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Management of refractory pemphigus vulgaris and pemphigus foliaceus

Management of refractory pemphigus vulgaris and pemphigus foliaceus
Literature review current through: Jan 2024.
This topic last updated: Jan 30, 2023.

INTRODUCTION — Pemphigus vulgaris and pemphigus foliaceus are autoimmune blistering diseases that may result in significant morbidity and death. 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. (See "Initial management of pemphigus vulgaris and pemphigus foliaceus".)

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 (algorithm 1). Patients for whom this is insufficient may benefit from other interventions, such as intravenous immune globulin (IVIG), immunoadsorption, plasmapheresis, and cyclophosphamide. (See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Assessing the response to therapy' and "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Failure to achieve disease control'.)

Therapeutic options for pemphigus vulgaris or pemphigus foliaceus refractory to escalation of initial therapy will be reviewed here. The initial management of pemphigus vulgaris and pemphigus foliaceus, escalation of treatment after failure to achieve disease control with initial therapy, and the management of relapses after initial disease control are reviewed separately.

(See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Initial therapy'.)

(See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Failure to achieve disease control'.)

(See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Management of relapses'.)

Paraneoplastic pemphigus is also reviewed separately.

(See "Paraneoplastic pemphigus".)

APPROACH TO THERAPY — The use of therapies generally reserved for refractory pemphigus (intravenous immune globulin [IVIG], immunoadsorption, cyclophosphamide, and plasmapheresis) involves the identification of appropriate treatment candidates and treatment selection. (See 'Candidates' below and 'Treatment options' below and 'Treatment selection' below.)

Whenever possible, the therapies utilized for refractory pemphigus should be administered by clinicians experienced in the use and adverse effects of these treatments. Referral to specialized treatment centers can be useful for additional access to treatments.

Candidates — Patients who fail to achieve disease control despite escalation of initial treatment are candidates for refractory disease therapies. Escalation of treatment typically consists of increasing the dose of the systemic glucocorticoid, adding rituximab (if not already received), and/or adding or adjusting conventional immunosuppressive therapy (algorithm 1). (See "Initial management of pemphigus vulgaris and pemphigus foliaceus".)

Patients with contraindications to initial therapies or who are unable to tolerate initial treatments may also benefit from treatments used for refractory disease.

Occasionally, refractory disease therapies are used prior to the failure of rituximab for patients presenting with severe disease. (See 'Use prior to failure of rituximab' below.)

Treatment options — The major therapeutic options for disease refractory to escalation of treatment include interventions that directly target the antibody-mediated pathogenesis of pemphigus (IVIG, immunoadsorption, and plasmapheresis) and cyclophosphamide, a drug that may be used as an alternative adjuvant immunosuppressant. These therapies are typically added to a baseline immunosuppressive regimen that consists of systemic glucocorticoids with or without an adjuvant conventional immunosuppressant. (See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Adjuvant conventional immunosuppressive therapies'.)

The availability of higher-quality data to support the efficacy of rituximab in pemphigus; high cost and technical requirements for the administration of IVIG, immunoadsorption, and plasmapheresis; and the unfavorable adverse effect profile of cyclophosphamide (eg, sterility, cytopenia, hemorrhagic cystitis, bladder cancer) contribute to the preferred use of these agents for refractory pemphigus rather than for new-onset disease. (See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Rituximab and systemic glucocorticoids'.)

Treatment selection — The paucity of high-quality studies on the treatment of refractory pemphigus with IVIG, immunoadsorption, plasmapheresis, or cyclophosphamide impedes both conclusions on the relative efficacies of these interventions and the formation of definitive guidelines on the best approach to the treatment of refractory disease. Thus, therapeutic choice remains heavily influenced by consideration of patient tolerance (including contraindications) for specific treatments and treatment availability.

Patient-specific considerations — Examples of clinical scenarios that have influenced the choice of therapy for our patients include:

Desire to preserve childbearing potential – Preference to avoid cyclophosphamide in a patient of childbearing potential due to the risk of cyclophosphamide-induced premature gonadal failure

Presence of severe heart disease – Preference to avoid extracorporeal therapies such as immunoadsorption and plasmapheresis in older patients with severe heart disease

Need for rapid-acting therapy – Preference for use of a rapid-acting therapy (eg, intravenous immunoglobulins, immunoadsorption, plasmapheresis) in patients with severe manifestations of the disease

Treatment availability — Treatment availability is a major factor in treatment selection that is based on both the ability to obtain a treatment and access to appropriate equipment and expertise to administer it safely. For example, although the use of cyclophosphamide for refractory pemphigus has decreased in clinical settings where patients have access to other, less toxic treatment options, the relatively higher cost and more limited access to rituximab, IVIG, immunoadsorption, and plasmapheresis has contributed to the continued use of cyclophosphamide in certain clinical settings.

Use prior to failure of rituximab — Rituximab has also been combined with IVIG, immunoadsorption, or plasmapheresis prior to assessing the response to rituximab, with the intent of taking advantage of the fast onset of action of these therapies [1-5]. We have used combination therapy with immunoadsorption and rituximab for patients with severe, refractory disease (extensive involvement or involvement of mucosal sites that may result in significant morbidity [conjunctiva, pharynx, larynx, or esophagus]).

Although rapid and long-lasting remissions have been reported in uncontrolled studies of patients with refractory pemphigus who were treated with combination therapy [1-5], the efficacy of rituximab given with and without these therapies has not been directly compared. Additional studies are necessary to confirm whether this approach is beneficial. The efficacy of efgartigimod, which may be another fast-acting therapy, is under investigation. (See 'Other therapies and regimens for pemphigus' below.)

INTRAVENOUS IMMUNE GLOBULIN — Intravenous immune globulin (IVIG) appears to be effective for refractory pemphigus. However, the mechanism through which IVIG improves pemphigus is not fully understood. Some authors have proposed that the infusion of IVIG may contribute to a reduction in circulating pemphigus autoantibodies by stimulating an increase in catabolism of immunoglobulins [6].

Administration and efficacy — IVIG therapy for adults is typically given as 2 g/kg given over two to five consecutive days every four weeks [7,8]. (See "Overview of intravenous immune globulin (IVIG) therapy".)

The highest-quality evidence for a beneficial therapeutic effect of IVIG in pemphigus is provided by an 85-day, multicenter, randomized trial in 61 adults with glucocorticoid-resistant pemphigus (defined as a failure to respond to the equivalent of 20 mg per day or more of prednisolone) [9]. Patients in the trial were treated with 400 mg/kg of IVIG per day for five days, 200 mg/kg of IVIG per day for five days, or a placebo infusion for five days. The primary endpoint in the trial was the duration of time that patients could be maintained on the treatment protocol before symptoms required additional treatment (ie, time to escape protocol).

The trial found that the time to escape protocol was significantly longer for patients in the 400 mg IVIG group compared with the patients in the placebo group [9], supporting a beneficial effect of the 400 mg dose of IVIG. The difference in the time to escape protocol for the 200 mg IVIG group and the placebo group was not statistically significant. Furthermore, a significant decrease in a pemphigus activity score was detected at all study observation points for patients in the 400 mg IVIG group and at all study observation points after day 15 in the 200 mg IVIG group. The pemphigus activity score did not decrease significantly at any time point in the placebo group.

Several uncontrolled studies and case series provide additional support for the use of IVIG for refractory pemphigus [6,10-14]. In most of the series, patients received IVIG at a dose of 2 g/kg/cycle consisting of two to four consecutive treatment days, and IVIG cycles were repeated in four- to six-week intervals. In some studies, clinical improvement following IVIG has been found to correlate with decreasing titers of desmoglein-specific immunoglobulin G (IgG) autoantibodies [6,14]. Additionally, a glucocorticoid-sparing effect of adjuvant IVIG was suggested by a small, retrospective study that found significant reductions in glucocorticoid requirements following treatment with adjuvant IVIG [13].

Adverse effects — In general, IVIG therapy is well tolerated. Adverse events are usually mild to moderate (eg, headache, back pain, increased blood pressure, abdominal discomfort) [9]. Aseptic meningitis is a serious side effect of IVIG therapy that requires immediate termination of treatment. Mostly, patients have a history of migraine or are prone to headache in general. Anaphylaxis is a potential risk of IVIG treatment in patients with a lack of immunoglobulin A (IgA). Therefore, absence of serum IgA (not deficiency) needs to be excluded prior to IVIG therapy. (See "Intravenous immune globulin: Adverse effects".)

IMMUNOADSORPTION — Immunoadsorption is a therapeutic option for pemphigus that functions through the removal of circulating autoantibodies. In contrast to plasmapheresis, which nonselectively removes plasma proteins from circulation, immunoadsorption removes circulating IgG with a very high specificity [15]. (See 'Plasmapheresis' below.)

The high cost and potential side effects (thrombophlebitis, venous thrombosis, bacterial infections, sepsis) of immunoadsorption limit use of this therapy. In addition, immunoadsorption for pemphigus is not available in some countries, including the United States. In light of the phase 2 data with efgartigimod, an antagonist of the neonatal Fc receptor that leads to a rapid turnover of immunoglobulins (including IgG autoantibodies), less invasive regimens leading to degradation of pathogenic autoantibodies may eventually replace more invasive procedures, such as immunoadsorption and plasmapheresis. (See 'Other therapies and regimens for pemphigus' below.)

Administration and efficacy — Immunoadsorption is administered as a minimum of two cycles of immunoadsorption performed over three to four consecutive days, with the cycles separated by four weeks [7].

Several apheresis systems for immunoadsorption have been successfully applied in pemphigus. The most effective columns include regenerative adsorber such as protein A or synthetic ligands that have a high affinity to the Fc portion of human IgG [16-19].

The efficacy of immunoadsorption for removing pemphigus autoantibodies is influenced by the adsorber utilized and treatment protocol. In one study in which protein A adsorber was utilized, levels of antibodies against desmogleins 1 and 3 were reduced by an average of 76 percent one month after the start of immunoadsorption treatment [16]. Immunoadsorption is typically administered as an adjuvant to immunosuppressive therapies in short three- to four-day cycles that are repeated every three to four weeks [16-18,20].

Data on the clinical efficacy of immunoadsorption in pemphigus are primarily limited to small, uncontrolled studies and case series [16-19]. The initial response to treatment can be rapid, occurring within a few weeks. Long-term improvement after immunoadsorption has been reported in several case series [16,18]. In our experience, patients with extensive skin involvement seem to benefit most from the addition of adjuvant immunoabsorption to immunosuppressive therapy.

Adverse effects — Most patients appear to tolerate immunoadsorption well. Infrequently reported adverse effects that may be directly related to immunoadsorption therapy include thrombophlebitis, venous thrombosis, bacterial infections, and sepsis from a central catheter [20].

CYCLOPHOSPHAMIDE — Treatment regimens that include cyclophosphamide may be useful for inducing remission in pemphigus and reducing dependence on systemic glucocorticoids [21]. The beneficial effect of cyclophosphamide in pemphigus is likely related to the drug's suppressive effect on B lymphocytes and the ensuing reduction in autoantibody production [22]. The adverse effect profile of cyclophosphamide contributes to the restriction of its use primarily for refractory disease [23]. (See 'Adverse effects' below.)

Administration and efficacy — Similar to azathioprine and mycophenolate mofetil, cyclophosphamide is usually prescribed as an adjuvant to systemic glucocorticoid therapy.

Several series have documented high rates of successful treatment of pemphigus with an intravenous pulsed regimen of dexamethasone and cyclophosphamide (monthly intravenous infusion of dexamethasone [100 mg for three days] and cyclophosphamide [500 mg for one day] plus daily 50 mg doses of oral cyclophosphamide in between pulsed therapy) [24-26]. However, less consistently favorable results with this regimen have also been reported [27]. Intravenous cyclophosphamide has also been utilized with other regimens (eg, 0.5 to 1 g/m2 body surface area per month for three to six months) [28,29].

A glucocorticoid-sparing effect of adjuvant cyclophosphamide given in a different regimen was demonstrated in a one-year, randomized trial (n = 120) that compared the efficacy of four different regimens for newly diagnosed pemphigus [21]. Although the rate of clinical response was similar among patients treated with both prednisolone (2 mg/kg per day followed by a taper) and cyclophosphamide (one 1000 mg intravenous dose per month for six months and every other month thereafter) and patients treated with prednisolone alone (73 and 77 percent, respectively), the cyclophosphamide group had a lower mean total dose of prednisolone (8276 versus 11,631 mg). Further, the glucocorticoid-sparing effects of cyclophosphamide were similar to the glucocorticoid-sparing effects of adjuvant azathioprine and mycophenolate mofetil.

The effects of treatment regimens with cyclophosphamide specifically on patients with refractory pemphigus have been evaluated in uncontrolled studies that have demonstrated favorable results in some patients [23,30]. Examples include:

In a prospective, uncontrolled study, 23 patients with pemphigus (20 with pemphigus vulgaris and 3 with pemphigus foliaceus) who had disease refractory to prednisone plus azathioprine and/or mycophenolate mofetil, who could not tolerate other therapies, or who had rapidly progressive, extensive disease were treated with oral cyclophosphamide (2 to 2.5 mg/kg of ideal body weight per day) and prednisone (1 mg/kg of ideal body weight per day followed by a taper after two to three months) [30]. Of note, nine patients with severe disease also received plasma exchange during the first two weeks of treatment.

Complete remission (defined as the absence of lesions for at least four weeks while on treatment with cyclophosphamide and less than 0.15 mg/kg per day of prednisone) was achieved by 17 of 20 patients with pemphigus vulgaris (85 percent) and two of three patients with pemphigus foliaceus. Three patients with pemphigus vulgaris failed to respond to treatment, and one patient with pemphigus foliaceus had a partial response. The median time to remission was 8.5 months for patients who did not receive plasma exchange and 8 months for those who received the additional treatment. Six of 12 patients who achieved complete remission and subsequently discontinued treatment with cyclophosphamide relapsed within a median time of six months.

In a retrospective study, 21 patients with pemphigus refractory to prednisolone plus azathioprine or methotrexate (18 with pemphigus vulgaris, 2 with pemphigus foliaceus, and 1 with paraneoplastic pemphigus) were treated with 4 to 22 pulses of intravenous methylprednisolone (1 g per day for three consecutive days) together with 500 mg of intravenous cyclophosphamide on the second day of treatment [23]. Between the monthly pulse treatments, patients were given oral cyclophosphamide (50 mg per day) and prednisolone. Continuation of adjuvant therapy with other immunosuppressives (mycophenolate mofetil and/or methotrexate) was allowed.

The study found a statistically significant reduction in skin and oral disease scores after treatment. Seven patients (33 percent) achieved an excellent response (defined as quiescent disease), and a lesser degree of response was observed in an additional 13 patients. The median number of pulses given to patients who achieved an excellent response was 12 (range 6 to 19). In addition, four patients with excellent responses achieved clinical remission (defined as complete resolution of blisters and erosions for at least six months) that lasted for six months to six years. One of these patients was able to completely discontinue treatment, while the other three remained on mycophenolate mofetil and low-dose prednisolone.

A few case reports have documented the successful use of immunoablative high-dose cyclophosphamide for severe, refractory pemphigus [31,32]. However, treatment is not uniformly effective, and a disease flare within weeks after treatment has been reported in a patient [31].

Adverse effects — Adverse effects of this cytotoxic drug include myelosuppression, systemic infections, urine bladder toxicity, increased malignancies, and premature gonadal failure. Patients receiving cyclophosphamide should be closely monitored for adverse effects of treatment. (See "General toxicity of cyclophosphamide in rheumatic diseases" and "General principles of the use of cyclophosphamide in rheumatic diseases", section on 'Monitoring of oral CYC dosing'.)

PLASMAPHERESIS — Compared with immunoadsorption, which specifically removes circulating IgG, plasmapheresis (also known as plasma exchange) nonselectively removes plasma proteins from circulation. Plasmapheresis is a more widely available therapy.

Given limited efficacy in removing pathogenic autoantibodies and the lack of high-quality trials confirming efficacy of plasmapheresis, plasmapheresis is no longer a mainstay in the treatment of refractory pemphigus. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)

Although small, uncontrolled studies and case reports have associated improvement in pemphigus with plasmapheresis [33-39], a randomized trial of 40 patients in which treatment with prednisolone alone was compared with prednisolone plus plasmapheresis found no significant difference in efficacy [40].

OTHER THERAPIES AND REGIMENS FOR PEMPHIGUS — In addition to the major therapeutic options for the initial treatment of pemphigus vulgaris and pemphigus foliaceus and the management of refractory disease, multiple other interventions have been reported to be of benefit in small numbers of patients. Additional studies are necessary to confirm efficacy of these therapies:

Intralesional rituximab – Limited data suggest that intralesional injection of rituximab may be an effective treatment modality for oral pemphigus. In an open study, all three patients given intralesional rituximab (5 mg/cm2 on days 1 and 15) for refractory oral pemphigus vulgaris had marked improvement [41]. One patient achieved clinical remission of oral lesions at week 12, and the remaining two patients achieved clinical remission at week 16. Adverse effects were limited to pain from injection in one patient. Of note, marked reductions in peripheral blood CD19+ B cell counts were noted in all patients two weeks after the initial treatment session. Patients were followed for up to six months; one patient relapsed five months after the start of therapy.

Low-dose rituximabRituximab administered in a lower dose than described above may be effective for pemphigus [42,43], though further study is necessary to clarify whether long-term outcomes are less favorable when compared with outcomes from higher-dose regimens [42-44]. Lower-dose regimens (eg, two 500 mg doses of rituximab separated by two weeks) may be associated with reduced duration of remission.

The comparative efficacy of low-dose rituximab (two 500 mg doses of rituximab separated by two weeks) and standard rheumatologic dosing of rituximab (two 1000 mg infusions separated by two weeks) was evaluated in a 48-week, randomized trial with 22 patients with pemphigus vulgaris or pemphigus foliaceus [43]. The study population included both patients who had failed other therapies and patients who received rituximab as initial treatment. Most patients received systemic glucocorticoids in addition to rituximab, and adjuvant immunosuppressants (primarily azathioprine) were added for patients with incomplete responses to treatment.

All 11 patients in the low-dose rituximab group and 10 of 11 patients in the standard rheumatologic dosing group achieved complete remission. Although the trial did not find statistically significant differences in the primary endpoints (time to disease control, time to end of consolidation phase, time to partial remission, or time to complete remission) between the two groups, there was a nonstatistically significant trend towards greater risk for relapse among patients treated with low-dose rituximab than among patients given the rheumatologic dose regimen (64 versus 36 percent relapsed, respectively). In addition, patients in the low-dose rituximab group had a significantly higher cumulative dose of azathioprine, and a statistically significant decline in enzyme-linked immunosorbent assay (ELISA) indices of desmoglein 1 and desmoglein 3 was evident only in the rheumatologic dose group.

Efgartigimod – An open-label, phase 2 study suggests intravenous efgartigimod, an engineered Fc fragment that reduced IgG levels through its affinity for the neonatal Fc receptor, may be a fast-acting treatment for mild to moderate pemphigus [45]. In the study, 28 of the 31 patients (90 percent) treated with efgartigimod alone or in combination with prednisone who were determined eligible for drug efficacy analysis achieved disease control, with a median time to disease control of 17 days.

Other therapies – Other examples include topical pimecrolimus [46], topical tacrolimus [47], sulfasalazine with pentoxifylline, gold [48], tetracyclines with or without nicotinamide [49], chlorambucil, mizoribine [50], and subcutaneous veltuzumab [51].

Although case reports have suggested benefit of the biologic tumor necrosis factor (TNF)-alpha inhibitors infliximab and etanercept in the treatment of pemphigus [52-56], a small, randomized trial that compared combination therapy with infliximab and prednisone with treatment with prednisone alone in 20 patients with pemphigus vulgaris found only nonstatistically significant trends towards better results with the addition of infliximab therapy [57]. The small size of the trial was a limiting factor; larger trials might clarify the effects of infliximab therapy.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pemphigus".)

SUMMARY AND RECOMMENDATIONS

Role of initial treatment – Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening disorders. Initial treatment for these diseases consists of either combination therapy with rituximab and a systemic glucocorticoid or a systemic glucocorticoid given with or without an adjuvant immunosuppressant, such as azathioprine or mycophenolate mofetil (algorithm 1). (See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Initial therapy'.)

Escalation of treatment is often the next step when patients fail to achieve disease control with the initial regimen (algorithm 1). Escalation of treatment generally consists of increasing the dose of the systemic glucocorticoid, adding rituximab (if not already received), and/or adding or adjusting conventional immunosuppressive therapy. (See 'Candidates' above and "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Failure to achieve disease control'.)

Role of treatments for refractory disease – Patients who do not respond sufficiently to initial treatment and escalation of treatment may benefit from other interventions, such as intravenous immune globulin (IVIG), immunoadsorption, cyclophosphamide, and plasmapheresis. (See 'Treatment options' above.)

Due to a lack of high-quality comparative trials, data are insufficient for definitive conclusions on the relative efficacies of therapies for refractory pemphigus. Factors such as patient tolerance for specific treatments and treatment availability influence treatment selection. (See 'Treatment selection' above.)

  1. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med 2006; 355:1772.
  2. Kasperkiewicz M, Shimanovich I, Meier M, et al. Treatment of severe pemphigus with a combination of immunoadsorption, rituximab, pulsed dexamethasone and azathioprine/mycophenolate mofetil: a pilot study of 23 patients. Br J Dermatol 2012; 166:154.
  3. Behzad M, Möbs C, Kneisel A, et al. Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris. Br J Dermatol 2012; 166:844.
  4. Shimanovich I, Nitschke M, Rose C, et al. Treatment of severe pemphigus with protein A immunoadsorption, rituximab and intravenous immunoglobulins. Br J Dermatol 2008; 158:382.
  5. Ahmed AR, Kaveri S, Spigelman Z. Long-Term Remissions in Recalcitrant Pemphigus Vulgaris. N Engl J Med 2015; 373:2693.
  6. Czernik A, Beutner EH, Bystryn JC. Intravenous immunoglobulin selectively decreases circulating autoantibodies in pemphigus. J Am Acad Dermatol 2008; 58:796.
  7. Joly P, Horvath B, Patsatsi Α, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol 2020; 34:1900.
  8. Murrell DF, Peña S, Joly P, et al. Diagnosis and management of pemphigus: Recommendations of an international panel of experts. J Am Acad Dermatol 2020; 82:575.
  9. Amagai M, Ikeda S, Shimizu H, et al. A randomized double-blind trial of intravenous immunoglobulin for pemphigus. J Am Acad Dermatol 2009; 60:595.
  10. Herzog S, Schmidt E, Goebeler M, et al. Serum levels of autoantibodies to desmoglein 3 in patients with therapy-resistant pemphigus vulgaris successfully treated with adjuvant intravenous immunoglobulins. Acta Derm Venereol 2004; 84:48.
  11. Seidling V, Hoffmann JH, Enk AH, Hadaschik EN. Analysis of high-dose intravenous immunoglobulin therapy in 16 patients with refractory autoimmune blistering skin disease: high efficacy and no serious adverse events. Acta Derm Venereol 2013; 93:346.
  12. Bystryn JC, Rudolph JL. IVI g TREATMENT OF PEMPHIGUS: how it works and how to use it. J Invest Dermatol 2005; 125:1093.
  13. Sami N, Qureshi A, Ruocco E, Ahmed AR. Corticosteroid-sparing effect of intravenous immunoglobulin therapy in patients with pemphigus vulgaris. Arch Dermatol 2002; 138:1158.
  14. Green MG, Bystryn JC. Effect of intravenous immunoglobulin therapy on serum levels of IgG1 and IgG4 antidesmoglein 1 and antidesmoglein 3 antibodies in pemphigus vulgaris. Arch Dermatol 2008; 144:1621.
  15. Eming R, Hertl M. Immunoadsorption in pemphigus. Autoimmunity 2006; 39:609.
  16. Schmidt E, Klinker E, Opitz A, et al. Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus. Br J Dermatol 2003; 148:1222.
  17. Lüftl M, Stauber A, Mainka A, et al. Successful removal of pathogenic autoantibodies in pemphigus by immunoadsorption with a tryptophan-linked polyvinylalcohol adsorber. Br J Dermatol 2003; 149:598.
  18. Eming R, Rech J, Barth S, et al. Prolonged clinical remission of patients with severe pemphigus upon rapid removal of desmoglein-reactive autoantibodies by immunoadsorption. Dermatology 2006; 212:177.
  19. Günther C, Laske J, Frind A, et al. Successful therapy of pemphigus vulgaris with immunoadsorption using the TheraSorb adsorber. J Dtsch Dermatol Ges 2008; 6:661.
  20. Schmidt E, Zillikens D. Immunoadsorption in dermatology. Arch Dermatol Res 2010; 302:241.
  21. Chams-Davatchi C, Esmaili N, Daneshpazhooh M, et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol 2007; 57:622.
  22. Zhu LP, Cupps TR, Whalen G, Fauci AS. Selective effects of cyclophosphamide therapy on activation, proliferation, and differentiation of human B cells. J Clin Invest 1987; 79:1082.
  23. Saha M, Powell AM, Bhogal B, et al. Pulsed intravenous cyclophosphamide and methylprednisolone therapy in refractory pemphigus. Br J Dermatol 2010; 162:790.
  24. Pasricha JS, Khaitan BK, Raman RS, Chandra M. Dexamethasone-cyclophosphamide pulse therapy for pemphigus. Int J Dermatol 1995; 34:875.
  25. Kaur S, Kanwar AJ. Dexamethasone-cyclophosphamide pulse therapy in pemphigus. Int J Dermatol 1990; 29:371.
  26. Sacchidanand S, Hiremath NC, Natraj HV, et al. Dexamethasone-cyclophosphamide pulse therapy for autoimmune-vesiculobullous disorders at Victoria hospital, Bangalore. Dermatol Online J 2003; 9:2.
  27. Rose E, Wever S, Zilliken D, et al. Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: results of a multicenter prospectively randomized study. J Dtsch Dermatol Ges 2005; 3:200.
  28. Saxena S, Khurana A, Sardana K. Pulsed cyclophosphamide sans pulse steroids in recalcitrant pemphigus: An effective, economical but underutilized modality. Dermatol Ther 2022; 35:e15392.
  29. Sesso R, Monteiro M, Sato E, et al. A controlled trial of pulse cyclophosphamide versus pulse methylprednisolone in severe lupus nephritis. Lupus 1994; 3:107.
  30. Cummins DL, Mimouni D, Anhalt GJ, Nousari CH. Oral cyclophosphamide for treatment of pemphigus vulgaris and foliaceus. J Am Acad Dermatol 2003; 49:276.
  31. Nousari CH, Brodsky R, Anhalt GJ. Evaluating the role of immunoablative high-dose cyclophosphamide therapy in pemphigus vulgaris. J Am Acad Dermatol 2003; 49:148.
  32. Hayag MV, Cohen JA, Kerdel FA. Immunoablative high-dose cyclophosphamide without stem cell rescue in a patient with pemphigus vulgaris. J Am Acad Dermatol 2000; 43:1065.
  33. Ranugha PS, Kumari R, Kartha LB, et al. Therapeutic plasma exchange as a crisis option in severe pemphigus vulgaris. Indian J Dermatol Venereol Leprol 2012; 78:508.
  34. Cotterill JA, Barker DJ, Millard LG. Plasma exchange in the treatment of pemphigus vulgaris. Br J Dermatol 1978; 98:243.
  35. Roujeau JC, Andre C, Joneau Fabre M, et al. Plasma exchange in pemphigus. Uncontrolled study of ten patients. Arch Dermatol 1983; 119:215.
  36. Tan-Lim R, Bystryn JC. Effect of plasmapheresis therapy on circulating levels of pemphigus antibodies. J Am Acad Dermatol 1990; 22:35.
  37. Søndergaard K, Carstens J, Jørgensen J, Zachariae H. The steroid-sparing effect of long-term plasmapheresis in pemphigus. Acta Derm Venereol 1995; 75:150.
  38. Turner MS, Sutton D, Sauder DN. The use of plasmapheresis and immunosuppression in the treatment of pemphigus vulgaris. J Am Acad Dermatol 2000; 43:1058.
  39. Liu Y, Zhang B, Ma J, et al. Double-filtration plasmapheresis combined with immunosuppressive treatment for severe pemphigus: 10 years' experience of a single center in China. J Clin Apher 2021; 36:20.
  40. Guillaume JC, Roujeau JC, Morel P, et al. Controlled study of plasma exchange in pemphigus. Arch Dermatol 1988; 124:1659.
  41. Vinay K, Kanwar AJ, Mittal A, et al. Intralesional Rituximab in the Treatment of Refractory Oral Pemphigus Vulgaris. JAMA Dermatol 2015; 151:878.
  42. Horváth B, Huizinga J, Pas HH, et al. Low-dose rituximab is effective in pemphigus. Br J Dermatol 2012; 166:405.
  43. Kanwar AJ, Vinay K, Sawatkar GU, et al. Clinical and immunological outcomes of high- and low-dose rituximab treatments in patients with pemphigus: a randomized, comparative, observer-blinded study. Br J Dermatol 2014; 170:1341.
  44. Amber KT, Hertl M. An assessment of treatment history and its association with clinical outcomes and relapse in 155 pemphigus patients with response to a single cycle of rituximab. J Eur Acad Dermatol Venereol 2015; 29:777.
  45. Goebeler M, Bata-Csörgő Z, De Simone C, et al. Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial. Br J Dermatol 2022; 186:429.
  46. Iraji F, Asilian A, Siadat AH. Pimecrolimus 1% cream in the treatment of cutaneous lesions of pemphigus vulgaris: a double-blind, placebo-controlled clinical trial. J Drugs Dermatol 2010; 9:684.
  47. Cohen SN, Lim RP, Paul CJ, Abdullah A. Equal efficacy of topical tacrolimus and clobetasone butyrate in pemphigus foliaceus. Int J Dermatol 2006; 45:1379.
  48. Salomon D, Saurat JH. Oral gold therapy (Auranofin) in pemphigus vulgaris. Dermatologica 1986; 172:310.
  49. Chen S, Lu X, Zhou G. Mild pemphigus foliaceus responding to combination therapy with niacinamide and tetracycline. Int J Dermatol 2003; 42:981.
  50. Hashimoto T. Treatment strategies for pemphigus vulgaris in Japan. Expert Opin Pharmacother 2008; 9:1519.
  51. Ellebrecht CT, Choi EJ, Allman DM, et al. Subcutaneous veltuzumab, a humanized anti-CD20 antibody, in the treatment of refractory pemphigus vulgaris. JAMA Dermatol 2014; 150:1331.
  52. Pardo J, Mercader P, Mahiques L, et al. Infliximab in the management of severe pemphigus vulgaris. Br J Dermatol 2005; 153:222.
  53. Jacobi A, Shuler G, Hertl M. Rapid control of therapy-refractory pemphigus vulgaris by treatment with the tumour necrosis factor-alpha inhibitor infliximab. Br J Dermatol 2005; 153:448.
  54. Berookhim B, Fischer HD, Weinberg JM. Treatment of recalcitrant pemphigus vulgaris with the tumor necrosis factor alpha antagonist etanercept. Cutis 2004; 74:245.
  55. Lin MH, Hsu CK, Lee JY. Successful treatment of recalcitrant pemphigus vulgaris and pemphigus vegetans with etanercept and carbon dioxide laser. Arch Dermatol 2005; 141:680.
  56. Shetty A, Marcum CB, Glass LF, Carter JD. Successful treatment of pemphigus vulgaris with etanercept in four patients. J Drugs Dermatol 2009; 8:940.
  57. Hall RP 3rd, Fairley J, Woodley D, et al. A multicentre randomized trial of the treatment of patients with pemphigus vulgaris with infliximab and prednisone compared with prednisone alone. Br J Dermatol 2015; 172:760.
Topic 15304 Version 16.0

References

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