Mycophenolate mofetil as a treatment for urticarial dermatitis

We report two cases of adults with urticarial dermatitis who could not be managed by a variety of treatments but who obtained good control with mycophenolate mofetil (MMF). A clinical response was seen 6‐8 weeks from treatment onset and they were maintained on MMF 1 g twice daily (case 1), and MMF 1 g omni mane and 500 mg omni nocte (case 2), with no major exacerbations for many years. MMF is an immunosuppressive agent, which is currently used off‐label for many dermatological conditions. To date, there have been no studies investigating the use of MMF as a treatment for urticarial dermatitis. The cases we present suggest that MMF is an effective treatment for this condition, and we recommend that MMF be considered as a treatment option.     

Mycophenolate mofetil

Mycophenolate mofetil (MMF) is a relatively new systemic immunosuppressive agent whose use is rapidly increasing within the field of dermatologic. Originally used in the 1970s for the treatment of psoriasis, MMF has demonstrated efficacy in multiple types of inflammatory skin diseases. Although the safety data within the dermatologic literature is sparse, MMF's extensive use within the field of organ transplantation has demonstrated a favorable safety profile. MMF's lack of hepatic or renal toxicity is a significant advantage over immunosuppressive medications currently used in dermatology and make MMF an attractive candidate for multidrug regimens. In this review the present authors discuss the pharmacology, mechanisms of action, side effects and current uses of MMF reported within the dermatologic literature. The present authors also provide practical information regarding the use of the MMF culled from the literature as well as from the present authors' own clinical experience with the medication.     

Efficacy and safety of mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis

Background Methotrexate (MTX) is a well‐known systemic drug for moderate to severe chronic plaque psoriasis. Recently, mycophenolate mofetil (MMF) has been recommended for psoriasis. Objective To compare the efficacy and safety of MMF vs. MTX for the treatment of chronic plaque psoriasis. Methods Thirty‐eight consecutive patients with Psoriasis Area and Severity Index (PASI) >10 were randomly assigned for 12 weeks of treatment with either MTX (18 patients; initial dose, 7.5 mg/week) or MMF (20 patients; dose; 2 g/day) and were followed for 12 weeks after discontinuing the treatment. The differences between the two groups were analysed at the end of treatment and follow‐up comparing with baseline values. Results After 12 weeks of treatment, the mean ± SD score for the PASI decreased from 16.46 ± 5.29 at baseline to 3.17 ± 2.35 among 15 patients treated with MTX, whereas the score decreased from 17.43 ± 7.42 to 3.97 ± 5.95 among 17 patients treated with MMF (P > 0.05). Twelve weeks after discontinuing the treatment, the scores were 4.77 ± 3.52 and 5.94 ± 4.27, respectively (P > 0.05). PASI ‐75 were achieved in 58.8% of patients in MMF group and 73.3% in MTX group (P > 0.05). Three months after discontinuing the treatment, PASI‐75 remained in 33.3% of patients in MMF and 53.3% of MTX group (P > 0.05). Both drugs were well tolerated and side‐effects were minor and transient. Conclusions No significant differences in efficacy were found between MTX and MMF groups. MMF may represent a good alternative for the treatment of psoriasis in patients who are unable to take MTX or other available drugs due to contraindication or toxicity.     

Mycophenolate use in dermatology: A clinical audit

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.     

Mycophenolate mofetil for severe childhood atopic dermatitis: experience in 14 patients

BACKGROUND: 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. OBJECTIVES: To evaluate the safety and efficacy of MMF in the treatment of severe childhood AD. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Chronic actinic dermatitis treated with mycophenolate mofetil

Chronic actinic dermatitis (CAD) is a persistent photodermatosis that usually affects elderly men. We report two male patients, aged 55 years (patient A) and 49 years (patient B), who presented with an eczematous eruption on sun-exposed skin. Phototesting revealed a markedly reduced 24-h minimal erythema dose (MED). Both patients had refractory disease and developed significant side-effects to conventional therapies, including topical steroids, prednisolone, psoralen with ultraviolet A, azathioprine and ciclosporin. They had each received at least 6 years of treatment prior to commencing mycophenolate mofetil (MMF). Each noted a significant improvement in symptoms within 6 weeks and subsequent clearing of the eczematous lesions. Patient A still requires continuous treatment with MMF 500 mg twice daily to prevent relapses. Patient B maintains remission by using MMF 1 g twice daily only during the spring and summer months. Both patients have tolerated the treatment well with no abnormalities in blood cell counts or liver biochemistry. Since commencing MMF, their quality of life has significantly improved. These observations suggests that MMF should be considered as an alternative treatment to conventional therapies for refractory CAD.     

Change of treatment from cyclosporin to mycophenolate mofetil in severe psoriasis

Eight patients whose severe psoriasis was treated with long-term cyclosporin (range 2-11 years; mean 7.6 years) were changed to mycophenolate mofetil (MMF), because of nephrotoxicity in seven and hypertension and lack of efficacy in one. In five patients psoriasis control significantly deteriorated and in three patients disease control deteriorated slightly in periods ranging from 2 to 32 weeks. Renal function improved in all six patients with cyclosporin-induced nephrotoxicity treated with MMF for more than 2 weeks. From this data it would appear that MMF is not as effective as cyclosporin in controlling severe psoriasis. However, MMF did offer reasonable disease control in three of eight patients and allowed renal function to improve, and so may have a place in the treatment of some patients unable to take cyclosporin because of renal toxicity.     

Treatment of atopic eczema with oral mycophenolate mofetil

BACKGROUND: 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. OBJECTIVES: In this pilot study, we examined the efficacy of MMF (CellCept(R), Hoffman La Roche, Grenzach-Wyhlen, Germany) in severe AE. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

First experience with enteric-coated mycophenolate sodium (Myfortic®) in severe recalcitrant adult atopic dermatitis: an open label study

Background Severe atopic dermatitis (AD) is often treated successfully with oral immunosuppressive drugs such as ciclosporin (CsA) or oral corticosteroids. However, some patients develop adverse effects or are unresponsive to these first‐choice oral immunosuppressive drugs. Objectives To evaluate whether enteric‐coated mycophenolate sodium (EC‐MPS) is an effective treatment in patients with severe, recalcitrant AD. Methods 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. Results 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. Conclusions 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.     

霉酚酸酯与环磷酰胺治疗狼疮性肾炎的疗效对比

为了观察霉酚酸酯治疗狼疮性肾炎的疗效及安全性,设置霉酚酸酯+泼尼松为治疗组和环磷酰胺+泼尼松为对照组,对肾活检确诊为狼疮性肾炎的患者进行临床疗效对比观察。结果发现治疗组虽有半数患者对环磷酰胺耐药,但疗效仍与对照组相当(P>0.05),而泼尼松减量速度则比对照组快(P<0.01)。提示霉酚酸酯治疗狼疮性肾炎的疗效优于环磷酰胺。     

An evaluation of the usefulness of mycophenolate mofetil in pemphigus

BACKGROUND: Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. OBJECTIVES: The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. METHODS: Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. RESULTS: Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. CONCLUSIONS: We found that MMF permitted a reduction in prednisolone dosage without disease relapse.     

Mycophenolate mofetil may serve as a steroid-sparing agent for sarcoidosis

Sarcoidosis is an inflammatory disease with potentially severe mucocutaneous manifestations. Mycophenolate mofetil (MMF) is an immunosuppressive drug extensively used in organ transplantation. Its use has been rapidly expanded into autoimmune and inflammatory diseases. We report the first successful and safe use of MMF in five patients with sarcoidosis.     

Plasma trough levels of mycophenolic acid do not correlate with efficacy and safety of mycophenolate mofetil in psoriasis

BACKGROUND: Mycophenolate mofetil (MMF) has been shown to be effective for systemic treatment of psoriasis. MMF is the prodrug of mycophenolic acid (MPA), the pharmacologically active compound. The measurement of plasma MPA levels could be useful for optimizing therapeutic management using MMF. OBJECTIVES: To investigate whether plasma trough levels of MPA correlate with the efficacy and safety of oral MMF in the treatment of patients with psoriasis. METHODS: Six patients (four women and two men, mean age 58 years) with severe chronic plaque-type psoriasis were treated with oral MMF 1 g twice daily. The Psoriasis Area and Severity Index (PASI), routine laboratory examinations and plasma MPA trough levels, measured by an enzyme-multiplied immunoassay (EMIT), were determined at 2 weeks and 1, 3, 5 and 7 months. RESULTS: All the patients experienced a marked improvement within the first 15 days and continued to do so for 5-7 months. Two patients achieved complete remission. MMF was well tolerated. MPA levels showed a wide intra- and interindividual variability. There was no significant correlation between MPA trough levels and the reduction of the PASI or the presence of adverse effects, but a good correlation with therapeutic compliance. CONCLUSIONS: The monitoring of MPA trough levels with EMIT appears to be a poor predictor of efficacy or toxicity. In contrast, it is a useful tool to evaluate the degree of therapeutic compliance.     

Mycophenolate in dermatology

Originally used to treat psoriasis nearly three decades ago, mycophenolic acid, reformulated as mycophenolate mofetil (MMF), has been rediscovered by the world of dermatology. As a relatively well-tolerated immunosuppressive used in organ transplant recipients, MMF has recently been reported to show promise for several dermatologic conditions, including psoriasis, pemphigus vulgaris, pyoderma gangrenosum, bullous lichen planus, and even connective tissue diseases such as lupus erythematosus and dermatomyositis. Although not intended to be exhaustive, this review discusses MMF with regard to its basic pharmacology, its side effects, and its reported efficacy in a variety of dermatologic indications. Relevant literature was retrieved by a Medline search combining the terms "mycophenolate" or "mycophenolic acid" and "skin" or "skin disease" or a number of specific conditions ("psoriasis", "dermatitis", "eczema", "pemphigoid", "pemphigus", "vasculitis", "pyoderma gangrenosum", "Crohn's disease", "graft-versus-host disease", "lichen planus"). As MMF has only been recently re-introduced for dermatologic application, the nature of much of the literature is admittedly that of case reports or case series. Nevertheless, the results are sufficiently promising to warrant further larger, control studies.     

Mycophenolate mofetil as an adjuvant therapy for classic and endemic pemphigus foliaceus

Pemphigus foliaceus is an autoimmune cutaneous disease with subcorneal acantholysis and pathogenic IgG4 autoantibodies directed against desmoglein 1. We present our experience with mycophenolate mofetil (MMF) in the treatment of one case of endemic pemphigus foliaceus (fogo selvagem) and two cases of the classic form. All patients had severe, refractory disease and developed marked adverse effects due to long-term corticosteroid therapy. MMF proved to be an effective corticosteroid-sparing agent at doses varying from 35 to 45 mg/kg/d. It was well tolerated, and we found no significant adverse effects from this drug.     

Enteric‐coated mycophenolate sodium in the treatment of refractory pemphigus

Background One of the major goals of pemphigus therapy is to reduce the patient’s cumulative exposure to systemic corticosteroids. To investigate the efficacy of enteric‐coated mycophenolate sodium (EC‐MPS), 10 patients with active, refractory pemphigus vulgaris (PV) or foliaceous (PF) were treated with EC‐MPS (1440 mg daily) and prednisone (75 mg daily) over 18 months. Observations Following EC‐MPS/prednisone therapy, disease progression was inhibited between days 30 and 45 in 9/10 patients (8 PV; 1 PF). At 18 months, 8/9 PV patients had clinically quiescent disease; EC‐MPS therapy was no longer required in two patients as a result of disease remission. The remaining PV patient showed no response to treatment. The PF patient also had clinically quiescent disease but with high levels of anti‐desmoglein‐1. ECMPS dose was reduced to 720 mg daily in 4/9 patients by month 6. Average daily prednisone requirement decreased to 25 mg at 6 months and to 15 mg at 18 months. Three adverse events were reported: headache (two cases; one mild and one moderate) and significant increase in blood glucose (one case; moderate). Conclusions Enteric‐coated mycophenolate sodium is effective and safe as an adjuvant therapy in patients with refractory pemphigus and may be effective even in patients whose disease is unresponsive to azathioprine.     

Sequential study on the treatment of moderate-to-severe chronic plaque psoriasis with mycophenolate mofetil and cyclosporin

BACKGROUND: There are numerous studies that individually evaluate the efficacy/effectiveness and toxicity of drugs in the systemic treatment of psoriasis. On the contrary, we can hardly find studies that compare each other. OBJECTIVE: To evaluate and compare the effectiveness and toxicity of mycophenolate mofetil and cyclosporin in chronic plaque psoriasis through a prospective, sequential, cross-over, non-randomized, two-phase, open-label study. PATIENTS/METHODS: Eight patients (five women and three men; mean age 57, range 35-78) with moderate-to-severe chronic plaque psoriasis were included in the study. They were treated with oral mycophenolate mofetil (30 mg/kg/day) over a period of 16 weeks. Following a variable washout period and after a new outbreak of the disease, oral cyclosporin was introduced at a dose of 4 mg/kg/day. During both treatment regimens, follow-up visits were performed at 3, 8 and 16 weeks. RESULTS: In both groups, the PASI started to decrease once treatment was begun. Cyclosporin was faster and statistically a lot more effective than mycophenolate mofetil, reaching a higher number of complete remissions and better percentages of PASI improvement from baseline (45.7%, 60.2% and 60.5% at 3, 8 and 16 weeks respectively for mycophenolate mofetil, and 89.7%, 95.3% and 95.3% respectively at the same intervals for cyclosporin). Cyclosporin was also more predictable in its action as the percentage of improvement along the follow-up visits had a much wider range for mycophenolate mofetil. Overall, the tolerability of both drugs was good. None of the patients had to discontinue treatment because of an adverse event. Two patients treated with cyclosporin showed increased plasma levels of creatinine. CONCLUSIONS: Cyclosporin is more effective, fast, and predictable in its effect than mycophenolate mofetil to control moderate-to-severe chronic plaque psoriasis. Both drugs are well tolerated in short courses of treatment.     

Inhibitors of purine and pyrimidine synthesis: mycophenolate, azathioprine, and leflunomide

The major goal in the treatment of autoimmune blistering diseases has changed from simply keeping the patient alive to suppressing disease while maintaining quality of life and minimizing drug side effects. Researchers and clinicians are constantly seeking steroid-sparing agents that would allow a dose reduction in corticosteroids with no loss of benefit. Purine and pyrimidine base inhibitors are commonly used for this purpose. These drugs act by inhibiting cell division and inducing cell death. The pharmacologic and clinical aspects of azathioprine, mycophenolate mofetil, and leflunomide are discussed in this review.     

Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. Some case reports and pilot studies have suggested efficacy against systemic lupus erythematosus (LE), particularly in the case of lupus nephritis. Reports on MMF treatment of skin manifestations of LE are still anecdotal. We report two cases with extensive skin lesions owing to subacute cutaneous LE (SCLE). Both patients had been treated with azathioprine and antimalarials without effect. Finally both patients were given highly dosed glucocorticosteroids, which were also ineffective but led to vertebral fractures because of long-term steroid treatment in one patient and steroid-induced psychosis in the other. MMF 2 g daily caused the skin manifestations to disappear within a few weeks in both patients. One patient was followed up for more than 24 months, and showed good toleration of MMF treatment. The skin remained stable over this period when at least 1 g MMF per day was administered. In conclusion, MMF appears to be an attractive treatment option in skin manifestations of SCLE, and seems to be beneficial for patients with steroid-refractory lesions that are also resistant to treatment with immunosuppressants or antimalarials. The observations suggest that further evaluation of this route in randomized controlled trials is warranted.     

Mycophenolate mofetil for the management of autoimmune bullous diseases

Immunosuppressive agents such as azathioprine, cyclophosphamide, and mycophenolate mofetil (MMF) are now widely used in the treatment of autoimmune bullous diseases. This article reviews the use of MMF for the treatment of several bullous conditions, and assesses the evidence gathered from clinical trials and case series. According to numerous case series, MMF could be of value in treating refractory disease. The few randomized clinical trials conducted to date of patients with pemphigus and bullous pemphigoid report a similar efficacy for MMF to other immunosuppressants.