mycophenolic-acid and Scleroderma--Localized

Many clinical trial results are available to inform best practices in the treatment of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD).Herein, we summarize the results of clinical trials, including patient-reported outcome instruments, for the treatment of patients with ILD associated with systemic sclerosis (SSc/scleroderma), rheumatoid arthritis, and idiopathic inflammatory myositis, the diseases with the most available data. For SSc-ILD, the US Food and Drug Administration approved nintedanib (a tyrosine kinase inhibitor) in 2020 and subcutaneous tocilizumab (an IL-6 receptor monoclonal antibody) in 2021. Rituximab was recently shown to have similar efficacy but better tolerability than intravenous cyclophosphamide (CYC) for CTD-ILD therapy. Scleroderma Lung Study II, conducted in patients with SSc-ILD, showed that oral CYC and mycophenolate mofetil (MMF) were comparable in their effects on lung function, but MMF was better tolerated. The increasing treatment armamentarium for patients with CTD-ILD offers physicians new opportunities to improve patient outcomes.

Topics: Connective Tissue Diseases; Cyclophosphamide; Humans; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Mycophenolic Acid; Scleroderma, Localized; Scleroderma, Systemic

Juvenile localized scleroderma (jLS) is a chronic autoimmune and fibrosing disease associated with a high risk for functional impairment. Antifibrotic options are limited, so current treatment strategies are focused on disease activity control. Pediatric rheumatologists are in consensus on the need to treat with systemic immunosuppressants, in particular, methotrexate. However, more than 30% of patients fail initial methotrexate treatment. This review provides an update on current management and reviews reports on potential alternative treatments.. An overview of current treatment recommendations and its efficacy are discussed. Recent studies have identified several factors associated with likelihood of treatment response. These include time to initiation of treatment, certain subtypes, and extracutaneous involvement. Findings from recent reports of alternative systemic immunomodulators, including biologic medications, will be summarized.. Methotrexate treatment has greatly improved outcome for most jLS patients but a substantial portion have refractory cutaneous and/or extracutaneous disease. Treatment response factors are being identified, which could lead to improved management strategies. Recent studies provide further support on mycophenolate mofetil as an alternative treatment. Data on biologic therapies is encouraging, with data suggesting efficacy for many extracutaneous manifestations but more studies are needed to evaluate these and other options for jLS.

Topics: Child; Consensus; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Scleroderma, Localized

Generalized morphea and eosinophilic fasciitis are difficult-to-treat inflammatory and sclerosing skin diseases. Few cases have been reported in which intravenous immunoglobulins were of benefit, possibly owing to their immunomodulatory and antifibrotic properties.. We present three new patients with generalized morphea treated with intravenous immunoglobulins as well as a review of the literature.. Three hospitalized patients (two men, age 66 and 65 years, respectively, and a 67-year-old woman) with generalized morphea who received therapy for the first time are described.. The three patients were treated with intravenous immunoglobulins (1.5-2 g/kg body weight over three to four consecutive days every four weeks). This was combined with corticosteroid pulse therapy in all patients, methotrexate in two patients and mycophenolate mofetil in one patient, respectively. Marked and steady improvement of skin sclerosis was evident in all patients, one to five months after treatment initiation. No adverse events were observed. To date, there are 12 reports of 16 patients with generalized morphea or eosinophilic fasciitis treated with intravenous immunoglobulins. The treatment was highly effective in the majority of patients (9/16) and yielded a favourable risk profile.. Our cases add to the hitherto limited evidence that the administration of intravenous immunoglobulins in combination with glucocorticoids and conventional immunosuppressive agents is a safe and effective therapy against morphea. It seems appropriate to verify these results in future high-quality studies.

Topics: Aged; Dermatologic Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Male; Methotrexate; Mycophenolic Acid; Pulse Therapy, Drug; Scleroderma, Localized; Treatment Outcome

Paediatric morphoea (localized scleroderma) is an inflammatory sclerosing disorder of the skin and subcutis associated with tissue atrophy. It is thought that the disease develops on the background of genetic predisposition (e.g. mosaicism for the common linear variant) initiated by various trigger factors, and that detected autoantibodies and inflammatory cytokines represent secondary epiphenomena. In contrast to the common belief that morphoea is a benign self-limiting disorder, long-term data indicate that its chronicity, relapsing nature and extracutaneous complications lead to significant morbidity, particularly when the disease starts in early childhood. Early recognition may be challenging, and the most important clinical clues are band-like distribution, atrophy of underlying tissue, skin sclerosis, and localized loss of body/scalp hair, eyelashes or eyebrows. Extracutaneous manifestations occur in up to 20% of patients, with arthritis/arthralgia and neurological symptoms being most frequently observed, followed by ophthalmological complications such as uveitis. Corticosteroids and methotrexate are highly effective as first-line therapy in morphoea, leading to partial reversal of skin manifestations. However, the development of atrophy is not sufficiently prevented by standard therapy. There is a relapse rate of 25%-48% within the first years after stopping treatment, thus long-term follow-up is warranted. Mycophenolate mofetil seems to be a beneficial second-line therapy, and a new drug, abatacept, also seems to be a promising and well-tolerated second-line treatment option. Additionally, autologous fat injections are beneficial and may be used as an adjunct to ongoing therapy.

Topics: Abatacept; Adrenal Cortex Hormones; Child; Dermatologic Agents; Early Diagnosis; Humans; Methotrexate; Mycophenolic Acid; Recurrence; Scleroderma, Localized

Paediatric morphoea is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Defining optimum management strategies in paediatric morphoea remains an ongoing challenge, owing to the varied presentations and a relative paucity of paediatric-specific studies. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected and results analysed before summarizing them. In Part 1 of this review, we described the epidemiology, aetiopathogenesis and clinical classification; in this part, we discuss the diagnosis, markers of disease activity, management and natural history in paediatric morphoea.

Topics: Adrenal Cortex Hormones; Biomarkers; Child; Humans; Methotrexate; Mycophenolic Acid; Phototherapy; Scleroderma, Localized; Scleroderma, Systemic

Treatment of scleroderma in children is challenging since little is known about its pathogenesis. Herein, we review the most recent evidence regarding the treatment of juvenile scleroderma.. According to the recent recommendations for Pediatric Rheumatology in Europe (SHARE), systemic treatment in localized scleroderma is needed when there is a risk for disability, such as in generalized or pansclerotic morphea and progressive linear scleroderma. In juvenile systemic sclerosis, the introduction of the severity score, J4S, has standardized the assessment of the patients in the daily practice and allowed a more tailored therapeutic approach. Since, to date, no clinical trial is available in JSSc, due to its rarity, the treatment is based on adults' experience. The recent recommendations for juvenile scleroderma represent an important instrument to standardize the treatment approach, confirm the role of methotrexate, and open new windows for effective experimental treatments, such as mycophenolate mofetil and biological agents, for severe or refractory cases.

Topics: Child; Humans; Methotrexate; Mycophenolic Acid; Scleroderma, Localized; Scleroderma, Systemic

Juvenile localized scleroderma (jLS) is an orphan disease that can lead to cosmetic disfiguration and orthopedic problems. Two recent publications review the current recommendations regarding diagnosis, assessment, follow up and treatment of pediatric localized scleroderma cases, both of which suggest the Localized Scleroderma Cutaneous Assessment Tool as an important instrument to assess activity and damage. This review focuses on the systemic treatment of jLS. Systemic treatment includes synthetic and biologic disease-modifying antirheumatic drugs. Systemic therapy is indicated if the lesion crosses any joint, or leads to potential cosmetic disfiguration or orthopedic problems. The only controlled trial of systemic treatment has shown the efficacy of methotrexate, which is the first choice of treatment. It appears superior to phototherapy according to a recently published meta-analysis. In case of methotrexate intolerance, mycophenolate mofetil is an option. In case of methotrexate nonresponse, addition of mycophenolate mofetil, tocilizumab or abatacept seems to be effective. Future treatment options derived and extrapolated from adult trials regarding treatment of skin involvement of systemic scleroderma or fibrosis are promising, as the final pathway in the skin seems to be similar in both diseases.

Topics: Antirheumatic Agents; Child; Humans; Methotrexate; Mycophenolic Acid; Phototherapy; Scleroderma, Localized

Disabling pansclerotic morphea of childhood (DPMC) is a rare subtype of juvenile localized scleroderma (JLS) characterized by pansclerosis mainly affecting children under the age of 14. This aggressive disease has a poor prognosis due to the rapid progression of deep musculoskeletal atrophy resulting in cutaneous ulceration and severe joint contractures. We describe the challenges in treating a previously well 5-year-old male who has refractory symptoms of DPMC. Over the 29 months, since his initial presentation, we trialed over ten therapies. There was subjective improvement with prednisolone and mycophenolate mofetil (MMF). However, other therapies including biologics and tyrosine kinase inhibitors (TKI) were ineffective. The patient has been referred for hematopoietic stem cell transplant given ongoing disease progression. We conducted a literature search focusing on English articles with keywords including DPMC. Publications with limited information or describing cases aged 20 and above were excluded. Thirty-seven case reports were identified and the reported treatments were evaluated. Methotrexate and corticosteroids have been the most commonly utilized. MMF has been anecdotally effective. Biologics, TKI, and Janus kinase inhibitors lack evidence in DPMC, but have had demonstrated efficacy in similar pathologies including systemic sclerosis, and, thus, have been used for DPMC. Phototherapy has been documented to be reducing skin thickness and stiffness of plaques. Eventually, most children require multi-modal and high-dose immunosuppressive therapies to reduce the inflammation inflicted by the disease. Long-term antibiotics and nutritional support are important in the ongoing care of these patients.

Topics: Antirheumatic Agents; Biological Products; Biopsy; Child, Preschool; Contracture; Edema; Hematopoietic Stem Cell Transplantation; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Janus Kinase Inhibitors; Male; Methylprednisolone; Mycophenolic Acid; Prednisolone; Protein Kinase Inhibitors; Scleroderma, Localized; Scleroderma, Systemic; Skin; Synovitis; Treatment Failure; Treatment Outcome

Juvenile localized scleroderma (jLS) and juvenile systemic sclerosis (jSS) are both orphan diseases, with jLS around 10 times more frequent than jSS. In recent years the time gap between the appearance of symptoms and diagnosis has become significantly shorter. This review focuses on the new classifications of jSS and jLS, and on the developments and adaptations of the outcome measures for certain organ involvements whereby progress has been made regarding pediatric patients.

Topics: Antibodies, Monoclonal, Humanized; Child; Glucocorticoids; Humans; Immunosuppressive Agents; Methotrexate; Microscopic Angioscopy; Mycophenolic Acid; Scleroderma, Localized; Scleroderma, Systemic; Skin; Thermography; Tomography, Optical Coherence; Ultrasonography, Doppler; Uveitis

Morphea is a rare fibrosing disorder of the skin and underlying tissues. The underlying pathogenesis of morphea is not completely understood at this time, but ultimately results in an imbalance of collagen production and destruction. Evidence-based treatment options of morphea are limited secondary to the rarity of the disease, and the lack of universally used validated outcome measures. The most commonly used outcome measures are skin scores, computerized surface area measurement, durometer, cutometer, thermography, and ultrasound measurements. The Localized Scleroderma Cutaneous Assessment Tool is a promising recently validated skin scoring tool that allows differentiation between activity and damage, is sensitive to change, and requires no additional equipment. The most robust data in the treatment of morphea exists for methotrexate in combination with systemic steroids and ultraviolet A1.

Topics: Adolescent; Adult; Child; Humans; Methotrexate; Mycophenolic Acid; Scleroderma, Localized; Skin; Steroids; Tacrolimus; Thermography; Treatment Outcome; Ultrasonography; Ultraviolet Therapy; Validation Studies as Topic

The treatment and curative effect evaluation of localized scleroderma (LS) still perplexes many clinical workers.. To investigate the efficiacy of methotrexate in the treatment of LS by the evaluation of ultrasonography.. A prospective study enrolled 10 patients treated with MTX for at least 6 months was conducted. Treatment outcome was evaluated by a clinical score and 15-MHz ultrasonography. Safety assessment included the monitoring of adverse drug reactions and clinical laboratory examinations.. Eight of the 10 patients achieved clinical remission only with MTX. One patient was relieved after MTX combined with corticosteroids, while another one does not improve after the treatment of mycophenolate mofetil and corticosteroids. The effective rate of MTX is 80%. Nine patients were significantly improved with a decrease of the Localized Scleroderma Cutaneous Assessment Tool (the mean score of the LoSCAT cutaneous activity dropped from 5.2 to 1.0, p < 0.001, the mean score of the LS cutaneous damage dropped from 4.3 to 2.3, p = 0.002). The average difference of thickness between skin lesions and normal skin evaluated by ultrasonography decreased from 0.13 cm to 0.04 cm (p = 0.009) in eight patients. No serious adverse reactions occurred.. Methotrexate is a safe and effective treatment for patients with LS. Ultrasonography can be considered as an efficient assessment tool for evaluation LS.

Topics: Dermatologic Agents; Drug Therapy, Combination; Glucocorticoids; Humans; Methotrexate; Mycophenolic Acid; Prospective Studies; Scleroderma, Localized; Skin; Treatment Outcome; Ultrasonography

Topics: Adolescent; Anti-Inflammatory Agents; Child, Preschool; Female; Follow-Up Studies; Humans; Male; Methylprednisolone; Mycophenolic Acid; Scleroderma, Localized; Scleroderma, Systemic; Treatment Outcome

To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma.. Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan-Meier analysis.. MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy.. The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment.

Topics: Antirheumatic Agents; Child; Female; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Methotrexate; Mycophenolic Acid; Retrospective Studies; Scleroderma, Localized; Thermography; Treatment Failure; Treatment Outcome

To evaluate the safety and efficacy of abatacept treatment for refractory juvenile localized scleroderma (jLS) in a retrospective study.. A multicentre cohort study was performed to evaluate jLS subjects treated with abatacept with follow-up for 12 months to maximum of 24 months. Assessments at 6-month intervals included skin activity measures and physician global assessment of activity (PGA-A). Descriptive statistical analysis was performed.. Eighteen subjects were studied with median age of 13.4 years, the majority had linear scleroderma subtype, and musculoskeletal involvement. All had previously failed MTX and/or mycophenolate mofetil treatment and glucocorticoids. Abatacept was added to the subject's maintenance DMARD treatment; 13 also received glucocorticoids at start of abatacept. No serious adverse events occurred. Skin activity and PGA-A scores declined in nearly all by 6 months and continued to improve from 6 to 12 months. At 12 months, 15 (83%) subjects were considered responders, two (11%) treatment failures, and one dropped out for adverse event. Response was sustained for 11 (61%) subjects to 18 months and eight (44%) to 24 months. Overall, four (22%) subjects were treatment failures and three (16.7%) discontinued abatacept for adverse event. Active musculoskeletal problems improved in most affected subjects. Ten subjects were able to discontinue initial glucocorticoid and six concomitant DMARD treatment.. Abatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept's efficacy.

Topics: Abatacept; Adolescent; Antirheumatic Agents; Child; Cohort Studies; Female; Humans; Male; Methotrexate; Mycophenolic Acid; Retrospective Studies; Scleroderma, Localized; Scleroderma, Systemic; Treatment Failure; Treatment Outcome

Topics: Disease Progression; Humans; Mycophenolic Acid; Scleroderma, Localized; Skin

First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)-referred to herein as mycophenolate-is recommended; however, evidence to support this recommendation remains weak.. To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea.. A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate.. The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea.. There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized morphea (37 [48%]), pansclerotic morphea (12 [16%]), and linear morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently.. This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cohort Studies; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Retrospective Studies; Scleroderma, Localized; Treatment Outcome; Young Adult

Topics: Adult; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Immunoglobulins, Intravenous; Mycophenolic Acid; Retreatment; Scleroderma, Localized

Bullous morphea is rare clinical variant of localized scleroderma characterized by the formation of bullae on sclerotic morphea plaques. Severe disease may be highly disabling and greatly impair quality of life. Current treatment strategies are based on anecdotal reports of clinical experience and include topical corticosteroids, methotrexate and phototherapy. Herein, we describe the case of a 56-year-old woman with progressive bullous sclerotic lesions who was successfully treated with mycophenolate mofetil after treatment failure with psoralen plus ultraviolet A therapy, ultraviolet A1 phototherapy, and methotrexate. Treatment with mycophenolate mofetil halted disease progression after 8 weeks. No major adverse effects were recorded in a 3-year follow-up with continuous treatment. This case suggests mycophenolate mofetil may be considered as an alternative for the treatment of resistant bullous morphea lesions. J Drugs Dermatol. 2018;17(10):1123-1125.

Topics: Dermatologic Agents; Female; Humans; Methotrexate; Middle Aged; Mycophenolic Acid; Phytotherapy; Quality of Life; Scleroderma, Localized; Treatment Outcome

Linear scleroderma is a characteristic form of scleroderma that typically affects children. Ocular manifestations may be present, especially when the frontoparietal area of the head is affected. We present the case of a 5-year-old boy with craniofacial linear scleroderma ("en coup de sabre") who developed exudative retinal detachment. Angiographic and neuroimaging findings are presented, and the importance of regular fundus examination is highlighted.

Topics: Child, Preschool; Drug Therapy, Combination; Enzyme Inhibitors; Exudates and Transudates; Facial Dermatoses; Fluorescein Angiography; Glucocorticoids; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Methotrexate; Methylprednisolone; Mycophenolic Acid; Retinal Detachment; Retinal Telangiectasis; Scalp Dermatoses; Scleroderma, Localized

To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events were documented. Seven patients with LoS were treated with MMF. Median age at MMF initiation was 15 years (range 7-74 years). Three patients received MMF due to MTX ineffectiveness and 4 due to MTX intolerance. Disease remission was achieved in 4 patients and maintained in one patient. One patient showed a favourable response, but had to discontinue treatment due to elevated liver enzymes. The remaining patient experienced disease progression. MMF was shown to improve the clinical condition of patients with refractory LoS and may be a relatively safe alternative in patients who are intolerant to MTX.

Topics: Adolescent; Adult; Aged; Child; Disease Progression; Drug Resistance; Drug Substitution; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Remission Induction; Retrospective Studies; Scleroderma, Localized; Severity of Illness Index; Skin; Time Factors; Treatment Outcome; Young Adult

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

We present two young patients with morphea or localized scleroderma undergoing systemic treatment, who developed papular lesions on pre-existing sclerotic plaques. Histology was compatible with a papular presentation of morphea and other entities in the differential diagnosis were ruled out. We believe this is a very uncommon presentation of activity in lesions of morphea and should be made known to clinicians so that activity and progression of the disease can be recognized and treated to avoid complications.

Topics: Adolescent; Anti-Inflammatory Agents; Child; Diagnosis, Differential; Disease Progression; Drug Therapy, Combination; Female; Folic Acid; Humans; Hypopigmentation; Immunosuppressive Agents; Male; Methotrexate; Methylprednisolone; Mycophenolic Acid; Scleroderma, Localized; Vitamin B Complex

T lymphocytes induce the transformation of fibroblasts into myofibroblasts, the main mediators of fibrogenesis. The inosine 5'-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF) and the anti-CD25 monoclonal antibody daclizumab (DCZ) have been reported to suppress the proliferation of T lymphocytes.. To evaluate the preventive effects of MMF and DCZ in early stages of bleomycin (BLM)-induced scleroderma.. This study involved five groups of Balb/c mice (n = 10 per group). Mice in four of the groups were injected subcutaneously (SC) with BLM [100 μg/day in 100 μL phosphate-buffered saline (PBS)] for 4 weeks; the remaining (control) group received only 100 μL PBS. Three of the BLM-treated groups also received either intraperitoneal MMF 50 or 150 mg/kg/day, or SC DCZ 100 μg/week. At the end of the fourth week, all mice were killed, and blood and tissue samples were obtained for further analysis.. In the BLM-treated group, increases were seen in inflammatory-cell infiltration, α-smooth muscle actin-positive (α-SMA+) fibroblastic cell count, tissue hydroxyproline content, and dermal thickness. Dermal fibrosis was histopathologically prominent. In BLM-treated mice also given MMF or DCZ, inflammatory-cell infiltration, tissue hydroxyproline content and dermal thickness were decreased. In the MMF groups, decreases were also noted in α-SMA+ fibroblastic cell count.. In this BLM-induced dermal fibrosis model, MMF and DCZ treatments prevented the development of dermal fibrosis. Further studies are needed to evaluate whether targeting T lymphocytes is effective in resolving pre-existing fibrosis in human scleroderma.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal, Humanized; Bleomycin; Cytokines; Daclizumab; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Hydroxyproline; Immunoglobulin G; Immunohistochemistry; Immunosuppressive Agents; Injections, Subcutaneous; Mice; Mice, Inbred BALB C; Mycophenolic Acid; Scleroderma, Localized; Skin

A 46-year-old man presented with suberythrodermia and an acral-accentuated sclerosis, which had been progressing over the past 6 months, with extensive, painful ulcers within the sclerotic areas of the calf. Due to acute myelotic leukemia (AML), an allogenic peripheral blood stem-cell transplantation with subsequent immunosupression with mycophenolatmofetil (MMF) and ciclosporin A had been performed 8 years previously. The patient had discontinued treatment on his own after about 2 years, having suffered a cerebroischemic insult in the meantime.. Histological examinations revealed sclerodermatous changes. Titres of antinuclear antibodies were unremarkable. Laser-Doppler-flowmetry also indicated an active inflammatory and sclerosing process. FACS analysis of the peripheral blood did not reveal signs of AML recurrence.. The histological pattern in conjunction with the anamnesis indicated a cutaneous chronic graft-versus-host disease (GvHD). No further organ involvement was observed. The MMF therapy which the patient had discontinued was restarted. In addition, PUVA therapy was initiated. These measures and intensive physiotherapeutic exercises in parallel prevented further progression of the sclerosis and secondary mobility limitations. The ulcers healed completely with pentoxifylline and anti-infective treatment.. After stem-cell transplantation, early diagnosis of GvHD is especially important due to possible irreversible sclerodermatous changes and other organ manifestations. Also for this reason, strict clinical follow-up is especially important with respect to compliance and efficacy of the immunosuppression.

Topics: Anti-Infective Agents; Cyclosporine; Graft vs Host Disease; Humans; Immunosuppressive Agents; Laser-Doppler Flowmetry; Leg Ulcer; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycophenolic Acid; Patient Compliance; Pentoxifylline; Peripheral Blood Stem Cell Transplantation; Physical Therapy Modalities; PUVA Therapy; Scleroderma, Localized; Transplantation, Homologous; Vasodilator Agents

To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of severe refractory juvenile localized scleroderma (JLS).. A retrospective chart review was performed in patients with JLS who had been treated with MMF after the failure of a combination of MTX and corticosteroids for at least 4 months, or whose JLS had concomitant severe extracutaneous manifestations. Outcome was assessed through clinical examination and thermography. Adverse events were recorded.. Ten patients (six females and four males) were enrolled in the study. JLS clinical subtypes were deep morphoea (two patients with disabling pansclerotic morphoea), generalized morphoea (three patients), linear scleroderma (five patients) affecting the limbs in two and face in three patients (en coup de sabre). The age at onset of disease was 8 (range 2-16) years, and the disease duration at the time of treatment with MMF was 18 (range 8-62) months. All MMF-treated patients experienced clinical improvement that allowed withdrawal or reduction of doses of corticosteroids and MTX. Over a follow-up of 27 (range 6-36) months, mild abdominal discomfort was reported in only one patient.. MMF appears to be effective in arresting disease progression in severe or MTX-refractory JLS and is generally well tolerated. Further controlled studies are needed to confirm these data.

Topics: Adolescent; Child; Child, Preschool; Drug Evaluation; Drug Resistance; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Retrospective Studies; Scleroderma, Localized; Treatment Outcome

Topics: Adrenal Cortex Hormones; Adult; Biopsy, Needle; Follow-Up Studies; Graft vs Host Disease; Humans; Immunohistochemistry; Lichen Sclerosus et Atrophicus; Male; Mycophenolic Acid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Scleroderma, Localized; Stem Cell Transplantation; Treatment Outcome

Topics: Anti-Inflammatory Agents, Non-Steroidal; Combined Modality Therapy; Female; Humans; Mycophenolic Acid; Photopheresis; Scleroderma, Localized

Cyclosporin and mycophenolate mofetil (MMF) are immunosuppressant agents now used frequently in the field of organ transplantation. More recently cyclosporin has been used for the treatment of a number of dermatological conditions, including severe psoriasis and eczema. Extensive diffuse morphoea is very difficult to treat. PUVA, UVA and a number of immunomodulating drugs have been used to attempt improvement but are most beneficial only in early disease. Combination treatments are often used in psoriasis, for example, but are not reported in morphoea. We present the case of a patient treated initially with cyclosporin and PUVA and subsequently with MMF and PUVA, with considerable improvement in his condition.

Topics: Adult; Combined Modality Therapy; Cyclosporine; Disease Progression; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; PUVA Therapy; Scleroderma, Localized

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA(1) therapy (single dose, 20 J/cm(2), 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease.

Topics: Adult; Bone Marrow Transplantation; Chronic Disease; Combined Modality Therapy; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Scleroderma, Localized; Ultraviolet Therapy