon gamma have rarely been studied in children, nor particularly in adults, and usually only in open studies. Their safe use in children, in the indication of severe atopic dermatitis obviously warrants comparative studies in large cohorts. Phototherapy should not be banned, even in this paediatric population, but modalities should be further defined, taking into account the real practical possibilities of this type of treatment, depending on the patients' age, and with long-term monitoring. Antileucotrienes have not yet sufficiently demonstrated their efficacy. In such severe forms, ideally, there should be the possibility of defining the predictable factors of efficacy and tolerance in each patient (biologically or with in vitro tests) that would optimise the use of these exceptional treatments, or even new molecules, in well targeted indications. The golden rule remains: patience, explanation, education, observation, monitoring and availability.

Topics: Azathioprine; Child; Chronic Disease; Dermatitis, Atopic; Humans; Immunologic Factors; Immunosuppressive Agents; Mycophenolic Acid; Severity of Illness Index

Immune response modifiers (IRMs) are agents that target the body's immune system (i.e., cytokines, receptors, and inflammatory cells) to combat disease. Topical IRM therapies, which encompass both proinflammatory and immunosuppressive therapeutics, have been used to successfully treat a number of dermatologic conditions. Proinflammatory treatments include Toll-like receptor agonists (e.g., imiquimod 5% cream) and interferon (e.g., interferon-alpha) therapies, which have been used in the treatment of external genital warts, basal cell carcinoma, and other dermatologic diseases. Immunosuppressive therapies include topical and intralesional corticosteroids, anti-tumor necrosis factor agents (e.g., infliximab and etanercept), and anti-CD4+ T-cell agents, including calcineurin inhibitors and mycophenolate. These agents have been used to treat a number of conditions, including atopic and seborrheic dermatitis and psoriasis. This article reviews the mechanism of action of IRMs and the application of IRMs in several dermatologic diseases.

Topics: Adjuvants, Immunologic; Alefacept; Aminoquinolines; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Calcineurin Inhibitors; CD11 Antigens; Dermatitis, Atopic; Glucocorticoids; Humans; Imiquimod; Interferons; Membrane Glycoproteins; Mycophenolic Acid; Psoriasis; Receptors, Cell Surface; Recombinant Fusion Proteins; Skin Diseases; Tacrolimus; Toll-Like Receptors

The optimal treatment of atopic dermatitis requires regular medical supervision. The course of this chronic skin disease is influenced by multiple triggers which are relevant for the treatment. The mainstays of topical therapy include regular use of emollients coupled with antimicrobial substances, corticosteroids and immune modulators as required. Ultraviolet radiation and immunosuppressive regimens represent further options for the treatment of severe exacerbations and may lead to long term improvement. Data from experimental studies provide insight into possible future treatment methods.

Topics: Adjuvants, Immunologic; Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Animals; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antifungal Agents; Azathioprine; Child; Child, Preschool; Cross-Over Studies; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Desensitization, Immunologic; Disease Models, Animal; Double-Blind Method; Histamine Antagonists; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infant; Leukotriene Antagonists; Medicine, Chinese Traditional; Mice; Mice, Nude; Mycophenolic Acid; Ointments; Photopheresis; Phototherapy; Placebos; Probiotics; PUVA Therapy; Randomized Controlled Trials as Topic; Ultraviolet Therapy

Topics: B-Lymphocytes; Calcineurin; Calcineurin Inhibitors; Cyclosporine; Dermatitis, Atopic; DNA-Binding Proteins; Forkhead Transcription Factors; Humans; Intracellular Signaling Peptides and Proteins; Mycophenolic Acid; Nuclear Proteins; Purines; Severity of Illness Index; T-Lymphocytes; Treatment Outcome; Tumor Necrosis Factor alpha-Induced Protein 3

Cyclosporin A (CsA) is frequently used in the treatment of severe atopic dermatitis (AD). Enteric-coated mycophenolate sodium (EC-MPS) may be an alternative with equal efficacy and fewer side effects.. The aim of this observer-blinded randomized controlled trial was to compare EC-MPS with CsA as long-term treatment in adult patients with severe AD.. Fifty five patients with AD were treated with CsA (5 mg/kg) in a 6-week run-in period. Thereafter, patients either received CsA (3 mg/kg; n = 26) or EC-MPS (1440 mg; n = 24) during a maintenance phase of 30 weeks and there was a 12-week follow-up period. Disease activity was measured using the objective SCORAD and serum thymus and activation-regulated chemokine (TARC) levels and side effects were registered.. During the first 10 weeks the objective SCORAD and serum TARC levels in the EC-MPS study arm were higher in comparison with the CsA study arm. In addition, 7 of the 24 patients treated with EC-MPS required short oral corticosteroid courses. During maintenance phase disease activity was comparable in both study arms. Side effects in both study arms were mild and transient. After study medication withdrawal, disease activity of the patients in the CsA study arm significantly increased compared with the EC-MPS study arm.. The nonblinding of patients and prescriber of rescue medication are limitations.. This study shows that EC-MPS is as effective as CsA as maintenance therapy in patients with AD. However, clinical improvement with EC-MPS is delayed in comparison with CsA. Clinical remission after stopping EC-MPS lasts longer compared with CsA.

Topics: Adult; Chemokine CCL17; Cyclosporine; Dermatitis, Atopic; Enzyme Inhibitors; Female; Humans; Immunoglobulin E; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Tablets, Enteric-Coated

Topics: Biomarkers; Chemokine CCL17; Cyclosporine; Dermatitis, Atopic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Ki-1 Antigen; Male; Mycophenolic Acid; Observer Variation; Pilot Projects; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Single-Blind Method; Tablets, Enteric-Coated; Treatment Outcome

Severe atopic dermatitis (AD) is often treated successfully with oral immunosuppressive drugs such as cyclosporin (CsA) or oral corticosteroids. However, some patients develop adverse effects or are unresponsive to these first-choice oral immunosuppressive drugs.. To evaluate whether enteric-coated mycophenolate sodium (EC-MPS) is an effective treatment in patients with severe, recalcitrant AD.. Ten patients with severe, recalcitrant AD were treated with EC-MPS 720 mg twice daily for 6 months. All patients had to discontinue other oral immunosuppressive drugs due to adverse effects (n = 8) or nonresponsiveness (n = 2). Disease activity was monitored using the Severity Scoring of Atopic Dermatitis (modified SCORAD) index and the Leicester Sign Score (LSS). Additionally, the level of serum thymus and activation-regulated cytokine (TARC) was measured. During treatment, safety laboratory examination was performed. Total serum immunoglobulin E (IgE) was followed during treatment. Use of topical corticosteroids was recorded before and during treatment.. Compared with baseline, the mean scores for disease activity significantly decreased during treatment with EC-MPS [modified SCORAD (P = 0.04), LSS severity (P = 0.01), LSS extent (P = 0.01)]. In addition, serum TARC levels and total serum IgE levels significantly decreased after treatment compared with before (P = 0.03; P = 0.05). Disease activity decreased after approximately 2 months of treatment and stabilized during the 6-month treatment period. No differences in the amount of topical corticosteroids used in the 6 months prior to treatment compared with the 6-month treatment period were found (P = 0.4). None of the patients discontinued use of EC-MPS and only mild adverse effects were seen.. In this study EC-MPS at a dose of 720 mg twice daily for 6 months has proven to be an effective and well-tolerated treatment for patients with severe, recalcitrant AD.

Topics: Adult; Aged; Biomarkers; Dermatitis, Atopic; Female; Humans; Immunoglobulin E; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Severity of Illness Index; Tablets, Enteric-Coated; Treatment Outcome; Young Adult

To evaluate whether mycophenolate mofetil, a new immunosuppressive agent, is effective for treating moderate-severe atopic dermatitis (AD).. In an open-label pilot study, mycophenolate mofetil, 1 g, was given orally twice daily for 4 weeks. At week 5, the dosage was reduced to 500 mg twice daily until study end (week 8). Patients were followed up for 20 weeks.. University hospital dermatology department.. Ten consecutive patients with moderate-severe AD nonresponsive to standard therapy.. Severity of AD as measured using the subjective SCORAD [SCORing Atopic Dermatitis] index.. Clinical efficacy was measured every 2 weeks using the subjective SCORAD index. Treatment with mycophenolate notably reduced the severity of AD within 4 weeks in all patients (P<.05), and after 8 weeks the mean +/- SD SCORAD index dropped from the pretreatment value of 49.2 +/- 13.8 to 21.9 +/- 26.5 (P<.01). One patient had to discontinue mycophenolate therapy after 4 weeks because of the development of herpes retinitis. Except for this event, mycophenolate was tolerated well in all patients. Six of 7 patients who had responded to mycophenolate monotherapy had no relapse of disease during 20-week follow-up. In the 7 patients who finished the study, the SCORAD index was reduced by 74%, from 44.0 +/- 7.8 before treatment to 11.4 +/- 5.9 at 20-week follow-up.. Mycophenolate is a highly effective drug for treating moderate-severe AD, with no serious adverse effects occurring in any patients. Thus, mycophenolate might develop into a promising alternative in the therapy of moderate-severe AD.

Topics: Administration, Oral; Adult; Aged; Dermatitis, Atopic; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Remission Induction; Retinitis; Severity of Illness Index; Treatment Outcome

Activated T and B lymphocytes are the predominant inflammatory cells in atopic eczema (AE) lesions. Mycophenolic acid, the active form of mycophenolate mofetil (MMF), blocks the proliferative responses of T and B lymphocytes.. In this pilot study, we examined the efficacy of MMF (CellCept(R), Hoffman La Roche, Grenzach-Wyhlen, Germany) in severe AE.. Ten patients with severe AE (severity index > 50) according to the Severity Scoring of Atopic Dermatitis (SCORAD) index were treated with oral MMF at an initial dose of 1 g daily during the first week and 2 g daily for a further 11 weeks. Laboratory examination including full blood count, lymphocyte subset analysis, serum immunoglobulins (IgE, IgG, IgM, IgA), total bilirubin, alkaline phosphatase, aminotransferases, lactate dehydrogenase and creatinine was performed every 2 weeks. Additionally, interleukin (IL)-10 and interferon (IFN)-gamma in serum were measured.. None of the 10 patients who received MMF discontinued the trial because of lack of efficacy or adverse events. Compared with the baseline, the median scores for disease severity (SCORAD index) improved by 68% during treatment with MMF. The median serum IgE level decreased significantly, from 10,300 kU L-1 before treatment to 7830 kU L-1 after 12 weeks. MMF induced a significant increase in the T-helper (Th)-1-related cytokine IFN-gamma and a significant decrease in IL-10, mainly produced by Th2 cells.. The present study demonstrates that oral MMF at a dose of 2 g daily is an effective, safe and well-tolerated immunosuppressive therapy for severe AE in adults.

Topics: Adult; Dermatitis, Atopic; Female; Humans; Immunoglobulin E; Immunosuppressive Agents; Interferon-gamma; Interleukin-10; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Severity of Illness Index; T-Lymphocyte Subsets

Paediatric atopic dermatitis (AD) can be burdensome, affecting mental health and impairing quality of life for children and caregivers. Comprehensive guidelines exist for managing paediatric AD, but practical guidance on using systemic therapy is limited, particularly for new therapies including biologics and Janus kinase (JAK) inhibitors, recently approved for various ages in this indication.. This expert consensus aimed to provide practical recommendations within this advancing field to enhance clinical decision-making on the use of these and other systemics for children and adolescents aged ≥2 years with moderate-to-severe AD.. Nineteen physicians from Northern Europe were selected for their expertise in managing childhood AD. Using a two-round Delphi process, they reached full or partial consensus on 37 statements.. Systemic therapy is recommended for children aged ≥2 years with a clear clinical diagnosis of severe AD and persistent disease uncontrolled after optimizing non-systemic therapy. Systemic therapy should achieve long-term disease control and reduce short-term interventions. Recommended are cyclosporine A for short-term use (all ages) and dupilumab or methotrexate for long-term use (ages ≥6 years). Consensus was not reached on the best long-term systemics for children aged 2-6 years, although new systemic therapies will likely become favourable: New biologics and JAK inhibitors will soon be approved for this age group, and more trial and real-world data will become available.. This article makes practical recommendations on the use of systemic AD treatments for children and adolescents, to supplement international and regional guidelines. It considers the systemic medication that was available for children and adolescents with moderate-to-severe AD at the time this consensus project was done: azathioprine, cyclosporine A, dupilumab, methotrexate, mycophenolate mofetil and oral glucocorticosteroids. We focus on the geographically similar Northern European countries, whose healthcare systems, local preferences for AD management and reimbursement structures nonetheless differ significantly.

Topics: Adolescent; Azathioprine; Biological Products; Child; Child, Preschool; Cyclosporine; Delphi Technique; Dermatitis, Atopic; Expert Testimony; Humans; Janus Kinase Inhibitors; Janus Kinases; Methotrexate; Mycophenolic Acid; Quality of Life

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

Topics: Adolescent; Azathioprine; Child; Cyclosporine; Dermatitis, Atopic; Eczema; Humans; Immunosuppressive Agents; Mycophenolic Acid

Atopic dermatitis (AD) is children's most frequent chronic inflammatory skin disease. In most patients, this condition is controlled with topical treatments; however, some patients with severe AD do not respond to these treatments, requiring systemic therapy. There is insufficient information about the ideal dose, time of use, clinical response, and safety of systemic therapy in children with severe AD. This study described the clinical characteristics of patients with severe AD who required systemic treatment, drugs used, their clinical course, adverse effects, and associated complications.. We conducted a retrospective review of the records of pediatric patients with severe AD treated in the Dermatology Clinic, Instituto Nacional de Pediatría (2000 to 2018), who required systemic treatment for more than 3 months.. We included 21 patients. The mean age at disease onset was 3.31 years. The drugs used were methotrexate (57.1%), thalidomide (38%), prednisone (42.8%), azathioprine (19%), mycophenolate mofetil (9.5%), cyclosporine (4.7%), and systemic steroids as bridging therapy (42.8%). Adverse effects were mild and were observed in two patients (9.5%) treated with methotrexate and mycophenolate mofetil.. Methotrexate was the most frequently used drug in > 50% of the patients, and most patients attained remission. Cyclosporine, azathioprine, and mycophenolate mofetil were also effective. Side effects were mild and infrequent. Comparative studies of systemic treatments for severe AD in the pediatric population are necessary.. La dermatitis atópica (DA) es la enfermedad inflamatoria crónica de la piel más común en niños. En la mayoría de los pacientes la enfermedad se controla con tratamientos tópicos; sin embargo, algunos pacientes con DA grave no responden a estos tratamientos, por lo que requieren de terapia sistémica. Existe poca información acerca de la dosis ideal, tiempo de uso, respuesta clínica y seguridad del tratamiento sistémico en niños con DA grave. Se realizó este estudio para describir las características clínicas de pacientes con DA grave que requirieron un tratamiento sistémico, los medicamentos utilizados, la evolución clínica, los efectos secundarios y las complicaciones asociadas.. Se llevó a cabo una revisión retrospectiva de los expedientes de pacientes pediátricos con DA grave atendidos en el Servicio de Dermatología, Instituto Nacional de Pediatría (2000 a 2018), que hayan requerido tratamiento sistémico por más de 3 meses.. Se incluyeron 21 pacientes. La media de edad de inicio de la enfermedad fue de 3.31 años. Los fármacos utilizados fueron metotrexato (57.1%), talidomida (38%), prednisona (42.8%), azatioprina (19%), mofetil micofenolato (9.5%), ciclosporina (4.7%) y esteroides sistémicos como terapia puente (42.8%). Se observaron efectos secundarios leves en dos pacientes (9.5%) tratados con metotrexato y mofetil micofenolato.. El metotrexato fue el medicamento utilizado en más del 50% de los pacientes con remisión en la mayoría de ellos. La ciclosporina, azatioprina y mofetil micofenolato también fueron efectivos. Los efectos secundarios fueron leves y poco frecuentes. Es necesario realizar estudios comparativos de tratamientos sistémicos para DA grave en la población pediátrica.

Topics: Azathioprine; Child; Child, Preschool; Cyclosporine; Dermatitis, Atopic; Humans; Methotrexate; Mycophenolic Acid; Prednisone; Thalidomide

Treatment of moderate-to-severe atopic dermatitis (AD) can be challenging and little is known about the sustainability of on- and off-label prescribed systemic therapies.. To compare drug survival (DS) rates and reasons for drug discontinuation of cyclosporine A (CyA), dupilumab (DUP), azathioprine (AZA), methotrexate (MTX) and mycophenolate mofetil (MMF) prescribed under real-world conditions.. In this retrospective study, 139 treatment courses for 94 adults with AD treated at two German dermatology departments were analysed.. Based on Cox regressions with CyA as reference category, hazard ratios for treatment discontinuation were 0.10 for DUP, 0.87 for MTX, 0.98 for MMF, and 1.18 for AZA. CyA, AZA, and MTX were most frequently interrupted due to adverse events, and MMF due to non-compliance. Only one patient (6.3%) discontinued DUP before the end of the observation period, which was due to ineffectiveness.. Systemic therapies for AD differ with regards to DS and reasons leading to treatment withdrawal; this should be considered in real-life practice.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Azathioprine; Child; Child, Preschool; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Female; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Male; Medication Adherence; Methotrexate; Middle Aged; Mycophenolic Acid; Outpatients; Patient Satisfaction; Probability; Proportional Hazards Models; Retrospective Studies; Young Adult

Topics: Azathioprine; Cross-Sectional Studies; Cyclosporine; Dermatitis, Atopic; Drug Eruptions; Drug Monitoring; Humans; Methotrexate; Mycophenolic Acid; Psoriasis; United States

Topics: Administration, Topical; Dermatitis, Atopic; Diagnosis, Differential; Glucocorticoids; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Multimorbidity; Mycophenolic Acid; Triamcinolone

Patients with severe atopic dermatitis (AD) may require potent immunosuppressive therapy to control their disease. Mycophenolate mofetil (MMF) has been suggested as a safe and effective drug in these cases.. To investigate effectiveness and tolerability of oral MMF in adult patients with severe recalcitrant AD.. During the years 2010-2017 oral MMF 2-3 g/day was administered to adult patients with severe recalcitrant AD who failed other major systemic drugs, or where other drugs, including cyclosporine (CSA), methotrexate, and azathioprine, were contraindicated.. Of 9 consecutive adult patients, 4 (44%) responded completely, 2 (22%) had partial response, and 3 (33%) did not respond at all. The MMF therapy was continued for 5-36 months (average 21 months) without major side effects.. Oral MMF may be an effective drug in AD. Due to its good safety profile, it may be recommended as a first-line systemic therapy, or successive to CSA in the long term.

Topics: Adult; Aged; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Young Adult

Although atopic dermatitis (AD) is a very common skin disease, data on the percentage of patients with really difficult-to-treat AD are scarce. From socio-economic perspective, it is important to have more insight into these numbers, as new very effective, but expensive, treatment options will be available in the near future for difficult-to-treat AD. Estimating the number of patients with AD using oral immunosuppressive drugs can give an impression of the percentage of difficult-to-treat patients in the total AD population.. To give an overview of the use of oral immunosuppressive drugs in patients with AD in the Netherlands.. Prescription data of oral immunosuppressive drugs in the Netherlands were extracted from a pharmaceutical database (NControl) containing data of 557 million prescriptions and 7.2 million patients. An algorithm, based on the WHO Anatomical Therapeutic Chemical (ATC) codes, was used to identify patients with AD. The prescription of oral immunosuppressive drugs in patients with AD between 1 January 2012 and 1 January 2017 was evaluated.. Based on the algorithm, 65 943 patients with AD were selected. 943 patients with AD (1.4%) used cyclosporine A, methotrexate, azathioprine or mycophenolic acid. Methotrexate was most commonly used, followed by azathioprine and cyclosporine A. A switch in medication was rarely seen. In the evaluation period, a decrease in the prescription of cyclosporine A was seen, together with an increase in the prescription of methotrexate. In 31% of the patients who stopped treatment, the discontinuation took place within the first months of treatment.. In this study population, 1.4% of the patients with AD used oral immunosuppressive drugs for their eczema in a 5-year period. Methotrexate was the most commonly used systemic drug in the Netherlands for the treatment of AD.

Topics: Administration, Oral; Azathioprine; Cyclosporine; Databases, Factual; Dermatitis, Atopic; Drug Prescriptions; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Netherlands

Topics: Azathioprine; Dermatitis, Atopic; Follow-Up Studies; Humans; Methotrexate; Mycophenolic Acid

Photosensitive atopic dermatitis (AD) is a rare disease entity that many physicians are not familiar with, thus it often is misdiagnosed. It can be life altering, as patients often strictly avoid the sun and may only leave the house at night. Effective treatments are available, and therefore diagnosis is key to improve quality of life for these patients. We describe a case of photosensitive AD exacerbated by UVB exposure. The diagnosis was made with phototesting, and the patient was able to begin treatment with narrowband UVB (NB-UVB) hardening while on immunosuppression. The literature on photosensitive AD is limited, and this entity typically is not found in the main dermatology textbooks. Our case emphasizes the diagnostic problems and complexity of photosensitive AD. Histopathologic findings are nonspecific. A thorough history and physical examination can provide the necessary clues for further workup. Phototesting should be performed to confirm the diagnosis and evaluate the degree of sensitivity to UV light and the specific wavelength eliciting the cutaneous response. Photoprovocation and photopatch testing also can be useful to confirm the diagnosis.

Topics: Anti-Inflammatory Agents; Dermatitis, Atopic; Diagnosis, Differential; Enzyme Inhibitors; Female; Humans; Middle Aged; Mycophenolic Acid; Prednisone; Ultraviolet Rays

The treatment of atopic dermatitis in adults is based on the use of topical steroids and emollients. When AD is resistant to a well-conducted topical treatment, phototherapy or systemic treatments can be used: ciclosporin, methotrexate, azathioprine or mycophenolate mofetil. The therapeutic landscape of adult AD is about to change and even be revolutionized by the imminent arrival of new treatments: topical phosphodiesterase 4 inhibitors, topical or systemic JAK inhibitors, anti-IL-4 and/or antiIL-13 biotherapies (dupilumab, tralokinumab, lebrikizumab), anti-IL-31 (nemolizumab), anti-TSLP.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Glucocorticoids; Humans; Methotrexate; Mycophenolic Acid; Piperidines; Pyrimidines; Pyrroles; Thalidomide; Ustekinumab

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93-80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage.

Topics: Adult; Antibiotics, Antineoplastic; Cyclosporine; Dermatitis, Atopic; Female; Genotype; Glucuronosyltransferase; Humans; Immunosuppressive Agents; Logistic Models; Male; Middle Aged; Mycophenolic Acid; Odds Ratio; Polymorphism, Single Nucleotide; Precision Medicine; Retrospective Studies; Severity of Illness Index; UDP-Glucuronosyltransferase 1A9

There is a paucity of literature to direct physicians in the prescribing of immunomodulators for patients with severe atopic dermatitis (AD).. To survey systemic agent prescribing practices for severe childhood AD among clinicians in the United States and Canada.. The TREatment of severe Atopic dermatitis in children Taskforce (TREAT), US&CANADA, a project of the Pediatric Dermatology Research Alliance (PeDRA), developed an online multiple-response survey to assess clinical practice, gather demographic information and details of systemic agent selection, and identify barriers to their use in patients with recalcitrant pediatric AD.. In total, 133 of 290 members (45.9%) of the Society for Pediatric Dermatology completed the survey, and 115 of 133 (86.5%) used systemic treatment for severe pediatric AD. First-line drugs of choice were cyclosporine (45.2%), methotrexate (29.6%), and mycophenolate mofetil (13.0%). The most commonly used second-line agents were methotrexate (31.3%) and mycophenolate mofetil (30.4%); azathioprine was the most commonly cited third-line agent. The main factors that discouraged use of systemic agents were side-effect profiles (82.6%) and perceived risks of long-term toxicity (81.7%).. Investigation of the sequence of systemic medications or combination systemic therapy was limited. Recall bias may have affected the results.. Great variation exists in prescribing practices among American and Canadian physicians using systemic agents for treatment of pediatric AD.

Topics: Adult; Azathioprine; Canada; Child; Cyclosporine; Dermatitis, Atopic; Dermatology; Drug Prescriptions; Female; Health Care Surveys; Humans; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Pediatrics; Practice Patterns, Physicians'; Severity of Illness Index; United States

The goal of clinical registries is to document the use and effectiveness of therapeutic interventions under real-life conditions. They are an indispensable prerequisite of evidence-based health care.. Initiated in 2011, the German Atopic Dermatitis Registry TREATgermany is the first registry of patients with severe atopic dermatitis worldwide. Adults with severe atopic dermatitis (current/prior systemic antiinflammatory treatment and/or objective SCORAD ≥ 40) are prospectively followed over the course of 24 months. Employed treatment modalities are documented, and validated measuring tools are used to assess clinical disease severity (EASI, objective SCORAD), quality of life (DLQI), symptoms (POEM), global disease severity, as well as patient satisfaction. Herein, we describe the characteristics, therapeutic selection, and effectiveness of systemic antiinflammatory treatments of patients enrolled in the registry until October 2014.. Overall, 78 individuals (mean age 39 years, 61 % men) were enrolled at five recruitment centers. Patients frequently made use of inpatient and outpatient services. Not only was cyclosporine the most frequently administered systemic treatment, but also the most effective (EASI 50 response rate 51 %; EASI 75 response rate 34 % at 12 weeks). Azathioprine, methotrexate, oral prednisolone, mycophenolate, alitretinoin, and leflunomide were also used in some patients.. The present analysis of the German Atopic Dermatitis Registry provides important data with respect to current medical care of adults with severe atopic dermatitis in Germany. It shows the high disease burden, the benefits of current treatment options, and the need for additional effective and safe long-term treatment options.

Topics: Adult; Alitretinoin; Anti-Inflammatory Agents; Azathioprine; Cyclosporine; Dermatitis, Atopic; Female; Follow-Up Studies; Humans; Leflunomide; Long-Term Care; Male; Methotrexate; Mycophenolic Acid; Prednisolone; Registries; Treatment Outcome

Topics: Adult; Azathioprine; Dermatitis, Atopic; Drug Resistance; Drug Substitution; Female; Humans; Kaplan-Meier Estimate; Male; Mycophenolic Acid

The Risk Evaluation and Mitigation Strategy program that the U.S. Food and Drug Administration has mandated has intensified the counseling associated with prescribing mycophenolate mofetil (MMF), because of its teratogenicity. In this brief report, two children are described who were prescribed MMF and within weeks developed psychiatric symptoms, with rapid resolution after discontinuation of the medication and no recurrence over 4 years of follow-up. Mood disorders are a rare but possible side effect that should be mentioned when discussing MMF with patients and families. Prompt discontinuation of the drug should lead to reversal of symptoms when the drug is implicated.

Topics: Administration, Oral; Adolescent; Dermatitis, Atopic; Dose-Response Relationship, Drug; Drug Administration Schedule; Facial Dermatoses; Female; Follow-Up Studies; Humans; Male; Mood Disorders; Mycophenolic Acid; Recurrence; Risk Assessment; Sampling Studies; Scleroderma, Localized; Severity of Illness Index; United States; United States Food and Drug Administration; Withholding Treatment

Topics: Adult; Dermatitis, Atopic; Enzyme Inhibitors; Female; Glucocorticoids; Histiocytes; Humans; Lung; Lung Diseases, Interstitial; Lymphocytes; Mycophenolic Acid; Prednisolone; Remission Induction; Thoracic Surgery, Video-Assisted; Tomography, X-Ray Computed; Treatment Outcome

To describe a case in which a patient developed Candida esophagitis (CE) after treatment of atopic dermatitis (AD) with mycophenolate mofetil (MMF) for 22 months.. A 59-year-old Caucasian female with long-standing history of AD successfully treated with MMF presented to the dermatology clinic for follow-up appointment with 3 months' history of projectile vomiting, choking, and trouble swallowing. Patient underwent esophagogastroduodenoscopy (EGD) that demonstrated whitish plaques in esophagus consistent with CE, which was confirmed by biopsy and cytology.. MMF is a lymphocyte selective immunosuppressive agent that has demonstrated very good therapeutic effects against cutaneous inflammatory skin disease and proved to have good efficacy and bioavailability. Generally, MMF is a safe medication with relatively low side effects. There are no case reports to date that describe CE in patients treated with MMF. Clinicians should be aware of this rare complication to enable timely intervention and treatment.

J Drugs Dermatol. 2016;15(10):1267-1269.

Topics: Candida; Candidiasis; Dermatitis, Atopic; Enzyme Inhibitors; Esophagitis; Female; Humans; Middle Aged; Mycophenolic Acid

There is a lack of information on the use oral immunosuppressive drugs in atopic dermatitis (AD) daily practice.. A 10-years overview of the use of oral immunosuppressive drugs in patients with severe AD.. Medical charts of patients with AD, who received oral immunosuppressive drugs at the Academic Medical Center Amsterdam and in the University Medical Center Utrecht between January 2001 and January 2011, were analysed. Particular attention was paid to patient characteristics, prior treatment, prescribed oral immunosuppressive drugs, the order of use, doses and treatment durations and reasons for discontinuation of treatment.. Of 334 patients [53% male, mean age at start of an oral immunosuppressive drug 36.9 years (SD 13.6)] with AD received oral immunosuppressive treatment of which 102 (31%) participated in clinical trials. Cyclosporine A (CyA) was given in 80% of the patients, mycophenolate mofetil or enteric-coated mycophenolate (MMF/EC-MPS) in 31%, azathioprine (AZA) in 14%, methotrexate (MTX) in 11%, systemic glucocorticosteroids in 7% and systemic tacrolimus in 5%. In these academic centra, CyA was the first choice oral immunosuppressive in 252 patients. Reasons for discontinuation of oral immunosuppressive drugs were controlled AD disease, ineffectiveness and adverse events.. Various types of oral immunosuppressive drugs have been used over the past 10 years for the treatment of severe AD with a prominent first choice for CyA. Adverse events and ineffectiveness were frequent reasons for discontinuation. A prospective database of patients using oral immunosuppressive treatments in daily practice will give more insight in the effectiveness and safety and may help to formulate future recommendations.

Topics: Academic Medical Centers; Administration, Oral; Adult; Azathioprine; Cyclosporine; Dermatitis, Atopic; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Tacrolimus; Young Adult

Rapamycin (RPM) and mycophenolic acid (MPA) are immunosuppressive drugs approved for use in preventing transplant rejection. These drugs have also been used in the field of dermatology as glucocorticoid sparing agents for autoimmune and inflammatory disorders such as atopic dermatitis (AD). The aim of this study was to investigate the therapeutic effect of topically applied RPM and/or MPA on AD-like skin lesions in NC/Nga mice. RPM (0.04% - 4%), MPA (0.2% - 5%), and formulations of both agents at various ratios were administrated topically to NC/Nga mice with 2-chloro-1,3,5-trinitrobenzene (TNCB)-induced AD-like skin lesions. The therapeutic effects of topical RPM, MPA, and the mixed formulations in TNCB-treated NC/Nga mice were assessed by measuring skin severity scores, ear thickness, and histological changes in the lesioned skin including mast cell count and total serum IgE levels. Expression of interleukin (IL)-4, and interferon (IFN)-γ was also assessed. Topical 4% RPM and/or 1% MPA treatment significantly improved clinical signs of AD such as erythema, edema, excoriation, and dryness on day 29 (P<0.05). In addition, 4% RPM, 1% MPA, and the mixed formulations significantly decreased epidermal thickening, dermal edema, and cellular infiltration into the dermis compared with the vehicle. RPM (4%) and/or MPA (1%) significantly reduced the expression of IL-4 and IFN-γ mRNA and protein levels compared with the vehicle (P<0.05). No significant change in the levels of total serum IgE was induced by topical 4% RPM and/or 1% MPA. The present results demonstrated that topical 4% RPM and/or 1% MPA improved TNCB-induced AD-like lesions of NC/Nga mice by suppressing expression of Th2-related cytokines (IL-4) and Th1-related cytokines (IFN-γ). These findings suggest that RPM and/or MPA may be promising topical therapeutic candidates for the treatment of AD.

Topics: Administration, Topical; Animals; Dermatitis, Atopic; Edema; Immunoglobulin E; Immunosuppressive Agents; Interferon-gamma; Interleukin-1; Mast Cells; Mice; Mice, Inbred Strains; Mycophenolic Acid; Sirolimus; Skin; Trinitrobenzenes

Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.

Topics: Anti-Infective Agents; Azathioprine; Cyclosporine; Dermatitis, Atopic; Histamine Antagonists; Humans; Immunologic Factors; Interferon-gamma; Methotrexate; Mycophenolic Acid; Phototherapy

Mycophenolate use in dermatology is growing due to its reputation as a steroid-sparing agent with a favourable side-effect profile. However, there are limited data on the efficacy and tolerability of mycophenolate for many dermatological indications. We conducted a retrospective clinical audit in 33 dermatology patients who had received mycophenolate at our institution between April 2010 and January 2012. The top indication was pyoderma gangrenosum (14 patients) followed by atopic dermatitis (seven patients). Overall 70 per cent of patients showed some benefit from mycophenolate treatment, with 12 per cent failing to respond. Side-effects were experienced by 45 per cent of patients, two of whom had serious side-effects. Female sex appears to be a risk factor for adverse effects. We conclude that although mycophenolate is a promising agent across a variety of dermatological conditions, further randomised controlled trials are required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Male; Medical Audit; Middle Aged; Mycophenolic Acid; Pyoderma Gangrenosum; Retrospective Studies; Young Adult

Atopic dermatitis (AD) includes severe forms that can be refractory to various systemic treatments. Mycophenolate mofetil (MMF) has been found to be useful in patients with severe forms of AD and to have fewer side effects than long-term treatment with oral corticosteroids or cyclosporine.. To evaluate the efficacy and adverse effects of MMF in patients seen in our skin allergy unit with severe adult AD refractory to other systemic treatments.. We performed a retrospective study of 8 patients with severe adult AD treated with MMF, analyzing the baseline characteristics, previous treatments used by the patients, and the outcome and adverse effects of treatment with MMF.. Five patients treated with MMF showed improvement in the fourth week of treatment. In addition, 5 of the 8 patients presented a clear, long-term improvement in their disease. Remission of AD occurred in 1 patient, making it possible to discontinue MMF; this patient remains stable with no relapses after 4 months without treatment. The other 4 patients continue on maintenance therapy. Three patients continued to have frequent acute outbreaks of AD despite treatment with MMF for 16 to 72 weeks. All patients tolerated the treatment and there were few adverse effects.. MMF can be an effective option in selected patients with severe forms of atopic dermatitis. Although the response is not as rapid as with oral corticosteroids or cyclosporine, it can be used for maintenance treatment with good clinical control and few adverse effects.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Severity of Illness Index; Young Adult

Topics: Aged, 80 and over; Dermatitis, Atopic; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Ultraviolet Rays

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that can be refractory to topical and systemic corticosteroids, phototherapy, topical immunomodulators and systemic immunosuppressive drugs. Recent studies have shown promise for the use of mycophenolate mofetil (MMF) to treat recalcitrant AD.. To assess the effectiveness and adverse effects of MMF used for moderate to severe AD in a university outpatient dermatology clinic.. A retrospective chart review of 20 patient charts was conducted for patient age, gender, duration of disease, prior therapies, concomitant therapy, clinical response and adverse side-effects.. Of the 20 patients, 17 improved within 4 weeks of starting MMF therapy. Ten patients had disease remission and were subsequently able to discontinue MMF. Seven attained satisfactory control of their AD using MMF as maintenance therapy. Overall, MMF was well tolerated, with mild headaches, gastrointestinal complaints and fatigue as the commonest side-effects. During therapy, herpes zoster developed in four patients, Staphylococcus aureus cutaneous infections in two, and herpes simplex in one. One patient discontinued MMF because of insufficient control of pruritus.. MMF can be rapidly effective and well tolerated in patients with moderate to severe AD resistant to conventional therapies. The limitations of this retrospective study include no control group and a lack of a standardized scoring index to assess improvement, and the concomitant use of adjuvant therapies makes the contribution of MMF alone difficult to assess. Larger controlled studies are needed.

Topics: Adult; Aged; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies

Reports of successful treatment of atopic dermatitis (AD) with mycophenolate mofetil (MMF) have thus far been limited to adults. Considering that the condition typically develops during childhood and is most active during this period, MMF would represent a valuable addition to the therapeutic armamentarium for paediatric AD.. To evaluate the safety and efficacy of MMF in the treatment of severe childhood AD.. A retrospective analysis was performed of all children treated with MMF as systemic monotherapy for severe, recalcitrant AD between August 2003 and August 2006 at New York University Medical Center. Fourteen patients meeting these criteria were identified.. Four patients (29%) achieved complete clearance, four (29%) had > 90% improvement (almost complete), five (35%) had 60-90% improvement and one (7%) failed to respond. Initial responses occurred within 8 weeks (mean 4 weeks), and maximal effects were attained after 8-12 weeks (mean 9 weeks) at MMF doses of 40-50 mg kg(-1) daily in younger children and 30-40 mg kg(-1) daily in adolescents. The medication was well tolerated in all patients, with no infectious complications or development of leucopenia, anaemia, thrombocytopenia or elevated aminotransferases.. This retrospective case series demonstrates that MMF can be a safe and effective treatment for severe, refractory AD in children. MMF represents a promising therapeutic alternative to traditional systemic immunosuppressive agents with less favourable side-effect profiles, and prospective controlled studies are warranted, further to assess its benefits in paediatric AD.

Topics: Adolescent; Child; Child, Preschool; Dermatitis, Atopic; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; New York; Retrospective Studies; Treatment Outcome

Topics: Aged; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Dermatitis, Atopic; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Liver; Male; Middle Aged; Mycophenolic Acid; Prodrugs

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Atopic; Dermatologic Agents; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid

Topics: Dermatitis, Atopic; Humans; Immunosuppressive Agents; Mycophenolic Acid; Reproducibility of Results; Treatment Outcome

Topics: Bacteremia; Contraindications; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Staphylococcal Infections

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Atopic; Female; Humans; Male; Middle Aged; Mycophenolic Acid; Treatment Outcome

Topics: Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Atopic; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycophenolic Acid