mycophenolic-acid and Edema

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

The appearance of edema limits the use of everolimus de novo together with tacrolimus and steroids in kidney transplantation. We aimed to investigate the frequency and characteristics of patients with edema and compare them according to the type of immunosuppression.. We studied 150 kidney transplant recipients between 2015 and 2017 based on receiving everolimus de novo (group A) or mycophenolic acid derivatives (group B).. We analyzed 50 patients in group A and 100 in group B. Follow-up was 26.2 ± 10 months. Fifty-six patients presented edema (37.3%): 54% in group A and 29% in group B (P = .003). Edema was mild in 74% of patients in group A and 57.1% in group B. The probability of edema was 10.1%, 22.4%, and 41% at 3, 6, and 12 months, respectively, in group A vs 10.1%, 20.3%, and 25.4% in group B (P = .006). Patients were treated mostly with diuretics (14.3% in group A vs 27.6% in group B) and discontinuation of calcium channel blockers (46.4% in group A vs 48.3% in group B). Improvement was 70.4% in group A vs 60.7% in group B; patient worsening was 0% in group A vs 10.7% in group B; and there was no change in 29.6% in group A vs 28.6% in group B. We did not find differences in patient or graft survival in those who presented edema, regardless of the treatment group.. The use of everolimus and standard doses of tacrolimus caused edema in 54% of patients, with no impact on renal function or survival compared with mycophenolic acid derivatives. The edema was mostly of low intensity and improved in most patients.

Topics: Edema; Everolimus; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Mycophenolic Acid; Tacrolimus

Topics: Abdomen; Abdominal Pain; Acute Kidney Injury; Administration, Intravenous; Adult; Anti-Inflammatory Agents; Ascites; Asthenia; Contrast Media; Creatinine; Disease Progression; Edema; Enzyme Inhibitors; Female; Humans; Jejunum; Lupus Erythematosus, Systemic; Methylprednisolone; Mycophenolic Acid; Prednisone; Tomography, X-Ray Computed; Ultrasonography; Vomiting

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

Topics: Adipose Tissue; Alopecia; Edema; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Scalp Dermatoses

Hypocomplementemic urticarial vasculitis syndrome is a rare disorder characterized by chronic urticarial vasculitis, arthralgia, arthritis, and hypocomplementemia. Previously, only six patients with concomitant hypocomplementemic urticarial vasculitis syndrome, Jaccoud's arthropathy, and valvular heart disease have been reported.. A 30-year-old Korean man presented with hypocomplementemic urticarial vasculitis syndrome. In addition to urticarial cutaneous lesions, he experienced polyarthralgia and arthritis that resulted in progressive deformity of the joints of both hands, cardiac valvulopathy with mitral, tricuspid, and aortic regurgitation, and intermittent neck swelling with laryngeal edema. He also developed nephritis with azotemia. His renal biopsy results revealed membranoproliferative glomerulonephritis, type I. He showed a partial response to a combination therapy of steroid, cyclophosphamide, and mycophenolate mofetil.. We describe, to the best of our knowledge, the first case of glomerulonephritis presenting a arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis syndrome. A combination of corticosteroids, cyclophosphamide, and mycophenolate mofetil appear to be a safe and effective treatment for nephropathy, however are less effective for cutaneous vasculitis, cardiac valvulopathy, and arthropathy.

Topics: Adult; Arthralgia; Arthritis; Biopsy; Complement System Proteins; Cyclophosphamide; Diagnosis, Differential; Drug Therapy, Combination; Edema; Glomerulonephritis, Membranoproliferative; Glucocorticoids; Heart Valve Diseases; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Urticaria; Vasculitis

We examined the experiences of heart transplant recipients receiving everolimus as maintenance therapy in different combinations over a long time.. Between 2004 and 2009, forty patients (29 men, 11 women; mean age, 51.6 y) were switched from a routine immunosuppressive regimen to everolimus. Indications were other (2), renal insufficiency (17), cardiac allograft vasculopathy (14), and ongoing cellular rejection (7). Combinations were either along with cyclosporine (24), mycophenolate mofetil (14), or others (2). Indications for the introduction of everolimus including safety, efficacy, different combinations of everolimus, biopsy-proven acute rejections, renal function, and infections were evaluated retrospectively.. Five patients died, 4 of them were still on everolimus at the time of death; they died from intracerebral hemorrhage (1), embolism (1), cardiac arrest (2), and unknown (1). Everolimus was discontinued in 6 patients owing to severe adverse effects: Edema (2), gastrointestinal adverse effects (3), and dermal adverse effects (1). Mean everolimus trough levels were 5.8 μmol/L at 6 months and 4.9 at 60 months. Mean cyclosporine levels were 67.62 μmol/L at 6 months and 47.3 μmol/L at 60 months. Mean serum creatinine levels were stable (147.9 μmol/L after 60 months). Four life-threatening infections (all pneumonia) occurred but resulted in complete recovery.. Everolimus is safe with different immunosuppressive combinations after receiving a heart transplant.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Cyclosporine; Drug Therapy, Combination; Edema; Everolimus; Female; Gastrointestinal Diseases; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Incidence; Longitudinal Studies; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Sirolimus; Treatment Outcome

Septic arthritis (SA) typically occurs in young children, often from Staphylococcus. With chronic immunosuppression, however, pathogens may be atypical. A 15-year-old African-American female developed Mycoplasma hominis SA in her right hip 2 months following cadaveric renal transplant (Tx). Her presentation was subtle and indolent, without fever or leukocytosis. Although reported in adult Tx recipients, M. hominis infections have not been described in pediatric recipients. Early immunosuppression (basiliximab, prednisone, tacrolimus, mycophenolate mofetil and Thymoglobulin) may have increased her susceptibility to M. hominis. Optimal therapy for M. hominis SA is not well established and relapses occur. This patient underwent joint incision and drainage, treatment for 8 weeks with doxycycline and levofloxacin guided by in vitro sensitivities, and a reduction in immunosuppression. She has been free of ongoing infection for 3 years with stable graft function (Cr 1.1 mg/dL) on moderate immunosuppression with prednisone, tacrolimus and MMF.

Topics: Adolescent; Arthritis, Infectious; Doxycycline; Edema; Female; Graft Survival; Hip; Humans; Immunocompromised Host; Immunosuppressive Agents; Inflammation; Kidney Transplantation; Levofloxacin; Magnetic Resonance Imaging; Mycophenolic Acid; Mycoplasma hominis; Ofloxacin; Pelvis; Prednisone; Radiography; Tacrolimus; Treatment Outcome

Topics: Adult; Creatinine; Cyclosporine; Edema; Female; Follow-Up Studies; Hemolytic-Uremic Syndrome; Hemorrhage; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Optic Nerve; Time Factors