Materiały źródłowe

• #1 Management of pemphigus vulgaris: challenges and solutions

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4622091/

  The main objective in the treatment of pemphigus vulgaris is to control the disease, prevent relapses, and avoid adverse events associated with the prolonged use of steroids and immunosuppressive agents. Systemic corticosteroids remain the gold standard treatment for pemphigus vulgaris. Azathioprine and mycophenolate mofetil are the first line of steroid-sparing treatment. Rituximab is extremely effective in recalcitrant pemphigus, when other treatments fail to control the disease. […] The primary objective of the therapeutic management of PV is initially to control the disease, heal the bullous skin and mucous lesions, and minimize the associated functional impairment. Subsequently, the real challenge is to prevent relapses in the long run and avoid adverse events associated with the prolonged use of steroids and immunosuppressive agents.

• #1 Pemphigus Vulgaris: A Complete Overview — DermNet

  https://dermnetnz.org/topics/pemphigus-vulgaris

  The primary aim of treatment of pemphigus vulgaris is to decrease blister formation, prevent infections and promote healing of blisters and erosions. Systemic corticosteroids are the mainstay of medical treatment for controlling the disease, usually in the form of moderate to high doses of oral prednisone or prednisolone, or as pulsed intravenous methylprednisolone. Since their use, many deaths from pemphigus vulgaris have been prevented (the mortality rate dropped from 99% to 515%). Corticosteroids are not a cure for the disease but improve the patient’s quality of life by reducing disease activity. The doses of corticosteroids needed to control pemphigus vulgaris and the length of time on treatment may result in serious side effects and risks. […] Other immunosuppressive drugs (mostly off-label) used to reduce the dose of steroids and may be required by patients with pemphigus vulgaris for years. These are most often: Azathioprine, Mycophenolate mofetil, Cyclophosphamide, Rituximab, which is now approved by the Food and Drug Administration (FDA) in the US.

• #1 Pemphigus – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pemphigus/diagnosis-treatment/drc-20350409

  Treatment for pemphigus usually starts with medicines to ease symptoms and prevent new blisters. These may include steroids and medicines that target the immune system. If your symptoms were caused by use of certain medicines, stopping that medicine may be enough to clear up your symptoms. […] Your healthcare professional may suggest one or more of the following medicines. The choice of medicines depends on the type of pemphigus you have, how severe your symptoms are and whether you have other medical conditions. […] For people with mild disease, corticosteroid cream or injections may be enough to control it. For others, the main treatment is a corticosteroid medicine taken by mouth, such as prednisone pills. […] Using corticosteroids for a long time or in high doses may cause severe side effects. These include diabetes, bone loss, an increased risk of infection, stomach ulcers and a shift of body fat.

• #1 Pemphigus: Diagnosis, Treatment, and Steps to Take

  https://www.niams.nih.gov/health-topics/pemphigus/diagnosis-treatment-and-steps-to-take

  There is no cure for pemphigus, but treatment can control the disease in most people. The initial goal of treatment is to clear existing blisters and help prevent relapses. Treatment typically depends on the severity and stage of the disease. […] Symptoms of pemphigus may go away after many years of treatment, but most people need to continue taking medications to keep the disease under control. Treatment for pemphigus may involve the following medications: […] Corticosteroids. These anti-inflammatory medicines are a mainstay of treatment for pemphigus. They may be applied topically as a cream or ointment, or by mouth or injection (systemically). Most people will be prescribed systemic corticosteroids, at least initially, to bring the disease under control. Because they are potent drugs, your doctor will prescribe the lowest dose possible to achieve the desired benefit.

• #1 Pemphigus – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pemphigus/diagnosis-treatment/drc-20350409

  To avoid these side effects, steroids may be used only for short periods of time to control flare-ups. And other medicines that target the immune system may be used long term to control the disease. […] Some medicines can stop your immune system from attacking healthy tissues. Examples are azathioprine (Imuran, Azasan), mycophenolate (Cellcept) and cyclophosphamide. […] If first line medicines aren’t helping you, your healthcare professional may suggest another drug, such as dapsone, intravenous immunoglobulin or rituximab-pvvr (Ruxience). […] Many people with pemphigus get better, especially if treatment is started early. But it may take years and can require taking medicine for a long time.

• #1 Treatments – IPPF

  https://www.pemphigus.org/treatments/

  Corticosteroids mimic the effect of the adrenal hormones your body naturally produces. Systemic corticosteroids are the most established therapy for the management of PV. In most cases, when used in high doses, they can rapidly control disease. The most common corticosteroids include Prednisone and Prednisolone. […] Once controlled, steroid use is slowly reduced to minimize side effects. Some patients then go into remission; however, many need a small maintenance dose to keep the disease under control. […] Topical steroids can be used for the treatment of pemphigus. To address oral erosion, steroid mouthwash, paste, ointment or aerosol can be used. Topical cyclosporine can also be used for the treatment of oral pemphigus lesions. […] Azathioprine (Imuran, Azasan) is used after initial treatment to manage pemphigus.

• #1 Treatment of pemphigus – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/treatment-of-pemphigus/

  Bystrin recommends adjuvant therapies only if there are relative contraindications to the use of corticosteroids or if the corticosteroid dose cannot be reduced because of repeated flares in disease activity. […] The rationale to use drugs other than corticosteroids to treat pemphigus is that they may reduce the need for corticosteroids and hence their side effects and may result in better control of the disease. […] Immunosuppressives are usually started after prednisolone has been tapered to 40mg daily. […] Cyclophosphamide appears to be more effective than azathioprine, but toxicity is more which includes bone marrow suppression, hemorrhagic cystitis, bladder fibrosis, sterility and increased risk of malignancy. […] Major toxicities of azathioprine include bone marrow suppression, hepato toxicity and a possible increased risk of malignancy.

• #1 Treatments – IPPF

  https://www.pemphigus.org/treatments/

  Mycophenolate (CellCept, Myfortic) is composed of several penicillium species that is used after initial treatment for pemphigus. […] Cyclophosphamide (Cytoxan) is an oral cyclophosphamide that is considered an alternative to azathioprine. Due to the potential toxicities, this drug should be reserved for patients who do not respond to other immunosuppressives. […] Rituximab is a B-cell antibody treatment option for patients with pemphigus that is being used as first line therapy by many clinicians. In June 2018, the FDA approved Rituxan for the treatment of adults with moderate to severe PV. […] Intravenous Immunoglobulin (IVIG) therapy is prepared from extracting the plasma in human blood. IVIG is given intravenously; under the skin via a syringe or catheter. The dosage required is patient-specific. To treat pemphigus, the doses are as high as 2000mg/kg.

• #1

  https://insight.jci.org/articles/view/92021

  Despite the rising incidence of autoimmunity, therapeutic options for patients with autoimmune disease still rely on decades-old immunosuppressive strategies that risk severe and potentially fatal complications. […] Current treatment strategies include topical and systemic corticosteroids in combination with other immunosuppressants, most often azathioprine or mycophenolate, although only a few randomized clinical trials have proven their efficacy. […] Treatment with the anti-CD20 antibody rituximab has been shown to be effective in inducing short-term disease remission in 95%-100% of PV patients associated with a decrease in anti-DSG antibody titers. […] However, 81% of pemphigus patients experience disease relapse after rituximab, and analyses of rituximab use in pemphigus and other autoimmune diseases demonstrated a 1.3%-1.9% rate of fatal infection, indicating the need for safer and more durable therapies.

• #1 Pemphigus Vulgaris (PV) | Diagnosis, Treatment & Management

  https://medically.roche.com/global/en/microsites/about-pv/pv-treatment-management.html

  For the therapeutic management of PV, the consensus group recommends corticosteroids or anti-CD20 monoclonal antibodies as first-line treatment. […] Systemic corticosteroids can be combined with an immunosuppressive adjuvant at the onset of therapy, especially in cases of increased risk of corticosteroid therapy, complications due to expected prolonged use, or dose dependency above minimal therapy. […] Anti-CD20 monoclonal antibody (rituximab) is recommended for first-line treatment in new onset moderate to severe pemphigus and/or for patients who do not achieve clinical remission with corticosteroids and/or immunosuppressive adjuvants. […] Once patients have started treatment, it is important to monitor the efficacy and safety of the treatment and to plan the gradual reduction of immunosuppressive treatment and the duration of maintenance therapy or its discontinuation.

• #1 Treatment of pemphigus vulgaris | PPA

  https://www.dovepress.com/role-of-rituximab-in-the-treatment-of-pemphigus-vulgaris-patient-selec-peer-reviewed-fulltext-article-PPA

  Moreover, differences in patient and disease characteristics that are highlighted in the literature strongly suggest that therapy should be tailored individually on a case-by-case basis: personalized treatment schedules may be necessary to optimize response to treatment and tolerability in different subjects, with the possibility of repeated infusions for severe forms and in case of relapse. […] In conclusion, the current literature suggests that lower-dose regimens of rituximab are not only tolerable and cost-effective but may also be associated with a positive response in pemphigus vulgaris, comparable to that achieved with higher doses especially in early disease. […] The optimal RTX regimen for PV has not been established yet. […] A 2021 review collected published evidence on the use of low-dose RTX for the treatment of PV: nine studies were included, with RTX dosages varying between modified dose (3375mg/m2 or 3500mg), low dose (2375mg/m2 or 2500mg), and ultra-low dose (500mg for a cycle, either single or multiple infusions).

• #1 Efficacy of Repeated Courses of Rituximab as Treatment for Pemphigus Vulgaris | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3649

  Rituximab targets the B-lymphocyte antigen CD20, providing pemphigus vulgaris patients with long-term remissions. However, the effects of repeated courses have not yet been established. This study aimed to evaluate the effect of repeated rituximab courses on remission length in pemphigus vulgaris. […] Rituximab remained efficacious in each course, irrespective of previous treatments (complete remission 75-81%). Following the 2nd and 3rd courses, the results indicated longer remissions with reduced flare-ups, and the remission length increased with each subsequent course. We conclude that rituximab serves as a disease-modifying agent, notably for patients with moderate-to-severe pemphigus vulgaris. […] A proportion of patients with pemphigus vulgaris treated with rituximab achieve complete remission; nevertheless, relapses generally occur at 6-12 months after the first treatment. We observed that with repeated cycles of treatment with rituximab, high efficacy is maintained and remission can be induced despite failures in previous cycles. With each subsequent cycle, an improvement is observed, with a substantially longer remission time, thus we conclude that rituximab is a potent disease-modifying agent in these patients.

• #1 Pemphigus: Diagnosis, Treatment, and Steps to Take

  https://www.niams.nih.gov/health-topics/pemphigus/diagnosis-treatment-and-steps-to-take

  Biologic response modifiers (or biologics). These target specific immune messages and interrupt the signal, helping to stop the immune system from attacking the skin. Rituximab is an approved biologic administered directly in the vein. It targets and depletes the immune cells that ultimately make the disease-causing antibodies. […] Antibiotics, antivirals, and antifungal medications to control or prevent infections. […] If the above treatments do not work or are not tolerated, other treatments may be considered. These treatments include: […] Immunosuppressants. Although less effective than rituximab, these are oral medications that help suppress or curb the overactive immune system and may help to lower the dose of daily steroid. […] Plasmapheresis or immunoadsorption. These are procedures that remove or dilute out damaging antibodies from the blood. […] Intravenous immunoglobulin therapy. This is an intravenous infusion of pooled antibodies from 1,000 or more healthy blood donors, which dilute out the bad antibodies and calm inflammation. […] Be sure to report any problems or side effects from medications to your doctor.

• #1 Refractory pemphigus vulgaris: Treatment options – Journal of Skin and Sexually Transmitted Diseases

  https://jsstd.org/refractory-pemphigus-vulgaris-treatment-options/

  Additional doses of rituximab are found effective in relapsed cases or in patients who fail to achieve remission after a single cycle of rituximab. […] Intravenous immunoglobulin Is effective for refractory pemphigus, it is used as adjuvant therapy to systemic corticosteroids and immunosuppressive adjuvants. […] Immunoadsorption- It is a therapeutic option for pemphigus. It exerts effect through the removal of circulating autoantibodies (IgG) with very high specificity. […] Plasmapheresis is an effective adjuvant therapy in severe pemphigus vulgaris patients for disease activity control by reducing serum levels of autoantibodies. […] Other therapies for pemphigus includes: Topical tacrolimus and pimecrolimus, Sulfasalazine with pentoxifylline, Gold, Tetracyclines with or without nicotinamide, Chlorambucil, Mizoribine, Subcutaneous veltuzumab. […] Meticulous research on the immunology and cell biology of pemphigus vulgaris should be a top priority since safer and more effective treatment options are the need of the hour for this potentially fatal autoimmune disease.

• #1 Emerging treatment options for the management of pemphigus vulgaris | TCRM

  https://www.dovepress.com/emerging-treatment-options-for-the-management-of-pemphigus-vulgaris-peer-reviewed-fulltext-article-TCRM

  Azathioprine is one of the main adjuvants used in the treatment of PV and is recommended as a first-line adjuvant immunosuppressant, according to both the EDF and BAD guidelines. […] MMF is a safe steroid-sparing agent that is recommended as a first-line adjuvant immunosuppressant, based on both the EDF and BAD guidelines. […] Rituximab is indicated for patients who remain dependent on 10 mg prednisolone in combination with an immunosuppressive adjuvant, according to the EDF guidelines. […] Plasmapheresis is a useful adjuvant therapy for quickly reducing the titers of circulating autoantibodies. This procedure should be considered for rapid control of severe pemphigus unresponsive to a combination of prednisone and immunosuppressive agents. […] Immunoadsorption is recommended as a second-line adjuvant agent by the EDF guidelines and as a third-line therapy by the BAD guidelines.

• #1 Pemphigus Vulgaris – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/pemphigus-vulgaris/

  Cyclophosphamide (50-200mg daily) is among the fastest agents for treating PV. However, its risk of blood count and liver test abnormalities, infertility, and hemorrhagic cystitis with bladder carcinoma, together with the advent of other effective therapies such as rituximab, have led to the decreased use of cyclophosphamide in the management of severe PV.

• #1 Emerging treatment options for the management of pemphigus vulgaris | TCRM

  https://www.dovepress.com/emerging-treatment-options-for-the-management-of-pemphigus-vulgaris-peer-reviewed-fulltext-article-TCRM

  Dapsone is recommended in combination with systemic corticosteroids at a dose of 100 mg/day (or 1.5 mg/kg/day) as a second-line steroid-sparing agent. […] Methotrexate at a dosage of 1020 mg/week is currently under consideration as a second-line steroid-sparing option in PV according to the EDF guidelines. […] Cyclophosphamide is considered a second-line immunosuppressive adjuvant agent, whereas the BAD guidelines consider cyclophosphamide as a third-line therapy. […] IVIg is usually administered in recalcitrant disease or in case of contraindications to immunosuppressive adjuvants, and is recommended as a second-line adjuvant by the EDF guidelines and as a third-line therapy by the BAD guidelines.

• #1 Treatments – IPPF

  https://www.pemphigus.org/treatments/

  Anti-inflammatory agents such as dapsone and tetracyclines are used as they also may have a steroid sparing effect in mild to moderate disease (e), often in patients who are in maintenance phase but corticosteroid-dependent. […] Dapsone must be started after glucose-6-P-dehydrogenase screening and is administered as 7.5mg/kg/day, up to 200mg/day. […] Tetracycline, doxycycline and minocycline have been used by some in glucocorticoid-dependent patients in the maintenance phase of therapy, often with niacinamide (nicotinamide). […] For multiple oral erosions, corticosteroid mouthwashes are practical, for example, soluble betamethasone sodium phosphate 0.5 mg tablet dissolved in 10 mL water may be used up to four times daily, holding the solution in the mouth for about 5 min. Isolated oral erosions could be treated with application of triamcinolone acetonide 0.1% in adhesive paste or clobetasol 0.05% gel. Topical cyclosporine (100 mg/ m1) in oral pemphigus has been described and may be of some benefit but is expensive.

• #1 Pemphigus Vulgaris: A Complete Overview — DermNet

  https://dermnetnz.org/topics/pemphigus-vulgaris

  Other medications that are sometimes used in pemphigus (often in combination) include: Dapsone, Methotrexate, Tetracyclines, Nicotinamide, Plasmapheresis, Intravenous immunoglobulin, Extracorporeal photopheresis, Immunoadsorption, The TNF inhibitor, infliximab. […] Topical therapy for cutaneous pemphigus vulgaris may include topical steroids and emollients. Treatment of mucosal pemphigus vulgaris may include various formulations of a topical steroid, intralesional steroid, topical tacrolimus, or topical ciclosporin. […] Appropriate wound care is particularly important, as this should promote healing of blisters and erosions. […] Patients should minimise activities that may traumatise the skin and mucous membranes during active phases of the disease. These include activities such as contact sports and eating or drinking food that may irritate or damage the inside of the mouth (spicy, acidic, hard and crunchy foods).

• #1 Pemphigus Vulgaris – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/pemphigus-vulgaris/

  Treatment options are summarized in Table I. […] Class I steroids, such as clobetasol, can be applied twice daily to new blisters and erosions on both the face and body. Topical tacrolimus ointment may also be helpful, particularly for lesions on the face where chronic steroid therapy is undesirable. For mucosal disease, dexamethasone elixir, swish and spit 5cc once to twice daily, is easy to use. Clobetasol ointment or gel can also be applied directly to mucosal erosions. Dental trays (fitted by oral medicine) facilitate occlusion of topical steroids to the gingiva at night. […] For mild disease, (transient lesions that heal within 1 week), monotherapy with topical corticosteroids may be sufficient. Mild mucosal or mucocutaneous disease may also respond to tetracyclines plus niacinamide (doxycycline 100mg twice daily plus niacinamide 500mg three times daily).

• #1 Pemphigus Vulgaris (PV) | Diagnosis, Treatment & Management

  https://medically.roche.com/global/en/microsites/about-pv/pv-treatment-management.html

  The consensus group also provides recommendations on supportive treatment, such as proper dental care, intralesional injections of corticosteroids, topical treatment with potent corticosteroids, antiseptic baths, analgesics, local anesthetics and nutritional management, and prophylaxis against side effects in prolonged corticosteroid therapy.

• #1 Content – Health Encyclopedia – University of Rochester Medical Center

  https://www.urmc.rochester.edu/encyclopedia/content?contenttypeid=134&contentid=110

  These are common treatments for pemphigus vulgaris: […] Good oral healthcare. Blistering may affect the health of your mouth. So working with your dentist to take the best care of your teeth and gums is important. […] Oral prednisone and topical steroid creams. These may be prescribed to treat inflammation. […] Immune suppressants. These medicines may be a helpful alternative to steroids for long-term use. […] Plasmapheresis or intravenous immunoglobulin. People who do not respond to other forms of treatment may need more intensive treatments. This may include replacing blood plasma and infusions with healthy immunoglobulin. […] Pain management. Pain medicine or other pain management strategies may be used to help with painful blisters. […] Follow up. This condition may return, even after successful treatment. Go to all follow-up appointments.

• #1 Pemphigus: Types, Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/21130-pemphigus

  Treatment is unique to each person diagnosed with pemphigus and could include: […] Taking medicine to prevent infections and help your skin heal. […] Stopping the use of medicines that cause your symptoms. […] Wound care for blisters and sores. […] Your healthcare provider will treat your condition in stages. Most people go through all three stages of treatment, which include: […] Control: High doses of medications control the spread of blisters and begin healing existing ones. […] Consolidation: Steady doses of medications continue healing blisters until most clear up. […] Maintenance: Reduced levels of medications keep new blisters from forming. […] Medicines used to treat pemphigus include: […] Corticosteroids: Medication to reduce inflammation (swelling), delivered by mouth, by injection (a shot) or topically (ointments or creams).

• #1 Refractory pemphigus vulgaris: Treatment options – Journal of Skin and Sexually Transmitted Diseases

  https://jsstd.org/refractory-pemphigus-vulgaris-treatment-options/

  The European Dermatology Forum (EDF) proposed a usable treatment algorithm for use after the consolidation phase. One to three months are the time required for complete healing of the lesions. […] Tapering of steroids is initiated once disease control is attained. Prednisolone is tapered by 25% once in 2 weeks. When the daily dose of prednisolone reaches 20 mg, further tapering is attempted more slowly. Most of the patients could be managed with 5 mg reduction every 4 weeks once it reaches 20 mg. […] Addition of an immunosuppressant is advised if oral corticosteroids are given as monotherapy. Patients who were already receiving combination treatment of systemic corticosteroids and an immunosuppressant may be treated by substituting the first line immunosuppressant with another one of the same group (azathioprine and mycophenolate mofetil) or by adding a second line immunosuppressant including immunoadsorption, intravenous immunoglobulin, or rituximab.

• #1 Pemphigus: Updated Review and Emerging Therapies

  https://www.dermatologytimes.com/view/pemphigus-updated-review-and-emerging-therapies

  As in all forms of pemphigus, systemic corticosteroids are first-line in the treatment of PF. The treatment algorithm for PF is similar to that of PV. However, in localized forms of PF with a limited number of lesions, topical or intralesional corticosteroids can be used. […] Prior to corticosteroid therapy, PF was fatal in approximately 60% of patients. Fortunately, steroids and other immunosuppressive therapies have greatly reduced mortality. […] There are many new treatments currently being tested for pemphigus. Second and third generation anti-CD20 monoclonal antibodies, such as veltuzumab, ocrelizumab, and obinutuzumab, have higher binding affinities and induce a more robust B-cell depletion compared to rituximab. The development of these next generation anti-CD20 monoclonal antibodies could lead to major progress in the treatment of pemphigus. Bruton tyrosine kinase (BTK) inhibitors, which downregulate several B-cell functions, and efgartigimod, an engineered Fc fragment derived from human IgG1, are also being studied for use in pemphigus treatment. Recently, researchers have engineered chimeric autoantibody receptor (CAAR)-T cells that recognize Dsg domains to selectively target autoreactive B-cells, which could become a precise therapy for pemphigus in the future. Other novel, potential therapies include cytokine inhibitors, anti-CD25 monoclonal antibodies, autologous hematopoietic stem cell transplantation, and polyclonal regulatory T cell (PolyTreg) therapy. Hopefully, one or more of these emerging therapies will soon be shown to be safe and effective in the treatment of pemphigus, and ultimately improve survival and quality of life for these patients.

• #1 Pemphigus: Types, Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/21130-pemphigus

  Treatment for pemphigus takes time before you see results. With treatment, youll notice new blisters stop forming after several weeks and your skin will begin to heal. It could take months for your blisters and sores to heal completely. […] No, there isnt a cure for pemphigus. Treatment is effective to alleviate symptoms.

• #1 Management of pemphigus vulgaris during acute phase – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/management-of-pemphigus-vulgaris-during-acute-phase/

  Strategies to minimize these side effects include alternate day therapy, administration of corticosteroid sparing agents and the use of adjuvant to decrease the corticosteroid dependency. […] Adjuvant therapy is meant to complement but not substitute for treatment with corticosteroids. […] The use of immunosuppressants must be tailored to the individual patient. […] Cyclophosphamide has been reported to be effective both as a first line adjuvant in patients with pemphigus and in the treatment of those whose disease has previously failed to respond to azathioprine. […] Cyclophosphamide is usually used in a single oral dose of 2 to 3 mg/kg/day. […] In our study we have not observed any serious side effects of cyclophosphamide including toxic effect on bone marrow and liver and hemorrhagic cystitis. […] The disease can be converted into an inactive state in the majority of the patients. Most patients will eventually enter a complete and durable remission that permits systemic therapy to be safely discontinued without an exacerbation of disease severity.

• #1 SciELO Brazil – Consensus on the treatment of autoimmune bullous dermatoses: pemphigus vulgaris and pemphigus foliaceus – Brazilian Society of Dermatology Consensus on the treatment of autoimmune bullous dermatoses: pemphigus vulgaris and pemphigus folia

  https://www.scielo.br/j/abd/a/k7TDXkwSmCqWRYgGnZTKfwM/

  Pemphigus are intraepidermal autoimmune bullous dermatoses that occur with lesions on the skin and / or mucous membranes. This consensus aims to present a complete and updated review of the treatment of these two more frequent forms of pemphigus, based on the literature and the personal experience of the authors. In moderate and severe cases of pemphigus vulgaris and foliaceus, systemic corticosteroid therapy (prednisone or prednisolone) is the treatment of choice. Adjuvant drugs, usually immunosuppressive drugs (azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide) may be prescribed as corticosteroid sparers in refractory cases or with contraindications to corticosteroids to minimize side effects. In severe and nonresponsive cases, corticosteroids in the form of intravenous pulse therapy, immunoglobulin and plasmapheresis / immunoadsorption can be administered. Immunobiological drugs, particularly rituximab, appear as a promising alternative. For milder cases, smaller doses of oral corticosteroid, dapsone and topical corticosteroids are options. The treatment of autoimmune bullous dermatoses, including PV is usually based on systemic medications, because they comprise a severe group of mucosal and cutaneous diseases with significant morbidity and mortality. Treatment should be started as early as possible, and its goal is to achieve and maintain disease remission. Thus, the treatment is often prolonged and can last many years (average 5 to 10 years). Systemic corticosteroids are the basis of the treatment for PV. They have potent anti-inflammatory and immunosuppressive activities. The introduction of these drugs in the 1950s was followed by a reduction in mortality from 75% to 30%. Corticosteroids act rapidly in PV, effecting improvement in several days and impeding the emergence of new lesions after 2 to 3 weeks. Complete re-epithelization can take up to 2 months. After the condition is controlled, defined as the disruption of the emergence of new lesions and total re-epithelialization of existing lesions, the corticosteroid dose is slowly reduced. The rate of this decrease should decline toward the end, which can sometimes take years, due to the lack of uniform protocols for this practice. To minimize the side effects, morbidity, and mortality of PV, contrary to what was advocated several decades ago, it is recommended that the daily dosage of prednisone does not exceed 1.5mg/kg/day-above this value, the likelihood of skin infection and evolution to septicemia (the main death cause in these patients) increases progressively. Thus, other drugs are recommended, in association with corticosteroids-termed adjuvant drugs (corticosteroid-sparing agents). Azathioprine is a cytotoxic drug that is used in most autoimmune diseases. The efficacy of AZA as a corticosteroid-sparing agent in autoimmune bullous diseases, particularly in PV, is well documented and is the oldest and most prescribed immunosuppressive medication in this context. The recommended dosage of AZA in PV is 100 to 200mg/ day (1 to 3mg/kg/day), orally, divided into 2 doses. Mycophenolate mofetil (MMF) has been used as an adjuvant to corticosteroids in patients with PV as first-line treatment and in non-responders to AZA. Several groups prefer MMF to AZA as the first-line adjuvant therapy in PV, due to its lower hepatotoxicity and comparable efficacy. Rituximab should be administered IV as a slow infusion (4 to 6 hours). There are many prospective and retrospective studies that have proven its efficacy, leading to complete and sustained remission in most patients in 3 to 4 months. Rituximab is generally well tolerated, and serious adverse effects are rare. Cyclophosphamide can also be used at 500mg IV as a bolus or 2mg/kg/d. It has corticosteroid-sparing effects, but the risk of sterility, hemorrhagic cystitis, and secondary malignant neoplasia should be considered. Treatment is indicated from the outset of symptoms in PF, even if the clinical manifestation is mild. The goal is to induce rapid control of the disease and complete remission, minimizing treatment-related adverse effects. Considering the serious side effects of high and prolonged doses of systemic corticosteroid therapy, systemic non-steroidal immunomodulatory medication is recommended, especially with azathioprine, mycophenolate mofetil, or methotrexate, the most important of which is azathioprine. For severe and refractory cases, rituximab, intravenous immunoglobulin (IVIG), and eventually cyclophosphamide can be indicated. Systemic corticosteroid therapy remains the most widely used, recognized, and established treatment option, due to its high efficacy and rapid control. Considering that the use of prolonged and high-dose systemic corticosteroids can lead to severe or even fatal adverse effects, it is necessary in patients with disseminated disease to administer a combination of corticoid-sparing drugs (adjuvants) early, including methotrexate, azathioprine, and mycophenolate mofetil. Rituximab (monoclonal anti-CD20) is indicated when the patient is refractory to conventional therapy or if prednisone is required at dosages of higher than 10mg/d in combination with an immunosuppressant for more than 6 months. Intravenous immunoglobulin (IVIG) is indicated for very severe, refractory patients, those who present with significant adverse effects, and severe and disseminated forms of pemphigus that require a more rapid clinical response.

• #1 Management of pemphigus vulgaris: challenges and solutions

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4622091/

  CSs remain the gold standard treatment for PV. Finding the most effective steroid-sparing agent has formed much of the focus of recent research; however, evidence is inconclusive. Azathioprine and MMF are the first line of steroid-sparing treatment. Rituximab is extremely effective in recalcitrant PV where other treatments fail to control the disease.

• #1 Treatment of pemphigus vulgaris | PPA

  https://www.dovepress.com/role-of-rituximab-in-the-treatment-of-pemphigus-vulgaris-patient-selec-peer-reviewed-fulltext-article-PPA

  The authors of the review suggested that low-dose and ultra-low-dose protocols should be used to induce the remission in patients with mild-to-moderate PV, with the possibility of repeated infusions for more severe forms. […] These data confirmed the results of a 2015 systematic review and meta-analysis, comparing different RTX regimens in the treatment of PV. […] While an updated approach to the management of PV may support RTX as a first-line adjuvant treatment, the optimum dosing and schedule of administration are still inconclusively defined. […] Overall, while a better safety profile may be theoretically achieved by low-dose RTX regimens, the literature suggests a similar tolerability of both high-dose and low-dose RTX. […] Further clinical studies with rigorous design are needed to characterize the efficacy and safety of a first-line ultra-low-dose RTX. […] The ultra-low dose of RTX is not only tolerable but has also been associated with a positive response of PV, comparable to that achieved with high doses, especially in early disease.

• #2 Pemphigus Vulgaris: A Complete Overview — DermNet

  https://dermnetnz.org/topics/pemphigus-vulgaris

  The primary aim of treatment of pemphigus vulgaris is to decrease blister formation, prevent infections and promote healing of blisters and erosions. Systemic corticosteroids are the mainstay of medical treatment for controlling the disease, usually in the form of moderate to high doses of oral prednisone or prednisolone, or as pulsed intravenous methylprednisolone. Since their use, many deaths from pemphigus vulgaris have been prevented (the mortality rate dropped from 99% to 515%). Corticosteroids are not a cure for the disease but improve the patient’s quality of life by reducing disease activity. The doses of corticosteroids needed to control pemphigus vulgaris and the length of time on treatment may result in serious side effects and risks. […] Other immunosuppressive drugs (mostly off-label) used to reduce the dose of steroids and may be required by patients with pemphigus vulgaris for years. These are most often: Azathioprine, Mycophenolate mofetil, Cyclophosphamide, Rituximab, which is now approved by the Food and Drug Administration (FDA) in the US.

• #2 SciELO Brazil – Consensus on the treatment of autoimmune bullous dermatoses: pemphigus vulgaris and pemphigus foliaceus – Brazilian Society of Dermatology Consensus on the treatment of autoimmune bullous dermatoses: pemphigus vulgaris and pemphigus folia

  https://www.scielo.br/j/abd/a/k7TDXkwSmCqWRYgGnZTKfwM/

  Pemphigus are intraepidermal autoimmune bullous dermatoses that occur with lesions on the skin and / or mucous membranes. This consensus aims to present a complete and updated review of the treatment of these two more frequent forms of pemphigus, based on the literature and the personal experience of the authors. In moderate and severe cases of pemphigus vulgaris and foliaceus, systemic corticosteroid therapy (prednisone or prednisolone) is the treatment of choice. Adjuvant drugs, usually immunosuppressive drugs (azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide) may be prescribed as corticosteroid sparers in refractory cases or with contraindications to corticosteroids to minimize side effects. In severe and nonresponsive cases, corticosteroids in the form of intravenous pulse therapy, immunoglobulin and plasmapheresis / immunoadsorption can be administered. Immunobiological drugs, particularly rituximab, appear as a promising alternative. For milder cases, smaller doses of oral corticosteroid, dapsone and topical corticosteroids are options. The treatment of autoimmune bullous dermatoses, including PV is usually based on systemic medications, because they comprise a severe group of mucosal and cutaneous diseases with significant morbidity and mortality. Treatment should be started as early as possible, and its goal is to achieve and maintain disease remission. Thus, the treatment is often prolonged and can last many years (average 5 to 10 years). Systemic corticosteroids are the basis of the treatment for PV. They have potent anti-inflammatory and immunosuppressive activities. The introduction of these drugs in the 1950s was followed by a reduction in mortality from 75% to 30%. Corticosteroids act rapidly in PV, effecting improvement in several days and impeding the emergence of new lesions after 2 to 3 weeks. Complete re-epithelization can take up to 2 months. After the condition is controlled, defined as the disruption of the emergence of new lesions and total re-epithelialization of existing lesions, the corticosteroid dose is slowly reduced. The rate of this decrease should decline toward the end, which can sometimes take years, due to the lack of uniform protocols for this practice. To minimize the side effects, morbidity, and mortality of PV, contrary to what was advocated several decades ago, it is recommended that the daily dosage of prednisone does not exceed 1.5mg/kg/day-above this value, the likelihood of skin infection and evolution to septicemia (the main death cause in these patients) increases progressively. Thus, other drugs are recommended, in association with corticosteroids-termed adjuvant drugs (corticosteroid-sparing agents). Azathioprine is a cytotoxic drug that is used in most autoimmune diseases. The efficacy of AZA as a corticosteroid-sparing agent in autoimmune bullous diseases, particularly in PV, is well documented and is the oldest and most prescribed immunosuppressive medication in this context. The recommended dosage of AZA in PV is 100 to 200mg/ day (1 to 3mg/kg/day), orally, divided into 2 doses. Mycophenolate mofetil (MMF) has been used as an adjuvant to corticosteroids in patients with PV as first-line treatment and in non-responders to AZA. Several groups prefer MMF to AZA as the first-line adjuvant therapy in PV, due to its lower hepatotoxicity and comparable efficacy. Rituximab should be administered IV as a slow infusion (4 to 6 hours). There are many prospective and retrospective studies that have proven its efficacy, leading to complete and sustained remission in most patients in 3 to 4 months. Rituximab is generally well tolerated, and serious adverse effects are rare. Cyclophosphamide can also be used at 500mg IV as a bolus or 2mg/kg/d. It has corticosteroid-sparing effects, but the risk of sterility, hemorrhagic cystitis, and secondary malignant neoplasia should be considered. Treatment is indicated from the outset of symptoms in PF, even if the clinical manifestation is mild. The goal is to induce rapid control of the disease and complete remission, minimizing treatment-related adverse effects. Considering the serious side effects of high and prolonged doses of systemic corticosteroid therapy, systemic non-steroidal immunomodulatory medication is recommended, especially with azathioprine, mycophenolate mofetil, or methotrexate, the most important of which is azathioprine. For severe and refractory cases, rituximab, intravenous immunoglobulin (IVIG), and eventually cyclophosphamide can be indicated. Systemic corticosteroid therapy remains the most widely used, recognized, and established treatment option, due to its high efficacy and rapid control. Considering that the use of prolonged and high-dose systemic corticosteroids can lead to severe or even fatal adverse effects, it is necessary in patients with disseminated disease to administer a combination of corticoid-sparing drugs (adjuvants) early, including methotrexate, azathioprine, and mycophenolate mofetil. Rituximab (monoclonal anti-CD20) is indicated when the patient is refractory to conventional therapy or if prednisone is required at dosages of higher than 10mg/d in combination with an immunosuppressant for more than 6 months. Intravenous immunoglobulin (IVIG) is indicated for very severe, refractory patients, those who present with significant adverse effects, and severe and disseminated forms of pemphigus that require a more rapid clinical response.

• #2 Emerging treatment options for the management of pemphigus vulgaris | TCRM

  https://www.dovepress.com/emerging-treatment-options-for-the-management-of-pemphigus-vulgaris-peer-reviewed-fulltext-article-TCRM

  The aim of treatment in PV is to induce and maintain remission, which clinically corresponds to the cessation of new vesicle formation, healing of old erosions, and the completion of treatment tapering to maintenance doses. […] The guidelines of the EDF and BAD define systemic corticosteroids as the first-line treatment of PV, recommending initial treatment with predniso(lo)ne at a dose of 0.51.5 mg/kg/day (EDF) and 1.0 mg/kg/day (BAD). […] Immunosuppressive adjuvants can be administered in combination with systemic corticosteroids. According to the EDF guidelines, the combination of predniso(lo)ne with azathioprine or mycophenolate mofetil (MMF) is considered as second-line treatment, whereas the combination of predniso(lo)ne with rituximab, intravenous immunoglobulin (IVIg), immunoadsorption, cyclophosphamide, dapsone, or methotrexate is considered as third-line treatment in PV.

• #2 Pemphigus Vulgaris – Sussex Community Dermatology Service

  https://sussexcds.co.uk/patient-information/pemphigus-vulgaris/

  Pemphigus vulgaris is a rare autoimmune disease that causes severe blistering of the skin and of the mucous membranes lining the mouth, nose, throat and genitals. […] Pemphigus does not go away by itself, and always needs treatment by a Dermatologist. […] Treatment is important because pemphigus vulgaris is serious and can be life threatening if not treated early and properly. […] The initial aim of treatment is to prevent new blisters forming and to heal the existing ones this is disease control. […] Treatment usually starts with a corticosteroid, which may later be combined with a so-called steroid-sparing drug. […] Pemphigus vulgaris is usually treated first with a corticosteroid. […] High doses of the corticosteroid, usually prednisolone, are given to bring the pemphigus vulgaris under control.

• #2 Treatment of pemphigus – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/treatment-of-pemphigus/

  Systemic corticosteroids remain the mainstay of therapy for pemphigus. Their use has transformed what was almost invariably a fatal illness into one whose mortality is now below 10%. […] Treatment regimens are dictated by the age of the patient, the degree of involvement, the rate of disease progression and the subtype of pemphigus. […] Most patients who die of pemphigus at present die of complications of therapy. This can be prevented to an extend by the use of various adjuvant therapies mostly immunosuppressives which can reduce the need for steroids. […] Patients with mild disease are treated with 40mg of prednisolone every other day together with a daily immunosuppressive agent, usually azathioprine for at least one year. Patients with extensive disease are treated as formerly with 200 to 400 mg/day of prednisolone for 5 to 10 weeks.

• #2 Pemphigus Vulgaris Treatment & Management: Medical Care, Complications, Diet

  https://emedicine.medscape.com/article/1064187-treatment

  The aims of treatment are the same in pemphigus vulgaris as in other autoimmune bullous diseasesnamely, to decrease blister formation, to promote healing of blisters and erosions, and to determine the minimal dose of medication necessary to control the disease process. Therapy must be tailored for each patient, taking into account preexisting and coexisting conditions. Patients may continue to experience mild disease activity while under optimal treatment. […] Treatment with corticosteroids has improved the overall mortality, but significant morbidity remains. Much of the mortality and morbidity in patients with pemphigus vulgaris is now related to the adverse effects of such therapy. […] Immunosuppressive drugs are steroid-sparing and should be considered early in the course of the disease. Mycophenolate mofetil and azathioprine have been the agents usually considered as initial choices.

• #2 Treatment of pemphigus – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/treatment-of-pemphigus/

  Bystrin recommends adjuvant therapies only if there are relative contraindications to the use of corticosteroids or if the corticosteroid dose cannot be reduced because of repeated flares in disease activity. […] The rationale to use drugs other than corticosteroids to treat pemphigus is that they may reduce the need for corticosteroids and hence their side effects and may result in better control of the disease. […] Immunosuppressives are usually started after prednisolone has been tapered to 40mg daily. […] Cyclophosphamide appears to be more effective than azathioprine, but toxicity is more which includes bone marrow suppression, hemorrhagic cystitis, bladder fibrosis, sterility and increased risk of malignancy. […] Major toxicities of azathioprine include bone marrow suppression, hepato toxicity and a possible increased risk of malignancy.

• #2 Treatments – IPPF

  https://www.pemphigus.org/treatments/

  Mycophenolate (CellCept, Myfortic) is composed of several penicillium species that is used after initial treatment for pemphigus. […] Cyclophosphamide (Cytoxan) is an oral cyclophosphamide that is considered an alternative to azathioprine. Due to the potential toxicities, this drug should be reserved for patients who do not respond to other immunosuppressives. […] Rituximab is a B-cell antibody treatment option for patients with pemphigus that is being used as first line therapy by many clinicians. In June 2018, the FDA approved Rituxan for the treatment of adults with moderate to severe PV. […] Intravenous Immunoglobulin (IVIG) therapy is prepared from extracting the plasma in human blood. IVIG is given intravenously; under the skin via a syringe or catheter. The dosage required is patient-specific. To treat pemphigus, the doses are as high as 2000mg/kg.

• #2 Pemphigus Vulgaris – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/pemphigus-vulgaris/

  Dapsone (100-200mg daily) can be effective in mucosal disease or to lower the daily corticosteroid dose in patients with stable disease. Dapsone can be used in addition to mycophenolate mofetil or azathioprine. As an advantage, dapsone 100mg daily provides Pneumocystis prophylaxis. […] In patients requiring greater than 10mg daily prednisone for control of disease activity, or in patients with contraindications to systemic corticosteroid therapy, other immunosuppressants are necessary to reduce or replace systemic corticosteroids. Mycophenolate mofetil and azathioprine have shown approximately equal efficacy and safety in clinical trials for PV, although there is a trend toward both greater efficacy and safety with mycophenolate mofetil. […] Mycophenolate mofetil (30-40 mg/kg/day divided twice daily) is generally well tolerated, although side effects of fatigue, gastrointestinal upset, and tremor are not uncommon, particularly at higher doses, and there is a small long-term risk of lymphoma and fatal infection or reactivation from JC virus with progressive multifocal leukencephalopathy. Reduction of corticosteroid dose can be initiated as early as one month after starting mycophenolate mofetil, although maximal effect of mycophenolate mofetil is not achieved until 2-3 months.

• #2 Rituxan Receives FDA Approval to Treat Pemphigus Vulgaris – IPPF

  https://www.pemphigus.org/rituxan-receives-fda-approval-to-treat-pemphigus-vulgaris/

  On Thursday, June 7th, the FDA approved Rituxan for the treatment of adults with moderate to severe pemphigus vulgaris (PV). […] Rituxan is the first biologic therapy approved by the FDA for PV and the first major advancement in the treatment of PV in more than 60 years. […] The consensus includes the recommendation to use an anti-CD20 monoclonal antibody (Rituxan) and corticosteroids as first line therapy options for moderate to severe pemphigus. […] If you are considering Rituxan as a potential therapy, please consult your healthcare provider.

• #2 RITUXAN® (rituximab) Treatment for Pemphigus Vulgaris (PV)

  https://www.rituxan.com/pv.html

  A study of people with PV showed that 9 out of 10 of those treated with Rituxan had no lesions at 2 years compared to 3 out of 10 people treated with only steroids. […] People who were treated with Rituxan (rituximab) were given European Union approved rituximab plus short-term steroids. […] Adults with Pemphigus Vulgaris (PV): to treat moderate to severe PV. […] Patients were given European Union approved rituximab + short-term steroids in a clinical study to measure their lesion improvement.

• #2

  https://dpcj.org/index.php/dpc/article/view/dermatol-pract-concept-articleid-dp1003a50

  Autoimmune bullous disorders are a heterogeneous spectrum of skin disorders characterized by the production of autoantibodies against adhesion molecules of the skin. […] The current first-line treatment of pemphigus is based on systemic corticosteroids that are often combined with immunosuppressive adjuvants, such as azathioprine, mycophenolate mofetil, and the anti-CD20 monoclonal antibody rituximab, usually at initiation of treatment. Rituximab efficacy is higher when it is administered early in the course of the disease. Therefore, it should be used as first-line treatment to improve efficacy and reduce cumulative doses of corticosteroids and their side effects. […] Treatment of bullous pemphigoid is based on disease extension. Localized and mild forms can be treated with superpotent topical corticosteroids or with nonimmunosuppressive agents. In patients with generalized disease or whose disease is resistant to the treatments described above, systemic corticosteroids are preferred and effective. Adjuvant immunosuppressants are often combined with steroids for their steroid-sparing effect.

• #2 Treatment of pemphigus vulgaris | PPA

  https://www.dovepress.com/role-of-rituximab-in-the-treatment-of-pemphigus-vulgaris-patient-selec-peer-reviewed-fulltext-article-PPA

  The authors of the review suggested that low-dose and ultra-low-dose protocols should be used to induce the remission in patients with mild-to-moderate PV, with the possibility of repeated infusions for more severe forms. […] These data confirmed the results of a 2015 systematic review and meta-analysis, comparing different RTX regimens in the treatment of PV. […] While an updated approach to the management of PV may support RTX as a first-line adjuvant treatment, the optimum dosing and schedule of administration are still inconclusively defined. […] Overall, while a better safety profile may be theoretically achieved by low-dose RTX regimens, the literature suggests a similar tolerability of both high-dose and low-dose RTX. […] Further clinical studies with rigorous design are needed to characterize the efficacy and safety of a first-line ultra-low-dose RTX. […] The ultra-low dose of RTX is not only tolerable but has also been associated with a positive response of PV, comparable to that achieved with high doses, especially in early disease.

• #2 Efficacy of Repeated Courses of Rituximab as Treatment for Pemphigus Vulgaris | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3649

  The current study has several limitations, including its retrospective nature, relatively small cohort, and lengthy follow-up period. […] Rituximab is a promising treatment option for severe PV. Complete remission is achieved in the majority of patients. Rituximab is an effective steroid-sparing agent and has a positive long-term clinical effect if used repeatedly during relapses. With each subsequent cycle, an improvement is observed with a substantially longer remission time, thus rendering rituximab a potent disease-modifying agent.

• #2 Pemphigus Vulgaris – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/pemphigus-vulgaris/

  Azathioprine can be started at 50mg daily and titrated upward by 50mg every 1-2 weeks until side effect, therapeutic effect, or the target dose of 2.5mg/kg/day occurs. […] In patients who have severe or persistent disease that cannot be controlled with corticosteroids and/or other immunosuppressives, other therapies such as rituximab, intravenous immunoglobulin, plasmapheresis, and cyclophosphamide can be considered. […] B-cell depletion therapy with rituximab (anti-CD20 monoclonal antibody) is an effective therapy for PV, and some experts have proposed that it should be considered for first-line therapy. […] Intravenous immunoglobulin (IVIG, 2 mg/kg, divided over 3-5 days) is effective for PV therapy and can be provided by hospital or home infusion. […] Plasmapheresis allows for the rapid removal of antibodies from the circulation, but must always be used in conjunction with adjunctive immunosuppressants to prevent new antibody production.

• #2 Initial management of pemphigus vulgaris and pemphigus foliaceus – UpToDate

  https://www.uptodate.com/contents/initial-management-of-pemphigus-vulgaris-and-pemphigus-foliaceus

  Initial management of pemphigus vulgaris and pemphigus foliaceus […] Systemic glucocorticoids and rituximab are the mainstays of therapy for pemphigus vulgaris and pemphigus foliaceus and are usually highly effective for obtaining control of disease. […] Other immunomodulatory agents, such as azathioprine and mycophenolate mofetil, are commonly prescribed in conjunction with systemic glucocorticoids in an attempt to minimize the risk for adverse effects of long-term, high-dose glucocorticoid therapy. […] Interventions such as intravenous immune globulin (IVIG), immunoadsorption, and cyclophosphamide are typically reserved for patients with refractory disease.

• #2

  https://link.springer.com/article/10.1684/ejd.2014.2483

  Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. […] Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris. […] Treatment of severe pemphigus with a combination of immunoadsorption, rituximab, pulsed dexamethasone and azathioprine/mycophenolate mofetil: a pilot study of 23 patients.

• #2 Treatment of pemphigus vulgaris. An overview in Mexico | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-treatment-of-pemphigus-vulgaris-an-13084220

  The treatment options for PV include substances known as adjuvant drugs, which are agents that support the effect of steroids administered fundamentally via the oral route. […] Azathioprine is one of the most common adjuvants to PV therapy, and has been shown to be effective in application to many diseases apart from PV, such as bullous pemphigoid and atopic dermatitis. […] The administration of azathioprine as adjuvant therapy in PV increases percentage disease remission up to 45 %. […] The use of oral cyclophosphamide as steroid-sparing adjuvant therapy in PV has been documented in many reviews published in the literature. […] PV treatment in the form of mixed pulses or DCP (dexamethasone-cyclophosphamide pulses) has been shown to be effective in application to recurrent PV and refractory presentations of the disease.

• #2 Treatments – IPPF

  https://www.pemphigus.org/treatments/

  Anti-inflammatory agents such as dapsone and tetracyclines are used as they also may have a steroid sparing effect in mild to moderate disease (e), often in patients who are in maintenance phase but corticosteroid-dependent. […] Dapsone must be started after glucose-6-P-dehydrogenase screening and is administered as 7.5mg/kg/day, up to 200mg/day. […] Tetracycline, doxycycline and minocycline have been used by some in glucocorticoid-dependent patients in the maintenance phase of therapy, often with niacinamide (nicotinamide). […] For multiple oral erosions, corticosteroid mouthwashes are practical, for example, soluble betamethasone sodium phosphate 0.5 mg tablet dissolved in 10 mL water may be used up to four times daily, holding the solution in the mouth for about 5 min. Isolated oral erosions could be treated with application of triamcinolone acetonide 0.1% in adhesive paste or clobetasol 0.05% gel. Topical cyclosporine (100 mg/ m1) in oral pemphigus has been described and may be of some benefit but is expensive.

• #2 Pemphigus Vulgaris Successfully Treated With Doxycycline Monotherapy | MDedge

  https://mdedge.com/cutis/article/109639/dermatopathology/pemphigus-vulgaris-successfully-treated-doxycycline

  Pemphigus vulgaris (PV) is an acquired autoimmune bullous disease with notable morbidity and mortality if not treated appropriately due to loss of epidermal barrier function and subsequent infection and loss of body fluids. […] The treatment of PV is challenging given the multiple side effects of steroids, especially in elderly patients. Tetracyclines have an advantageous side-effect profile and they have been shown to be efficacious in treating PV when combined with nicotinamide or when used as adjuvant therapy to steroids. […] Our case shows a patient who was treated exclusively with doxycycline and achieved complete remission.

• #2 Treatment of pemphigus vulgaris. An overview in Mexico | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-treatment-of-pemphigus-vulgaris-an-13084220

  Mycophenolic acid has been used for the management of psoriasis during the past three decades; at present, it has been re-formulated as mofetil mycophenolate and is used as an immunosuppressor in transplantation patients. […] The current uses of mycophenolate in PV have focused on active and steroid-refractory presentations of the disease. […] While the utility of methotrexate as monotherapy for PV has always been the subject of discussion, it is most widely accepted as an adjuvant. […] The combination of these two drugs has been tested not only in application to PV but also to patients with foliaceous pemphigus. […] Dapsone is one of the most useful agents in application to many diseases, including leprosy. […] Many other treatments for PV are also under study, and some have demonstrated good efficacy compared with steroid treatment. […] The management of choice is steroid therapy via the oral or intravenous route, which offers an adequate response and favorably modifies the prognosis.

• #2 Pemphigus Vulgaris – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/pemphigus-vulgaris/

  Treatment options are summarized in Table I. […] Class I steroids, such as clobetasol, can be applied twice daily to new blisters and erosions on both the face and body. Topical tacrolimus ointment may also be helpful, particularly for lesions on the face where chronic steroid therapy is undesirable. For mucosal disease, dexamethasone elixir, swish and spit 5cc once to twice daily, is easy to use. Clobetasol ointment or gel can also be applied directly to mucosal erosions. Dental trays (fitted by oral medicine) facilitate occlusion of topical steroids to the gingiva at night. […] For mild disease, (transient lesions that heal within 1 week), monotherapy with topical corticosteroids may be sufficient. Mild mucosal or mucocutaneous disease may also respond to tetracyclines plus niacinamide (doxycycline 100mg twice daily plus niacinamide 500mg three times daily).

• #2 Pemphigus Vulgaris – Sussex Community Dermatology Service

  https://sussexcds.co.uk/patient-information/pemphigus-vulgaris/

  However, the prednisolone can seldom be stopped completely and most patients need a small maintenance dose to keep their disease under control. […] For this reason, other medications are often used as well. […] These are known as steroid-sparing drugs or adjuvant drugs and they work well when combined with corticosteroids. […] Immunosuppressives: azathioprine, cyclophosphamide, mycophenolate mofetil, ciclosporin and rituximab. […] A steroid cream may be used on skin blisters so that the dose of steroid tablets can be kept lower. […] Plasmapheresis, intravenous immunoglobulin and rituximab may be considered if high doses of steroids are not effective. […] Further research continues to find better treatments or combinations to treat PV.

• #2 Pemphigus Vulgaris Treatment & Management: Medical Care, Complications, Diet

  https://emedicine.medscape.com/article/1064187-treatment

  Intravenous immunoglobulin (IVIG) therapy has been suggested as efficacious in pemphigus vulgaris treatment. […] Cyclophosphamide is used for refractory disease. […] Plasmapheresis has been used in refractory cases, usually in conjunction with cytotoxic therapy. […] Wound care for erosions includes daily gentle cleaning, application of topical agents to promote wound healing, and use of nonadhesive dressings. The goal of wound care is to promote healing, minimize trauma to the surrounding skin, and diminish scarring. Epidermal growth factor (EGF) may speed healing of localized lesions.

• #2 Content – Health Encyclopedia – University of Rochester Medical Center

  https://www.urmc.rochester.edu/encyclopedia/content?contenttypeid=134&contentid=110

  These are common treatments for pemphigus vulgaris: […] Good oral healthcare. Blistering may affect the health of your mouth. So working with your dentist to take the best care of your teeth and gums is important. […] Oral prednisone and topical steroid creams. These may be prescribed to treat inflammation. […] Immune suppressants. These medicines may be a helpful alternative to steroids for long-term use. […] Plasmapheresis or intravenous immunoglobulin. People who do not respond to other forms of treatment may need more intensive treatments. This may include replacing blood plasma and infusions with healthy immunoglobulin. […] Pain management. Pain medicine or other pain management strategies may be used to help with painful blisters. […] Follow up. This condition may return, even after successful treatment. Go to all follow-up appointments.

• #2 Pemphigus Vulgaris | University Hospitals

  https://www.uhhospitals.org/health-information/health-and-wellness-library/article/diseases-and-conditions/pemphigus-vulgaris

  These are common treatments for pemphigus vulgaris: […] Oral prednisone and topical steroid creams. These may be prescribed to treat inflammation. […] Immune suppressants. These medicines may be a helpful alternative to steroids for long-term use. […] Plasmapheresis or intravenous immunoglobulin. People who do not respond to other forms of treatment may need more intensive treatments. This may include replacing blood plasma and infusions with healthy immunoglobulin. […] Pain management. Pain medicine or other pain management strategies may be used to help with painful blisters. […] Follow up. This condition may return, even after successful treatment. Go to all follow-up appointments. […] You may be advised to use baths and special wound dressings to help sores heal. If you get an infection, your provider may prescribe antibiotic, antifungal, or antiviral medicines. People with severe cases of pemphigus vulgaris may need to be hospitalized to get wound care and intravenous (IV) fluids or electrolytes if mouth sores make it difficult to eat and drink. […] It can take months or even years to treat and control this condition. Also, treatments may have serious side effects. Talk with your provider about possible side effects and how to manage them.

• #2 The Treatment of Pemphigus Vulgaris and Pemphigus Foliaceus | Plastic Surgery Key

  https://plasticsurgerykey.com/the-treatment-of-pemphigus-vulgaris-and-pemphigus-foliaceus/

  54.1 Introduction […] Thus, adjuvant therapies are commonly employed in the long-term management of pemphigus in patients who do not respond to high-dose steroids, are unable to taper the steroids, or cannot tolerate the steroids due to systemic complications. Treatment for pemphigus can be categorized into three phases: control phase, consolidation phase, and maintenance phase. The control phase is the acute phase in which high doses are required to suppress the disease. In the consolidation phase, the current dose of medications is continued until resolution of most lesions. These are of the order of weeks, usually. The maintenance phase consists of tapering of medications and selection of appropriate doses which prevent the formation of new lesions and is of the order of several months to a year.

• #2 Refractory pemphigus vulgaris: Treatment options – Journal of Skin and Sexually Transmitted Diseases

  https://jsstd.org/refractory-pemphigus-vulgaris-treatment-options/

  Interventions that directly target the antibody-mediated pathogenesis of pemphigus such as rituximab, intravenous immunoglobulins (Ig), immunoadsorption, plasmapheresis, and intralesional immunomodulators are made use of, in the management of refractory pemphigus. […] The treatment selection in refractory pemphigus is depended on the availability of a particular therapeutic option, which, in turn, is based on the accessibility to treatment and the facility to administer it safely. Use of intravenous IgG, plasmapheresis, immunoadsorption, and rituximab are limited by their cost while side effects and toxicity might be the limiting factor in case of cyclophosphamide. […] Rituximab is a monoclonal antibody directed against CD20 antigen on B lymphocytes. This attains long-lasting B cell depletion. A dose regimen similar to that used in the treatment of rheumatologic disease (1g infusion on day 1 and day 15 of treatment) is administered in combination with a tapering dose of systemic glucocorticoids.

• #2

  https://insight.jci.org/articles/view/92021

  If disease relapse is caused by the persistence and reexpansion of autoreactive B cells that are not effectively eliminated by rituximab, then strategies to completely eliminate DSG3-reactive B cells are likely to induce long-term remission in PV patients. […] Taken together, the basic, translational, and clinical research studies in the field have considerably expanded our understanding of PV pathogenesis and positioned PV to be a model autoimmune disease for the development of targeted therapeutic strategies that can avoid systemic immunosuppression. […] Using antigen-specific immunoadsorbers that exclusively extract the disease-causing autoantibodies represents an attractive approach to therapy, as it avoids hypogammaglobulinemia associated with non-specific immunoadsorption strategies and hence the risks of generalized immunosuppression. […] The DSG3 CAAR approach offers several therapeutic advantages and fewer toxicities compared with antibody-based B cell depletion or CART therapy of cancer.

• #2 Pemphigus: Diagnosis and treatment

  https://www.aad.org/public/diseases/a-z/pemphigus-treatment

  Researchers are looking for better treatment options. […] This could lead to better treatment for pemphigus vulgaris. […] Today, the outcome looks good. For most people, the disease can be controlled with treatment. […] Thanks to medicines and other treatments, this has changed. Few people die of pemphigus.

• #2 Pemphigus vulgaris* | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-pemphigus-vulgaris-articulo-S0365059620306048

  At this phase, the objective is to control the condition, interrupting the appearance of new bullous lesions and promoting re-epithelialization of the existing lesions. […] The drug doses are slowly reduced to minimize the side effects. […] Complete remission of the disease is possible, and has been observed in 38%, 50%, and 75% of the cases after three, five, and ten years of diagnosis, respectively. […] The main cause of death in PV patients is septicemia.

• #2 Pemphigus: Updated Review and Emerging Therapies

  https://www.dermatologytimes.com/view/pemphigus-updated-review-and-emerging-therapies

  As in all forms of pemphigus, systemic corticosteroids are first-line in the treatment of PF. The treatment algorithm for PF is similar to that of PV. However, in localized forms of PF with a limited number of lesions, topical or intralesional corticosteroids can be used. […] Prior to corticosteroid therapy, PF was fatal in approximately 60% of patients. Fortunately, steroids and other immunosuppressive therapies have greatly reduced mortality. […] There are many new treatments currently being tested for pemphigus. Second and third generation anti-CD20 monoclonal antibodies, such as veltuzumab, ocrelizumab, and obinutuzumab, have higher binding affinities and induce a more robust B-cell depletion compared to rituximab. The development of these next generation anti-CD20 monoclonal antibodies could lead to major progress in the treatment of pemphigus. Bruton tyrosine kinase (BTK) inhibitors, which downregulate several B-cell functions, and efgartigimod, an engineered Fc fragment derived from human IgG1, are also being studied for use in pemphigus treatment. Recently, researchers have engineered chimeric autoantibody receptor (CAAR)-T cells that recognize Dsg domains to selectively target autoreactive B-cells, which could become a precise therapy for pemphigus in the future. Other novel, potential therapies include cytokine inhibitors, anti-CD25 monoclonal antibodies, autologous hematopoietic stem cell transplantation, and polyclonal regulatory T cell (PolyTreg) therapy. Hopefully, one or more of these emerging therapies will soon be shown to be safe and effective in the treatment of pemphigus, and ultimately improve survival and quality of life for these patients.

• #3 Pemphigus vulgaris* | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-pemphigus-vulgaris-articulo-S0365059620306048

  Systemic corticosteroids are the basis of PV treatment, as they present potent anti-inflammatory and immunosuppressive action. […] The introduction of this drug in the 1950s was followed by a reduction in mortality from 75% to 30%. […] Prednisone is the most commonly used oral corticosteroid, followed by prednisolone and deflazacort. […] Corticosteroids may also be administered in the form of pulse therapy in cases where control with prednisone above 1 mg/kg/day cannot be achieved. […] The efficacy of AZA as a corticosteroid sparer in autoimmune bullous diseases, particularly in PV, is well documented; it is the oldest and most prescribed immunosuppressive medication for this condition. […] Following oral administration, mycophenolate mofetil/sodium (MMF) is absorbed and converted to its active metabolite, mycophenolic acid.

• #3 Pemphigus Vulgaris – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/pemphigus-vulgaris/

  With persistent or widespread disease, oral corticosteroids such as prednisone are indicated. For moderate disease, 0.5mg/kg/day of prednisone or equivalent may be sufficient. Doses generally do not need to exceed 1mg/kg/day of prednisone. If patients flare on 1mg/kg/day of prednisone, the dose can be split to twice daily or three times daily dosing, which increases the therapeutic efficacy without increasing the total daily dose. […] Before starting high-dose steroids, tuberculosis screening should be performed (via tuberculin skin testing or Quantiferon-gold blood assay). If patients will be on chronic corticosteroids (at least 5mg daily prednisone equivalent for at least 3 months), osteoporosis counseling and prevention is indicated. Additionally, Pneumocystis prophylaxis should be considered for patients on chronic prednisone, particularly with daily prednisone doses of 15mg or higher. Patients should remain on high-dose steroids until new lesions cease to form, and then the dose can be gradually tapered to the minimum required to control disease. If patients can be managed with 10mg (or ideally 5mg) daily prednisone or less, corticosteroid monotherapy is feasible.

• #3 Emerging treatment options for the management of pemphigus vulgaris | TCRM

  https://www.dovepress.com/emerging-treatment-options-for-the-management-of-pemphigus-vulgaris-peer-reviewed-fulltext-article-TCRM

  Azathioprine is one of the main adjuvants used in the treatment of PV and is recommended as a first-line adjuvant immunosuppressant, according to both the EDF and BAD guidelines. […] MMF is a safe steroid-sparing agent that is recommended as a first-line adjuvant immunosuppressant, based on both the EDF and BAD guidelines. […] Rituximab is indicated for patients who remain dependent on 10 mg prednisolone in combination with an immunosuppressive adjuvant, according to the EDF guidelines. […] Plasmapheresis is a useful adjuvant therapy for quickly reducing the titers of circulating autoantibodies. This procedure should be considered for rapid control of severe pemphigus unresponsive to a combination of prednisone and immunosuppressive agents. […] Immunoadsorption is recommended as a second-line adjuvant agent by the EDF guidelines and as a third-line therapy by the BAD guidelines.

• #3 Treatment of pemphigus – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/treatment-of-pemphigus/

  Dexamethasone-Cyclophosphamide pulse therapy has been used recently for pemphigus unresponsive to high doses of oral corticosteroids. […] The major side effect of this regime is secondary infection leading to septicemia, particularly in the first phase. […] Mycophenolate mofetil has recently been used 2 g daily with prednisolone 2 mg/kg daily with good success. […] Other adjuvant treatment in pemphigus includes immuno modulatory procedures like plasmapheresis and extracorporeal photopheresis. […] At present plasmapheresis appears to be worthwhile in patients with severe pemphigus unresponsive to conventional therapy.

• #3 Is It Time to Reconsider Rituximab Dosing Regimens for Pemphigus Vulgaris?

  https://www.mdpi.com/2073-4468/13/1/4

  Rituximab is currently approved for patients affected by moderate-to-severe pemphigus vulgaris, a severe autoimmune blistering skin disease that can be life-threatening. The standard rituximab dosing regimens, originally established for B-cell non-Hodgkin’s lymphomas, have been recognized to exceed the effective dose required for inducing B-cell depletion, considering that the B-cell burden in pemphigus vulgaris is considerably lower than in lymphoproliferative disorders. […] Conventional treatments for PV include high doses of systemic corticosteroids and adjuvant steroid-sparing immunosuppressor and/or immunomodulant approaches such as azathioprine, mycophenolate mofetil, methotrexate, dapsone, tetracyclines, plasmapheresis, and high-dose intravenous immunoglobulins. […] The optimal RTX dosing regimen to adopt in PV is still a matter of debate. Conventional RTX dosing regimens for PV, initially adapted from the protocols used in lymphoproliferative diseases, may exceed the required doses for inducing B-cell depletion. Recent studies support low-dose and ultra-low-dose RTX regimens for PV treatment.

• #3

  https://link.springer.com/article/10.1007/s13555-024-01191-3

  Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis (AIBD) characterized by painful blistering of the skin and mucosa caused by autoantibodies that lead to loss of adhesion in the epidermis. Standard therapy for PV is corticosteroids, either alone or in combination with steroid-sparing immunosuppressants or infusions with rituximab. According to the published European guideline, high-dose intravenous immunoglobulin (IVIg) therapy with a dosage of 2 g per kg body weight distributed over 25 days every 4 weeks is a promising treatment option, especially for severe or refractory disease. […] Intravenous immunoglobulin (IVIg) therapy is a promising treatment option for severe pemphigus vulgaris (PV), particularly in the case of failure on standard treatment with steroids and additional immunosuppressants.

• #3 Pemphigus Vulgaris – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/pemphigus-vulgaris/

  Azathioprine can be started at 50mg daily and titrated upward by 50mg every 1-2 weeks until side effect, therapeutic effect, or the target dose of 2.5mg/kg/day occurs. […] In patients who have severe or persistent disease that cannot be controlled with corticosteroids and/or other immunosuppressives, other therapies such as rituximab, intravenous immunoglobulin, plasmapheresis, and cyclophosphamide can be considered. […] B-cell depletion therapy with rituximab (anti-CD20 monoclonal antibody) is an effective therapy for PV, and some experts have proposed that it should be considered for first-line therapy. […] Intravenous immunoglobulin (IVIG, 2 mg/kg, divided over 3-5 days) is effective for PV therapy and can be provided by hospital or home infusion. […] Plasmapheresis allows for the rapid removal of antibodies from the circulation, but must always be used in conjunction with adjunctive immunosuppressants to prevent new antibody production.

• #3 Management of pemphigus vulgaris during acute phase – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/management-of-pemphigus-vulgaris-during-acute-phase/

  We present our experience with 21 patients of pemphigus vulgaris seen over a period of 10 years managed in service hospitals during acute phase of the disease. […] The treatment comprised of potassium permanganate lotion bath (1:10000) and 1 framycetin gauze dressing of the denuded areas, maintenance of fluid and electrolyte balance. […] The corticosteroids were usually administered as a single dose of prednisolone 1 mg/kg/day. Cyclophosphamide was given at an initial dose of 50mg/day and the dose was escalated to 100mg/day. […] Out of 21 patients receiving corticosteroids, cyclophosphamide and other supportive therapy, 20(95%) had undergone clinical resolution of the disease. […] In this study we have made an attempt to study the efficacy of systemic corticosteroids and cyclophosphamide therapy in pemphigus vulgaris during acute phase.

• #3 Pemphigus vulgaris* | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-pemphigus-vulgaris-articulo-S0365059620306048

  Chimeric monoclonal anti-CD 20 antibody (which depletes both normal and pathogenic B lymphocytes) has been used in severe and refractory cases of PV since 2006. […] Rituximab is generally well tolerated, and serious adverse events are rare. […] Plasmapheresis was first used in 1978 for the treatment of PV, in order to remove pathogenic autoantibodies from the circulation. […] Systemic antibiotic therapy is indicated only in cases with clinical and/or laboratory evidence of secondary infection, never prophylactically. […] Topical treatment of PV lesions aims to reduce pain and prevent secondary infection. […] New anti-B-cell immunobiological drugs are being investigated in clinical research regarding their efficacy, safety, and cost for patients with PV. […] PV treatment should include two phases, induction and maintenance of remission.

• #3 Management of refractory pemphigus vulgaris and pemphigus foliaceus – UpToDate

  https://www.uptodate.com/contents/management-of-refractory-pemphigus-vulgaris-and-pemphigus-foliaceus

  Management of refractory pemphigus vulgaris and pemphigus foliaceus […] Treatment with either rituximab and a systemic glucocorticoid or with a systemic glucocorticoid with or without an adjuvant immunosuppressive medication (eg, mycophenolate mofetil, azathioprine) is the mainstay of initial treatment. […] Patients who do not achieve disease control with the selected initial therapy generally first proceed to escalation of initial treatment with systemic glucocorticoids, rituximab, and/or adjuvant immunosuppressants. […] Patients for whom this is insufficient may benefit from other interventions, such as intravenous immune globulin (IVIG), immunoadsorption, plasmapheresis, and cyclophosphamide. […] Therapeutic options for pemphigus vulgaris or pemphigus foliaceus refractory to escalation of initial therapy will be reviewed here.

• #3 Pemphigus Vulgaris (PV) Clinical Trials :: Cabaletta Bio, Inc. (CABA)

  https://www.cabalettabio.com/patients/phase-12-trial-in-pemphigus-vulgaris

  RESET-PVTM trial is a Phase 1/2 clinical trial being conducted to evaluate the effects of the investigational cell treatment CABA-201 in patients with pemphigus vulgaris (PV) who have active disease. […] CABA-201 is the investigational treatment used in the RESET-PV trial. This clinical trial evaluates the safety, tolerability and effectiveness of CABA-201 in the treatment of pemphigus vulgaris. […] CABA-201 is an investigational chimeric antigen receptor (CAR) T cell therapy designed to treat pemphigus vulgaris by targeting the B cells that may be causing the disease. […] CABA-201 is made from your own T cells, a type of white blood cell, and uses your own immune system to get rid of the disease-causing B cells and to restore healthy B cells in your body. […] Therapy with CAR T cells may cause serious and potentially life-threatening side effects. The potential risks of participating in this clinical trial will be explained to you before you decide whether to participate.

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