mycophenolic-acid and Alopecia

Topics: Adult; Alopecia; Azetidines; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Janus Kinase 1; Janus Kinase 2; Janus Kinase Inhibitors; Lupus Erythematosus, Systemic; Mycophenolic Acid; Prednisolone; Purines; Pyrazoles; Retreatment; Risk Assessment; Sulfonamides; Tacrolimus; Treatment Outcome

Topics: Alopecia; Anti-Inflammatory Agents; Cicatrix; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pemphigus; Scalp Dermatoses

Hemophagocytic lymphohistiocytosis is an aggressive life-threatening syndrome of excessive immune activation. Hemophagocytic lymphohistiocytosis due to systemic lupus erythematosus is described as acute lupus hemophagocytic syndrome. Acute lupus hemophagocytic syndrome presenting with negative antinuclear antibody is uncommon.. A 57-year-old Sri Lankan woman presented with intermittent fever, weight loss, episodic confusion, and alopecia for 3 months. Investigations showed pancytopenia. Her erythrocyte sedimentation rate was 76 mm/hour and C-reactive protein was 2 mg/l. Septic screen was negative except for a positive sputum culture for Gram-negative coliforms. Chest X-ray was normal. Direct antiglobulin test was positive. Fever persisted with clinical worsening despite treatment with intravenous antibiotics. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were negative. Bone marrow aspiration revealed features compatible with hemophagocytosis. Her serum ferritin and triglycerides were elevated. Diagnosis of hemophagocytic lymphohistiocytosis due to an evolving autoimmune disorder was made and she was treated with steroids. She showed a dramatic improvement and was discharged on oral steroids. After 6 months, while the steroids were being tapered she experienced oral ulcers, frothy urine, and ankle swelling and she was rehospitalized. Urine analysis revealed proteinuria with active sediment. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were positive. Complement C3 and C4 were reduced. A renal biopsy revealed class IV-G lupus nephritis with immunofluorescence pattern consistent with systemic lupus erythematosus. Steroid dose was increased and mycophenolate mofetil was commenced. She improved.. This case showcases an uncommon presentation of acute lupus hemophagocytic syndrome with initial negative antinuclear antibody probably due to its cytokine-mediated pathogenesis. This is the first such reported case in South Asia to the best of our knowledge. According to the American College of Rheumatology criteria, our patient did not fulfill the criteria for systemic lupus erythematosus diagnosis for the initial hospitalization. But, according to the 2012 Systemic Lupus International Collaborating Clinics criteria, she did fulfill the criteria for systemic lupus erythematosus even in the first hospitalization which was subsequently proven with renal biopsy findings. This case confirms the increased sensitivity of Systemic Lupus International Collaborating Clinics criteria over American College of Rheumatology criteria in diagnosis of systemic lupus erythematosus.

Topics: Alopecia; Confusion; Female; Fever; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Mycophenolic Acid; Pancytopenia; Proteinuria; Steroids; Treatment Outcome; Weight Loss

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.

Topics: Alanine Transaminase; Alopecia; Antibiotics, Antineoplastic; Aspartate Aminotransferases; Azathioprine; Female; Hepatitis, Autoimmune; Humans; Liver; Middle Aged; Mycophenolic Acid; Pancytopenia; Prednisolone

Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, has anti-inflammatory effects, and is widely used as an immunomodulatory agent. However, the beneficial effect of MPA in hair-loss disorders is not fully understood.. To investigate the direct effect of MPA on dermal papilla cells (DPCs), and to examine the hair growth-stimulating effects of MPA topically applied to mouse skin.. Cultured DPCs were treated with various concentrations of MPA and analysed by MTT assay. Expressions of hair growth-related genes, including Wnt/β-catenin pathway-related genes and cellular apoptosis-regulating genes, such as Bcl-2, Bax and caspase-9, were examined using reverse transcription (RT)-PCR and western blotting. The Wnt/extracellular signal-regulated kinase (ERK) pathway was analysed by western blotting. The effect of topically applied MPA on anagen hair follicle induction after microneedle (MN) treatment with or without minoxidil (MXD) was evaluated by histopathological examination and RT-PCR.. MPA showed a promoting effect on DPC proliferation, which was associated with increased Axin2 transcription levels. In addition, phospho-ERK protein was detected in the MPA-treated DPCs. An increased Bcl-2/Bax transcript ratio contributed to cellular proliferation, and this was maintained in the MPA-treated environment. Topically applied MPA promoted anagen hair follicle induction in mice. The effect of MPA on hair follicles was compatible with that of MXD, and this effect was accelerated by MN treatment.. MPA promotes proliferation of DPCs and induction of anagen hair follicles in mice. This finding raises the possibility that MPA could be used as a treatment option for hair-loss disorders.

Topics: Alopecia; Animals; Apoptosis; Blotting, Western; Cell Proliferation; Cells, Cultured; Dermis; Disease Models, Animal; Female; Gene Expression Regulation; Growth Substances; Hair Follicle; Immunosuppressive Agents; Mice; Mice, Inbred C3H; Mitogen-Activated Protein Kinases; Mycophenolic Acid; Proto-Oncogene Proteins; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transforming Growth Factor beta; Wnt Signaling Pathway

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

Recently, various immunosuppressant drugs have been shown to induce hair growth in normal hair as well as in alopecia areata and androgenic alopecia; however, the responsible mechanism has not yet been fully elucidated. In this study, we investigate the influence of mycophenolate (MPA), an immunosuppressant, on the proliferation of human dermal papilla cells (hDPCs) and on the growth of human hair follicles following catagen induction with interferon (IFN)-γ. IFN-γ was found to reduce β-catenin, an activator of hair follicle growth, and activate glycogen synthase kinase (GSK)-3β, and enhance expression of the Wnt inhibitor DKK-1 and catagen inducer transforming growth factor (TGF)-β2. IFN-γ inhibited expression of ALP and other dermal papillar cells (DPCs) markers such as Axin2, IGF-1, and FGF 7 and 10. MPA increased β-catenin in IFN-γ-treated hDPCs leading to its nuclear accumulation via inhibition of GSK3β and reduction of DKK-1. Furthermore, MPA significantly increased expression of ALP and other DPC marker genes but inhibited expression of TGF-β2. Therefore, we demonstrate for the first time that IFN-γ induces catagen-like changes in hDPCs and in hair follicles via inhibition of Wnt/β-catenin signaling, and that MPA stabilizes β-catenin by inhibiting GSK3β leading to increased β-catenin target gene and DP signature gene expression, which may, in part, counteract IFN-γ-induced catagen in hDPCs.

Topics: Alopecia; beta Catenin; Cell Division; Cells, Cultured; Dermis; Drug Evaluation, Preclinical; Gene Expression Profiling; Gene Expression Regulation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hair Follicle; Humans; Immunosuppressive Agents; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Mycophenolic Acid; Transforming Growth Factor beta2; Wnt Signaling Pathway

Lichen planopilaris (LPP) is a chronic inflammatory disorder that causes permanent scalp hair loss and significant patient discomfort.. We sought to determine the efficacy and safety of mycophenolate mofetil (MMF) for treatment of LPP in patients who had failed prior topical, intralesional, or oral anti-inflammatory medications such as hydroxychloroquine or cyclosporine.. We conducted a retrospective chart review of 16 adult patients with LPP treated with at least 6 months of MMF in an open-label, single-center study from 2003 to 2007. Subjective and objective end points were quantified using the LPP Activity Index (LPPAI) and scores before and after treatment were assessed using a paired t test. Adverse events were monitored.. Patients who completed treatment with MMF had significantly decreased signs and symptoms of active LPP despite having failed multiple prior therapies (P < .005). Five of 12 patients were complete responders (LPPAI score decreased>85%), 5 of 12 patients were partial responders (LPPAI score decreased 25%-85%), and two of 12 patients were treatment failures (LPPAI score decreased<25%). Four patients withdrew from the trial because of adverse events.. Retrospective analysis and small sample size were limitations.. MMF was effective at reducing the signs and symptoms of active LPP in 83% of patients (10 of 12) who had failed multiple prior treatments after at least 6 months of treatment.

Topics: Adult; Aged; Alopecia; Female; Humans; Immunosuppressive Agents; Lichen Planus; Male; Middle Aged; Mycophenolic Acid; Scalp Dermatoses; Severity of Illness Index

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession. Currently, there are no evidence-based studies to guide treatment for patients with FFA; thus, treatment options vary among clinicians.. We report clinical findings and treatment outcomes of 36 patients with FFA, the largest cohort to date. Further, we report the first evidence-based study of the efficacy of hydroxychloroquine in FFA using a quantitative clinical score, the Lichen Planopilaris Activity Index (LPPAI).. A retrospective case note review was performed of 36 adult patients with FFA. Data were collected on demographics and clinical findings. Treatment responses to hydroxychloroquine, doxycycline and mycophenolate mofetil were assessed using the LPPAI. Adverse events were monitored.. Most patients in our cohort were female (97%), white (92%) and postmenopausal (83%). Apart from hairline recession, 75% also reported eyebrow loss. Scalp pruritus (67%) and perifollicular erythema (86%) were the most common presenting symptom and sign, respectively. A statistically significant reduction in signs and symptoms in subjects treated with hydroxychloroquine (P < 0·05) was found at both 6- and 12-month follow up.. In FFA, hairline recession, scalp pruritus, perifollicular erythema and eyebrow loss are common at presentation. Despite the limitations of a retrospective review, our data reveal that hydroxychloroquine is significantly effective in reducing signs and symptoms of FFA after both 6 and 12 months of treatment. However, the lack of a significant reduction in signs and symptoms between 6 and 12 months indicates that the maximal benefits of hydroxychloroquine are evident within the first 6 months of use.

Topics: Adult; Aged; Aged, 80 and over; Alopecia; Anti-Bacterial Agents; Cohort Studies; Dermatologic Agents; Doxycycline; Enzyme Inhibitors; Erythema; Eyebrows; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Mycophenolic Acid; Pruritus; Retrospective Studies; Scalp; Severity of Illness Index; Time Factors

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.

Topics: Activities of Daily Living; Adult; Alopecia; Amenorrhea; Cyclophosphamide; Drug Evaluation; Fatigue; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Infections; Kidney Function Tests; Lupus Nephritis; Male; Middle Aged; Mycophenolic Acid; Patient Acceptance of Health Care; Prednisolone; Quality of Life; Remission Induction; Retrospective Studies; Severity of Illness Index

Mycophenolate mofetil (MMF) is an immunosuppressive drug that has recently been used to treat autoimmune and inflammatory skin diseases. We report the first case of lichen planopilaris (LPP) successfully treated with MMF. The treatment of our patient demonstrates a novel therapeutic option for patients with LPP; MMF treatment may be preferable to azathioprine treatment because MMF has a safer adverse-effect profile. Larger studies must be performed to establish the risk-benefit ratio of various therapeutic dosages of MMF for these patients.

Topics: Adult; Alopecia; Humans; Immunosuppressive Agents; Lichen Planus; Male; Mycophenolic Acid; Pruritus; Remission Induction; Scalp Dermatoses; T-Lymphocytes

Tufted hair folliculitis (THF) is a rare disease which is characterized by the emergence of multiple hairs from widely dilated follicular orifices surrounded by an inflammatory infiltrate resulting in scarring alopecia. The pathogenesis is not yet fully understood. Although colonization with Staphylococcus aureus could not always be detected and systemic treatment with antibiotics alone is not sufficient, this microorganism is considered to play an important role. Around 30 patients with THF have been reported since the first publication. We present a patient with pemphigus vulgaris who developed THF. To our knowledge, this is the fourth case with an association of these two entities. Amongst other causing mechanisms, the autoimmune reaction may play an important role for the development of THF.

Topics: Administration, Topical; Alopecia; Anti-Infective Agents, Local; Anti-Inflammatory Agents; Dermatologic Agents; Drug Therapy, Combination; Folliculitis; Glucocorticoids; Humans; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pemphigus; Povidone-Iodine; Staphylococcal Skin Infections; Staphylococcus aureus